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What changed in BeyondSpring Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of BeyondSpring Inc.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+582 added−617 removedSource: 10-K (2026-03-25) vs 10-K (2025-03-27)

Top changes in BeyondSpring Inc.'s 2025 10-K

582 paragraphs added · 617 removed · 489 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

210 edited+40 added−43 removed415 unchanged
Biggest changeFurther, the failure to maintain compliance with regulatory requirements may result in administrative or judicial actions, such as fines, untitled or warning letters, holds on clinical trials, product seizures, product detention or refusal to permit the import or export of products, refusal to approve pending applications or supplements, restrictions on marketing or manufacturing, injunctions or consent decrees, or civil or criminal penalties, or may lead to voluntary product recalls.
Biggest changeFurther, the failure to maintain compliance with regulatory requirements may result in administrative or judicial actions, such as fines, untitled or warning letters, holds on clinical trials, product seizures, product detention or refusal to permit the import or export of products, refusal to approve pending applications or supplements, restrictions on marketing or manufacturing, injunctions or consent decrees, or civil or criminal penalties, or may lead to voluntary product recalls. 27 Patent Term Restoration and Marketing Exclusivity Depending upon the timing, duration and specifics of FDA approval of the use of our product candidates, or any future product candidates we may develop, some of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Act.
The drug registration applicant may submit an application for priority review and approval for their drug applications simultaneously with filing the drug marketing application upon confirmation with the CDE beforehand. The drug marketing review time limit is stipulated as 130 working days for the drug applications, which enjoy a priority procedure for drug marketing authorization.
The drug registration applicant may submit an application for priority review and approval for their drug applications simultaneously with filing the drug marketing application upon confirmation with the CDE beforehand. The drug marketing review time limit is stipulated as 130 working days for the drug applications, which enjoy a priority procedure for drug marketing authorization.
Patents relating to utility-models and designs are effective for ten years from the initial date the patent application was filed, patents relating to designs are effective for fifteen years from the initial date the patent application was filed, and patents relating to invention are effective for twenty years from the initial date the patent application was filed.
Patents relating to utility-models are effective for ten years from the initial date the patent application was filed, patents relating to designs are effective for fifteen years from the initial date the patent application was filed, and patents relating to invention are effective for twenty years from the initial date the patent application was filed.
Plinabulin’s effect in preventing CIN has been demonstrated in six clinical trials so far, namely Study 101, DUBLIN-3, PROTECTIVE-1 (Phase 2 and Phase 3), and PROTECTIVE-2 (Phase 2 and Phase 3), with consistent data for CIN prevention early onset benefit in week 1 after chemotherapy. ● In the Phase 2 portion of Study 101, the addition of Plinabulin to a standard regimen of docetaxel resulted in a statistically significant reduction (p=0.002) in the incidence of grade 3 and 4 neutropenia adverse events from 26% of patients in the docetaxel monotherapy arm to 7% in the Plinabulin plus docetaxel arm based upon a retrospective analysis of the data. ● In DUBLIN-3, a Phase 3 study for NSCLC, we evaluated 559 patients on a secondary endpoint of grade 4 neutropenia reduction in Cycle 1 Day 8 and demonstrated Plinabulin’s ability to reduce docetaxel induced grade 4 neutropenia in NSCLC patients by 80% (p ● In our registration program for CIN, Plinabulin has been studied in two Phase 2/3 clinical trials, the first in Plinabulin monotherapy compared to pegfilgrastim for the prevention of CIN caused by intermediate-risk chemotherapy with high risk factors, composed solely of Taxotere (docetaxel), in various cancer including NSCLC, breast cancer and prostate cancer patients (PROTECTIVE-1), and the second in the Plinabulin and pegfilgrastim combination compared to pegfilgrastim alone for the prevention of CIN caused by high-risk chemotherapy, a myelosuppressive chemotherapeutic regimen composed of three agents, Taxotere (docetaxel), Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), in breast cancer patients (PROTECTIVE-2).
Plinabulin’s effect in preventing CIN has been demonstrated in six clinical trials so far, namely Study 101, DUBLIN-3, PROTECTIVE-1 (Phase 2 and Phase 3), and PROTECTIVE-2 (Phase 2 and Phase 3), with consistent data for CIN prevention early onset benefit in week 1 after chemotherapy. ● In the Phase 2 portion of Study 101, the addition of Plinabulin to a standard regimen of docetaxel resulted in a statistically significant reduction (p=0.002) in the incidence of grade 3 and 4 neutropenia adverse events from 26% of patients in the docetaxel monotherapy arm to 7% in the Plinabulin plus docetaxel arm based upon a retrospective analysis of the data. 12 ● In DUBLIN-3, a Phase 3 study for NSCLC, we evaluated 559 patients on a secondary endpoint of grade 4 neutropenia reduction in Cycle 1 Day 8 and demonstrated Plinabulin’s ability to reduce docetaxel induced grade 4 neutropenia in NSCLC patients by 80% (p ● In our registration program for CIN, Plinabulin has been studied in two Phase 2/3 clinical trials, the first in Plinabulin monotherapy compared to pegfilgrastim for the prevention of CIN caused by intermediate-risk chemotherapy with high risk factors, composed solely of Taxotere (docetaxel), in various cancer including NSCLC, breast cancer and prostate cancer patients (PROTECTIVE-1), and the second in the Plinabulin and pegfilgrastim combination compared to pegfilgrastim alone for the prevention of CIN caused by high-risk chemotherapy, a myelosuppressive chemotherapeutic regimen composed of three agents, Taxotere (docetaxel), Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), in breast cancer patients (PROTECTIVE-2).
The process required by the FDA before a drug may be marketed in the U.S. generally involves the following: ● completion of nonclinical laboratory tests, preclinical studies and formulation studies according to Good Laboratory Practices, or GLP, regulations; ● submission to the FDA of an IND, which must become effective before human clinical trials may begin; ● approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated; ● performance of adequate and well-controlled human clinical trials according to Good Clinical Practice requirements, or GCPs, to establish the safety and efficacy of the proposed product for its intended use; ● preparation and submission to the FDA of an NDA, for a drug; ● satisfactory completion of an FDA advisory committee review, if applicable; ● satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the product, or components thereof, are produced to assess compliance with current Good Manufacturing Practices, or cGMP; ● satisfactory completion of FDA inspection of selected clinical investigators, clinical trial sites and/or the clinical trial sponsor, to assure compliance with GCP requirements and the integrity of the clinical data; ● payment of user fees and 22 ● FDA review and approval of the NDA.
The process required by the FDA before a drug may be marketed in the U.S. generally involves the following: ● completion of nonclinical laboratory tests, preclinical studies and formulation studies according to Good Laboratory Practices, or GLP, regulations; ● submission to the FDA of an IND, which must become effective before human clinical trials may begin; ● approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated; ● performance of adequate and well-controlled human clinical trials according to Good Clinical Practice requirements, or GCPs, to establish the safety and efficacy of the proposed product for its intended use; ● preparation and submission to the FDA of an NDA, for a drug; ● satisfactory completion of an FDA advisory committee review, if applicable; ● satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the product, or components thereof, are produced to assess compliance with current Good Manufacturing Practices, or cGMP; ● satisfactory completion of FDA inspection of selected clinical investigators, clinical trial sites and/or the clinical trial sponsor, to assure compliance with GCP requirements and the integrity of the clinical data; ● payment of user fees and ● FDA review and approval of the NDA.
Data highlights include: ● Preclinical effectiveness: The triple immuno-oncology combination of Plinabulin, anti-PD-1 and radiation (triple combination) achieved a 100% complete response in a breast cancer model that is not responsive to PD-1 antibody alone. ● Sequential benefit: Plinabulin’s effects on dendritic cell maturation are greater when administered after each dose of fractionated radiotherapy, compared to administration before radiation, or administration only once after the first dose of radiotherapy. ● Abscopal effect: The Plinabulin triple combination anti-cancer effects in both irradiated and non-irradiated tumors in the same mice indicate the activation of a systemic anti-cancer immune response.
Data highlights include: ● Preclinical effectiveness: The triple immuno-oncology combination of Plinabulin, anti-PD-1 and radiation (triple combination) achieved a 100% complete response in a breast cancer model that is not responsive to PD-1 antibody alone. 8 ● Sequential benefit: Plinabulin’s effects on dendritic cell maturation are greater when administered after each dose of fractionated radiotherapy, compared to administration before radiation, or administration only once after the first dose of radiotherapy. ● Abscopal effect: The Plinabulin triple combination anti-cancer effects in both irradiated and non-irradiated tumors in the same mice indicate the activation of a systemic anti-cancer immune response.
This work forms the structural basis for the selection of small molecules to be studied as a potential “molecular glue.” In November 2020, SEED completed its Series A-1/A-2 financing where SEED issued and sold an aggregate of 1,194,030 of its Series A-1 Preferred Shares to BeyondSpring and SEED Technology Limited, a majority-owned indirect subsidiary of the Company, or, collectively, the BYSI Entities, for an aggregate purchase price of $3.0 million, and 1,990,000 of its Series A-2 Preferred Shares to Eli Lilly for an aggregate purchase price of $5.0 million, each at a cash purchase price of $2.5125 per share.
This work forms the structural basis for the selection of small molecules to be studied as a potential “molecular glue.” 16 In November 2020, SEED completed its Series A-1/A-2 financing where SEED issued and sold an aggregate of 1,194,030 of its Series A-1 Preferred Shares to BeyondSpring and SEED Technology Limited, a majority-owned indirect subsidiary of the Company, or, collectively, the BYSI Entities, for an aggregate purchase price of $3.0 million, and 1,990,000 of its Series A-2 Preferred Shares to Eli Lilly for an aggregate purchase price of $5.0 million, each at a cash purchase price of $2.5125 per share.
The Affordable Care Act also expanded the universe of Medicaid utilization subject to drug rebates by requiring pharmaceutical manufacturers to pay rebates on Medicaid managed care utilization and expanding the population potentially eligible for Medicaid drug benefits. 29 ● In order for a pharmaceutical product to receive federal reimbursement under the Medicare Part B and Medicaid programs or to be sold directly to U.S. government agencies, the manufacturer must extend discounts to entities eligible to participate in the 340B drug pricing program.
The Affordable Care Act also expanded the universe of Medicaid utilization subject to drug rebates by requiring pharmaceutical manufacturers to pay rebates on Medicaid managed care utilization and expanding the population potentially eligible for Medicaid drug benefits. ● In order for a pharmaceutical product to receive federal reimbursement under the Medicare Part B and Medicaid programs or to be sold directly to U.S. government agencies, the manufacturer must extend discounts to entities eligible to participate in the 340B drug pricing program.
Corporate Information BeyondSpring Inc. was incorporated as an exempted company under the laws of the Cayman Islands on November 21, 2014. In July 2015, we completed our internal restructuring. 54 Our principal executive offices are located at 100 Campus Drive, West Side, 4th Floor, Suite 410, Florham Park, New Jersey 07932 and our telephone number is +1 (646) 305-6387.
Corporate Information BeyondSpring Inc. was incorporated as an exempted company under the laws of the Cayman Islands on November 21, 2014. In July 2015, we completed our internal restructuring. Our principal executive offices are located at 100 Campus Drive, West Side, 4th Floor, Suite 410, Florham Park, New Jersey 07932 and our telephone number is +1 (646) 305-6387.
Where the applicant plans to make use of the data derived from the international multi-center clinical trials for application to NMPA for approval of an NDA, such international multi-center clinical trials shall satisfy, in addition to the requirements set forth in the PRC Drug Administration Law and its implementation regulations, Provisions for Drug Registration and relevant laws and regulations, the following requirements: 39 ● The applicant shall first conduct an overall evaluation on the global clinical trial data and further make trend analysis of the Asian and Chinese clinical trial data.
Where the applicant plans to make use of the data derived from the international multi-center clinical trials for application to NMPA for approval of an NDA, such international multi-center clinical trials shall satisfy, in addition to the requirements set forth in the PRC Drug Administration Law and its implementation regulations, Provisions for Drug Registration and relevant laws and regulations, the following requirements: ● The applicant shall first conduct an overall evaluation on the global clinical trial data and further make trend analysis of the Asian and Chinese clinical trial data.
We announce material information to the public about the Company, the progress and results of its clinical trials and research and development programs, and other matters through a variety of means, including filings with the SEC, press releases, public webcasts and presentations, the Company’s website (www.beyondspringpharma.com), and/or social media, including its LinkedIn account (https://www.linkedin.com/company/beyondspring-pharmaceuticals/) and X account (@BeyondSpringInc), in order to achieve broad, non-exclusionary distribution of information to the public.
We announce material information to the public about the Company, the progress and results of its clinical trials and research and development programs, and other matters through a variety of means, including filings with the SEC, press releases, public webcasts and presentations, the Company’s website (www.beyondspringpharma.com), and/or social media, including its LinkedIn account (www.linkedin.com/company/beyondspring-pharmaceuticals/) and X account (@BeyondSpringInc), in order to achieve broad, non-exclusionary distribution of information to the public.
Our data suggested that combining Plinabulin with Neulasta reverses the immune-suppressive profile of Neulasta by lowering the percentage of patients with a neutrophil-to-lymphocyte ratio of less than 5 (p 12 In the Phase 3 portion of PROTECTIVE-2 (double-blind, active-controlled, registration superiority study), 221 patients were enrolled to evaluate the CIN prevention effect of the Plinabulin and pegfilgrastim combination compared with pegfilgrastim alone.
Our data suggested that combining Plinabulin with Neulasta reverses the immune-suppressive profile of Neulasta by lowering the percentage of patients with a neutrophil-to-lymphocyte ratio of less than 5 (p In the Phase 3 portion of PROTECTIVE-2 (double-blind, active-controlled, registration superiority study), 221 patients were enrolled to evaluate the CIN prevention effect of the Plinabulin and pegfilgrastim combination compared with pegfilgrastim alone.
The clinical trials under the breakthrough therapeutic drug procedure may enjoy the following priority: (i) the applicant may submit an application for communication to the CDE during the key phase of the clinical trial of drugs, and the CDE shall arrange for review officers to communicate with the applicant; (ii) the applicant may submit research materials in phases to the CDE; and (iii) the CDE shall, based on the available research materials, give opinions or recommendations pertaining to the next step of the research scheme and feedback to the applicant.
The clinical trials under the breakthrough therapeutic drug procedure may enjoy the following priority: (i) the applicant may submit an application for communication to the CDE during the key phase of the clinical trial of drugs, and the CDE shall arrange for review officers to communicate with the applicant; (ii) the applicant may submit research materials in phases to the CDE, and the CDE shall, based on the available research materials, give opinions or recommendations pertaining to the next step of the research scheme and feedback to the applicant.
Risk Factors—Risks Related to Our Doing Business in China—Chinese regulations relating to investments in offshore companies by Chinese residents may subject our future Chinese resident beneficial owners or our Chinese subsidiaries to liability or penalties, limit our ability to inject capital into our Chinese subsidiaries or limit our Chinese subsidiaries’ ability to increase their registered capital or distribute profits.” 49 We have completed the foreign exchange registration of PRC resident shareholders of Mr.
Risk Factors—Risks Related to Our Doing Business in China—Chinese regulations relating to investments in offshore companies by Chinese residents may subject our future Chinese resident beneficial owners or our Chinese subsidiaries to liability or penalties, limit our ability to inject capital into our Chinese subsidiaries or limit our Chinese subsidiaries’ ability to increase their registered capital or distribute profits.” We have completed the foreign exchange registration of PRC resident shareholders of Mr.
Patients treated with Plinabulin had statistically significant increases in CD34+ levels at Day 8 in a dose-dependent manner (p In the Phase 3 portion of PROTECTIVE-1 (double-blind, active-controlled), 105 NSCLC, breast cancer and prostate cancer patients were enrolled to compare Plinabulin with Neulasta in CIN prevention benefit, with DSN in cycle 1 as the primary endpoint.
Patients treated with Plinabulin had statistically significant increases in CD34+ levels at Day 8 in a dose-dependent manner (p 13 In the Phase 3 portion of PROTECTIVE-1 (double-blind, active-controlled), 105 NSCLC, breast cancer and prostate cancer patients were enrolled to compare Plinabulin with Neulasta in CIN prevention benefit, with DSN in cycle 1 as the primary endpoint.
Any uncertainties or negative publicity regarding such approval requirement could materially and adversely affect our business, prospects, financial condition, reputation, and the trading price of our ordinary shares. 52 Rest of the World Regulation For other countries outside of the U.S. and China, the requirements governing the conduct of clinical trials, drug licensing, pricing and reimbursement vary from country to country.
Any uncertainties or negative publicity regarding such approval requirement could materially and adversely affect our business, prospects, financial condition, reputation, and the trading price of our ordinary shares. Rest of the World Regulation For other countries outside of the U.S. and China, the requirements governing the conduct of clinical trials, drug licensing, pricing and reimbursement vary from country to country.
Therefore, patents and patent applications relating to drugs similar to our current product candidates and any future drugs, discoveries or technologies we might develop may have already been issued or filed, which could prohibit us from commercializing our product candidates. 19 The biotechnology and pharmaceutical industries are characterized by extensive litigation regarding patents and other intellectual property rights.
Therefore, patents and patent applications relating to drugs similar to our current product candidates and any future drugs, discoveries or technologies we might develop may have already been issued or filed, which could prohibit us from commercializing our product candidates. The biotechnology and pharmaceutical industries are characterized by extensive litigation regarding patents and other intellectual property rights.
Penalties for a False Claims Act violation include three times the actual damages sustained by the government, plus mandatory civil penalties, and the potential for exclusion from participation in federal healthcare programs. The applicable civil penalties are subject to an annual increase based on inflation; for 2025, the penalties are between $14,308 and $28,619 for each separate false claim.
Penalties for a False Claims Act violation include three times the actual damages sustained by the government, plus mandatory civil penalties, and the potential for exclusion from participation in federal healthcare programs. The applicable civil penalties are subject to an annual increase based on inflation; for 2025, the penalties were between $14,308 and $28,619 for each separate false claim.
If all requirements are met, a GCP Certification will be issued by the NMPA and the result will be published on the NMPA’s website. On December 1, 2019, the newly revised PRC Drug Administration Law came into effect, which provides that instead of the aforesaid certification, the drug clinical trial institutions are now subject to a record-filing system.
If all requirements are met, a GCP Certification will be issued by the NMPA and the result will be published on the NMPA’s website. 39 On December 1, 2019, the newly revised PRC Drug Administration Law came into effect, which provides that instead of the aforesaid certification, the drug clinical trial institutions are now subject to a record-filing system.
With the proceeds of these payments, SEED has invested in developing additional breakthrough and proprietary methods for “molecular glue” discovery, in order to enhance its advantage in growing “molecular glue” drug discovery and development efforts. 15 Eisai In August 2024, SEED entered into strategic research collaboration with Eisai to discover and develop novel molecular glue degraders for neurodegeneration and oncology indications.
With the proceeds of these payments, SEED has invested in developing additional breakthrough and proprietary methods for “molecular glue” discovery, in order to enhance its advantage in growing “molecular glue” drug discovery and development efforts. Eisai In August 2024, SEED entered into strategic research collaboration with Eisai to discover and develop novel molecular glue degraders for neurodegeneration and oncology indications.
Adoption of government controls and measures, and tightening of restrictive policies in jurisdictions with existing controls and measures, could limit payments for pharmaceuticals including our product candidates, if any achieve approval. 27 The marketability of any products for which we receive regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide adequate coverage and reimbursement.
Adoption of government controls and measures, and tightening of restrictive policies in jurisdictions with existing controls and measures, could limit payments for pharmaceuticals including our product candidates, if any achieve approval. The marketability of any products for which we receive regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide adequate coverage and reimbursement.
If the research fails to be completed as required within the prescribed time limit or fails to prove that the benefits outweigh the risks, then, at the worst, the drug marketing license may be revoked. On January 22, 2020, the revised Provisions for Drug Registration were issued by the SAMR, which came into effect on July 1, 2020.
If the research fails to be completed as required within the prescribed time limit or fails to prove that the benefits outweigh the risks, then, at the worst, the drug marketing license may be revoked. 38 On January 22, 2020, the revised Provisions for Drug Registration were issued by the SAMR, which came into effect on July 1, 2020.
Alternatively, persons whose trade secrets are being misappropriated may file lawsuits in a Chinese court for loss and damages caused by the misappropriation. 46 The measures to protect trade secrets include oral or written agreements or other reasonable measures to require the employees of, or persons in business contact with, legal owners or holders to keep trade secrets confidential.
Alternatively, persons whose trade secrets are being misappropriated may file lawsuits in a Chinese court for loss and damages caused by the misappropriation. The measures to protect trade secrets include oral or written agreements or other reasonable measures to require the employees of, or persons in business contact with, legal owners or holders to keep trade secrets confidential.
The FDA is not bound by the recommendation of an advisory committee, but it considers such recommendations when making decisions. 24 The approval process is lengthy and difficult and the FDA may refuse to approve an NDA if the applicable regulatory criteria are not satisfied or may require additional clinical data or other data and information.
The FDA is not bound by the recommendation of an advisory committee, but it considers such recommendations when making decisions. The approval process is lengthy and difficult and the FDA may refuse to approve an NDA if the applicable regulatory criteria are not satisfied or may require additional clinical data or other data and information.
Future FDA and state inspections may identify compliance issues at the facilities of our contract manufacturers that may disrupt production or distribution or may require substantial resources to correct. 25 The FDA may withdraw a product approval if compliance with regulatory requirements is not maintained or if problems occur after the product reaches the market.
Future FDA and state inspections may identify compliance issues at the facilities of our contract manufacturers that may disrupt production or distribution or may require substantial resources to correct. The FDA may withdraw a product approval if compliance with regulatory requirements is not maintained or if problems occur after the product reaches the market.
Any of these measures may materially affect the potential market and profitability of the product. Failure to satisfy FDA post-marketing requirements can result in FDA enforcement action, up to and including withdrawal of NDA approval, and the FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.
Any of these measures may materially affect the potential market and profitability of the product. 26 Failure to satisfy FDA post-marketing requirements can result in FDA enforcement action, up to and including withdrawal of NDA approval, and the FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.
Plinabulin, Our Lead Drug Candidate Plinabulin is a first-in-class, novel small molecule derived from a natural compound found in marine microorganisms. It is a Selective Immunomodulating Microtubule-Binding Agent, which may provide multiple therapeutic opportunities. As a low molecular weight small molecule, Plinabulin is relatively simple to manufacture.
Plinabulin, Our Lead Drug Candidate Plinabulin is a first-in-class, novel small molecule derived from a natural compound found in marine microorganisms. It is a Selective Immunomodulating Microtubule-Binding Agent (SIMBA), which may provide multiple therapeutic opportunities. As a low molecular weight small molecule, Plinabulin is relatively simple to manufacture.
Additionally, the data demonstrated that the Plinabulin combination was able to re-sensitize tumors to immune-oncology therapy, that had previously progressed on prior immunotherapies, with a 43% ORR. 9 In October 2021, the first patient was enrolled in the Phase 2 portion of this investigator-initiated study.
Additionally, the data demonstrated that the Plinabulin combination was able to re-sensitize tumors to immune-oncology therapy, that had previously progressed on prior immunotherapies, with a 43% ORR. In October 2021, the first patient was enrolled in the Phase 2 portion of this investigator-initiated study.
The study is ongoing. 8 Plinabulin + PD-1/PD-L1 antibody + Radiation in multiple cancers of PD-1/PD-L1 failed patients in Multiple Cancer Types In July 2018, we entered into a sponsored research agreement with MD Anderson to evaluate the benefits of adding Plinabulin to radiation therapy plus immune checkpoint antibodies.
The study is ongoing. Plinabulin + PD-1/PD-L1 antibody + Radiation in multiple cancers of PD-1/PD-L1 failed patients in Multiple Cancer Types In July 2018, we entered into a sponsored research agreement with MD Anderson to evaluate the benefits of adding Plinabulin to radiation therapy plus immune checkpoint antibodies.
The purpose of a clinical trial is to determine the therapeutic efficacy and safety of the drug. 31 In April 2020, the NMPA and the National Health Commission promulgated the revised Administration Rules of Quality of Drug Clinical Practice, which became effective in July 2020, in order to further ensure the quality of clinical trials and the safety of human subjects.
The purpose of a clinical trial is to determine the therapeutic efficacy and safety of the drug. In April 2020, the NMPA and the National Health Commission promulgated the revised Administration Rules of Quality of Drug Clinical Practice, which became effective in July 2020, in order to further ensure the quality of clinical trials and the safety of human subjects.
Additionally, in the Phase 2 portion of PROTECTIVE-1, Plinabulin was shown to reduce thrombocytopenia and demonstrated a superior immune profile compared to Neulasta based on promyelocytes and immature neutrophil data. 11 One of the secondary endpoints evaluated in PROTECTIVE-1 was the reduction of bone pain.
Additionally, in the Phase 2 portion of PROTECTIVE-1, Plinabulin was shown to reduce thrombocytopenia and demonstrated a superior immune profile compared to Neulasta based on promyelocytes and immature neutrophil data. One of the secondary endpoints evaluated in PROTECTIVE-1 was the reduction of bone pain.
These include the Patient-Centered Outcomes Research Institute, established to oversee, identify priorities in, and conduct comparative clinical effectiveness research and the Center for Medicare and Medicaid Innovation within the Centers for Medicare and Medicaid Services, to test innovative payment and service delivery models to lower Medicare and Medicaid spending.
These include the Patient-Centered Outcomes Research Institute, established to oversee, identify priorities in, and conduct comparative clinical effectiveness research and the Center for Medicare and Medicaid Innovation (CMMI) within the Centers for Medicare and Medicaid Services, to test innovative payment and service delivery models to lower Medicare and Medicaid spending.
To the extent that any provision set forth in the Security Assessment Measures is inconsistent with the provisions set forth in the provisions, the provisions prevail. 42 On September 24, 2024, the State Council published the Administrative Regulations on the Internet Data Security, effective from January 1, 2025, or the Data Security Measures.
To the extent that any provision set forth in the Security Assessment Measures is inconsistent with the provisions set forth in the provisions, the provisions prevail. On September 24, 2024, the State Council published the Administrative Regulations on the Internet Data Security, effective from January 1, 2025, or the Data Security Measures.
The FDA also can impose partial clinical holds, for example, prohibiting the initiation of clinical trials of a certain duration or for a certain dose. We are conducting our current clinical trials under two INDs. Investigator-led clinical trials are being conducted under separate INDs.
The FDA also can impose partial clinical holds, for example, prohibiting the initiation of clinical trials of a certain duration or for a certain dose. 24 We are conducting our current clinical trials under two INDs. Investigator-led clinical trials are being conducted under separate INDs.
It is impossible to predict whether further legislative or FDA regulation, policy, funding or staffing changes will be enacted or implemented and what the impact of such changes, if any, may be. U.S.
It is impossible to predict whether further legislative or FDA regulation, policy, funding or staffing changes will be enacted or implemented and what the impact of such changes, if any, may be. 23 U.S.
Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product drug does not undergo unacceptable deterioration over its shelf life. U.S.
Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product drug does not undergo unacceptable deterioration over its shelf life. 25 U.S.
Information that is contained in and can be accessed through our website, our LinkedIn posts and our X posts, are not incorporated into, and does not form a part of, this Annual Report.
Information that is contained in and can be accessed through our website, our LinkedIn posts and our X posts, are not incorporated into, and does not form a part of, this Annual Report. 55
SAFE Circular 29 further specifies that the domestic equity investment set forth in SAFE Circular 28 is not limited to direct investment in a domestic enterprise but also includes equity investment conducted in the form of “equity transfer.” 48 Our Chinese subsidiaries’ distributions to the offshore parent and carrying out cross-border foreign exchange activities shall comply with the various SAFE registration requirements described above.
SAFE Circular 29 further specifies that the domestic equity investment set forth in SAFE Circular 28 is not limited to direct investment in a domestic enterprise but also includes equity investment conducted in the form of “equity transfer.” 49 Our Chinese subsidiaries’ distributions to the offshore parent and carrying out cross-border foreign exchange activities shall comply with the various SAFE registration requirements described above.
Current investigator-initiated studies on these Plinabulin combinations aim to help design an optimum registrational study for these indications for patients who failed PD-1/PD-L1 inhibitors, especially in NSCLC. Preclinical study data supporting Plinabulin in immuno-oncology Checkpoint inhibitors (PD-1/PD-L1 inhibitors) alleviate immune system blocks at a relatively late stage in the overall immune process—at the point when T-cells recognize cancer cells.
Current investigator-initiated studies on these Plinabulin combinations aim to help design an optimum registrational study for these indications for patients who progressed on PD-1/PD-L1 inhibitors, especially in NSCLC. Preclinical study data supporting Plinabulin in immuno-oncology Checkpoint inhibitors (PD-1/PD-L1 inhibitors) alleviate immune system blocks at a relatively late stage in the overall immune process—at the point when T-cells recognize cancer cells.
In October 2018, the Standing Committee of the National People’s Congress issued the Decisions on Extending the Term of the Pilot Program for the Drug Marketing Authorization Holder System in Several Regions, which extended the expiration date of the pilot program from November 4, 2018 to November 4, 2019. 35 On December 1, 2019, the newly revised PRC Drug Administration Law came into effect, which formally adopts and signals the nationwide implementation of the drug marketing authorization holder system.
In October 2018, the Standing Committee of the National People’s Congress issued the Decisions on Extending the Term of the Pilot Program for the Drug Marketing Authorization Holder System in Several Regions, which extended the expiration date of the pilot program from November 4, 2018 to November 4, 2019. 36 On December 1, 2019, the newly revised PRC Drug Administration Law came into effect, which formally adopts and signals the nationwide implementation of the drug marketing authorization holder system.
The elucidation of this mechanism was a multi-year collaborative effort among us, University of Basel, Massachusetts General Hospital, and MD Anderson. In aggregate, as of the date of this Annual Report on Form 10-K, Plinabulin has been administered to over 700 patients with advanced cancer and thus far is generally well-tolerated.
The elucidation of Plinabulin’s unique mechanism was a multi-year collaborative effort among us, University of Basel, Massachusetts General Hospital, and MD Anderson. In aggregate, as of the date of this Annual Report on Form 10-K, Plinabulin has been administered to over 700 patients with advanced cancer and thus far is generally well-tolerated.
Government Regulation and Product Approval Government authorities in the U.S. at the federal, state and local level extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing, export and import of drug products such as those we are developing.
Government Regulation and Product Approval Government authorities in the U.S. at the federal, state and local levels extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing, export and import of drug products such as those we are developing.
The immune mechanism of Plinabulin can effectively add more T-cells, or “hit the gas” to kill cancer cells, while PD-1/PD-L1 antibodies are known to let T-cells “see” cancer cells, or “release the break.” Thus, combining Plinabulin, PD-1/PD-L1 antibodies, and chemotherapy or radiation have the potential to elevate the anti-cancer benefit and re-sensitize patients who progressed on immunotherapies.
The immune mechanism of Plinabulin can effectively add more T-cells, or “hit the gas” to kill cancer cells, while PD-1/PD-L1 antibodies are known to let T-cells “see” cancer cells, or “release the break.” Thus, combining Plinabulin, and chemotherapy or radiation, with or without PD-1/PD-L1 antibodies have the potential to elevate the anti-cancer benefit and re-sensitize patients who progressed on immunotherapies.
The system for importing overseas marketed drugs with urgent clinical needs shall also be improved. 36 Non-Inferiority Standard In China, a drug may receive regulatory approval without showing superiority in its primary endpoint. Rather, a drug may be approved for use if it shows non-inferiority in its primary endpoint and superiority in one of its secondary endpoints.
The system for importing overseas marketed drugs with urgent clinical needs shall also be improved. 37 Non-Inferiority Standard In China, a drug may receive regulatory approval without showing superiority in its primary endpoint. Rather, a drug may be approved for use if it shows non-inferiority in its primary endpoint and superiority in one of its secondary endpoints.
Any such administrative or judicial enforcement or other action could have a material adverse effect on us. 21 U.S. Regulation U.S.
Any such administrative or judicial enforcement or other action could have a material adverse effect on us. U.S. Regulation U.S.
Although a number of these and other proposed measures will require authorization through additional legislation to become effective, Congress and the current Trump administration have each indicated that they will continue to seek new legislative and/or administrative measures to control drug costs.
Although a number of proposed measures will require authorization through additional legislation to become effective, Congress and the current Trump administration have each indicated that they will continue to seek new legislative and/or administrative measures to control drug costs.
These cGMP conditions are regulatory requirements for the production of pharmaceuticals that will be used in humans. 53 Organizational Structure The diagram below depicts our current organizational structure. Human Capital Resources We are a research and development-focused biotechnology organization.
These cGMP conditions are regulatory requirements for the production of pharmaceuticals that will be used in humans. Organizational Structure The diagram below depicts our current organizational structure. 54 Human Capital Resources We are a research and development-focused biotechnology organization.
We believe Plinabulin, if approved, could have significant commercial potential in the U.S. and globally as an anti-cancer agent across several substantial solid tumor patient populations, such as NSCLC and ES-SCLC, among others.
We believe Plinabulin, if approved, could have significant commercial potential in the U.S. and globally as an anti-cancer agent across several substantial solid tumor patient populations, such as NSCLC, head and neck cancer, and ES-SCLC, among others.
Trade Secrets According to the Law Against Unfair Competition of the PRC promulgated in September 1993 and amended in November 2017 and April 23, 2019, respectively, the term “trade secrets” refers to technical information, business operation information and other commercial information that are not known to the public and have commercial value and for which corresponding confidentiality measures have been taken by their rights holders.
Trade Secrets According to the Law Against Unfair Competition of the PRC promulgated in September 1993 and amended in November 2017, April 2019 and June 2025, respectively, the term “trade secrets” refers to technical information, business operation information and other commercial information that are not known to the public and have commercial value and for which corresponding confidentiality measures have been taken by their rights holders.
Currently we have 10 invention patents granted by CNIPA and 15 invention patents under the application process. Patent Enforcement Unauthorized use of patents without consent from owners of patents, forgery of the patents belonging to other persons, or engagement in other infringement acts against patent rights, will subject the infringers to tortious liabilities.
Currently we have 10 invention patents granted by CNIPA and 18 invention patents under the application process. 45 Patent Enforcement Unauthorized use of patents without consent from owners of patents, forgery of the patents belonging to other persons, or engagement in other infringement acts against patent rights, will subject the infringers to tortious liabilities.
On December 10, 2020, the NMPA issued the revised Administration Measures for the Communication of Drug Development and Technical Review which stipulated detailed procedural rules of the communication.
On December 10, 2020, the CDE issued the revised Administration Measures for the Communication of Drug Development and Technical Review which stipulated detailed procedural rules of the communication.
The laws that may affect our ability to operate include: ● the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order, or recommendation of, an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs; ● federal civil and criminal false claims laws, false statement laws, and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent, or making a false statement or record material to payment of a false claim or avoiding, decreasing, or concealing an obligation to pay money to the federal government; ● Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes federal criminal and civil liability for executing a scheme to defraud any healthcare benefit program, including private third-party payors and making false statements relating to healthcare matters; ● the federal transparency laws, including the federal Physician Payments Sunshine Act, which is part of the Affordable Care Act, that requires applicable manufacturers of covered drugs to disclose payments and other transfers of value provided to physicians and teaching hospitals and physician ownership and investment interests; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, also imposes certain requirements relating to the privacy, security and transmission of individually identifiable health information; and ● state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers, state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines, and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and are not preempted by HIPAA, thus complicating compliance efforts. 28 The Affordable Care Act broadened the reach of the fraud and abuse laws by, among other things, amending the intent requirement of the federal Anti-Kickback Statute and the applicable criminal healthcare fraud statutes contained within 42 U.S.C. § 1320a-7b.
The laws that may affect our ability to operate include: 29 ● the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order, or recommendation of, an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs; ● federal civil and criminal false claims laws, false statement laws, and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent, or making a false statement or record material to payment of a false claim or avoiding, decreasing, or concealing an obligation to pay money to the federal government; ● Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes federal criminal and civil liability for executing a scheme to defraud any healthcare benefit program, including private third-party payors and making false statements relating to healthcare matters; ● the federal transparency laws, including the federal Physician Payments Sunshine Act, which is part of the Affordable Care Act, that requires applicable manufacturers of covered drugs to disclose payments and other transfers of value provided to physicians and teaching hospitals and physician ownership and investment interests; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, also imposes certain requirements relating to the privacy, security and transmission of individually identifiable health information; and ● state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers, state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines, and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and are not preempted by HIPAA, thus complicating compliance efforts.
As a potential “pipeline in a drug,” Plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and potentially allow patients who progressed on PD-1/PD-L1 antibodies to respond to PD-1/PD-L1 combination with Plinabulin.
As a potential “pipeline in a drug,” Plinabulin is being broadly studied in combination with chemotherapy, radiation, or various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and potentially allow patients who progressed on PD-1/PD-L1 antibodies to respond to Plinabulin regimen.
In November 2015, the CFDA released the Circular concerning Several Policies on Drug Registration Review and Approval, which further clarified the following policies potentially simplifying and accelerating the approval process of clinical trials: ● A one-time umbrella approval procedure allowing approval of all phases of a new drug’s clinical trials at once, rather than the current phase-by-phase approval procedure, will be adopted for new drugs’ clinical trial applications; ● A fast-track drug registration or clinical trial approval pathway will be available for the following applications: (1) registration of innovative new drugs treating and preventing HIV, malignant tumors, serious infectious diseases and orphan diseases, etc.; (2) registration of pediatric drugs; (3) registration of geriatric drugs that treat China-prevalent geriatric diseases; (4) registration of drugs sponsored by national science and technology major projects and national major research and development plans ; (5) registration for drugs with urgent clinical need using advanced technology, using innovative treatment methods, or having distinctive clinical benefits; (6) registration of foreign innovative drugs to be manufactured locally in China; (7) concurrent applications for new drug clinical trials which are already approved in the U.S. or European Union, or concurrent drug registration applications for drugs which have applied for marketing authorization and passed onsite inspections in the U.S. or European Union and are manufactured with the same production line in China; and (8) clinical trial applications for drugs with urgent clinical need and patent expiry within three years, and marketing authorization applications for drugs with urgent clinical need and patent expiry within one year. 34 In December 2017, the CFDA released the Opinions on Encouraging Drug Innovations and Implying the Prioritized Review and Approval System, which further stipulated the scope of priority review and approval.
In November 2015, the CFDA released the Circular concerning Several Policies on Drug Registration Review and Approval, which further clarified the following policies potentially simplifying and accelerating the approval process of clinical trials: 35 ● A one-time umbrella approval procedure allowing approval of all phases of a new drug’s clinical trials at once, rather than the phase-by-phase approval procedure, will be adopted for new drugs’ clinical trial applications; ● A fast-track drug registration or clinical trial approval pathway will be available for the following applications: (1) registration of innovative new drugs treating and preventing HIV, malignant tumors, serious infectious diseases and orphan diseases, etc.; (2) registration of pediatric drugs; (3) registration of geriatric drugs that treat China-prevalent geriatric diseases; (4) registration of drugs sponsored by national science and technology major projects and national major research and development plans ; (5) registration for drugs with urgent clinical need using advanced technology, using innovative treatment methods, or having distinctive clinical benefits; (6) registration of foreign innovative drugs to be manufactured locally in China; (7) concurrent applications for new drug clinical trials which are already approved in the U.S. or European Union, or concurrent drug registration applications for drugs which have applied for marketing authorization and passed onsite inspections in the U.S. or European Union and are manufactured with the same production line in China; and (8) clinical trial applications for drugs with urgent clinical need and patent expiry within three years, and marketing authorization applications for drugs with urgent clinical need and patent expiry within one year.
While we believe that our development and commercialization experience, commercial strategy, Breakthrough Therapy Designation status, scientific knowledge and industry relationships provide us with competitive advantages, we face competition from pharmaceutical and biotechnology companies, including specialty pharmaceutical companies, and generic drug companies, academic institutions, government agencies and research institutions.
While we believe that our development and commercialization experience, commercial strategy, scientific knowledge and industry relationships provide us with competitive advantages, we face competition from pharmaceutical and biotechnology companies, including specialty pharmaceutical companies, and generic drug companies, academic institutions, government agencies and research institutions.
Investigator-initiated studies in Plinabulin in immuno-oncology We have explored and plan to continue to explore the role of Plinabulin in stimulating the activity of other immuno-oncology agents in clinical programs: 7 Plinabulin + Pembrolizumab + Docetaxel in 2L NSCLC who progressed on PD-1/PD-L1 (Study 303) Docetaxel remains the standard of care for second-line and third-line treatments of patients with NSCLC without targetable alterations who progress on immune checkpoint inhibitors with and without standard chemotherapy.
Investigator-initiated studies in Plinabulin in immuno-oncology We have explored and plan to continue to explore the role of Plinabulin in stimulating the activity of other immuno-oncology agents in clinical programs: Plinabulin + Pembrolizumab + Docetaxel in 2L NSCLC who progressed on PD-1/PD-L1 inhibitors (Study 303) Docetaxel remains the standard of care for second-line and third-line treatments of patients with EHFR wild type NSCLC who progress on immune checkpoint inhibitors with and without standard chemotherapy.
We believe that the activation of dendritic cells is a key to unlocking the next boost to the efficacy of immuno-oncology agents. Activated dendritic cells, which are the most potent antigen presenting cells, present foreign tumor antigens to T-cells to induce cancer-directed immune attacks.
We believe that the maturation of dendritic cells is a key to unlocking the next boost to the efficacy of immuno-oncology agents. Matured dendritic cells, which are the most potent antigen presenting cells, present foreign tumor antigens to T-cells to induce cancer-directed immune attacks.
The study was completed and the topline data was presented at the ASCO in June 2023. Other Programs In addition to exploring Plinabulin’s therapeutic potential in combination with immuno-oncology agents, we have a pipeline of immuno-oncology product candidates and have utilized our research collaborators to advance these programs.
Enrollment of this Phase 1 study was completed in March 2023. The study was completed and the topline data was presented at the ASCO in June 2023. Other Programs In addition to exploring Plinabulin’s therapeutic potential in combination with immuno-oncology agents, we have a pipeline of immuno-oncology product candidates and have utilized our research collaborators to advance these programs.
The Affordable Care Act has been subject to challenges, as well as numerous ongoing efforts by the U.S. Congress and the administrations of President Trump to repeal or amend the Affordable Care Act in whole or in part.
The Affordable Care Act has been subject to challenges, as well as numerous ongoing efforts by the U.S. Congress and the administrations of President Trump to repeal or amend the Affordable Care Act in whole or in part. For example, in March 2023, the U.S.
None of following circumstances are deemed an infringement of the patent rights, and any person may manufacture, use, sell or import patented drugs without authorization granted by patent owner as follows: ● Any person who uses, promises to sell, sells or imports any patented product or product directly obtained in accordance with the patented methods after such product is sold by the patent owner or by its licensed entity or individual; 45 ● Any person who has manufactured an identical product, has used an identical method or has made necessary preparations for manufacture or use prior to the date of patent application continues to manufacture such product or use such method only within the original scope; ● Any foreign transportation facility that temporarily passes through the territory, territorial waters or territorial airspace of China uses the relevant patents in its devices and installations for its own needs in accordance with any agreement concluded between China and that country to which the foreign transportation facility belongs, or any international treaty to which both countries are party, or on the basis of the principle of reciprocity; ● Any person who uses the relevant patents solely for the purposes of scientific research and experimentation; or ● Any person who manufactures, uses or imports patented drugs or patented medical equipment for the purpose of providing information required for administrative approval, or manufactures, uses or imports patented drugs or patented medical equipment for the abovementioned person.
None of following circumstances are deemed an infringement of the patent rights, and any person may manufacture, use, sell or import patented drugs without authorization granted by patent owner as follows: ● Any person who uses, promises to sell, sells or imports any patented product or product directly obtained in accordance with the patented methods after such product is sold by the patent owner or by its licensed entity or individual; ● Any person who has manufactured an identical product, has used an identical method or has made necessary preparations for manufacture or use prior to the date of patent application continues to manufacture such product or use such method only within the original scope; ● Any foreign transportation facility that temporarily passes through the territory, territorial waters or territorial airspace of China uses the relevant patents in its devices and installations for its own needs in accordance with any agreement concluded between China and that country to which the foreign transportation facility belongs, or any international treaty to which both countries are party, or on the basis of the principle of reciprocity; ● Any person who uses the relevant patents solely for the purposes of scientific research and experimentation; or ● Any person who manufactures, uses or imports patented drugs or patented medical equipment for the purpose of providing information required for administrative approval, or manufactures or imports patented drugs or patented medical equipment for the abovementioned person. 46 However, even if patented drugs are utilized on the ground of exemptions for unlicensed manufacture, use, sell or import of patented drugs prescribed in Patent Law of the PRC, such patented drugs cannot be manufactured, used, sold or imported for any commercial purposes without authorization granted by the patent owner.
Hengrui will receive a pre-determined percentage of the net sales in each quarter. Wanchunbulin received an upfront payment of RMB 200 million (approximately $31 million), and will receive regulatory and sales milestones of up to RMB 1.1 billion (approximately $171 million). Hengrui will be responsible for all costs associated with commercialization of Plinabulin in the Greater China markets.
Hengrui will receive a pre-determined percentage of the net sales in each quarter. Wanchunbulin received an upfront payment of RMB 200 million (approximately $28.6 million), and will receive regulatory and sales milestones of up to RMB 1.1 billion (approximately $157.3 million). Hengrui will be responsible for all costs associated with commercialization of Plinabulin in the Greater China markets.
In November 2016, the SCNPC promulgated the Cyber Security Law, which became effective in June 2017. The Cyber Security Law requires network operators to perform certain functions related to cybersecurity protection and strengthen the network information management.
In November 2016, the SCNPC promulgated the Cyber Security Law, which became effective in June 2017 and was amended in October 2025. The Cyber Security Law requires network operators to perform certain functions related to cybersecurity protection and strengthen the network information management.
Plinabulin + Pegfilgrastim (n=111) Pegfilgrastim (n=110) p value Primary Endpoint: Rate of prevention of grade 4 neutropenia 31.5% 13.6% p=0.0015 Key Secondary Endpoints: Mean ANC Nadir 0.538 x 10^9 cells/L 0.538 x 10^9 cells/L p=0.0002 Rate of prevention of grade 3 neutropenia 20.7% 4.6% p=0.003 We had previously submitted an NDA to each of the FDA and the NMPA based on positive results in our PROTECTIVE-2 Study, supported by five additional clinical studies as described above, for the use of Plinabulin in combination with G-CSF for the prevention of CIN.
Results of comparison of CIN prevention benefit between combo arm (Plinabulin+pegfilgrastim, n=111) and peg arm (pegfilgrastim alone, n=110) are detailed below. 14 Plinabulin + Pegfilgrastim (n=111) Pegfilgrastim (n=110) p value Primary Endpoint: Rate of prevention of grade 4 neutropenia 31.5% 13.6% p=0.0015 Key Secondary Endpoints: Mean ANC Nadir 0.538 x 10^9 cells/L 0.538 x 10^9 cells/L p=0.0002 Rate of prevention of grade 3 neutropenia 20.7% 4.6% p=0.003 We had previously submitted an NDA to each of the FDA and the NMPA based on positive results in our PROTECTIVE-2 Study, supported by five additional clinical studies as described above, for the use of Plinabulin in combination with G-CSF for the prevention of CIN.
For the non-squamous subset patients, median OS (mOS) in Plinabulin/docetaxel arm was 11.4 months vs. 8.8 months in the docetaxel arm, with mOS benefit of 2.6 months. ● Improved OS benefit with more cycles of treatment (≥ 4, 6, 8, 10, or 12 cycles): for patients who used at least 4 cycles of treatment, OS HR=0.64, p=0.0027, with mOS benefit of 4.8 months (Plinabulin/docetaxel arm n=133; docetaxel arm n=127). 5 ● Plinabulin/docetaxel combination is well-tolerated: Treatment-emergent adverse-events occurred in 273/274 (99·6%) of patients in the Plinabulin group and 276/278 (99·3%) in the control group.
For the Plinabulin mechanism targeted non-squamous subset patients, median OS (mOS) in Plinabulin/docetaxel arm was 11.4 months vs. 8.8 months in the docetaxel arm, with mOS benefit of 2.6 months (OS HR 0.72, p=0.0078): mOS 11.2 months in DP (n=154) vs. mOS 8.8 months in D (n=178). ● Improved OS benefit with more cycles of treatment (≥ 4, 6, 8, 10, or 12 cycles): for patients who used at least 4 cycles of treatment, OS HR=0.64, p=0.0027, with mOS benefit of 4.8 months (Plinabulin/docetaxel arm n=133; docetaxel arm n=127). ● Plinabulin/docetaxel combination is well-tolerated: Treatment-emergent adverse-events occurred in 273/274 (99·6%) of patients in the Plinabulin group and 276/278 (99·3%) in the control group.
Regulation of Dividend Distribution The principal laws, rules and regulations governing dividend distribution by FIEs in China are the Company Law of the PRC, which was most recently amended on December 29, 2023 and will become effective on July 1, 2024, the Foreign Investment Law, which took effect on January 1, 2020, and its implementation regulations, which took effect on January 1, 2020.
Linqing Jia. 50 Regulation of Dividend Distribution The principal laws, rules and regulations governing dividend distribution by FIEs in China are the Company Law of the PRC, which was most recently amended on December 29, 2023 and became effective on July 1, 2024, the Foreign Investment Law, which took effect on January 1, 2020, and its implementation regulations, which took effect on January 1, 2020.
On August 24, 2023, the NMPA issued the revised draft Protocol for Review and Approval of Conditional Approval of Drugs Marketing Applications (Trial) and the policy interpretations for such protocol for public comments.
On August 24, 2023, the NMPA issued the revised draft Protocol for Review and Approval of Conditional Approval of Drugs Marketing Applications (Trial) and the policy interpretations for such protocol for public comments, and on July 7, 2025, the NMPA issued the revised draft Protocol for Review and Approval of Conditional Approval of Drugs Marketing Applications (Trial) and the policy interpretations for such protocol for public comments again.
Court of Appeals for the Fifth Circuit held, among other things, that the Affordable Care Act’s requirement that group health plans and health insurance issuers cover certain preventative services without cost-sharing is unconstitutional. The parties have petitioned to appeal the case to the U.S. Supreme Court, which granted certiorari in January 2025.
Court of Appeals for the Fifth Circuit held, among other things, that the Affordable Care Act’s requirement that group health plans and health insurance issuers cover certain preventative services without cost-sharing is unconstitutional. The parties appealed the case to the U.S. Supreme Court, which granted certiorari in January 2025 and upheld the constitutionality of the requirement in June 2025.
The RMB converted from relevant foreign exchange will be kept in a designated account, and if a domestic enterprise needs to make further payment from such account, it still must provide supporting documents and go through the review process with the banks.
The RMB converted from relevant foreign exchange will be kept in a designated account, and if a domestic enterprise needs to make further payment from such account, it still must provide supporting documents for the use of funds from the previous foreign exchange settlement and go through the review process with the banks.
Phase 3 refers to clinical trials undertaken to confirm the therapeutic effectiveness of a drug. Phase 3 is used to further verify the drug’s therapeutic effectiveness and safety on patients with target indication(s), to evaluate overall benefit-risk relationships of the drug, and ultimately to provide sufficient evidence for the review of drug registration application.
Phase 3 is used to further verify the drug’s therapeutic effectiveness and safety on patients with target indication(s), to evaluate overall benefit-risk relationships of the drug, and ultimately to provide sufficient evidence for the review of drug registration application.
Preliminary data was presented in August 2022 at the 19th International Myeloma Society Annual Meeting, showing that Plinabulin is well tolerated and only one out of the 10 patients enrolled (10%) had non-engraftment related neutropenic fevers or febrile neutropenia (FN) with Plinabulin and pegfilgrastim, compared to a historical number of 60% of FN with standard of care. 13 Enrollment of this Phase 1 study was completed in March 2023.
Preliminary data was presented in August 2022 at the 19th International Myeloma Society Annual Meeting, showing that Plinabulin is well tolerated and only one out of the 10 patients enrolled (10%) had non-engraftment related neutropenic fevers or febrile neutropenia (FN) with Plinabulin and pegfilgrastim, compared to a historical number of 60% of FN with standard of care.
These U.S. patents were scheduled to expire between 2025 and 2039, excluding any potential patent term restorations. The patent portfolio also contained counterpart patents granted in 32 foreign jurisdictions including Japan, South Korea, China, European countries, and other countries. The term of individual patents may vary based on the countries in which they are obtained.
These U.S. patents were scheduled to expire between 2033 and 2042, excluding any potential patent term restorations. The patent portfolio also contained patents granted in 34 foreign jurisdictions including Japan, South Korea, China, European countries, and other countries. 20 The term of individual patents may vary based on the countries in which they are obtained.
As of the date of this Annual Report on Form 10-K, the BYSI Entities own approximately 40.12% of the outstanding equity interest in SEED, and are expected to own approximately 28.02% and 14.37% of the outstanding equity interest in SEED after the second and third closings, respectively, in each case calculated on an as-converted basis (excluding any shares that may be reserved under an employee stock ownership plan, or similar arrangement), and assuming there is no other change to SEED’s share capital prior to such closings.
As of the date of this Annual Report on Form 10-K, the BYSI Entities own approximately 38.03% of the outstanding equity interest in SEED, and are expected to own approximately 26.56% and 13.62% of the outstanding equity interest in SEED after the second and third closings, respectively, in each case calculated on an as-converted basis (excluding any shares that may be reserved under an employee stock ownership plan, or similar arrangement), and assuming there is no other change to SEED’s share capital prior to such closings.
The DUBLIN-3 study enrolled 559 patients at 58 clinical sites globally and the final results from the study showed that the Plinabulin and docetaxel combination had statistically significant and clinically meaningful overall survival benefit compared to standard of care docetaxel alone.
The DUBLIN-3 study enrolled 559 patients at 58 clinical sites globally and the final results from the study showed that the Plinabulin and docetaxel combination had statistically significant and clinically meaningful overall survival benefit compared to standard of care (SOC) docetaxel alone with doubling 2-year and 3-year OS rate.
A Category 1 drug is a new drug that has never been marketed in any country. 32 Pursuant to the revised Provisions for Drug Registration, during the clinical trial for new drugs used for severe life-threatening diseases or diseases which seriously impact the quality of life and for which there is no other effective treatment approach or there is adequate evidence to prove that said new drugs have obvious clinical advantages over existing treatment approach(es), the applicant may request for application of breakthrough therapeutic drug procedure.
Pursuant to the revised Provisions for Drug Registration, during the clinical trial for new drugs used for severe life-threatening diseases or diseases which seriously impact the quality of life and for which there is no other effective treatment approach or there is adequate evidence to prove that said new drugs have obvious clinical advantages over existing treatment approach(es), the applicant may request for application of breakthrough therapeutic drug procedure.
And 82% relative reduction in grade 4 neutropenia in Cycle 1 Day 8 (p ● Consistent OS benefit in 24-month follow-up after the database lock: OS HR=0.81 in the ITT population, with better OS benefit in the non-squamous subset (OS HR=0.72, p=0.0078).
Durable anti-cancer benefits in doubling 24-months and 36-months OS rates. And 82% relative reduction in grade 4 neutropenia in Cycle 1 Day 8 (p ● Consistent OS benefit in 24-month follow-up after the database lock: OS HR=0.81 in the ITT population, with better OS benefit in the non-squamous subset (OS HR=0.72, p=0.0078).
Of these, 24 were engaged in full-time research and development and laboratory operations and 16 were engaged in full-time general and administrative functions. As of February 28, 2025, 13 of our employees were located in China and 27 were located in the U.S.
Of these, 25 were engaged in full-time research and development and laboratory operations and 19 were engaged in full-time general and administrative functions. As of February 27, 2026, 16 of our employees were located in China and 28 were located in the U.S.
In January 2025, we entered into definitive agreements to sell a portion of our Series A-1 Preferred Shares of SEED for $35.4 million, or $4.25 per share, to certain third-party investors in three installments. The first closing of approximately $7.35 million occurred in February 2025.
Certain Relationships and Related Transactions, and Director Independence— Purchase of SEED’s Preferred Shares.” In January 2025, we entered into definitive agreements to sell a portion of our Series A-1 Preferred Shares of SEED for $35.4 million, or $4.25 per share, to certain third-party investors in three installments. The first closing of approximately $7.35 million occurred in February 2025.
Although we cannot predict the full effect on our business of the implementation of existing legislation or the enactment of additional legislation pursuant to healthcare and other legislative reform, we believe that legislation or regulations that would reduce reimbursement for, or restrict coverage of, our products could adversely affect how much or under what circumstances healthcare providers will prescribe or administer our product candidates if we gain approval for any of them.
Although we cannot predict the full effect on our business of the implementation of existing legislation or the enactment of additional legislation pursuant to healthcare and other legislative reform, we believe that legislation or regulations that would reduce reimbursement for, or restrict coverage of, our products could adversely affect how much or under what circumstances healthcare providers will prescribe or administer our product candidates if we gain approval for any of them. 31 Chinese Regulation In China, we operate in an increasingly complex legal and regulatory environment.
The goal of these studies is to advance Plinabulin in clinical trials to investigate its therapeutic potential immuno-oncology agent in multiple cancers, especially in PD-1/PD-L1 antibody progressed patients, which we believe represent high unmet medical needs. ● Advance Plinabulin through global clinical trials and obtain regulatory approvals in select geographies.
The goal of these studies is to advance Plinabulin in clinical trials to investigate its therapeutic potential immuno-oncology agent in multiple cancers, especially in PD-1/PD-L1 antibody progressed patients, which we believe represent high unmet medical needs. 18 ● Advance Plinabulin through global clinical trials and obtain regulatory approvals in select geographies in second- and third-line non-squamous EGFR wild type NSCLC.
In October 2020, the Standing Committee of the National People’s Congress of the PRC, or the SCNPC, promulgated the China Biosecurity Law, which became effective on April 15, 2021 and was amended on April 26, 2024.
In October 2020, the Standing Committee of the National People’s Congress of the PRC, or the SCNPC, promulgated the China Biosecurity Law, which became effective on April 15, 2021 and was amended on April 26, 2024. The China Biosecurity Law reaffirms the regulatory requirements stipulated by the HGR Regulation.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIn response to the SEC’s July 30, 2021 statement, the CSRC announced on August 1, 2021, that “it is our belief that Chinese and U.S. regulators shall continue to enhance communication with the principle of mutual respect and cooperation, and properly address the issues related to the supervision of China-based companies listed in the U.S. so as to form stable policy expectations and create benign rules framework for the market.” While the CSRC will continue to communicate “closely with relevant departments to further coordinate and handle the relationships among investors, and relevant authorities and to further promote transparency and certainty of policies and implementing measures,” it emphasized that it “has always been open to companies’ choices to list their securities on international or domestic markets in compliance with relevant laws and regulations.” If any new legislation, executive orders, tariffs, laws and/or regulations are implemented, if existing trade agreements are renegotiated, if the U.S. or Chinese governments take retaliatory actions due to the recent U.S.-China tension or if the Chinese government exerts more oversight and control over securities offerings that are conducted in the United States, such changes could have an adverse effect on our business, financial condition and results of operations, our ability to raise capital and the market price of our ordinary shares.
Biggest changeIf any new legislation, executive orders, tariffs, laws and/or regulations are implemented, if existing trade agreements are renegotiated, if the U.S. or Chinese governments take retaliatory actions due to the recent U.S.-China tension or if the Chinese government exerts more oversight and control over securities offerings that are conducted in the United States, such changes could have an adverse effect on our business, financial condition and results of operations, our ability to raise capital and the market price of our ordinary shares. 104 There are uncertainties regarding the interpretation and enforcement of Chinese laws, rules and regulations.
In the Complete Response Letter, the FDA indicated the results of the single registrational trial (PROTECTIVE-2 Phase 3) were not sufficiently robust to demonstrate benefit and that a second well-controlled trial would be required to satisfy the substantial evidence requirement to support the CIN indication.
In the Complete Response Letter, the FDA indicated the results of the single registrational trial (PROTECTIVE-2 Phase 3) were not sufficiently robust to demonstrate benefit and that a second well-controlled trial would be required to satisfy the substantial evidence requirement to support the CIN indication.
The Overseas Listing Trial Measures comprehensively improves and reforms the existing regulatory regime for overseas offering and listing of PRC domestic companies’ securities and regulates both direct and indirect overseas offering and listing of PRC domestic companies’ securities by adopting a filing-based regulatory regime.
The Overseas Listing Trial Measures comprehensively improves and reforms the existing regulatory regime for overseas offering and listing of PRC domestic companies’ securities and regulates both direct and indirect overseas offering and listing of PRC domestic companies’ securities by adopting a filing-based regulatory regime.
Delays in clinical trials, regulatory approvals or rejections of applications for regulatory approval in the U.S., China, Europe or other markets may result from many factors, including: ● our inability to obtain sufficient funds required to conduct or continue a clinical trial, including lack of funding due to unforeseen costs or business decisions; ● failure to reach agreement with, or inability to comply with conditions imposed by, the FDA, NMPA, EMA or other regulators regarding the scope or design of our clinical trials or other aspects of the regulatory approval process; ● clinical holds, other regulatory objections or conditions to commencing or continuing a clinical trial or the inability to obtain regulatory approval to commence a clinical trial in countries that require such approvals; ● our inability to reach agreements on acceptable terms with prospective CROs with the requisite experience and expertise, and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; ● our inability to obtain approval from IRBs or ethics committees to conduct clinical trials at their respective sites; ● our inability to enroll in a clinical trial a sufficient number of patients who meet the applicable inclusion and exclusion criteria of the clinical trial; ● our inability to retain a sufficient number of patients in a clinical trial; ● our inability to conduct a clinical trial in accordance with regulatory requirements or our clinical protocols; 68 ● clinical sites and investigators deviating from trial protocol, failing to conduct the trial in accordance with regulatory requirements, withdrawing from or dropping out of a trial, or becoming ineligible to participate in a trial; ● inability to identify and maintain a sufficient number of trial sites, many of which may already be engaged in other clinical trial programs, including some that may be for the same indication; ● delay or failure in adding new clinical trial sites; ● failure of our CROs or third-party clinical trial managers to comply with legal and regulatory requirements, satisfy their contractual duties or meet expected deadlines; ● manufacturing issues, including delays or other problems with manufacturing, quality issues or timely obtaining from third parties sufficient quantities of a product candidate for use in a clinical trial; ● difficulty in maintaining contact with patients after treatment, resulting in incomplete data; ● ambiguous or negative interim or final results, or results that are inconsistent with earlier results; ● unfavorable or inconclusive results of clinical trials or supportive studies in animals; ● regulatory requests for additional analyses, reports, data, or studies in animals or clinical trials, or regulatory questions regarding the interpretation of data, or regulatory requests for re-filing of NDAs; ● feedback from the FDA, NMPA, EMA, an IRB, data safety monitoring boards, or comparable entities, or results from earlier stage or concurrent studies in animals or clinical trials, regarding our product candidates or other drug products, including which might require modification of a trial protocol or suspension or termination of a clinical trial; ● unacceptable benefit-risk profile or unforeseen safety issues or adverse side effects in our product candidates or other drug products; ● a decision by the FDA, NMPA, EMA, an IRB, comparable entities, or us, or recommendation by a data safety monitoring board or comparable regulatory entity, to suspend or terminate clinical trials at any time for safety issues or for any other reason; and ● failure to demonstrate a benefit from using a drug.
Delays in clinical trials, regulatory approvals or rejections of applications for regulatory approval in the U.S., China, Europe or other markets may result from many factors, including: ● our inability to obtain sufficient funds required to conduct or continue a clinical trial, including lack of funding due to unforeseen costs or business decisions; ● failure to reach agreement with, or inability to comply with conditions imposed by, the FDA, NMPA, EMA or other regulators regarding the scope or design of our clinical trials or other aspects of the regulatory approval process; ● clinical holds, other regulatory objections or conditions to commencing or continuing a clinical trial or the inability to obtain regulatory approval to commence a clinical trial in countries that require such approvals; ● our inability to reach agreements on acceptable terms with prospective CROs with the requisite experience and expertise, and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; ● our inability to obtain approval from IRBs or ethics committees to conduct clinical trials at their respective sites; ● our inability to enroll in a clinical trial a sufficient number of patients who meet the applicable inclusion and exclusion criteria of the clinical trial; ● our inability to retain a sufficient number of patients in a clinical trial; ● our inability to conduct a clinical trial in accordance with regulatory requirements or our clinical protocols; ● clinical sites and investigators deviating from trial protocol, failing to conduct the trial in accordance with regulatory requirements, withdrawing from or dropping out of a trial, or becoming ineligible to participate in a trial; ● inability to identify and maintain a sufficient number of trial sites, many of which may already be engaged in other clinical trial programs, including some that may be for the same indication; ● delay or failure in adding new clinical trial sites; ● failure of our CROs or third-party clinical trial managers to comply with legal and regulatory requirements, satisfy their contractual duties or meet expected deadlines; ● manufacturing issues, including delays or other problems with manufacturing, quality issues or timely obtaining from third parties sufficient quantities of a product candidate for use in a clinical trial; ● difficulty in maintaining contact with patients after treatment, resulting in incomplete data; ● ambiguous or negative interim or final results, or results that are inconsistent with earlier results; ● unfavorable or inconclusive results of clinical trials or supportive studies in animals; ● regulatory requests for additional analyses, reports, data, or studies in animals or clinical trials, or regulatory questions regarding the interpretation of data, or regulatory requests for re-filing of NDAs; ● feedback from the FDA, NMPA, EMA, an IRB, data safety monitoring boards, or comparable entities, or results from earlier stage or concurrent studies in animals or clinical trials, regarding our product candidates or other drug products, including which might require modification of a trial protocol or suspension or termination of a clinical trial; 69 ● unacceptable benefit-risk profile or unforeseen safety issues or adverse side effects in our product candidates or other drug products; ● a decision by the FDA, NMPA, EMA, an IRB, comparable entities, or us, or recommendation by a data safety monitoring board or comparable regulatory entity, to suspend or terminate clinical trials at any time for safety issues or for any other reason; and ● failure to demonstrate a benefit from using a drug.
The success of Plinabulin and any other potential product candidates will depend on many factors, including: ● successful enrollment in, and completion of, studies in animals and clinical trials; ● third parties’ ability in conducting our clinical trials safely, efficiently and according to the agreed protocol; ● timely receipt of regulatory approvals from the FDA, NMPA, EMA and other comparable regulatory authorities for our product candidates; ● our ability to obtain regulatory approvals for the target indications; ● establishing commercial manufacturing capabilities by making arrangements with third-party manufacturers; ● launching commercial sales of our product candidates, if and when approved; ● ensuring we do not infringe, misappropriate or otherwise violate the patent, trade secret or other intellectual property rights of third parties; ● obtaining acceptance of our product candidates by doctors and patients; 61 ● obtaining reimbursement from third-party payors for our product candidates, if and when approved; ● our ability to compete against other product candidates and drugs; ● maintaining an acceptable safety profile for our product candidates following regulatory approval, if and when received; and ● obtaining and maintaining patent, trade secret and other intellectual property protection and regulatory exclusivity.
The success of Plinabulin and any other potential product candidates will depend on many factors, including: ● successful enrollment in, and completion of, studies in animals and clinical trials; ● third parties’ ability in conducting our clinical trials safely, efficiently and according to the agreed protocol; ● timely receipt of regulatory approvals from the FDA, NMPA, EMA and other comparable regulatory authorities for our product candidates; ● our ability to obtain regulatory approvals for the target indications; ● establishing commercial manufacturing capabilities by making arrangements with third-party manufacturers; ● launching commercial sales of our product candidates, if and when approved; ● ensuring we do not infringe, misappropriate or otherwise violate the patent, trade secret or other intellectual property rights of third parties; ● obtaining acceptance of our product candidates by doctors and patients; ● obtaining reimbursement from third-party payors for our product candidates, if and when approved; ● our ability to compete against other product candidates and drugs; ● maintaining an acceptable safety profile for our product candidates following regulatory approval, if and when received; and ● obtaining and maintaining patent, trade secret and other intellectual property protection and regulatory exclusivity.
Risks Related to Obtaining Regulatory Approval for Our Product Candidates ● The regulatory approval processes of the FDA, the NMPA, which is the successor to the CFDA, the EMA, and other comparable regulatory authorities are lengthy, time consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our current product candidates or any future product candidates we may develop, our business will be substantially harmed. ● Regulatory approval may be substantially delayed or may not be obtained for one or all of our product candidates or target indications if regulatory authorities require additional time or studies to assess the safety or efficacy of our product candidates. ● Changes in funding or staffing for the FDA and other government agencies could hinder new products and services from being developed or commercialized in a timely manner, which could negatively impact our business. ● The results from our Phase 2/3 trials in CIN (PROTECTIVE-1 and PROTECTIVE-2) and our Phase 3 trial in advanced NSCLC (DUBLIN-3) may not be sufficiently robust to support the submission or approval of marketing applications for our product candidates.
Risks Related to Obtaining Regulatory Approval for Our Product Candidates ● The regulatory approval processes of the FDA, the NMPA, which is the successor to the CFDA, the EMA, and other comparable regulatory authorities are lengthy, time consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our current product candidates or any future product candidates we may develop, our business will be substantially harmed. ● Regulatory approval may be substantially delayed or may not be obtained for one or all of our product candidates or target indications if regulatory authorities require additional time or studies to assess the safety or efficacy of our product candidates. 56 ● Changes in funding or staffing for the FDA and other government agencies could hinder new products and services from being developed or commercialized in a timely manner, which could negatively impact our business. ● The results from our Phase 2/3 trials in CIN (PROTECTIVE-1 and PROTECTIVE-2) and our Phase 3 trial in advanced NSCLC (DUBLIN-3) may not be sufficiently robust to support the submission or approval of marketing applications for our product candidates.
Our future funding requirements will depend on many factors, including, but not limited to: ● the costs of our current, planned and potential future clinical trials; ● the outcome, timing and cost of regulatory approvals by the FDA, NMPA, EMA, and comparable regulatory authorities, including any additional studies we may be required to perform; ● the cost of commercialization of our product candidates; ● the cost and timing of completion of commercial-scale outsourced manufacturing activities; ● the amount of profit we earn from product candidates that we succeed in commercializing, if any; 59 ● the cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; ● the expenses associated with any potential future collaborations, licensing or other arrangements that we may establish; ● cash requirements of any future acquisitions; ● the costs of operating as a public company; ● the time and cost necessary to respond to technological and market developments; and ● the number and characteristics of product candidates that we may develop and expenses associated with that development.
Our future funding requirements will depend on many factors, including, but not limited to: ● the costs of our current, planned and potential future clinical trials; ● the outcome, timing and cost of regulatory approvals by the FDA, NMPA, EMA, and comparable regulatory authorities, including any additional studies we may be required to perform; ● the cost of commercialization of our product candidates; ● the cost and timing of completion of commercial-scale outsourced manufacturing activities; ● the amount of profit we earn from product candidates that we succeed in commercializing, if any; ● the cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; ● the expenses associated with any potential future collaborations, licensing or other arrangements that we may establish; ● cash requirements of any future acquisitions; ● the costs of operating as a public company; ● the time and cost necessary to respond to technological and market developments; and ● the number and characteristics of product candidates that we may develop and expenses associated with that development.
In addition to market and industry factors, the price and trading volume for our ordinary shares may be highly volatile for specific business reasons, including: ● announcements of regulatory approval or a complete response letter, or specific label indications or patient populations for the use of our product candidates, or changes or delays in the regulatory review process; ● announcements of therapeutic innovations or new products by us or our competitors; ● adverse actions taken by regulatory agencies with respect to our clinical trials, manufacturing supply chain or sales and marketing activities; ● any adverse changes to our relationship with manufacturers or suppliers; ● the results of our testing and clinical trials; ● the results of our efforts to acquire or license additional product candidates; ● variations in the level of expenses related to our existing product candidates or preclinical studies and clinical trials; ● any intellectual property infringement actions in which we may become involved; ● announcements concerning our competitors or the pharmaceutical industry in general; ● achievement of expected product sales and profitability; ● manufacturing, supply or distribution shortages; ● variations in our results of operations; ● announcements about our earnings that are not in line with analyst expectations; ● publication of operating or industry metrics by third parties, including government statistical agencies, that differ from expectations of industry or financial analysts; ● research reports and changes in financial estimates by securities research analysts; ● announcements made by us or our competitors of new product and service offerings, acquisitions, sales, strategic relationships, joint ventures or capital commitments; ● press reports, whether or not true, about our business; ● additions to, or departures of, our management; ● fluctuations of exchange rates between the RMB and the U.S. dollar; ● release or expiry of lock-up or other transfer restrictions on our outstanding ordinary shares; ● sales or perceived potential sales of additional ordinary shares; ● sales of our ordinary shares by us, our executive officers and directors or our shareholders in the future; 118 ● general economic and market conditions and overall fluctuations in the U.S. equity markets; ● changes in accounting principles; and ● changes or developments in the Chinese or global regulatory environment.
In addition to market and industry factors, the price and trading volume for our ordinary shares may be highly volatile for specific business reasons, including: 115 ● announcements of regulatory approval or a complete response letter, or specific label indications or patient populations for the use of our product candidates, or changes or delays in the regulatory review process; ● announcements of therapeutic innovations or new products by us or our competitors; ● adverse actions taken by regulatory agencies with respect to our clinical trials, manufacturing supply chain or sales and marketing activities; ● any adverse changes to our relationship with manufacturers or suppliers; ● the results of our testing and clinical trials; ● the results of our efforts to acquire or license additional product candidates; ● variations in the level of expenses related to our existing product candidates or preclinical studies and clinical trials; ● any intellectual property infringement actions in which we may become involved; ● announcements concerning our competitors or the pharmaceutical industry in general; ● achievement of expected product sales and profitability; ● manufacturing, supply or distribution shortages; ● variations in our results of operations; ● announcements about our earnings that are not in line with analyst expectations; ● publication of operating or industry metrics by third parties, including government statistical agencies, that differ from expectations of industry or financial analysts; ● research reports and changes in financial estimates by securities research analysts; ● announcements made by us or our competitors of new product and service offerings, acquisitions, sales, strategic relationships, joint ventures or capital commitments; ● press reports, whether or not true, about our business; ● additions to, or departures of, our management; ● fluctuations of exchange rates between the RMB and the U.S. dollar; ● release or expiry of lock-up or other transfer restrictions on our outstanding ordinary shares; ● sales or perceived potential sales of additional ordinary shares; ● sales of our ordinary shares by us, our executive officers and directors or our shareholders in the future; ● general economic and market conditions and overall fluctuations in the U.S. equity markets; ● changes in accounting principles; and ● changes or developments in the Chinese or global regulatory environment.
For example, the results of Study 101 were not statistically significant; ● failure to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; ● disagreement with regulators regarding our interpretation of data from studies in animals or clinical trials; ● insufficiency of data collected from clinical trials of our product candidates to support the submission and filing of an NDA, or other submission or to obtain regulatory approval; 66 ● the FDA, NMPA, EMA or a comparable regulatory authority’s finding of deficiencies related to the manufacturing processes or facilities of third-party manufacturers with whom we contract for clinical and commercial supplies; and ● changes in approval policies or regulations that render our preclinical studies and clinical data insufficient for approval.
For example, the results of Study 101 were not statistically significant; ● failure to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; ● disagreement with regulators regarding our interpretation of data from studies in animals or clinical trials; ● insufficiency of data collected from clinical trials of our product candidates to support the submission and filing of an NDA, or other submission or to obtain regulatory approval; ● the FDA, NMPA, EMA or a comparable regulatory authority’s finding of deficiencies related to the manufacturing processes or facilities of third-party manufacturers with whom we contract for clinical and commercial supplies; and ● changes in approval policies or regulations that render our preclinical studies and clinical data insufficient for approval.
If we are unable to commercialize Plinabulin or any of our other product candidates, or experience significant delays in doing so, our business will be materially harmed. 55 ● If the FDA does not approve our NDA for Plinabulin in combination with G-CSF for the prevention of CIN, or the FDA’s review or approval of our NDA for Plinabulin in such indication is significantly delayed or prolonged, or the continued development of Plinabulin in such indication is significantly delayed or terminated, our business and results of operations could be significantly adversely affected. ● All of our current clinical trials involve Plinabulin for multiple indications and we may not be successful in our efforts to identify or discover additional product candidates.
If we are unable to commercialize Plinabulin or any of our other product candidates, or experience significant delays in doing so, our business will be materially harmed. ● If the FDA does not approve our NDA for Plinabulin in combination with G-CSF for the prevention of CIN, or the FDA’s review or approval of our NDA for Plinabulin in such indication is significantly delayed or prolonged, or the continued development of Plinabulin in such indication is significantly delayed or terminated, our business and results of operations could be significantly adversely affected. ● All of our current clinical trials involve Plinabulin for multiple indications and we may not be successful in our efforts to identify or discover additional product candidates.
Other potential consequences include, among other things: ● restrictions on the marketing or manufacturing of our drugs, withdrawal of the product from the market, or voluntary or mandatory product recalls; ● fines, untitled or warning letters, or holds on clinical trials; 72 ● refusal by the FDA to approve pending applications or supplements to approved applications filed by us or suspension or revocation of license approvals; ● product seizure or detention, or refusal to permit the import or export of our product candidates; and ● injunctions or the imposition of civil or criminal penalties.
Other potential consequences include, among other things: ● restrictions on the marketing or manufacturing of our drugs, withdrawal of the product from the market, or voluntary or mandatory product recalls; ● fines, untitled or warning letters, or holds on clinical trials; ● refusal by the FDA to approve pending applications or supplements to approved applications filed by us or suspension or revocation of license approvals; ● product seizure or detention, or refusal to permit the import or export of our product candidates; and ● injunctions or the imposition of civil or criminal penalties.
In any of these cases, such a license may not be available on commercially reasonable terms or at all. Third parties who bring successful claims against us for infringement of their intellectual property rights may obtain injunctive or other equitable relief, which could prevent us from developing and commercializing one or more of our product candidates.
In any of these cases, such a license may not be available on commercially reasonable terms or at all. 86 Third parties who bring successful claims against us for infringement of their intellectual property rights may obtain injunctive or other equitable relief, which could prevent us from developing and commercializing one or more of our product candidates.
Risks Related to Our Ordinary Shares ● The trading prices of our ordinary shares are likely to be volatile, which could result in substantial losses to you. 57 ● Sales or the availability for sales of substantial amounts of our ordinary shares in the public market could cause the price of our ordinary shares to decline significantly. ● Because we do not expect to pay dividends in the foreseeable future, you must rely on price appreciation of the ordinary shares for return on your investment.
Risks Related to Our Ordinary Shares ● The trading prices of our ordinary shares are likely to be volatile, which could result in substantial losses to you. ● Sales or the availability for sales of substantial amounts of our ordinary shares in the public market could cause the price of our ordinary shares to decline significantly. ● Because we do not expect to pay dividends in the foreseeable future, you must rely on price appreciation of the ordinary shares for return on your investment.
Moreover, any negative news about the proceedings against these audit firms may cause investor uncertainty regarding China-based, U.S.-listed companies and the market price of our ordinary shares may be adversely affected. 111 In the past, we had engaged certain China affiliates of one of the “big four” accounting firms as our independent registered public accounting firm.
Moreover, any negative news about the proceedings against these audit firms may cause investor uncertainty regarding China-based, U.S.-listed companies and the market price of our ordinary shares may be adversely affected. In the past, we had engaged certain China affiliates of one of the “big four” accounting firms as our independent registered public accounting firm.
If we are unable to obtain and maintain patent protection for our technology and drugs, our competitors could develop and commercialize technology and drugs similar or identical to ours, and our ability to successfully commercialize our technology and drugs may be adversely affected. 56 ● We may not be able to protect our intellectual property rights throughout the world. ● We may become involved in lawsuits to protect or enforce our intellectual property rights, which could be expensive, time consuming and unsuccessful.
If we are unable to obtain and maintain patent protection for our technology and drugs, our competitors could develop and commercialize technology and drugs similar or identical to ours, and our ability to successfully commercialize our technology and drugs may be adversely affected. ● We may not be able to protect our intellectual property rights throughout the world. ● We may become involved in lawsuits to protect or enforce our intellectual property rights, which could be expensive, time consuming and unsuccessful.
The inability for an overseas securities regulator to directly conduct investigation or evidence collection activities within China may further increase difficulties faced by you in protecting your interests. 103 The pharmaceutical industry in China is highly regulated and such regulations are subject to change which may affect approval and commercialization of our drugs.
The inability for an overseas securities regulator to directly conduct investigation or evidence collection activities within China may further increase difficulties faced by you in protecting your interests. The pharmaceutical industry in China is highly regulated and such regulations are subject to change which may affect approval and commercialization of our drugs.
We may experience difficulties enrolling and retaining appropriate patients in our clinical trials for a variety of reasons, including: ● emergence of a pandemic or other widespread health emergencies or concerns over the possibility of such an emergency, including the COVID-19 pandemic, which, in particular, affected our enrollment of patients in Ukraine and China, and enrollment was shifted to other clinical sites.
We may experience difficulties enrolling and retaining appropriate patients in our clinical trials for a variety of reasons, including: 63 ● emergence of a pandemic or other widespread health emergencies or concerns over the possibility of such an emergency, including the COVID-19 pandemic, which, in particular, affected our enrollment of patients in Ukraine and China, and enrollment was shifted to other clinical sites.
We may not be able to protect our intellectual property rights throughout the world. Filing, prosecuting, maintaining and defending patents on product candidates in all countries throughout the world could be prohibitively expensive for us, and our intellectual property rights in some non-U.S. countries can have a different scope and strength than do those in the U.S.
We may not be able to protect our intellectual property rights throughout the world. 84 Filing, prosecuting, maintaining and defending patents on product candidates in all countries throughout the world could be prohibitively expensive for us, and our intellectual property rights in some non-U.S. countries can have a different scope and strength than do those in the U.S.
On January 10, 2024, the arbitral tribunal at China International Economic and Trade Arbitration Committee issued a final award, denying all claims made by Hengrui. 102 The outcome of any claim, litigation, arbitration or investigation, regardless of its merits, is inherently uncertain and may differ substantially from our expectations.
On January 10, 2024, the arbitral tribunal at China International Economic and Trade Arbitration Committee issued a final award, denying all claims made by Hengrui. The outcome of any claim, litigation, arbitration or investigation, regardless of its merits, is inherently uncertain and may differ substantially from our expectations.
We may not have or in the future be able to obtain adequate funding to complete the necessary steps for approval for our product candidates or any future product candidate. Studies in animals and clinical trials required to demonstrate the safety and efficacy of our product candidates are time consuming and expensive and take several years or more to complete.
We may not have or in the future be able to obtain adequate funding to complete the necessary steps for approval for our product candidates or any future product candidate. 68 Studies in animals and clinical trials required to demonstrate the safety and efficacy of our product candidates are time consuming and expensive and take several years or more to complete.
It is unclear how these or other healthcare reform measures will impact healthcare laws and regulations or our business. In the U.S., there also has been particular and increased public and governmental scrutiny of the cost of drugs and drug pricing strategies, including by the U.S. Congress and federal and state prosecutors.
It is unclear how these or other healthcare reform measures will impact healthcare laws and regulations or our business. 80 In the U.S., there also has been particular and increased public and governmental scrutiny of the cost of drugs and drug pricing strategies, including by the U.S. Congress and federal and state prosecutors.
Even if our product candidates are approved for commercial sale, we anticipate incurring significant costs associated with the commercial launch of these drugs. Even if we are able to generate revenues from the sale of any products we may develop, we may not become profitable on a sustainable basis or at all.
Even if our product candidates are approved for commercial sale, we anticipate incurring significant costs associated with the commercial launch of these drugs. 61 Even if we are able to generate revenues from the sale of any products we may develop, we may not become profitable on a sustainable basis or at all.
More generally, if we are unable to comply with the requirements of Section 404 of the Sarbanes-Oxley Act, if we are unable to assert that our internal control over financial reporting is effective, or when required in the future, if our independent registered public accounting firm is unable to express an opinion as to the effectiveness of our internal control over financial reporting, investors may lose confidence in the accuracy and completeness of our financial reports and the market price of our ordinary shares could be adversely affected, and we could become subject to investigations by the stock exchange on which our securities are listed, the SEC, or other regulatory authorities, which could require additional financial and management resources. 98 We are subject to the risk of doing business internationally.
More generally, if we are unable to comply with the requirements of Section 404 of the Sarbanes-Oxley Act, if we are unable to assert that our internal control over financial reporting is effective, or when required in the future, if our independent registered public accounting firm is unable to express an opinion as to the effectiveness of our internal control over financial reporting, investors may lose confidence in the accuracy and completeness of our financial reports and the market price of our ordinary shares could be adversely affected, and we could become subject to investigations by the stock exchange on which our securities are listed, the SEC, or other regulatory authorities, which could require additional financial and management resources. 97 We are subject to the risk of doing business internationally.
Moreover, failure to comply with the various SAFE registration requirements described above could result in liability under Chinese law for evasion of foreign exchange controls. We believe Mr. Linqing Jia, as one of our shareholders, is a Chinese resident under SAFE Circular 37. Although Mr.
Moreover, failure to comply with the various SAFE registration requirements described above could result in liability under Chinese law for evasion of foreign exchange controls. 105 We believe Mr. Linqing Jia, as one of our shareholders, is a Chinese resident under SAFE Circular 37. Although Mr.
Any uncertainties or negative publicity regarding such approval requirement could materially and adversely affect our business, prospects, financial condition, reputation, and the trading price of our ordinary shares. 117 Risks Related to Our Ordinary Shares The trading prices of our ordinary shares are likely to be volatile, which could result in substantial losses to you.
Any uncertainties or negative publicity regarding such approval requirement could materially and adversely affect our business, prospects, financial condition, reputation, and the trading price of our ordinary shares. Risks Related to Our Ordinary Shares The trading prices of our ordinary shares are likely to be volatile, which could result in substantial losses to you.
If we were to be sued, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business. 121 We may be a passive foreign investment company ( “ PFIC ” ), for U.S. federal income tax purposes, which could result in adverse U.S. federal income tax consequences for our U.S. shareholders.
If we were to be sued, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business. We may be a passive foreign investment company ( “ PFIC ” ), for U.S. federal income tax purposes, which could result in adverse U.S. federal income tax consequences for our U.S. shareholders.
Nevertheless, if we fail to maintain an effective system of internal controls, we may not be able to accurately or timely report our financial condition or results of operations, which may adversely affect investor confidence in us and, as a result, the value of our ordinary shares.
If we fail to maintain an effective system of internal controls, we may not be able to accurately or timely report our financial condition or results of operations, which may adversely affect investor confidence in us and, as a result, the value of our ordinary shares.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, some of our confidential information could be compromised by disclosure during this type of litigation. 86 We may be subject to claims challenging the inventorship of our patents and other intellectual property.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, some of our confidential information could be compromised by disclosure during this type of litigation. We may be subject to claims challenging the inventorship of our patents and other intellectual property.
Additionally, a product is misbranded under the regulations if, in an effort to promote the product, a responsible party makes a false or misleading representation with respect to a competing drug, device or biologic. We have limited intellectual property rights to Plinabulin inside China.
Additionally, a product is misbranded under the regulations if, in an effort to promote the product, a responsible party makes a false or misleading representation with respect to a competing drug, device or biologic. 94 We have limited intellectual property rights to Plinabulin inside China.
In that case, it is possible that dividends paid to us as the parent company by our Chinese subsidiaries will not be subject to Chinese withholding tax. 108 Dividends payable to our foreign investors may be subject to Chinese withholding tax and gains on the sale of our ordinary shares by our foreign investors may be subject to Chinese tax.
In that case, it is possible that dividends paid to us as the parent company by our Chinese subsidiaries will not be subject to Chinese withholding tax. Dividends payable to our foreign investors may be subject to Chinese withholding tax and gains on the sale of our ordinary shares by our foreign investors may be subject to Chinese tax.
The HFCAA states that if the SEC determines that an issuer has filed audit reports issued by a registered public accounting firm that has not been subject to inspection by the PCAOB for two consecutive years, the SEC shall prohibit the securities of the issuer from being traded on a national securities exchange or in the over the counter trading market in the United States. 110 On December 16, 2021, the PCAOB issued a report to notify the SEC of its determination that the PCAOB was unable to inspect or investigate completely registered public accounting firms headquartered in mainland China and Hong Kong, and our former auditor was subject to that determination.
The HFCAA states that if the SEC determines that an issuer has filed audit reports issued by a registered public accounting firm that has not been subject to inspection by the PCAOB for two consecutive years, the SEC shall prohibit the securities of the issuer from being traded on a national securities exchange or in the over the counter trading market in the United States. 109 On December 16, 2021, the PCAOB issued a report to notify the SEC of its determination that the PCAOB was unable to inspect or investigate completely registered public accounting firms headquartered in mainland China and Hong Kong, and our former auditor was subject to that determination.
Regardless of the merits or eventual outcome, liability claims may result in: ● decreased demand for our drugs; ● injury to our reputation; 100 ● withdrawal of clinical trial participants and inability to continue clinical trials; ● initiation of investigations by regulators; ● costs to defend the related litigation; ● a diversion of management’s time and our resources; ● substantial monetary awards to trial participants or patients; ● product recalls, withdrawals or labeling, marketing or promotional restrictions; ● loss of revenue; ● exhaustion of any available insurance and our capital resources; ● the inability to commercialize any product candidate; and ● a decline in our ordinary share price.
Regardless of the merits or eventual outcome, liability claims may result in: 99 ● decreased demand for our drugs; ● injury to our reputation; ● withdrawal of clinical trial participants and inability to continue clinical trials; ● initiation of investigations by regulators; ● costs to defend the related litigation; ● a diversion of management’s time and our resources; ● substantial monetary awards to trial participants or patients; ● product recalls, withdrawals or labeling, marketing or promotional restrictions; ● loss of revenue; ● exhaustion of any available insurance and our capital resources; ● the inability to commercialize any product candidate; and ● a decline in our ordinary share price.
Our inability to obtain additional funding when we need it could seriously harm our business. Raising additional capital may cause dilution to our shareholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.
Our inability to obtain additional funding when we need it could seriously harm our business. 60 Raising additional capital may cause dilution to our shareholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.
In addition, Cayman Islands companies may not have standing to initiate a shareholder derivative action in a federal court of the United States. 119 In addition, as shareholders of a Cayman Islands exempted company, our shareholders have no general rights under Cayman Islands law to inspect corporate records (other than the memorandum and articles of association, our register of mortgages and charges and special resolutions passed by our shareholders), or to obtain a copy of our register of members.
In addition, Cayman Islands companies may not have standing to initiate a shareholder derivative action in a federal court of the United States. 117 In addition, as shareholders of a Cayman Islands exempted company, our shareholders have no general rights under Cayman Islands law to inspect corporate records (other than the memorandum and articles of association, our register of mortgages and charges and special resolutions passed by our shareholders), or to obtain a copy of our register of members.
Damage or extended periods of interruption to our corporate or our contract manufacturer’s development or research facilities due to fire, natural disaster, power loss, communications failure, unauthorized entry or other events could cause us to cease or delay development of some or all of our product candidates. 99 We face risks related to health epidemics, pandemics and other outbreaks, which could significantly disrupt our operations.
Damage or extended periods of interruption to our corporate or our contract manufacturer’s development or research facilities due to fire, natural disaster, power loss, communications failure, unauthorized entry or other events could cause us to cease or delay development of some or all of our product candidates. 98 We face risks related to health epidemics, pandemics and other outbreaks, which could significantly disrupt our operations.
Substantially all of our operating losses have resulted from costs incurred in connection with our research and development programs and from general and administrative costs associated with our operations.
Substantially all of our operating losses have resulted from costs incurred in connection with our research and development programs and from general and administrative expenses associated with our operations.
However, we have been classified as a PFIC in prior years and may again be classified as a PFIC in the future, which could result in adverse U.S. federal income tax consequences for our U.S. shareholders. Our PFIC status for the current taxable year ending December 31, 2025, will not be determinable until after the close of the taxable year.
However, we have been classified as a PFIC in prior years and may again be classified as a PFIC in the future, which could result in adverse U.S. federal income tax consequences for our U.S. shareholders. Our PFIC status for the current taxable year ending December 31, 2026, will not be determinable until after the close of the taxable year.
Foreign currency fluctuations are unpredictable and may adversely affect our financial condition, results of operations and cash flows. 101 The value of the RMB against the U.S. dollar and other currencies may fluctuate and is affected by, among other things, changes in political and economic conditions and the foreign exchange policy adopted by the Chinese and other non-U.S. governments.
Foreign currency fluctuations are unpredictable and may adversely affect our financial condition, results of operations and cash flows. 100 The value of the RMB against the U.S. dollar and other currencies may fluctuate and is affected by, among other things, changes in political and economic conditions and the foreign exchange policy adopted by the Chinese and other non-U.S. governments.
In March 2023, we withdrew this NDA submission from the NMPA. 70 Our product candidates may cause adverse events or have other properties that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following any regulatory approval.
In March 2023, we withdrew this NDA submission from the NMPA. 71 Our product candidates may cause adverse events or have other properties that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following any regulatory approval.
We cannot be sure whether additional legislative changes will be enacted, whether President Trumps administration will propose other initiatives, or whether FDA regulations, guidance or interpretations will be changed, and if so, what the impact of such changes on the regulatory approvals or commercialization of our product candidates, if any, may be.
We cannot be sure whether additional legislative changes will be enacted, whether President Trump’s administration will propose other initiatives, or whether FDA regulations, guidance or interpretations will be changed, and if so, what the impact of such changes on the regulatory approvals or commercialization of our product candidates, if any, may be.
For example, the FDA has issued a series of guidance documents in connection with the Drug Competition Action Plan. 79 We must receive adequate reimbursement coverage for our product to successfully commercialize our product candidates or any future product candidate we may develop.
For example, the FDA has issued a series of guidance documents in connection with the Drug Competition Action Plan. 78 We must receive adequate reimbursement coverage for our product to successfully commercialize our product candidates or any future product candidate we may develop.
Supreme Court held that certain claims to naturally-occurring substances are not patentable. In the case, Mayo Collaborative Servs. v. Prometheus Labs, Inc. , the U.S. Supreme Court held that certain claims to methods of optimizing therapeutic efficacy constitute unpatentable laws of nature.
Myriad Genetics, Inc. , the U.S. Supreme Court held that certain claims to naturally-occurring substances are not patentable. In the case, Mayo Collaborative Servs. v. Prometheus Labs, Inc. , the U.S. Supreme Court held that certain claims to methods of optimizing therapeutic efficacy constitute unpatentable laws of nature.
Further, collaborations involving our product candidates are subject to numerous risks, which may include the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to a collaboration; 93 ● collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in their strategic focus due to the acquisition of competitive drugs, availability of funding, or other external factors, such as a business combination that diverts resources or creates competing priorities; ● collaborators may delay clinical trials, provide insufficient funding for a clinical trial, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials, or require a new formulation of a product candidate for clinical testing; ● collaborators could independently develop, or develop with third parties, drugs that compete directly or indirectly with our drugs or product candidates; ● a collaborator with marketing and distribution rights to one or more drugs may not commit sufficient resources to their marketing and distribution; ● collaborators may not properly maintain or defend our intellectual property rights or may use our intellectual property or proprietary information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential liability; ● disputes may arise between us and a collaborator that cause the delay or termination of the research, development or commercialization of our product candidates, or that result in costly litigation or arbitration that diverts management attention and resources; ● collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates; ● collaborators may own or co-own intellectual property covering our drugs that results from our collaborating with them, and in such cases, we would not have the exclusive right to commercialize such intellectual property; ● the collaboration may result in increased operating expenses or the assumption of indebtedness or contingent liabilities; and ● the collaboration arrangement may result in the loss of key personnel and uncertainties in our ability to maintain key business relationships.
If and when we collaborate with a third party for development and commercialization of a product candidate, we can expect to relinquish some or all of the control over the future success of that product candidate to the third party. 92 Further, collaborations involving our product candidates are subject to numerous risks, which may include the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to a collaboration; ● collaborators may not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in their strategic focus due to the acquisition of competitive drugs, availability of funding, or other external factors, such as a business combination that diverts resources or creates competing priorities; ● collaborators may delay clinical trials, provide insufficient funding for a clinical trial, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials, or require a new formulation of a product candidate for clinical testing; ● collaborators could independently develop, or develop with third parties, drugs that compete directly or indirectly with our drugs or product candidates; ● a collaborator with marketing and distribution rights to one or more drugs may not commit sufficient resources to their marketing and distribution; ● collaborators may not properly maintain or defend our intellectual property rights or may use our intellectual property or proprietary information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential liability; ● disputes may arise between us and a collaborator that cause the delay or termination of the research, development or commercialization of our product candidates, or that result in costly litigation or arbitration that diverts management attention and resources; ● collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates; ● collaborators may own or co-own intellectual property covering our drugs that results from our collaborating with them, and in such cases, we would not have the exclusive right to commercialize such intellectual property; ● the collaboration may result in increased operating expenses or the assumption of indebtedness or contingent liabilities; and ● the collaboration arrangement may result in the loss of key personnel and uncertainties in our ability to maintain key business relationships.
Our research programs and those of our collaborators may initially show promise in identifying potential indications and/or product candidates, yet fail to yield results for clinical development for a number of reasons, including: ● the research methodology used may not be successful in identifying potential indications and/or product candidates; ● potential product candidates may, after further study, be shown to have harmful adverse effects or other characteristics that indicate they are unlikely to be effective drugs; or ● it may take greater human and financial resources to identify additional therapeutic opportunities for our product candidates or to develop suitable potential product candidates through internal research programs than we will possess, thereby limiting our ability to diversify and expand our drug portfolio. 62 Because we have limited financial and managerial resources, we focus on research programs and product candidates for specific indications.
Our research programs and those of our collaborators may initially show promise in identifying potential indications and/or product candidates, yet fail to yield results for clinical development for a number of reasons, including: ● the research methodology used may not be successful in identifying potential indications and/or product candidates; ● potential product candidates may, after further study, be shown to have harmful adverse effects or other characteristics that indicate they are unlikely to be effective drugs; or ● it may take greater human and financial resources to identify additional therapeutic opportunities for our product candidates or to develop suitable potential product candidates through internal research programs than we will possess, thereby limiting our ability to diversify and expand our drug portfolio.
Although we try to ensure that our employees do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these employees have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such employee’s former employer.
We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers. 88 Although we try to ensure that our employees do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these employees have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such employee’s former employer.
The IRA is currently subject to legal challenges and it is unclear how the IRA will be effectuated or changed under the Trump administration, but it is possible that the IRA could have a material adverse effect on our business, financial condition, results of operations and cash flows in the future. 81 President Trump and the U.S.
The IRA is currently subject to legal challenges and it is unclear how the IRA will be effectuated or changed under the Trump administration, but it is possible that the IRA could have a material adverse effect on our business, financial condition, results of operations and cash flows in the future.
If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our product candidates or other testing, if the results of these trials or tests are not positive or are only modestly positive or if they raise safety concerns, we may: ● be delayed in obtaining regulatory approval for our product candidates; ● not obtain regulatory approval at all; ● obtain approval for indications that are not as broad as intended; ● have a drug removed from the market after obtaining regulatory approval; ● be subject to additional post-marketing testing requirements; ● be subject to restrictions on how a drug is distributed or used; or ● be unable to obtain reimbursement for use of a drug. 65 Delays in testing or approvals may result in increases in our drug development costs.
If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our product candidates or other testing, if the results of these trials or tests are not positive or are only modestly positive or if they raise safety concerns, we may: ● be delayed in obtaining regulatory approval for our product candidates; ● not obtain regulatory approval at all; ● obtain approval for indications that are not as broad as intended; ● have a drug removed from the market after obtaining regulatory approval; ● be subject to additional post-marketing testing requirements; ● be subject to restrictions on how a drug is distributed or used; or ● be unable to obtain reimbursement for use of a drug.
Even if patents covering our product candidates are obtained, we may be open to competition from other companies as well as generic medications once the patent life has expired for a drug. The granted U.S. patents directed to Plinabulin synthesis, use, compositions, and polymorphic forms are scheduled to expire between 2025 and 2039, excluding any potential patent term restoration.
Even if patents covering our product candidates are obtained, we may be open to competition from other companies as well as generic medications once the patent life has expired for a drug. The granted U.S. patents directed to Plinabulin use, compositions, and polymorphic forms are scheduled to expire between 2033 and 2042, excluding any potential patent term restoration.
For example, the Cyber Security Law of the PRC, or the Cyber Security Law, which became effective in June 2017, created China’s first national-level data protection regime for “network operators,” which may include all organizations in China that provide services over the internet or another information network.
For example, the Cyber Security Law of the PRC, or the Cyber Security Law, which became effective in June 2017 and amended in October 2025, created China’s first national-level data protection regime for “network operators,” which may include all organizations in China that provide services over the internet or another information network.
In addition, a new manufacturer would have to be educated in, or develop substantially equivalent processes for, production of our drugs; ● our manufacturers may have little or no experience with manufacturing our product candidates, and therefore may require a significant amount of support from us to implement and maintain the infrastructure and processes required to manufacture our product candidates; ● our third-party manufacturers might be unable to timely manufacture our product candidates or produce the quantity and quality required to meet our clinical and commercial needs, if any; ● our contract manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately; ● our contract manufacturers may not perform as agreed, may not devote sufficient resources to our product candidates, or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store and distribute our drugs; ● any potential third-party manufacturer may be unable to initially pass federal, state or international regulatory inspections in a timely or cost-effective manner; ● manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies in the U.S. and other regulatory authorities to ensure strict compliance with cGMPs and other government regulations and corresponding non-U.S. requirements and our third-party manufacturers may fail to comply with these regulations and requirements; ● we may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates; ● our third-party manufacturers could breach or terminate their agreements with us; ● our contract manufacturers and critical reagent suppliers may be subject to inclement weather, as well as natural or man-made disasters; ● our contract manufacturers may have unacceptable or inconsistent product quality success rates and yields; and ● we may not be able to obtain raw materials and components used in the manufacturing process that are suitable or acceptable for use, particularly where we have no other source or supplier for the raw materials or components.
In addition, a new manufacturer would have to be educated in, or develop substantially equivalent processes for, production of our drugs; ● our manufacturers may have little or no experience with manufacturing our product candidates, and therefore may require a significant amount of support from us to implement and maintain the infrastructure and processes required to manufacture our product candidates; ● our third-party manufacturers might be unable to timely manufacture our product candidates or produce the quantity and quality required to meet our clinical and commercial needs, if any; ● our contract manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately; ● our contract manufacturers may not perform as agreed, may not devote sufficient resources to our product candidates, or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store and distribute our drugs; ● any potential third-party manufacturer may be unable to initially pass federal, state or international regulatory inspections in a timely or cost-effective manner; ● manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies in the U.S. and other regulatory authorities to ensure strict compliance with cGMPs and other government regulations and corresponding non-U.S. requirements and our third-party manufacturers may fail to comply with these regulations and requirements; ● we may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates; ● our third-party manufacturers could breach or terminate their agreements with us; ● our contract manufacturers and critical reagent suppliers may be subject to inclement weather, as well as natural or man-made disasters; ● our contract manufacturers may have unacceptable or inconsistent product quality success rates and yields; and ● we may not be able to obtain raw materials and components used in the manufacturing process that are suitable or acceptable for use, particularly where we have no other source or supplier for the raw materials or components. 91 Each of these risks could delay or prevent the completion of our clinical trials or the approval of any of our product candidates by the FDA, NMPA, EMA or other comparable regulatory authorities, result in higher costs or adversely impact commercialization of our product candidates.
While we cannot predict if the SEC will further challenge the four China-based accounting firms’ compliance with U.S. law in connection with U.S. regulatory requests for audit work papers or if the results of such a challenge would result in the SEC imposing penalties such as suspensions, if the SEC restarts the administrative proceedings, depending upon the final outcome, listed companies in the U.S. with major Chinese operations may find it difficult or impossible to retain auditors with respect to their operations in China, which could result in financial statements being determined not to be in compliance with the requirements of the Exchange Act, including possible delisting.
The four-year mark occurred on February 6, 2019. 110 While we cannot predict if the SEC will further challenge the four China-based accounting firms’ compliance with U.S. law in connection with U.S. regulatory requests for audit work papers or if the results of such a challenge would result in the SEC imposing penalties such as suspensions, if the SEC restarts the administrative proceedings, depending upon the final outcome, listed companies in the U.S. with major Chinese operations may find it difficult or impossible to retain auditors with respect to their operations in China, which could result in financial statements being determined not to be in compliance with the requirements of the Exchange Act, including possible delisting.
If applications claiming priority to these PCT applications were to issue, they would nominally expire between 2043 and 2044. 84 With respect to issued patents in certain jurisdictions, for example, the U.S. and Europe, we may be entitled to obtain a patent term extension to extend the patent expiration date provided we meet the applicable requirements for obtaining such patent term extensions.
If applications claiming priority to these PCT applications were to issue, they would nominally expire in 2045. With respect to issued patents in certain jurisdictions, for example, the U.S. and Europe, we may be entitled to obtain a patent term extension to extend the patent expiration date provided we meet the applicable requirements for obtaining such patent term extensions.
We cannot commercialize product candidates without first obtaining regulatory approval to market each drug from the FDA, NMPA, EMA and comparable regulatory authorities. Plinabulin is currently being developed in combination with standard of care (SOC) agents for multiple cancer indications. It is currently being studied in two clinical developmental programs.
We cannot commercialize product candidates without first obtaining regulatory approval to market each drug from the FDA, NMPA, EMA and comparable regulatory authorities. Plinabulin is currently being developed in combination with standard of care (SOC) agents for multiple cancer indications. It has finished in two phase 3 clinical developmental programs.
As a result, we and non-resident enterprises in such transactions may become at risk of being subject to filing obligations or being taxed under Bulletin 7 and Bulletin 37, and may be required to expend valuable resources to comply with them or to establish that we and our non-resident enterprises should not be taxed under these regulations, which may have a material adverse effect on our financial condition and results of operations.
As a result, we and non-resident enterprises in such transactions may become at risk of being subject to filing obligations or being taxed under Bulletin 7 and Bulletin 37, and may be required to expend valuable resources to comply with them or to establish that we and our non-resident enterprises should not be taxed under these regulations, which may have a material adverse effect on our financial condition and results of operations. 108 There are uncertainties as to the application of Bulletin 7.
Nevertheless, if we fail to maintain an effective system of internal controls, we may not be able to accurately or timely report our financial condition or results of operations, which may adversely affect investor confidence in us and, as a result, the value of our ordinary shares.” In addition, as of January 1, 2025, we have lost our status as a “foreign private issuer,” as defined in the SEC’s rules and regulations and, consequently, we are now subject to all of the disclosure requirements applicable to public companies organized within the U.S.
Risk Factors—Risks Related to Our Industry, Business and Operation—If we fail to maintain an effective system of internal controls, we may not be able to accurately or timely report our financial condition or results of operations, which may adversely affect investor confidence in us and, as a result, the value of our ordinary shares.” In addition, as of January 1, 2025, we have lost our status as a “foreign private issuer,” as defined in the SEC’s rules and regulations and, consequently, we are now subject to all of the disclosure requirements applicable to public companies organized within the U.S.
Our product candidates will require the completion of regulatory review, significant marketing efforts and substantial investment before they can provide us with any product sales revenue. Our operations have consumed substantial amounts of cash since inception. The net cash used for operating activities was $16.5 million and $16.4 million for the years ended December 31, 2023 and 2024, respectively.
Our product candidates will require the completion of regulatory review, significant marketing efforts and substantial investment before they can provide us with any product sales revenue. 59 Our operations have consumed substantial amounts of cash since inception. The net cash used for operating activities was $19.8 million and $16.4 million for the years ended December 31, 2025 and 2024, respectively.
In addition, in the United States, at both the federal and state levels, and in territories outside of Mainland China where we have rights to and plan to develop and commercialize our in-licensed product candidates, including Hong Kong, Macau, Singapore, South Korea, Taiwan and Thailand, we are subject to laws and regulations that address privacy, personal information protection and data security.
In addition, the interpretation and application of data protection laws in China and elsewhere are often uncertain and in flux. 113 In addition, in the United States, at both the federal and state levels, and in territories outside of Mainland China where we have rights to and plan to develop and commercialize our in-licensed product candidates, including Hong Kong, Macau, Singapore, South Korea, Taiwan and Thailand, we are subject to laws and regulations that address privacy, personal information protection and data security.
Among these shares, 18,619,795 ordinary shares have been registered under the Securities Act and are freely transferable by persons other than our “affiliates” without restriction or registration; the remaining shares outstanding have not been registered under the Securities Act and may be offered or sold only pursuant to an effective registration statement or pursuant to an available exemption from the registration requirements.
Among these shares, 19,423,295 ordinary shares have been registered under the Securities Act and are freely transferable by persons other than our “affiliates” without restriction or registration; the remaining shares outstanding have not been registered under the Securities Act and may be offered or sold only pursuant to an effective registration statement or pursuant to an available exemption from the registration requirements.
We and our major shareholders have been, and may in the future become, subject to claims, litigation, arbitration and investigations, any of which may require significant management attention, could result in significant legal expenses and may result in unfavorable outcomes, all or any of which could have a material adverse impact on our financial condition and results of operations, harm our reputation or otherwise negatively impact our business.
We and our major shareholders have been, and may in the future become, subject to claims, litigation, arbitration and investigations, any of which may require significant management attention, could result in significant legal expenses and may result in unfavorable outcomes, all or any of which could have a material adverse impact on our financial condition and results of operations, harm our reputation or otherwise negatively impact our business. 101 We and our major shareholders have been, and may in the future become, subject to claims, litigation, arbitration or investigations arising in or outside the ordinary course of business that could negatively affect our business operations and financial condition.
As of December 31, 2024, these restricted net assets were nil. 107 The EIT Law, and its implementation rules, both of which became effective on January 1, 2008 and have been amended certain times thereafter, provide that China-sourced income of foreign enterprises, such as dividends paid by a Chinese subsidiary to its equity holders that are non-Chinese resident enterprises, will normally be subject to Chinese withholding tax at a rate of 10%, unless any such foreign investor’s jurisdiction of incorporation has a tax treaty with China that provides for a different withholding arrangement.
The EIT Law, and its implementation rules, both of which became effective on January 1, 2008 and have been amended certain times thereafter, provide that China-sourced income of foreign enterprises, such as dividends paid by a Chinese subsidiary to its equity holders that are non-Chinese resident enterprises, will normally be subject to Chinese withholding tax at a rate of 10%, unless any such foreign investor’s jurisdiction of incorporation has a tax treaty with China that provides for a different withholding arrangement.
The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including: ● the clinical indications for which our product candidates are approved; ● physicians, hospitals, cancer treatment centers and patients considering our product candidates as a safe and effective treatment; ● the potential and perceived advantages of our product candidates over alternative treatments; ● the prevalence and severity of any side effects; ● product labeling or product insert requirements of the FDA, NMPA, EMA or other comparable regulatory authorities; ● limitations or warnings contained in the labeling approved by the FDA, NMPA, EMA or other comparable regulatory authorities; ● the timing of market introduction of our product candidates as well as competitive drugs; ● the cost of treatment, including in relation to alternative treatments and their relative benefits; ● the amount of upfront costs or training required for physicians to administer our product candidates; ● the availability of adequate coverage, reimbursement and pricing by third-party payors and government authorities; ● the willingness of patients to pay out-of-pocket in the absence of coverage and reimbursement by third-party payors and government authorities; ● relative convenience and ease of administration, including as compared to alternative treatments and competitive therapies; and ● the effectiveness of our sales and marketing efforts. 77 If our product candidates are approved but fail to achieve market acceptance among physicians, patients, hospitals, cancer treatment centers or others in the medical community, we will not be able to generate significant revenue.
The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including: ● the clinical indications for which our product candidates are approved; ● physicians, hospitals, cancer treatment centers and patients considering our product candidates as a safe and effective treatment; ● the potential and perceived advantages of our product candidates over alternative treatments; ● the prevalence and severity of any side effects; ● product labeling or product insert requirements of the FDA, NMPA, EMA or other comparable regulatory authorities; ● limitations or warnings contained in the labeling approved by the FDA, NMPA, EMA or other comparable regulatory authorities; ● the timing of market introduction of our product candidates as well as competitive drugs; ● the cost of treatment, including in relation to alternative treatments and their relative benefits; ● the amount of upfront costs or training required for physicians to administer our product candidates; ● the availability of adequate coverage, reimbursement and pricing by third-party payors and government authorities; 76 ● the willingness of patients to pay out-of-pocket in the absence of coverage and reimbursement by third-party payors and government authorities; ● relative convenience and ease of administration, including as compared to alternative treatments and competitive therapies; and ● the effectiveness of our sales and marketing efforts.
We had 16 families of pending patent applications directed to use of Plinabulin in neutropenia reduction, use of Plinabulin for treating RAS mutant tumors and brain tumors, polymorphic forms of Plinabulin, use of Plinabulin in combination with checkpoint inhibitors, use of Plinabulin in reduction of immunotherapy related adverse events, use of Plinabulin in the treatment of thrombocytopenia, use of Plinabulin in combination with G-CSF therapy, use of Plinabulin for treating EGFR mutant tumors, use of Plinabulin in combination with an immune checkpoint inhibitor and a farnesyl pyrophosphate synthase inhibitor for treating cancer, use of Plinabulin in treating immune checkpoint inhibitor-resistant patients, Plinabulin impurities, use of Plinabulin as a monotherapy in treating certain cancers, and kits and methods for providing and administering Plinabulin.
We had 20 families of pending patent applications directed to use of Plinabulin in neutropenia reduction, use of Plinabulin for treating RAS mutant tumors and brain tumors, polymorphic forms of Plinabulin, use of Plinabulin in combination with checkpoint inhibitors, use of Plinabulin in reduction of immunotherapy related adverse events, use of Plinabulin in the treatment of thrombocytopenia, use of Plinabulin in combination with G-CSF therapy, use of Plinabulin for treating EGFR mutant tumors, use of Plinabulin in combination with an immune checkpoint inhibitor and a farnesyl pyrophosphate synthase inhibitor for treating cancer, use of Plinabulin in treating immune checkpoint inhibitor-resistant patients, Plinabulin impurities, use of Plinabulin as a monotherapy in treating certain cancers, kits and methods for providing and administering Plinabulin, use of Plinabulin in combination with a PARP inhibitor, Plinabulin micelle compositions, use of Plinabulin in combination with a cyclin-dependent kinase inhibitor, and use of biomarkers for Plinabulin therapy.
On August 24, 2023, the NMPA issued the revised draft Protocol for Review and Approval of Conditional Approval of Drugs Marketing Applications (Trial) and the policy interpretations for such protocol for public comments.
On August 24, 2023, the NMPA issued the revised draft Protocol for Review and Approval of Conditional Approval of Drugs Marketing Applications (Trial) and the policy interpretations for such protocol for public comments，and on July 7, 2025, the NMPA issued the revised draft Protocol for Review and Approval of Conditional Approval of Drugs Marketing Applications (Trial) and the policy interpretations for such protocol for public comments again.
Risks Related to Our Industry, Business and Operation ● We may be limited in the promotional claims we can make and may not be able to use information about competing therapies to promote or market Plinabulin, if approved, without incurring significant legal, regulatory or enforcement risks. ● We have limited intellectual property rights to Plinabulin inside China.
Risks Related to Our Industry, Business and Operation We may be limited in the promotional claims we can make and may not be able to use information about competing therapies to promote or market Plinabulin, if approved, without incurring significant legal, regulatory or enforcement risks.
We have entered into an investigator-initiated clinical trial agreement with UCSD, and Dr. Lyudmila Bazhenova, an employee of UCSD and the principal investigator, and a clinical study agreement with the University of Washington, in connection with the investigator-initiated Phase 1/2 studies of Plinabulin in combination with Bristol-Myers Squibb’s PD-1 antibody, nivolumab in patients with metastatic NSCLC.
Lyudmila Bazhenova, an employee of UCSD and the principal investigator, and a clinical study agreement with the University of Washington, in connection with the investigator-initiated Phase 1/2 studies of Plinabulin in combination with Bristol-Myers Squibb’s PD-1 antibody, nivolumab in patients with metastatic NSCLC.
Congress, the federal courts and the USPTO, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future. For example, in the case, Assoc. for Molecular Pathology v. Myriad Genetics, Inc. , the U.S.
Depending on decisions by the U.S. Congress, the federal courts and the USPTO, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future. For example, in the case, Assoc. for Molecular Pathology v.
Marcum is headquartered in Manhattan, New York. Marcum was not included in the list of PCAOB Identified Firms in the PCAOB Determination Report issued in December 2021, and was inspected by the PCAOB on a regular basis. For this reason, we do not expect to be identified as a Commission-Identified Issuer under the HFCAA.
CBIZ is headquartered in Cleveland, Ohio. CBIZ was not included in the list of PCAOB Identified Firms in the PCAOB Determination Report issued in December 2021, and was inspected by the PCAOB on a regular basis. For this reason, we do not expect to be identified as a Commission-Identified Issuer under the HFCAA.
This streamlining initiative included a reduction in force program impacting a number of employees. To meet our long-term growth strategy, we will need to increase the size and capabilities of our organization, and we may experience difficulties in managing our growth. As of February 28, 2025, we had 40 full-time employees, including 19 employed by SEED.
This streamlining initiative included a reduction in force program impacting a number of employees. To meet our long-term growth strategy, we will need to increase the size and capabilities of our organization, and we may experience difficulties in managing our growth. As of February 27, 2026, we had 44 full-time employees, including 34 employed by SEED.
Through December 31, 2024, we have raised approximately $299.0 million in equity financing, $10.2 million of issuance of noncontrolling interests, $34.0 million from the sale of preferred shares of SEED, $2.1 million from bank loans, of which $0.6 million has been forgiven in July 2021 and $1.5 million has been repaid in March 2022, $2.5 million in third party loans, of which $1.0 million has since been converted into an equity investment and $1.5 million has been repaid, and $14.4 million in shareholder loans, of which $6.0 million has been repaid and $8.4 million was assumed by Wanchun Biotech, the former holding company of our U.S. subsidiary, on July 20, 2015 pursuant to our internal restructuring, $10.0 million upfront payment to SEED from Eli Lilly, and approximately $31.0 million upfront payment to our partially owned subsidiary, Wanchunbulin, from Hengrui.
Through December 31, 2025, we have raised approximately $301.0 million in equity financing, $10.2 million of issuance of noncontrolling interests, $37.0 million from the sale of preferred shares of SEED in connection with its Series A-2/A-3 financings and $7.4 million from the sale of preferred shares of SEED by the Company to third-party investors, $2.1 million from bank loans, of which $0.6 million has been forgiven in July 2021 and $1.5 million has been repaid in March 2022, $2.5 million in third party loans, of which $1.0 million has since been converted into an equity investment and $1.5 million has been repaid, and $14.4 million in shareholder loans, of which $6.0 million has been repaid and $8.4 million was assumed by Wanchun Biotech, the former holding company of our U.S. subsidiary, on July 20, 2015 pursuant to our internal restructuring, $10.0 million upfront payment to SEED from Eli Lilly, and approximately $31.0 million upfront payment to our partially owned subsidiary, Wanchunbulin, from Hengrui.
Compliance with GCPs can be costly and if we or any of our CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA, NMPA, EMA or comparable regulatory authorities may require us to perform additional clinical trials before approving our marketing applications. 64 We may experience numerous unexpected events during, or as a result of, clinical trials that could delay or prevent our ability to receive regulatory approval or commercialize our product candidates, including: ● regulators, IRBs, or ethics committees may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; ● clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon drug development programs; ● the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment may be insufficient or slower than we anticipate or patients may drop out at a higher rate than we anticipate; ● our third-party contractors and investigators may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; ● we might have to suspend or terminate clinical trials of our product candidates for various reasons, including a lack of clinical response or a determination that participants are being exposed to unacceptable health risks; ● regulators, IRBs or ethics committees may require that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements; ● the cost of clinical trials of our product candidates may be greater than we anticipate; ● the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; and ● our product candidates may cause adverse events or have undesirable side effects or other unexpected characteristics, causing us, our investigators, or regulators to suspend or terminate the trials.
We may experience numerous unexpected events during, or as a result of, clinical trials that could delay or prevent our ability to receive regulatory approval or commercialize our product candidates, including: ● regulators, IRBs, or ethics committees may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; 65 ● clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon drug development programs; ● the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment may be insufficient or slower than we anticipate or patients may drop out at a higher rate than we anticipate; ● our third-party contractors and investigators may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; ● we might have to suspend or terminate clinical trials of our product candidates for various reasons, including a lack of clinical response or a determination that participants are being exposed to unacceptable health risks; ● regulators, IRBs or ethics committees may require that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements; ● the cost of clinical trials of our product candidates may be greater than we anticipate; ● the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; and ● our product candidates may cause adverse events or have undesirable side effects or other unexpected characteristics, causing us, our investigators, or regulators to suspend or terminate the trials.
Our directors, executive officers and shareholders holding more than 10% of our ordinary shares beneficially owned approximately 30.04% of our ordinary shares as of February 28, 2025. These shareholders, if acting together, could exert substantial influence over matters such as electing directors and approving material mergers, acquisitions or other business combination transactions.
Our directors, executive officers and shareholders holding more than 10% of our ordinary shares beneficially owned approximately 18.17% of our ordinary shares as of February 27, 2026. These shareholders, if acting together, could exert substantial influence over matters such as electing directors and approving material mergers, acquisitions or other business combination transactions.
Of these, 24 were engaged in full-time research and development and laboratory operations and 16 were engaged in full-time general and administrative functions. As of February 28, 2025, 13 of our employees were located in China and 27 were located in the U.S.
Of these, 25 were engaged in full-time research and development and laboratory operations and 19 were engaged in full-time general and administrative functions. As of February 27, 2026, 16 of our employees were located in China and 28 were located in the U.S.
Additionally, if one or more of our current or future product candidates receives regulatory approval, and we or others later identify undesirable side effects caused by such drugs, a number of potentially significant negative consequences could result, including: ● we may limit or suspend marketing of the drug; ● regulatory authorities may withdraw approvals of the drug; ● regulatory authorities may require additional warnings on the label; ● we may be required to develop a REMS for the drug or, if a REMS is already in place, to incorporate additional requirements under the REMS, or to develop a similar strategy as required by a comparable regulatory authority; ● we may be required to conduct post-market studies; ● we could be sued and held liable for harm caused to subjects or patients; and ● our reputation may suffer. 71 Any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations and prospects.
Additionally, if one or more of our current or future product candidates receives regulatory approval, and we or others later identify undesirable side effects caused by such drugs, a number of potentially significant negative consequences could result, including: ● we may limit or suspend marketing of the drug; ● regulatory authorities may withdraw approvals of the drug; ● regulatory authorities may require additional warnings on the label; ● we may be required to develop a REMS for the drug or, if a REMS is already in place, to incorporate additional requirements under the REMS, or to develop a similar strategy as required by a comparable regulatory authority; ● we may be required to conduct post-market studies; ● we could be sued and held liable for harm caused to subjects or patients; and ● our reputation may suffer.
In addition, under Chinese laws, rules and regulations, our subsidiaries incorporated in China are restricted in their ability to transfer a portion of their respective net assets to their shareholders as dividends. Registered share capital and capital reserve accounts are also restricted from withdrawal in China.
In addition, under Chinese laws, rules and regulations, our subsidiaries incorporated in China are restricted in their ability to transfer a portion of their respective net assets to their shareholders as dividends. Registered share capital and capital reserve accounts are also restricted from withdrawal in China. As of December 31, 2025, these restricted net assets were approximately $12 thousand.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, payment of user fees and reauthorization of user fee programs and ability to hire and retain key personnel, as well as statutory, regulatory and policy changes, and average review times at the FDA have fluctuated in recent years as a result.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, payment of user fees and reauthorization of user fee programs and ability to hire and retain key personnel, as well as statutory, regulatory and policy changes.
Business—Commercialization.” Plinabulin has been granted Breakthrough Therapy Designation by the NMPA. Additionally, Plinabulin has achieved status as a 2017 National Science and Technology Major Project in China, or the 2017 Grant. As a result of the 2017 Grant, Plinabulin has been included in the National Drug Priority Review List in China.
Business—Commercialization.” Plinabulin has achieved status as a 2017 National Science and Technology Major Project in China, or the 2017 Grant. As a result of the 2017 Grant, Plinabulin has been included in the National Drug Priority Review List in China.
Risks Related to Our Intellectual Property A portion of our intellectual property portfolio currently comprises pending patent applications that have not yet been issued as granted patents and if our pending patent applications fail to issue, our business will be adversely affected.
This could adversely affect our ability to operate our business and our results of operations. 83 Risks Related to Our Intellectual Property A portion of our intellectual property portfolio currently comprises pending patent applications that have not yet been issued as granted patents and if our pending patent applications fail to issue, our business will be adversely affected.
The Chinese legal system is a civil law system based on written statutes. 105 In 1979, the Chinese government began to promulgate a comprehensive system of laws, rules and regulations governing economic matters in general. The overall effect of legislation over the past four decades has significantly enhanced the protections afforded to various forms of foreign investment in China.
In 1979, the Chinese government began to promulgate a comprehensive system of laws, rules and regulations governing economic matters in general. The overall effect of legislation over the past four decades has significantly enhanced the protections afforded to various forms of foreign investment in China.
If we fail to enter into collaborations and do not have sufficient funds or expertise to undertake the necessary development and commercialization activities, we may not be able to further develop our product candidates or bring them to market and generate product sales revenue, which would harm our business prospects, financial condition and results of operations.
If we fail to enter into collaborations and do not have sufficient funds or expertise to undertake the necessary development and commercialization activities, we may not be able to further develop our product candidates or bring them to market and generate product sales revenue, which would harm our business prospects, financial condition and results of operations. 93 We have entered into an investigator-initiated clinical trial agreement with UCSD, and Dr.
If the FDA does not approve our NDA for Plinabulin in combination with G-CSF for the prevention of CIN, or the FDA ’ s review or approval of our NDA for Plinabulin in such indication is significantly delayed or prolonged, or the continued development of Plinabulin in such indication is significantly delayed or terminated, our business and results of operations could be significantly adversely affected.
If the FDA does not approve our NDA for Plinabulin in combination with G-CSF for the prevention of CIN, or the FDA ’ s review or approval of our NDA for Plinabulin in such indication is significantly delayed or prolonged, or the continued development of Plinabulin in such indication is significantly delayed or terminated, our business and results of operations could be significantly adversely affected. 62 In November 2021, we received a Complete Response Letter from the FDA for Plinabulin in combination with G-CSF for the prevention of CIN.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeThis proactive surveillance ensures that any anomalies or suspicious activities are swiftly identified and addressed, minimizing the window of vulnerability. Complementing this arsenal is the deployment of an EDR (Endpoint Detection and Response) agent, a cutting-edge technology that places us at the forefront of cybersecurity innovation.
Biggest changeThis proactive surveillance ensures that any anomalies or suspicious activities are swiftly identified and addressed, minimizing the window of vulnerability. 120 Complementing this arsenal is the deployment of an EDR (Endpoint Detection and Response) agent, a cutting-edge technology that places us at the forefront of cybersecurity innovation.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeUpon the lease’s expiration on December 31, 2024, we transitioned to a new office space in Dalian, China, under a lease agreement with a different landlord. The new office, effective January 1, 2025, measures 210.65 square meters, with a monthly rent of $1,404. The lease expires on December 31, 2027.
Biggest changeWe lease office space in Dalian, China, with total space of 210.65 square meters and a monthly rent of RMB 10,252 (approximately $1,466). The lease expires on December 31, 2027. Payments under the lease are expensed on a straight-line basis over the period of the lease.
Item 2. Properties. We currently lease office space in New Jersey, with total space of 9,727 square feet. The lease expires in February 2027. Our current rent is $25,939 per month. Starting in August 2025, our annual rent will increase by $0.50 per square foot leased.
Item 2. Properties. We currently lease office space in New Jersey, with total space of 9,727 square feet. The lease expires in February 2027. Our current rent is $26,344 per month. Starting in August 2026, our annual rent will increase by $0.50 per square foot leased.
We additionally pay for the cost of utilities, as well as our share of building real estate taxes and building operating expenses. Payments under the lease are expensed on a straight-line basis over the period of the lease. As of December 31, 2024, we occupied office space in Dalian, China, under a rent-free arrangement with the local government.
We additionally pay for the cost of utilities, as well as our share of building real estate taxes and building operating expenses. Payments under the lease are expensed on a straight-line basis over the period of the lease.
Its current rent is $40,125 per month. Starting in June 2025, SEED’s annual rent will increase by 3%. SEED additionally pays for the cost of its utilities, as well as its proportionate share of building real estate taxes, and building operating expenses, and has paid approximately $0.9 million for improvements to the leased property on behalf of the lessor.
SEED additionally pays for the cost of its utilities, as well as its proportionate share of building real estate taxes, and building operating expenses, and has paid approximately $0.9 million for improvements to the leased property on behalf of the lessor. Payments under the lease are expensed on a straight-line basis over the period of the lease.
Payments under the lease are expensed on a straight-line basis over the period of the lease. Additionally, SEED has also purchased lab equipment of approximately $1.9 million as of December 31, 2024.
Additionally, SEED has also purchased lab equipment of approximately $1.9 million as of December 31, 2025.
Removed
This space, measuring 860.12 square meters, remained in use throughout 2024 while our formal application for rent exemption was under review. The local government office has since approved the rent-free subsidy for the 2024 lease, and as of March 1, 2025, the subsidy is pending disbursement by the government’s finance department.
Added
SEED currently leases permanent office space and lab space in Pennsylvania, with a total space of approximately 10,086 square feet. Its current rent is $41,327 per month. Starting in June 2026, SEED’s annual rent will increase by 3%.
Removed
Payments under the lease are expensed on a straight-line basis over the period of the lease. 123 SEED has completed the build-out of a wet lab in Pennsylvania to support research and development efforts for the Ubiquitin Platform Technology. SEED currently leases permanent office space and lab space in Pennsylvania, with a total space of approximately 10,086 square feet.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

13 edited+1 added−2 removed93 unchanged
Biggest changeTreasury regulations promulgated thereunder, or the Regulations, judicial decisions, administrative pronouncements, the income tax treaty between the United States and China, or the Treaty, and other relevant authorities, all as in effect as of the date hereof and all of which are subject to change or differing interpretations (possibly with retroactive effect). 127 This summary does not address U.S. federal estate, gift or other non-income tax considerations, the alternative minimum tax, the Medicare tax on certain net investment income, or any state, local or non-U.S. tax considerations, relating to the ownership or disposition of our ordinary shares, nor does it address all aspects of U.S. federal income taxation that may be relevant to a particular U.S.
Biggest changeThis summary does not address U.S. federal estate, gift or other non-income tax considerations, the alternative minimum tax, the Medicare tax on certain net investment income, or any state, local or non-U.S. tax considerations, relating to the ownership or disposition of our ordinary shares, nor does it address all aspects of U.S. federal income taxation that may be relevant to a particular U.S.
Holders subject to special treatment under U.S. federal income tax law, such as: ● banks and other financial institutions; ● insurance companies; ● pension plans; ● cooperatives; ● regulated investment companies; ● real estate investment trusts; ● broker-dealers; ● traders that elect to use a mark-to-market method of accounting; ● certain former citizens or long-term residents of the United States; ● tax-exempt entities (including private foundations); ● persons that acquire our ordinary shares pursuant to any employee share option or otherwise as compensation; ● persons that hold our ordinary shares as part of a straddle, hedge, conversion, constructive sale or other integrated transaction for U.S. federal income tax purposes; ● persons whose functional currency is not the U.S.
Holders subject to special treatment under U.S. federal income tax law, such as: 124 ● banks and other financial institutions; ● insurance companies; ● pension plans; ● cooperatives; ● regulated investment companies; ● real estate investment trusts; ● broker-dealers; ● traders that elect to use a mark-to-market method of accounting; ● certain former citizens or long-term residents of the United States; ● tax-exempt entities (including private foundations); ● persons that acquire our ordinary shares pursuant to any employee share option or otherwise as compensation; ● persons that hold our ordinary shares as part of a straddle, hedge, conversion, constructive sale or other integrated transaction for U.S. federal income tax purposes; ● persons whose functional currency is not the U.S.
According to Circular 82, a Chinese-controlled offshore incorporated enterprise will be regarded as a PRC tax resident by virtue of having a “de facto management body” in China and will be subject to Chinese enterprise income tax on its worldwide income only if all of the following criteria are met: ● the primary location of the enterprise’s senior executives of the day-to-day operational management and senior management departments performing their duties is in China; ● decisions relating to the enterprise’s financial and human resource matters are made or are subject to approval by organizations or personnel in China; 126 ● the enterprise’s primary assets, accounting books and records, company seals, and board and shareholder meeting minutes are located or maintained in China; and ● 50% or more of voting board members or senior executives habitually reside in China.
According to Circular 82, a Chinese-controlled offshore incorporated enterprise will be regarded as a PRC tax resident by virtue of having a “de facto management body” in China and will be subject to Chinese enterprise income tax on its worldwide income only if all of the following criteria are met: ● the primary location of the enterprise’s senior executives of the day-to-day operational management and senior management departments performing their duties is in China; ● decisions relating to the enterprise’s financial and human resource matters are made or are subject to approval by organizations or personnel in China; 123 ● the enterprise’s primary assets, accounting books and records, company seals, and board and shareholder meeting minutes are located or maintained in China; and ● 50% or more of voting board members or senior executives habitually reside in China.
Furthermore, prior to the commercialization of any of our drug candidates, interest and other passive income could constitute more than 75% of our gross income for any taxable year. 130 If we are a PFIC for any taxable year during which a U.S. Holder holds our ordinary shares, the U.S.
Furthermore, prior to the commercialization of any of our drug candidates, interest and other passive income could constitute more than 75% of our gross income for any taxable year. If we are a PFIC for any taxable year during which a U.S. Holder holds our ordinary shares, the U.S.
Holder will not be required to take into account the mark-to-market income or loss described above during any period that we are not classified as a PFIC. 131 The mark-to-market election is available only for “marketable stock” which is stock that is traded in other than de minimis quantities on at least 15 days during each calendar quarter(“regularly traded”) on a qualified exchange or other market, as defined in applicable regulations.
Holder will not be required to take into account the mark-to-market income or loss described above during any period that we are not classified as a PFIC. 128 The mark-to-market election is available only for “marketable stock” which is stock that is traded in other than de minimis quantities on at least 15 days during each calendar quarter(“regularly traded”) on a qualified exchange or other market, as defined in applicable regulations.
Performance Graph The performance graph has been omitted as permitted under rules applicable to smaller reporting companies. Recent Sales of Unregistered Securities None. 125 Issuer Purchases of Equity Securities None. Taxation The following is a summary of the Cayman Islands, Chinese and U.S. federal income tax considerations relevant to the ownership and disposition of our ordinary shares.
Performance Graph The performance graph has been omitted as permitted under rules applicable to smaller reporting companies. Recent Sales of Unregistered Securities None. 122 Issuer Purchases of Equity Securities None. Taxation The following is a summary of the Cayman Islands, Chinese and U.S. federal income tax considerations relevant to the ownership and disposition of our ordinary shares.
As discussed below under “—Passive Foreign Investment Company,” although there can be no assurances regarding our PFIC status for any taxable year, we believe that we were not a PFIC for our 2024 taxable year. Thus, dividends paid on our ordinary shares to individuals and other non-corporate U.S.
As discussed below under “—Passive Foreign Investment Company,” although there can be no assurances regarding our PFIC status for any taxable year, we believe that we were not a PFIC for our 2025 taxable year. Thus, dividends paid on our ordinary shares to individuals and other non-corporate U.S.
Partnerships holding our ordinary shares and their partners should consult their tax advisors regarding an investment in our ordinary shares. 128 Tax Residence of BeyondSpring Inc. for U.S. Federal Income Tax Purposes Under current U.S. federal income tax law, a corporation is generally considered a tax resident in the jurisdiction of its organization or incorporation.
Partnerships holding our ordinary shares and their partners should consult their tax advisors regarding an investment in our ordinary shares. 125 Tax Residence of BeyondSpring Inc. for U.S. Federal Income Tax Purposes Under current U.S. federal income tax law, a corporation is generally considered a tax resident in the jurisdiction of its organization or incorporation.
Holders, whether or not they are Treaty-eligible, should consult their tax advisors regarding the availability of foreign tax credits and the deductibility of foreign taxes in light of their particular circumstances. 129 Sale or Other Disposition of Our Ordinary Shares A U.S.
Holders, whether or not they are Treaty-eligible, should consult their tax advisors regarding the availability of foreign tax credits and the deductibility of foreign taxes in light of their particular circumstances. 126 Sale or Other Disposition of Our Ordinary Shares A U.S.
Our PFIC status for the current taxable year ending December 31, 2025, will not be determinable until after the close of the year, and it is possible that we may be classified as a PFIC for the current taxable year and for future taxable years.
Our PFIC status for the current taxable year ending December 31, 2026, will not be determinable until after the close of the year, and it is possible that we may be classified as a PFIC for the current taxable year and for future taxable years.
Item 5. Market for Registrant ’ s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Market Information Our ordinary shares have been listed on the Nasdaq Capital Market since March 9, 2017 under the symbol “BYSI.” Holders As of February 28, 2025, we had approximately 67 holders of record of our ordinary shares.
Item 5. Market for Registrant ’ s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Market Information Our ordinary shares have been listed on the Nasdaq Capital Market since March 9, 2017 under the symbol “BYSI.” Holders As of February 27, 2026, we had approximately 70 holders of record of our ordinary shares.
Notwithstanding the foregoing, as discussed elsewhere in this Annual Report on Form 10-K, for purposes of U.S. federal securities law, we have become a domestic issuer for purposes of U.S. federal securities law. As a domestic issuer for purposes of U.S. federal securities law, we, among other obligations, must file this Annual Report on Form 10-K and not Form 20-F.
Notwithstanding the foregoing, in 2025, we became a domestic issuer for purposes of U.S. federal securities law. As a domestic issuer for purposes of U.S. federal securities law, we, among other obligations, must file this Annual Report on Form 10-K and not Form 20-F.
Based on an analysis of our income and the value of our assets, we believe that we were not a PFIC for the taxable year ended December 31, 2024, although no assurance can be given due to the highly factual nature of such analysis.
We will be treated as owning a proportionate share of the assets and earning a proportionate share of the income of any other corporation in which we own, directly, indirectly or constructively, 25% or more (by value) of its stock. 127 Based on an analysis of our income and the value of our assets, we believe that we were not a PFIC for the taxable year ended December 31, 2025, although no assurance can be given due to the highly factual nature of such analysis.
Removed
This summary is based on the Code, U.S.
Added
This summary is based on the Code, U.S. Treasury regulations promulgated thereunder, or the Regulations, judicial decisions, administrative pronouncements, the income tax treaty between the United States and China, or the Treaty, and other relevant authorities, all as in effect as of the date hereof and all of which are subject to change or differing interpretations (possibly with retroactive effect).
Removed
We will be treated as owning a proportionate share of the assets and earning a proportionate share of the income of any other corporation in which we own, directly, indirectly or constructively, 25% or more (by value) of its stock.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeDollars (“$”)) % Revenue — — — Operating expenses Research and development (2,644 ) (7,272 ) -64 % General and administrative (6,110 ) (7,809 ) -22 % Loss from operations (8,754 ) (15,081 ) -42 % Other income (expense) Foreign exchange loss, net (96 ) (128 ) -25 % Interest income 59 322 -82 % Other income, net 22 964 -98 % Total other income (expense) (15 ) 1,158 -101 % Net loss before income tax (8,769 ) (13,923 ) -37 % Income tax expenses (96 ) (92 ) 4 % Net loss from continuing operations (8,865 ) (14,015 ) -37 % Discontinued operations: Loss from discontinued operations (7,828 ) (7,919 ) -1 % Income tax expenses — (14 ) -100 % Net loss from discontinued operations (7,828 ) (7,933 ) -1 % Net loss (16,693 ) (21,948 ) -24 % 137 Research and Development Expenses Research and development (R&D) expenses were $2.6 million for the year ended December 31, 2024 compared to $7.3 million for the year ended December 31, 2023.
Biggest changeDollars (“$”)) % Revenue — — — Operating expenses Research and development (4,388 ) (2,644 ) 66 % General and administrative (4,557 ) (6,110 ) -25 % Loss from operations (8,945 ) (8,754 ) 2 % Other income (expense) Foreign exchange gain (loss), net 165 (96 ) -272 % Interest income 78 59 32 % Other income, net 77 22 250 % Total other income (expense) 320 (15 ) -2233 % Net loss before income tax (8,625 ) (8,769 ) -2 % Income tax expenses (90 ) (96 ) -6 % Net loss from continuing operations (8,715 ) (8,865 ) -2 % Discontinued operations: Loss from discontinued operations (12,488 ) (7,828 ) 60 % Gain on sale of subsidiary interests 6,986 — — Income tax expenses — — — Net loss from discontinued operations (5,502 ) (7,828 ) -30 % Net loss (14,217 ) (16,693 ) -15 % Research and Development Expenses Research and development (R&D) expenses were $4.4 million for the year ended December 31, 2025 compared to $2.6 million for the year ended December 31, 2024.
Our future capital requirements will depend on many factors, including: ● the costs, timing and outcome of regulatory reviews and approvals; ● the ability of our product candidates to progress through clinical development successfully; ● the initiation, progress, timings, costs and results of studies in animals and clinical trials for our other programs and potential product candidates; ● the number and characteristics of the product candidates we pursue; ● the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; ● the extent to which we acquire or in-license other products and technologies; 140 ● our ability to establish and maintain arrangements partnership with other pharmaceutical companies for the development, licensing and commercialization of our assets; and ● our ability to maintain and establish collaboration arrangements on favorable terms, if at all.
Our future capital requirements will depend on many factors, including: ● the costs, timing and outcome of regulatory reviews and approvals; ● the ability of our product candidates to progress through clinical development successfully; ● the initiation, progress, timings, costs and results of studies in animals and clinical trials for our other programs and potential product candidates; ● the number and characteristics of the product candidates we pursue; ● the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; ● the extent to which we acquire or in-license other products and technologies; ● our ability to establish and maintain arrangements partnership with other pharmaceutical companies for the development, licensing and commercialization of our assets; and ● our ability to maintain and establish collaboration arrangements on favorable terms, if at all.
This unpredictability is due to the numerous risks and uncertainties associated with the duration and cost of clinical trials and commercialization of product candidates, which vary significantly over the life of a project as a result of many factors, including: ● the number of clinical sites included in the trials; ● the design of the trial and changes to the design of the trial; ● establishing an appropriate safety profile; ● the length of time required to enroll suitable patients; ● the number of patients that ultimately participate in the trials; ● the number of doses patients receive; ● the duration of patient follow-up; ● the results of our clinical trials; ● making arrangements with third-party manufacturers; ● receipt of marketing approvals from applicable regulatory authorities; ● commercializing the product candidates, if and when approved, whether alone or in collaboration with others; ● obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product candidates; 136 ● continued acceptable safety profiles of the products following approval; and ● retention of key research and development personnel.
This unpredictability is due to the numerous risks and uncertainties associated with the duration and cost of clinical trials and commercialization of product candidates, which vary significantly over the life of a project as a result of many factors, including: ● the number of clinical sites included in the trials; ● the design of the trial and changes to the design of the trial; ● establishing an appropriate safety profile; 133 ● the length of time required to enroll suitable patients; ● the number of patients that ultimately participate in the trials; ● the number of doses patients receive; ● the duration of patient follow-up; ● the results of our clinical trials; ● making arrangements with third-party manufacturers; ● receipt of marketing approvals from applicable regulatory authorities; ● commercializing the product candidates, if and when approved, whether alone or in collaboration with others; ● obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product candidates; ● continued acceptable safety profiles of the products following approval; and ● retention of key research and development personnel.
Significant judgments and estimates are made in determining the accrued balances at the end of any reporting period. Actual results could differ from our estimates. Our historical accrual estimates have not been materially different from the actual costs. Recent Accounting Pronouncements See Note 2 to our consolidated financial statements included in this Annual Report for recent accounting pronouncements.
Significant judgments and estimates are made in determining the accrued balances at the end of any reporting period. Actual results could differ from our estimates. Our historical accrual estimates have not been materially different from the actual costs. Recent Accounting Pronouncements See Note 2 to our consolidated financial statements included in this Annual Report for recent accounting pronouncements. 139
Our drug development capabilities are facilitated by strong interest from clinical investigators in the U.S. as well as by our understanding of the pharmaceutical industry, clinical resources and regulatory system in China. We have partnered with Hengrui to commercialize Plinabulin, if approved, in Greater China through our subsidiary, Wanchunbulin.
Our drug development capabilities are facilitated by strong interest from clinical investigators in the U.S. as well as by our understanding of the pharmaceutical industry, clinical resources and regulatory system in China. 130 We have partnered with Hengrui to commercialize Plinabulin, if approved, in Greater China through our subsidiary, Wanchunbulin.
Accordingly, we anticipate that we will need additional funding in connection with our future operations. Our liquidity is affected by financing activities, our clinical trials, and research and development and general and administrative expenses. We will need, among other things, additional capital resources to fund our business activities.
Accordingly, we anticipate that we will need additional funding in connection with our future operations. 137 Our liquidity is affected by financing activities, our clinical trials, and research and development and general and administrative expenses. We will need, among other things, additional capital resources to fund our business activities.
Otherwise, Wanchunbulin may be required to refund the grants. 141 Critical Accounting Estimates Our discussion and analysis of our financial condition and results of operations is based on our financial statements, which have been prepared in accordance with U.S. GAAP.
Otherwise, Wanchunbulin may be required to refund the grants. Critical Accounting Estimates Our discussion and analysis of our financial condition and results of operations is based on our financial statements, which have been prepared in accordance with U.S. GAAP.
SEED is partnering with Eli Lilly and Eisai to discover and develop new chemical entities through this proprietary TPD platform which could produce therapeutic benefits to patients suffering from oncology and CNS disease, among others. 132 Plinabulin is being studied as an anti-cancer agent in a number of company-sponsored studies and investigator-initiated studies.
SEED is partnering with Eli Lilly and Eisai to discover and develop new chemical entities through this proprietary TPD platform which could produce therapeutic benefits to patients suffering from oncology and CNS disease, among others. 129 Plinabulin is being studied as an anti-cancer agent in a number of company-sponsored studies and investigator-initiated studies.
Certain of these estimates are considered critical as they involve a significant level of estimation uncertainty and have had or are reasonably likely to have a material impact on our consolidated financial statements. Our critical accounting estimates are summarized below.
Certain of these estimates are considered critical as they involve a significant level of estimation uncertainty and have had or are reasonably likely to have a material impact on our consolidated financial statements. Our critical accounting estimate is summarized below.
Liquidity and Capital Resources Since inception, we have incurred net losses and negative cash flows from our operations. Substantially all of our negative cash flows have resulted from funding our research and development programs and general and administrative costs associated with our operations.
Liquidity and Capital Resources Since inception, we have incurred net losses and negative cash flows from our operations. Substantially all of our negative cash flows have resulted from funding our research and development programs and general and administrative expenses associated with our operations.
Research and development expenses also include activities related to: ● employee-related expenses, including salaries, benefits, share-based compensation and travel expense for research and development personnel; 135 ● expenses incurred under agreements with CROs, contract manufacturing organizations, and consultants that conduct and support clinical trials and preclinical studies; ● costs associated with preclinical studies and development activities; ● costs associated with regulatory operations; ● costs associated with protecting intellectual property; ● share-based compensation to employees, directors and non-employee consultants; and ● other expenses, which include direct and allocated expenses for rent, insurance and other supplies used in research and development activities.
Research and development expenses also include activities related to: ● employee-related expenses, including salaries, benefits, share-based compensation and travel expense for research and development personnel; ● expenses incurred under agreements with CROs, contract manufacturing organizations, and consultants that conduct and support clinical trials and preclinical studies; ● costs associated with preclinical studies and development activities; ● costs associated with regulatory operations; ● costs associated with protecting intellectual property; ● other expenses, which include direct and allocated expenses for rent, insurance and other supplies used in research and development activities.
In 2024, our discontinued operations generated $2.0 million of revenue through SEED’s research collaboration and license agreement with Eli Lilly and our continuing operations did not generate any revenue.
In 2025, our discontinued operations generated $2.0 million of revenue through SEED’s research collaboration and license agreement with Eli Lilly and our continuing operations did not generate any revenue.
Other expenses consist primarily of foreign exchange losses. Results of Operations Comparison of Years Ended December 31, 2024 and 2023 The following table summarizes the results of our operations for the years ended December 31, 2024 and 2023, respectively, together with the percentage changes in those items: Years Ended December 31, 2024 2023 Change (in thousands of U.S.
Other expenses consist primarily of foreign exchange losses. Results of Operations Comparison of Years Ended December 31, 2025 and 2024 The following table summarizes the results of our operations for the years ended December 31, 2025 and 2024, respectively, together with the percentage changes in those items: 134 Years Ended December 31, 2025 2024 Change (in thousands of U.S.
The following table provides information regarding our consolidated cash flows for the years ended December 31, 2024 and 2023: Year Ended December 31, 2024 2023 (in thousands of U.S.
The following table provides information regarding our consolidated cash flows for the years ended December 31, 2025 and 2024: Year Ended December 31, 2025 2024 (in thousands of U.S.
The RMB 200 million (approximately $31 million) upfront payment received by Wanchunbulin from Hengrui is recorded as deferred revenue and will be recognized as revenue over time after product approval using unit of delivery measure of progress.
The RMB 200 million (approximately $28.6 million) upfront payment received by Wanchunbulin from Hengrui is recorded as deferred revenue and will be recognized as revenue over time after product approval using unit of delivery measure of progress.
The following table summarizes the research and development expenses for the years ended December 31, 2024 and 2023: Year Ended December 31, 2024 2023 Change (in thousands of U.S.
The following table summarizes the research and development expenses for the years ended December 31, 2025 and 2024: Year Ended December 31, 2025 2024 Change (in thousands of U.S.
We currently do not expect to incur significant pre-commercialization costs in the near future. We also incur legal, compliance, accounting, directors and officers insurance, and investor and public relations expenses associated with being a public company. Other Income (Expenses) Other income consists primarily of government grants received and interest income earned on our cash and cash equivalents.
We currently do not expect to incur significant pre-commercialization costs in the near future. We also incur legal, compliance, accounting, directors and officers insurance, and investor and public relations expenses associated with being a public company. Other Income (Expenses) Other income consists primarily of foreign exchange gains and interest income earned on our cash and cash equivalents.
The DUBLIN-3 study enrolled 559 patients at 58 clinical sites globally and the final results from the study showed that the Plinabulin and docetaxel combination had statistically significant and clinically meaningful overall survival benefit compared to standard of care docetaxel alone.
The DUBLIN-3 study enrolled 559 patients at 58 clinical sites globally and the final results from the study showed that the Plinabulin and docetaxel combination had statistically significant and clinically meaningful overall survival benefit compared to standard of care docetaxel alone with doubling 2-year and 3-year OS rate.
Our operating activities used $16.4 million and $16.5 million of cash, including $7.7 million and $5.5 million used in discontinued operating activities, during the years ended December 2024 and 2023, respectively. We have financed our operations with a combination of equity offerings, shareholder and third-party loans, including bank loans, sale of subsidiary interests and collaboration arrangements.
Our operating activities used $19.8 million and $16.4 million of cash, including $12.3 million and $7.7 million used in discontinued operating activities, during the years ended December 2025 and 2024, respectively. We have financed our operations with a combination of equity offerings, shareholder and third-party loans, including bank loans, sale of subsidiary interests and collaboration arrangements.
Through December 31, 2024, we have raised approximately $299.0 million in equity financings, $10.2 million of issuance of non-controlling interests, $34.0 million from the sale of preferred shares of SEED, $2.1 million from bank loans, of which $0.6 million has been forgiven in July 2021 and $1.5 million has been repaid in March 2022, $2.5 million in third party loans, of which $1.0 million has since been converted into an equity investment and $1.5 million has been repaid, and $14.4 million in shareholder loans, of which $6.0 million has been repaid and $8.4 million was assumed by Wanchun Biotech, the former holding company of our U.S. subsidiary, on July 20, 2015 pursuant to our internal restructuring, $10.0 million upfront payment to SEED from Eli Lilly, and approximately $31.0 million upfront payment to Wanchunbulin from Hengrui.
Through December 31, 2025, we have raised approximately $301.0 million in equity financings, $10.2 million of issuance of non-controlling interests, $37.0 million from the sale of preferred shares of SEED in connection with its Series A-2/A-3 financings and $7.4 million from the sale of preferred shares of SEED by the Company to third-party investors, $2.1 million from bank loans, of which $0.6 million has been forgiven in July 2021 and $1.5 million has been repaid in March 2022, $2.5 million in third party loans, of which $1.0 million has since been converted into an equity investment and $1.5 million has been repaid, and $14.4 million in shareholder loans, of which $6.0 million has been repaid and $8.4 million was assumed by Wanchun Biotech, the former holding company of our U.S. subsidiary, on July 20, 2015 pursuant to our internal restructuring, $10.0 million upfront payment to SEED from Eli Lilly, and approximately $31.0 million upfront payment to Wanchunbulin from Hengrui.
The TPD platform segment was comprised of SEED’s operations. As a result of SEED’s operations being reclassified as discontinued operations, the TPD platform segment is excluded from the Company’s continuing operations at year end 2024. See Note 14 (Segment reporting and geographic information) to our consolidated financial statements for additional information.
As a result of SEED’s operations being reclassified as discontinued operations, the TPD platform segment is excluded from the Company’s continuing operations. See Note 14 (Segment reporting and geographic information) to our consolidated financial statements for additional information.
Net Cash Used in Operating Activities The cash used in operating activities for the years ended December 31, 2024 and 2023 resulted primarily from our net losses of $16.7 million and $21.9 million, respectively, adjusted for non-cash charges and changes in components of working capital.
Net Cash Used in Operating Activities The cash used in operating activities for the years ended December 31, 2025 and 2024 resulted primarily from our net losses of $14.2 million and $16.7 million, respectively, adjusted for non-cash charges and changes in components of working capital.
As of the date of this Annual Report on Form 10-K, the BYSI Entities own approximately 40.12% of the outstanding equity interest in SEED, and are expected to own approximately 28.02% and 14.37% of the outstanding equity interest in SEED after the second and third closings, respectively, in each case calculated on an as-converted basis (excluding any shares that may be reserved under an employee stock ownership plan, or similar arrangement), and assuming there is no other change to SEED’s share capital prior to such closings.
As of the date of this Annual Report on Form 10-K, the BYSI Entities own approximately 38.03% of the outstanding equity interest in SEED, and are expected to own approximately 26.56% and 13.62% of the outstanding equity interest in SEED after the second and third closings, respectively, in each case calculated on an as-converted basis (excluding any shares that may be reserved under an employee stock ownership plan, or similar arrangement), and assuming there is no other change to SEED’s share capital prior to such closings.
Plinabulin is also being studied in a Phase 2 investigator-initiated study (Study 302) in combination with Keytruda®, etoposide and platinum for the first-line treatment of ES-SCLC patients at Wuhan Union Hospital in China, where the current standard of care has limited median PFS.
Plinabulin’s rapid DC maturation biomarker analysis was observed in responding patients. Plinabulin is also being studied in a Phase 2 investigator-initiated study (Study 302) in combination with Keytruda®, etoposide and platinum for the first-line treatment of ES-SCLC patients at Wuhan Union Hospital in China, where the current standard of care has limited median PFS.
Dollars (“$”)) Net cash used in discontinued operating activities (7,665 ) (5,474 ) Net cash used in discontinued investing activities (12,012 ) (91 ) Net cash provided by discontinued financing activities 23,815 4 Cash inflows generated by our discontinued operations were used to support their own operations, including funding their own R&D activities, rather than being transferred to or used by the continuing operations.
Dollars (“$”)) Net cash used in discontinued operating activities (12,314 ) (7,665 ) Net cash provided by (used in) discontinued investing activities 8,207 (12,012 ) Net cash provided by discontinued financing activities 2,980 23,815 Cash inflows generated by our discontinued operations were used to support their own operations, including funding their own R&D activities, rather than being transferred to or used by the continuing operations.
Our first-in-class lead asset, Plinabulin, which has been administered to over 700 cancer patients with generally good tolerability, is being developed as a potential “pipeline in a drug” in various cancer indications as a direct anti-cancer agent. We are also developing three small molecule immune agents, which are currently in pre-clinical stages.
Plinabulin has been administered to over 700 cancer patients with generally good tolerability and is being developed as a potential “pipeline in a drug” in various cancer indications as a direct anti-cancer agent with safety benefit of CIN. We are also developing three small molecule immune agents, which are currently in pre-clinical stages.
Additional investigator initiated studies with Plinabulin include: 1) in combination with nivolumab, a PD-1 antibody, for the treatment of NSCLC at UCSD and the University of Washington (Phase 1 completed); 2) in combination with nivolumab and ipilimumab, a CTLA-4 antibody, for the treatment of ES-SCLC at the Rutgers University and other U.S. clinical centers (Phase 1 completed, Phase 2 completed for patients who progressed on PD-1/PD-L1 antibodies); and 3) in combination with PD-1 or PD-L1 antibodies and radiation for the treatment of patients with various cancers who progressed from PD-1/PD-L1 antibodies at MD Anderson (Phase 1 completed and presented at SITC 2023).
Additional completed investigator initiated studies with Plinabulin include: 1) in combination with nivolumab, a PD-1 antibody, for the treatment of NSCLC at UCSD and the University of Washington (Phase 1 completed); and 2) in combination with nivolumab and ipilimumab, a CTLA-4 antibody, for the treatment of ES-SCLC at the Rutgers University and other U.S. clinical centers (Phase 1 completed, Phase 2 completed for patients who progressed on PD-1/PD-L1 antibodies).
For so long as the BYSI Entities remain holders of a majority of the Series A-1 Preferred Shares of SEED, they have the right to elect two directors of SEED.
For so long as the BYSI Entities remain holders of a majority of the Series A-1 Preferred Shares of SEED, they have the right to elect two directors of SEED. In addition, holders of a majority of the Series A-1 Preferred Shares and ordinary shares of SEED will have the right to elect two independent directors of SEED.
Our advances to suppliers and other current assets, accounts payable and accrued expense balances in all periods presented were affected by the timing of vendor invoicing and payments. Net Cash Used in Investing Activities Net cash used in investing activities for the year ended December 31, 2024 and 2023 was $12.0 million and $0.1 million, respectively.
Our advances to suppliers and other current assets, accounts payable and accrued expense balances in all periods presented were affected by the timing of vendor invoicing and payments. Net Cash Provided by (Used in) Investing Activities Net cash provided by investing activities for the year ended December 31, 2025 was $10.8 million.
We incurred consolidated net losses of $16.7 million and $21.9 million for the years ended December 31, 2024 and 2023, respectively. As of December 31, 2024 and 2023, we had an accumulated deficit of $407.4 million and $396.3 million, respectively. Our primary use of cash is to fund research and development costs and for general and administrative costs.
We incurred consolidated net losses of $14.2 million and $16.7 million for the years ended December 31, 2025 and 2024, respectively. As of December 31, 2025 and 2024, we had an accumulated deficit of $408.4 million and $407.4 million, respectively. Our primary use of cash is to fund research and development costs and for general and administrative expenses.
Dollars (“$”)) Net cash used in operating activities (16,443 ) (16,474 ) Net cash used in investing activities (12,012 ) (100 ) Net cash provided by financing activities 26,785 4 Net effect of foreign exchange rate changes (33 ) (76 ) Net decrease in cash, cash equivalents and restricted cash (1,703 ) (16,646 ) The following table provides information regarding cash flows of discontinued operations for the years ended December 31, 2024 and 2023: Year Ended December 31, 2024 2023 (in thousands of U.S.
Dollars (“$”)) Net cash used in operating activities (19,769 ) (16,443 ) Net cash provided by (used in) investing activities 10,787 (12,012 ) Net cash provided by financing activities 4,968 26,785 Net effect of foreign exchange rate changes 105 (33 ) Net decrease in cash and cash equivalents (3,909 ) (1,703 ) 136 The following table provides information regarding cash flows of discontinued operations for the years ended December 31, 2025 and 2024: Year Ended December 31, 2025 2024 (in thousands of U.S.
Once patients progress on these regimens, docetaxel is the recommended in the second line, but it has modest clinical benefit and high severe neutropenia.
Once patients progress on these regimens, docetaxel, a drug approved over 25 years ago, is recommended in the second- and third-line, but it has modest clinical benefit and high severe neutropenia.
During 2024, these non-cash charges mainly consisted of $2.3 million of non-cash share-based compensation and $0.7 million of non-cash operating lease expenses. Net cash used in operating activities was $16.4 million for the year ended December 31, 2024, compared to $16.5 million for the year ended December 31, 2023.
During 2025, these non-cash charges mainly consisted of $7.0 million of gain on sale of subsidiary interests, $0.7 million of non-cash share-based compensation and $0.7 million of non-cash operating lease expenses. Net cash used in operating activities was $19.8 million for the year ended December 31, 2025, compared to $16.4 million for the year ended December 31, 2024.
Net cash provided by financing activities for the year ended December 31, 2023 was $4.0 thousand. During 2024, we received aggregate net cash proceeds of $3.0 million from the issuance of our equity securities. SEED received $20.0 million from the issuance of its Series A-3 Preferred Shares.
Net Cash Provided by Financing Activities Net cash provided by financing activities for the year ended December 31, 2025 and 2024 was $5.0 million and $26.8 million, respectively. During 2025, we received aggregate net cash proceeds of $2.0 million from the issuance of our equity securities. SEED received $3.0 million from the sale of its Series A-3 Preferred Shares.
Contractual Obligations Lease commitments The principal commitments from continuing operations consist of obligations under our operating leases for office space. We lease all of our facilities and believe our current facilities are sufficient to meet our needs. Our principal executive offices are located in New Jersey, and we also have offices in Beijing and Dalian, China.
Contractual Obligations Lease commitments The principal commitments from continuing operations consist of obligations under our operating leases for office space. We lease all of our facilities and believe our current facilities are sufficient to meet our needs.
Wanchunbulin also undertakes not to establish additional entities in other jurisdictions within Greater China for the purposes of conducting research, development, and commercialization activities related to Plinabulin, provided such activities fall within the scope of the government grant agreement.
Wanchunbulin commits to staying within designated districts, maintaining current tax jurisdictions, and retaining its registered capital, until 2033. Wanchunbulin also undertakes not to establish additional entities in other jurisdictions within Greater China for the purposes of conducting research, development, and commercialization activities related to Plinabulin, provided such activities fall within the scope of the government grant agreement.
We presented the early data of disease control rate and prolonged PFS from this study at ESMO 2024 and SITC 2024.
We presented clinical meaningful data of high disease control rate and prolonged PFS from this study at ESMO 2024, SITC 2024, and ASCO 2025.
Cash flows from discontinued operations are not reclassified in the Consolidated Statements of Cash Flows but are disclosed in the accompanying financial footnotes. See Note 3 (Discontinued operations) to our consolidated financial statements for additional information. Segments From 2022 to 2024, we operated in two reportable segments, namely Plinabulin pipeline and TPD platform.
See Note 3 (Discontinued operations) to our consolidated financial statements for additional information. Segments From 2022 to 2024, we operated in two reportable segments, namely Plinabulin pipeline and TPD platform. The TPD platform segment was comprised of SEED’s operations.
Operating Expenses Research and Development Expenses The largest component of our total operating expenses has historically been our investment in research and development activities. Research and development expenses consist of costs associated with our research and development activities, conducting preclinical studies and clinical trials of Plinabulin and development of our pipeline of immune-oncology product candidates.
Research and development expenses consist of costs associated with our research and development activities, conducting preclinical studies and clinical trials of Plinabulin and development of our pipeline of immune-oncology product candidates.
In particular, inflation and high interest rates across the global economy, governments’ monetary policy in response to inflation concerns, concerns around tariffs and a possible recession, the ongoing hostilities between Russia and Ukraine and the current war between Israel and Hamas have caused, and may continue to cause, market volatility, and under such market conditions, we may not be able to obtain funding on reasonable terms or at all.
In particular, inflation and high interest rates across the global economy, governments’ monetary policy in response to inflation concerns, concerns around tariffs and a possible recession, the ongoing hostilities between Russia and Ukraine and escalating geopolitical tensions and military conflicts in the Middle East, including conflicts involving Israel, Hamas, Iran and other regional actors, have caused, and may continue to cause, market volatility, and under such market conditions, we may not be able to obtain funding on reasonable terms or at all. 131 Discontinued Operations SEED was founded by us in 2019.
In the U.S. and for the rest of the world, we currently plan to seek a co-development and commercialization partner to maximize Plinabulin’s potential in multiple cancer indications, if approved. 133 Since the inception of Wanchun Biotech, the former holding company of our U.S. subsidiary, in 2010, our operations have focused on organizing and staffing our company, business planning, raising capital, establishing our intellectual property portfolio, including protecting the rights to Plinabulin, and conducting studies in animals and clinical trials of Plinabulin.
Since the inception of Wanchun Biotech, the former holding company of our U.S. subsidiary, in 2010, our operations have focused on organizing and staffing our company, business planning, raising capital, establishing our intellectual property portfolio, including protecting the rights to Plinabulin, and conducting studies in animals and clinical trials of Plinabulin.
During 2023, net cash was primarily provided by the proceed of employees’ exercise of share options issued by SEED. Future Liquidity and Material Cash Requirements We do not expect to generate significant revenue from product sales unless and until we obtain regulatory approval of and commercialize any of our current product candidates.
Future Liquidity and Material Cash Requirements We do not expect to generate significant revenue from product sales unless and until we obtain regulatory approval of and commercialize any of our current product candidates.
In January 2025, we entered into definitive agreements to sell a portion of our Series A-1 Preferred Shares of SEED for $35.4 million, or $4.25 per share, to certain third-party investors in three installments. The first closing of 1,730,454 shares for approximately $7.35 million occurred in February 2025.
As of December 31, 2025, the BYSI Entities owned an aggregate of 10,289,545 Series A-1 Preferred Shares of SEED. In January 2025, we entered into definitive agreements to sell a portion of our Series A-1 Preferred Shares of SEED for $35.4 million, or $4.25 per share, to certain third-party investors in three installments.
We provide financial support for these various investigator-initiated clinical trials as well as the drug supply of Plinabulin. We expect each of these studies to benefit from our previous investigation of Plinabulin as an agent that has been studied in two randomized, controlled Phase 3 clinical studies to have demonstrated a statistically significant reduction in CIN.
We expect each of these studies to benefit from our previous investigation of Plinabulin as an agent that has been studied in two randomized, controlled Phase 3 clinical studies to have demonstrated a statistically significant reduction in CIN. In total, over 700 patients have been treated with Plinabulin, where improvements in CIN have been repeatedly observed.
Payments under the lease are expensed on a straight-line basis over the period of the lease. Other contractual obligations We enter into agreements in the normal course of business with CROs and institutions to license intellectual property. These contracts are cancelable at any time by us with prior written notice.
Other contractual obligations We enter into agreements in the normal course of business with CROs and institutions to license intellectual property. These contracts are cancelable at any time by us with prior written notice. Our subsidiary Wanchunbulin has entered into a government grant agreement with specific local authorities in the PRC.
SEED is utilizing a proprietary Targeted Protein Degradation (TPD) drug discovery platform, or “molecular glue” technology, to develop innovative therapeutic agents from internal research and development efforts and with our collaborators on currently undruggable protein targets.
SEED is utilizing a proprietary TPD drug discovery platform, or “molecular glue” technology, to develop innovative therapeutic agents from internal research and development efforts and with our collaborators on currently undruggable protein targets. SEED has advanced its wholly owned lead oncology asset, a novel RBM39 degrader into phase 1 clinical studies in January 2026.
For the year ended December 31, 2024, we have received aggregate net cash proceeds of $3.0 million from the issuance of our equity securities. As of December 31, 2024, our continuing operations had cash and cash equivalents of $2.9 million.
For the year ended December 31, 2025, we have received aggregate net cash proceeds of $2.0 million from the issuance of our equity securities. As of December 31, 2025, our continuing operations had cash and cash equivalents of $7.8 million. Our liquidity is affected by financing activities, our clinical trials, and research and development and general and administrative expenses.
Dollars (“$”)) % Clinical expenses 417 2,483 -83 % Preclinical expenses 45 113 -60 % Professional services 994 1,363 -27 % Personnel compensation and related costs 1,015 2,815 -64 % Facility and other expenses 173 498 -65 % Total research and development 2,644 7,272 -64 % General and Administrative Expenses General and administrative (G&A) expenses were $6.1 million for the year ended December 31, 2024, compared to $7.8 million for the year ended December 31, 2023.
Dollars (“$”)) % Clinical expenses 1,235 417 196 % Preclinical expenses 395 45 778 % Professional services 1,170 994 18 % Personnel compensation and related costs 1,336 1,015 32 % Facility and other expenses 252 173 46 % Total research and development 4,388 2,644 66 % General and Administrative Expenses General and administrative (G&A) expenses were $4.6 million for the year ended December 31, 2025, compared to $6.1 million for the year ended December 31, 2024.
In the future, we may generate revenue from a combination of product sales, reimbursements, upfront payments, milestone payments and royalties in connection with existing and future collaborations. If we fail to complete the development of our product candidates in a timely manner or fail to obtain their regulatory approval, we will not generate revenue from product sales in the future.
In the future, we may generate revenue from a combination of product sales, reimbursements, upfront payments, milestone payments and royalties in connection with existing and future collaborations.
The second closing of 3,103,055 shares for approximately $13.19 million and the third closing of 3,500,128 shares for approximately $14.88 million are expected to occur no later than December 15, 2025 and 2026, respectively.
The first closing of 1,730,454 shares for approximately $7.35 million occurred in February 2025. The second closing of 3,103,055 shares for approximately $13.19 million is expected to be completed in 2026. Under the terms of the definitive agreements, the third closing of 3,500,128 shares for approximately $14.88 million is scheduled to occur no later than December 15, 2026.
We reclassified the financial results of SEED to Discontinued Operations in the Consolidated Statements of Comprehensive Loss for all periods presented. We also reclassified the related assets and liabilities as current and noncurrent assets and liabilities of discontinued operations on the accompanying Consolidated Balance Sheets as of December 31, 2024 and 2023.
We also reclassified the related assets and liabilities as current and noncurrent assets and liabilities of discontinued operations on the accompanying Consolidated Balance Sheets as of December 31, 2025 and 2024. Cash flows from discontinued operations are not reclassified in the Consolidated Statements of Cash Flows but are disclosed in the accompanying financial footnotes.
We additionally pay for the cost of utilities, as well as our share of building real estate taxes and building operating expenses. Payments under the lease are expensed on a straight-line basis over the period of the lease. As of December 31, 2024, we occupied office space in Dalian, China, under a rent-free arrangement with the local government.
Starting in August 2026, our annual rent will increase by $0.50 per square foot leased. We additionally pay for the cost of utilities, as well as our share of building real estate taxes and building operating expenses. Payments under the lease are expensed on a straight-line basis over the period of the lease.
During 2024, net cash was primarily used for acquiring time deposits. During 2023, net cash was primarily used for acquiring property and equipment. Net Cash Provided by Financing Activities Net cash provided by financing activities for the year ended December 31, 2024 was $26.8 million.
Net cash used in investing activities for the year ended December 31, 2024 was $12.0 million. During 2025, net cash was primarily provided by maturity of time deposits, partially offset by cash used in acquiring structured deposits. During 2024, net cash was primarily used for acquiring time deposits.
Substantially all of our losses have resulted from funding our preclinical studies, clinical trials, manufacturing our drug product, our research and development programs and from general and administrative costs associated with our operations. We expect to continue to incur significant expenses and operating losses for the foreseeable future.
As of December 31, 2025 and 2024, we had an accumulated deficit of $408.4 million and $407.4 million, respectively. Substantially all of our losses have resulted from funding our preclinical studies, clinical trials, manufacturing our drug product, our research and development programs and from general and administrative expenses associated with our operations.
Business—SEED’s Targeted Protein Degradation (TPD) Platform and Pipeline.” Since inception we have incurred operating losses. Our consolidated net losses were $21.9 million and $16.7 million for the years ended December 31, 2023 and 2024, respectively. As of December 31, 2023 and 2024, we had an accumulated deficit of $396.3 million and $407.4 million, respectively.
As of December 31, 2025, our continuing operations had cash and cash equivalents of $7.8 million. Since inception we have incurred operating losses. Our consolidated net losses were $14.2 million and $16.7 million for the years ended December 31, 2025 and 2024, respectively.
Upon the lease’s expiration on December 31, 2024, we transitioned to a new office space in Dalian, China, under a lease agreement with a different landlord. The new office, effective January 1, 2025, measures 210.65 square meters, with a monthly rent of $1,404. The lease is set to expire on December 31, 2027.
We lease office space in Dalian, China, with total space of 210.65 square meters and a monthly rent of RMB 10,252 (approximately $1,466). The lease is set to expire on December 31, 2027. Payments under the lease are expensed on a straight-line basis over the period of the lease.
We currently lease office space in New Jersey, with total space of 9,727 square feet. The lease expires in February 2027. Our current rent is $25,939 per month. Starting in August 2025, our annual rent will increase by $0.50 per square foot leased.
Our principal executive offices are located in New Jersey, and we also have offices in Beijing and Dalian, China. 138 We currently lease office space in New Jersey, with total space of 9,727 square feet. The lease expires in February 2027. Our current rent is $26,344 per month.
There were no major changes to the scale of operating activities on a consolidated basis. 139 The primary use of our cash in the periods presented was to fund the development of our research and development, regulatory and other clinical trial costs and related administrative costs.
The $3.4 million increase was primarily due to increase of operating cash expenditures by our discontinued operations to fund their own R&D activities. The primary use of our cash in the periods presented was to fund our research and development, regulatory and other clinical trial costs and related administrative expenses.
We plan to use our best efforts to file an NDA with the NMPA as soon as possible. The current standard of care for first-line NSCLC without driver mutations is chemotherapy plus PD-1/PD-L1 antibodies, with 60% patients progress on these therapies.
We plan to use our best efforts to file an NDA with the NMPA as soon as possible.
We completed a randomized global Phase 3 study of Plinabulin in combination with docetaxel compared with docetaxel alone for second- and third- line treatment of NSCLC, EGFR wild type (DUBLIN-3 Phase 3 registration study).
After a successful phase 3 study (DUBLIN-3) in NSCLC, Plinabulin regimen is in a confirmatory global phase 3 study in second- and third-line NSCLC with epidermal growth factor receptor (EGFR) wild type after progression on prior immune checkpoint inhibitors, a severe unmet medical need.
The $1.7 million decrease was primarily due to lower professional services costs. There were also decreases in costs in facilities, financial operations and miscellaneous items such as travel and entertainment, as results of process optimization and workflow streamlining. Other Income (Expenses) Other income for the year ended December 31, 2024 consisted primarily of foreign exchange losses, offset by interest income.
Other income for the year ended December 31, 2024 consisted primarily of foreign exchange losses, offset by interest income.
Removed
In total, over 700 patients have been treated with Plinabulin, where improvements in CIN have been repeatedly observed.
Added
Our first-in-class lead asset, Plinabulin is a novel brain-penetrant microtubule modulator with dendritic cell maturation and vasculature modulation mechanism, which has the potential to help mitigate “acquired resistance” from prior ICI treatment in cancer patients.
Removed
As of December 31, 2024, our continuing operations had cash and cash equivalents of $2.9 million. In February 2025, we received approximately $7.35 million in cash as consideration for the first closing of the sale of a portion of our equity interests in SEED, as further described under “Item 1.
Added
Because DUBLIN-3 study had over 80% patients from Asia, we plan to initiate a confirmatory global phase 3 study in second- and third-line non-squamous NSCLC with epidermal growth factor receptor (EGFR) wild type after progression on prior immune checkpoint inhibitors, based on productive discussion with US regulatory agency.
Removed
Discontinued Operations SEED was founded by us in 2019. As of December 31, 2024, the BYSI Entities owned an aggregate of 12,019,999 Series A-1 Preferred Shares of SEED.
Added
The current standard of care for first-line EGFR wild type NSCLC is PD-1/PD-L1 antibodies with or without platinum doublet. However, over 60% patients progress on these therapies, defined as “acquired resistance” due to “T cell exhaustion” and/or “APC pathway mutation” (Memon et al., Cancer Cell 2024).
Removed
In addition, holders of a majority of the Series A-1 Preferred Shares and ordinary shares of SEED will have the right to elect two independent directors of SEED. 134 As a result, SEED’s operations met the criteria under ASC 205-20 as discontinued operations for financial reporting purposes.
Added
In addition, our collaborators at MD Anderson Cancer Center have completed a phase 1 IIT study in Plinabulin combination with PD-1 or PD-L1 antibodies and radiation for the treatment of patients in eight cancers who progressed from PD-1/PD-L1 antibodies, with disease control rate of 54%. This paper was published in Cell Press “Med” in June 2025.
Removed
The $4.7 million decrease was primarily due to lower clinical development expense, lower professional services expense, lower personnel costs and lower facility and other expenses, as results of completion of DUBLIN-3, PROTECTIVE-1 and PROTECTIVE-2 studies.
Added
In the U.S. and for the rest of the world, we currently plan to seek a co-development and commercialization partner to maximize Plinabulin’s potential in multiple cancer indications, if approved.
Removed
Other income for the year ended December 31, 2023 consisted primarily of $0.8 million of cash government grants received for R&D expenses incurred in the past and $0.3 million of interest income.
Added
We expect to continue to incur significant expenses and operating losses for the foreseeable future.
Removed
In February 2025, we received approximately $7.35 million in cash as consideration for the first closing of the sale of a portion of our equity interests in SEED, as further described under “Item 1.
Added
In September 2025, SEED entered into share purchase agreements with certain third-party investors to sell an aggregate of 1,411,761 of its Series A-3 Preferred Shares for an aggregate purchase price of $6 million at a cash purchase price of $4.25 per share.
Removed
Business—SEED’s Targeted Protein Degradation (TPD) Platform and Pipeline.” 138 Our liquidity is affected by financing activities, our clinical trials, and research and development and general and administrative expenses. We will need, among other things, additional capital resources.
Added
As a result, SEED’s operations met the criteria under ASC 205-20 as discontinued operations for financial reporting purposes. We reclassified the financial results of SEED to Discontinued Operations in the Consolidated Statements of Comprehensive Loss for all periods presented. In connection with the first closing described above, we recorded a gain on sale of subsidiary interests of $7.0 million.
Removed
This space, measuring 860.12 square meters, remained in use throughout 2024 while our formal application for rent exemption was under review. The local government office has since approved the rent-free subsidy for the 2024 lease, and as of March 1, 2025, the subsidy is pending disbursement by the government’s finance department.
Added
If we fail to complete the development of our product candidates in a timely manner or fail to obtain their regulatory approval, we will not generate revenue from product sales in the future. 132 Operating Expenses Research and Development Expenses The largest component of our total operating expenses has historically been our investment in research and development activities.
Removed
Our subsidiary Wanchunbulin has entered into a government grant agreement with specific local authorities in the PRC. Wanchunbulin commits to staying within designated districts, maintaining current tax jurisdictions, and retaining its registered capital, until 2033.

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