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What changed in Traws Pharma, Inc.'s 10-K — 2022 vs 2023

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Paragraph-level year-over-year comparison of Traws Pharma, Inc.'s 2022 and 2023 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 2023 report.

+271 added−281 removedSource: 10-K (2024-04-01) vs 10-K (2023-03-30)

Top changes in Traws Pharma, Inc.'s 2023 10-K

271 paragraphs added · 281 removed · 235 edited across 5 sections

Item 1. Business

Business — how the company describes what it does

119 edited+19 added−19 removed266 unchanged
Biggest changeThe steps required before a new drug may be marketed in the United States generally include: ● Completion of preclinical or nonclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice (GLP), regulations and other applicable laws and regulations; ● Submission to the FDA of an IND to support human clinical testing; ● Approval by an IRB at each clinical site or centrally before each trial may be initiated; ● Performance of adequate and well-controlled clinical trials in accordance with federal regulations and with current good clinical practices (GCPs) to establish the safety and efficacy of the investigational drug product for each targeted indication; 14 Table of Contents ● Submission of an NDA to the FDA; ● Satisfactory completion of an FDA Advisory Committee review, if applicable; ● Satisfactory completion of an FDA inspection of the manufacturing facilities at which the investigational product is produced to assess compliance with cGMPs, and to assure that the facilities, methods and controls are adequate, as well as satisfactory completion of FDA inspections of selected clinical trial sites to ensure that clinical trials were conducted in accordance with GCPs; and ● FDA review and approval of the NDA.
Biggest changeThese sanctions could include the imposition by the FDA or an institutional review board (IRB), or Independent Ethics Committee (IEC) of a hold on clinical trials, refusal to approve pending marketing applications or supplements, withdrawal of approval, warning letters, untitled letters, cyber letters, product recalls, product seizures or detention, prohibition on importing or exporting, total or partial suspension of production or distribution, injunctions, fines, civil penalties, adverse publicity, disgorgement, restitution, FDA debarment, debarment from government contracting or refusal of future orders under existing contracts, exclusion from Federal healthcare programs, corporate integrity agreements, consent decrees, or criminal prosecution. 14 Table of Contents The steps required before a new drug may be marketed in the United States generally include: ● Completion of preclinical or nonclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice (GLP), regulations and other applicable laws and regulations; ● Submission to the FDA of an IND to support human clinical testing; ● Approval by an IRB at each clinical site or centrally before each trial may be initiated; ● Performance of adequate and well-controlled clinical trials in accordance with federal regulations and with current good clinical practices (GCPs) to establish the safety and efficacy of the investigational drug product for each targeted indication; ● Submission of an NDA to the FDA; ● Satisfactory completion of an FDA Advisory Committee review, if applicable; ● Satisfactory completion of an FDA inspection of the manufacturing facilities at which the investigational product is produced to assess compliance with cGMPs, and to assure that the facilities, methods and controls are adequate, as well as satisfactory completion of FDA inspections of selected clinical trial sites to ensure that clinical trials were conducted in accordance with GCPs; and ● FDA review and approval of the NDA.
In addition, using a cellular based assay that measures kinase activity in intact cells, NanoBret technology, it was determined that narazaciclib inhibited ARK5 3 Table of Contents with an IC50 value of 30 nM, while 2 published inhibitors, HTH-015-01 and WZ4003, had IC50 values of >10,000 nM.
In addition, using a cellular based assay that measures kinase activity in intact cells, NanoBret technology, it was determined that narazaciclib inhibited ARK5 with an IC50 value of 3 Table of Contents 30 nM, while 2 published inhibitors, HTH-015-01 and WZ4003, had IC50 values of >10,000 nM.
At baseline, the patient had extensive, unresectable cSCC involving the left elbow region as well nodal disease noted on PET-CT scan. After 4 cycles of oral rigosertib starting at 560 mg PO BID, there was reportedly complete clinical remission of all cSCC lesions. The patient has tolerated oral rigosertib and remains on therapy.
At baseline, the patient had extensive, unresectable cSCC involving the left elbow region as well as nodal disease noted on PET-CT scan. After 4 cycles of oral rigosertib starting at 560 mg PO BID, there was reportedly complete clinical remission of all cSCC lesions. The patient has tolerated oral rigosertib and remains on therapy.
In addition, the Affordable Care Act provides that the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a per se false or fraudulent claim for purposes of the civil False Claims Act (discussed below) or the civil monetary penalties statute, which imposes penalties against any person who is determined to have presented or caused to be presented a claim to a federal healthcare program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent.
In addition, the Affordable Care Act provides that the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a per se false or fraudulent claim for purposes of the civil False Claims Act (discussed below), which imposes penalties against any person who is determined to have presented or caused to be presented a claim to a federal healthcare program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent.
We believe our CDK inhibitor is differentiated from other agents in the market or in development due to its multi-targeted kinase inhibition profile. ​ ​ ​ ​ ​ ​ ​ Narazaciclib Palbociclib Ribociclib Abemaciclib Sponsor Onconova Pfizer Novartis Lilly ​ ​ CDK Family ​ ​ CDK4/cyclin D1 2 2 3 0.8 CDK6/cyclin D1 0.6 0.8 6.0 0.6 CDK1/cyclin A 2190 >10,000 >10,000 270 CDK2/cyclin E 69 2300 >10,000 130 CDK9/T1 48 630 390 7 ​ ​ Other Kinases ​ ​ CSF1R 0.7 >10,000 >10,000 >10,000 ARK 5/NUAK 1 5 1,400 1,540 773 FLT3 6.0 496 753 72 ​ Source: Reaction Biology 2021 In addition to CDK 4/6, narazaciclib also inhibits ARK5 (NUAK1) with high potency with a 50% inhibitory concentration (IC50) of 4.95 nM (Report EPR-123300-001 and Reddy 2014) while palbociclib, ribociclib, and abemaciclib do not.
We believe our CDK inhibitor is differentiated from other agents in the market or in development due to its multi-targeted kinase inhibition profile. ​ ​ ​ ​ ​ ​ ​ Narazaciclib Palbociclib Ribociclib Abemaciclib Sponsor Onconova Pfizer Novartis Lilly ​ ​ CDK Family ​ ​ CDK4/cyclin D1 2 2 3 0.8 CDK6/cyclin D1 0.6 0.8 6.0 0.6 CDK1/cyclin A 2190 >10,000 >10,000 270 CDK2/cyclin E 69 2300 >10,000 130 CDK9/T1 48 630 390 7 ​ ​ Other Kinases ​ ​ CSF1R 0.7 >10,000 >10,000 >10,000 ARK 5/NUAK 1 5 1,400 1,540 773 FLT3 6.0 496 753 72 ​ Source: Reaction Biology 2021 In addition to CDK 4/6, narazaciclib also inhibits ARK5 (NUAK1) with a 50% inhibitory concentration (IC50) of 4.95 nM (Report EPR-123300-001 and Reddy 2014) while palbociclib, ribociclib, and abemaciclib do not.
Second-generation compounds (palbociclib and ribociclib) specifically inhibit CDK4 and 6, thereby inhibiting retinoblastoma (RB) protein phosphorylation. Abemaciclib is a multi-targeted kinase CDK4/6 inhibitor with low nano molar activity against CDK4/6. The second generation CDK4/6 inhibitors have substantially improved clinical outcomes for patients with hormonal-receptor (HR) positive metastatic breast cancer (Hortobagyi 2018, Sledge 2017, Finn 2016).
Second-generation compounds (palbociclib and ribociclib) specifically inhibit CDK4 and 6, thereby inhibiting retinoblastoma protein phosphorylation. Abemaciclib is a multi-targeted kinase CDK4/6 inhibitor with low nano molar activity against CDK4/6. The second generation CDK4/6 inhibitors have substantially improved clinical outcomes for patients with hormonal-receptor (HR) positive metastatic breast cancer (Hortobagyi 2018, Sledge 2017, Finn 2016).
Under the Veterans Health Care Act, or VHCA, drug companies are required to offer “covered drugs” (including all drugs approved under an NDA) at no more than a statutory ceiling price, calculated based on a manufacturer’s required price calculations, to four federal agencies including the U.S. Department of Veterans Affairs and DoD, the Public Health Service.
Under the Veterans Health Care Act, or VHCA, drug companies are required to offer “covered drugs” (including all drugs approved under an NDA) at no more than a statutory ceiling price, calculated based on a manufacturer’s required price calculations, to four federal agencies including the U.S. Department of Veterans Affairs, Indian Health Service, DoD, and the Public Health Service.
The Affordable Care Act further created new federal requirements for reporting, by applicable manufacturers of covered drugs, of information related to payments and other transfers of value made to or at the request of covered recipients, namely US-licensed physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family.
The Affordable Care Act further created new federal requirements for reporting, by applicable manufacturers of covered drugs, of information related to payments and other transfers of value made to or at the request of covered recipients, namely US-licensed physicians and teaching hospitals, as well as ownership and investment interests held by physicians and members of their immediate family.
These requirements include required fees, rebates, discounts and payment reductions, required price reporting and pricing transparency, caps on price increases, requirements around price negotiation, and requirements to enter into agreements with government agencies and certain healthcare entities that may result in significant limits on the prices we may charge for our products.
These requirements include permissable fees, rebates, discounts and payment reductions, required price reporting and pricing transparency, caps on price increases, requirements around price negotiation, and requirements to enter into agreements with government agencies and certain healthcare entities that may result in significant limits on the prices we may charge for our products.
The allowable patent term extension is calculated as half of the drug’s testing phase — the time between IND application and NDA submission — and all of the review phase — the time between NDA submission and approval up to a maximum of five years.
The allowable patent term extension is calculated as half of the drug’s testing phase — the time between IND application and full NDA submission — and all of the review phase — the time between full NDA submission and approval up to a maximum of five years.
The length of the patent term extension is determined based upon the time from the IND effective date to the NDA submission date, and the time from NDA submission date and the eventual application approval, as further described below.
The length of the patent term extension is determined based upon the time from the IND effective date to the full NDA submission date, and the time from NDA submission date and the eventual application approval, as further described below.
These sanctions could include the imposition by the FDA or an institutional review board, or IRB, of a hold on clinical trials, refusal to approve pending marketing applications or 21 Table of Contents supplements, withdrawal of approval, warning letters, untitled letters, cyber letters, product recalls, product seizures or detention, prohibition on importing or exporting, total or partial suspension of production or distribution, injunctions, fines, civil penalties, adverse publicity, disgorgement, restitution, FDA debarment, debarment from government contracting or refusal of future orders under existing contracts, exclusion from Federal healthcare programs, corporate integrity agreements, consent decrees, or criminal prosecution.
These sanctions could include the imposition by the FDA or an institutional review board, or IRB, of a hold on clinical trials, refusal to approve pending marketing applications or supplements, withdrawal of approval, warning letters, untitled letters, cyber letters, product recalls, product seizures or detention, prohibition on importing or exporting, total or partial suspension of production or distribution, injunctions, fines, civil penalties, adverse publicity, disgorgement, restitution, FDA debarment, debarment from government contracting or refusal of future orders under existing contracts, exclusion from Federal healthcare programs, corporate integrity agreements, consent decrees, or criminal prosecution.
Preclinical investigations demonstrated overexpression of polo like kinase 1 (PLK1) in RDEB-associated SCC tumor cells. These tumors show a highly aggressive, early metastasizing course, making them the primary cause of death for these patients, with a cumulative risk of death of 70% and 78.7% by age 45 and 55, respectively (Mellerio, 2016), (Fine, 2016).
Preclinical investigations demonstrated overexpression of polo like kinase 1 (PLK1) in RDEB-associated SCC tumor cells. These tumors show a highly aggressive, early metastasizing course, making them the primary cause of death for these patients, with a cumulative risk of death of 70% and 78.7% by age 45 and 55, 7 Table of Contents respectively (Mellerio, 2016), (Fine, 2016).
Intellectual Property Patents and Proprietary Rights Our intellectual property is derived through our internal research, licensing agreements with Temple University, or Temple, and licensing research agreements with the Mount Sinai School of Medicine, or Mount Sinai.
Intellectual Property Patents and Proprietary Rights Our intellectual property is derived through our internal research, the Temple Licensing Agreement with Temple University, or Temple, and licensing research agreements with the Mount Sinai School of Medicine, or Mount Sinai.
There are several ongoing clinical trials aimed at expanding the use of approved chemotherapeutic and immunomodulatory agents in the diseases we are studying, as well as several new clinical programs testing novel technologies. Companies with marketed CDK 4/6 inhibitors in the HR+/ HER2- metastatic breast cancer space include Pfizer (palbociclib), Novartis (ribociclib) and Eli Lilly (abemacicilib).
There are several ongoing clinical trials aimed at expanding the use of approved chemotherapeutic and immunomodulatory agents in the diseases we are studying, as well as several new clinical programs testing novel technologies. Companies with marketed CDK 4/6 inhibitors in the HR+/ HER2- metastatic breast cancer space include Pfizer (palbociclib), Novartis (ribociclib) and Eli Lilly (abemaciclib).
Rigosertib Patents As of March 2023, we owned or exclusively licensed issued patents and pending patent applications covering composition-of-matter, process, formulation and various indications for method-of-use for rigosertib filed worldwide, including in the United States. The U.S. composition-of-matter patent for rigosertib, which we in-licensed pursuant to the license agreement with Temple, currently expires in 2026.
Rigosertib Patents As of March 2024, we owned or exclusively licensed issued patents and pending patent applications covering composition-of-matter, process, formulation and various indications for method-of-use for rigosertib filed worldwide, including in the United States. The U.S. composition-of-matter patent for rigosertib, which we in-licensed pursuant to the license agreement with Temple, currently expires in 2026.
As we disclosed in December 2021 early preliminary data from this study were presented at the Austrian Society of Dermatology and Venerology Annual Conference 2021, which took place from November 25 – 27, 2021 and more recently at the World Congress on Rare Skin Diseases which took place in Paris, from June 7-9, 2022.
As we disclosed in December 2021 early preliminary data from this study were presented at the Austrian Society of Dermatology and Venerology Annual Conference 2021, which took place from November 25–27, 2021 and at the World Congress on Rare Skin Diseases which took place in Paris, from June 7-9, 2022.
For example, we have received adjustments of 1,139 days extension to the patent term for the rigosertib composition of matter patent (US 7,598,232), 1,155 days extension for the patent covering the process for making rigosertib (US 8,143,453) and 751 days extension for rigosertib formulation patent (US 8,063,109) under the provisions of 35 U.S.C. §154.
Patent and Trademark Office. For example, we have received adjustments of 1,139 days extension to the patent term for the rigosertib composition of matter patent (US 7,598,232), 1,155 days extension for the patent covering the process for making rigosertib (US 8,143,453) and 751 days extension for rigosertib formulation patent (US 8,063,109) under the provisions of 35 U.S.C. §154.
Human Capital We believe that our success is largely dependent upon our ability to attract and retain qualified employees. As of December 31, 2022, we had 17 employees (16 of which were full-time employees), in addition to several consultants or independent contractors working for us.
Human Capital We believe that our success is largely dependent upon our ability to attract and retain qualified employees. As of December 31, 2023, we had 17 employees (16 of which were full-time employees), in addition to several consultants or independent contractors working for us.
Product Candidates / Compounds Narazaciclib (ON 123300) — Differentiated Multi-Kinase Inhibitor Targeting CDK4/6 Pursuant to a license agreement with Temple University dated January 1, 1999 as amended March 21, 2013, we licensed compounds including our product candidate narazaciclib from Temple University.
Product Candidates / Compounds Narazaciclib (ON 123300) — Differentiated Multi-Kinase Inhibitor Targeting CDK4/6 Pursuant to a license agreement with Temple University dated January 1, 1999, as amended March 21, 2013 (the Temple Licensing Agreement), we licensed compounds from Temple University including our product candidate narazaciclib.
The upfront payment is being recognized ratably through December 2037, the expected term of the agreement. We recognize revenues related to the supply agreement with SymBio when control of the product is transferred to Symbio. Revenues related to the supply agreement were $0 and $0 for the fiscal years ended December 31, 2022 and 2021, respectively.
The upfront payment is being recognized ratably through December 2037, the expected term of the agreement. We recognize revenues related to the supply agreement with SymBio when control of the product is transferred to Symbio. Revenues related to the supply agreement were $0 and $0 for the fiscal years ended December 31, 2023 and 2022, respectively.
ARK5 is involved in the increased invasiveness, migration and metastatic potential of breast cancer cells (Chang, 2012), colorectal cancer (Kusakai, 2004), gastric cancer (Chen, 2017), and multiple myeloma (Suzuki et al., 2005). Narazaciclib inhibits ARK5 which may result in down regulation of the mTOR/MYC/RB1 pathways leading to cell cycle arrest and apoptosis.
ARK5 is involved in the increased invasiveness, migration, and metastatic potential of breast cancer cells (Chang, 2012), colorectal cancer (Kusakai, 2004), gastric cancer (Chen, 2017), and multiple myeloma (Suzuki et al., 2005). Narazaciclib 5 Table of Contents inhibits ARK5 which may result in down regulation of the mTOR/MYC/RB1 pathways leading to cell cycle arrest and apoptosis.
Mirza and colleagues presented the results of the randomized 6 Table of Contents phase 2 study NSGO-PALEO / ENGOT-EN3 trial at ESMO 2020 and reported that palbociclib and letrozole yielded meaningful PFS benefit in women with ER+ recurrent endometrial cancer (Mirza et al. 2020). Endometrial carcinoma (EC) is the most common gynecological malignancy (American Cancer Society 2021).
Mirza and colleagues presented the results of the randomized phase 2 study NSGO-PALEO / ENGOT-EN3 trial at ESMO 2020 and reported that palbociclib and letrozole yielded meaningful PFS benefit in women with ER+ recurrent endometrial cancer (Mirza et al. 2020). Endometrial carcinoma (EC) is the most common gynecological malignancy (American Cancer Society 2021).
These efforts may result in a decrease in the amount of reimbursement we received for our drugs from Medicare or other government programs for our drugs, once approved, and any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private payors.
These efforts may result in a decrease in the amount of reimbursement we receive for our drugs from Medicare or other government programs for our drugs, once approved, and any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private payors.
Moreover, pediatric exclusivity attaches to all formulations, dosage forms, and indications for products with existing marketing exclusivity or Orange Book listed patent life that contain the same 24 Table of Contents active moiety as that which was studied. Applications under the BPCA for labeling changes receive priority review designation, with all of the benefits that designation confers.
Moreover, pediatric exclusivity attaches to all formulations, dosage forms, and indications for products with existing marketing exclusivity or Orange Book listed patent life that contain the same active moiety as that which was studied. Applications under the BPCA for labeling changes receive priority review designation, with all of the benefits that designation confers.
Under the terms of the agreement, we received an upfront payment, and will receive regulatory and commercial milestone payments, as well as royalties on any future Chinese sales if the drug is approved.
Under the terms of the HanX License Agreement, we received an upfront payment, and will receive regulatory and commercial milestone payments, as well as royalties on any future Chinese sales if the drug is approved.
Although we periodically monitor the FDA compliance of our third-party CMOs, we cannot be certain that our present or future third-party CMOs will consistently comply with cGMP and other applicable FDA regulatory requirements. 13 Table of Contents Commercial Operations We do not currently have an organization for the sales, marketing and distribution of pharmaceutical products.
Although we periodically monitor the FDA compliance of our third-party CMOs, we cannot be certain that our present or future third-party CMOs will consistently comply with cGMP and other applicable FDA regulatory requirements. Commercial Operations We do not currently have an organization for the sales, marketing and distribution of pharmaceutical products.
This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products. Post-Approval Regulations After regulatory approval of a drug is obtained, a company is required to comply with a number of post-approval requirements.
This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products. 18 Table of Contents Post-Approval Regulations After regulatory approval of a drug is obtained, a company is required to comply with a number of post-approval requirements.
The Company has established a Compensation Committee of the Board of Directors which considers the impact of our corporate performance in determining compensation for named executive officers, as well as each named executive officer’s individual performance, macroeconomic conditions generally, and data from peer group companies. Corporate Information We were incorporated in Delaware in December 1998.
The Company has established a Compensation Committee of the Board of Directors which considers the impact of our corporate performance in 29 Table of Contents determining compensation for named executive officers, as well as each named executive officer’s individual performance, macroeconomic conditions generally, and data from peer group companies. Corporate Information We were incorporated in Delaware in December 1998.
Moreover, under the 21st Century Cures Act, manufacturers or distributors of investigational drugs for the diagnosis, monitoring, or treatment of one or more serious diseases or conditions must have a publicly available policy concerning expanded access to investigational drugs. Further, the manufacture of investigational drugs for the conduct of human clinical trials is subject to cGMP requirements.
Moreover, under the 21st Century Cures Act, manufacturers or distributors of investigational drugs for the diagnosis, monitoring, or treatment of one or more serious diseases or conditions must have a publicly available policy concerning expanded access to investigational drugs. 16 Table of Contents Further, the manufacture of investigational drugs for the conduct of human clinical trials is subject to cGMP requirements.
The FCPA also obligates companies whose securities are listed in the United States to comply with accounting provisions requiring the company to maintain books and records that accurately and 20 Table of Contents fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.
The FCPA also obligates companies whose securities are listed in the United States to comply with accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.
Mol Cancer 20, 85; 2021) which demonstrated that rigosertib synergistically combined with a CPI improved tumor growth inhibition and survival in a murine melanoma model that did not respond to a CPI alone. It was postulated that rigosertib’s anti-cancer activity was due to its ability to reverse immunosuppressive tumor microenvironments.
Mol Cancer 20, 85; 2021) which demonstrated that rigosertib synergistically combined with a check point inhibitor (CPI) improved tumor growth inhibition and survival in a murine melanoma model that did not respond to a CPI alone. It was postulated that rigosertib’s anti-cancer activity was due to its ability to reverse immunosuppressive tumor microenvironments.
Royalties will be payable under the SymBio agreement on a country- by-country basis in the licensed territory, until the later of the expiration of marketing exclusivity in those countries, a specified period of time after first commercial sale of rigosertib in such country, or the expiration of all valid claims of the licensed patents covering rigosertib or the manufacture or use of rigosertib in such country.
Royalties will be payable under the SymBio agreement on a country- by-country basis in the licensed territory, until the later of the expiration of marketing exclusivity in those countries, a specified period of time after first commercial sale of rigosertib in such country, or the expiration of all valid claims of the licensed patents covering rigosertib or the 9 Table of Contents manufacture or use of rigosertib in such country.
Additionally, before approving an NDA, the FDA will typically inspect or conduct a remote regulatory assessment of one or more clinical sites to assure compliance with GCP. After the FDA evaluates the NDA and the manufacturing facilities, it issues either an approval letter or a complete response letter.
Additionally, before approving an NDA, the FDA will typically inspect or 17 Table of Contents conduct a remote regulatory assessment of one or more clinical sites to assure compliance with GCP. After the FDA evaluates the NDA and the manufacturing facilities, it issues either an approval letter or a complete response letter.
Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance. 18 Table of Contents We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our product candidates.
Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance. We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our product candidates.
The inhibition of ARK5 has been shown to be lethal in MYC overexpressing tumors (Liu, 2012, Perumal, 2016) 5 Table of Contents and targeting ARK5 in the inhibitory profile of narazaciclib has the potential to overcome the emergence of resistance to CDK4/6 inhibitors due to the loss of retinoblastoma function and C-Myc overexpression.
The inhibition of ARK5 has been shown to be lethal in MYC overexpressing tumors (Liu, 2012, Perumal, 2016) and targeting ARK5 in the inhibitory profile of narazaciclib has the potential to overcome the emergence of resistance to CDK4/6 inhibitors due to the loss of retinoblastoma function and C-Myc overexpression.
The 23 Table of Contents drug may be subject to accelerated withdrawal procedures if such studies do not verify the product’s clinical benefit or other evidence shows a lack of safety or efficacy pursuant to a streamlined process that is outlined in the FDC Act.
The drug may be subject to accelerated withdrawal procedures if such studies do not verify the product’s clinical benefit or other evidence shows a lack of safety or efficacy pursuant to a streamlined process that is outlined in the FDC Act.
ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring, and the use of patient registries. The requirement for a REMS can materially affect 17 Table of Contents the potential market and profitability of the drug.
ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring, and the use of patient registries. The requirement for a REMS can materially affect the potential market and profitability of the drug.
The categories of covered recipients later was expanded to include physician assistants, nurse practitioners, clinical nurse specialists, certified nurse midwives and certified registered nurse anesthetists. Payments made to physicians and certain research institutions for clinical trials are included within the ambit of this law.
The categories of covered recipients later was expanded to include physician assistants, nurse practitioners, clinical nurse specialists, certified nurse midwives and certified registered nurse anesthetists. Payments made to physicians, other principal investigators, and certain research institutions for clinical trials are included within the ambit of this law.
We have the following two clinical-stage programs: 1. narazaciclib (ON 123300), a multi-targeted kinase inhibitor in solid tumors and hematological malignancies as a single agent or in combination with other anti-cancer therapies; and 2. rigosertib administered alone or in combination for the treatment of various cancers. We are currently evaluating potential compounds for in-licensing opportunities.
We have the following two clinical-stage programs: (1) narazaciclib (ON 123300), a multi-targeted kinase inhibitor in solid tumors and hematological malignancies as a single agent or in combination with other anti-cancer therapies; and (2) rigosertib administered alone or in combination for investigation in various cancers. We are currently evaluating compounds for in-licensing opportunities.
The Health Insurance Portability and Accountability Act of 1996 (HIPAA) created new federal criminal statutes that prohibits, among other things, knowingly and willfully executing a scheme to defraud any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.
The Health Insurance Portability and Accountability Act of 1996 (HIPAA) created new federal criminal statutes that prohibit, among other things, knowingly and willfully executing a scheme to defraud any healthcare benefit program, including private third-party payors, and knowingly and willfully falsifying, concealing or covering up a material fact or 27 Table of Contents making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.
As an apoptotic and antiproliferative agent, narazaciclib modulates the levels and activities of regulatory proteins of the cell cycle, including cyclin D1 and inhibits retinoblastoma (Rb) protein binding. Narazaciclib inhibits cancer cell growth and suppresses deoxyribonucleic acid (DNA) synthesis by preventing CDK-mediated G1-S phase transition, followed by tumor cell death by induction of mitochondria-mediated apoptosis.
As an apoptotic and antiproliferative agent, narazaciclib modulates the levels and activities of regulatory proteins of the cell cycle, including cyclin D1 and inhibits retinoblastoma (Rb) protein binding. Narazaciclib is believed to inhibit cancer cell growth and suppresses deoxyribonucleic acid (DNA) synthesis by preventing CDK-mediated G1-S phase transition, followed by tumor cell death by induction of mitochondria-mediated apoptosis.
Although there are a number of statutory exemptions and regulatory safe harbors protecting some business arrangements from prosecution, the exemptions and safe harbors are drawn narrowly and practices that involve remuneration intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exemption or safe harbor, as well as if they do.
Although there are a number of statutory exceptions and regulatory safe harbors protecting some business arrangements from prosecution, the exceptions and safe harbors are drawn narrowly and practices that involve remuneration intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exception or safe harbor, as well as if they do.
We and HanX also intended for these studies to comply with the FDA standards. Accordingly, such studies were used by us for an IND filing with the FDA in November 2020. The FDA Study May Proceed letter was received in December 2020.
The Chinese IND was approved in January 2020. We and HanX also intended for these studies to comply with the FDA standards. Accordingly, such studies were used by us for an IND filing with the FDA in November 2020. The FDA Study May Proceed letter was received in December 2020.
In December 2017, we entered into a license and collaboration agreement with HanX Biopharmaceuticals, Inc. (HanX), a company focused on development of novel oncology products, for the manufacturing, clinical development, registration and commercialization in China of narazaciclib.
In December 2017, we entered into a license and collaboration agreement with HanX Biopharmaceuticals, Inc. (HanX), a company focused on development of novel oncology products, for the manufacturing, clinical development, 4 Table of Contents registration and commercialization in China of narazaciclib (the HanX License Agreement).
Participation under the VHCA requires submission of pricing data and calculation of discounts and rebates pursuant to complex statutory formulas, as well as the entry into government procurement contracts governed by the Federal Acquisition Regulation.
Participation under the VHCA requires submission of pricing data and calculation of discounts and rebates 28 Table of Contents pursuant to complex statutory formulas, as well as the entry into government procurement contracts governed by the Federal Acquisition Regulation.
Specifically, the applicant must certify that: (i) the required patent information has not been filed; (ii) the listed patent has expired; 19 Table of Contents (iii) the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration; or (iv) the listed patent is invalid or will not be infringed by the new product.
Specifically, the applicant must certify that: (i) the required patent information has not been filed; (ii) the listed patent has expired; (iii) the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration; or (iv) the listed patent is invalid or will not be infringed by the new product.
For these reasons, since 2004, False Claims Act lawsuits against biopharmaceutical companies have increased significantly in volume and breadth, leading to several substantial civil and criminal settlements, as much as $3.0 billion, regarding certain sales 26 Table of Contents practices and promoting off label uses.
For these reasons, since 2004, False Claims Act lawsuits against biopharmaceutical companies have increased significantly in volume and breadth, leading to several substantial civil and criminal settlements, as much as $3.0 billion, regarding certain sales practices and promoting off label uses.
Also 27 Table of Contents under the VHCA, manufacturers are required to offer drugs for sale at no more than a separate statutory ceiling price calculated by the manufacturer to Public Health Service designated entities in order to participate in other federal funding programs including Medicaid.
Also, under the VHCA, manufacturers are required to offer drugs for sale at no more than a separate statutory ceiling price calculated by the manufacturer to Public Health Service designated entities in order to participate in other federal funding programs including Medicaid.
In addition to patents, we rely upon unpatented trade secrets, know-how and continuing technological innovation to develop and maintain a competitive position. We seek to protect our proprietary information, in part, through confidentiality agreements with our employees, collaborators, contractors and consultants, and invention assignment 12 Table of Contents agreements with our employees.
In addition to patents, we rely upon unpatented trade secrets, know-how and continuing technological innovation to develop and maintain a competitive position. We seek to protect our proprietary information, in part, through confidentiality agreements with our employees, collaborators, contractors and consultants, and invention assignment agreements with our employees.
If SymBio terminates the license agreement in these circumstances, its licenses to rigosertib will survive, subject to SymBio’s milestone and royalty obligations, which SymBio may elect to defer and offset against any damages that may be determined to be due 9 Table of Contents from us.
If SymBio terminates the license agreement in these circumstances, its licenses to rigosertib will survive, subject to SymBio’s milestone and royalty obligations, which SymBio may elect to defer and offset against any damages that may be determined to be due from us.
Phase 2 clinical trials are typically well-controlled, closely monitored, and conducted in a limited patient population, usually involving no more than several hundred participants. 15 Table of Contents ● Phase 3. Phase 3 clinical trials are controlled clinical trials conducted in an expanded patient population at geographically dispersed clinical trial sites.
Phase 2 clinical trials are typically well-controlled, closely monitored, and conducted in a limited patient population, usually involving no more than several hundred participants. ● Phase 3. Phase 3 clinical trials are controlled clinical trials conducted in an expanded patient population at geographically dispersed clinical trial sites.
Broadly speaking, a manufacturer may not promote a drug for off-label use, but may engage in non-promotional, balanced communication regarding off-label use under specified conditions.
Broadly speaking, a manufacturer may not promote a drug for off-label use, but may engage in non-promotional, balanced scientific communications regarding off-label use under specified conditions.
Based on rigosertib’s activity as a potent PLK-1 pathway inhibitor (Antanasova, 2019), a Phase 2 open label IIS with rigosertib monotherapy in patients with advanced/metastatic squamous cell carcinoma associated with recessive dystrophic epidermolysis bullosa (RDEB-SCC) is enrolling patients.
Based on rigosertib’s activity as a potent PLK-1 pathway inhibitor (Atanasova, 2019), a Phase 2 open label investigator initiated study (IIS) with rigosertib monotherapy in patients with advanced/metastatic squamous cell carcinoma associated with recessive dystrophic epidermolysis bullosa (RDEB-SCC) is enrolling patients.
Under the terms of the agreement, we received an upfront payment, and will receive regulatory and commercial milestone payments, as well as royalties on Chinese sales. The key feature of the collaboration is that HanX provides all funding required for Chinese IND enabling studies performed for Chinese health authority IND approval. The Chinese IND was approved in January 2020.
Under the terms of the HanX License Agreement, we received an upfront payment, and will receive regulatory and commercial milestone payments, as well as royalties on Chinese sales. The key feature of the collaboration is that HanX provides all funding required for Chinese IND enabling studies performed for Chinese health authority IND approval.
The time can be shortened if the FDA determines that the applicant did not pursue approval with due diligence. The total patent term after the extension may not exceed 14 years from the date of approval. Similar extension rules apply in the EU.
The time can be shortened if the FDA determines that the applicant did not pursue approval with due diligence. The total patent term after the extension may not exceed 14 years from the date of approval. Similar extension rules apply in the EU, though the specific calculations are different.
Oral Rigosertib and PD-1 Combination in KRAS-Mutated Cancers We are currently supporting an investigator-initiated study (IIS) that is exploring the use of oral rigosertib for cancers driven by mutated K-Ras genes, a Phase 1/2a study of rigosertib in combination with a PD-1 inhibitor (nivolumab) for patients with check point inhibitor (CPI) resistant K-Ras mutated non-small cell lung cancer (NSCLC).
We have supported an investigator-initiated study (IIS) that is exploring the use of oral rigosertib for cancers driven by mutated K-Ras genes, a Phase 1/2a study of rigosertib in combination with a PD-1 inhibitor (nivolumab) for patients with check point inhibitor (CPI) resistant K-Ras mutated non-small cell lung cancer (NSCLC).
As part of the CARES Act implementation, the FDA recently issued a guidance on the reporting of the volume of drugs produced, which reporting will require additional administrative efforts by drug manufacturers.
As part of the CARES Act implementation, the FDA issued a guidance on the reporting of the volume of drugs produced, which reporting requires additional administrative efforts by drug manufacturers.
Interim data presented at the European Society of Medical Oncology (ESMO) meeting in September 2022 showed an early and encouraging signal of efficacy in the trial’s extensively pre-treated population, with one complete response, two partial responses, and one instance of stable disease achieved in fourteen evaluable patients.
Interim data presented at the European Society of Medical Oncology (ESMO) meeting in September 2022 showed an early and encouraging 8 Table of Contents signal of a treatment effect in the trial’s extensively pre-treated population, with one complete response, two partial responses, and one instance of stable disease achieved in fourteen evaluable patients.
Medicines authorized across the EU with the results of studies from a pediatric investigation plan included in the product information are eligible for an extension of their supplementary protection certificate by six months. This is the case even when the studies’ results are negative. For orphan medicines, the incentive is an additional two years of market exclusivity.
Medicines authorized across the EU with the results of studies from a pediatric investigation plan included in the product information are eligible for an extension of their supplementary protection certificate by six months. This is the case even when the studies’ results are negative.
To obtain regulatory approval to commercialize a new drug under European Union regulatory systems, we must submit a marketing authorization application, or MAA. The MAA is comparable to the NDA.
To obtain regulatory approval to commercialize a new drug under European Union regulatory systems, we must submit a marketing authorization application, or MAA.
If a drug product is reimbursed by Medicare or Medicaid, pricing and rebate programs must comply with, as applicable, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 as well as the Medicaid rebate requirements of the Omnibus Budget Reconciliation Act of 1990, or the OBRA, and the Veterans Health Care Act of 1992, each as amended.
If a drug product is reimbursed by Medicare or Medicaid, pricing and rebate programs must comply with, as applicable, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 as well as the Medicaid rebate requirements of the Omnibus Budget Reconciliation Act of 1990, or the OBRA, the Veterans Health Care Act of 1992, Deficit Reduction Act of 2005, Patient Protection and Affordable Care Act, and the Inflation Reduction Act of 2022, each as amended.
Moreover, product approval may require substantial post-approval testing, clinical trials, and surveillance to monitor the drug’s safety or efficacy. Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or if problems are identified following initial marketing.
Moreover, product approval may require substantial post-approval testing, clinical trials, and surveillance to monitor the drug’s safety or efficacy, or to establish the product’s safety and efficacy in a more diverse or representative population. Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or if problems are identified following initial marketing.
For other countries outside of the European Union, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country.
The MAA is comparable to the NDA. 21 Table of Contents For other countries outside of the European Union, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country.
The three phases of an investigation are as follows: ● Phase 1. Phase 1 includes the initial introduction of an investigational drug into humans. Phase 1 clinical trials may be conducted in patients with the target disease or condition or healthy volunteers.
Phase 1 includes the initial introduction of an investigational drug into humans. Phase 1 clinical trials may be conducted in patients with the target disease or condition or healthy volunteers.
The U.S. composition-of-matter patent for narazaciclib expires in 2031. We have recently filed new patent applications covering methods of treatment in target indications that are projected to extend to 2043 before any possible patent term extensions. Patent term extensions may be available, depending on various provisions in the law.
We have recently filed new patent applications covering methods of treatment in target indications that are projected to extend to 2043 before any possible patent term extensions. Patent term extensions may be available, depending on various provisions in the law.
Our IND submission to the US FDA was submitted in November 2020 and the FDA Study May Proceed letter was issued in December 2020. Enrollment into the complementary US phase 1 study (Study 19-01) with narazaciclib commenced in May 2021.
The study is ongoing. Our IND submission to the US FDA was submitted in November 2020 and the FDA Study May Proceed letter was issued in December 2020. Enrollment into the complementary US phase 1 study (Study 19-01) with narazaciclib commenced in May 2021. In Study 19-01 in the US, narazaciclib is dosed on a continuous daily schedule.
The term of a patent that covers an FDA-approved drug may be eligible for additional patent term extension, which provides patent term restoration to account for the patent term lost during product development and the FDA regulatory review process.
If an application is timely filed with the Patent and Trademark Office, the term of a patent that covers an FDA-approved drug may be eligible for additional patent term extension, which provides patent term restoration to account for the patent term lost during product development and the FDA regulatory review process.
Such exclusivity in the EU under a broadly equivalent regime is 10 years. An ANDA or a 505(b)(2) application may be submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed.
Such exclusivity in the EU under a broadly equivalent regime is 10 years, though this may be decreased in the future pending current European Commission review. An ANDA or a 505(b)(2) application may be submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed.
We believe this supports further investigation of rigosertib in combination with CPI in KRAS mutated NSCLC. On June 17, 2021, we announced a publication in Molecular Cancer (Yan, C., Saleh, N., Yang, J. et al. Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade.
Oral Rigosertib and PD-1 Combination in KRAS-Mutated Cancers On June 17, 2021, we announced a publication in Molecular Cancer (Yan, C., Saleh, N., Yang, J. et al. Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade.
An IND is a request for authorization from the FDA to administer an investigational drug product to humans. This authorization is required before interstate shipping and administration of any new drug product to humans that is not the subject of an approved NDA.
Sponsors will also be required to provide FDA with diversity action plans. An IND is a request for authorization from the FDA to administer an investigational drug product to humans. This authorization is required before interstate shipping and administration of any new drug product to humans that is not the subject of an approved NDA.
Under the terms of the License Agreement, we granted Knight (i) a non-exclusive, royalty-bearing license, with the right to sublicense, under certain Company patent rights and know-how to develop and manufacture any product (the Knight Licensed Product) containing rigosertib for Canada (and Israel should Knight exercise its option) (the Knight Territory) and in human uses (the Knight Licensed Field), and (ii) an exclusive, royalty-bearing license, with the right to sublicense, under certain Company patent rights and know-how to commercialize the Knight Licensed Product in the Knight Territory and in the Knight Licensed Field.
Under the terms of the License Agreement, we granted Knight (i) a non-exclusive, royalty-bearing license, with the right to sublicense, under certain Company patent rights and know-how to develop and manufacture any product (the Knight Licensed Product) containing rigosertib for Canada (and Israel should Knight exercise its option) (the Knight Territory) and in human uses (the Knight Licensed Field), and (ii) an exclusive, royalty-bearing license, with the right to sublicense, under certain Company patent rights and know-how to commercialize the Knight Licensed Product in the Knight Territory and in the Knight Licensed Field. 10 Table of Contents Knight has also agreed to obtain from us all of Knight’s requirements of the Knight Licensed Products for the Knight Territory, and we have agreed to supply Knight with all of its requirements of the Knight Licensed Products.
Clinical trials are conducted under protocols that detail the parameters to be used in monitoring safety, and the efficacy criteria to be evaluated. Each protocol involving testing on U.S. patients and subsequent protocol amendments must be submitted to the FDA as part of the IND. Under newly enacted legislation, diversity plans will also be required.
Clinical trials are conducted under protocols that detail the parameters to be used in monitoring safety, and the efficacy criteria to be evaluated. Each protocol involving testing on U.S. patients and subsequent protocol amendments must be submitted to the FDA as part of the IND. The informed written consent of each participating subject is required.
Exclusivity Upon NDA approval of a new chemical entity, or NCE, which is a drug that contains no active moiety that has been approved by the FDA in any other NDA, that drug receives five years of marketing exclusivity during which the FDA cannot receive any ANDA or a 505(b)(2) application for the same active moiety.
This bill also included provisions on shared and individual REMS for generic drug products. 20 Table of Contents Exclusivity Upon NDA approval of a new chemical entity, or NCE, which is a drug that contains no active moiety that has been approved by the FDA in any other NDA, that drug receives five years of marketing exclusivity during which the FDA cannot receive any ANDA or a 505(b)(2) application for the same active moiety.
Healthcare Regulation Following approval of any product candidate, the product would be subject to a comprehensive system of laws and regulations on the state and federal level that govern how drug products are reimbursed , healthcare financing, and drug manufacturers’ relationships and interactions with healthcare professionals, including potential prescribers.
For orphan medicines, the incentive is an additional two years of market exclusivity. 25 Table of Contents Healthcare Regulation Following approval of any product candidate, the product would be subject to a comprehensive system of laws and regulations on the state and federal level that govern how drug products are reimbursed, healthcare financing, and drug manufacturers’ relationships and interactions with healthcare professionals, including potential prescribers.
Healthcare providers are permitted to prescribe drugs for “off-label” uses — that is, uses not approved by the FDA and therefore not described in the drug’s labeling — because the FDA does not regulate the practice of medicine.
Healthcare providers are permitted to prescribe drugs for “off-label” uses — that is, uses not approved by the FDA and therefore not described in the drug’s labeling — because the FDA does not regulate the practice of medicine. However, FDA regulations impose stringent restrictions on manufacturers’ communications regarding off-label uses.
In addition, we have granted Knight an exclusive right of first refusal with respect to all or any part of the Knight Territory, to store, market, promote, sell, offer for sale and/or distribute any ROFR Products.
We may, at our discretion, use the services of a contract manufacturer to manufacture and package the Knight Licensed Products. In addition, we have granted Knight an exclusive right of first refusal with respect to all or any part of the Knight Territory, to store, market, promote, sell, offer for sale and/or distribute any ROFR Products.
The informed written consent of each participating subject is required. Special clinical trial ethical considerations also must be taken into account if a study involves children. The clinical investigation of an investigational drug is generally divided into three phases. Although the phases are usually conducted sequentially, they may overlap or be combined.
Special clinical trial ethical considerations also must be taken into account if a study involves children. The clinical investigation of an 15 Table of Contents investigational drug is generally divided into three phases. Although the phases are usually conducted sequentially, they may overlap or be combined. The three phases of an investigation are as follows: ● Phase 1.
Claims under the civil False Claims Act may be brought by the government or private parties on behalf of the government, called “qui tam” actions, which may proceed even if the government does not join as a party.
A claim includes “any request or demand” for money or property presented to the U.S. government. Claims under the civil False Claims Act may be brought by the government or private parties on behalf of the government, called “qui tam” actions, which may proceed even if the government does not join as a party.
This data has been reinforced by phase 2 data presented with ribociclib and letrozole as well as abemaciclib and letrozole in this patient population. Onconova will initiate a multi-center Phase 1/2a trial evaluating its multi-kinase inhibitor, narazaciclib, in combination with letrozole as a second- or third-line therapy for the treatment of recurrent metastatic low-grade endometrioid endometrial cancer (LGEEC) in 1Q23.
This data has been reinforced by phase 2 data presented with ribociclib and letrozole as well as abemaciclib and letrozole in this patient population. Onconova initiated a multi-center Phase 1/2a trial evaluating its multi-kinase inhibitor, narazaciclib, in combination with letrozole for the treatment of recurrent metastatic endometrial cancer and other gynecologic malignancies.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIn addition, we would be required to notify Nasdaq of our intention to cure the minimum bid price deficiency during the second compliance period, by effecting a reverse stock split, if necessary. ​ If we do not regain compliance within the allotted compliance period(s), including any extensions that may be granted by Nasdaq, Nasdaq will provide notice that the Company’s common stock will be subject to delisting.
Biggest changeTheir determination to grant the second compliance period was based on our meeting the continued listing requirement for market value of publicly held shares and all other initial listing standards for The Nasdaq Capital Market, except for the minimum bid price requirement, and our notification to Nasdaq of its intention to cure the minimum bid price deficiency during the second compliance period, by effecting a reverse stock split, if necessary. ​ If we do not regain compliance by September 25, 2024, Nasdaq will provide notice that the Company’s common stock will be delisted.
Cybersecurity attacks are evolving and include, but are not limited to, malicious software, attempts to gain unauthorized access to data and other electronic security breaches that could lead to disruptions in systems, misappropriation of our confidential or otherwise protected information, corruption of data.
Cybersecurity attacks are evolving and include, but are not limited to, malicious software, attempts to gain unauthorized access to data and other electronic security breaches that could lead to disruptions in systems, misappropriation of our confidential or otherwise protected information, and corruption of data.
We do not have the funding resources necessary to carry out all of our proposed operating activities. We will need to obtain additional financing in the future in order to fully fund rigosertib or any other product candidates through the regulatory approval process. Accordingly, we may delay or pause our planned clinical trials, until we secure adequate additional funding.
We do not have the funding resources necessary to carry out all of our proposed operating activities. We will need to obtain additional financing in the future in order to fully fund narazaciclib, rigosertib or any other product candidates through the regulatory approval process. Accordingly, we may delay or pause our planned clinical trials, until we secure adequate additional funding.
While we currently have no specific plans to acquire any other specific businesses, we may, in the future, make acquisitions of, or investments in, or otherwise engage in business combinations or collaborations with companies that we believe have products or capabilities that are a strategic or commercial fit with our current product candidates and business or otherwise offer opportunities for our company.
While we currently have no specific plans to acquire any other specific business, we may, in the future, make acquisitions of, or investments in, or otherwise engage in business combinations or collaborations with companies that we believe have products or capabilities that are a strategic or commercial fit with our current product candidates and business or otherwise offer opportunities for our company.
Our future capital requirements will depend on many factors, including: ● timing and success of our clinical trials; ● continued progress of and increased spending related to our research and development activities; ● conditions in the capital markets and the biopharmaceutical industry, particularly with respect to raising capital or entering into strategic arrangements; ● progress with preclinical experiments and clinical trials, including regulatory approvals necessary for advancement and continuation of our development programs; ● changes in regulatory requirements and guidance of the FDA and other regulatory authorities, which may require additional cl inical trials to evaluate safety and/or efficacy, and thus have significant impacts on our timelines, cost projections, and financial requirements; ● ongoing general and administrative expenses related to our reporting obligations under the Exchange Act; ● cost, timing, and results of regulatory reviews and approvals; ● costs of any legal proceedings, claims, lawsuits and investigations; ● success, timing, and financial consequences of any existing or future collaborative, licensing and other arrangements t hat we may establish, including potential granting of licenses to one or more of our programs in various territories, or otherwise monetizing one or more of our programs; ● cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; ● costs of commercializing any of our product candidates; ● technological and market developments; ● compliance with Nasdaq's continued listing requirements; 38 Table of Contents ● cost of manufacturing development; and ● timing and volume of sales of products for which we obtain marketing approval.
Our future capital requirements will depend on many factors, including: ● timing and success of our clinical trials; ● continued progress of and increased spending related to our research and development activities; ● conditions in the capital markets and the biopharmaceutical industry, particularly with respect to raising capital or entering into strategic arrangements; ● progress with preclinical experiments and clinical trials, including regulatory approvals necessary for advancement and continuation of our development programs; ● changes in regulatory requirements and guidance of the FDA and other regulatory authorities, which may require additional cl inical trials to evaluate safety and/or efficacy, and thus have significant impacts on our timelines, cost projections, and financial requirements; ● ongoing general and administrative expenses related to our reporting obligations under the Exchange Act; ● cost, timing, and results of regulatory reviews and approvals; ● costs of any legal proceedings, claims, lawsuits and investigations; ● success, timing, and financial consequences of any existing or future collaborative, licensing and other arrangements t hat we may establish, including potential granting of licenses to one or more of our programs in various territories, or otherwise monetizing one or more of our programs; ● cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights; ● costs of commercializing any of our product candidates; ● technological and market developments; ● compliance with Nasdaq's continued listing requirements; ● cost of manufacturing development; and ● timing and volume of sales of products for which we obtain marketing approval.
As such, the FDA or comparable foreign regulatory authorities may require us to perform additional API and drug product manufacturing before continuing clinical trials or approving our marketing applications, may require us to conduct additional studies, and any such deficient product we supply to any collaboration partner may subject us to certain obligations under relevant agreements.
As such, the FDA or comparable foreign regulatory authorities may require us to perform additional API and drug product manufacturing and manufacturing development before continuing clinical trials or approving our marketing applications, may require us to conduct additional studies, and any such deficient product we supply to any collaboration partner may subject us to certain obligations under relevant agreements.
Any product candidate we advance into clinical trials may not have favorable results in later-stage clinical trials or receive regulatory approval. ● Clinical drug development involves a lengthy and expensive process with an uncertain outcome. ● Our product candidates may cause undesirable side effects 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 marketing approval. ● Failure to follow the FDA’s applicable regulatory requirements may result in enforcement action. ● Changes in product candidate manufacturing or formulation may result in additional costs or delay. ● Healthcare legislation, including potentially unfavorable pricing regulations or other healthcare reform initiatives, may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain. ● Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could cause significant liability for us and harm our reputation. ● We face substantial competition, which may result in others discovering, developing or commercializing products before or more successfully than we do. ● If we breach our license agreements or fail to negotiate new agreements pertaining to our product candidates, we could lose the ability to continue the development and potential commercialization of these product candidates. ● Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop. ● We may engage in future business combinations or collaborations that could disrupt our business, cause dilution to our stockholders and harm our financial condition and operating results. 29 Table of Contents ● We depend on information technology and computer systems to operate our business; our business and operations would suffer in the event of any failures or interruptions of our computer system, such as a data breach or cybersecurity incident. ● Climate change, environmental, social and governance and sustainability initiatives may result in regulatory or structural industry changes that could require significant operational changes and expenditures, reduce demand for the Company’s products and adversely affect our business, financial condition, and results of operations. ● Business disruptions could seriously harm our future revenues and financial condition and increase our costs and expenses. ● Our future success depends on our ability to retain our executive officers and to attract, retain and motivate qualified personnel. ● The COVID-19 pandemic could adversely impact our business, including our clinical trials, drug manufacturing and nonclinical activities. ● Our recurring operating losses, negative cash flows from operations, and accumulated deficit raise substantial doubt about our ability to continue as a going concern absent obtaining adequate new financings. ● The report of our independent registered accounting firm on our audited financial statements for the fiscal year ended December 31, 2022 contains an explanatory paragraph relating to our ability to continue as a going concern. ● We need to obtain additional funding to continue as a going concern; if we are unable to meet our needs for additional funding in the future, we will be required to limit, scale back or cease operations. ● We have incurred significant losses since our inception and anticipate that we will continue to incur losses in the future. ● We currently have no source of product revenue and may never become profitable. ● We need to obtain additional funding to further develop our products in future clinical trials and through regulatory processes; if we are unable to meet our needs for additional funding in the future, we will be required to limit, scale back or cease operations. ● Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates. ● Adverse developments affecting financial institutions, companies in the financial services industry or the financial services industry generally, such as actual events or concerns involving liquidity, defaults or non-performance, could adversely affect our operations and liquidity. ● Changes in United States and China relations, as well as relations with other countries, and/or regulations may adversely impact our business, our operating results, our ability to raise capital and the market price of our shares. ● We rely on third parties to conduct our preclinical and clinical trials.
Any product candidate we advance into clinical trials may not have favorable results in later-stage clinical trials or receive regulatory approval. ● Clinical drug development involves a lengthy and expensive process with an uncertain outcome. ● Our product candidates may cause undesirable side effects 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 marketing approval. ● Failure to follow the FDA’s applicable regulatory requirements may result in enforcement action. ● Changes in product candidate manufacturing or formulation may result in additional costs or delay. ● Healthcare legislation, including potentially unfavorable pricing regulations or other healthcare reform initiatives, may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain. ● Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could cause significant liability for us and harm our reputation. ● We face substantial competition, which may result in others discovering, developing or commercializing products before or more successfully than we do. ● If we breach our license agreements or fail to negotiate new agreements pertaining to our product candidates, we could lose the ability to continue the development and potential commercialization of these product candidates. ● Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop. ● We may engage in future business combinations or collaborations that could disrupt our business, cause dilution to our stockholders and harm our financial condition and operating results. ● We depend on information technology and computer systems to operate our business; our business and operations would suffer in the event of any failures or interruptions of our computer system, such as a data breach or cybersecurity incident. 30 Table of Contents ● Climate change, environmental, social and governance and sustainability initiatives may result in regulatory or structural industry changes that could require significant operational changes and expenditures, reduce demand for the Company’s products and adversely affect our business, financial condition, and results of operations. ● Business disruptions could seriously harm our future revenues and financial condition and increase our costs and expenses. ● Our future success depends on our ability to retain our executive officers and to attract, retain and motivate qualified personnel. ● The recent COVID-19 pandemic, or the widespread outbreak of any other communicable disease, could adversely impact our business, including our clinical trials, drug manufacturing and nonclinical activities. ● Our recurring operating losses, negative cash flows from operations, and accumulated deficit raise substantial doubt about our ability to continue as a going concern absent obtaining adequate new financings. ● The report of our independent registered accounting firm on our audited financial statements for the fiscal year ended December 31, 2023 contains an explanatory paragraph relating to our ability to continue as a going concern. ● We need to obtain additional funding to continue as a going concern; if we are unable to meet our needs for additional funding in the future, we will be required to limit, scale back or cease operations. ● We have incurred significant losses since our inception and anticipate that we will continue to incur losses in the future. ● We currently have no source of product revenue and may never become profitable. ● We need to obtain substantial additional funding to further develop our products in future clinical trials and through regulatory processes; if we are unable to meet our needs for additional funding in the future, we will be required to limit, scale back or cease operations. ● Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates. ● Adverse developments affecting financial institutions, companies in the financial services industry or the financial services industry generally, such as actual events or concerns involving liquidity, defaults, or non-performance could adversely affect our operations and liquidity. ● Changes in United States and China relations, as well as relations with other countries, and/or regulations may adversely impact our business, our operating results, our ability to raise capital and the market price of our shares. ● We rely on third parties to conduct our preclinical and clinical trials.
We face competition with respect to our current product candidates and will face competition with respect to any product candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide.
We face competition with respect to our current product candidates and will face competition with respect to any product candidate that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide.
The auditor’s opinion on our audited financial statements for the year ended December 31, 2022 includes an explanatory paragraph stating that we have incurred recurring losses from operations that raise substantial doubt about our ability to continue as a going concern for the next twelve months from the date of the financial statements included in this Annual Report on Form 10-K.
The auditor’s opinion on our audited financial statements for the year ended December 31, 2023 includes an explanatory paragraph stating that we have incurred recurring losses from operations that raise substantial doubt about our ability to continue as a going concern for the next twelve months from the date of the financial statements included in this Annual Report on Form 10-K.
If we are unable to comply with the continued listing requirements of the Nasdaq Capital Market, our Common Stock could be delisted, which could affect our Common Stock's market price and liquidity and reduce our ability to raise capital. ● Our share price and the liquidity of our stock may be volatile and result in substantial losses to our stockholders. ● We may be subject to securities litigation, which is expensive and could divert management attention. ● Some provisions of our charter documents and Delaware law may have anti-takeover effects that could discourage an acquisition of us by others, even if an acquisition would be beneficial to our stockholders and may prevent attempts by our stockholders to replace or remove our current management.
If we are unable to comply with the continued listing requirements of the Nasdaq Capital Market, our Common Stock could be delisted, which could affect our Common Stock's market price and liquidity and reduce our ability to raise capital. 31 Table of Contents ● Our share price and the liquidity of our stock may be volatile and result in substantial losses to our stockholders. ● We may be subject to securities litigation, which is expensive and could divert management attention. ● Some provisions of our charter documents and Delaware law may have anti-takeover effects that could discourage an acquisition of us by others, even if an acquisition would be beneficial to our stockholders and may prevent attempts by our stockholders to replace or remove our current management.
Changes in product candidate manufacturing or formulation may result in additional costs or delay. As product candidates are developed through preclinical studies to late-stage clinical trials towards approval and commercialization, it is common that various aspects of the development program, such as manufacturing methods and formulation, are altered along the way in an effort to optimize processes and results.
Changes in product candidate manufacturing or formulation may result in additional costs or delay. As product candidates are developed through preclinical studies to later-stage clinical trials towards approval and commercialization, it is common that various aspects of the development program, such as manufacturing methods and formulation, are altered along the way in an effort to optimize processes and results.
There can be no assurance that the FDA, an IRB, or a comparable foreign regulatory authority will permit our clinical trials to commence and will not put clinical trials of any of our product candidates on clinical hold in the future. Study results may also cause us to 31 Table of Contents discontinue trials.
There can be no assurance that the FDA, an IRB, or a comparable foreign regulatory authority will permit our clinical trials to commence and will not put clinical trials of any of our product candidates on clinical hold in the future. Study results may also cause us to 36 Table of Contents discontinue trials.
If adequate funds are unavailable, we may be required, among other things, to: ● delay, reduce the scope of or eliminate one or more of our research or development programs; ● license rights to technologies, product candidates or products at an earlier stage or for indications or territories than otherwise would be desirable, or on terms that are less favorable to us than might otherwise be available; ● obtain funds through arrangements that may require us to relinquish rights to product candidates or products that we would otherwise seek to develop or commercialize by ourselves; or ● further reduce or cease operations.
If adequate funds are unavailable, we may be required, among other things, to: 33 Table of Contents ● delay, reduce the scope of or eliminate one or more of our research or development programs; ● license rights to technologies, product candidates or products at an earlier stage or for indications or territories than otherwise would be desirable, or on terms that are less favorable to us than might otherwise be available; ● obtain funds through arrangements that may require us to relinquish rights to product candidates or products that we would otherwise seek to develop or commercialize by ourselves; or ● further reduce or cease operations.
If we are unable to protect our intellectual property rights, our competitive position could be harmed. ● We may become involved in lawsuits to protect or enforce our intellectual property, which could be expensive, time consuming and unsuccessful. ● Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could harm our business. ● We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers. 30 Table of Contents ● We may not comply with the Nasdaq continued listing requirements.
If we are unable to protect our intellectual property rights, our competitive position could be harmed. ● We may become involved in lawsuits to protect or enforce our intellectual property, which could be expensive, time consuming and unsuccessful. ● Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could harm our business. ● We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers. ● We may not comply with the Nasdaq continued listing requirements.
If we or any of our sites or CROs fail to comply with applicable GCP, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications. We or they may also face regulatory enforcement.
If we or any of our sites or CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications. We or they may also face regulatory enforcement.
If CROs or sites do not successfully carry out their contractual duties or obligations or meet expected deadlines or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or 41 Table of Contents successfully commercialize our product candidates.
If CROs or sites do not successfully carry out their contractual duties or obligations or meet expected deadlines or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates.
Any failure by our third-party manufacturers to comply with cGMP or failure to scale up manufacturing processes, including any failure to deliver sufficient quantities of product candidates in a timely manner, could lead to a delay in, or failure to obtain, regulatory approval of any of our product candidates.
Any failure by our third-party manufacturers to comply with cGMPs or failure to scale up manufacturing processes, including any failure to deliver sufficient quantities of product candidates in a timely manner, could lead to a delay in, or failure to obtain, regulatory approval of any of our product candidates.
These include provisions that will: ● permit our board of directors to issue up to 5,000,000 shares of preferred stock, with any rights, preferences and privileges as they may designate (as of February 28, 2023, we had no shares of preferred stock issued and outstanding); ● provide that all vacancies on our board of directors, including as a result of newly created directorships, may, except as otherwise required by law, be filled by the affirmative vote of a majority of directors then in office, even if less than a quorum; ● require that any action to be taken by our stockholders must be effected at a duly called annual or special meeting of stockholders and not be taken by written consent; ● provide that stockholders seeking to present proposals before a meeting of stockholders or to nominate candidates for election as directors at a meeting of stockholders must provide advance notice in writing, and also specify requirements as to the form and content of a stockholder’s notice; ● not provide for cumulative voting rights, thereby allowing the holders of a majority of the shares of common stock entitled to vote in any election of directors to elect all of the directors standing for election; and ● provide that special meetings of our stockholders may be called only by the board of directors or by such person or persons requested by a majority of the board of directors to call such meetings.
These include provisions that will: ● permit our board of directors to issue up to 5,000,000 shares of preferred stock, with any rights, preferences and privileges as they may designate (as of February 29, 2024, we had no shares of preferred stock issued and outstanding); ● provide that all vacancies on our board of directors, including as a result of newly created directorships, may, except as otherwise required by law, be filled by the affirmative vote of a majority of directors then in office, even if less than a quorum; ● require that any action to be taken by our stockholders must be effected at a duly called annual or special meeting of stockholders and not be taken by written consent; ● provide that stockholders seeking to present proposals before a meeting of stockholders or to nominate candidates for election as directors at a meeting of stockholders must provide advance notice in writing, and also specify requirements as to the form and content of a stockholder’s notice; ● not provide for cumulative voting rights, thereby allowing the holders of a majority of the shares of common stock entitled to vote in any election of directors to elect all of the directors standing for election; and ● provide that special meetings of our stockholders may be called only by the board of directors or by such person 47 Table of Contents or persons requested by a majority of the board of directors to call such meetings.
Furthermore, future business combinations could pose numerous additional risks to our operations, including: problems integrating the businesses, products or technologies; increases to our expenses; the failure to discover undisclosed liabilities of an acquired asset or transaction partner; diversion of management’s attention from their day-to-day responsibilities; and harm to our operating results or financial condition.
Furthermore, future business combinations could pose numerous additional risks to our operations, including, but not limited to problems integrating the businesses, products or technologies, increases to our expenses, the failure to discover undisclosed liabilities of an acquired asset or transaction partner, diversion of management’s attention from their day-to-day responsibilities, and harm to our operating results or financial condition.
The report of our independent registered accounting firm on our audited financial statements for the fiscal year ended December 31, 2022 contains an explanatory paragraph relating to our ability to continue as a going concern.
The report of our independent registered accounting firm on our audited financial statements for the fiscal year ended December 31, 2023 contains an explanatory paragraph relating to our ability to continue as a going concern.
Any uncured, material breach under the license agreement could result in our loss of exclusive rights and may lead to a complete termination of our product development and any commercialization efforts for the applicable product candidates. 34 Table of Contents Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.
Any uncured, material breach under the license agreement could result in our loss of exclusive rights and may lead to a complete termination of our product development and any commercialization efforts for the applicable product candidates. Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.
Even if we are able to complete the development and regulatory process for any product candidates, we anticipate incurring significant costs associated with commercializing these products. Even if we are able to generate revenues from the sale of our products, we may not become profitable and may need to obtain additional funding to 39 Table of Contents continue operations.
Even if we are able to complete the development and regulatory process for any product candidates, we anticipate incurring significant costs associated with commercializing these products. Even if we are able to generate revenues from the sale of our products, we may not become profitable and may need to obtain additional funding to continue operations.
There can be no assurance that our efforts, or the efforts of our partners and vendors, will prevent service interruptions, or identify breaches in our systems, that could adversely affect our business and operations and/or result in the loss of critical or sensitive information, which could result in financial, legal, 35 Table of Contents business or reputational harm to us.
There can be no assurance that our efforts, or the efforts of our partners and vendors, will prevent service interruptions, or identify breaches in our systems, that could adversely affect our business and operations and/or result in the loss of critical or sensitive information, which could result in financial, legal, business or reputational harm to us.
Failure to comply with these regulations may require us to repeat preclinical and clinical trials, which would delay the regulatory approval process. We may also face liability and/or regulatory enforcement action should any of the third parties that we rely upon fail to comply with legal and/or regulatory requirements.
Failure to comply with these regulations may require us to repeat preclinical and clinical trials, which would delay the regulatory approval process. We may also face liability 42 Table of Contents and/or regulatory enforcement action should any of the third parties that we rely upon fail to comply with legal and/or regulatory requirements.
In addition, the FDA and other regulatory authorities require that our product candidates and any products that we may eventually commercialize be manufactured according to cGMP and similar foreign standards.
In addition, the FDA and other regulatory authorities require that our product candidates and any products that we may eventually commercialize be manufactured according to cGMPs and similar foreign standards.
These potential disruptions may include but 36 Table of Contents are not limited to delays or difficulties in clinical site initiation and patient recruitment, patient withdrawals, postponement of planned clinical or preclinical studies, redirection of site resources from studies, study modification, suspension, or termination, the introduction of remote study procedures and modified informed consent procedures, study site changes, direct delivery of investigational products to patient homes requiring state licensing, study deviations or noncompliance, diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials, delays in receiving approval from local regulatory authorities to initiate our planned clinical trials, delays in obtaining supplies of our product candidate or other materials that may be necessary for the conduct of our development program, delays in obtaining necessary inspections from the FDA or other regulatory authorities, changing laws and regulations in responses to the COVID-19 pandemic, and changes or delays in site monitoring.
These potential disruptions may include but are not limited to delays or difficulties in clinical site initiation and patient recruitment, patient withdrawals, postponement of planned clinical or preclinical studies, redirection of site resources from studies, study modification, suspension, or termination, the introduction of remote study procedures and modified informed consent procedures, study site changes, direct delivery of investigational products to patient homes requiring state licensing, study deviations or noncompliance, diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials, delays in receiving approval from local regulatory authorities to initiate our planned clinical trials, delays in obtaining supplies of our product candidate or other materials that may be necessary for the conduct of our development program, delays in obtaining necessary inspections from the FDA or other regulatory authorities, changing laws and regulations, and changes or delays in site monitoring.
If we are unable to regain compliance with the continued listing requirements of the Nasdaq Capital Market, our Common Stock could be delisted, which could affect our Common Stock's market price and liquidity and reduce our ability to raise capital. ​ We are required to meet certain qualitative and financial tests to maintain the listing of our securities on The Nasdaq Capital Market.
If we are unable to comply with the continued listing requirements of the Nasdaq Capital Market, our Common Stock could be delisted, which could affect our common stock's market price and liquidity and reduce our ability to raise capital. ​ We are required to meet certain qualitative and financial tests to maintain the listing of our securities on the Nasdaq Capital Market (Nasdaq).
While we have not experienced any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our drug development programs.
While we have not experienced any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our drug development 40 Table of Contents programs.
If we are unable to arrange for alternative third-party manufacturing sources, or to do so 42 Table of Contents on commercially reasonable terms or in a timely manner, we may not be able to complete development of our product candidates, or market or distribute them.
If we are unable to arrange for alternative third-party manufacturing sources, or to do so on commercially reasonable terms or in a timely manner, we may not be able to complete development of our product candidates, or market or distribute them.
Under Delaware law, a corporation may not, in general, engage in a business combination with any holder of 15% or more of 46 Table of Contents its capital stock unless the holder has held the stock for three years or, among other things, the board of directors has approved the transaction.
Under Delaware law, a corporation may not, in general, engage in a business combination with any holder of 15% or more of its capital stock unless the holder has held the stock for three years or, among other things, the board of directors has approved the transaction.
Our consolidated financial statements for the year ended December 31, 2022 have been prepared assuming we will continue to operate as a going concern.
Our consolidated financial statements for the year ended December 31, 2023 have been prepared assuming we will continue to operate as a going concern.
At that time, we may appeal the Nasdaq Staff’s determination to a Nasdaq Hearings Panel. ​ We intend to monitor the closing bid price of the Company’s common stock and consider our available options to resolve the noncompliance with the minimum bid price requirement. ​ There can be no assurance that we will be able to regain compliance with the minimum bid price requirement or will otherwise be in compliance with other Nasdaq listing criteria. ​ If we are unable to maintain compliance with the continued listing requirements of the Nasdaq Capital Market, our Common Stock could be delisted, making it could be more difficult to buy or sell our securities and to obtain accurate quotations, and the price of our securities could suffer a material decline.
At that time, we may appeal the Nasdaq staff’s determination to a Nasdaq Hearings Panel.​ ​ We intend to monitor the closing bid price of the Company’s common stock and continue to consider our available options to resolve the noncompliance with the minimum bid price requirement. 46 Table of Contents ​ There can be no assurance that we will be able to regain compliance with the minimum bid price requirement or will otherwise be in compliance with other Nasdaq listing criteria. ​ If we are unable to maintain compliance with the continued listing requirements of Nasdaq, our common stock could be delisted, making it could be more difficult to buy or sell our securities and to obtain accurate quotations, and the price of our securities could suffer a material decline.
We believe that we have sufficient resources available to support our development activities and business operations and satisfy our obligations into the first quarter of 2024.
We believe that we have sufficient resources available to support our development activities and business operations and satisfy our obligations into the third quarter of 2024.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interests of existing stockholders will be diluted, and the terms may include liquidation or other preferences that adversely affect the rights of existing stockholders.
To the extent that we raise additional capital through the sale of equity or 34 Table of Contents convertible debt securities, the ownership interests of existing stockholders will be diluted, and the terms may include liquidation or other preferences that adversely affect the rights of existing stockholders.
We may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectual property rights with respect to our products and technology, including interference or derivation proceedings before the USPTO. Third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future.
We may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectual property rights with respect to our products and technology, including interference or derivation proceedings 45 Table of Contents before the USPTO. Third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future.
Risks Related to Ownership of Our Common Stock and Common Stock Warrants We may not be able to comply with the Nasdaq continued listing requirements.
Risks Related to Ownership of Our Common Stock and Common Stock Warrants We may not comply with the Nasdaq continued listing requirements.
The rights already granted under any of our currently issued patents and those that may be granted under future issued patents may not provide us with the proprietary protection or competitive advantages we are seeking.
The 44 Table of Contents rights already granted under any of our currently issued patents and those that may be granted under future issued patents may not provide us with the proprietary protection or competitive advantages we are seeking.
Because we continue to experience net operating losses, our ability to continue as a going concern is subject to our ability to successfully raise sufficient additional capital, through future financings or through strategic and collaborative arrangements. If we are unable to obtain additional funding, we may not be able to continue as a going concern.
Because we continue to experience net operating losses, our ability to continue as a going concern is subject to our ability to 32 Table of Contents successfully raise sufficient additional capital, through future financings or through strategic and collaborative arrangements. If we are unable to obtain additional funding, we may not be able to continue as a going concern.
To alleviate the conditions that raise substantial doubt about our ability to continue as a going concern, we plan to explore various dilutive and non-dilutive sources of funding, including equity financings, strategic alliances, business development and other sources. The future success of the Company is dependent upon our ability to obtain additional funding.
To alleviate the conditions that raise substantial doubt about our ability to continue as a going concern, we plan to explore various dilutive and non-dilutive opportunities, including equity financings, strategic alliances, business development and/or combinations, and other transactions. The future success of the Company is dependent upon our ability to obtain additional funding.
Management has concluded that substantial doubt exists about our ability to continue as a going concern for the next twelve months from the date of the financial statements included in this Annual Report on Form 10-K. As of December 31, 2022, we had cash and cash equivalents of $38.8 million and current liabilities of $8.0 million.
Management has concluded that substantial doubt exists about our ability to continue as a going concern for the next twelve months from the date of the financial statements included in this Annual Report on Form 10-K. As of December 31, 2023, we had cash and cash equivalents of $20.8 million and current liabilities of $9.2 million.
Regulatory authorities enforce GCP through periodic inspections of trial sponsors, principal investigators and trial sites.
Regulatory authorities enforce GCPs through periodic inspections of trial sponsors, principal investigators and trial sites.
If we or our CMO fail to comply with applicable cGMP, the manufacturing data generated and subsequent API lots and drug product batches in our supply chain may be deemed unreliable. Clinical trials using the product candidate may also be deemed to be unreliable.
If we or our CMO fail to comply with applicable cGMPs, the manufacturing data generated and subsequent API lots and drug product batches in 43 Table of Contents our supply chain may be deemed unreliable. Clinical trials using the product candidate may also be deemed to be unreliable.
Our future success depends on our ability to retain our executive officers and to attract, retain and motivate qualified personnel. We are highly dependent upon Steven Fruchtman, M.D., President and Chief Executive Officer, Mark Guerin, C.P.A., Chief Operating and Chief Financial Officer, and Mark Gelder, M.D., Chief Medical Officer, and our other executive officers.
Our future success depends on our ability to retain our executive officers and to attract, retain and motivate qualified personnel. 41 Table of Contents We are highly dependent upon Steven Fruchtman, M.D., President and Chief Executive Officer, Mark Guerin, C.P.A., Chief Operating and Chief Financial Officer, and Victor Moyo, M.D., Chief Medical Officer, and our other executive officers.
This may make it difficult for us to achieve market acceptance at desired levels in a timely manner to ensure viability of our business. More established companies may have a competitive advantage over us due to their greater size, cash flows and institutional experience. Compared to us, many of our competitors may have significantly greater financial, technical and human resources.
This may make it difficult for us to achieve market acceptance at desired levels in a timely manner to ensure viability of our business. More established companies may have a competitive advantage over us due to their greater size, cash flows and institutional experience.
Clinical trials may be delayed, suspended or prematurely terminated and development programs may not be successful for a variety of reasons, including: ● delay or failure in reaching identifying, contracting with, and retaining contract research organizations, or CROs, and clinical trial sites; ● delay or failure in recruiting and enrolling suitable subjects to participate in a trial and/or retaining subjects; ● failure to follow the study procedures or applicable regulatory requirements; ● negative or ambiguous study results; ● manufacturing or product quality issues; ● the need to conduct additional development work, including clinical trials; ● changes in governmental laws, regulations, policies, or administrative actions; and ● regulatory authority disagreements regarding the design or implementation of our clinical trials.
Clinical trials may be delayed, suspended or prematurely terminated and development programs may not be successful for a variety of reasons, including: ● delay or failure in reaching identifying, contracting with, and retaining contract research organizations, or CROs, and clinical trial sites; ● delay or failure in recruiting and enrolling suitable subjects to participate in a trial and/or retaining subjects; ● failure to follow the study procedures or applicable regulatory requirements; ● change in standards of care which may necessitate the modification of our clinical trials or the conduct of new trials; ● negative or ambiguous study results; ● manufacturing or product quality issues; ● the need to conduct additional development work, including clinical trials; ● unanticipated clinical trial costs or insufficient funding, including paying substantial application user fees; ● changes in governmental laws, regulations, policies, or administrative actions; and ● regulatory authority disagreements regarding the design or implementation of our clinical trials.
The loss of the services of any of these persons could impede the achievement of our research, development and commercialization objectives. The COVID-19 pandemic could adversely impact our business, including our clinical trials, drug manufacturing and nonclinical activities.
The loss of the services of any of these persons could impede the achievement of our research, development and commercialization objectives. The recent COVID-19 pandemic, or the widespread outbreak of any other communicable disease, could adversely impact our business, including our clinical trials, drug manufacturing and nonclinical activities.
Such changes may also require additional testing, FDA notification, or FDA approval. This could delay completion of clinical trials; require the conduct of bridging clinical trials or studies, or the repetition of one or more clinical trials; increase clinical trial costs; delay approval of our product candidates; and jeopardize our ability to commence product sales and generate revenue.
This could delay completion of clinical trials; require the conduct of bridging clinical trials or studies, or the repetition of one or more clinical trials; increase clinical trial costs; delay approval of our product candidates; and jeopardize our ability to commence product sales and generate revenue.
States, in the US, have also enacted laws requiring pharmaceutical companies to, among other things, establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities, cap or regulate price increases, negotiate or pay increased supplemental rebates and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing specified physician prescribing data to pharmaceutical companies for use in sales and marketing, and to prohibit other specified sales and marketing practices.
States, in the US, have also enacted laws requiring pharmaceutical companies to, among other things, establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities, cap or regulate price increases, negotiate or pay increased supplemental rebates and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing specified physician prescribing data to pharmaceutical companies for use in sales and marketing, and to prohibit other specified sales and marketing practices. 38 Table of Contents Some countries require approval of the sale price of a drug before it can be marketed.
The continued listing standard will be met if the Company’s common stock has a minimum closing bid price of at least $1.00 per share for a minimum of ten consecutive business days during the 180 calendar day grace period. ​ If we are not in compliance by September 25, 2023, we may be afforded a second 180 calendar day period to regain compliance.
The continued listing standard will be met if the Company’s common stock has a minimum closing bid price of at least $1.00 per share for a minimum of ten consecutive business days during the 180-calendar day grace period.​ ​ We did not regain compliance with the minimum bid price requirement by March 25, 2024.
For the years ended December 31, 2022, and 2021, we reported net losses of $19.0 million and $16.2 million, respectively, and we had an accumulated deficit of $463.7 million at December 31, 2022. We expect to continue to incur significant expenses and operating losses for the foreseeable future.
For the years ended December 31, 2023, and 2022, we reported net losses of $18.9 million and $19.0 million, respectively, and we had an accumulated deficit of $482.6 million at December 31, 2023. We expect to continue to incur significant expenses and operating losses for the foreseeable future.
Risks Related to Our Dependence on Third Parties We rely on third parties to conduct our preclinical and clinical trials. If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we may not be able to obtain regulatory approval for or commercialize our product candidates.
If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we may not be able to obtain regulatory approval for or commercialize our product candidates.
Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted.
In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted.
It is possible that this may impact how regulators or others view the development of rigosertib for alternative indications. If later-stage clinical trials do not produce favorable results, our ability to achieve regulatory approval for any of our product candidates may be adversely impacted. Clinical drug development involves a lengthy and expensive process with an uncertain outcome.
If later-stage clinical trials do not produce favorable results, our ability to achieve regulatory approval for any of our product candidates may be adversely impacted. Clinical drug development involves a lengthy and expensive process with an uncertain outcome.
Nasdaq Listing Rule 5550(a) (2) requires that companies listed on Nasdaq maintain a minimum closing bid price of at least $1.00 per share. ​ Under Nasdaq Listing Rule 5810(c)(3)(A), we have a 180 calendar day grace period, or until September 25, 2023, to regain compliance by meeting the continued listing standard.
As of March 25, 2024, we were not in compliance with the Nasdaq continued listing requirements related to minimum bid price.​ ​ On September 25, 2023, we received a letter from Nasdaq indicating that we failed to comply with the minimum bid price requirement of Nasdaq Listing Rule 5550(a)(2), which requires that companies listed on Nasdaq maintain a minimum closing bid price of at least $1.00 per share.​ ​ Under Nasdaq Listing Rule 5810(c)(3)(A), we had a 180 calendar day grace period, or until March 25, 2024, to regain compliance by meeting the continued listing standard.
Consequently, you should not consider the following to be a complete discussion of all potential risks or uncertainties.
You should understand that it is not possible to predict or identify all such risks. Consequently, you should not consider the following to be a complete discussion of all potential risks or uncertainties.
If we seek additional financing to fund our business activities in the future and there remains substantial doubt about our ability to continue as a going concern, investors or other financing sources may be unwilling to provide additional funding on commercially reasonable terms or at all. 37 Table of Contents We need to obtain additional funding to continue as a going concern; if we are unable to meet our needs for additional funding in the future, we will be required to limit, scale back or cease operations.
If we seek additional financing to fund our business activities in the future and there remains substantial doubt about our ability to continue as a going concern, investors or other financing sources may be unwilling to provide additional funding on commercially reasonable terms or at all.
If we or our third party contractors are not able to follow the FDA’s regulatory requirements, we or they may face enforcement actions that may materially harm our business, including, but not limited to: ● warning letters or untitled letters or otherwise unacceptable inspectional findings; ● injunctions, penalties, fines, or debarment; 32 Table of Contents ● suspension any ongoing clinical studies, clinical holds, or regulatory authority refusal to approve marketing applications; ● restrictions on operations, product seizure or detention, refusal to permit the import or export of products, or product recalls; or ● adverse publicity.
If we or our third-party contractors are not able to follow the FDA’s or comparable foreign regulatory authorities’ regulatory requirements, we or they may face enforcement actions that may materially harm our business, including, but not limited to: 37 Table of Contents ● warning letters, untitled letters, cyber letters or otherwise unacceptable inspectional findings; ● injunctions, penalties, fines, restitution, consent decrees, corporate integrity agreements, suspension or debarment; ● suspension or termination of any ongoing clinical studies, imposition of a clinical hold, or regulatory authority refusal to approve pending marketing applications; ● modification of promotional materials or labeling, provision of corrective information, imposition of post-market requirements including the need for additional testing; ● restrictions on operations, product seizure or detention, refusal to permit the import or export of products, or product recalls; or ● adverse publicity.
Many of our employees, including our senior management, were previously employed at other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Some of these employees, including each member of our senior management, executed proprietary rights, non-disclosure and non-competition agreements in connection with such previous employment.
Some of these employees, including each member of our senior management, executed proprietary rights, non-disclosure and non-competition agreements in connection with such previous employment.
The trading price of our common stock is highly volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond our control.
Delisting could also impair our ability to raise capital. ​ Our share price and the liquidity of our stock may be volatile and result in substantial losses to our stockholders. The trading price of our common stock is highly volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond our control.
If we are unable to obtain regulatory approval for our product candidates in one or more jurisdictions, we may not be able to obtain sufficient funding or generate sufficient revenue to continue the development of our product candidates. The results of preclinical testing or earlier clinical studies are not necessarily predictive of future results.
If we are unable to obtain regulatory approval or designations we may seek, such as orphan designation, for our product candidates in one or more jurisdictions, we may not be able to obtain sufficient funding or generate sufficient revenue to continue the development of our product candidates.
Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates. Until we can generate substantial revenue from product sales, if ever, we expect to seek additional capital through a combination of private and public equity offerings, debt financings, strategic collaborations and alliances and licensing arrangements.
Until we can generate substantial revenue from product sales, if ever, we expect to continue to seek additional capital through a combination of private and public equity offerings, debt financings, strategic collaborations and alliances and licensing arrangements.
We need to obtain additional funding to further develop our products in future clinical trials and through regulatory processes; if we are unable to meet our needs for additional funding in the future, we will be required to limit, scale back or cease operations.
We need to obtain additional funding to continue as a going concern; if we are unable to meet our needs for additional funding in the future, we will be required to limit, scale back or cease operations.
If we breach our license agreements or fail to negotiate new agreements pertaining to our product candidates, we could lose the ability to continue the development and potential commercialization of these product candidates.
Compared to us, many of our competitors may have significantly greater financial, technical and human resources. 39 Table of Contents If we breach our license agreements or fail to negotiate new agreements pertaining to our product candidates, we could lose the ability to continue the development and potential commercialization of these product candidates.
ITEM 1A. RISK FACTORS You should carefully consider the following risk factors together with the other information contained in this Annual Report, including our financial statements and the related notes appearing in this report. We cannot assure you that any of the events discussed in the risk factors below will not occur.
ITEM 1A. RISK FACTORS You should carefully consider the following risk factors together with the other information contained in this Annual Report, including our financial statements, the related notes and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” appearing in this report.
Further, the examination process may require us or our licensor to narrow the claims for our pending patent applications, which may limit the scope of patent protection that may be obtained if these 43 Table of Contents applications issue.
Our pending applications cannot be enforced against third parties practicing the technology claimed in such applications unless and until a patent issues from such applications. Further, the examination process may require us or our licensor to narrow the claims for our pending patent applications, which may limit the scope of patent protection that may be obtained if these applications issue.
Any product candidate we advance into clinical trials may not have favorable results in later-stage clinical trials or receive regulatory approval. Encouraging results in preclinical testing and earlier clinical studies do not ensure that later clinical trials will generate adequate data to demonstrate the efficacy and safety of an investigational drug.
Encouraging results in preclinical testing and earlier clinical studies do not ensure that later clinical trials will generate adequate data to demonstrate the efficacy and safety of an investigational drug. Additionally, mechanisms of action, studies in small or single patient populations, and interim study results may not be predictive of later stage studies.
We rely on trade secret, patent, copyright and trademark laws, and confidentiality, licensing and other agreements with employees and third parties, all of which offer only limited protection. Our commercial success will depend in large part on our ability to obtain and maintain patent protection in the United States and other countries with respect to our proprietary technology and products.
Our commercial success will depend in large part on our ability to obtain and maintain patent protection in the United States and other countries with respect to our proprietary technology and products.
A finding of infringement could prevent us from commercializing our product candidates or force us to cease some of our business operations, which could materially harm our business.
A finding of infringement could prevent us from commercializing our product candidates or force us to cease some of our business operations, which could materially harm our business. Any claims by third parties that we have misappropriated their confidential information or trade secrets could have a similar negative impact on our business.
The manufacturing facilities that we use must also be approved by the FDA under a pre-approval inspection. If the facilities cannot pass these inspections, the FDA will not approve our marketing application. These manufacturing facilities will further be subject to continuing regulatory oversight and inspection, and, thus, they must continue to expend time and resources to maintain regulatory compliance.
Noncompliance with the applicable manufacturing requirements may also require costly corrective and preventative actions. The manufacturing facilities that we use must also be approved by the FDA under a pre-approval inspection. If the facilities cannot pass these inspections, the FDA will not approve our marketing application.
For example, on March 10, 2023, Silicon Valley Bank, (SVB), was closed by the California Department of Financial Protection and Innovation, which appointed the Federal Deposit Insurance Corporation, or the FDIC, as receiver. As of March 10, 2023, we had nearly all of our cash and cash equivalent balances in segregated custodial accounts held by U.S.
For example, on March 10, 2023, Silicon Valley Bank was closed by the California Department of Financial Protection and Innovation, which appointed the Federal Deposit Insurance Corporation, or the FDIC, as receiver, and created uncertainty and liquidity concerns for us, at that time, and in the broader financial services industry remain.
Additionally, mechanisms of action, studies in small or single patient populations, and interim study results may not be predictive of later stage studies. The development of a product for one indication may further impact its development for other indications. By example, our phase III study of intravenous rigosertib for HR MDS did not meet its primary endpoints.
The development of a product for one indication may further impact its development for other indications. By example, our phase III study of intravenous rigosertib for HR MDS did not meet its primary endpoints. It is possible that this may impact how regulators or others view the development of rigosertib for alternative indications and via different methods of administration.
Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates even if our product candidates obtain marketing approval.
Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates even if our product candidates obtain marketing approval. We cannot be sure that timely coverage and adequate reimbursement will be available for any product that we commercialize and, if reimbursement is available, what the level of coverage and reimbursement will be.
If any of the following risks actually occur, they may materially harm our business and our financial condition and results of operations. In this event, the market price of our securities could decline and your investment could be lost. You should understand that it is not possible to predict or identify all such risks.
The occurrence of any of the following risks, or of additional risks and uncertainties not presently known to us or that we currently believe to be immaterial, could materially and adversely affect our business and our financial condition and results of operations. In this event, the market price of our securities could decline and your investment could be lost.
Department of Treasury, FDIC and Federal Reserve Board will provide access to uninsured funds in the future in the event of the closure of other banks or financial institutions in a timely fashion or at all. 40 Table of Contents Changes in United States and China relations, as well as relations with other countries, and/or regulations may adversely impact our business, our operating results, our ability to raise capital and the market price of our shares.
There is no guarantee that a similar event will not occur again and that our liquidity will not be adversely affected. Changes in United States and China relations, as well as relations with other countries, and/or regulations may adversely impact our business, our operating results, our ability to raise capital and the market price of our shares.
The foregoing may require that we consult with relevant review and ethics committees, IRBs, and the FDA. The foregoing may also impact the integrity of our study data. The effects of the COVID-19 pandemic may also increase the need for clinical trial patient monitoring and regulatory reporting of adverse effects.
The foregoing may require that we consult with relevant review and ethics committees, IRBs, and the FDA. The foregoing may also impact the integrity of our study data, which may not become evident until later in our development programs.
Risks Related to Our Business and Industry Our product development efforts may not be successful. The focus of our development efforts is currently on narazaciclib and oral rigosertib.
Clinical and non-clinical development is expensive, time-consuming, and uncertain as to the outcome. The focus of our development efforts is currently on narazaciclib and oral rigosertib.
Risks Related to Our Intellectual Property We could be required to incur significant expenses to perfect our intellectual property rights, and our intellectual property rights may be inadequate to protect our competitive position. If we are unable to protect our intellectual property rights, our competitive position could be harmed. We depend on our ability to protect our proprietary technology.
These manufacturing facilities will further be subject to continuing regulatory oversight and inspection, and, thus, they must continue to expend time and resources to maintain regulatory compliance. Risks Related to Our Intellectual Property We could be required to incur significant expenses to perfect our intellectual property rights, and our intellectual property rights may be inadequate to protect our competitive position.
Any claims by third parties that we have misappropriated their confidential information or trade secrets could have a similar negative impact on our business. 44 Table of Contents We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.
We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers. Many of our employees, including our senior management, were previously employed at other biotechnology or pharmaceutical companies, including our competitors or potential competitors.
Removed
We cannot be sure that timely coverage and adequate 33 Table of Contents reimbursement will be available for any product that we commercialize and, if reimbursement is available, what the level of coverage and reimbursement will be.
Added
Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.

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Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeITEM 3. LEGAL PROCEEDINGS We are not a party to any legal proceedings and we are not aware of any such proceedings contemplated by government authorities. ITEM 4. MINE SAFETY DISCLOSURES Not applicable. ​ 47 Table of Contents PART II
Biggest changeITEM 3. LEGAL PROCEEDINGS We are not a party to any legal proceedings and we are not aware of any such proceedings contemplated by government authorities. ITEM 4. MINE SAFETY DISCLOSURES Not applicable. ​ 49 Table of Contents PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Market Information Our common stock is listed under the symbol ONTX on the Nasdaq Capital Market. Stockholders As of February 28, 2023, there were approximately 97 holders of record for shares of our common stock.
Biggest changeITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Market Information Our common stock is listed under the symbol ONTX on the Nasdaq Capital Market. Stockholders As of February 29, 2024, there were approximately 96 holders of record for shares of our common stock.

Item 7. Management's Discussion & Analysis

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

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Biggest changeThe Company has not performed any detailed analysis as it expects these to expire before utilization and has provided for a full valuation allowance but will perform a Section 382 and 383 study if any tax attributes are to be utilized in a given year. 52 Table of Contents Results of Operations Comparison of the Years Ended December 31, 2022 and 2021 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ ​ ​ ​ ​ 2022 2021 Change Revenue ​ $ 226,000 ​ $ 226,000 ​ $ — Operating expenses: ​ ​ ​ ​ General and administrative ​ ​ 8,447,000 ​ 9,425,000 ​ 978,000 Research and development ​ ​ 11,406,000 ​ 7,297,000 ​ 4,109,000 Total operating expenses ​ 19,853,000 ​ 16,722,000 ​ 3,131,000 Loss from operations ​ (19,627,000) ​ (16,496,000) ​ (3,131,000) Change in fair value of warrant liability ​ — ​ 321,000 ​ (321,000) Other income, net ​ 663,000 ​ 12,000 ​ 651,000 Net loss before income taxes ​ (18,964,000) ​ (16,163,000) ​ (2,801,000) Income taxes ​ — ​ — ​ — Net loss ​ $ (18,964,000) ​ $ (16,163,000) ​ $ (2,801,000) ​ Revenues Revenues for 2022 were consistent with 2021 and were due to the recognition of deferred revenue from our collaboration with SymBio.
Biggest changeResults of Operations Comparison of the Years Ended December 31, 2023 and 2022 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ ​ ​ ​ ​ 2023 2022 Change Revenue ​ $ 226,000 ​ $ 226,000 ​ $ — Operating expenses: ​ ​ ​ ​ General and administrative ​ ​ 9,094,000 ​ 8,447,000 ​ (647,000) Research and development ​ ​ 11,430,000 ​ 11,406,000 ​ (24,000) Total operating expenses ​ 20,524,000 ​ 19,853,000 ​ (671,000) Loss from operations ​ (20,298,000) ​ (19,627,000) ​ (671,000) Other income, net ​ 1,350,000 ​ 663,000 ​ 687,000 Net loss ​ $ (18,948,000) ​ $ (18,964,000) ​ $ 16,000 ​ Revenues Revenues for 2023 were consistent with 2022 and were due to the recognition of deferred revenue from our collaboration with SymBio.
Our operations to date have included our organization and staffing, business planning, raising capital, in-licensing technology from research institutions, identifying potential product candidates, developing product candidates and building strategic alliances, as well as undertaking preclinical studies and clinical trials of our product candidates. 48 Table of Contents Since commencing operations, we have dedicated a significant portion of our resources to the development of our clinical-stage product candidates, particularly narazaciclib and rigosertib.
Our operations to date have included our organization and staffing, business planning, raising capital, in-licensing technology from research institutions, identifying potential product candidates, developing product candidates and building strategic alliances, as well as undertaking preclinical studies and clinical trials of our product candidates. 50 Table of Contents Since commencing operations, we have dedicated a significant portion of our resources to the development of our clinical-stage product candidates, particularly narazaciclib and rigosertib.
We believe that our cash and cash equivalents will be sufficient to fund our ongoing trials and business operations into the first quarter of 2024; however, based on current projections, we do not have sufficient cash and cash equivalents as of the date of this Annual Report on Form 10-K to support our operations for at least the 12 months following the date that the financial statements are issued.
We believe that our cash and cash equivalents will be sufficient to fund our ongoing trials and business operations into the third quarter of 2024; however, based on current projections, we do not have sufficient cash and cash equivalents as of the date of this Annual Report on Form 10-K to support our operations for at least the 12 months following the date that the financial statements are issued.
We believe that our cash and cash equivalents will be sufficient to fund our ongoing trials and operations into the first quarter of 2024; however, based on current projections, we do not have sufficient cash and cash equivalents as of the date of this Annual Report on Form 10-K to support our operations for at least the 12 months following the date that the financial statements are issued.
We believe that our cash and cash equivalents will be sufficient to fund our ongoing trials and operations into the third quarter of 2024; however, based on current projections, we do not have sufficient cash and cash equivalents as of the date of this Annual Report on Form 10-K to support our operations for at least the 12 months following the date that the financial statements are issued.
Accordingly, substantial doubt exists with respect to our ability to continue as a going concern within one year after the date that these financial statements are issued. Financial Overview Revenue During the years ended December 31, 2022 and 2021, our revenues were derived exclusively from activities conducted in accordance with our collaboration arrangement with SymBio.
Accordingly, substantial doubt exists with respect to our ability to continue as a going concern within one year after the date that these financial statements are issued. Financial Overview Revenue During the years ended December 31, 2023 and 2022, our revenues were derived exclusively from activities conducted in accordance with our collaboration arrangement with SymBio.
We are recognizing the $7.5 million upfront payment received in 2011 under the SymBio collaboration agreement as revenue on a straight-line basis through December 2037, reflecting our estimate of when we will complete our obligations under the agreement. For the years ended December 31, 2022 and 2021, we recognized revenues of $226,000 and $226,000, respectively, under the SymBio collaboration agreement.
We are recognizing the $7.5 million upfront payment received in 2011 under the SymBio collaboration agreement as revenue on a straight-line basis through December 2037, reflecting our estimate of when we will complete our obligations under the agreement. For the years ended December 31, 2023 and 2022, we recognized revenues of $226,000 and $226,000, respectively, under the SymBio collaboration agreement.
These conditions raise substantial doubt about our ability to continue as a going concern through the one-year period after the date that the financial statements are issued. 55 Table of Contents We are exploring various sources of funding for continued development of narazaciclib and any potential in-licensed compounds as well as our ongoing operations.
These conditions raise substantial doubt about our ability to continue as a going concern through the one-year period after the date that the financial statements are issued. We are exploring various sources of funding for continued development of narazaciclib and any potential in-licensed compounds as well as our ongoing operations.
Although we do not expect our estimates to be materially different from amounts actually incurred, our understanding of the status and 51 Table of Contents timing of services performed relative to the actual status and timing of services performed may vary and may result in us reporting amounts that are too high or too low for any particular period.
Although we do not expect our estimates to be materially different from amounts actually incurred, our understanding of the status and timing of services performed relative to the actual status and timing of services performed may vary and may result in us reporting amounts that are too high or too low for any particular period.
We believe that our cash and cash equivalents will be sufficient to fund our ongoing trials and operations into the first quarter of 2024; however, based on current projections, we do not have sufficient cash and cash equivalents as of the date of this Annual Report on Form 10-K to support our operations for at least the 12 months following the date that the financial statements are issued.
We believe that our cash and cash equivalents will be sufficient to fund our ongoing trials and operations into the third quarter of 2024; however, based on current projections, we do not have sufficient cash and cash equivalents as of the date of this Annual Report on Form 10-K to support our operations for at least the 12 months 56 Table of Contents following the date that the financial statements are issued.
We incurred research and development expenses of $11.4 million and $7.3 million during the years ended December 31, 2022 and 2021, respectively. We anticipate that a significant portion of our operating expenses will continue to be related to research and development as we continue to advance narazaciclib and our other programs.
We incurred research and development expenses of $11.4 million and $11.4 million during the years ended December 31, 2023 and 2022, respectively. We anticipate that a significant portion of our operating expenses will continue to be related to research and development as we continue to advance narazaciclib and our other programs.
Accordingly, we do not allocate expenses to individual projects or 50 Table of Contents product candidates, although we do allocate some portion of our research and development expenses by functional area and by compound.
Accordingly, we do not allocate expenses to individual projects or product candidates, although we do allocate some portion of our research and development expenses by functional area and by compound.
Changes in operating assets and liabilities resulted in a net decrease in cash of $3.6 million.
Changes in operating assets and liabilities resulted in a net decrease in cash of $0.3 million.
Liquidity and Capital Resources Since our inception, we have incurred net losses and experienced negative cash flows from our operations. We incurred net losses of $19.0 million and $16.2 million for the years ended December 31, 2022 and 2021, respectively.
Liquidity and Capital Resources Since our inception, we have incurred net losses and experienced negative cash flows from our operations. We incurred net losses of $18.9 million and $19.0 million for the years ended December 31, 2023 and 2022, respectively.
The accompanying financial statements have been prepared on a going concern basis, which contemplates the realization of assets and satisfaction of liabilities in the normal course of business, and do not include any adjustments relating to recoverability and classification of recorded asset amounts or the amounts and classification of liabilities that might be necessary should we be unable to continue as a going concern. 54 Table of Contents Cash Flows The following table summarizes our cash flows for the year ended December 31, 2022 and 2021: ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2022 2021 Net cash (used in) provided by: ​ ​ Operating activities ​ $ (16,294,000) ​ $ (19,487,000) Financing activities ​ — ​ 55,560,000 Effect of foreign currency translation ​ (19,000) ​ (28,000) Net (decrease) increase in cash and cash equivalents ​ $ (16,313,000) ​ $ 36,045,000 ​ Net cash used in operating activities Net cash used in operating activities was $16.3 million for the year ended December 31, 2022 and consisted primarily of a net loss of $19.0 million, including $1.2 million of noncash stock-based compensation and depreciation expense.
The accompanying financial statements have been prepared on a going concern basis, which contemplates the realization of assets and satisfaction of liabilities in the normal course of business, and do not include any adjustments relating to recoverability and classification of recorded asset amounts or the amounts and classification of liabilities that might be necessary should we be unable to continue as a going concern. 55 Table of Contents Cash Flows The following table summarizes our cash flows for the year ended December 31, 2023 and 2022: ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2023 2022 Net cash (used in) provided by: ​ ​ Operating activities ​ $ (17,932,000) ​ $ (16,294,000) Investing activities ​ (14,000) ​ — Financing activities ​ — ​ — Effect of foreign currency translation ​ 10,000 ​ (19,000) Net decrease in cash and cash equivalents ​ $ (17,936,000) ​ $ (16,313,000) ​ Net cash used in operating activities Net cash used in operating activities was $17.9 million for the year ended December 31, 2023 and consisted primarily of a net loss of $18.9 million, including $1.3 million of noncash stock-based compensation and depreciation expense.
For the years ended December 31, 2022 and 2021, we allocated stock-based compensation as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2022 2021 General and administrative ​ $ 538,000 $ 490,000 Research and development ​ 617,000 ​ 86,000 ​ ​ $ 1,155,000 ​ $ 576,000 ​ Fair Value Estimates We estimate the fair value of share-based awards to employees and non-employees using the Black-Scholes option pricing model.
For the years ended December 31, 2023 and 2022, we allocated stock-based compensation as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2023 2022 General and administrative ​ $ 586,000 $ 538,000 Research and development ​ 715,000 ​ 617,000 ​ ​ $ 1,301,000 ​ $ 1,155,000 53 Table of Contents ​ Fair Value Estimates We estimate the fair value of share-based awards to employees and non-employees using the Black-Scholes option pricing model.
As of December 31, 2022, we had an accumulated deficit of $463.7 million. We expect to incur significant expenses and operating losses for the foreseeable future as we continue the development and clinical trials of, and seek regulatory approval for, our product candidates, even if milestones under our license and collaboration agreements may be met.
We expect to incur significant expenses and operating losses for the foreseeable future as we continue the development and clinical trials of, and seek regulatory approval for, our product candidates, even if milestones under our license and collaboration agreements may be met. As of December 31, 2023 we had $20.8 million in cash and cash equivalents.
General and administrative expenses General and administrative expenses decreased by $1.0 million or 10.4%, to $8.4 million for the year ended December 31, 2022 from $9.4 million for the year ended December 31, 2021.
General and administrative expenses General and administrative expenses increased by $0.6 million or 7.7%, to $9.1 million for the year ended December 31, 2023 from $8.4 million for the year ended December 31, 2022.
The guidance is effective for fiscal years beginning after December 15, 2022, and interim periods within those years, for companies deemed to be smaller reporting companies as of November 15, 2019, with early adoption permitted. We will adopt the guidance as of January 1, 2023. The guidance is not expected to have a material effect on the Company. ITEM 7A.
The guidance is effective for fiscal years beginning after December 15, 2022, and interim periods within those years, for companies deemed to be smaller reporting companies, with early adoption permitted. We adopted the guidance effective January 1, 2023. The guidance did not have a material effect on our consolidated financial statements. ITEM 7A.
Deferred revenue decreased $0.2 million due to recognition of the unamortized portion of the upfront payment under our collaboration agreement with SymBio. Net cash provided by financing activities There was no net cash used in or provided by financing activities in the 2022 period.
Deferred revenue decreased $0.2 million due to recognition of the unamortized portion of the upfront payment under our collaboration agreement with SymBio. Net cash used in investing activities Net cash used in investing activities was $14,000 in the 2023 period related to information technology asset purchases. There was no net cash used in investing activities in the 2022 period.
Our operating activities used $16.3 million and $19.5 million of net cash during the year ended December 31, 2022 and 2021, respectively. At December 31, 2022, we had an accumulated deficit of $463.7 million, working capital of $31.3 million, and cash and cash equivalents of $38.8 million.
Our operating activities used $17.9 million and $16.3 million of net cash during the year ended December 31, 2023 and 2022, respectively. At December 31, 2023, we had an accumulated deficit of $482.6 million, working capital of $13.4 million, and cash and cash equivalents of $20.8 million.
Critical Accounting Policies and Estimates This management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with US generally accepted accounting principles (GAAP).
Other Income, Net Other income, net consists principally of interest income earned on cash and cash equivalent balances and foreign exchange gains and losses. 52 Table of Contents Critical Accounting Policies and Estimates This management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with US generally accepted accounting principles (GAAP).
We will require substantial additional financing to fund our ongoing clinical trials and operations, and to continue to execute our strategy. To alleviate the conditions that raise substantial doubt about our ability to continue as a going concern, we plan to explore various dilutive and non-dilutive sources of funding, including equity financings, strategic alliances, business development and other sources.
To alleviate the conditions that raise substantial doubt about our ability to continue as a going concern, we plan to explore various dilutive and non-dilutive sources of funding, including equity financings, strategic alliances, business development and/or combinations, and other sources. The future success of the Company is dependent upon our ability to obtain additional funding.
In addition, we recognized revenues of $0 and $0 for the years ended December 31, 2022 and 2021, respectively, related to the supply agreement. 49 Table of Contents Operating Expenses The following table summarizes our operating expenses for the years ended December 31, 2022 and 2021: ​ ​ ​ ​ ​ ​ ​ ​ 2022 2021 General and administrative ​ $ 8,447,000 ​ $ 9,425,000 Research and development ​ 11,406,000 ​ 7,297,000 Total operating expenses ​ $ 19,853,000 ​ $ 16,722,000 ​ General and Administrative Expenses General and administrative expenses consist principally of salaries and related costs for executive and other administrative personnel, including stock-based compensation and travel expenses.
Operating Expenses The following table summarizes our operating expenses for the years ended December 31, 2023 and 2022: ​ ​ ​ ​ ​ ​ ​ ​ 2023 2022 General and administrative ​ $ 9,094,000 ​ $ 8,447,000 Research and development ​ 11,430,000 ​ 11,406,000 Total operating expenses ​ $ 20,524,000 ​ $ 19,853,000 ​ General and Administrative Expenses General and administrative expenses consist principally of salaries and related costs for executive and other administrative personnel, including stock-based compensation and travel expenses.
The failure to obtain sufficient capital on acceptable terms when needed would have a material adverse effect on our business, results of operations, and financial condition. Accordingly, we have concluded that substantial doubt exists with respect to our ability to continue as a going concern within one year after the date that these financial statements are issued.
Accordingly, we have concluded that substantial doubt exists with respect to our ability to continue as a going concern within one year after the date that these financial statements are issued.
The details of our general and administrative expenses are: ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ 2022 2021 Professional & consulting fees ​ $ 1,824,000 ​ $ 1,649,000 Stock based compensation ​ ​ 538,000 ​ ​ 490,000 Personnel related ​ 3,408,000 ​ 3,180,000 Commercial ​ ​ — ​ ​ 101,000 Public company costs ​ 1,382,000 ​ 2,587,000 Insurance & other ​ ​ 1,295,000 ​ ​ 1,418,000 ​ ​ $ 8,447,000 ​ $ 9,425,000 ​ Research and development expenses Research and development expenses increased by $4.1 million, or 56.3%, to $11.4 million for the year ended December 31, 2022 from $7.3 million for the year ended December 31, 2021.
The details of our general and administrative expenses are: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ ​ 2023 2022 Professional & consulting fees ​ $ 2,162,000 ​ $ 1,824,000 ​ Stock based compensation ​ ​ 715,000 ​ ​ 538,000 ​ Personnel related ​ 3,264,000 ​ 3,408,000 ​ Public company costs ​ 1,968,000 ​ 1,382,000 ​ Insurance & other ​ ​ 985,000 ​ ​ 1,295,000 ​ ​ ​ $ 9,094,000 ​ $ 8,447,000 ​ ​ 54 Table of Contents Research and development expenses Research and development expenses were flat in 2023 compared to 2022 at $11.4 million.
Other general and administrative expenses include facility-related costs, communication expenses, insurance, board of directors expenses and professional fees for legal, patent review, consulting and accounting services. We anticipate that our general and administrative expenses will remain consistent in the short-term, but would increase in the future with the continued research and development and potential commercialization of our product candidates.
We anticipate that our general and administrative expenses will remain consistent in the short-term, but would increase in the future with the continued research and development and potential commercialization of our product 51 Table of Contents candidates.
Net cash used in operating activities was $19.5 million for the year ended December 31, 2021 and consisted primarily of a net loss of $16.2 million, including a favorable change in fair value of warrant liability of $0.3 million and $0.6 million of noncash stock-based compensation and depreciation expense.
Deferred revenue decreased $0.2 million due to recognition of the unamortized portion of the upfront payment under our collaboration agreement with SymBio. Net cash used in operating activities was $16.3 million for the year ended December 31, 2022 and consisted primarily of a net loss of $19.0 million, including $1.2 million of noncash stock-based compensation and depreciation expense.
These contracts generally provide for termination following a certain period after notice and therefore we believe that, currently, our non-cancelable obligations under these agreements are not material.
We enter into contracts in the normal course of business with third-party contract organizations for clinical trials, preclinical studies, manufacturing and other services and products for operating purposes. These contracts generally provide for termination following a certain period after notice and therefore we believe that, currently, our non-cancelable obligations under these agreements are not material.
The future success of the Company is dependent upon our ability to obtain additional funding. There can be no assurance, however, that we will be successful in obtaining such funding in sufficient amounts, on terms acceptable to us, or at all.
There can be no assurance, however, that we will be successful in obtaining such funding in sufficient amounts, on terms acceptable to us, or at all. The failure to obtain sufficient capital on acceptable terms when needed would have a material adverse effect on our business, results of operations, and financial condition.
The decrease was attributable primarily to $1.2 million lower expenses for investor relations, proxy solicitation, and fees related to our shareholder meetings in the 2021 period which did not recur in the 2022 period, $0.1 million lower facilities related costs, $0.1 million lower insurance expenses and $0.1 million lower commercial consulting expenses in the 2022 period.
The increase was attributable primarily to $0.6 million higher expenses for investor relations, proxy solicitation, and fees related to our shareholder meetings in the 2023 period, $0.3 million higher professional and consulting fees, and $0.2 million higher stock-based compensation costs in 2023.
Significant changes in operating assets and liabilities included a decrease in accounts payable and accrued liabilities of $3.9 million as a result of the timing of clinical trial and other accruals, and receipt and payment of vendor invoices, and the reduction of prepaid expenses of $0.5 million primarily as a result of recognition of insurance expense.
Significant changes in operating assets and liabilities included a $1.3 million increase in prepaid assets and other current assets related to our agreements with clinical and manufacturing vendors, partially offset by $1.2 million higher accounts payable and accrued liabilities as a result of the timing of clinical trial and other accruals, and receipt and payment of vendor invoices.
Material Cash Requirements We have not achieved profitability since our inception and we expect to continue to incur net losses for the foreseeable future. We expect net cash expended in 2023 to be higher than 2022 due to clinical trials with narazaciclib and increased headcount in our clinical and regulatory groups.
Net cash provided by financing activities There was no net cash used in or provided by financing activities in the 2023 or 2022 periods. Material Cash Requirements We have not achieved profitability since our inception and we expect to continue to incur net losses for the foreseeable future.
These increases were partially offset by a $0.3 million decrease in consulting expenses in the 2022 period. 53 Table of Contents The details of our research and development expenses are: ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2022 2021 Preclinical & clinical develop ent ​ $ 4,206,000 ​ $ 2,242,000 Personnel related ​ 2,399,000 ​ 1,955,000 Manufacturing, formulation & development ​ 2,851,000 ​ 1,336,000 Stock based compensation ​ 617,000 ​ 86,000 Consulting fees ​ 1,333,000 ​ 1,678,000 ​ ​ $ 11,406,000 ​ $ 7,297,000 ​ Change in fair value of warrant liability The fair value of the warrant liability was reduced to $0 during the third quarter of 2021, following the expiration of the underlying tradable warrants.
The details of our research and development expenses are: ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended December 31, ​ 2023 2022 Preclinical & clinical development ​ $ 4,060,000 ​ $ 4,206,000 Personnel related ​ 2,400,000 ​ 2,399,000 Manufacturing, formulation & development ​ 2,798,000 ​ 2,851,000 Stock based compensation ​ 586,000 ​ 617,000 Consulting fees ​ 1,586,000 ​ 1,333,000 ​ ​ $ 11,430,000 ​ $ 11,406,000 ​ Other income, net Other income, net, increased by $0.7 million for the year ended December 31, 2023 compared to the year ended December 31, 2022 due primarily to $0.7 million higher interest income in the 2023 period, partially offset by $49,000 higher foreign currency exchange loss in the 2023 period.
We also expect an increase in costs for potential in-licensing, the timing of which will be determined by the timing of any potential in-licensing. We enter into contracts in the normal course of business with third-party contract organizations for clinical trials, preclinical studies, manufacturing and other services and products for operating purposes.
We expect net cash expended in 2024 to be higher than 2023 due to clinical trials with narazaciclib and increased headcount in our clinical and regulatory groups. We also expect an increase in costs for potential in-licensing, the timing of which will be determined by the timing of any potential in-licensing.
These decreases were partially offset by $0.2 million higher personnel related costs and $0.2 higher professional and consulting fees during the 2022 period.
These increases were partially offset by $0.3 million lower insurance and other costs and lower personnel related costs of $0.1 million in the 2023 period due to lower bonus accrual and headcount.
Through September 30, 2021, we sold 109,523 shares under the agreement and net proceeds were approximately $0.5 million. There were no other sales during the years ended December 31, 2022 and 2021. Our net losses were $19.0 million and $16.2 million for the years ended December 31, 2022 and 2021, respectively.
Our net losses were $18.9 million and $19.0 million for the years ended December 31, 2023 and 2022, respectively. As of December 31, 2023, we had an accumulated deficit of $482.6 million.
Removed
In January 2021, we closed on an offering of common stock. We issued 1,303,408 shares of common stock and net proceeds were approximately $8.5 million. In February 2021, we closed on an offering of common stock. We issued 1,916,667 shares of common stock and net proceeds were approximately $26.7 million.
Added
In addition, we recognized revenues of $0 and $0 for the years ended December 31, 2023 and 2022, respectively, related to the supply agreement.
Removed
In September 2021, we closed on an offering of common stock. We issued 5,000,000 shares of common stock and net proceeds were approximately $19.5 million. In August 2021, we entered into an at-the-market equity distribution agreement for the sale of up to $25.0 million of common stock.
Added
Other general and administrative expenses include facility-related costs, communication expenses, insurance, board of directors expenses and professional fees for legal, patent review, consulting and accounting services.
Removed
As of December 31, 2022 we had $38.8 million in cash and cash equivalents.
Added
There was an increase of $0.3 million in consulting fees, which was offset by decreases of $0.1 million preclinical and clinical development, as well as $0.1 million lower manufacturing and formulation costs.
Removed
Interest Expense and Other Income, Net Other income, net consists principally of interest income earned on cash and cash equivalent balances and foreign exchange gains and losses.
Added
We will require substantial additional financing to fund our ongoing clinical trials and operations, and to continue to execute our strategy.
Removed
Income Taxes We recorded deferred tax assets of $170.1 million as of December 31, 2022, which have been fully offset by a valuation allowance due to uncertainties surrounding our ability to realize these tax benefits.
Removed
The deferred tax assets are primarily composed of federal and state tax net operating loss (NOL), carry forwards and research and development tax credit carry forwards.
Removed
As of December 31, 2022, we had federal NOL carry forwards of $298.1 million, state NOL carry forwards of $257.8 million, federal research and development tax credit carry forwards of $89.7 million and state research and development tax credit carry forwards of $1.1 million available to reduce future taxable income, if any.
Removed
Federal NOL carry forwards generated before 2018 will begin to expire at various dates starting in 2023. The state NOL carry forwards will begin to expire at various dates starting in 2025.
Removed
In general, if we experience a greater than 50 percentage point aggregate change in ownership of specified significant stockholders over a three-year period, utilization of our pre-change US NOL, tax credit and other tax attribute carry forwards may be subject to an annual limitations under Sections 382 and 383 of the U.S.
Removed
Internal Revenue Code of 1986, as amended (the Code) and similar state laws. Such limitations may result in expiration of a portion of the NOL carry forwards before utilization and may be substantial. The amount of the annual limitation, if any, will be determined based on the value of the Company immediately prior to the ownership change.
Removed
Subsequent ownership changes may further affect the limitation in future years. The Company believes such a change occurred and may impact available net operating losses and carry over research credits generated.
Removed
This increase was caused primarily by $2.0 million higher clinical and preclinical development expenses related to narazaciclib, by $1.5 million higher manufacturing costs related to narazaciclib drug substance and drug product, and also by $0.9 million higher personnel and stock compensation expense during the 2022 period.
Removed
The change in the fair value of the warrant liability was an increase of $0.3 million during the year ended December 31, 2021 based on the change in market value of the tradable warrants in the 2021 period.
Removed
Other income, net Other income, net, increased by $0.6 million for the year ended December 31, 2022 compared to the year ended December 31, 2021 due primarily to $0.6 million higher interest income in the 2022 period and $27,000 higher foreign currency exchange gain in the 2022 period.
Removed
Deferred revenue decreased $0.2 million due to recognition of the unamortized portion of the upfront payment under our collaboration agreement with SymBio.
Removed
Net cash provided by financing activities for the year ended December 31, 2021 was $55.6 million, which resulted from the proceeds received from the sale of common stock in January, February, and September 2021 and through the at-the-market facility during August and September 2021. An additional $0.5 million was provided by the exercise of common stock warrants.

Other TRAW 10-K year-over-year comparisons