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What changed in Genprex, Inc.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of Genprex, Inc.'s 2023 and 2024 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 2024 report.

+460 added−367 removedSource: 10-K (2025-04-01) vs 10-K (2024-04-01)

Top changes in Genprex, Inc.'s 2024 10-K

460 paragraphs added · 367 removed · 314 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

169 edited+80 added−32 removed382 unchanged
Biggest changeLicense Agreement with University of Pittsburgh - Of the Commonwealth System of Higher Education On February 11, 2020, we entered into an exclusive license agreement, as amended on August 17, 2022 and November 3, 2022 (collectively the “2020 UP License Agreement”), with the University of Pittsburgh - Of the Commonwealth System of Higher Education (“University of Pittsburgh” or “UP”) pursuant to which UP granted us a worldwide, exclusive license to certain licensed technology, and a worldwide, non-exclusive license to use certain related know-how, all related to diabetes gene therapy.
Biggest changeLicense Agreement with University of Pittsburgh - Of the Commonwealth System of Higher Education As noted above, on February 17, 2025, the Company and UP entered into an amended and restated Exclusive License Agreement (the “New UP License Agreement”), which updates and consolidates into a single agreement the Prior License Agreements (as defined below).
REQORSA is injected intravenously and specifically targets cancer cells. Cancer cells have elevated metabolism compared to healthy cells and as a result, are negatively charged compared to healthy cells, which are generally charge neutral. REQORSA is designed to deliver the functioning TUSC2 gene to cancer cells while minimizing uptake by normal tissue.
REQORSA is designed to deliver the functioning TUSC2 gene to cancer cells while minimizing uptake by normal tissue. REQORSA is injected intravenously and specifically targets cancer cells. Cancer cells have elevated metabolism compared to healthy cells and as a result, are negatively charged compared to healthy cells, which are generally charge neutral.
Our diabetes product candidates are currently being evaluated and optimized in preclinical studies at the University of Pittsburgh. GPX-002 is being developed using the same construct for the treatment of both Type 1 diabetes and Type 2 diabetes.
Our diabetes product candidates are currently being evaluated and optimized in preclinical studies at the University of Pittsburgh. GPX-002 is being developed using the same construct for the treatment of both Type 1 diabetes and Type 2 diabetes.
GPX-002 for Type 1 diabetes is designed to work by transforming alpha cells in the pancreas into functional beta-like cells, which can produce insulin but may be distinct enough from beta cells to evade the body’s immune system.
GPX-002 for Type 1 diabetes is designed to work by transforming alpha cells in the pancreas into functional beta-like cells, which can produce insulin but may be distinct enough from beta cells to evade the body’s immune system.
In a similar approach, GPX-002 for Type 2 diabetes (formerly known as GPX-003), where autoimmunity is not at play, is believed to work by replenishing and rejuvenating exhausted beta cells that make insulin.
In a similar approach, GPX-002 for Type 2 diabetes (formerly known as GPX-003), where autoimmunity is not at play, is believed to work by replenishing and rejuvenating exhausted beta cells that make insulin.
Biological Products Development Process The process required by the FDA before a biological product, including our REQORSA, GPX-002, and potential future product candidates, may be marketed in the United States generally involves the following: ● completion of nonclinical laboratory tests and animal studies according to Good Laboratory Practices (“GLPs”), and applicable requirements for the humane use of laboratory animals or other applicable regulations; ● submission to the FDA of an application for an IND, which must become effective before human clinical trials may begin; ● performance of adequate and well-controlled human clinical trials according to the FDA’s regulations, commonly referred to as Good Clinical Practices (“GCPs”) and any additional requirements for the protection of human research patients and their health information, to establish the safety, purity, and potency of the proposed biological product for its intended use; ● compiling of information demonstrating that the product can be properly formulated, manufactured and stored; ● submission to the FDA of a BLA for marketing approval that includes substantive evidence of safety, purity, and potency from results of nonclinical testing and clinical trials; ● satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the product is produced and tested to assess compliance with GMP requirements to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; ● potential FDA audit of the nonclinical and clinical trial sites that generated the data in support of the BLA; and ● FDA review and approval, or licensure, of the BLA. 30 Within the FDA, the Center for Biologics Evaluation and Research (“CBER”) regulates gene therapy products.
Biological Products Development Process The process required by the FDA before a biological product, including our REQORSA, GPX-002, and potential future product candidates, may be marketed in the United States generally involves the following: ● completion of nonclinical laboratory tests and animal studies according to Good Laboratory Practices (“GLPs”), and applicable requirements for the humane use of laboratory animals or other applicable regulations; ● submission to the FDA of an application for an IND, which must become effective before human clinical trials may begin; ● performance of adequate and well-controlled human clinical trials according to the FDA’s regulations, commonly referred to as Good Clinical Practices (“GCPs”) and any additional requirements for the protection of human research patients and their health information, to establish the safety, purity, and potency of the proposed biological product for its intended use; ● compiling of information demonstrating that the product can be properly formulated, manufactured and stored; ● submission to the FDA of a BLA for marketing approval that includes substantive evidence of safety, purity, and potency from results of nonclinical testing and clinical trials; ● satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the product is produced and tested to assess compliance with GMP requirements to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; ● potential FDA audit of the nonclinical and clinical trial sites that generated the data in support of the BLA; and ● FDA review and approval, or licensure, of the BLA. 35 Within the FDA, the Center for Biologics Evaluation and Research (“CBER”) regulates gene therapy products.
As further described in the “Licenses and Research Collaborations” section below, we hold a worldwide, exclusive license from MD Anderson to patents covering the therapeutic use of TUSC2 and other genes that have been shown to have cancer fighting properties, including 20 issued patents and 12 pending patent applications for technologies developed at MD Anderson and The University of Texas Southwestern Medical Center.
As further described in the “Licenses and Research Collaborations” section below, we hold a worldwide, exclusive license from MD Anderson to patents covering the therapeutic use of TUSC2 and other genes that have been shown to have cancer fighting properties, including 12 issued patents and 12 pending patent applications for technologies developed at MD Anderson and The University of Texas Southwestern Medical Center.
A subset of NSCLC patients carry a mutation in EGFR, which makes their tumors sensitive to EGFR tyrosine kinase inhibitors (“EGFR TKIs”). The two most common are referred to as exon 19 deletion and exon 21 substitution. Several pharmacological and biological approaches, including EGFR TKIs, have been developed specifically to block activated EGFR for cancer therapy.
A subset of NSCLC patients carry a mutation in EGFR, which makes their tumors sensitive to EGFR tyrosine kinase inhibitors (“EGFR TKIs”). The two most common mutations are referred to as exon 19 deletion and exon 21 substitution. Several pharmacological and biological approaches, including EGFR TKIs, have been developed specifically to block activated EGFR for cancer therapy.
TUSC2 functions to mediate apoptosis in cancer cells through interaction with Apaf1 and also down-regulates multiple tyrosine kinases that control cell growth, including EGFR, AKT, platelet-derived growth factor receptor (“PDGFR”), c-Kit, and c-Abl. In normal cells, the proteins involved in the PI3K/AKT/mTOR pathway play an important role in cellular function and cellular trafficking.
TUSC2 functions to mediate apoptosis in cancer cells through interaction with Apaf1 and also down-regulates multiple tyrosine kinases that control cell growth, including EGFR, AKT, platelet-derived growth factor receptor (“PDGFR”), c-Kit, and c-Abl. 6 In normal cells, the proteins involved in the PI3K/AKT/mTOR pathway play an important role in cellular function and cellular trafficking.
Data from preclinical studies performed by MD Anderson researchers and others suggest that TUSC2, the active agent in REQORSA, could be effective against other types of cancer, including glioblastoma, head and neck, breast (including triple-negative breast cancer), renal cell (kidney), thyroid, and soft tissue sarcoma, as well as NSCLC and SCLC.
Data from preclinical studies performed by MD Anderson researchers and others suggest that TUSC2, the active agent in REQORSA, could be effective against other types of cancer, including glioblastoma, mesothelioma, head and neck, breast (including triple-negative breast cancer), renal cell (kidney), thyroid, and soft tissue sarcoma, as well as NSCLC and SCLC.
Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic. 36 The BPCIA includes, among other provisions: ● A 12-year exclusivity period from the date of first licensure, or BLA approval, of the reference product, during which approval of a 351(k) application referencing that product may not be made effective; ● A four-year exclusivity period from the date of first licensure of the reference product, during which a 351(k) application referencing that product may not be submitted; and ● An exclusivity period for certain biological products that have been approved through the 351(k) pathway as interchangeable biosimilars.
Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic. 41 The BPCIA includes, among other provisions: ● A 12-year exclusivity period from the date of first licensure, or BLA approval, of the reference product, during which approval of a 351(k) application referencing that product may not be made effective; ● A four-year exclusivity period from the date of first licensure of the reference product, during which a 351(k) application referencing that product may not be submitted; and ● An exclusivity period for certain biological products that have been approved through the 351(k) pathway as interchangeable biosimilars.
Operation of the ONCOPREX Delivery System The cationic (positive) charge of the lipoplexes helps to target cancer cells, which have a slight negative charge due to their high glycolytic rate. A Phase 1 clinical trial showed that intravenous REQORSA therapy selectively and preferentially targeted tumor cells, resulting in anticancer activity.
Operation of the ONCOPREX Delivery System The cationic (positive) charge of the lipoplexes helps to target cancer cells, which have a slight negative charge due to their high glycolytic rate. A Phase 1 monotherapy clinical trial showed that intravenous REQORSA therapy selectively and preferentially targeted tumor cells, resulting in anticancer activity.
Even if we complete the necessary clinical trials, we cannot predict when, or if, we will obtain regulatory approval to commercialize our product candidates, and the approval may be for a narrower indication than we seek. ● Even if we obtain regulatory approval of our current and future product candidates, the products may not gain market acceptance among physicians, patients, hospitals, treatment centers, third-party payors and others in the medical community. ● REQORSA®, GPX-002, and other current or future product candidates may have undesirable side effects that may delay or prevent marketing approval, or, if approval is received, require them to be taken off the market, require them to include safety warnings or otherwise limit their sales. ● If a product liability claim is successfully brought against us for uninsured liabilities, or such claim exceeds our insurance coverage, we could be forced to pay substantial damage awards that could materially harm our business. ● Security breaches and other disruptions could compromise our information and expose us to liability, which would cause our business and reputation to suffer. ● We face risks related to health epidemics and outbreaks, including COVID-19, which could significantly disrupt our preclinical studies and clinical trials.
Even if we complete the necessary clinical trials, we cannot predict when, or if, we will obtain regulatory approval to commercialize our product candidates, and the approval may be for a narrower indication than we seek. ● Even if we obtain regulatory approval of our current and future product candidates, the products may not gain market acceptance among physicians, patients, hospitals, treatment centers, third-party payors and others in the medical community. ● REQORSA®, GPX-002, and other current or future product candidates may have undesirable side effects that may delay or prevent marketing approval, or, if approval is received, require them to be taken off the market, require them to include safety warnings or otherwise limit their sales. ● If a product liability claim is successfully brought against us for uninsured liabilities, or such claim exceeds our insurance coverage, we could be forced to pay substantial damage awards that could materially harm our business. ● Security breaches and other disruptions could compromise our information and expose us to liability, which would cause our business and reputation to suffer. ● We face risks related to health epidemics and outbreaks which could significantly disrupt our preclinical studies and clinical trials.
This trial showed that REQORSA was well tolerated and established the single-agent MTD and the therapeutic dosage for REQORSA at 0.06 mg/kg administered every 21 days. This MTD was established based on the occurrence of an asymptomatic, Grade 3 laboratory abnormality in 2 patients.
This trial showed that REQORSA was well tolerated and established the single-agent MTD and the therapeutic dosage for REQORSA at 0.06 mg/kg administered every 21 days. This MTD was established based on the occurrence of an asymptomatic, Grade 3 laboratory abnormality (hypophosphatemia) in 2 patients.
The information contained in the SEC’s website is not intended to be a part of this filing. We have proprietary rights to a number of trademarks, including GENPREX, ONCOPREX and REQORSA, that are used in this Annual Report on Form 10-K.
The information contained in the SEC’s website is not intended to be a part of this filing. We have proprietary rights to a number of trademarks, including GENPREX, ONCOPREX, CONVERGEN and REQORSA, that are used in this Annual Report on Form 10-K.
The FDA reviews the BLA to determine, among other things, whether the proposed product is safe and potent, or effective, for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with GMP to assure and preserve the product’s identity, safety, strength, quality, potency and purity. 33 The FDA may refer applications for novel products or products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.
The FDA reviews the BLA to determine, among other things, whether the proposed product is safe and potent, or effective, for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with GMP to assure and preserve the product’s identity, safety, strength, quality, potency and purity. 38 The FDA may refer applications for novel products or products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.
The primary endpoint of the Phase 2a expansion portion is overall response rate (ORR). The primary endpoint of the Phase 2b randomized portion of the trial is PFS which is defined as time from randomization to disease progression) or death. Patients will be followed for survival.
The primary endpoint of the Phase 2a expansion portion is overall response rate (ORR). The primary endpoint of the Phase 2b randomized portion of the trial is PFS which is defined as time from randomization to disease progression) or death. Patients will also be followed for survival.
For a further discussion of the challenges we face from competition, please see the "Risk Factors" section in Part I, Item 1A of this Annual Report. 29 Government Regulation Government authorities in the U.S., at the federal, state and local level, and other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, recordkeeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of products such as those we are developing.
For a further discussion of the challenges we face from competition, please see the "Risk Factors" section in Part I, Item 1A of this Annual Report. 34 Government Regulation Government authorities in the U.S., at the federal, state and local level, and other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, recordkeeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of products such as those we are developing.
Metabolic Tumor Response in a Metastatic Lung Cancer Subject This subject survived after subsequent therapy more than seven years after the final treatment with REQORSA, to our knowledge, without evidence of cancer progression in the responding sites. 14 ONC-002: Phase 1/2 - Trial Combining REQORSA with Tarceva (Phase 1 portion completed; Phase 2 portion closed in order to conduct Acclaim-1 instead) Phase 1 Portion: The Phase 1 Monotherapy Trial showed that REQORSA is well tolerated, that high levels of TUSC2 expression are detected in the tumor post-treatment, and that there was evidence of tumor growth suppression.
Metabolic Tumor Response in a Metastatic Lung Cancer Subject This subject survived after subsequent therapy more than seven years after the final treatment with REQORSA, to our knowledge, without evidence of cancer progression in the responding sites. 15 ONC-002: Phase 1/2 - Trial Combining REQORSA with Tarceva (Phase 1 portion completed; Phase 2 portion closed in order to conduct Acclaim-1 instead) Phase 1 Portion: The Phase 1 Monotherapy Trial showed that REQORSA is well tolerated, that high levels of TUSC2 expression are detected in the tumor post-treatment, and that there was evidence of tumor growth suppression.
Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the investigational product candidate has been associated with unexpected serious harm to patients. 32 Concurrently with clinical trials, companies usually complete additional animal studies and also develop additional information about the physical characteristics of the components of a product as well as finalize processes for manufacturing the components in commercial quantities in accordance with GMP requirements.
Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the investigational product candidate has been associated with unexpected serious harm to patients. 37 Concurrently with clinical trials, companies usually complete additional animal studies and also develop additional information about the physical characteristics of the components of a product as well as finalize processes for manufacturing the components in commercial quantities in accordance with GMP requirements.
Other types of changes to the approved product, such as adding new indications and additional labeling claims, are also subject to further FDA review and approval. 35 We also must comply with the FDA’s advertising and promotion requirements, such as those related to direct-to-consumer advertising, the prohibition on promoting products for uses or in patient populations that are not described in the product’s approved labeling (known as “off-label use”), industry-sponsored scientific and educational activities, and promotional activities involving the internet.
Other types of changes to the approved product, such as adding new indications and additional labeling claims, are also subject to further FDA review and approval. 40 We also must comply with the FDA’s advertising and promotion requirements, such as those related to direct-to-consumer advertising, the prohibition on promoting products for uses or in patient populations that are not described in the product’s approved labeling (known as “off-label use”), industry-sponsored scientific and educational activities, and promotional activities involving the internet.
These results demonstrate the potent tumor suppressing activity of the TUSC2 gene, supporting the feasibility of using nanovesicles for systemic plasmid delivery to metastases as well as to primary tumors, and implicating REQORSA as a promising therapeutic agent for primary and disseminated human lung cancer. 18 REQORSA Synergizes with Pembrolizumab It was previously shown that the combination of REQORSA and an anti-PD1 antibody inhibited tumor growth synergistically in subcutaneous and metastatic NSCLC KRAS mutant syngeneic mouse models.
These results demonstrate the potent tumor suppressing activity of the TUSC2 gene, supporting the feasibility of using nanovesicles for systemic plasmid delivery to metastases as well as to primary tumors, and implicating REQORSA as a promising therapeutic agent for primary and disseminated human lung cancer. 19 REQORSA Synergizes with Pembrolizumab It was previously shown that the combination of REQORSA and an anti-PD1 antibody inhibited tumor growth synergistically in subcutaneous and metastatic NSCLC KRAS mutant syngeneic mouse models.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. 38 Federal false claims and civil monetary penalties laws, including the federal civil False Claims Act, prohibit, among other things, any person or entity from knowingly presenting, or causing to be presented, a false, fictitious or fraudulent claim for payment to, or approval by, the federal government, or knowingly making, using, or causing to be made or used, a false statement to get a false claim paid.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. 43 Federal false claims and civil monetary penalties laws, including the federal civil False Claims Act, prohibit, among other things, any person or entity from knowingly presenting, or causing to be presented, a false, fictitious or fraudulent claim for payment to, or approval by, the federal government, or knowingly making, using, or causing to be made or used, a false statement to get a false claim paid.
This gene therapy approach has been tested in vivo in mice and NHPs using an earlier construct as described below. 22 Preclinical Mouse Studies In studies in mice treated to destroy insulin producing beta cells and in non-obese diabetic (“NOD”) mice, both of which are models of Type 1 diabetes, our gene therapy approach restored normal blood glucose levels for an extended period of time, and markedly increased the mass of insulin producing beta cells.
This gene therapy approach has been tested in vivo in mice and NHPs using an earlier construct as described below. 23 Preclinical Mouse Studies In studies in mice treated to destroy insulin producing beta cells and in non-obese diabetic (“NOD”) mice, both of which are models of Type 1 diabetes, our gene therapy approach restored normal blood glucose levels for an extended period of time, and markedly increased the mass of insulin producing beta cells.
We believe this new mechanism and novel approach targeting lung cancer, which comes with a strong safety profile and early signs of efficacy, is paving new ground in the fight against lung cancer. 11 Acclaim-2 In December 2021, we received Fast Track Designation from the FDA for use of REQORSA in combination with the checkpoint inhibitor Keytruda for the treatment of advanced NSCLC patients whose tumors progressed after treatment with Keytruda.
We believe this new mechanism and novel approach targeting lung cancer, which comes with a strong safety profile and early signs of efficacy, is paving new ground in the fight against lung cancer. 12 Acclaim-2 In December 2021, we received Fast Track Designation from the FDA for use of REQORSA in combination with the checkpoint inhibitor Keytruda for the treatment of advanced NSCLC patients whose tumors progressed after treatment with Keytruda.
Even if favorable coverage and reimbursement status is attained for one or more products for which we or our collaborators receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. 40 Legislative and Regulatory Changes, Including Health Care Reform The laws and regulation that affect our business are subject to change from time to time, and entirely new laws and regulations are sometimes adopted.
Even if favorable coverage and reimbursement status is attained for one or more products for which we or our collaborators receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future. 45 Legislative and Regulatory Changes, Including Health Care Reform The laws and regulation that affect our business are subject to change from time to time, and entirely new laws and regulations are sometimes adopted.
Results from the Phase 2 portion for the 10 patients show that: ● One patient had a response of CR for a study CR rate of 10% and the overall response rate (CR + PR) was also 10%; ● Three patients had tumor regression; and ● Disease control rate was 70%. 15 The patient with the CR, a 58-year-old female, upon enrollment in the study had metastatic NSCLC following 6 cycles of pemetrexed and carboplatin and after two cycles of maintenance pemetrexed had cancer progression.
Results from the Phase 2 portion for the 10 patients show that: ● One patient had a response of CR for a study CR rate of 10% and the overall response rate (CR + PR) was also 10%; ● Three patients had tumor regression; and ● Disease control rate was 70%. 16 The patient with the CR, a 58-year-old female, upon enrollment in the study had metastatic NSCLC following 6 cycles of pemetrexed and carboplatin and after two cycles of maintenance pemetrexed had cancer progression.
Our collaborators at University of Pittsburgh have also received grants from the NIH in connection with preclinical work on GPX-002 and so, the rights we have obtained pursuant to our UP License Agreements are made subject to the rights of the U.S. government to the extent that the technology covered by the licensed intellectual property was developed under a funding agreement between the University of Pittsburgh and the U.S. government.
Our collaborators at University of Pittsburgh have also received grants from the NIH in connection with preclinical work on GPX-002 and so, the rights we have obtained pursuant to our New UP License Agreement are made subject to the rights of the U.S. government to the extent that the technology covered by the licensed intellectual property was developed under a funding agreement between the University of Pittsburgh and the U.S. government.
For a discussion of the challenges we face in obtaining or maintaining patent, trademark and/or trade secret protection, please see the risk factors under the heading “Risks Related to Our Intellectual Property” in Part I, Item 1A of this Annual Report. 26 Licenses and Research Collaborations Agreements with MD Anderson Our ONCOPREX and REQORSA technologies are exclusively licensed pursuant to a Patent and Technology License Agreement dated July 20, 1994, with MD Anderson, as amended on September 1, 1996, August 11, 1997, July 31, 1994 and October 4, 2001 (collectively, the "1994 MD Anderson License Agreement"), between MD Anderson and Introgen Therapeutics, Inc.
For a discussion of the challenges we face in obtaining or maintaining patent, trademark and/or trade secret protection, please see the risk factors under the heading “Risks Related to Our Intellectual Property” in Part I, Item 1A of this Annual Report. 31 Licenses and Research Collaborations Agreements with MD Anderson Our ONCOPREX and REQORSA technologies are exclusively licensed pursuant to a Patent and Technology License Agreement dated July 20, 1994, with MD Anderson, as amended on September 1, 1996, August 11, 1997, July 31, 1994 and October 4, 2001 (collectively, the “1994 MD Anderson License Agreement”), between MD Anderson and Introgen Therapeutics, Inc.
General Risk Factors ● Obligations associated with being a public company in the United States are expensive and time-consuming, and our management will be required to devote substantial time to compliance matters. ● Business disruptions could seriously harm our future revenue and financial condition and increase our costs and expenses. ● We may be at risk of securities class action litigation. 45
General Risk Factors ● Obligations associated with being a public company in the United States are expensive and time-consuming, and our management will be required to devote substantial time to compliance matters. ● Business disruptions could seriously harm our future revenue and financial condition and increase our costs and expenses. ● We may be at risk of securities class action litigation. 50
We are no longer enrolling the Phase 2 portion of the Phase 1/2 Combination Tarceva Trial in favor of conducting the Acclaim-1 trial, which combines REQORSA with Tagrisso, since Tagrisso has been shown to be more effective than Tarceva as initial therapy for patients with NSCLC with EGFR mutations. 16 Preclinical Studies of REQORSA Supporting Our Conduct of Acclaim-1 REQORSA and Tyrosine Kinases.
We are no longer enrolling the Phase 2 portion of the Phase 1/2 Combination Tarceva Trial in favor of conducting the Acclaim-1 trial, which combines REQORSA with Tagrisso, since Tagrisso has been shown to be more effective than Tarceva as initial therapy for patients with NSCLC with EGFR mutations. 17 Preclinical Studies of REQORSA Supporting Our Conduct of Acclaim-1 REQORSA and Tyrosine Kinases.
It is believed that blocking the PD-1/PD-L1 interaction pathway and other similar checkpoints, such as cytotoxic T-lymphocyte-associated protein 4, or CTLA-4, with drugs called checkpoint inhibitors can prevent cancer cells from inactivating T cells, leading to an attack of the immune system on the cancer. Current Treatment of NSCLC.
It is believed that blocking the PD-1/PD-L1 interaction pathway and other similar checkpoints, such as cytotoxic T-lymphocyte-associated protein 4, or CTLA-4, with drugs called checkpoint inhibitors, such as Keytruda or Tecentriq, can prevent cancer cells from inactivating T cells, leading to an attack of the immune system on the cancer. Current Treatment of NSCLC.
REQORSA is also delivered systemically as opposed to many other gene therapies which are locally delivered. 9 REQORSA Origins, Development Rationale, and Strategy TUSC2 was discovered through a lung cancer research consortium from MD Anderson and The University of Texas Southwestern Medical Center along with the National Cancer Institute. The TUSC2 discovery teams included Jack A.
REQORSA is also delivered systemically as opposed to many other gene therapies which are locally delivered. 10 REQORSA Origins, Development Rationale, and Strategy TUSC2 was discovered through a lung cancer research consortium from MD Anderson and The University of Texas Southwestern Medical Center along with the National Cancer Institute. The TUSC2 discovery teams included Jack A.
Liability under the UK Bribery Act is strict, but a defense of having in place adequate procedures designed to prevent bribery is available. 41 Government Regulation Outside of the United States In addition to regulations in the United States, we will be subject to a variety of regulations in other jurisdictions governing, among other things, clinical trials and any commercial sales and distribution of our products.
Liability under the UK Bribery Act is strict, but a defense of having in place adequate procedures designed to prevent bribery is available. 46 Government Regulation Outside of the United States In addition to regulations in the United States, we will be subject to a variety of regulations in other jurisdictions governing, among other things, clinical trials and any commercial sales and distribution of our products.
Synergistic Antitumor Effect of REQORSA Immunogene Therapy with Pembrolizumab on KRAS/LKB1 Mutant Lung Metastases in the Humanized Mouse Model 20 Preclinical Studies of TUSC2 Supporting Our Conduct of Acclaim-3 Transfection of SCLC cells in vitro with TUSC2 showed growth inhibition and a marked suppression of colony formation compared to cells transfected with a control vector.
Synergistic Antitumor Effect of REQORSA Immunogene Therapy with Pembrolizumab on KRAS/LKB1 Mutant Lung Metastases in the Humanized Mouse Model 21 Preclinical Studies of TUSC2 Supporting Our Conduct of Acclaim-3 Transfection of SCLC cells in vitro with TUSC2 showed growth inhibition and a marked suppression of colony formation compared to cells transfected with a control vector.
Any failure to comply with the regulations may result in significant criminal and civil penalties as well as damage to our credibility in the marketplace. 39 Coverage and Reimbursement In many of the markets where we may do business in the future, the prices of pharmaceutical products are subject to direct price controls (by law) and to reimbursement programs with varying price control mechanisms.
Any failure to comply with the regulations may result in significant criminal and civil penalties as well as damage to our credibility in the marketplace. 44 Coverage and Reimbursement In many of the markets where we may do business in the future, the prices of pharmaceutical products are subject to direct price controls (by law) and to reimbursement programs with varying price control mechanisms.
The TUSC2 gene, which is the key component of REQORSA and plays a vital role in cancer suppression and normal cell regulation, is one of a series of genes on the short arm of Chromosome 3 whose therapeutic use is covered by our exclusive worldwide licenses from The University of Texas MD Anderson Cancer Center (“MD Anderson”).
The TUSC2 gene, which is the key component of REQORSA and plays a vital role in cancer suppression and normal cell metabolism, is one of a series of genes on the short arm of Chromosome 3 whose therapeutic use is covered by our exclusive worldwide licenses from The University of Texas MD Anderson Cancer Center (“MD Anderson”).
One subject with stable disease, a 54-year-old female with a large cell neuroendocrine carcinoma who received 12 cycles of REQORSA therapy before having disease progression, had evidence of a durable metabolic response, which is a lasting reduction of metabolic activity in the tumor, as shown by positron emission tomography ("PET") imaging.
One subject with stable disease, a 54-year-old female with a large cell neuroendocrine carcinoma who received 12 cycles of REQORSA therapy before having disease progression, had evidence of a durable metabolic response, which is a lasting reduction of metabolic activity in the tumor, as shown by positron emission tomography (“PET”) imaging.
Omitting components of the development program that are necessary for such a determination can significantly delay, or even preclude, marketing approval. 34 Breakthrough Therapy Designation indicates that preliminary clinical evidence demonstrates the drug may have substantial improvement on one or more clinically significant endpoints over available therapy.
Omitting components of the development program that are necessary for such a determination can significantly delay, or even preclude, marketing approval. 39 Breakthrough Therapy Designation indicates that preliminary clinical evidence demonstrates the drug may have substantial improvement on one or more clinically significant endpoints over available therapy.
All other trademarks, trade names and service marks appearing in this Annual Report on Form 10-K are the property of their respective owners. 43 RISK FACTOR SUMMARY Our business is subject to significant risks and uncertainties that make an investment in us speculative and risky.
All other trademarks, trade names and service marks appearing in this Annual Report on Form 10-K are the property of their respective owners. 48 RISK FACTOR SUMMARY Our business is subject to significant risks and uncertainties that make an investment in us speculative and risky.
Risks Related to Our Dependence on Third Parties ● We may not be successful in establishing and maintaining development and commercialization collaborations, which could adversely affect our ability to develop our current and future product candidates and our financial condition and operating results could be adversely affected. ● We rely, in part, and expect to continue to rely, in part, on third parties to conduct, supervise and monitor our clinical trials, and if these third parties perform in an unsatisfactory manner, it may harm our business. ● We rely, and expect to continue to rely, on third parties to distribute, manufacture and perform release testing for our current and future product candidates and other key materials and if such third parties do not carry out their contractual duties or meet expected deadlines, we may not be able to obtain regulatory approvals for our product candidates. ● We have completed and may in the future complete related party transactions that were not and may not be conducted on an arm’s length basis. ● Disruptions in the global economy and supply chains may have a material adverse effect on our business, financial condition and results of operations. 44 Risks Related to Our Intellectual Property ● If we fail to comply with obligations pursuant to our license agreements, we could lose intellectual property and other rights that are important to our business; if we fail to obtain licenses to advance our research and development that may be required we may be unable to develop the affected product exclusively, on acceptable terms or at all. ● The intellectual property rights we have licensed from MD Anderson and the UP are subject to the rights of the U.S. government. ● If we are unable to protect our intellectual property rights or if our intellectual property rights are inadequate for our technology and product candidates, our competitive position could be harmed. ● Third-party claims of intellectual property infringement may prevent or delay our development and commercialization efforts. ● We may not be successful in obtaining or maintaining necessary rights to product components and processes for our development pipeline through acquisitions and in-licenses. ● Confidentiality agreements with employees and others may not adequately prevent disclosure of trade secrets and other proprietary information and may not adequately protect our intellectual property. ● Our reliance on third parties may require us to share our trade secrets, which increases the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed. ● We may be involved in lawsuits to protect or enforce our patents or the patents of our licensors, which could be expensive, time-consuming and unsuccessful. ● Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements. ● Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court. ● We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties or that our employees have wrongfully used or disclosed alleged trade secrets of their former employers. ● We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property. ● Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our products. ● We have in the past and may again in the future have trademark applications in the United States and/or certain other countries, and failure to secure these registrations could adversely affect our business; additionally, we may need to enforce our trademark rights against third parties and expend significant resources to enforce such rights against infringement. ● We may not be able to protect our intellectual property rights throughout the world.
Risks Related to Our Dependence on Third Parties ● We may not be successful in establishing and maintaining development and commercialization collaborations, which could adversely affect our ability to develop our current and future product candidates and our financial condition and operating results could be adversely affected. ● We rely, in part, and expect to continue to rely, in part, on third parties to conduct, supervise and monitor our clinical trials, and if these third parties perform in an unsatisfactory manner, it may harm our business. ● Changes in the U.S. political and regulatory environment could affect availability of government funding that we or our third party collaborators may rely on, which could negatively impact the development of our product candidates. ● We rely, and expect to continue to rely, on third parties to distribute, manufacture and perform release testing for our current and future product candidates and other key materials and if such third parties do not carry out their contractual duties or meet expected deadlines, we may not be able to obtain regulatory approvals for our product candidates. ● We have completed and may in the future complete related party transactions that were not and may not be conducted on an arm’s length basis. ● Disruptions in the global economy and supply chains may have a material adverse effect on our business, financial condition and results of operations. 49 Risks Related to Our Intellectual Property ● If we fail to comply with obligations pursuant to our license agreements, we could lose intellectual property and other rights that are important to our business; if we fail to obtain licenses to advance our research and development that may be required we may be unable to develop the affected product exclusively, on acceptable terms or at all. ● The intellectual property rights we have licensed from MD Anderson and the University of Pittsburgh are subject to the rights of the U.S. government. ● If we are unable to protect our intellectual property rights or if our intellectual property rights are inadequate for our technology and product candidates, our competitive position could be harmed. ● Third-party claims of intellectual property infringement may prevent or delay our development and commercialization efforts. ● We may not be successful in obtaining or maintaining necessary rights to product components and processes for our development pipeline through acquisitions and in-licenses. ● Confidentiality agreements with employees and others may not adequately prevent disclosure of trade secrets and other proprietary information and may not adequately protect our intellectual property. ● Our reliance on third parties may require us to share our trade secrets, which increases the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed. ● We may be involved in lawsuits to protect or enforce our patents or the patents of our licensors, which could be expensive, time-consuming and unsuccessful. ● Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements. ● Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court. ● We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties or that our employees have wrongfully used or disclosed alleged trade secrets of their former employers. ● We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property. ● Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our products. ● We have in the past and may again in the future have trademark applications in the United States and/or certain other countries, and failure to secure these registrations could adversely affect our business; additionally, we may need to enforce our trademark rights against third parties and expend significant resources to enforce such rights against infringement. ● We may not be able to protect our intellectual property rights throughout the world.
While the beta cell produces insulin, the only blood glucose-lowering hormone of the body, the alpha cell releases glucagon, which elevates blood glucose. 21 In people with Type 1 diabetes, however, beta cells are destroyed by the immune system and no longer secrete insulin, leading to an absolute deficit of insulin.
While the beta cell produces insulin, the only blood glucose-lowering hormone of the body, the alpha cell releases glucagon, which elevates blood glucose. 22 In people with Type 1 diabetes, however, beta cells are destroyed by the immune system and no longer secrete insulin, leading to an absolute deficit of insulin.
The extended PFS of each of these patients is consistent with long-term PFS seen in several patients in prior early stage clinical trials of REQORSA and is not expected with treatment with Tagrisso alone after progression on Tagrisso. REQORSA administration was generally well tolerated and there were no DLTs.
The extended PFS of each of these patients is consistent with long-term PFS seen in several patients in prior early stage clinical trials of REQORSA and is not expected with treatment with Tagrisso alone after progression on Tagrisso containing regimens. REQORSA administration was generally well tolerated and there were no DLTs.
The 2020 License Agreement shall expire on the later to occur of (a) the expiration of all patents issued under the Licensed IP and the cancellation, withdrawal, or express abandonment of all patent applications under the Licensed IP, or (b) 30 years after the MD Effective Date, unless earlier terminated pursuant to the terms thereof.
The 2020 License Agreement will expire on the later to occur of (a) the expiration of all patents issued under the Licensed IP and the cancellation, withdrawal, or express abandonment of all patent applications under the Licensed IP, or (b) 30 years after the MD Effective Date, unless earlier terminated pursuant to the terms thereof.
Our study in SCLC builds on the preclinical data showing that REQORSA enhances the immune response to cancer, and that the combination of REQORSA and immune checkpoint inhibitors demonstrates a therapeutic benefit over immune checkpoint inhibitors alone. Immune checkpoint inhibitors, such as Tecentriq, have recently been approved for use in ES-SCLC.
Our study in SCLC builds on the preclinical data showing that REQORSA enhances the immune response to cancer, and that the combination of REQORSA and immune checkpoint inhibitors demonstrates a significant benefit over immune checkpoint inhibitors alone. Immune checkpoint inhibitors, such as Tecentriq, have recently been approved for use in ES-SCLC.
The IBC assesses the safety of the research and identifies any potential risk to public health or the environment. 31 Clinical trials to support BLAs for marketing approval are typically conducted in three sequential phases that may overlap or be combined: ● Phase 1.
The IBC assesses the safety of the research and identifies any potential risk to public health or the environment. 36 Clinical trials to support BLAs for marketing approval are typically conducted in three sequential phases that may overlap or be combined: ● Phase 1.
Current Treatment of SCLC . SCLC is staged as limited stage, in which the cancer is only on one side of the chest and can be treated with a single radiation therapy field, or as extensive stage (ES), which includes all other patients.
Current Treatment of SCLC . SCLC is staged as limited stage, in which the cancer is only on one side of the chest and can be treated with a single radiation therapy field, or as extensive stage (“ES”), which includes all other patients.
Data from these clinical and preclinical studies indicates that combining REQORSA with these other therapies yields results more favorable than either these therapies or REQORSA alone, with minimal side effects relative to other lung cancer drugs, thereby potentially making REQORSA a therapy complementary to these cancer treatments. 10 Acclaim-1 As described above, in January 2020, we received Fast Track Designation from the FDA for use of REQORSA in combination with TKI Tagrisso for the treatment of NSCLC patients with EGFR mutations whose tumors progressed after treatment with Tagrisso.
Data from these clinical and preclinical studies indicates that combining REQORSA with these other therapies yields results more favorable than either these therapies or REQORSA alone, with minimal side effects relative to other lung cancer drugs, thereby potentially making REQORSA a therapy complementary to these cancer treatments. 11 Acclaim-1 As described above, in January 2020, we received Fast Track Designation from the FDA for use of REQORSA in combination with TKI Tagrisso for the treatment of NSCLC patients with EGFR mutations whose tumors progressed on treatment with Tagrisso.
The response was documented with PET scans performed after the second, fourth and sixth doses, all showing markedly decreased metabolic activity in the tumor with no changes in size or number of metastases by computed tomography ("CT") imaging.
The response was documented with PET scans performed after the second, fourth and sixth doses, all showing markedly decreased metabolic activity in the tumor with no changes in size or number of metastases by computed tomography (“CT”) imaging.
Center for Disease Control as of 2023, 38.4 million Americans, or approximately 11.6% of the U.S. population, have diabetes. It is also believed that more than 97 million Americans aged 18 years or older have prediabetes.
Center for Disease Control as of 2024, 38.4 million Americans, or approximately 11.6% of the U.S. population, have diabetes. It is also believed that more than 97 million Americans aged 18 years or older have prediabetes.
Diabetes Gene Therapy In diabetes, we have exclusively licensed from the University of Pittsburgh of the Commonwealth System of Higher Education (“University of Pittsburgh”) multiple technologies relating to the development of a gene therapy product for each of Type 1 and Type 2 diabetes.
Diabetes Gene Therapy In diabetes, we have exclusively licensed from the University of Pittsburgh of the Commonwealth System of Higher Education (“University of Pittsburgh” or “UP”) multiple technologies relating to the development of a gene therapy product for each of Type 1 and Type 2 diabetes.
If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension, or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution in those countries. Employees and Human Capital As of March 15, 2024, we had 26 total employees, all of which were full-time.
If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension, or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution in those countries. Employees and Human Capital As of March 15, 2025, we had 15 total employees, all of which were full-time.
Patients must have histologically confirmed unresectable stage III or IV EGFR-positive NSCLC (any histology) with: ● radiological progression on Tagrisso (third generation EGFR-TKI); and ● ECOG performance status of 0 to 1.
Patients must have histologically confirmed unresectable stage III or IV EGFR-positive NSCLC (any histology) with: ● radiological progression on Tagrisso (third generation EGFR-TKI) or Tagrisso-containing regimens; and ● ECOG performance status of 0 to 1.
REQORSA targeting is partly due to the attraction of opposite charges (REQORSA has a positive charge, normal cells no charge, and most cancer cells have a negative charge), and partly due to enhanced endocytosis by tumor cells, and is enhanced by the leakiness that is characteristic of tumor vasculature.
REQORSA targeting is partly due to the attraction of opposite charges (REQORSA has a positive charge, normal cells no charge, and most cancer cells have a negative charge), and partly due to increased endocytosis by tumor cells, and is enhanced by the leakiness that is characteristic of tumor vasculature compared to normal vasculature.
In the Phase 1 Monotherapy Trial, REQORSA was injected intravenously in stage IV (metastatic) lung cancer patients who had received traditional platinum combination chemotherapy but had tumor progression at the time of entry into the study. Thirty-one subjects were treated at six dose levels. Seventy percent of subjects had received two or more prior chemotherapy regimens.
In the Phase 1 Monotherapy Trial, REQORSA was administered intravenously to stage IV (metastatic) lung cancer patients who had received traditional platinum combination chemotherapy but had tumor progression at the time of entry into the study. Thirty-one subjects were treated at six dose levels. Seventy percent of subjects had received two or more prior chemotherapy regimens.
Cancer results from genetic mutations. Mutations that lead to cancer are usually present in two major classes of genes: oncogenes, which are involved in functions such as signal transduction and transcription; and tumor suppressor genes, which play multiple roles in governing cell growth and proliferation. Transduction is the process by which chemical and physical signals are transmitted into cells.
Mutations that lead to cancer are usually present in two major classes of genes: oncogenes, which are involved in functions such as signal transduction and transcription; and tumor suppressor genes, which play multiple roles in governing cell growth and proliferation. Transduction is the process by which chemical and physical signals are transmitted into cells.
See also “Note 7 – Commitments and Contingencies” to our financial statements included in this Annual Report on Form 10-K. 28 Grants Our technology discoveries and research and development programs have been the subject of numerous peer-reviewed publications and have been supported by Small Business Innovation Research ("SBIR") grants and grants from the National Institutes of Health ("NIH"), the United States Department of Treasury, and the State of Texas through its Texas Emerging Technology Fund.
See also “Note 7 – Commitments and Contingencies” and “Note 10 – Subsequent Events” to our financial statements included in this Annual Report on Form 10-K. 33 Grants Our technology discoveries and research and development programs have been the subject of numerous peer-reviewed publications and have been supported by Small Business Innovation Research ("SBIR") grants and grants from the National Institutes of Health ("NIH"), the United States Department of Treasury, and the State of Texas through its Texas Emerging Technology Fund.
Preclinical studies by MD Anderson researchers have included combining REQORSA with: ● the EGFR TKI gefitinib (marketed as Iressa® by AstraZeneca Pharmaceuticals) in animals and in human NSCLC cells; ● third generation EGFR TKIs such as osimertinib (marketed as Tagrisso® by AstraZeneca Pharmaceuticals); ● MK2206 in animals (MK2206 is an inhibitor of AKT kinases, which affect cell signaling pathways downstream from tyrosine kinases); ● the anti-PD-1 antibody pembrolizumab (the checkpoint inhibitor marketed as Keytruda® by Merck & Co.) in animals; ● the anti-PD-1 antibody nivolumab (the checkpoint inhibitor marketed as Opdivo® by Bristol-Myers Squibb Company) in animals; and ● the anti-CTLA4 antibody ipilimumab (marketed as Yervoy® by Bristol-Myers Squibb Company) in animals.
Preclinical studies by MD Anderson researchers have included combining REQORSA with: ● the EGFR TKI gefitinib (marketed as Iressa® by AstraZeneca Pharmaceuticals) in animals and in human NSCLC cells; ● third generation EGFR TKIs such as osimertinib (marketed as Tagrisso® by AstraZeneca Pharmaceuticals); ● MK2206 in animals (MK2206 is an inhibitor of AKT kinases, which affect cell signaling pathways downstream from tyrosine kinases); ● the anti-PD-1 antibody pembrolizumab (the checkpoint inhibitor marketed as Keytruda® by Merck & Co.) in animals; ● the anti-PD-1 antibody nivolumab (the checkpoint inhibitor marketed as Opdivo® by Bristol-Myers Squibb Company) in animals; ● the anti-CTLA4 antibody ipilimumab (marketed as Yervoy® by Bristol-Myers Squibb Company) in animals; and ● the anti-PD-L1 antibody atezolizumab (marketed as Tecentriq by Genentech/Roche) in animals.
These patents comprise various therapeutic, diagnostic, technical and processing claims relating to REQORSA and our ONCOPREX Delivery System. We expect these patents and patent applications, if issued, to expire from 2024 to 2038.
These patents comprise various therapeutic, diagnostic, technical and processing claims relating to REQORSA and our ONCOPREX Delivery System. We expect these patents and patent applications, if issued, to expire from 2025 to 2038.
For a further description and discussion of these laws, exclusivities and their regulatory background, please see the “Business – Government Regulation” section below in this Part I, Item 1 of this Annual Report. We also have received trademark registrations for the trademarks GENPREX, REQORSA, and ONCOPREX.
For a further description and discussion of these laws, exclusivities and their regulatory background, please see the “Business – Government Regulation” section below in this Part I, Item 1 of this Annual Report. We also have received trademark registrations for the trademarks GENPREX, REQORSA, and ONCOPREX and we have a pending application for the trademark CONVERGEN.
Further, each clinical trial must be reviewed and approved by an independent institutional review board ("IRB") at or servicing each institution or site at which the clinical trial will be conducted.
Further, each clinical trial must be reviewed and approved by an independent institutional review board (“IRB”) at or servicing each institution or site at which the clinical trial will be conducted.
Risks Related to Development and Commercialization of Our Current and Future Product Candidates ● Our success depends greatly on the success of our development of REQORSA for the treatment of NSCLC and SCLC, and our other product candidates, including GPX-002 for the treatment of diabetes. ● If we are unable to secure contract manufacturers with capabilities to produce the products that we require, we could experience delays in conducting our planned clinical trials. ● Negative public opinion and increased regulatory scrutiny of gene therapy and genetic research may damage public perception of our current and potential product candidates or adversely affect our ability to conduct our business or obtain regulatory approvals for our current and potential product candidates. ● Conducting successful clinical studies may require the enrollment of large numbers of patients, and suitable patients may be difficult to identify and recruit. ● Delays in the commencement, enrollment and completion of clinical trials could result in increased costs to us and delay or limit our ability to obtain regulatory approval for REQORSA and other current or future product candidates. ● Fast track designation of our products by FDA and designation under any other FDA expedited development program may not actually lead to a faster development or regulatory review or approval process, nor will it assure FDA approval of our product candidates. ● We may not be able to obtain or maintain orphan drug designation or exclusivity for our product candidates. ● A product candidate can fail at any stage of preclinical and clinical development. ● REQORSA®, GPX-002, and any other product candidate we advance through clinical trials may not have favorable results in later clinical trials or receive regulatory approval.
Risks Related to Development and Commercialization of Our Current and Future Product Candidates ● Our success depends greatly on the success of our development of REQORSA for the treatment of NSCLC and SCLC, and our other product candidates, including GPX-002 for the treatment of diabetes. ● The biopharmaceutical industry is subject to extensive regulatory obligations and policies that may be subject to change, including due to judicial challenges. ● If we are unable to secure contract manufacturers with capabilities to produce the products that we require, we could experience delays in conducting our planned clinical trials. ● Negative public opinion and increased regulatory scrutiny of gene therapy and genetic research may damage public perception of our current and potential product candidates or adversely affect our ability to conduct our business or obtain regulatory approvals for our current and potential product candidates. ● Conducting successful clinical studies may require the enrollment of large numbers of patients, and suitable patients may be difficult to identify and recruit. ● Delays in the commencement, enrollment and completion of clinical trials could result in increased costs to us and delay or limit our ability to obtain regulatory approval for REQORSA and other current or future product candidates. ● Fast track designation of our products by FDA and designation under any other FDA expedited development program may not actually lead to a faster development or regulatory review or approval process, nor will it assure FDA approval of our product candidates. ● We may not be able to obtain or maintain orphan drug designation or exclusivity for our product candidates. ● A product candidate can fail at any stage of preclinical and clinical development. ● REQORSA®, GPX-002, and any other product candidate we advance through clinical trials may not have favorable results in later clinical trials or receive regulatory approval.
In this nonclinical study, TUSC2 expression in three ALK+ cell lines were evaluated before and after exposure to REQORSA, referred to as TUSC2 gene therapy in the abstract.
In this nonclinical study, TUSC2 expression in three ALK+ cell lines was evaluated before and after exposure to REQORSA, referred to as TUSC2 gene therapy in the abstract.
We believe that our ONCOPREX Delivery System allows for delivery of a number of cancer-fighting genes, alone or in combination with other cancer therapies, to combat multiple types of cancer and we are in early stages of discovery programs to identify other cancer candidates.
We believe that our ONCOPREX Delivery System allows for the delivery of a number of cancer-fighting tumor suppressor genes, alone or in combination with other cancer therapies, to combat multiple types of cancer and we are in early stages of discovery programs to identify other cancer candidates.
In February 2023, the Company’s research collaborators at the University of Pittsburgh presented preclinical data in a NHP model of Type 1 diabetes highlighting the therapeutic potential of GPX-002 at the 16th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD 2023) in Berlin, Germany.
In February 2023, the Company’s research collaborators at UP presented preclinical data in a NHP model of Type 1 diabetes highlighting the therapeutic potential of GPX-002 at the 16th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD 2023) in Berlin, Germany.
It up-regulates TUSC2 expression in the cell, and also increases the anti-tumor immune cell population and down-regulates PD-L1, thereby potentially boosting the immune response to cancer. REQORSA consists of a TUSC2 gene expressing plasmid encapsulated in non-viral lipid-based nanoparticles in a lipoplex form (our ONCOPREX Delivery System), which has a positive charge.
It reexpresses TUSC2 protein in the cell, and also increases the anti-tumor immune cell population and down-regulates PD-L1, thereby potentially boosting the immune response to cancer. REQORSA consists of a TUSC2 gene expressing plasmid encapsulated in non-viral lipid-based nanoparticles in a lipoplex form (our ONCOPREX Delivery System), which has a positive charge.
In October 2023, we entered into a one-year extension to our August 2022 sponsored research agreement with the University of Pittsburgh for the use of GPX-002 in a non-human primate (“NHP”) model in Type 2 diabetes.
In October 2023, we entered into a one-year extension to our August 2022 sponsored research agreement with UP for the use of GPX-002 in a non-human primate (“NHP”) model in Type 2 diabetes.
As shown in Figure 1 , intratumoral administration of REQORSA (referred to as FUS1 in Figure 1 ) to subcutaneous NSCLC H1299 tumor xenografts resulted in inhibition of tumor growth. 17 Figure 1.
As shown in Figure 1 , intratumoral administration of REQORSA (referred to as FUS1 in Figure 1 ) to subcutaneous NSCLC H1299 tumor xenografts resulted in inhibition of tumor growth. 18 Figure 1.
Thus, these data suggest that the synergy of REQORSA with immune checkpoint inhibitors is not limited to pembrolizumab. 19 Figure 2.
Thus, these data suggest that the synergy of REQORSA with immune checkpoint inhibitors is not limited to pembrolizumab. 20 Figure 2.
Based on a review of safety data which showed no dose limiting toxicities (“DLTs”), the Acclaim-1 SRC determined that the recommended Phase 2 dose (“RP2D”) of REQORSA will be 0.12 mg/kg.
Based on a review of safety data which showed no dose limiting toxicities (“DLTs”), the Acclaim-1 SRC determined the recommended Phase 2 dose (“RP2D”) of REQORSA to be 0.12 mg/kg.
As further described in the “Licenses and Research Collaborations” section below, we also hold worldwide, exclusive licenses to an issued patent and 8 pending patent applications for diabetes technologies developed at the University of Pittsburgh. We expect these patents and patent applications, if issued, to expire from 2035 to 2043.
As further described in the “Licenses and Research Collaborations” section below, we also hold worldwide, exclusive licenses to an issued patent and 10 pending patent applications for diabetes technologies developed at the University of Pittsburgh. We expect these patents and patent applications, if issued, to expire from 2035 to 2044.
Researchers in the University of Michigan Rogel Cancer Center Judith Tam ALK NSCLC research initiative found that overexpressing TUSC2 via REQORSA treatment in ALK+ lung cancer cell lines had the ability to inhibit colony formation by 50%, which is believed to indicate that REQORSA inhibits growth of ALK+ cells.
Researchers in the University of Michigan Rogel Cancer Center Judith Tam ALK NSCLC research initiative found that overexpressing TUSC2 via REQORSA treatment in ALK+ lung cancer cell lines had the ability to inhibit colony formation by 50%, which indicates that REQORSA inhibits the growth of ALK+ cells.
Applications under the BPCA are treated as priority applications, with all of the benefits that designation confers. 37 Additional U.S.
Applications under the BPCA are treated as priority applications, with all of the benefits that designation confers. 42 Additional U.S.
Key TUSC2 anti-cancer mechanisms of action include the inactivation of multiple oncogenic kinases, the induction of apoptosis, the control of cell signaling and inflammation, and modulation of the immune system to fight cancer. REQORSA has been shown to be complementary with targeted drugs and immunotherapies.
Key TUSC2 anti-cancer mechanisms of action include decreasing tumor glucose metabolism, inactivation of multiple oncogenic kinases, the induction of apoptosis, the control of cell signaling and inflammation, and modulation of the immune system to fight cancer. REQORSA has been shown to be complementary with targeted drugs and immunotherapies.
The study further suggested that REQORSA may play an important role as a cancer treatment to target and disrupt the metabolism of cancer cells, leading to a decrease in the rate of glycolysis. 8 ONCOPREX® Delivery System Our oncology platform consists of DNA plasmids expressing tumor suppressor genes contained in non-viral lipid-based nanoparticles in a lipoplex form (“lipoplexes”) delivered intravenously.
The study further suggested that REQORSA may play an important role as a cancer treatment to target and disrupt the metabolism of cancer cells, leading to a decrease in the rate of glycolysis. 8 REQORSA Decreases Glycolysis and ATP Production in A549 Lung Cancer Cells 9 ONCOPREX® Delivery System Our oncology platform consists of DNA plasmids expressing tumor suppressor genes contained in non-viral lipid-based nanoparticles in a lipoplex form (“lipoplexes”) delivered intravenously.
The Acclaim-2 trial uses a combination of REQORSA and Merck & Co.’s Keytruda® in patients with late-stage NSCLC whose disease has progressed after treatment with Keytruda.
Acclaim – 2: The Acclaim-2 trial involved a combination of REQORSA and Merck & Co.’s Keytruda® ( pembrolizumab ) in patients with late-stage NSCLC whose disease has progressed after treatment with Keytruda.
Preclinical and clinical data support our belief that REQORSA may provide medical benefit in several subpopulations of NSCLC patients for which there is an unmet medical need, such as NSCLC patients with EGFR mutations, and ALK positive NSCLC patients.
Preclinical and clinical data support our belief that REQORSA may provide medical benefit in several subpopulations of NSCLC patients for which there is an unmet medical need such as NSCLC patients with EGFR mutations, ALK positive NSCLC patients, and NSCLC patients progressing on RAS inhibitors.
Specifically, one patient at the 0.06 mg/kg dose level, previously treated with carboplatin, pemetrexed, and Tagrisso, had a partial remission by investigator evaluation and treatment is now ongoing in the trial after 28 cycles, which is approximately 19.5 months.
Specifically, one patient at the 0.06 mg/kg dose level, previously treated with carboplatin, pemetrexed, and Tagrisso, had a partial remission by investigator evaluation and treatment is now ongoing in the trial after 47 cycles, which is approximately 35 months.
A potential resurgence of COVID-19, or any future disease outbreak, epidemic or pandemic, could disrupt our clinical trials and supply chain and materially adversely affect our business and operations. ● We face competition from other biotechnology and pharmaceutical companies, particularly those that are gene therapy companies, and our operating results will suffer if we fail to compete effectively.
Any future disease outbreak, epidemic or pandemic, could disrupt our clinical trials and supply chain and materially adversely affect our business and operations. ● We face competition from other biotechnology and pharmaceutical companies, particularly those that are gene therapy companies, and our operating results will suffer if we fail to compete effectively.
Acclaim – 1: We currently are enrolling and treating patients in the Phase 2a expansion portion of our Phase 1/2 Acclaim-1 clinical trial. The Acclaim-1 trial uses a combination of REQORSA and AstraZeneca’s Tagrisso® in patients with late-stage NSCLC that has activating epidermal growth factor receptor (“EGFR”) mutations and progression after treatment with Tagrisso.
Acclaim – 1: We currently are enrolling and treating patients in the Phase 2a expansion portion of our Phase 1/2 Acclaim-1 clinical trial. The Acclaim-1 trial uses a combination of REQORSA and AstraZeneca’s Tagrisso® ( osimertinib ) in patients with late-stage NSCLC that has activating epidermal growth factor receptor (“EGFR”) mutations and progression on treatment with Tagrisso or Tagrisso-containing regimens.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIn connection with the March 2024 registered direct offering, we amended certain existing warrants to reduce the exercise price and extend the term thereof as discussed above in Part I, Item 1 of this Annual Report in the section captioned Recent Developments – March 2024 Registered Direct Offering”. 46 We may seek additional funding through a combination of equity offerings, drawdowns on our ATM pursuant to our At The Market Offering Agreement with H.C.
Biggest changeAs of December 31, 2024, all of the 1,377,112 March 2024 Pre-Funded Warrants had been exercised for shares of common stock of the Company. 51 We may seek additional funding through a combination of equity offerings, drawdowns on our ATM pursuant to our ATM Agreement with H.C.
With the advancement of the development of GPX-002, we also are working to optimize the manufacture of this product candidate and to source high quality and integrated vendors capable of producing it in accordance with GMP.
With the advancement of the development of GPX-002, we also are working to optimize the manufacture of this product candidate and to source high quality and integrated vendors capable of producing it in accordance with GMP.
Pursuant to the 1994 MD Anderson License Agreement and subsequent Amendments thereto, as well as the 2020 MD Anderson License Agreement, we hold worldwide, exclusive license rights to certain inventions covering the therapeutic use of TUSC2 and other genes and polypeptides that have been shown to have cancer fighting properties, as well as a number of related technologies.
Pursuant to the 1994 MD Anderson License Agreement and subsequent Amendments thereto, as well as the 2020 MD Anderson License Agreement and subsequent Amendments thereto, we hold worldwide, exclusive license rights to certain inventions covering the therapeutic use of TUSC2 and other genes and polypeptides that have been shown to have cancer fighting properties, as well as a number of related technologies.
The rights we have obtained pursuant to our license agreements with MD Anderson and the UP are made subject to the rights of the U.S. government to the extent that the technology covered by the licensed intellectual property was developed under a funding agreement between such institution and the U.S. government.
The rights we have obtained pursuant to our license agreements with MD Anderson and UP are made subject to the rights of the U.S. government to the extent that the technology covered by the licensed intellectual property was developed under a funding agreement between such institution and the U.S. government.
Wainwright at any time throughout the term of the At The Market Offering Agreement covering up to such number or dollar amount of shares of our common stock as registered on the prospectus supplement covering the ATM offering, as may be amended or supplemented from time to time; pursuant to such agreement, we have the discretion, subject to market demand, to vary the timing, prices, and quantity of shares sold, and there is no minimum or maximum sales price.
Wainwright at any time throughout the term of the ATM Agreement covering up to such number or dollar amount of shares of our common stock as registered on the prospectus supplement covering the ATM offering, as may be amended or supplemented from time to time; pursuant to such agreement, we have the discretion, subject to market demand, to vary the timing, prices, and quantity of shares sold, and there is no minimum or maximum sales price.
Our stock price could be subject to wide fluctuations in response to a variety of factors, including the following: ● inability to obtain additional funding; ● adverse results or delays in preclinical or clinical trials; ● ● reports of adverse events in other gene therapy products or clinical trials of such products; manufacturing and supply issues related to our existing or future products; ● any delay in filing an IND or BLA for our product candidates and any adverse development or perceived adverse development with respect to the FDA’s review of that IND or BLA; ● failure to develop successfully and commercialize our product candidates; ● failure to maintain our existing strategic collaborations or enter into new collaborations; ● failure by us or our licensors and strategic collaboration partners to prosecute, maintain or enforce our intellectual property rights; ● changes in laws or regulations applicable to our products and product candidates; ● inability to obtain adequate product supply for our product candidates or inability to do so at acceptable prices; ● adverse regulatory decisions; ● introduction of new products, services or technologies by our competitors; ● failure to meet or exceed financial projections we may provide to the public; ● failure to meet or exceed the financial projections of the investment community; ● the perception of the pharmaceutical and biotechnology industries by the public, legislatures, regulators and the investment community; ● announcements of significant acquisitions, strategic partnerships, joint ventures, capital commitments or other material corporate transactions or events by us, our strategic collaboration partners or our competitors; ● disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; ● additions or departures of key scientific or management personnel; ● significant lawsuits, including patent or stockholder litigation; ● changes in the market valuations of similar companies; ● sales of our common stock by us or our stockholders; ● trading volume of our common stock; ● material announcements or changes impacting our common stock or our capitalization, or the perception that such changes could occur; and ● General economic conditions in the United States and abroad; and other events or factors, many of which may be out of our control, including, but not limited to, pandemics, war, or other acts of God. 70 In addition, companies trading in the stock market in general, and The Nasdaq Capital Market in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies.
Our stock price could be subject to wide fluctuations in response to a variety of factors, including the following: ● inability to obtain additional funding; ● adverse results or delays in preclinical or clinical trials; ● ● reports of adverse events in other gene therapy products or clinical trials of such products; manufacturing and supply issues related to our existing or future products; ● any delay in filing an IND or BLA for our product candidates and any adverse development or perceived adverse development with respect to the FDA’s review of that IND or BLA; ● failure to develop successfully and commercialize our product candidates; ● failure to maintain our existing strategic collaborations or enter into new collaborations; ● failure by us or our licensors and strategic collaboration partners to prosecute, maintain or enforce our intellectual property rights; ● changes in laws or regulations applicable to our products and product candidates; ● inability to obtain adequate product supply for our product candidates or inability to do so at acceptable prices; ● adverse regulatory decisions; ● introduction of new products, services or technologies by our competitors; ● failure to meet or exceed financial projections we may provide to the public; ● failure to meet or exceed the financial projections of the investment community; ● the perception of the pharmaceutical and biotechnology industries by the public, legislatures, regulators and the investment community; ● announcements of significant acquisitions, strategic partnerships, joint ventures, capital commitments or other material corporate transactions or events by us, our strategic collaboration partners or our competitors; ● disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; ● additions or departures of key scientific or management personnel; ● significant lawsuits, including patent or stockholder litigation; ● changes in the market valuations of similar companies; ● sales of our common stock by us or our stockholders; ● trading volume of our common stock; ● material announcements or changes impacting our common stock or our capitalization, or the perception that such changes could occur; and ● General economic conditions in the United States and abroad; and other events or factors, many of which may be out of our control, including, but not limited to, pandemics, war, or other acts of God. 75 In addition, companies trading in the stock market in general, and The Nasdaq Capital Market in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies.
These include provisions: ● requiring at least 66-2/3% of the voting power of all of our then-outstanding shares of capital stock entitled to vote generally in the election of directors, voting together as a single class, to amend the Amended and Restated Bylaws; ● providing that the authorized number of directors may be changed only by resolution of the board of directors; ● providing that the directors may only be removed with cause and the affirmative vote of the holders of at least 66-2/3% of the voting power of all of our then outstanding shares of capital stock entitled to vote generally at the election of directors; ● providing that all vacancies, including 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; ● dividing our board of directors into three classes; ● requiring 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; ● providing 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 notice in writing in a timely manner and also specify requirements as to the form and content of a stockholder’s notice; ● that do not provide for cumulative voting rights (therefore 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, if they should so choose); and ● providing that special meetings of our stockholders may be called only by the Chairman of the board, our Chief Executive Officer or by the board of directors pursuant to a resolution adopted by a majority of the total number of authorized directors. 73 In addition, Delaware law makes it difficult for stockholders that recently have acquired a large interest in a corporation to cause the merger or acquisition of the corporation against the directors’ wishes.
These include provisions: ● requiring at least 66-2/3% of the voting power of all of our then-outstanding shares of capital stock entitled to vote generally in the election of directors, voting together as a single class, to amend the Amended and Restated Bylaws; ● providing that the authorized number of directors may be changed only by resolution of the board of directors; ● providing that the directors may only be removed with cause and the affirmative vote of the holders of at least 66-2/3% of the voting power of all of our then outstanding shares of capital stock entitled to vote generally at the election of directors; ● providing that all vacancies, including 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; ● dividing our board of directors into three classes; ● requiring 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; ● providing 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 notice in writing in a timely manner and also specify requirements as to the form and content of a stockholder’s notice; ● that do not provide for cumulative voting rights (therefore 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, if they should so choose); and ● providing that special meetings of our stockholders may be called only by the Chairman of the board, our Chief Executive Officer or by the board of directors pursuant to a resolution adopted by a majority of the total number of authorized directors. 78 In addition, Delaware law makes it difficult for stockholders that recently have acquired a large interest in a corporation to cause the merger or acquisition of the corporation against the directors’ wishes.
In addition, regulators in other jurisdictions have their own procedures for approval of product candidates. 54 The FDA or regulators in other jurisdictions could delay, limit or deny approval of a product candidate for many reasons, including because they: ● may not deem our product candidate to be safe and effective; ● determine that the product candidate does not have an acceptable benefit-risk profile; ● determine in the case of a BLA seeking accelerated approval that the BLA does not provide evidence that the product candidate represents a meaningful advantage over available therapies; ● determine that the results on our primary endpoints are not clinically meaningful; ● may not agree that the data collected from preclinical studies and clinical trials are acceptable or sufficient to support the approval of a BLA or other submission or to obtain regulatory approval, and may impose requirements for additional preclinical studies or clinical trials; ● may determine that adverse events experienced by participants in our clinical trials represent an unacceptable level of risk; ● may determine that population studied in the clinical trial may not be sufficiently broad or representative to assure safety in the full population for which we seek approval; ● may disagree regarding the formulation or the specifications of our product candidates; ● may not approve the manufacturing processes associated with our product candidate or may determine that a manufacturing facility does not have an acceptable compliance status; or ● may change approval policies or adopt new regulations.
In addition, regulators in other jurisdictions have their own procedures for approval of product candidates. 59 The FDA or regulators in other jurisdictions could delay, limit or deny approval of a product candidate for many reasons, including because they: ● may not deem our product candidate to be safe and effective; ● determine that the product candidate does not have an acceptable benefit-risk profile; ● determine in the case of a BLA seeking accelerated approval that the BLA does not provide evidence that the product candidate represents a meaningful advantage over available therapies; ● determine that the results on our primary endpoints are not clinically meaningful; ● may not agree that the data collected from preclinical studies and clinical trials are acceptable or sufficient to support the approval of a BLA or other submission or to obtain regulatory approval, and may impose requirements for additional preclinical studies or clinical trials; ● may determine that adverse events experienced by participants in our clinical trials represent an unacceptable level of risk; ● may determine that population studied in the clinical trial may not be sufficiently broad or representative to assure safety in the full population for which we seek approval; ● may disagree regarding the formulation or the specifications of our product candidates; ● may not approve the manufacturing processes associated with our product candidate or may determine that a manufacturing facility does not have an acceptable compliance status; or ● may change approval policies or adopt new regulations.
If we fail to comply with applicable regulatory requirements for any product following approval, a regulatory authority may: ● issue a warning or untitled letter asserting that we are in violation of the law; ● seek an injunction or impose administrative, civil or criminal penalties or monetary fines; ● suspend or withdraw regulatory approval; ● suspend any ongoing clinical trials; ● refuse to approve a pending BLA or comparable foreign marketing application (or any supplements thereto) submitted by us or our strategic partners; ● restrict the marketing or manufacturing of the product; ● seize or detain the product or otherwise demand or require the withdrawal or recall of the product from the market; ● refuse to permit the import or export of products; ● request and publicize a voluntary recall of the product; or ● refuse to allow us to enter into supply contracts, including government contracts. 56 Any government investigation of alleged violations of law could require us to expend significant time and resources in response and could generate negative publicity.
If we fail to comply with applicable regulatory requirements for any product following approval, a regulatory authority may: ● issue a warning or untitled letter asserting that we are in violation of the law; ● seek an injunction or impose administrative, civil or criminal penalties or monetary fines; ● suspend or withdraw regulatory approval; ● suspend any ongoing clinical trials; ● refuse to approve a pending BLA or comparable foreign marketing application (or any supplements thereto) submitted by us or our strategic partners; ● restrict the marketing or manufacturing of the product; ● seize or detain the product or otherwise demand or require the withdrawal or recall of the product from the market; ● refuse to permit the import or export of products; ● request and publicize a voluntary recall of the product; or ● refuse to allow us to enter into supply contracts, including government contracts. 61 Any government investigation of alleged violations of law could require us to expend significant time and resources in response and could generate negative publicity.
Factors relating to our business that may contribute to these fluctuations include: ● any delays in regulatory review and approval (assuming that our data support approval) of our current and future product candidates in clinical development, including our ability to receive approval from the FDA for REQORSA or GPX-002; ● delays in the commencement, enrollment and timing of clinical trials; ● the success of our current and future product candidates through all phases of preclinical and clinical development, including the ability of our third-party suppliers or manufacturers to supply or manufacture our products on a timely, consistent basis in a manner sufficient and appropriate as is commensurate to meet our clinical trial timing, courses of treatment, and other requisite fulfillment considerations necessary to adequately advance our development programs; ● potential side effects of our current and future product candidates that could delay or prevent approval or cause an approved drug to be taken off the market; ● our ability to obtain additional funding to develop our current and future product candidates; ● our identification and development of additional drug candidates beyond REQORSA, GPX-002, and our other current product candidates; ● competition from existing products or new products that continue to emerge; ● the ability of patients or healthcare providers to obtain coverage or sufficient reimbursement for our products; ● our ability to adhere to clinical trial requirements directly or with third parties such as contract research organizations ("CROs"); ● our dependency on third-party suppliers or manufacturers to manufacture our key ingredients and/or raw materials, products and/or product components and successfully carry out a sustainable, reproducible and scalable manufacturing process in accordance with specifications or applicable regulations; ● our ability to establish or maintain collaborations, licensing, sponsored research or other arrangements, particularly with MD Anderson and UP and otherwise relating to REQORSA, and GPX-002; ● our ability to defend against any challenges to our intellectual property including claims of patent infringement; ● our ability to enforce our intellectual property rights against potential competitors; ● our ability to secure additional intellectual property protection for our product candidates and associated technologies as may be required or desirable as the development of the product candidates progresses; ● our ability to attract and retain key personnel to manage our business effectively; and ● potential product liability claims. 47 Our ability to utilize our net operating loss carryforwards may be limited , resulting in income taxes sooner than currently anticipated .
Factors relating to our business that may contribute to these fluctuations include: ● any delays in regulatory review and approval (assuming that our data support approval) of our current and future product candidates in clinical development, including our ability to receive approval from the FDA for REQORSA or GPX-002; ● delays in the commencement, enrollment and timing of clinical trials; ● the success of our current and future product candidates through all phases of preclinical and clinical development, including the ability of our third-party suppliers or manufacturers to supply or manufacture our products on a timely, consistent basis in a manner sufficient and appropriate as is commensurate to meet our clinical trial timing, courses of treatment, and other requisite fulfillment considerations necessary to adequately advance our development programs; ● potential side effects of our current and future product candidates that could delay or prevent approval or cause an approved drug to be taken off the market; ● our ability to obtain additional funding to develop our current and future product candidates; ● our identification and development of additional drug candidates beyond REQORSA, GPX-002, and our other current product candidates; ● competition from existing products or new products that continue to emerge; ● the ability of patients or healthcare providers to obtain coverage or sufficient reimbursement for our products; ● our ability to adhere to clinical trial requirements directly or with third parties such as contract research organizations (“CROs”); ● our dependency on third-party suppliers or manufacturers to manufacture our key ingredients and/or raw materials, products and/or product components and successfully carry out a sustainable, reproducible and scalable manufacturing process in accordance with specifications or applicable regulations; ● our ability to establish or maintain collaborations, licensing, sponsored research or other arrangements, particularly with MD Anderson and UP and otherwise relating to REQORSA, and GPX-002; ● our ability to defend against any challenges to our intellectual property including claims of patent infringement; ● our ability to enforce our intellectual property rights against potential competitors; ● our ability to secure additional intellectual property protection for our product candidates and associated technologies as may be required or desirable as the development of the product candidates progresses; ● our ability to attract and retain key personnel to manage our business effectively; and ● potential product liability claims. 52 Our ability to utilize our net operating loss carryforwards may be limited , resulting in income taxes sooner than currently anticipated .
We do not know and cannot predict whether future trials or studies of other current or future product candidates, including later stages of our Acclaim trials, and any for GPX-002, will begin as planned, if at all, and we do not know and cannot predict whether our Acclaim-1, Acclaim-2 and Acclaim-3 clinical trials or any future trials or studies of other current or future product candidates will be completed on schedule, if at all.
We do not know and cannot predict whether future trials or studies of other current or future product candidates, including later stages of our Acclaim trials, and any for GPX-002, will begin as planned, if at all, and we do not know and cannot predict whether our Acclaim-1 and Acclaim-3 clinical trials or any future trials or studies of other current or future product candidates will be completed on schedule, if at all.
Historically, part of our manufacturing process was conducted in manufacturing facilities at MD Anderson. We have completed the technology transfer from MD Anderson to experienced commercial contract development and manufacturing organizations and have scaled-up clinical production of REQORSA appropriate for our Acclaim-1, Acclaim-2 and Acclaim-3 clinical trials.
Historically, part of our manufacturing process was conducted in manufacturing facilities at MD Anderson. We have completed the technology transfer from MD Anderson to experienced commercial contract development and manufacturing organizations and have scaled-up clinical production of REQORSA appropriate for our Acclaim-1 and Acclaim-3 clinical trials.
If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through strategic collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate, or we may allocate internal resources to a product candidate in a therapeutic area in which it would have been more advantageous to enter into a partnering arrangement. 69 If we engage in future acquisitions or strategic partnerships, this may increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities, and subject us to other risks.
If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through strategic collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate, or we may allocate internal resources to a product candidate in a therapeutic area in which it would have been more advantageous to enter into a partnering arrangement. 74 If we engage in future acquisitions or strategic partnerships, this may increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities, and subject us to other risks.
Clinical development is very expensive and can take many years. Delays in the commencement, enrollment and/or completion of our Acclaim-1, Acclaim-2 and Acclaim-3 clinical trials or any future clinical trials could increase our product development costs or delay or limit the regulatory approval of REQORSA or other product candidates.
Clinical development is very expensive and can take many years. Delays in the commencement, enrollment and/or completion of our Acclaim-1 and Acclaim-3 clinical trials or any future clinical trials could increase our product development costs or delay or limit the regulatory approval of REQORSA or other product candidates.
The continuing efforts of the government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare and/or impose price controls may adversely affect: ● the demand for our current and potential product candidates, if we obtain regulatory approval; ● our ability to set a price that we believe is fair for our products; ● our ability to generate revenue and achieve or maintain profitability; ● the level of taxes that we are required to pay; and ● the availability of capital. 60 We are subject to a variety of risks associated with international operations which could materially adversely affect our business.
The continuing efforts of the government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare and/or impose price controls may adversely affect: ● the demand for our current and potential product candidates, if we obtain regulatory approval; ● our ability to set a price that we believe is fair for our products; ● our ability to generate revenue and achieve or maintain profitability; ● the level of taxes that we are required to pay; and ● the availability of capital. 65 We are subject to a variety of risks associated with international operations which could materially adversely affect our business.
The regulatory changes discussed herein as well as other existing and future regulatory developments may cause unexpected delays and challenges for companies seeking approval of gene therapy products, like REQORSA, GPX-002, and our other current or future product candidates. 55 These regulatory review committees and advisory groups, and the new guidelines they promulgate, may lengthen the regulatory review process, require us to perform additional studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our current and potential product candidates or lead to significant post-approval limitations or restrictions.
The regulatory changes discussed herein as well as other existing and future regulatory developments may cause unexpected delays and challenges for companies seeking approval of gene therapy products, like REQORSA, GPX-002, and our other current or future product candidates. 60 These regulatory review committees and advisory groups, and the new guidelines they promulgate, may lengthen the regulatory review process, require us to perform additional studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our current and potential product candidates or lead to significant post-approval limitations or restrictions.
We have initiated our Acclaim-1, Acclaim-2 and Acclaim-3 clinical trials pursuant to an existing IND. We have previously filed with the FDA amendments to our IND consisting of an updated chemistry, manufacturing and controls section, and the protocol for the respective clinical trial.
We have initiated our Acclaim-1 and Acclaim-3 clinical trials pursuant to an existing IND. We have previously filed with the FDA amendments to our IND consisting of an updated chemistry, manufacturing and controls section, and the protocol for the respective clinical trial.
Any of these events could prevent us or our potential future collaborators from achieving or maintaining market acceptance of our products or could substantially increase commercialization costs and expenses, which in turn could delay or prevent us from generating revenues from the sale of our products. 52 If a product liability claim is successfully brought against us for uninsured liabilities, or such claim exceeds our insurance coverage, we could be forced to pay substantial damage awards that could materially harm our business.
Any of these events could prevent us or our potential future collaborators from achieving or maintaining market acceptance of our products or could substantially increase commercialization costs and expenses, which in turn could delay or prevent us from generating revenues from the sale of our products. 57 If a product liability claim is successfully brought against us for uninsured liabilities, or such claim exceeds our insurance coverage, we could be forced to pay substantial damage awards that could materially harm our business.
Any delay in the availability of product supply or product component supply could result in a delay in our clinical trials, including our Acclaim-1, Acclaim-2 and Acclaim-3 clinical trials as well as the commencement of clinical trials for GPX-002.
Any delay in the availability of product supply or product component supply could result in a delay in our clinical trials, including our Acclaim-1 and Acclaim-3 clinical trials as well as the commencement of clinical trials for GPX-002.
In addition, the approval and commercialization of any of our current and potential product candidates outside the United States will also likely subject us to foreign equivalents of the healthcare laws mentioned above, among other foreign laws. 58 Coverage and reimbursement may be limited or unavailable in certain market segments for REQORSA, GPX-002, and our other current or future product candidates, if approved, which could make it difficult for us to sell REQORSA, GPX-002, and our other current or future product candidates profitably.
In addition, the approval and commercialization of any of our current and potential product candidates outside the United States will also likely subject us to foreign equivalents of the healthcare laws mentioned above, among other foreign laws. 63 Coverage and reimbursement may be limited or unavailable in certain market segments for REQORSA, GPX-002, and our other current or future product candidates, if approved, which could make it difficult for us to sell REQORSA, GPX-002, and our other current or future product candidates profitably.
We will likely incur increased costs and devote additional management time to public company reporting and compliance obligations as a result of exiting “ emerging growth company ” status .
We will likely continue to incur increased costs and devote additional management time to public company reporting and compliance obligations as a result of exiting “ emerging growth company ” status .
Any of the foregoing scenarios could materially harm the commercial prospects for our product candidates and materially and adversely affect our business, financial condition, results of operations and prospects. 51 Even if we obtain regulatory approval of our current and future product candidates, the products may not gain market acceptance among physicians, patients, hospitals, treatment centers, third-party payors and others in the medical community.
Any of the foregoing scenarios could materially harm the commercial prospects for our product candidates and materially and adversely affect our business, financial condition, results of operations and prospects. 56 Even if we obtain regulatory approval of our current and future product candidates, the products may not gain market acceptance among physicians, patients, hospitals, treatment centers, third-party payors and others in the medical community.
As a result, we may be unable to commercialize products or programs if we are unable to engage a suitable collaborator, which may have a material adverse effect on our operating results and financial condition. 61 We rely, in part, and expect to continue to rely, in part, on third parties to conduct, supervise and monitor our clinical trials, and if these third parties perform in an unsatisfactory manner, it may harm our business.
As a result, we may be unable to commercialize products or programs if we are unable to engage a suitable collaborator, which may have a material adverse effect on our operating results and financial condition. 66 We rely, in part, and expect to continue to rely, in part, on third parties to conduct, supervise and monitor our clinical trials, and if these third parties perform in an unsatisfactory manner, it may harm our business.
Costly and time-consuming litigation could be necessary to enforce and determine the scope of our proprietary rights, and failure to obtain or maintain trade secret protection could adversely affect our competitive business position. 66 Our reliance on third parties may require us to share our trade secrets, which increases the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed.
Costly and time-consuming litigation could be necessary to enforce and determine the scope of our proprietary rights, and failure to obtain or maintain trade secret protection could adversely affect our competitive business position. 71 Our reliance on third parties may require us to share our trade secrets, which increases the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed.
Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license. 68 Risks Related to Employee Matters and Managing Growth We have no sales, marketing or distribution experience and we will have to invest significant resources to develop those capabilities or enter into acceptable third-party sales and marketing arrangements.
Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license. 73 Risks Related to Employee Matters and Managing Growth We have no sales, marketing or distribution experience and we will have to invest significant resources to develop those capabilities or enter into acceptable third-party sales and marketing arrangements.
Even if orphan designation is granted it may be withdrawn by the FDA for non-compliance with regulations. 50 A product candidate can fail at any stage of preclinical and clinical development. The historical failure rate for product candidates is high due to scientific feasibility, safety, efficacy, changing standards of medical care and other variables.
Even if orphan designation is granted it may be withdrawn by the FDA for non-compliance with regulations. 55 A product candidate can fail at any stage of preclinical and clinical development. The historical failure rate for product candidates is high due to scientific feasibility, safety, efficacy, changing standards of medical care and other variables.
Our management has concluded that our internal controls over financial reporting were, and continue to be, ineffective, and as of the year ended December 31, 2023 as a result of material weaknesses in our internal controls due to the lack of segregation of duties between accounting and other functions and the absence of sufficient depth of in-house accounting personnel with the ability to properly account for complex transactions.
Our management has concluded that our internal controls over financial reporting were, and continue to be, ineffective, and as of the year ended December 31, 2024 as a result of material weaknesses in our internal controls due to the lack of segregation of duties between accounting and other functions and the absence of sufficient depth of in-house accounting personnel with the ability to properly account for complex transactions.
In addition, any failure to achieve and maintain compliance with these laws, regulations and standards could subject us to the risk that we may have to suspend the manufacturing of our current and future product candidates or that obtained approvals could be revoked, which would adversely affect our business and reputation. 62 In addition, any significant disruption in our supplier relationships could harm our business.
In addition, any failure to achieve and maintain compliance with these laws, regulations and standards could subject us to the risk that we may have to suspend the manufacturing of our current and future product candidates or that obtained approvals could be revoked, which would adversely affect our business and reputation. 67 In addition, any significant disruption in our supplier relationships could harm our business.
It is impossible to predict whether legislative changes will be enacted, regulations, policies, or guidance changed, or interpretations by agencies or courts changed, or what the impact of such changes, if any, may be. 59 Healthcare legislative reform measures may have a material adverse effect on our business and results of operations.
It is impossible to predict whether legislative changes will be enacted, regulations, policies, or guidance changed, or interpretations by agencies or courts changed, or what the impact of such changes, if any, may be. 64 Healthcare legislative reform measures may have a material adverse effect on our business and results of operations.
We are authorized to issue up to 10,000,000 shares of preferred stock, none of which are outstanding as of March 15, 2024. This preferred stock may be issued in one or more series, the terms of which may be determined at the time of issuance by our board of directors without further action by stockholders.
We are authorized to issue up to 10,000,000 shares of preferred stock, none of which are outstanding as of March 15, 2025. This preferred stock may be issued in one or more series, the terms of which may be determined at the time of issuance by our board of directors without further action by stockholders.
Several investigations into these types of programs have resulted in significant civil and criminal settlements. 57 We are exposed to the risk of fraud, misconduct or other illegal activity by our employees, independent contractors, consultants, principal investigators, CROs, commercial partners and vendors.
Several investigations into these types of programs have resulted in significant civil and criminal settlements. 62 We are exposed to the risk of fraud, misconduct or other illegal activity by our employees, independent contractors, consultants, principal investigators, CROs, commercial partners and vendors.
Such a loss of patent protection would have a material adverse impact on our business. 67 We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties or that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.
Such a loss of patent protection would have a material adverse impact on our business. 72 We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties or that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.
If any shares of our common stock are sold, or if it is perceived that they will be sold, in the public market, the market price of our common stock could decline. 72 Future sales and issuances of our securities could result in additional dilution of the percentage ownership of our stockholders and could cause our share price to fall.
If any shares of our common stock are sold, or if it is perceived that they will be sold, in the public market, the market price of our common stock could decline. 77 Future sales and issuances of our securities could result in additional dilution of the percentage ownership of our stockholders and could cause our share price to fall.
Further, such an outcome could damage investor confidence in the accuracy and reliability of our financial statements. 71 Effective internal controls over financial reporting are necessary for us to provide reliable financial reports and, together with adequate disclosure controls and procedures, are designed to prevent fraud.
Further, such an outcome could damage investor confidence in the accuracy and reliability of our financial statements. 76 Effective internal controls over financial reporting are necessary for us to provide reliable financial reports and, together with adequate disclosure controls and procedures, are designed to prevent fraud.
In some cases, it may be difficult or impossible to detect third-party infringement or misappropriation of our intellectual property rights, even in relation to issued patent claims, and proving any such infringement may be even more difficult. 65 Third-party claims of intellectual property infringement may prevent or delay our development and commercialization efforts.
In some cases, it may be difficult or impossible to detect third-party infringement or misappropriation of our intellectual property rights, even in relation to issued patent claims, and proving any such infringement may be even more difficult. 70 Third-party claims of intellectual property infringement may prevent or delay our development and commercialization efforts.
If we face such litigation, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business and results in a decline in the market price of our common stock. 75 Item 1B. Unresolved Staff Comments. None.
If we face such litigation, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business and results in a decline in the market price of our common stock. 80 Item 1B. Unresolved Staff Comments. None.
This royalty obligation continues for 21 years after the later of the termination of the 1994 MD Anderson License Agreement and the termination of the sublicense assigned by IRI to us. IRI is controlled by Rodney Varner and IRI is owned by trusts for the benefit of Mr. Varner’s descendants. Mr.
This royalty obligation continues for 21 years after the later of the termination of the 1994 MD Anderson License Agreement and the termination of the sublicense assigned by IRI to us. IRI was controlled by Rodney Varner and IRI is currently owned by trusts for the benefit of Mr. Varner’s descendants. Mr.
In addition, pursuant to the UP License Agreements, UP granted us a worldwide, exclusive license to certain licensed technology, and a worldwide, non-exclusive license to use certain related know-how, all related to diabetes gene therapy. In addition, we expect to enter into additional license agreements in the future.
In addition, pursuant to the New UP License Agreement, UP granted us a worldwide, exclusive license to certain licensed technology, and a worldwide, non-exclusive license to use certain related know-how, all related to diabetes gene therapy. In addition, we expect to enter into additional license agreements in the future.
We have obtained trademark registrations in the United States for GENPREX, ONCOPREX and REQORSA and we may in the future have pending trademark applications in the United States and/or certain other countries. During trademark registration proceedings, our application may be rejected.
We have obtained trademark registrations in the United States for GENPREX, ONCOPREX and REQORSA, we have a pending application in the United States for the trademark CONVERGEN, and we may in the future have pending trademark applications in the United States and/or certain other countries. During trademark registration proceedings, our application may be rejected.
At this time, we are actively pursuing the development of REQORSA for NSCLC through our Acclaim-1 and Acclaim-2 clinical trials and for SCLC through our Acclaim-3 clinical trial, which are all currently enrolling patients. We are also pursuing the development of preclinical gene therapy GPX-002 for Type 1 and Type 2 diabetes, as well as earlier discovery programs.
At this time, we are actively pursuing the development of REQORSA for NSCLC through our Acclaim-1 clinical trial and for SCLC through our Acclaim-3 clinical trial, which are both currently enrolling patients. We are also pursuing the development of preclinical gene therapy GPX-002 for Type 1 and Type 2 diabetes, as well as earlier discovery programs.
Our ability to obtain clinical supplies of our current and potential product candidates could be disrupted if the operations of our contract manufacturers are affected by a man-made or natural disaster or other business interruption. 74 In addition, the global macroeconomic environment could be negatively affected by, among other things, new variants of the COVID-19 pandemic or other epidemics, instability in global economic markets, increased U.S. trade tariffs and trade disputes with other countries, supply chain weaknesses, instability in the global credit markets, severely diminished liquidity and credit availability, rising interest and inflation rates, declines in consumer confidence, declines in economic growth, increases in unemployment rates, uncertainty about economic stability, instability in the geopolitical environment, the Russian invasion of the Ukraine and other political tensions, including in the Middle East, and foreign governmental debt concerns.
Our ability to obtain clinical supplies of our current and potential product candidates could be disrupted if the operations of our contract manufacturers are affected by a man-made or natural disaster or other business interruption. 79 In addition, the global macroeconomic environment could be negatively affected by, among other things, new pandemics or epidemics, instability in global economic markets, increased U.S. trade tariffs and trade disputes with other countries, supply chain weaknesses, instability in the global credit markets, severely diminished liquidity and credit availability, rising interest and inflation rates, declines in consumer confidence, declines in economic growth, increases in unemployment rates, uncertainty about economic stability, instability in the geopolitical environment, the Russian invasion of the Ukraine and other political tensions, including in the Middle East, and foreign governmental debt concerns.
As of March 15, 2024, we had 26 total employees, all of which were full-time. As we advance our product candidates through preclinical studies and clinical trials, we will need to increase our clinical trial management, product development, manufacturing, regulatory, and administrative headcount to manage these programs.
As of March 15, 2025, we had 15 total employees, all of which were full-time. As we advance our product candidates through preclinical studies and clinical trials, we will need to increase our clinical trial management, product development, manufacturing, regulatory, and administrative headcount to manage these programs.
Although we expect that our existing cash will be sufficient to fund our current operations and planned clinical trial activities into the third quarter of 2024, this period could be shortened if there are any significant increases in planned spending on current or additional development programs or more rapid progress of these development programs than anticipated.
Although we expect that our existing cash will be sufficient to fund our current operations and planned clinical trial activities into the second quarter of 2025, this period could be shortened if there are any significant increases in planned spending on current or additional development programs or more rapid progress of these development programs than anticipated.
We face risks related to health epidemics and outbreaks, including COVID-19, which could significantly disrupt our preclinical studies and clinical trials. Our business has previously been adversely affected by the coronavirus pandemic which delayed our clinical trials and disrupted our supply chain.
We face risks related to health epidemics and outbreaks which could significantly disrupt our preclinical studies and clinical trials. Our business has previously been adversely affected by the coronavirus pandemic which delayed our clinical trials and disrupted our supply chain.
If disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on acceptable terms, we may be unable to successfully develop and commercialize the affected product candidates. 64 The intellectual property rights we have licensed from MD Anderson and the UP are subject to the rights of the U.S. government.
If disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on acceptable terms, we may be unable to successfully develop and commercialize the affected product candidates. 69 The intellectual property rights we have licensed from MD Anderson and the University of Pittsburgh are subject to the rights of the U.S. government.
The impacts of a potential resurgence of COVID-19 could pose the risk that we or our employees, suppliers, customers and others may be restricted or prevented from conducting business activities for indefinite or intermittent periods of time, including as a result of employee health and safety concerns, shutdowns, shelter in place orders, travel restrictions and other actions and restrictions that may be prudent or required by governmental authorities.
The impacts of a potential new epidemic or pandemic could pose the risk that we or our employees, suppliers, customers and others may be restricted or prevented from conducting business activities for indefinite or intermittent periods of time, including as a result of employee health and safety concerns, shutdowns, shelter in place orders, travel restrictions and other actions and restrictions that may be prudent or required by governmental authorities.
We expect the cash and cash equivalents of approximately $6.7 million at December 31, 2023 to be insufficient to meet our operating and capital requirements at least 12 months from the filing of this Annual Report on Form 10-K.
We expect the cash and cash equivalents of approximately $1.6 million at December 31, 2024 to be insufficient to meet our operating and capital requirements at least 12 months from the filing of this Annual Report on Form 10-K.
On December 13, 2023, we entered into an At The Market (“ATM”) Offering Agreement (the “Agreement”) with H.C. Wainwright & Co., LLC, serving as agent (“H.C.
On December 13, 2023, we entered into an At The Market (“ATM”) Offering Agreement (the “ATM Agreement”) with H.C. Wainwright & Co., LLC, serving as agent (“H.C.
Accordingly, our business may fail, in which case you would lose the entire amount of your investment in our securities. Our recurring losses from operations have raised substantial doubt regarding our ability to continue as a going concern. We have recognized recurring losses, and as of December 31, 2023, had an accumulated deficit of approximately $133.9 million.
Accordingly, our business may fail, in which case you would lose the entire amount of your investment in our securities. Our recurring losses from operations have raised substantial doubt regarding our ability to continue as a going concern. We have recognized recurring losses, and as of December 31, 2024, had an accumulated deficit of approximately $154.8 million.
We have never been profitable and do not expect to be profitable in the foreseeable future. We have not yet submitted any drug candidates for approval by regulatory authorities in the United States or elsewhere. From our inception on April 1, 2009, to December 31, 2023, we incurred an accumulated deficit of approximately $133.9 million.
We have never been profitable and do not expect to be profitable in the foreseeable future. We have not yet submitted any drug candidates for approval by regulatory authorities in the United States or elsewhere. From our inception on April 1, 2009, to December 31, 2024, we incurred an accumulated deficit of approximately $154.8 million.
Disease outbreaks, epidemics and pandemics, including COVID-19, in regions where we have concentrations of clinical trial sites and other business operations, could adversely affect our business, including by causing significant disruptions in our operations and/or in the operations of manufacturers and CROs upon whom we rely.
Disease outbreaks, epidemics and pandemics, such as we experienced previously with COVID-19, in regions where we have concentrations of clinical trial sites and other business operations, could adversely affect our business, including by causing significant disruptions in our operations and/or in the operations of manufacturers and CROs upon whom we rely.
We incurred net losses of approximately $31.0 million and approximately $23.7 million for the years ended December 31, 2023 and 2022, respectively. To date, we have devoted most of our financial resources to our corporate overhead and research and development, including our preclinical development activities, manufacturing processes and clinical trials. We have not generated any revenues from product sales.
We incurred net losses of approximately $21.1 million and approximately $31.0 million for the years ended December 31, 2024 and 2023, respectively. To date, we have devoted most of our financial resources to our corporate overhead and research and development, including our preclinical development activities, manufacturing processes and clinical trials. We have not generated any revenues from product sales.
We have experienced a variety of these challenges to varying degrees in connection with performance by our CDMOs, which have resulted in delays in our Acclaim-1, Acclaim-2 and Acclaim-3 clinical trials in the past.
We have experienced a variety of these challenges to varying degrees in connection with performance by our CDMOs, which have resulted in delays in our Acclaim clinical trials in the past.
We may sell a substantial number of shares of our common stock pursuant to our existing At The Market Offering Agreement with H.C. Wainwright, pursuant to which we have the discretion to deliver placement notices to H.C.
We may sell a substantial number of shares of our common stock pursuant to our existing ATM Agreement with H.C. Wainwright, pursuant to which we have the discretion to deliver placement notices to H.C.
Wainwright as Agent, debt financings, government or other third-party funding, commercialization, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements, some of which may require us to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us.
Wainwright as Agent and/or through other third-party ATM agreements in the future, debt financings, government or other third-party funding, commercialization, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements, some of which may require us to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us.
If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may need to delay, limit or terminate ongoing or planned clinical trials, any of which would have an adverse effect on our business. 49 Delays in the commencement, enrollment and completion of clinical trials could result in increased costs to us and delay or limit our ability to obtain regulatory approval for REQORSA and other current or future product candidates.
If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, such as we have experienced with the Acclaim-2 clinical trial for example, we may need to delay, limit or terminate ongoing or planned clinical trials, any of which would have an adverse effect on our business. 54 Delays in the commencement, enrollment and completion of clinical trials could result in increased costs to us and delay or limit our ability to obtain regulatory approval for REQORSA and other current or future product candidates.
Despite the actions we have undertaken to minimize the impacts from disruptions to the global economy, there can be no assurances that unforeseen future events in the global supply chain, and inflationary pressures, will not have a material adverse effect on our business, financial condition and results of operations. 63 Risks Related to Our Intellectual Property If we fail to comply with obligations pursuant to our license agreements, we could lose intellectual property and other rights that are important to our business ; if we fail to obtain licenses to advance our research and development that may be required we may be unable to develop the affected product exclusively, on acceptable terms or at all .
Despite the actions we have undertaken to minimize the impacts from disruptions to the global economy, there can be no assurances that unforeseen future events in the global supply chain, including the threat and risk of potential cross-border tariffs, the potential adoption and expansion of trade restrictions or the occurrence of trade wars and inflationary pressures, will not have a material adverse effect on our business, financial condition and results of operations. 68 Risks Related to Our Intellectual Property If we fail to comply with obligations pursuant to our license agreements, we could lose intellectual property and other rights that are important to our business ; if we fail to obtain licenses to advance our research and development that may be required we may be unable to develop the affected product exclusively, on acceptable terms or at all .
In addition, fluctuations in demand and other implications associated with the COVID-19 pandemic have resulted in, and could continue resulting in, certain supply chain constraints and challenges in the broader markets and economy generally, which could impact our business and supply sources, including our CDMOs. 53 We face competition from other biotechnology and pharmaceutical companies , particularly those that are gene therapy companies, and our operating results will suffer if we fail to compete effectively.
In addition, fluctuations in demand and other implications associated with such pandemic could result in certain supply chain constraints and challenges in the broader markets and economy generally, which could impact our business and supply sources, including our CDMOs. 58 We face competition from other biotechnology and pharmaceutical companies , particularly those that are gene therapy companies, and our operating results will suffer if we fail to compete effectively.
We have agreed to pay the Agent a commission equal to three percent (3%) of the gross sales proceeds of any Shares sold through the Agent under the Agreement, and also have provided the Agent with customary indemnification and contribution rights. As of December 31, 2023 we had not sold any Shares through the Agent under the Agreement.
We have agreed to pay the Agent a commission equal to three percent (3%) of the gross sales proceeds of any Shares sold through the Agent under the ATM Agreement, and also have provided the Agent with customary indemnification and contribution rights.
Now that we have exited emerging growth company status and we are no longer eligible to take advantage of the corresponding exemptions, we expect our management and other personnel to devote more time and the Company to incur additional costs to comply with the more stringent reporting requirements applicable to companies that are not emerging growth companies.
Having exited emerging growth company status and not able to take advantage of the corresponding exemptions, we expect our management and other personnel to continue to devote more time and the Company to incur additional costs to comply with the more stringent reporting requirements applicable to companies that are not emerging growth companies.
As of December 31, 2023, we had federal net operating loss carryforwards (“NOLs”) of approximately $80.5 million for federal income tax purposes of which approximately $1.3 million will begin to expire in 2030 and approximately $79.2 million can be carried forward indefinitely.
As of December 31, 2024, we had federal net operating loss carryforwards (“NOLs”) of approximately $96.3 million for federal income tax purposes of which approximately $1.3 million will begin to expire in 2030 and approximately $86.6 million can be carried forward indefinitely.
For instance, delays or difficulties in patient enrollment or difficulties in retaining trial participants can result in increased costs, longer development times or termination of a clinical trial.
For instance, delays or difficulties in patient enrollment or difficulties in retaining trial participants can result in increased costs, longer development times or termination of a clinical trial, such as the Acclaim-2 program.
Sales of a substantial number of shares of our common stock in the public market could cause our stock price to fall. If our existing stockholders sell, or indicate an intention to sell, substantial amounts of our common stock in the public market, the market price of our common stock could decline.
If our existing stockholders sell, or indicate an intention to sell, substantial amounts of our common stock in the public market, the market price of our common stock could decline.
Varner was neither a member of our board of directors nor an executive officer of Genprex. When the 2011 IRI Collaboration Agreement was entered into, Mr. Varner was deemed to be an “affiliate” of the Company due to his beneficial ownership of approximately 39% of our issued and outstanding shares at that time.
When the 2011 IRI Collaboration Agreement was entered into, Mr. Varner was deemed to be an “affiliate” of the Company due to his beneficial ownership of approximately 39% of our issued and outstanding shares at that time.
A potential resurgence of COVID-19, or any future disease outbreak, epidemic or pandemic, could disrupt our clinical trials and supply chain and materially adversely affect our business and operations .
Any future disease outbreak, epidemic or pandemic, could disrupt our clinical trials and supply chain and materially adversely affect our business and operations .
Any sales of equity securities, whether pursuant to our At The Market Offering Agreement or otherwise, may also result in material dilution to our existing stockholders, and new investors could gain rights superior to our existing stockholders.
Any sales of equity securities, whether pursuant to our existing ATM Agreement or other third-party ATM agreements in the future, or otherwise, may also result in material dilution to our existing stockholders, and new investors could gain rights superior to our existing stockholders.
We have experienced delays in opening our clinical sites for our Acclaim-1 and Acclaim-2 trials in the past; for example, during the COVID-19 pandemic there was a delay due to a back-log in protocol review at the clinical trial sites.
We have experienced delays in opening our clinical sites for our Acclaim-1 and Acclaim-2 trials in the past; for example, during the COVID-19 pandemic there was a delay due to a back-log in protocol review at the clinical trial sites and with Acclaim-2 due to competition for investigators and eligible patients with numerous other trials involving the same patient population.
This delay has the potential to impact the timing of the conduct of our clinical trials. We have taken steps to minimize the impact of these increased costs by working closely with our suppliers and locating redundant or comparable sources.
We have taken steps to minimize the impact of these increased costs by working closely with our suppliers and locating redundant or comparable sources.
Historically, part of our manufacturing process was conducted in manufacturing facilities at MD Anderson. We have transferred all of the steps of our manufacturing process to CDMOs and scaled-up clinical production in order to supply our Acclaim-1, Acclaim-2 and Acclaim-3 clinical trials.
We have transferred all of the steps of our manufacturing process to CDMOs and scaled-up clinical production in order to supply our Acclaim-1 and Acclaim-3 clinical trials.
Global credit and financial markets have experienced volatility and disruptions in past years, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates, concerns about medical epidemics, and uncertainty about economic stability.
Unstable market and economic conditions may have serious adverse consequences on our business, financial condition and stock price. Global credit and financial markets have experienced volatility and disruptions in past years, including severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates, concerns about medical epidemics, and uncertainty about economic stability.
During the COVID-19 pandemic, we had also experienced disruptions in our supply chain regarding our manufacturing and testing operations. The future progression of the COVID-19 epidemic and its effects on our business and operations are uncertain.
During the COVID-19 pandemic, we had also experienced disruptions in our supply chain regarding our manufacturing and testing operations.
On March 21, 2024, we completed a registered direct offering, in which we sold to an institutional investor an aggregate of (i) 165,000 shares of our common stock, (ii) March 2024 Pre-Funded Warrants exercisable for up to an aggregate of 1,377,112 shares of our common stock, and (iii) March 2024 Common Warrants exercisable for up to an aggregate of 1,542,112 shares of our common stock, at a combined offering price of $4.215 per share of common stock (or $4.2149 per March 2024 Pre-Funded Warrant in lieu thereof) and accompanying March 2024 Common Warrant, for net proceeds of approximately $5.8 million.
On March 21, 2024, we completed a registered direct offering, in which we sold to an institutional investor an aggregate of (i) 165,000 shares of our common stock, (ii) March 2024 Pre-Funded Warrants (the “March 2024 Pre-Funded Warrants”) exercisable for up to an aggregate of 1,377,112 shares of our common stock, and (iii) common warrants (the “March 2024 Common Warrants”) exercisable for up to an aggregate of 1,542,112 shares of our common stock.
As of December 31, 2023, we had outstanding options to purchase an aggregate of 285,883 shares of our common stock at a weighted average exercise price of $121.11 per share and warrants to purchase an aggregate of 346,440 shares of our common stock at a weighted average exercise price of $57.79 per share.
As of December 31, 2024, we had outstanding options to purchase an aggregate of 283,636 shares of our common stock at a weighted average exercise price of $121.67 per share and warrants to purchase an aggregate of 1,981,079 shares of our common stock at a weighted average exercise price of $10.05 per share.
The disruptions to the global economy since the COVID-19 global pandemic commenced in 2020 has impeded global supply chains, resulting in longer lead times and also increased critical component costs and freight expenses. We have experienced this impact most notably in our manufacturing operations due to the delay in our ability to acquire raw materials for our drug product.
Disruptions to the global economy since the COVID-19 global pandemic commenced in 2020 have impeded global supply chains, resulting in longer lead times and also increased critical component costs and freight expenses.
From January 1, 2024 through the date of filing of this Annual Report on Form 10-K, we have sold 158,474 Shares for net proceeds to us totaling $881,946 through the Agent under the Agreement.
As of December 31, 2024, we had sold 7,684,953 Shares for net proceeds to us totaling $6,100,562 through the Agent under the ATM Agreement. From January 1, 2025 through the date of filing of this Annual Report on Form 10-K, we have sold 13,278,666 Shares for net proceeds to us totaling $6,028,104 through the Agent under the ATM Agreement.
In addition, any future marketing authorization granted by the European Commission may not be indicative of what the FDA may require for approval and vice versa. 48 If we are unable to secure contract manufacturers with capabilities to produce the products that we require, we could experience delays in conducting our planned clinical trials. Manufacturing REQORSA involves several manufacturing steps.
If we are unable to secure contract manufacturers with capabilities to produce the products that we require, we could experience delays in conducting our planned clinical trials. Manufacturing REQORSA involves several manufacturing steps. Historically, part of our manufacturing process was conducted in manufacturing facilities at MD Anderson.
Varner is currently Chairman of our board of directors, having joined our board of directors on August 15, 2012, and has been our Chief Executive Officer since August 29, 2012 and President since August 10, 2020; accordingly, in 2009 and 2011, when the above referenced agreements between IRI and Genprex were entered into, Mr.
Varner, who prior to his passing in May 2024, was our President, Chief Executive Officer and Chairman of our board of directors; however, in 2009 and 2011, when the above referenced agreements between IRI and Genprex were entered into, Mr. Varner was neither a member of our board of directors nor an executive officer of Genprex.
We expect that compliance with these requirements will increase our legal and financial compliance costs and will make some activities more time consuming and costly. We cannot predict or estimate the amount of additional costs we may incur as a result of our exit from emerging growth company status, or the timing of the incurrence of such costs.
We expect that compliance with these requirements will continue to increase our legal and financial compliance costs and will make some activities more time consuming and costly.
As previously reported in 2022, our Chairman, President and Chief Executive Officer, Rodney Varner, had been diagnosed with a cutaneous lymphoma and has been undergoing chemotherapy and other treatments since then. Mr.
As previously reported, our prior Chairman, President and Chief Executive Officer, Rodney Varner, passed away unexpectedly in May 2024 due to complications following his diagnosis of a cutaneous lymphoma in 2022. Mr.
Although our common stock is currently listed on The Nasdaq Capital Market, we may not be able to continue to meet the exchange’s minimum listing requirements, including the minimum bid price requirement and other applicable corporate governance requirements, or those of any other national exchange.
If we fail to regain compliance with the continued listing requirements of Nasdaq, our common stock may be delisted and the price of our common stock and our ability to access the capital markets could be negatively impacted. Our common stock is currently listed for trading on Nasdaq.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

2 edited+0 added−1 removed9 unchanged
Biggest changeTo effectively prevent, detect, and respond to cybersecurity threats, we maintain a cyber risk management program, which is comprised of a wide array of policies, standards, architecture, and processes.
Biggest changeTo effectively prevent, detect, and respond to cybersecurity threats, we maintain a cyber risk management program, which is comprised of a wide array of policies, standards, architecture, and processes. The cyber risk management program falls under the responsibility of our Chief Financial Officer, who has more than 15 years of experience, including cross-functional expertise in business operations and technology strategy.
Under the guidance of our Director of IT & GxP Quality Systems, reporting up to our Chief Financial Officer, we develop, maintain, and evidence the policies, standards, and processes in a manner consistent with applicable legal requirements. We also utilize a variety of cybersecurity software from reputable vendors in cybersecurity.
Under the guidance of our Chief Financial Officer, we develop, maintain, and evidence the policies, standards, and processes in a manner consistent with applicable legal requirements. We also utilize a variety of cybersecurity software from reputable vendors in cybersecurity.
Removed
The cyber risk management program falls under the responsibility of our Director of IT & GxP Quality Systems, who has more than 15 years of experience, including cross-functional expertise in IT compliance and GXP systems.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeItem 2. Properties. Our principal offices are located at 3300 Bee Cave Road, #650-227, Austin, Texas 78746. We operate primarily as a virtual company, and we believe our current facilities and those that we believe are available to us are sufficient to meet our current needs and that suitable space will be available as and when needed.
Biggest changeItem 2. Properties. Our principal offices are located at 3300 Bee Cave Road, #650-227, Austin, Texas 78746. We operate primarily as a virtual company, and we believe our current facilities and other facilities available to us are sufficient to meet our current needs and that suitable space will be available as and when needed.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeRegardless of the outcome, litigation can be costly and time consuming, and it can divert management’s attention from important business matters and initiatives, negatively impacting our overall operations. Item 4. Mine Safety Disclosures. Not applicable. 76 PART II
Biggest changeRegardless of the outcome, litigation can be costly and time consuming, and it can divert management’s attention from important business matters and initiatives, negatively impacting our overall operations. Item 4. Mine Safety Disclosures. Not applicable. 81 PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

3 edited+0 added−0 removed5 unchanged
Biggest changeRecent Sales of Unregistered Securities For the quarter ended December 31, 2023, we issued and sold the following unregistered securities: 1) On October 2, 2023, we issued an aggregate of 5,000 shares of our common stock to a consultant in consideration of services during the three months ended December 31, 2023.
Biggest changeRecent Sales of Unregistered Securities For the quarter ended December 31, 2024, we issued and sold the following unregistered securities: 1) On October 2, 2024, we issued an aggregate of 5,000 shares of our common stock to a consultant in consideration of services during the three months ended December 31, 2024.
During the year ended December 31, 2023, there were no other unregistered sales of our securities except as previously reported in a Current Report on Form 8-K or a Quarterly Report on Form 10-Q. Item 6. [Reserved] 77
During the year ended December 31, 2024, there were no other unregistered sales of our securities except as previously reported in a Current Report on Form 8-K or a Quarterly Report on Form 10-Q. Item 6. [Reserved] 82
Holders of Record As of March 25, 2024, there were approximately 158 stockholders of record of our common stock. The actual number of stockholders is greater than this number of record holders and includes stockholders who are beneficial owners but whose shares are held in street name by brokers and other nominees.
Holders of Record As of March 15, 2025, there were approximately 171 stockholders of record of our common stock. The actual number of stockholders is greater than this number of record holders and includes stockholders who are beneficial owners but whose shares are held in street name by brokers and other nominees.

Item 6. [Reserved]

Selected Financial Data — reserved (removed by SEC in 2021)

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Biggest changeItem 6. [ Reserved ] 77 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 78 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 85 Item 8. Financial Statements and Supplementary Data 85 Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure 85 Item 9A. Controls and Procedures 86
Biggest changeItem 6. [ Reserved ] 82 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 83 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 90 Item 8. Financial Statements and Supplementary Data 90 Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure 90 Item 9A. Controls and Procedures 91

Item 7. Management's Discussion & Analysis

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

57 edited+32 added−15 removed37 unchanged
Biggest changeAs of December 31, 2023, we had no outstanding debt. Depreciation Expense. Depreciation expense was $15,004 and $25,575 for the years ended December 31, 2023 and 2022, respectively. The decrease of $10,571, or 41%, in depreciation was primarily due to the timing of purchases of computer equipment for new employees. Net Loss .
Biggest changeThere was no interest expense for the years ended December 31, 2024 and 2023 because we had no debt obligations. As of December 31, 2024, we had no outstanding debt. Depreciation Expense. Depreciation expense was $6,693 and $15,004 for the years ended December 31, 2024 and 2023, respectively.
We believe that the following accounting policies are the most critical to aid in fully understanding and evaluating our reported financial results, and they require our most difficult, subjective or complex judgments, resulting from the need to make estimates about the effect of matters that are inherently uncertain .
We believe that the following accounting policies and estimates are the most critical to aid in fully understanding and evaluating our reported financial results, and they require our most difficult, subjective or complex judgments, resulting from the need to make estimates about the effect of matters that are inherently uncertain .
Until such time as we can generate substantial revenue from product sales, if ever, we expect to finance our operating activities through a combination of equity offerings, drawdowns on our ATM pursuant to our Agreement with the Agent, and debt financings and we may seek to raise additional capital through strategic collaborations or transactions.
Until such time as we can generate substantial revenue from product sales, if ever, we expect to finance our operating activities through a combination of equity offerings, drawdowns on our ATM pursuant to our ATM Agreement with the Agent, and debt financings and we may seek to raise additional capital through strategic collaborations or transactions.
We expect our research and development expenses to increase in the future as we (i) continue to advance our current and future product candidates into and through clinical trials, (ii) transition some of our manufacturing activities to new vendors for a variety of reasons, such as to incorporate more advanced processes and scale production, including any additional work that has been or may be required to successfully adapt our process to these new processes, (iii) pursue regulatory approval of our current and potential product candidates in the United States and Europe, and (iv) expand our research programs to include new therapies and new therapy combinations.
We expect our research and development expenses to increase in the future as we (i) advance our current and future product candidates into and through clinical trials, (ii) transition some of our manufacturing activities to new vendors for a variety of reasons, such as to incorporate more advanced processes and scale production, including any additional work that has been or may be required to successfully adapt our process to these new processes, (iii) pursue regulatory approval of our current and potential product candidates in the United States and Europe, and (iv) expand our research programs to include new therapies and new therapy combinations.
We record the costs of research and development activities based upon the amount of services provided, and we include these costs in accrued liabilities in the condensed balance sheets and within research and development expense in the condensed statements of operations. These costs are a significant component of our research and development expenses.
We record the costs of research and development activities based upon the amount of services provided, and we include these costs in accrued liabilities in the balance sheets and within research and development expense in the statements of operations. These costs are a significant component of our research and development expenses.
The TUSC2 gene, which is the key component of REQORSA and plays a vital role in cancer suppression and normal cell regulation, is one of a series of genes on the short arm of Chromosome 3 whose therapeutic use is covered by our exclusive worldwide licenses from The University of Texas MD Anderson Cancer Center (“MD Anderson”).
The TUSC2 gene, which is the key component of REQORSA and plays a vital role in cancer suppression and normal cell metabolism, is one of a series of genes on the short arm of Chromosome 3 whose therapeutic use is covered by our exclusive worldwide licenses from The University of Texas MD Anderson Cancer Center (“MD Anderson”).
We have provided a full valuation allowance on our deferred tax assets, which primarily consist of cumulative net operating losses from April 1, 2009 (inception) to December 31, 2023. Due to our history of operating losses since inception and losses expected to be incurred in the foreseeable future, a full valuation allowance was considered necessary.
We have provided a full valuation allowance on our deferred tax assets, which primarily consist of cumulative net operating losses from April 1, 2009 (inception) to December 31, 2024. Due to our history of operating losses since inception and losses expected to be incurred in the foreseeable future, a full valuation allowance was considered necessary.
We currently have certain fixed cash obligations with respect to development of materials used in our clinical studies and payment obligations associated with our ongoing conduct and monitoring of our Acclaim clinical trials, and we expect that we will have insufficient cash to cover these requirements through fiscal year 2024 without raising additional working capital.
We currently have certain fixed cash obligations with respect to development of materials used in our clinical studies and payment obligations associated with our ongoing conduct and monitoring of our Acclaim clinical trials, and we expect that we will have insufficient cash to cover these requirements through fiscal year 2025 without raising additional working capital.
Accordingly, we anticipate that we will need to raise additional capital to fund our future operations, which include conducting our Acclaim-1, Acclaim-2, and Acclaim-3 clinical trials (of which Acclaim-1, Acclaim-2 and Acclaim-3 are currently enrolling) and completing preclinical work for potential other oncology candidates and completing preclinical work and conducting clinical trials for our diabetes program.
Accordingly, we anticipate that we will need to raise additional capital to fund our future operations, which include conducting our Acclaim-1 and Acclaim-3 clinical trials (of which both Acclaim-1 and Acclaim-3 are currently enrolling) and completing preclinical work for potential other oncology candidates and completing preclinical work and conducting clinical trials for our diabetes program.
As a result of the uncertainties discussed above, we are unable to determine the duration and completion costs of our research and development projects or when and to what extent we will generate revenue from the commercialization and sale of our product candidates, if at all. General and administrative .
As a result of the uncertainties discussed above, we are unable to determine the duration and completion costs of our research and development projects or when and to what extent we will generate revenue from the commercialization and sale of our product candidates, if at all.
Diabetes Gene Therapy In diabetes, we have exclusively licensed from the University of Pittsburgh of the Commonwealth System of Higher Education (“University of Pittsburgh”) multiple technologies relating to the development of a gene therapy product for each of Type 1 and Type 2 diabetes.
Diabetes Gene Therapy In diabetes, we have exclusively licensed from the University of Pittsburgh of the Commonwealth System of Higher Education (“University of Pittsburgh” or “UP”) multiple technologies relating to the development of a gene therapy product for each of Type 1 and Type 2 diabetes.
Impairment of Long-Lived Assets Management reviews long-lived assets for impairment whenever events or changes in circumstances indicate that the carrying amount may not be realizable or at a minimum annually during the fourth quarter of the year.
Impairment of Long-Lived Assets Management evaluates long-lived assets for impairment whenever events or changes in circumstances indicate that the carrying amount may not be realizable or at a minimum annually during the fourth quarter of the year.
On July 21, 2023, we raised approximately $6.7 million in net proceeds in a registered direct offering pursuant to which we sold 185,644 shares of common stock and warrants to purchase up to 185,644 shares of common stock. On December 13, 2023, we entered into an At The Market (“ATM”) Offering Agreement (the “Agreement”) with H.C.
On July 21, 2023, we raised approximately $6.7 million in net proceeds in a registered direct offering pursuant to which we sold 185,644 shares of common stock and warrants to purchase up to 185,644 shares of common stock. On December 13, 2023, we entered into an At The Market (“ATM”) Offering Agreement (the “ATM Agreement”) with H.C.
The preparation of these financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, as well as the reported expenses incurred during the reporting periods.
The preparation of these financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, and the reported amounts of expenses incurred during the reporting periods.
Our future capital requirements depend on many factors, including, but not limited to: ● the costs and timing of our development activities and preclinical and clinical trials; ● the cost of manufacturing our existing and future products; ● the expenses needed to attract and retain skilled personnel; ● the costs associated with being a public company; ● the costs associated with additional business development or mergers and acquisitions activity, including acquisition-related costs, earn-outs or other contingent payments and costs of developing and commercializing any technologies to which we obtain rights; ● third-party costs associated with the development and commercialization of our existing and future products and the ability of our development partners to satisfy our requirements on a timely basis; ● the scope and terms of our business plans from time to time, and our ability to realize upon our business plans; and ● the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing possible patent claims, including litigation costs and the outcome of any such litigation. 84 Cash used in operating activities Net cash used in operating activities was $24,738,603 and $17,621,498 for the years ended December 31, 2023 and 2022, respectively.
Our future capital requirements depend on many factors, including, but not limited to: ● the costs and timing of our development activities and preclinical and clinical trials; ● the cost of manufacturing our existing and future products; ● the expenses needed to attract and retain skilled personnel; ● the costs associated with being a public company; ● the costs associated with additional business development or mergers and acquisitions activity, including acquisition-related costs, earn-outs or other contingent payments and costs of developing and commercializing any technologies to which we obtain rights; ● third-party costs associated with the development and commercialization of our existing and future products and the ability of our development partners to satisfy our requirements on a timely basis; ● the scope and terms of our business plans from time to time, and our ability to realize upon our business plans; and ● the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing possible patent claims, including litigation costs and the outcome of any such litigation. 89 Cash used in operating activities Net cash used in operating activities was $17,149,088 and $24,738,603 for the years ended December 31, 2024 and 2023, respectively.
Wainwright & Co., LLC, serving as agent (the “Agent”) with respect to an at-the-market offering program under which we may offer and sell through the Agent, from time to time at our sole discretion, up to such number or dollar amount of shares of our common stock (the “Shares”) as registered on the prospectus supplement covering the ATM offering, as may be amended or supplemented from time to time.
Wainwright & Co., LLC, serving as agent (the “Agent”) with respect to an at-the-market offering program (our “2023 ATM Facility”) under which we may offer and sell through the Agent, from time to time at our sole discretion, up to such number or dollar amount of shares of our common stock (the “Shares”) as registered on the prospectus supplement covering the 2023 ATM Facility offering, as may be amended or supplemented from time to time.
We believe that our ONCOPREX Delivery System allows for delivery of a number of cancer-fighting genes, alone or in combination with other cancer therapies, to combat multiple types of cancer and we are in early stages of discovery programs to identify other cancer candidates.
We believe that our ONCOPREX Delivery System allows for the delivery of a number of cancer-fighting tumor suppressor genes, alone or in combination with other cancer therapies, to combat multiple types of cancer and we are in early stages of discovery programs to identify other cancer candidates.
In February 2023, the Company’s research collaborators at the University of Pittsburgh presented preclinical data in a NHP model of Type 1 diabetes highlighting the therapeutic potential of GPX-002 at the 16th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD 2023) in Berlin, Germany.
In February 2023, the Company’s research collaborators at UP presented preclinical data in a NHP model of Type 1 diabetes highlighting the therapeutic potential of GPX-002 at the 16th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD 2023) in Berlin, Germany.
In October 2023, we entered into a one-year extension to our August 2022 sponsored research agreement with the University of Pittsburgh for the use of GPX-002 in a non-human primate (“NHP”) model in Type 2 diabetes.
In October 2023, we entered into a one-year extension to our August 2022 sponsored research agreement with UP for the use of GPX-002 in a non-human primate (“NHP”) model in Type 2 diabetes.
Based on a review of safety data which showed no dose limiting toxicities (“DLTs”), the Acclaim-1 SRC determined that the recommended Phase 2 dose (“RP2D”) of REQORSA will be 0.12 mg/kg.
Based on a review of safety data which showed no dose limiting toxicities (“DLTs”), the Acclaim-1 SRC determined the recommended Phase 2 dose (“RP2D”) of REQORSA to be 0.12 mg/kg.
Recently Issued Accounting Pronouncements A description of recently issued accounting pronouncements that may potentially impact our financial position and results of operations is disclosed in Note 2 to our financial statements appearing in this Annual Report on Form 10-K. 79 Critical Accounting Policies and Significant Judgments and Estimates Our financial statements have been prepared in accordance with generally accepted accounting principles in the United States (“GAAP”).
Recently Issued Accounting Pronouncements A description of recently issued accounting pronouncements that may potentially impact our financial position and results of operations is disclosed in Note 2 to our financial statements appearing in this Annual Report on Form 10-K. 84 Critical Accounting Policies and Significant Judgments and Estimates Our financial statements have been prepared in accordance with generally accepted accounting principles in the United States (“US GAAP”).
We depreciate our assets over their estimated useful life. We estimate furniture and computer and office equipment to have a five-year life. 81 Results of Operations Comparison of the Years Ended December 31, 2023 and 2022 The following summarizes our results of operations for the years ended December 31, 2023 and 2022. Research and Development Expense.
We depreciate our assets over their estimated useful life. We estimate furniture and computer and office equipment to have a five-year life. 86 Results of Operations Comparison of the Years Ended December 31, 2024 and 2023 The following summarizes our results of operations for the years ended December 31, 2024 and 2023. Research and Development Expense.
Long Term Cash Requirements We regularly evaluate our business plans and strategy. These evaluations often result in changes to our business plans and strategy, some of which may be material and significantly change our cash requirements. Ongoing business development activity may require us to use some of our liquidity for an acquisition, or additional capital to fund newly acquired operations.
These evaluations often result in changes to our business plans and strategy, some of which may be material and significantly change our cash requirements. Ongoing business development activity may require us to use some of our liquidity for an acquisition, or additional capital to fund newly acquired operations.
Acclaim – 1: We currently are enrolling and treating patients in the Phase 2a expansion portion of our Phase 1/2 Acclaim-1 clinical trial. The Acclaim-1 trial uses a combination of REQORSA and AstraZeneca’s Tagrisso® in patients with late-stage NSCLC that has activating epidermal growth factor receptor (“EGFR”) mutations and progression after treatment with Tagrisso.
Acclaim – 1: We currently are enrolling and treating patients in the Phase 2a expansion portion of our Phase 1/2 Acclaim-1 clinical trial. The Acclaim-1 trial uses a combination of REQORSA and AstraZeneca’s Tagrisso® ( osimertinib ) in patients with late-stage NSCLC that has activating epidermal growth factor receptor (“EGFR”) mutations and progression on treatment with Tagrisso or Tagrisso-containing regimens.
The Acclaim-3 clinical trial uses a combination of REQORSA and Genentech, Inc.’s Tecentriq® as maintenance therapy in patients with extensive stage small cell lung cancer (“ES-SCLC”) who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. Patients are treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced.
The Acclaim-3 clinical trial uses a combination of REQORSA and Genentech, Inc.’s Tecentriq® ( atezolizumab ) as maintenance therapy for patients with extensive stage small cell lung cancer (“ES-SCLC”) who developed tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. Patients are treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced.
Based on our current cash, we estimate that we will be able to fund our expenditure requirements for our current operations and planned clinical trial activities into the third quarter of 2024.
Based on our current cash, we estimate that we will be able to fund our expenditure requirements for our current operations and planned clinical trial activities into the second quarter of 2025.
Oncology Platform Our lead oncology drug candidate, REQORSA® Immunogene Therapy (generic name: quaratusugene ozeplasmid), previously referred to as GPX-001, is initially being developed in combination with prominent, approved cancer drugs to treat Non-Small Cell Lung Cancer (“NSCLC”) and Small Cell Lung Cancer (“SCLC”).
Oncology Platform Our lead oncology drug candidate, REQORSA® gene therapy (generic name: quaratusugene ozeplasmid ), previously referred to as GPX-001, is initially being developed in combination with prominent, approved cancer drugs to treat Non-Small Cell Lung Cancer (“NSCLC”) and Small Cell Lung Cancer (“SCLC”). REQORSA has multimodal effects on cancer cells.
We agreed to pay JMP Securities a commission equal to three percent (3%) of the gross sales proceeds of any shares sold under the Equity Distribution Agreement, and also provided JMP Securities with customary indemnification and contribution rights. For the year ended December 31, 2022, we sold 98 shares of our common stock for net proceeds to us totaling $4,532.
We agreed to pay JMP Securities a commission equal to three percent (3%) of the gross sales proceeds of any shares sold under the Equity Distribution Agreement, and also provided JMP Securities with customary indemnification and contribution rights. For the year ended December 31, 2023, we sold 1,342 shares of our common stock for net proceeds to us totaling $78,355.
We have agreed to pay the Agent a commission equal to three percent (3%) of the gross sales proceeds of any Shares sold through the Agent under the Agreement, and also have provided the Agent with customary indemnification and contribution rights. As of December 31, 2023 we had not sold any Shares through the Agent under the Agreement.
We have agreed to pay the Agent a commission equal to three percent (3%) of the gross sales proceeds of any Shares sold through the Agent under the ATM Agreement, and also have provided the Agent with customary indemnification and contribution rights.
Subsequent to year-end 2023, on March 21, 2024, we raised approximately $5.8 million in net proceeds in a registered direct offering pursuant to which we sold (i) 165,000 shares of our common stock, (ii) pre-funded warrants exercisable for up to an aggregate of 1,377,112 shares of our common stock, and (iii) warrants exercisable for up to an aggregate of 1,542,112 shares of our common stock.
On March 21, 2024, we completed a registered direct offering in which we sold (i) 165,000 shares of our common stock, (ii) pre-funded warrants exercisable for up to an aggregate of 1,377,112 shares of our common stock, and (iii) warrants exercisable for up to an aggregate of 1,542,112 shares of our common stock, to an accredited healthcare-focused institutional investor for aggregate net proceeds of approximately $5.8 million.
We expect enrollment in each of the cohorts of the Phase 2a expansion portion of the Acclaim-1 trial to be completed by the end of 2024. We expect enrollment in the Phase 1 dose escalation portion of the Acclaim-2 trial to be completed by the second half of 2024.
We expect interim enrollment of the Phase 2a expansion portion of the Acclaim-1 trial to be completed by the end of 2025. We expect interim enrollment in the Phase 2 dose expansion portion of the Acclaim-3 trial to be completed in the second half of 2025.
Our strategy is to develop REQORSA in combination with current approved therapies and we believe REQORSA’s unique attributes position it to provide treatments that improve on these current therapies for patients with NSCLC, SCLC, and possibly other cancers.
In preclinical studies, REQORSA has been shown to be complementary with targeted drugs and immunotherapies. Our strategy is to develop REQORSA in combination with currently approved therapies and we believe REQORSA’s unique attributes position it to provide treatments that improve on these current therapies for patients with NSCLC, SCLC, and possibly other cancers.
The following table sets forth the primary sources and uses of cash for the years ended December 31, 2023 and 2022: Years Ended December 31, 2023 2022 Net cash used in operating activities $ (24,738,603 ) $ (17,621,498 ) Net cash used in investing activities (71,214 ) (59,735 ) Net cash provided by financing activities 10,593,377 6,426 Net decrease in cash (14,216,440 ) (17,674,807 ) 83 Short Term Cash Requirements We believe that our existing cash is sufficient to fund our expected short-term needs into the third quarter of 2024, but will need additional fundraising activities and cash on hand by such time.
The following table sets forth the primary sources and uses of cash for the years ended December 31, 2024 and 2023: Years Ended December 31, 2024 2023 Net cash used in operating activities $ (17,149,088 ) $ (24,738,603 ) Net cash provided by (used in) investing activities 1,166 (71,214 ) Net cash provided by financing activities 12,011,953 10,593,377 Net decrease in cash (5,135,969 ) (14,216,440 ) 88 Short Term Cash Requirements We believe that our existing cash is sufficient to fund our expected short-term needs into the second quarter of 2025, but will need additional fundraising activities and cash on hand by such time.
As of December 31, 2023, we had an accumulated deficit of $133,688,280. We have funded our operations primarily through the sale and issuance of capital stock.
As of December 31, 2024, we had an accumulated deficit of $154,799,443. We have funded our operations primarily through the sale and issuance of capital stock.
Research and development (“R&D”) expense was $17,616,605 for the year ended December 31, 2023 as compared to $11,510,074 for the year ended December 31, 2022.
Research and development (“R&D”) expense was $10,535,446 for the year ended December 31, 2024 as compared to $17,616,605 for the year ended December 31, 2023.
We had a net loss of $30,860,461, for the fiscal year ended December 31, 2023 compared to a net loss of $23,740,621 for the fiscal year ended December 31, 2022.
We had a net loss of $21,111,163, for the fiscal year ended December 31, 2024 compared to a net loss of $30,860,461 for the fiscal year ended December 31, 2023.
There will be an interim analysis following the treatment of 19 patients in each cohort. We expect to complete the enrollment of 19 patients in each cohort of the Phase 2a expansion portion of the study by the end of 2024, and thus we expect the interim analyses in early 2025.
There will be an interim analysis following the treatment of 19 patients in the Phase 2a portion of the Acclaim-1 study. We expect to complete the enrollment of the first 19 patients for interim analysis in the Phase 2a expansion portion of the study by the end of 2025 and expect the interim analysis in the first half of 2026.
This was the highest dose level delivered in the Phase 1 portion of the study and is twice the highest dose level delivered in the Company’s prior clinical trial combining REQORSA with Tarceva® for the treatment of late-stage lung cancer. We opened the Phase 2a expansion portion of the study and enrolled and dosed the first patient in January 2024.
This was the highest dose level delivered in the Phase 1 portion of the study and is twice the highest dose level delivered in our prior clinical trial combining REQORSA with Tarceva® ( erlotinib ) for the treatment of late-stage lung cancer.
As a result of the FDA’s response, the Company will continue with its planned additional nonclinical studies before requesting regulatory guidance in 2024 for the IND-enabling studies.
As a result of the FDA’s response, we decided to continue with our planned additional nonclinical studies before requesting regulatory guidance for the IND-enabling studies.
If an evaluation is required, the estimated future undiscounted cash flows associated with the asset are compared to the asset’s carrying value to determine if an impairment of such asset is necessary.
If an evaluation is required, the estimated future undiscounted cash flows associated with the asset are compared to the asset’s carrying value to determine if an impairment of such asset is necessary. The effect of any impairment would be to expense the difference between the fair value of such asset and its carrying value based upon discounted cash flows.
The Food and Drug Administration (“FDA”) has granted Fast Track Designation for the Acclaim-1 treatment combination of REQORSA and Tagrisso in NSCLC patients who have progressed after Tagrisso treatment. Acclaim – 2: We currently are enrolling and treating patients in the Phase 1 dose escalation portion of our Phase 1/2 Acclaim-2 clinical trial.
The Food and Drug Administration (“FDA”) has granted Fast Track Designation for the Acclaim-1 treatment combination of REQORSA and Tagrisso in NSCLC patients who have progressed on Tagrisso treatment.
For the year ended December 31, 2022, we sold 1,342 shares of our common stock for net proceeds to us totaling $78,355. On December 12, 2023, we provided notice to JMP Securities of our termination of the 2022 ATM Facility. The termination of the Equity Distribution Agreement with JMP Securities was effective as of December 13, 2023.
On December 12, 2023, we provided notice to JMP Securities of our termination of the 2022 ATM Facility. The termination of the Equity Distribution Agreement with JMP Securities was effective as of December 13, 2023.
For the year ended December 31, 2023, we sold an aggregate of 1,342 shares of common stock for total net proceeds of $78,355 pursuant to our 2022 ATM facility as governed by the Equity Distribution Agreement (as further described below).
For the year ended December 31, 2023, we (i) sold an aggregate of 1,342 shares of common stock for total net proceeds of $78,355 pursuant to our 2022 ATM Facility (defined below) as governed by the Equity Distribution Agreement (as further described below), (ii) issued 500 shares of common stock upon the exercise of options for gross proceeds of $5,960, and (iii) completed a registered direct offerings where we sold 280,883 shares of our common stock for net proceeds of approximately $10.5 million.
The foregoing conditions raise substantial doubt regarding our ability to continue as a going concern for a period of one year after the date the financial statements included in this Annual Report are issued. Lack of necessary funds may require us, among other things, to delay, scale back or eliminate some or all of our ongoing and/or planned clinical trials.
The foregoing conditions raise substantial doubt regarding our ability to continue as a going concern for a period of one year after the date the financial statements included in this Annual Report are issued.
See also “Note 7 – Commitments and Contingencies” to our financial statements included in this Annual Report on Form 10-K.
See also “Note 4 - Equity - At-The-Market Offering” to our audited financial statements included in this Annual Report on Form 10-K.
In connection with the March 2024 registered direct offering, we amended certain existing warrants to reduce the exercise price and extend the term thereof. See “Note 9 – Subsequent Events – March 2024 Registered Direct Offering” to the Financial Statements included in this Annual Report on Form 10-K.
In connection with the March 2024 registered direct offering, we amended certain existing warrants to reduce the exercise price and extend the term thereof.
REQORSA has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for apoptosis, or programmed cell death, in cancer cells, and modulates the immune response against cancer cells. In early studies, REQORSA has been shown to be complementary with targeted drugs and immunotherapies.
It harms the metabolism of cancer cells, which leads to reduced cancer cell growth. It has a mechanism of action whereby it decreases tumor glucose metabolism, interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for apoptosis, or programmed cell death, in cancer cells, and increases the immune response against cancer cells.
The expansion portion of these studies provides us the advantage of early insight into drug effectiveness in defined and distinct patient populations at the MTD or RP2D in order to better evaluate efficacy and increase the likelihood of a successful randomized Phase 2 trial which will follow the expansion portion of each study. 78 Acclaim – 3: We currently are enrolling patients in the Phase 1 dose escalation portion of our Phase 1/2 Acclaim-3 clinical trial.
The Phase 2a expansion portion of the Acclaim-1 study provides us the advantage of early insight into drug effectiveness in defined and distinct patient populations at the maximum tolerated dose (the “MTD”) or RP2D in order to better evaluate efficacy and increase the likelihood of a successful randomized Phase 2 trial which will follow the expansion portion of the study. 83 Acclaim – 2: The Acclaim-2 trial involved a combination of REQORSA and Merck & Co.’s Keytruda® ( pembrolizumab ) in patients with late-stage NSCLC whose disease has progressed after treatment with Keytruda.
General and Administrative Expense. General and administrative (“G&A”) expense for the year ended December 31, 2023 was $13,443,961 as compared to $12,295,070 for the year ended December 31, 2022.
General and administrative (“G&A”) expense for the year ended December 31, 2024 was $10,632,028 as compared to $13,425,285 for the year ended December 31, 2023, a decrease of $2,793,257, or 21%.
The Phase 2a expansion portion of the trial is expected to enroll approximately 66 patients; half will be patients who received only prior Tagrisso treatment and the other half will be patients who received prior Tagrisso treatment and chemotherapy. The aim is to determine toxicity and efficacy profiles of patients with different eligibility criteria.
The initial trial design of the Phase 2a expansion portion of the study included two cohorts with half being patients who received only prior Tagrisso treatment and the other half being patients who received prior Tagrisso treatment and chemotherapy.
The effect of any impairment would be to expense the difference between the fair value of such asset and its carrying value. 80 Components of our Results of Operations and Financial Condition Operating expenses We classify our operating expenses into three categories: research and development, general and administrative, and depreciation. Research and development .
For all other modifications, the incremental change in fair value is recognized as a deemed dividend. 85 Components of our Results of Operations and Financial Condition Operating expenses We classify our operating expenses into three categories: research and development, general and administrative, and depreciation. Research and development .
The extension includes a revised research plan to encompass our most recent technologies to which we acquired exclusive rights from the University of Pittsburgh in July 2023. These include a MafB promoter to drive expression of the Pdx1 and MafA transcription factors that can potentially be used for both Type 1 and Type 2 diabetes.
These include a MafB promoter to drive expression of the Pdx1 and MafA transcription factors that can potentially be used for both Type 1 and Type 2 diabetes. See also “Note 7 – Commitments and Contingencies” to our financial statements included in this Annual Report on Form 10-K.
Changes in intellectual property and research and development supplies during this period were negligible. Cash provided by financing activities Net cash provided by financing activities was $10,593,377 and $6,426 for the years ended December 31, 2023 and 2022, respectively.
This difference in period-over-period net cash used in investing activities was primarily due to timing associated with filing and patent prosecution costs of our intellectual property. Cash provided by financing activities Net cash provided by financing activities was $12,011,953 and $10,593,377 for the years ended December 31, 2024 and 2023, respectively.
The expansion portion of both the Acclaim-1 and Acclaim-2 trials are Phase 2 studies.
Acclaim – 3: We are currently enrolling and treating patients in the Phase 2 expansion portion of our Phase 1/2 Acclaim-3 clinical trial.
Cash used in investing activities Net cash used in investing activities was $71,214 and $59,735 for the years ended December 31, 2023 and 2022, respectively.
Cash used in investing activities Net cash provided by investing activities was $1,166 for the year ended December 31, 2024, compared to net cash used in investing activities of $71,214 for the year ended December 31, 2023, or a net change of $72,380.
This increase of $125,011 was primarily due to changes in balances and a significant increase in interest rates of our money market instruments for the year ended December 31, 2023 as compared to the prior year. Interest Expense. There was no interest expense for the years ended December 31, 2023 and 2022 because we had no debt obligations.
Interest Income. Interest income was $63,574 and $215,109 for the years ended December 31, 2024 and 2023, respectively. This decrease of $151,535 was primarily due to lower cash balances held in interest bearing accounts for the year ended December 31, 2024 as compared to the prior year. Interest Expense.
The increase of $10,586,951, or 100%, in net cash provided by financing activities was primarily due to the registered direct offerings in February 2023 and July 2023 and there were no comparable capital raising activities throughout the year ended December 31, 2022.
The increase of $1,418,576, or 13%, in net cash provided by financing activities was primarily due to (i) differences in amounts raised by sales of our securities in capital raising activities and (ii) differences in financing strategies used during the years ended December 31, 2024 and 2023, respectively.
Removed
The Acclaim-2 trial uses a combination of REQORSA and Merck & Co.’s Keytruda® in patients with late-stage NSCLC whose disease has progressed after treatment with Keytruda.
Added
Additionally, we are collaborating with MD Anderson to discover, develop and utilize biomarkers to select the patient population most likely to respond to REQORSA and enable decisions on progression of our drug candidates to the next phase of development.
Removed
Patients are currently being treated at the 0.06 mg/kg dose level in the first cohort of patients and, subject to Acclaim-2 Safety Review Committee (“Acclaim-2 SRC”) approval, will be treated at successive dose levels of 0.09 mg/kg and 0.12 mg/kg.
Added
MD Anderson is currently analyzing biomarkers that would indicate lack of response in lung cancer that could enrich our population of responders in our clinical trials and enhance patient screening and enrollment in order to increase the likelihood of potential success of the Acclaim studies for the Company.
Removed
In March 2023, we amended the Acclaim-2 protocol to include additional treatments in the control group with the goal of accelerating enrollment in the study by making the trial more attractive to a wider variety of investigators. We expect enrollment in the dose escalation portion of the study to be completed in the second half of 2024.
Added
There were three patients originally enrolled in the Phase 1 dose escalation portion of the study who had prolonged progression-free survival (“PFS”). One patient attained a partial remission after the second course of REQORSA and Tagrisso and has maintained this response through 47 courses of treatment (approximately 35 months) and continues to receive REQORSA and Tagrisso treatment to date.
Removed
We will then initiate and evaluate patients in the Phase 2a expansion portion of the study at the maximum tolerated dose (the “MTD”) or RP2D. The FDA has granted Fast Track Designation for the Acclaim-2 treatment combination of REQORSA and Keytruda in NSCLC patients who have progressed after Keytruda treatment.
Added
A second patient had stable disease without disease progression through 32 courses of treatment (approximately 24 months) but recently had disease progression and is no longer receiving treatment. We opened the Phase 2a expansion portion of the study and enrolled and dosed the first patient in January 2024.
Removed
In January 2024, we opened the Phase 1 portion of the Acclaim-3 study for enrollment. We expect to complete the Phase 1 dose escalation portion of the study during the second half of 2024 and we expect to start the Phase 2 expansion portion of our Acclaim-3 study in the second half of 2024.
Added
However, as previously announced in August 2024, based on resource prioritization and to focus on the patients for whom REQORSA is most likely to show a benefit, we decided to limit our enrollment efforts moving forward to patients who received only prior Tagrisso treatment and cease enrollment of the second cohort (patients who received prior Tagrisso treatment and chemotherapy).
Removed
In June 2023, the FDA granted Fast Track Designation for the Acclaim-3 treatment combination of REQORSA and Tecentriq as maintenance therapy in patients with ES-SCLC who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. In August 2023, the FDA granted Orphan Drug Designation to REQORSA for the treatment of SCLC.
Added
However, noting that both of the patients with prolonged PFS in the Phase 1 portion of the study had previously received both chemotherapy and Tagrisso, in February 2025, we amended the protocol to allow entry of patients progressing on Tagrisso or Tagrisso-containing regimens.
Removed
This increase of $6,106,531, or 53%, is primarily due to (i) changes in our manufacturing programs due to our transition to more capable contract development and manufacturing organizations (“CDMOs”), (ii) increased manufacturing and testing of our drug product for our Acclaim-1 and Acclaim-2 clinical trials, and (iii) increase in third-party vendors to support our manufacturing and preclinical and clinical programs.
Added
The Phase 2a expansion portion of the trial is now expected to enroll approximately 33 patients; all of whom have progressed on Tagrisso or Tagrisso-containing regimens. The Phase 2b randomized portion of the study, in which patients progressing on prior Tagrisso treatment will be randomized 1:1 to either REQORSA and Tagrisso combination therapy or to platinum-based chemotherapy, will remain unchanged.
Removed
The increase of $1,148,891, or 9% is primarily due to (i) an increase in professional services and third-party vendors to support corporate programs, and (ii) greater share-based compensation associated with G&A employees and service providers. Interest Income. Interest income was $215,109 and $90,098 for the years ended December 31, 2023 and 2022, respectively.
Added
As previously announced in August 2024, based on a number of factors, including enrollment challenges and delays due to competition for investigators and eligible patients with numerous other trials involving the same patient population, we decided to cease enrollment of new patients in the Acclaim-2 trial to prioritize our resources and focus on the other two Acclaim trials in SCLC and NSCLC, respectively.
Removed
The increase of $7,119,840, or 30%, in net loss was primarily due to the expansion of our manufacturing to more qualified CDMOs as well as increased manufacturing and testing of our drug product to support our Acclaim-1 and Acclaim-2 clinical trials. 82 Liquidity and Capital Resources From inception through December 31, 2023, we have never generated revenue from product sales and have incurred net losses in each year.
Added
There are no longer any patients receiving study treatment in the Acclaim-2 trial. Although the Acclaim-2 study in patients progressing on Keytruda containing regimens has been closed due to, among other factors, slow enrollment, we continue to believe that this combination could be beneficial.
Removed
For the year ended December 31, 2022, we sold an aggregate of 98 shares of common stock for total net proceeds of $4,532 pursuant to our 2022 ATM facility as governed by the Equity Distribution Agreement (as further described below) and issued 2,925 shares of common stock upon the exercise of options for gross proceeds of $1,755.
Added
On December 16, 2024, we announced that we had completed the Phase 1 dose escalation portion of the Acclaim-3 clinical trial.
Removed
From January 1, 2024 through the date of filing of this Annual Report on Form 10-K, subsequent to the December 31, 2023 balance sheet date, we have sold 158,474 Shares for net proceeds to us totaling $881,946 through the Agent under the Agreement. As of December 31, 2023, we had $6,737,629 in cash.
Added
Based on full safety data, which showed no DLTs, the Acclaim-3 Safety Review Committee (“Acclaim-3 SRC”) determined that the RP2D of REQORSA will be 0.12 mg/kg, which was the highest dose level delivered in the Phase 1 portion of the trial, and approved the opening of the Phase 2 expansion portion of the trial.
Removed
Additionally, as noted above, we received net proceeds totaling $881,946 through the Agent under the ATM Agreement subsequent to year-end 2023 .

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Other GNPX 10-K year-over-year comparisons