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

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Paragraph-level year-over-year comparison of Genprex, Inc.'s 2022 and 2023 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2023 report.

+488 added−414 removedSource: 10-K (2024-04-01) vs 10-K (2023-03-31)

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

488 paragraphs added · 414 removed · 335 edited across 5 sections

Item 1. Business

Business — how the company describes what it does

185 edited+92 added−37 removed306 unchanged
Biggest changeWe received net proceeds of approximately $3.6 million after commissions and estimated expenses, excluding any proceeds that may be received in the future from any exercise of the warrants. 2 Our Pipeline Our technologies are designed to administer disease-fighting genes to provide new treatment options for large patient populations with cancer and diabetes who currently have limited treatment options.
Biggest changeIn connection with the offering, we also amended certain existing warrants to purchase up to an aggregate of 194,248 shares of our common stock that were previously issued to investors in March 2023 and July 2023, with exercise prices of $44.00 and $35.40 per share and expiration dates of March 1, 2028 and July 21, 2028 for $0.125 per amended warrant, such that the amended warrants have a reduced exercise price of $4.09 per share and an expiration date of five years from the closing of this offering. 2 Our Pipeline Our technologies are designed to administer disease-fighting genes to provide new therapies for large patient populations with cancer and diabetes who currently have limited treatment options.
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 non-obese diabetic (“NOD”) mice and in mice treated to destroy insulin producing beta cells, 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. 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.
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 and GPX-003 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, GPX-003, 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. ● 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.
Our employees, independent contractors, consultants, principal investigators, CROs, commercial partners and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements. ● Coverage and reimbursement may be limited or unavailable in certain market segments for REQORSA, GPX-002, GPX-003, and our other current or future product candidates, if approved, which could make it difficult for us to sell REQORSA, GPX-002, GPX-003, and our other current or future product candidates profitably. ● Concerns about gene therapy, genetic testing, and genetic research could result in new and/or additional government regulations and requirements that restrict or prohibit the processes we use or delay or prevent the regulatory approval of our current and potential product candidates. ● Healthcare legislative reform measures may have a material adverse effect on our business and results of operations. ● We are subject to a variety of risks associated with international operations which could materially adversely affect our business. ● If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of our business.
Our employees, independent contractors, consultants, principal investigators, CROs, commercial partners and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements. ● 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. ● Concerns about gene therapy, genetic testing, and genetic research could result in new and/or additional government regulations and requirements that restrict or prohibit the processes we use or delay or prevent the regulatory approval of our current and potential product candidates. ● Healthcare legislative reform measures may have a material adverse effect on our business and results of operations. ● We are subject to a variety of risks associated with international operations which could materially adversely affect our business. ● If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of our business.
Risks Related to Regulatory Approval and Marketing of Our Current and Future Product Candidates and Other Legal Compliance Matters ● We cannot provide assurance that REQORSA, GPX-002, GPX-003, or any of our other current or future product candidates will receive regulatory approval, and without regulatory approval we will not be able to market them. ● Even if we obtain regulatory approval for our product candidates, our products will remain subject to regulatory oversight. ● If the FDA does not find the manufacturing facilities of our current or future contract manufacturers acceptable for commercial production, we may not be able to commercialize REQORSA, GPX-002, GPX-003, or any of our other current or future product candidates. ● We may be subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims laws and other federal and state healthcare laws, and the failure to comply with such laws could result in substantial penalties.
Risks Related to Regulatory Approval and Marketing of Our Current and Future Product Candidates and Other Legal Compliance Matters ● We cannot provide assurance that REQORSA, GPX-002, or any of our other current or future product candidates will receive regulatory approval, and without regulatory approval we will not be able to market them. ● Even if we obtain regulatory approval for our product candidates, our products will remain subject to regulatory oversight. ● If the FDA does not find the manufacturing facilities of our current or future contract manufacturers acceptable for commercial production, we may not be able to commercialize REQORSA, GPX-002, or any of our other current or future product candidates. ● We may be subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims laws and other federal and state healthcare laws, and the failure to comply with such laws could result in substantial penalties.
As illustrated in the schematic below, the TUSC2 protein interacts via various apoptotic signaling pathways such as Apa1 to stimulate programmed cell death via the release of caspases, enzymes that play a significant role in apoptosis. 6 Pan-Kinase Inhibition by TUSC2 Stimulation of Apoptotic Signaling by TUSC2 7 Our clinical and preclinical data indicate that the combination of REQORSA with EGFR TKIs, may increase anti-tumor activity in cancers with or without EGFR mutations and in cancers that have become resistant to EGFR TKI therapy, thus expanding the number of patients who could benefit from those drugs.
As illustrated in the schematic below, the TUSC2 protein interacts via various apoptotic signaling pathways such as Apa1 to stimulate programmed cell death via the release of caspases, enzymes that play a significant role in apoptosis. 6 Pan-Kinase Inhibition by TUSC2 Stimulation of Apoptotic Signaling by TUSC2 7 Our clinical and preclinical data indicate that the combination of REQORSA with EGFR TKIs, may increase anti-tumor activity in cancers with or without EGFR mutations and in cancers that have become resistant to EGFR TKI therapy, thus potentially expanding the number of patients who could benefit from those drugs.
Interim 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%. 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.
We believe that the ONCOPREX Nanoparticle Delivery System may be applicable to delivery of a range of therapeutic and prophylactic plasmid DNA and RNA interference constructs and shows efficacy in cancers beyond lung cancer. We also believe that the manufacturing methods we have developed for REQORSA may be useful for a wide array of disease treatments.
We believe that the ONCOPREX Delivery System may be applicable to delivery of a range of therapeutic and prophylactic plasmid DNA and RNA interference constructs and shows efficacy in cancers beyond lung cancer. We also believe that the manufacturing methods we have developed for REQORSA may be useful for a wide array of disease treatments.
The same general novel approach is used in each of Type 1 and Type 2 whereby an adeno-associated virus (“AAV”) vector containing the Pdx1 and MafA genes is administered directly into the pancreatic duct. In humans, this can be done with a routine endoscopy procedure.
The same general novel approach is used in each of Type 1 and Type 2 diabetes whereby an adeno-associated virus (“AAV”) vector containing the Pdx1 and MafA genes is administered directly into the pancreatic duct. In humans, this can be done with a routine endoscopy procedure.
Once REQORSA is taken up into a cancer cell, the TUSC2 gene is expressed and TUSC2 protein is capable of restoring certain defective functions in the cancer cell. REQORSA has been designed using the ONCOPREX Nanoparticle Delivery System to deliver the functioning TUSC2 gene to cancer cells while minimizing their uptake by normal tissue.
Once REQORSA is taken up into a cancer cell, the TUSC2 gene is expressed and TUSC2 protein is capable of restoring certain defective functions in the cancer cell. REQORSA has been designed using the ONCOPREX Delivery System to deliver the functioning TUSC2 gene to cancer cells while minimizing their uptake by normal tissue.
Introduction – Diabetes Diabetes Mellitus. Diabetes mellitus refers to a group of metabolic diseases that affect how the body produces and uses blood sugar (glucose). Glucose is vital to health because it is an important source of energy for the cells that make up the body’s muscles and tissues. It is also the brain's main source of fuel.
Diabetes mellitus refers to a group of metabolic diseases that affect how the body produces and uses blood sugar (glucose). Glucose is vital to health because it is an important source of energy for the cells that make up the body’s muscles and tissues. It is also the brain’s main source of fuel.
Additionally, the federal Physician Payments Sunshine Act under the Affordable Care Act, and its implementing regulations, require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with certain exceptions, annually report to CMS information related to certain payments or other transfers of value made or distributed to physicians, physician assistants, certain types of advanced practice nurses and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals and to report annually certain ownership and investment interests held by physicians and their immediate family members.
Additionally, the federal Physician Payments Sunshine Act and its implementing regulations require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with certain exceptions, annually report to CMS information related to certain payments or other transfers of value made or distributed to physicians, physician assistants, certain types of advanced practice nurses and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals and to report annually certain ownership and investment interests held by physicians and their immediate family members.
Clinical data from the use of REQORSA has shown that the ONCOPREX Nanoparticle Delivery System is well tolerated in humans and can be delivered at high therapeutic doses. Rights to other Tumor Suppressor Genes.
Clinical data from the use of REQORSA has shown that the ONCOPREX Delivery System is well tolerated in humans and can be delivered at high therapeutic doses. Rights to other Tumor Suppressor Genes.
On our website, investors can obtain, free of charge, copies of our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, our Code of Business Conduct and Ethics, including disclosure related to any amendments or waivers thereto, other reports and any amendments thereto filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act of 1934, as amended, as soon as reasonably practicable after we file such material electronically with, or furnish it to, the Securities and Exchange Commission ("SEC").
On our website, investors can obtain, free of charge, copies of our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, our Code of Business Conduct and Ethics, including disclosure related to any amendments or waivers thereto, other reports and any amendments thereto filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act of 1934, as amended, as soon as reasonably practicable after we file such material electronically with, or furnish it to, the Securities and Exchange Commission (“SEC”).
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 ● an 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); and ● ECOG performance status of 0 to 1.
Effect of REQORSA on the Growth of A549 Subcutaneous Tumor Xenografts in Nude Mice Moreover, intravenous injections of REQORSA into mice bearing experimental A549 lung metastases resulted in a decrease in the number of metastatic tumor nodules.
Effect of REQORSA on the Growth of H1299 Subcutaneous Tumor Xenografts in Nude Mice Moreover, intravenous injections of REQORSA into mice bearing experimental A549 lung metastases resulted in a decrease in the number of metastatic tumor nodules.
These patents comprise various therapeutic, diagnostic, technical and processing claims relating to REQORSA and our ONCOPREX Nanoparticle 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 2024 to 2038.
License 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 8, 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.
License 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.
After many years of such increased secretion, the beta cells become "tired" from working overtime, and the fatigue process begins. This fatigue tends to be progressive, and in time the compensation for insulin resistance disappears. At that point, blood glucose levels start going up. Current Treatments for Diabetes. Advances in new treatments have helped many people better manage the disease.
After many years of such increased secretion, the beta cells become “tired” from working overtime, and the fatigue process begins. This fatigue tends to be progressive, and in time the compensation for insulin resistance disappears. At that point, blood glucose levels start going up. Current Treatments for Diabetes. Advances in new treatments have helped many people better manage the disease.
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 still showed 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 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.
Biological Products Development Process The process required by the FDA before a biological product, including our REQORSA, GPX-002, GPX-003, and potential future product candidates, may be marketed in the United States generally involves the following: ● completion of preclinical 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. 30 Within the FDA, the Center for Biologics Evaluation and Research (“CBER”) regulates gene therapy products.
As shown in the figures below, the TUSC2 protein, a potent pan-kinase inhibitor, blocks multiple cell-signaling pathways downstream of the receptor (EGFR in the figures), leading to cell cycle interruption and thereby preventing cancer cell proliferation and survival. Under stress conditions, such as oncogenic stress, cells go through a regulated process of programmed cell death, also known as apoptosis.
As shown in the figures below, the TUSC2 protein, a potent pan-kinase inhibitor, blocks multiple cell-signaling pathways downstream of the EGFR receptor and leads to cell cycle interruption, thereby preventing cancer cell proliferation and survival. Under stress conditions, such as oncogenic stress, cells go through a regulated process of programmed cell death, also known as apoptosis.
In 2019, preclinical data were presented by MD Anderson collaborators relating to the combination of TUSC2, the active agent in REQORSA, with Keytruda showing that TUSC2 combined with the checkpoint blockade mechanism of action of Keytruda was more effective than Keytruda alone in increasing the survival of mice with a human immune system (humanized mice) that had metastatic lung cancer.
In 2019, preclinical data were presented by MD Anderson collaborators relating to the combination of REQORSA, with Keytruda showing that TUSC2 combined with the checkpoint blockade mechanism of action of Keytruda was more effective than Keytruda alone in increasing the survival of mice with a human immune system (humanized mice) that had metastatic lung cancer with a human lung cancer.
Pre-clinical 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; and ● the anti-CTLA4 antibody ipilimumab (marketed as Yervoy® by Bristol-Myers Squibb Company) in animals.
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. REQORSA has been shown to be complementary with targeted drugs and immunotherapies.
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.
These genetic alterations facilitate such malignant growth by affecting signal transduction pathways and transcription, thus inhibiting normal growth signaling in the cell, circumventing the natural process of apoptosis, evading the immune system’s response to cancer, and inducing angiogenesis, which is the formation of new blood vessels that supply cancer cells.
These genetic alterations facilitate malignant growth by affecting signal transduction pathways and transcription, such as inhibiting normal growth signaling in the cell, circumventing the natural process of apoptosis, evading the immune system’s response to cancer, and inducing angiogenesis, which is the formation of new blood vessels that supply cancer cells.
This also involves the investigation of novel advanced technologies to incorporate in these processes. GPX-002 and GPX-003 involve the delivery of the Pdx1 and MafA genes into the pancreas via the pancreatic duct utilizing an AAV vector. We manage our manufacturing arrangements with our CDMOs and other vendors through various agreements.
This also involves the investigation of novel advanced technologies to incorporate in these processes. GPX-002 involves the delivery of the Pdx1 and MafA genes into the pancreas via the pancreatic duct utilizing an AAV vector. We manage our manufacturing arrangements with our CDMOs and other vendors through various agreements.
Regulation In the United States, our activities are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including but not limited to, the Centers for Medicare and Medicaid Services ("CMS"), other divisions of the U.S. Department of Health and Human Services, for instance the Office of Inspector General, the U.S.
Regulation In the United States, our activities are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including but not limited to, the Centers for Medicare and Medicaid Services (“CMS”), other divisions of the U.S. Department of Health and Human Services, for instance the Office of Inspector General, the U.S.
Resistance to targeted drugs and checkpoint inhibitors develop through activation of alternate bypass pathways. For example, when PD-1 is blocked, the TIM-3 checkpoint is up-regulated. We believe that REQORSA’s multimodal activity will block emerging bypass pathways, thereby potentially reducing the probability that drug resistance develops.
Resistance to targeted drugs and checkpoint inhibitors often develops through activation of alternate bypass pathways. For example, when PD-1 is blocked, the TIM-3 checkpoint is up-regulated. We believe that REQORSA’s multimodal activity will block emerging bypass pathways, thereby potentially reducing the probability that drug resistance develops.
In the case of biologics, the section of the FDCA that governs the approval of drugs via New Drug Applications (“NDAs”) does not apply to the approval of biologics. Rather, biologics, such as gene therapy products, are approved for marketing under provisions of the Public Health Service Act ("PHSA") via a Biologics License Application (“BLA”).
In the case of biologics, the section of the FDCA that governs the approval of drugs via New Drug Applications (“NDAs”) does not apply to the approval of biologics. Rather, biologics, such as gene therapy products, are approved for marketing under provisions of the Public Health Service Act (“PHSA”) via a Biologics License Application (“BLA”).
As further described in the “Licenses and Research Collaborations” section below, we also hold worldwide, exclusive licenses to an issued patent and 7 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 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.
We are developing our lead product candidate REQORSA to be administered with targeted therapies and with immunotherapies for NSCLC and SCLC.
We are developing our lead oncology product candidate REQORSA to be administered with targeted therapies and with immunotherapies for NSCLC and SCLC.
Thus, mutations in PI3K (overexpression) and its upstream activators, such as EGFR, have been associated with many forms of cancers.
Thus, mutations in PI3K and its upstream activators, such as EGFR, have been associated with many forms of cancers.
There was no effect of pembrolizumab on NK/activated NK cells, whereas REQORSA alone enhanced their levels significantly, indicating REQORSA regulation of NK activation, which is consistent with the previous finding reported in syngeneic mice. The combination had a similar effect as REQORSA monotherapy ( Figure 2E ).
There was no effect of pembrolizumab on NK/activated NK cells, whereas REQORSA alone enhanced their levels significantly, indicating REQORSA regulation of NK activation, which is consistent with the previous findings reported in syngeneic mice. The combination had a similar effect as REQORSA monotherapy ( Figure 2E ).
Chronic diabetes conditions include Type 1 diabetes and Type 2 diabetes, both of which lead to excess sugar in the blood and can cause serious health problems. Left untreated, high blood sugar levels can damage the eyes, kidneys, nerves, and the heart, and can also lead to coma and death. Epidemiology of Diabetes. According to the U.S.
Chronic diabetes conditions include Type 1 diabetes and Type 2 diabetes, both of which lead to excess glucose in the blood and can cause serious health problems. Left untreated, high blood glucose levels can damage the eyes, kidneys, nerves, and the heart, and can also lead to coma and death. Epidemiology of Diabetes. According to the U.S.
In addition, TUSC2 has been found to down-regulate PD-L1 on the surface of cancer cells. These data, along with our previous pre-clinical and clinical data, provided the basis for the receipt from the FDA in December 2021 of our second Fast Track Designation.
In addition, TUSC2 has been found to down-regulate PD-L1 on the surface of cancer cells. These data, along with our previous preclinical and clinical data, provided the basis for the receipt from the FDA in December 2021 of our second Fast Track Designation.
This trial showed that REQORSA was well tolerated and established the 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 in 2 patients.
Type 2 diabetes is due to "insulin resistance," an initial resistance of the body's cells to obey the direction from insulin. To overcome this resistance, the beta cells secrete more insulin, and glucose is eventually forced into the cells. Glucose is maintained within normal limits, but at the expense of increased insulin secretion by the beta cells.
Type 2 diabetes is due to “insulin resistance,” an initial resistance of the body’s cells to obey the direction from insulin. To overcome this resistance, the beta cells secrete more insulin, and glucose is eventually forced into the cells. Glucose is maintained within normal limits, but at the expense of increased insulin secretion by the beta cells.
As consideration for this assignment, we agreed to assume all of IRI’s obligations to MD Anderson under the 1994 MD Anderson License Agreement, including ongoing patent related expenses and royalty obligations. The IRI Collaboration Agreement was amended by an Amended Collaboration and Assignment Agreement dated July 1, 2011 ("2011 IRI Collaboration Agreement").
As consideration for this assignment, we agreed to assume all of IRI’s obligations to MD Anderson under the 1994 MD Anderson License Agreement, including ongoing patent related expenses and royalty obligations. The IRI Collaboration Agreement was amended by an Amended Collaboration and Assignment Agreement dated July 1, 2011 (“2011 IRI Collaboration Agreement”).
On February 26, 2010, IRI and P53, Inc., which subsequently changed its name to MultiVir Inc., (“P53”) entered into a Technology License Agreement ("P53 License Agreement") pursuant to which IRI granted to P53 a worldwide, exclusive license under certain patents related to the ONCOPREX Nanoparticle Delivery System that we are now using for the delivery of TUSC2, but only for P53’s use in gene therapy products in which the sole active genes are P53 and MDA-7.
On February 26, 2010, IRI and P53, Inc., which subsequently changed its name to MultiVir Inc., (“P53”) entered into a Technology License Agreement (“P53 License Agreement”) pursuant to which IRI granted to P53 a worldwide, exclusive license under certain patents related to the ONCOPREX Delivery System that we are now using for the delivery of TUSC2, but only for P53’s use in gene therapy products in which the sole active genes are P53 and MDA-7.
The most common genetic alterations present in lung cancer are in tumor suppressor genes. No targeted small molecule drugs have successfully been developed against tumor suppressor gene mutations in NSCLC or SCLC. Another genetic condition often associated with lung cancer are mutations of tyrosine kinases.
The most common genetic alterations present in lung cancer are in tumor suppressor genes. No targeted small molecule drugs have successfully been developed against tumor suppressor gene mutations in NSCLC or SCLC. Another genetic condition often associated with lung cancer is the presence of mutations of tyrosine kinases.
Additionally, Fast Track Designation or Breakthrough Therapy Designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process, including considering any new drug or biologic approvals that later the unmet medical need.
Additionally, Fast Track Designation or Breakthrough Therapy Designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process, including considering any new drug or biologic approvals that address the unmet medical need.
These data provided strong support for the ONC-002 trial, which combined REQORSA with Tarceva. REQORSA in Tagrisso resistant cell lines . Osimertinib, the only third-generation EGFR inhibitor, shows robust clinical activity, yet patients inevitably develop secondary resistance.
These data provided strong support for the ONC-002 trial, which combined REQORSA with Tarceva. REQORSA in Tagrisso resistant cell lines . Tagrisso (osimertinib), a third-generation EGFR inhibitor, shows robust clinical activity, yet patients inevitably develop secondary resistance.
We believe that our ONCOPREX Nanoparticle 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 are in early stages of discovery programs to identify early-stage candidates.
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.
While we continue to use third-party contract development and manufacturing organizations ("CDMOs") in the manufacture of our product candidates, we believe we have a competitive advantage in our field based on core competencies we have developed that we are leveraging in the manufacture of our product candidates.
While we continue to use third-party contract development and manufacturing organizations (“CDMOs”) in the manufacture of our product candidates, we believe we have a competitive advantage in our field based on core competencies we have developed that we are leveraging in the manufacture of our product candidates.
Normal TUSC2 function is often inactivated at the early onset of cancer development, making TUSC2 a potential target for all stages of cancer, including metastatic disease. The TUSC2 protein is reduced or absent in approximately 82% of NSCLCs and in 100% of SCLCs.
Normal TUSC2 function is often inactivated early in cancer development, making TUSC2 a potential target for all stages of cancer, including metastatic disease. The TUSC2 protein is reduced or absent in approximately 82% of NSCLCs and in 100% of SCLCs.
Studies in mice showed that the uptake of TUSC2 in tumor cells after REQORSA treatment was 10 to 33 times the uptake in normal cells, and studies in three NSCLC patients showed a major increase in TUSC2 expression in tumor tissue one day after REQORSA administration.
Laboratory studies showed that the uptake of TUSC2 in tumor cells after REQORSA treatment was 10 to 33 times the uptake in normal cells, and studies in three NSCLC patients showed a major increase in TUSC2 expression in tumor tissue one day after REQORSA administration.
Data from preclinical studies at MD Anderson has shown a therapeutic benefit from the combination of TUSC2 and anti-PD-1 antibody and a key role for TUSC2 in regulating immune cell subpopulations including cytokines, natural killer ("NK") cells, and T lymphocytes. In addition, TUSC2 has been found to down-regulate PD-L1 on the surface of cancer cells.
Data from preclinical studies at MD Anderson has shown a benefit from the combination of TUSC2 and anti-PD-1 antibody and a key role for TUSC2 in regulating immune cell subpopulations including cytokines, natural killer (“NK”) cells, and T lymphocytes. In addition, TUSC2 has been found to down-regulate PD-L1 on the surface of cancer cells.
REQORSA is also delivered systemically as opposed to many other gene therapies. 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. 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.
On May 4, 2020 (the “MD Effective Date”), we entered into a Patent and Technology License Agreement with MD Anderson, as amended on March 3, 2021 (collectively, the “2020 License Agreement” and together with the 1994 MD Anderson License Agreement, collectively, the "MD Anderson License Agreements").
On May 4, 2020 (the “MD Effective Date”), we entered into a Patent and Technology License Agreement with MD Anderson, as amended on March 3, 2021 (collectively, the “2020 License Agreement” and together with the 1994 MD Anderson License Agreement, collectively, the “MD Anderson License Agreements”).
Department of Justice ("DOJ"), and individual U.S. Attorney offices within the DOJ, and state and local governments.
Department of Justice (“DOJ”), and individual U.S. Attorney offices within the DOJ, and state and local governments.
Tyrosine kinases are enzymes that play an important role in signal transduction through the modification of proteins by adding (phosphorylation) phosphate groups on the amino acid tyrosine, to change the proteins’ function.
Tyrosine kinases are enzymes that play an important role in signal transduction through the modification of proteins by adding phosphate groups (phosphorylation) onto the amino acid tyrosine, to change the proteins’ function.
Our pre-clinical data indicate that REQORSA in combination with both EGFR TKIs and with immunotherapies can achieve results more favorable than results achieved with either REQORSA or such other therapies alone, and may make those drugs effective for patients with drug resistance who would not otherwise benefit from them.
Our preclinical data indicate that REQORSA in combination with both EGFR TKIs and with immunotherapies can achieve results more favorable than results achieved with either REQORSA or such other therapies alone, and may make those drugs effective for patients with drug resistance who would not otherwise benefit from them.
One subject with stable disease, a 54-year-old female with a large cell neuroendocrine carcinoma who received 12 cycles of REQORSA therapy, 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.
Non-obese diabetic mice develop diabetes due to an immune attack that destroys the insulin producing beta cells in the pancreas. The figures below show that starting approximately a week after injection of the engineered AAV construct (labeled AAV8-PM) into the pancreatic duct the blood glucose level markedly improved in NOD mice.
NOD mice develop diabetes due to an immune attack that destroys the insulin producing beta cells in the pancreas. The figures below show that starting approximately a week after injection of the engineered AAV construct (labeled AAV8-PM) into the pancreatic duct the blood glucose level markedly improved in NOD mice.
Roth, MD, FACS, chairman of our Scientific Advisory Board. Our goal is to utilize our novel gene therapy platform to provide more effective treatments to large patient populations suffering from devastating illness. REQORSA, our lead product candidate, initially is being developed as a potential treatment for NSCLC.
Roth, MD, FACS, chairman of our Scientific Advisory Board. Our goal is to utilize our novel gene therapy platform to provide more effective treatments to large patient populations suffering from devastating illness. REQORSA, our lead oncology product candidate, initially is being developed as a potential treatment for NSCLC and SCLC.
The dose expansion 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 dose expansion portion of each study.
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.
Clinical trials involving biological product candidates also must be reviewed by an institutional biosafety committee ("IBC"), a local institutional committee that reviews and oversees basic and clinical research conducted at that institution.
Clinical trials involving biological product candidates also must be reviewed by an institutional biosafety committee (“IBC”), a local institutional committee that reviews and oversees basic and clinical research conducted at that institution.
NSCLC represents about 82% of all lung cancers and the five-year survival rate for patients with NSCLC with distant spread is 7 percent. SCLC represents about 14% of lung cancer patients and the five-year survival rate for patients with SCLC with distant spread is 3 percent.
NSCLC represents about 82% of all lung cancers and the five-year survival rate for patients with NSCLC with distant spread is 9 percent. SCLC represents about 14% of lung cancer patients and the five-year survival rate for patients with SCLC with distant spread is 3 percent.
Of the 39 patients planned for the Phase 2 portion of the trial, 10 were enrolled (three of whom were also subjects of the Phase 1 portion of the Phase 1/2 Combination Tarceva Trial). None of the 10 subjects treated in the Phase 2 portion of the Phase 1/2 Combination Tarceva Trial suffered a DLT.
Of the 39 patients planned for the Phase 2 portion of the trial, 10 were enrolled (three of whom were also subjects of the Phase 1 portion of the Phase 1/2 Combination Tarceva Trial). None of the 10 subjects treated in the Phase 2 portion of the Phase 1/2 Combination Tarceva Trial had a DLT.
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 14 issued patents and 13 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 20 issued patents and 12 pending patent applications for technologies developed at MD Anderson and The University of Texas Southwestern Medical Center.
Our study in SCLC builds on the pre-clinical 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 therapeutic benefit over immune checkpoint inhibitors alone. Immune checkpoint inhibitors, such as Tecentriq, have recently been approved for use in ES-SCLC.
Substantial research has been performed in the emerging field of immuno-oncology to discover drugs or antibodies that could block PD-L1 and similar receptors.
Substantial research has been performed in the emerging field of immuno-oncology to discover drugs or antibodies that could block PD-1 and similar receptors.
For our diabetes program, which is an earlier stage program than our oncology program, we are working with our academic collaborators at University of Pittsburgh to transfer the technologies associated with the manufacture of our GPX-002 and GPX-003 constructs to an appropriate integrated network of CDMOs and other vendors.
For our diabetes program, which is an earlier stage program than our oncology program, we are working with our academic collaborators at University of Pittsburgh to transfer the technologies associated with the manufacture of our GPX-002 construct to an appropriate integrated network of CDMOs and other vendors.
The requirements and process governing the conduct of clinical trials, product licensing, pricing, and reimbursement vary from country to country. In all cases, the clinical trials are to be conducted in accordance with GCP, applicable regulatory requirements, and the ethical principles that have their origin in the Declaration of Helsinki.
The requirements and process governing the conduct of clinical trials, product licensing, manufacturing, sales and marketing, pricing, and reimbursement vary from country to country. In all cases, the clinical trials are to be conducted in accordance with GCP, applicable regulatory requirements, and the ethical principles that have their origin in the Declaration of Helsinki.
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, 2023, we had 28 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, 2024, we had 26 total employees, all of which were full-time.
TUSC2 functions to mediate apoptosis in cancer cells through interaction with Apaf1 and also down-regulates multiple tyrosine kinases that regulate 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. In normal cells, the proteins involved in the PI3K/AKT/mTOR pathway play an important role in cellular function and cellular trafficking.
Successful tech transfer of REQORSA from MD Anderson, where it was developed and previously manufactured, to CDMOs has been achieved as well as scale-up of our clinical grade manufacturing production in accordance with cGMP. The clinical grade material is being used to supply our Acclaim-1 and Acclaim-2 clinical trials and will be used to supply our Acclaim-3 clinical trials.
Successful tech transfer of REQORSA from MD Anderson, where it was developed and previously manufactured, to CDMOs has been achieved as well as scale-up of our clinical grade manufacturing production in accordance with cGMP. As noted above, the clinical grade material is being used to supply our Acclaim-1, Acclaim-2 and Acclaim-3 clinical trials.
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.
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.
Pre-clinical data also have shown that REQORSA enhances the immune response to cancer. Data from preclinical studies at MD Anderson have shown a therapeutic benefit from the combination of TUSC2 and anti-PD-1 antibody and a key role for TUSC2 in regulating immune cell subpopulations including cytokines, NK cells, and T lymphocytes.
Preclinical data also have shown that REQORSA enhances the immune response to cancer. Data from preclinical studies at MD Anderson have shown a therapeutic benefit from the combination of TUSC2 and anti-PD-1 antibody or anti-PD-L1 antibody and a key role for TUSC2 in regulating immune cell subpopulations including cytokines, NK cells, and T lymphocytes.
Therefore, three additional subjects were treated at this dose level (six subjects total), none of whom suffered a DLT. At dose level 2, there were no DLTs.
Therefore, three additional subjects were treated at this dose level (six subjects total), none of whom had a DLT. At dose level 2, there were no DLTs.
For example, sales, marketing and scientific/educational grant programs must comply with the anti-fraud and abuse provisions of the Social Security Act, the false claims laws, the physician payment transparency laws, the privacy and security provisions of the Health Insurance Portability and Accountability Act ("HIPAA"), as amended by the Health Information Technology for Economic and Clinical Health Act ("HITECH") and similar state laws, each as amended.
For example, sales, marketing and scientific/educational grant programs must comply with the anti-fraud and abuse provisions of the Social Security Act, the false claims laws, the physician payment transparency laws, the privacy and security provisions of the Health Insurance Portability and Accountability Act (“HIPAA”), as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”) and similar state laws, each as amended.
As shown in Figure 1 , intratumoral administration of REQORSA (referred to as FUS1 in Figure 1 ) to subcutaneous NSCLC A549 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. 17 Figure 1.
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. 27 License Agreement with P53, Inc.
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.
Our diabetes technology is designed to work in Type 1 diabetes by transforming alpha cells in the pancreas into functional beta-like cells, which can produce insulin but are distinct enough from beta cells to evade the body’s immune system. In Type 2 diabetes, our technology is believed to work by replenishing and rejuvenating the beta cells that make insulin.
Our diabetes technology is designed to work in Type 1 diabetes 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 Type 2 diabetes, our technology is believed to work by replenishing and rejuvenating exhausted beta cells that make insulin.
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 by the end of 2023.
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.
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 positively charged, or charge neutral. REQORSA is designed to deliver the functioning TUSC2 gene to cancer cells while minimizing their 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. REQORSA is designed to deliver the functioning TUSC2 gene to cancer cells while minimizing uptake by normal tissue.
In experimental mouse xenograft models, the ONCOPREX delivery system was shown to efficiently deliver several therapeutic tumor suppressor genes ( TP53 , FHIT , TUSC2 ) to disseminated human cancer cells. Metastatic tumor growth was suppressed, and survival prolonged, after systemic administration of the genes via a nanovesicle vector. Human NSCLC A549 cells have no functional TUSC2 gene expression.
In experimental mouse xenograft models, the ONCOPREX delivery system was shown to efficiently deliver several therapeutic tumor suppressor genes ( TP53 , FHIT , TUSC2 ) to disseminated human cancer cells. Metastatic tumor growth was suppressed, and survival prolonged, after systemic administration of the genes via a nanovesicle vector. Human NSCLC A549 cells have virtually no TUSC2 protein.
These data suggest that REQORSA, when combined with other therapies, may be effective in a large population of lung cancer patients. 5 TUSC2, the Active Agent in REQORSA® TUSC2 is a multifunctional gene that plays a vital role in cancer suppression and normal cell regulation.
These data suggest that REQORSA, when combined with other therapies, may be effective in a large population of lung cancer patients. 5 TUSC2, the Tumor Suppressor Gene in REQORSA® TUSC2 is a multifunctional gene that plays a vital role in cancer suppression and normal cell regulation.
With limited benefit from current therapies, we believe there is a significant unmet medical need for new treatments for NSCLC and SCLC in the United States and globally, and we believe REQORSA may be suitable for the majority of lung cancer patients.
With limited benefit from current therapies, we believe there is a significant unmet medical need for new treatments for NSCLC and SCLC in the U.S. and globally, and we believe REQORSA may be suitable for the majority of lung cancer patients.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeFactors 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, GPX-002, or GPX-003; ● delays in the commencement, enrollment and timing of clinical trials; ● the success of our current and future product candidates through all phases of pre-clinical and clinical development; ● 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, GPX-003 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 manufacturers to manufacture our products and key ingredients; ● our ability to establish or maintain collaborations, licensing, sponsored research or other arrangements, particularly with MD Anderson and UP and otherwise relating to REQORSA, GPX-002, and GPX-003; ● 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 .
Biggest changeFactors 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 .
We may not have the financial resources to continue development of, or to enter into collaborations for, a product candidate if we experience any problems or other unforeseen events that delay or prevent regulatory approval of, or our ability to commercialize, product candidates, including: ● inability to obtain sufficient funds required for clinical development; ● inability to reach agreements on acceptable terms with current or prospective vendors, CROs and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different vendors, CROs and trial sites; ● negative or inconclusive results from our clinical studies or the clinical studies of others for product candidates similar to ours, leading to a decision or requirement to conduct additional preclinical testing or clinical trials or abandon a program; ● serious and unexpected side effects experienced by subjects in our clinical trials or by individuals using drugs similar to our current and future product candidates; ● conditions imposed by the FDA or comparable foreign authorities regarding the scope or design of our clinical trials; ● unexpected results from pre-clinical testing and development; ● inability or delays in enrolling research subjects in clinical trials; ● high drop-out rates and high fail rates of research subjects; ● inadequate supply or quality of product candidate components or materials or other supplies necessary for the conduct of pre-clinical or clinical testing; ● greater than anticipated clinical trial costs; ● poor effectiveness of our current and potential product candidates during clinical trials; or ● unfavorable FDA or other regulatory agency inspection and review of a clinical trial site or vendor.
We may not have the financial resources to continue development of, or to enter into collaborations for, a product candidate if we experience any problems or other unforeseen events that delay or prevent regulatory approval of, or our ability to commercialize, product candidates, including: ● inability to obtain sufficient funds required for clinical development; ● inability to reach agreements on acceptable terms with current or prospective vendors, CROs and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different vendors, CROs and trial sites; ● negative or inconclusive results from our clinical studies or the clinical studies of others for product candidates similar to ours, leading to a decision or requirement to conduct additional preclinical testing or clinical trials or abandon a program; ● serious and unexpected side effects experienced by subjects in our clinical trials or by individuals using drugs similar to our current and future product candidates; ● conditions imposed by the FDA or comparable foreign authorities regarding the scope or design of our clinical trials; ● unexpected results from preclinical testing and development; ● inability or delays in enrolling research subjects in clinical trials; ● high drop-out rates and high fail rates of research subjects; ● inadequate supply or quality of product candidate components or materials or other supplies necessary for the conduct of preclinical or clinical testing; ● greater than anticipated clinical trial costs; ● poor effectiveness of our current and potential product candidates during clinical trials; or ● unfavorable FDA or other regulatory agency inspection and review of a clinical trial site or vendor.
The amount and timing of our future funding requirements will depend on many factors, including, but not limited to: ● the progress, costs, results and timing of our preclinical development and clinical trials for REQORSA, GPX-002, GPX-003, and other current or future product candidates; ● the outcome, costs and timing of seeking and obtaining FDA and any other regulatory approvals; ● the ability of third parties to deliver materials and provide services for us; ● the costs associated with securing and establishing commercialization and manufacturing capabilities; ● market acceptance of our current and future product candidates; ● the costs of acquiring, licensing or investing in businesses, products, product candidates and technologies; ● our ability to obtain, maintain, expand and enforce intellectual property rights for our products and product candidates, including the amount and timing of any payments we may be required to make, or that we may receive, in connection with the licensing, filing, prosecution, defense and enforcement of any patents or other intellectual property rights; ● our need and ability to hire additional management and scientific and medical personnel; ● the effect of competing drug candidates and new product approvals; ● our need to implement additional internal systems and infrastructure, including financial and reporting systems; and ● the economic and other terms, timing of and success of our existing licensing arrangements and any collaboration, licensing or other arrangements into which we may enter in the future.
The amount and timing of our future funding requirements will depend on many factors, including, but not limited to: ● the progress, costs, results and timing of our preclinical development and clinical trials for REQORSA, GPX-002, and other current or future product candidates; ● the outcome, costs and timing of seeking and obtaining FDA and any other regulatory approvals; ● the ability of third parties to deliver materials and provide services for us; ● the costs associated with securing and establishing commercialization and manufacturing capabilities; ● market acceptance of our current and future product candidates; ● the costs of acquiring, licensing or investing in businesses, products, product candidates and technologies; ● our ability to obtain, maintain, expand and enforce intellectual property rights for our products and product candidates, including the amount and timing of any payments we may be required to make, or that we may receive, in connection with the licensing, filing, prosecution, defense and enforcement of any patents or other intellectual property rights; ● our need and ability to hire additional management and scientific and medical personnel; ● the effect of competing drug candidates and new product approvals; ● our need to implement additional internal systems and infrastructure, including financial and reporting systems; and ● the economic and other terms, timing of and success of our existing licensing arrangements and any collaboration, licensing or other arrangements into which we may enter in the future.
If REQORSA, GPX-002, GPX-003, or any of our other current or future product candidates receives marketing approval and we or others later identify undesirable or unacceptable side effects caused by such products: ● regulatory authorities may require the addition of labeling statements, specific warnings, a contraindication or field alerts to physicians and pharmacies; ● we may be required to change instructions regarding the way the product is administered, conduct additional clinical trials or change the labeling of the product; ● we may be subject to limitations on how we may promote the product; ● sales of the product may decrease significantly; ● regulatory authorities may require us to take our approved product off the market; ● we may be subject to litigation or product liability claims; and ● our reputation may suffer.
If REQORSA, GPX-002, or any of our other current or future product candidates receives marketing approval and we or others later identify undesirable or unacceptable side effects caused by such products: ● regulatory authorities may require the addition of labeling statements, specific warnings, a contraindication or field alerts to physicians and pharmacies; ● we may be required to change instructions regarding the way the product is administered, conduct additional clinical trials or change the labeling of the product; ● we may be subject to limitations on how we may promote the product; ● sales of the product may decrease significantly; ● regulatory authorities may require us to take our approved product off the market; ● we may be subject to litigation or product liability claims; and ● our reputation may suffer.
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, GPX-003, 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. 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.
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, GPX-003, and our other current or future product candidates, if approved, which could make it difficult for us to sell REQORSA, GPX-002, GPX-003, 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. 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.
Because REQORSA, GPX-002, GPX-003 and our other current product candidates are based upon novel technology, it is difficult to predict whether, either as stand-alone therapies or in combination with other drugs, they will show consistently favorable results and to predict the time and cost of their development and of subsequently obtaining regulatory approval.
Because REQORSA, GPX-002 and our other current product candidates are based upon novel technology, it is difficult to predict whether, either as stand-alone therapies or in combination with other drugs, they will show consistently favorable results and to predict the time and cost of their development and of subsequently obtaining regulatory approval.
A showing that REQORSA, GPX-002, GPX-003, or any of our other current or future product candidates cause undesirable or unacceptable side effects could interrupt, delay or halt clinical trials and result in the failure to obtain or suspension or termination of marketing approval from the FDA and other regulatory authorities, or result in marketing approval from the FDA and other regulatory authorities only with restrictive label warnings.
A showing that REQORSA, GPX-002, or any of our other current or future product candidates cause undesirable or unacceptable side effects could interrupt, delay or halt clinical trials and result in the failure to obtain or suspension or termination of marketing approval from the FDA and other regulatory authorities, or result in marketing approval from the FDA and other regulatory authorities only with restrictive label warnings.
Moreover, in the event we need to obtain licenses from third parties to advance our research and development or allow commercialization of our product candidates, including additional technology that may be required or advisable to advance REQORSA, GPX-002, or GPX-003, we may fail to obtain any of such licenses at a reasonable cost or on reasonable terms, if at all.
Moreover, in the event we need to obtain licenses from third parties to advance our research and development or allow commercialization of our product candidates, including additional technology that may be required or advisable to advance REQORSA or GPX-002, we may fail to obtain any of such licenses at a reasonable cost or on reasonable terms, if at all.
We anticipate that any such losses could be significant for the next several years. If REQORSA, GPX-002, GPX-003, or any of our other current or future product candidates fail in clinical trials or does not gain regulatory approval, or if our drug candidates do not achieve market acceptance, we may never become profitable.
We anticipate that any such losses could be significant for the next several years. If REQORSA, GPX-002, or any of our other current or future product candidates fail in clinical trials or does not gain regulatory approval, or if our drug candidates do not achieve market acceptance, we may never become profitable.
If such third-party manufacturers are unable to produce REQORSA, GPX-002, GPX-003, or other product candidates in the necessary quantities, or in compliance with cGMP or in compliance with pertinent regulatory requirements, and within our planned time frame and cost parameters, the development and sales of our products, if approved, would be materially harmed.
If such third-party manufacturers are unable to produce REQORSA, GPX-002, or other product candidates in the necessary quantities, or in compliance with cGMP or in compliance with pertinent regulatory requirements, and within our planned time frame and cost parameters, the development and sales of our products, if approved, would be materially harmed.
If the FDA requires that we perform additional preclinical studies or clinical trials beyond what we currently anticipate, our expenses will further increase beyond what we currently expect and the anticipated timing of any potential approval of REQORSA, GPX-002, GPX-003, and our other current or future product candidates would likely be delayed.
If the FDA requires that we perform additional preclinical studies or clinical trials beyond what we currently anticipate, our expenses will further increase beyond what we currently expect and the anticipated timing of any potential approval of REQORSA, GPX-002, and our other current or future product candidates would likely be delayed.
These laws may limit or restrict the advertising and promotion of our products to the general public and may impose limitations on our promotional activities with health care professionals. These laws require that promotional materials and advertising for medicinal products are consistent with the product’s Summary of Product Characteristics ("SmPC") as approved by the competent authorities.
These laws may limit or restrict the advertising and promotion of our products to the general public and may impose limitations on our promotional activities with health care professionals. These laws require that promotional materials and advertising for medicinal products are consistent with the product’s Summary of Product Characteristics ( “ SmPC ” ) as approved by the competent authorities.
We cannot provide you any assurance that we will be able to successfully advance REQORSA, GPX-002, GPX-003 or any of our other current or future product candidates through the development process, or that any development problems we experience in the future will not cause significant delays or unanticipated costs, or that such development problems can be solved.
We cannot provide you any assurance that we will be able to successfully advance REQORSA, GPX-002 or any of our other current or future product candidates through the development process, or that any development problems we experience in the future will not cause significant delays or unanticipated costs, or that such development problems can be solved.
There is a substantial amount of litigation, both within and outside the United States, involving patent and other intellectual property rights in the biotechnology and pharmaceutical industries, including patent infringement lawsuits, interferences, oppositions and other post grant proceedings before the US Patent and Trademark Office ("USPTO") and corresponding foreign patent offices.
There is a substantial amount of litigation, both within and outside the United States, involving patent and other intellectual property rights in the biotechnology and pharmaceutical industries, including patent infringement lawsuits, interferences, oppositions and other post grant proceedings before the US Patent and Trademark Office ( “ USPTO ” ) and corresponding foreign patent offices.
REQORSA ® , GPX-002, GPX-003, 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.
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 we are unable to obtain approval from the FDA or other regulatory agencies for REQORSA, GPX-002, GPX-003, or our other current or future product candidates, or if, subsequent to approval, we are unable to successfully commercialize REQORSA, GPX-002, GPX-003, or our other current or future product candidates, we will not be able to generate sufficient revenue to become profitable or to continue our operations.
If we are unable to obtain approval from the FDA or other regulatory agencies for REQORSA, GPX-002, or our other current or future product candidates, or if, subsequent to approval, we are unable to successfully commercialize REQORSA, GPX-002, or our other current or future product candidates, we will not be able to generate sufficient revenue to become profitable or to continue our operations.
We rely, and expect to continue to rely on third-party CDMOs to produce REQORSA and expect to do so with GPX-002 and GPX-003 and other current and future product candidates and other key materials and on third-party contract testing organizations, or CTOs, for the establishment and performance of validated product release assays.
We rely, and expect to continue to rely on third-party CDMOs to produce REQORSA and expect to do so with GPX-002 and other current and future product candidates and other key materials and on third-party contract testing organizations, or CTOs, for the establishment and performance of validated product release assays.
Furthermore, we believe that our existing capital will not be sufficient to enable us to complete the development and commercialization of REQORSA, GPX-002, GPX-003, and our other current or future product candidates. Accordingly, we expect that we will need to raise additional funds in the future.
Furthermore, we believe that our existing capital will not be sufficient to enable us to complete the development and commercialization of REQORSA, GPX-002, and our other current or future product candidates. Accordingly, we expect that we will need to raise additional funds in the future.
Risks Related to Regulatory Approval and Marketing of Our Current and Future Product Candidates and Other Legal Compliance Matters We cannot provide assurance that REQORSA, GPX-002, GPX-003, or any of our other current or future product candidates will receive regulatory approval, and without regulatory approval we will not be able to market them.
Risks Related to Regulatory Approval and Marketing of Our Current and Future Product Candidates and Other Legal Compliance Matters We cannot provide assurance that REQORSA, GPX-002, or any of our other current or future product candidates will receive regulatory approval, and without regulatory approval we will not be able to market them.
We are using the proceeds from our sales of securities to advance REQORSA through clinical development, and to advance our other pre-clinical development programs as well as for other corporate purposes. Developing pharmaceutical products, including conducting preclinical studies and clinical trials, is expensive.
We are using the proceeds from our sales of securities to advance REQORSA through clinical development, and to advance our other preclinical development programs as well as for other corporate purposes. Developing pharmaceutical products, including conducting preclinical studies and clinical trials, is expensive.
Our business currently depends largely on the successful development and commercialization of REQORSA, GPX-002, GPX-003, and our other current product candidates. Our ability to generate revenue related to product sales will depend on the successful development and regulatory approval of REQORSA for the treatment of cancer and/or GPX-002 and GPX-003 for diabetes.
Our business currently depends largely on the successful development and commercialization of REQORSA, GPX-002, and our other current product candidates. Our ability to generate revenue related to product sales will depend on the successful development and regulatory approval of REQORSA for the treatment of cancer and/or GPX-002 for diabetes.
We and our CROs are required to comply with good clinical practices (GCPs) for conducting, recording and reporting the results of clinical trials to assure that the data and reported results are credible and accurate and that the rights, integrity and confidentiality of clinical trial participants are protected.
We and our CROs are required to comply with good clinical practices ( “ GCPs ” ) for conducting, recording and reporting the results of clinical trials to assure that the data and reported results are credible and accurate and that the rights, integrity and confidentiality of clinical trial participants are protected.
Advertising and promotional materials must comply with the Federal Food, Drug, and Cosmetic Act ("FDCA") and implementing regulations and are subject to FDA oversight and post-marketing reporting obligations, in addition to other potentially applicable federal and state laws.
Advertising and promotional materials must comply with the Federal Food, Drug, and Cosmetic Act ( “ FDCA ” ) and implementing regulations and are subject to FDA oversight and post-marketing reporting obligations, in addition to other potentially applicable federal and state laws.
If the FDA does not find the manufacturing facilities of our current or future contract manufacturers acceptable for commercial production, we may not be able to commercialize REQORSA, GPX-002, GPX-003, or any of our other current or future product candidates.
If the FDA does not find the manufacturing facilities of our current or future contract manufacturers acceptable for commercial production, we may not be able to commercialize REQORSA, GPX-002, or any of our other current or future product candidates.
If REQORSA, GPX-002 or GPX-003 or other current or future product candidates are found to be unsafe or lack efficacy, we will not be able to obtain regulatory approval for it and our business would be harmed.
If REQORSA, GPX-002 or other current or future product candidates are found to be unsafe or lack efficacy, we will not be able to obtain regulatory approval for it and our business would be harmed.
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, 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. 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.
If we are unable to bring REQORSA, GPX-002, GPX-003 or other product candidates to market, or acquire other products that are on the market or can be developed, our ability to create stockholder value will be limited.
If we are unable to bring REQORSA, GPX-002 or other product candidates to market, or acquire other products that are on the market or can be developed, our ability to create stockholder value will be limited.
Undesirable side effects for REQORSA, GPX-002, GPX-003, or any of our other current or future product candidates could arise either during clinical development or, if approved, after the approved product has been marketed.
Undesirable side effects for REQORSA, GPX-002, or any of our other current or future product candidates could arise either during clinical development or, if approved, after the approved product has been marketed.
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 and GPX-003.
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.
We will require substantial additional future capital to complete clinical development and commercialize REQORSA and for preclinical and clinical development and commercialization of our gene therapy for diabetes, GPX-002, GPX-003, and our other product candidates.
We will require substantial additional future capital to complete clinical development and commercialize REQORSA and for preclinical and clinical development and commercialization of our gene therapy for diabetes, GPX-002, and our other product candidates.
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 and GPX-003 for the treatment of diabetes.
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.
REQORSA ® , GPX-002, GPX-003, and any other product candidate we advance through clinical trials may not have favorable results in later clinical trials or receive regulatory approval.
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.
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 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 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.
We are authorized to issue up to 10,000,000 shares of preferred stock, none of which are outstanding as of March 15, 2023. 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, 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.
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 or capital commitments 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; ● 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 such as COVID-19, 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. 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.
If we are unable to obtain funding on a timely basis, we may be required to significantly curtail one or more of our pre-clinical or clinical development programs, our ability to continue to support our business growth and to respond to business challenges could be significantly limited, and we may be required to curtail or cease operations.
If we are unable to obtain funding on a timely basis, we may be required to significantly curtail one or more of our preclinical or clinical development programs, our ability to continue to support our business growth and to respond to business challenges could be significantly limited, and we may be required to curtail or cease operations.
We may encounter other delays in our pre-clinical or clinical studies, or we may fail to demonstrate safety and efficacy to the satisfaction of FDA and other regulatory authorities. We may not be successful in our efforts to identify or discover additional product candidates, or to develop product candidates that we have identified.
We may encounter other delays in our preclinical or clinical studies, or we may fail to demonstrate safety and efficacy to the satisfaction of FDA and other regulatory authorities. We may not be successful in our efforts to identify or discover additional product candidates, or to develop product candidates that we have identified.
However, there is no guarantee that the FDA will grant orphan drug designation for any of our drug candidates for any future indication, which would make us ineligible for the additional exclusivity and other benefits of orphan drug designation.
However, there is no guarantee that the FDA will grant orphan drug designation for any of our other drug candidates for any future indication, which would make us ineligible for the additional exclusivity and other benefits of orphan drug designation for those other drug candidates in the future.
While management is working to remediate the material weakness, there is no assurance that such changes, when economically feasible and sustainable, will remediate the identified material weaknesses or that the controls will prevent or detect future material weaknesses.
While management is working to remediate these material weaknesses, there is no assurance that such changes, when economically feasible and sustainable, will remediate the identified material weaknesses or that the controls will prevent or detect future material weaknesses.
Our Amended and Restated Certificate of Incorporation and Amended and Restated Bylaws provide that, unless we consent in writing to the selection of an alternative forum, the following actions must be brought solely and exclusively in the Court of Chancery of the State of Delaware (i) any derivative action or proceeding brought on behalf of us; (ii) any action asserting a claim of breach of a fiduciary duty owed by any director, officer or other employee of the Company to us or our stockholders; (iii) any action asserting a claim against us or any director or officer or other employee of the Company arising pursuant to any provision of the DGCL, our certificate of incorporation or our bylaws; or (iv) any action asserting a claim against us or any director or officer or other employee of the Company governed by the internal affairs doctrine.
Our Amended and Restated Certificate of Incorporation, as may be further amended and restated from time to time, and Amended and Restated Bylaws, as may be further amended from time to time, provide that, unless we consent in writing to the selection of an alternative forum, the following actions must be brought solely and exclusively in the Court of Chancery of the State of Delaware (i) any derivative action or proceeding brought on behalf of us; (ii) any action asserting a claim of breach of a fiduciary duty owed by any director, officer or other employee of the Company to us or our stockholders; (iii) any action asserting a claim against us or any director or officer or other employee of the Company arising pursuant to any provision of the DGCL, our certificate of incorporation or our bylaws; or (iv) any action asserting a claim against us or any director or officer or other employee of the Company governed by the internal affairs doctrine.
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. REQORSA has received two fast track designations from FDA.
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. REQORSA has received three fast track designations from the FDA.
If we are not able to remediate this material weakness or maintain effective internal control over financial reporting, this could result in a material misstatement in our consolidated financial statements and a failure to meet our reporting and financial obligations, which could have a material adverse effect on our business.
If we are not able to remediate the material weaknesses or maintain effective internal control over financial reporting, this could result in a material misstatement in our consolidated financial statements and a failure to meet our reporting and financial obligations, which could have a material adverse effect on our business.
Additionally, site initiation, participant recruitment and enrollment, participant dosing, distribution of clinical trial materials, study monitoring, data analysis, and laboratory research activities may be paused or delayed due to changes in hospital or university policies, federal, state or local regulations, prioritization of hospital resources toward pandemic efforts, or other reasons related to the COVID-19 pandemic.
Additionally, site initiation, participant recruitment and enrollment, participant dosing, distribution of clinical trial materials, study monitoring, data analysis, and laboratory research activities had been paused or delayed due to changes in hospital or university policies, federal, state or local regulations, prioritization of hospital resources toward pandemic efforts, or other reasons related to the COVID-19 pandemic.
We have initiated our Acclaim-1 and Acclaim-2 clinical trials and plan to initiate our Acclaim-3 clinical trial pursuant to an existing IND. We have 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, 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 do not know and cannot predict whether future trials or studies of other current or future product candidates, including Acclaim-3, GPX-002 and GPX-003 will begin as planned, if at all, and we do not know and cannot predict whether our Acclaim-1 and Acclaim-2 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, 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.
As of March 15, 2023, we had 28 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, 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.
For GPX-002 and GPX-003 we have not yet filed an IND and cannot predict all of the challenges and issues that may arise in connection with the preparation and filing of these INDs, or whether these INDs will be filed at all.
For GPX-002 we have not yet filed an IND and cannot predict all of the challenges and issues that may arise in connection with the preparation and filing of an IND, or whether this IND will be filed at all.
More recently, the closures of Silicon Valley Bank, or SVB, and Signature Bank and their placement into receivership with the Federal Deposit Insurance Corporation, or the FDIC, created bank-specific and broader financial institution liquidity risk and concerns.
In 2023, the closures of Silicon Valley Bank, or SVB, and Signature Bank and their placement into receivership with the Federal Deposit Insurance Corporation, or the FDIC, created bank-specific and broader financial institution liquidity risk and concerns.
The manufacture of gene therapy products is complex, and for CDMOs with whom we have agreements, there is no guarantee that they will be able to perform as required under the applicable governing agreement.
The manufacture of gene therapy products is complex, and for CDMOs with whom we have agreements, there is no guarantee that they will be able to perform as required on a timely, consistent basis under the applicable governing agreement.
Any sales of equity securities, whether pursuant to our Equity Distribution 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 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.
Risks Related to our Securities The market price of our common stock may be highly volatile, and you may lose all or part of your investment. The market price of our common stock is likely to be volatile.
Risks Related to our Securities The market price of our common stock may be highly volatile, and you may lose all or part of your investment. The market price of our common stock has been volatile in the past and is likely to be volatile in the future.
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.
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.
As of December 31, 2022, we had federal net operating loss carryforwards (“NOLs”) of approximately $68.9 million for federal income tax purposes of which approximately $1.3 million will begin to expire in 2030 and approximately $59.2 million can be carried forward indefinitely.
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.
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 Equity Distribution Agreement, and also have provided the Agent with customary indemnification and contribution rights.
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.
Genetic testing has raised concerns regarding the appropriate utilization and the confidentiality of information provided by genetic testing. Genetic tests for assessing a person’s likelihood of developing a chronic disease have focused public attention on the need to protect the privacy of genetic information. Genetic testing information is also subject to significant restrictions under both federal and state law.
Genetic tests for assessing a person’s likelihood of developing a chronic disease have focused public attention on the need to protect the privacy of genetic information. Genetic testing information is also subject to significant restrictions under both federal and state law.
With the advancement of the development of GPX-002 and GPX-003, we also are working to optimize the manufacture of these product candidates and to source high quality and integrated vendors capable of producing them 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.
With the advancement of the development of GPX-002 and GPX-003, we also are working to optimize the manufacture of these product candidates and to source high quality and integrated vendors capable of producing them 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.
We cannot assure you that further deterioration in credit and financial markets and confidence in economic conditions will not occur, particularly as a result of the ongoing COVID-19 pandemic. Our general business strategy may be adversely affected by any such economic downturn, volatile business environment or continued unpredictable and unstable market conditions.
We cannot assure you that further deterioration in credit and financial markets and confidence in economic conditions will not occur. Our general business strategy may be adversely affected by any such economic downturn, volatile business environment or continued unpredictable and unstable market conditions.
As a result of COVID-19, our business operations have been interrupted and delayed. Specifically, we have experienced delays in engaging clinical sites as a result of a backlog of clinical trial protocols requiring site review created by an accumulation of protocols while clinical trials and the clinical trial review process have been widely disrupted during the pandemic.
Specifically, we experienced delays in engaging clinical sites as a result of a backlog of clinical trial protocols requiring site review created by an accumulation of protocols while clinical trials and the clinical trial review process had been widely disrupted during the pandemic.
We cannot be sure that issues will not arise in connection with the filing of these amendments or otherwise that will result in the FDA imposing a clinical hold which could result in the delay of either or both of these clinical trials.
We cannot be sure that issues will not arise in the future in connection with potential subsequent amendments or otherwise that might result in the FDA imposing a clinical hold which could result in the delay of any of these clinical trials.
On March 1, 2023, we completed a registered direct offering, in which we sold to an accredited healthcare-focused institutional investor an aggregate of 3,809,524 shares of our common stock and a like number of warrants, at a combined offering price of $1.05 per share of common stock and accompanying warrant, for net proceeds of approximately $3.6 million.
On March 1, 2023, we completed a registered direct offering, in which we sold to an accredited healthcare-focused institutional investor an aggregate of (i) 95,239 shares of our common stock and (ii) warrants to purchase up to 95,239 shares of our common stock, at a combined offering price of $42.00 per share of common stock and accompanying warrant, for net proceeds of approximately $3.6 million.
We do not have the internal infrastructure or facilities to manufacture ourselves REQORSA, or earlier stage GPX-002 or GPX-003 which are in pre-clinical development, or any other current or future product candidate, and intend to rely on CDMOs for clinical trial needs and commercial supply.
We do not have the internal infrastructure or facilities to manufacture ourselves REQORSA, or earlier stage GPX-002 which is in preclinical development, or any other current or future product candidate, and intend to rely on CDMOs for clinical trial needs and commercial supply. However, our strategy could change in the future and we could choose to develop such infrastructure.
For as long as we continue to be an emerging growth company, we may take advantage of exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies, including not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements and exemptions from the requirements of holding nonbinding advisory votes on executive compensation and stockholder approval of any golden parachute payments not previously approved.
While we were an emerging growth company, we were able to take advantage of exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies, including reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements and exemptions from the requirements of holding nonbinding advisory votes on executive compensation and stockholder approval of any golden parachute payments not previously approved.
There is also a risk that due to regulatory changes, such as suspensions on the use of NOLs, or other unforeseen reasons, our existing NOLs could expire or otherwise be unavailable to offset future income tax liabilities. On March 27, 2020, the Coronavirus Aid, Relief, and Economic Security (the “CARES Act”), was signed into law.
There is also a risk that due to regulatory changes, such as suspensions on the use of NOLs, or other unforeseen reasons, our existing NOLs could expire or otherwise be unavailable to offset future income tax liabilities.
To date we have experienced delays in opening our clinical sites for our Acclaim-1 and Acclaim-2 trials. This has been due to a back-log in protocol review at the clinical trial sites due to the COVID-19 pandemic which has mostly resolved.
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.
Concern about the environmental spread of our product, whether real or anticipated, could also hinder the commercialization of our products. Prior to receiving REQORSA in our Acclaim-1 clinical trial, patients are required to undergo genetic screening to detect EGFR mutations and in the Acclaim-2 clinical trial genetic screening to detect PD-L1 as well as other mutations relevant to cancer.
Concern about the environmental spread of our product, whether real or anticipated, could also hinder the commercialization of our products. Prior to receiving REQORSA in our Acclaim-1 clinical trial, patients are required to undergo genetic screening to detect EGFR mutations. Genetic testing has raised concerns regarding the appropriate utilization and the confidentiality of information provided by genetic testing.
Although we have experienced a variety of these challenges to varying degrees in connection with performance by our CDMOs, to date they have not resulted in any measurable delay in our Acclaim-1 or Acclaim-2 clinical trials.
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.
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 $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.
Established pharmaceutical companies may also invest heavily to accelerate discovery and development of novel compounds or to in-license novel compounds that could make the product candidates that we develop obsolete.
These companies also have significantly greater research, sales and marketing capabilities and collaborative arrangements in our target markets with leading companies and research institutions. Established pharmaceutical companies may also invest heavily to accelerate discovery and development of novel compounds or to in-license novel compounds that could make the product candidates that we develop obsolete.
We expect that our eligibility to qualify as an “emerging growth company” will end on December 31, 2023, the last day of our fiscal year following the fifth anniversary of the date of our initial public offering.
We no longer qualify as an emerging growth company under the JOBS Act (our eligibility to qualify as an emerging growth company ended on December 31, 2023, the last day of our fiscal year following the fifth anniversary of our initial public offering).
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, 2022 as a result of a material weakness in our internal controls due to the lack of segregation of duties.
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.
As of December 31, 2022, we had outstanding options to purchase an aggregate of 11,374,327 shares of our common stock at a weighted average exercise price of $3.08 per share and warrants to purchase an aggregate of 2,131,111 shares of our common stock at a weighted average exercise price of $4.34 per share.
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.
We may sell a substantial number of shares of our common stock pursuant to our existing Equity Distribution Agreement with JMP Securities, pursuant to which we have the discretion to deliver placement notices to JMP Securities at any time throughout the term of the Equity Distribution Agreement covering shares of our common stock up to the aggregate offering price of $50 million; 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 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.
We may not be able to obtain or maintain orphan drug designation or exclusivity for our product candidates. We may seek orphan drug designation in the United States and in the European Union for our product candidates.
We may seek other orphan drug designations in the future in the United States and in the European Union for our product candidates.
In addition, we have scientific and clinical advisors and consultants who assist us in formulating our research, development and clinical strategies. These advisors are not our employees and may have commitments to, or consulting or advisory contracts with, other entities that may limit their availability to us and typically they will not enter into non-compete agreements with us.
These advisors are not our employees and may have commitments to, or consulting or advisory contracts with, other entities that may limit their availability to us and typically they will not enter into non-compete agreements with us. If a conflict of interest arises between their work for us and their work for another entity, we may lose their services.
If a conflict of interest arises between their work for us and their work for another entity, we may lose their services. In addition, our advisors may have arrangements with other companies to assist those companies in developing products or technologies that may compete with ours.
In addition, our advisors may have arrangements with other companies to assist those companies in developing products or technologies that may compete with ours.
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. The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological change. This is particularly so in the fast growing gene therapy space.
The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological change. This is particularly so in the fast-growing gene therapy space. We face competition from domestic and international competitors including major multinational pharmaceutical and biotechnology companies, specialty pharmaceutical and generic drug companies, academic institutions, government agencies and other public and private research institutions.
As of December 31, 2022 we have sold 3,886 shares of our common stock for net proceeds to us totaling $4,532. 46 We may seek additional funding through a combination of equity offerings, drawdowns on our ATM pursuant to our Equity Distribution Agreement with JMP Securities 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, 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.
Upon receipt of regulatory approval, orphan drug status will provide us with seven years of market exclusivity in the United States under the Orphan Drug Act.
We may not be able to obtain or maintain orphan drug designation or exclusivity for our product candidates. In August 2023, the FDA granted Orphan Drug Designation to REQORSA for the treatment of SCLC. Upon receipt of regulatory approval, orphan drug status will provide us with seven years of market exclusivity in the United States under the Orphan Drug Act.

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Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeItem 3. Legal Proceedings. From time to time, we may become involved in various lawsuits and legal proceedings. Litigation is subject to inherent uncertainties, and an adverse result in these or other matters may arise from time to time that may harm our business.
Biggest changeItem 3. Legal Proceedings. From time to time, we may be involved in legal proceedings that arise during the ordinary course of business.
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We are currently not aware of any such legal proceedings or claims that will have, individually or in the aggregate, a material adverse effect on our business, financial condition or operating results. Item 4. Mine Safety Disclosures. Not applicable. 76 PART II
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Although the results of legal proceedings cannot be predicted with certainty, we do not currently have any pending litigation to which we are a party or to which our property is subject that we believe to be material.
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Regardless 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

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeRecent Sales of Unregistered Securities For the year ended December 31, 2022, we issued and sold the following unregistered securities: 1) On October 1, 2022, 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, 2022. 2) On December 5, 2022, we issued an aggregate of 76,752 shares of our common stock to a consultant in consideration of services. 3) On December 20, 2022, we issued a warrant to purchase up to 3,000 shares of our common stock at an exercise price of $5.00 per share to a consultant in consideration for services.
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.
The foregoing issuance of securities was not registered under the Securities Act or the securities laws of any state, and the securities were offered and issued in reliance on the exemption from registration under the Securities Act afforded by Section 4(a)(2). Item 6. [Reserved] 77
The foregoing issuance of securities was not registered under the Securities Act or the securities laws of any state, and the securities were offered and issued in reliance on the exemption from registration under the Securities Act afforded by Section 4(a)(2).
Holders of Record As of March 15, 2023, there were approximately 145 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 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.
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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

Item 7. Management's Discussion & Analysis

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

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Biggest changeThe dose expansion 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 dose expansion portions of each study. 78 Acclaim – 3: In November 2022, we filed with the FDA our protocol for our Phase 1/2 Acclaim-3 clinical trial using 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.
Biggest changeThe 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.
However, we may be unable to raise additional funds or enter into such arrangements when needed on favorable terms, or at all, which would have a negative impact on our financial condition and could force us to delay, limit, reduce or terminate our development programs or commercialization efforts or grant rights to others to develop or market product candidates that we would otherwise prefer to develop and market ourselves.
However, we may be unable to raise additional funds or enter into such arrangements when needed on favorable terms, or at all, which would have a negative impact on our financial condition and could force us to delay, limit, reduce or terminate our research and development programs or commercialization efforts or grant rights to others to develop or market product candidates that we would otherwise prefer to develop and market ourselves.
The same general novel approach is used in each of Type 1 and Type 2 whereby an adeno-associated virus (“AAV”) vector containing the Pdx1 and MafA genes is administered directly into the pancreatic duct. In humans, this can be done with a routine endoscopy procedure.
The same general novel approach is used in each of Type 1 and Type 2 diabetes whereby an adeno-associated virus (“AAV”) vector containing the Pdx1 and MafA genes is administered directly into the pancreatic duct. In humans, this can be done with a routine endoscopy procedure.
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. 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”).
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. REQORSA has been shown to be complementary with targeted drugs and immunotherapies.
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.
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, 2022. 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, 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 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, 2022 and 2021 The following summarizes our results of operations for the years ended December 31, 2022 and 2021. 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. 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 believe that our ONCOPREX Nanoparticle 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 are in early stages of discovery programs to identify early-stage candidates.
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.
Patients are currently being treated at the 0.06 mg/kg dose level in the first cohort of patients and, subject to the Acclaim-2 Safety Review Committee approval, will be treated at successive dose levels of 0.09 mg/kg and 0.12 mg/kg.
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.
The process of conducting the necessary clinical research to obtain regulatory approval is costly and time-consuming.
The process of conducting the necessary preclinical and clinical research to obtain regulatory approval is costly and time-consuming.
Purchased materials to be used in future research are capitalized and included in research and development supplies. We estimate the amount of work completed through discussions with internal personnel and external service providers as to the progress or stage of completion of the services and the agreed-upon fee to be paid for such services.
Purchased materials to be used in future research are valued at cost and capitalized and included in research and development supplies. We estimate the amount of work completed through discussions with internal personnel and external service providers as to the progress or stage of completion of the services and the agreed-upon fee to be paid for such services.
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 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 third quarter of 2024.
Our diabetes technology is designed to work in Type 1 diabetes by transforming alpha cells in the pancreas into functional beta-like cells, which can produce insulin but are distinct enough from beta cells to evade the body’s immune system. In Type 2 diabetes, our technology is believed to work by replenishing and rejuvenating the beta cells that make insulin.
Our diabetes technology is designed to work in Type 1 diabetes 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 Type 2 diabetes, our technology is believed to work by replenishing and rejuvenating exhausted beta cells that make insulin.
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 by the end of 2023.
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.
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 $17,778,964 and $14,284,924 for the years ended December 31, 2022 and 2021, 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. 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.
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 Equity Distribution Agreement with JMP Securities as Agent, and debt financings and we may seek to raise additional capital through strategic collaborations.
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.
For the year ended December 31, 2022, we sold an aggregate of 3,886 shares of common stock for total net proceeds of $4,532 pursuant to our ATM facility as governed by the Equity Distribution Agreement (as further described below) and issued 116,973 shares of common stock upon the exercise of options for gross proceeds of $1,755.
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.
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 and Acclaim-2 are currently enrolling) and completing pre-clinical 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, 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.
Our diabetes product candidates are currently being evaluated and optimized in preclinical studies at the University of Pittsburgh. GPX-002 is being developed for the treatment of Type 1 diabetes and GPX-003 is being developed for the treatment of 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.
We will then evaluate patients in the dose expansion portion of the study at 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.
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.
In August 2022, we entered into a sponsored research agreement with MD Anderson to support further pre-clinical studies of TUSC2 and other tumor suppressor genes.
In August 2022, we entered into a three-year sponsored research agreement with MD Anderson to support further preclinical studies of TUSC2 and other tumor suppressor genes.
On November 18, 2022, we entered into our Equity Distribution Agreement with JMP Securities as Agent, with respect to an at-the-market offering program (our “ATM”) under which we may offer and sell, from time to time at our sole discretion, shares of our common stock, having an aggregate offering price of up to $50.0 million through the Agent.
On November 18, 2022, we entered into an Equity Distribution Agreement with JMP Securities, with respect to an at-the-market offering program (our “2022 ATM Facility”) under which we could offer and sell, from time to time at our sole discretion, shares of our common stock, having an aggregate offering price of up to $50.0 million.
The increase in net cash provided by investing activities of $181,527, or 217%, was primarily due to greater use of R&D materials associated with testing and clinical use in our Acclaim clinical trials in the year ended December 31, 2022 compared to the year ended December 31, 2021.
The increase in net cash provided by investing activities of $11,479, or 19%, was primarily due to greater use of R&D materials associated with testing and clinical use in our Acclaim clinical trials in the year ended December 31, 2023 compared to the year ended December 31, 2022.
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 Equity Distribution Agreement, and also have provided the Agent with customary indemnification and contribution rights.
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.
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 $6,426 and $25,677,911 for the years ended December 31, 2022 and 2021, respectively.
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.
We previously have experienced delays in engaging clinical sites as a result of disruptions at these clinical sites caused by the COVID-19 pandemic. We also have experienced delays in clinical trial enrollment as a result of competition for patients.
We previously have experienced delays in engaging clinical sites as a result of disruptions at these clinical sites caused by the COVID-19 pandemic.
As of December 31, 2022, we had an accumulated deficit of $102,827,819. We have funded our operations primarily through the sale and issuance of capital stock.
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.
This increase of $84,965 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, 2022 as compared to the prior year. Interest Expense.
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.
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 top-selling cancer drugs to treat Non-Small Cell Lung Cancer (“NSCLC”) and Small Cell Lung Cancer (“SCLC”). The active agent in REQORSA is a plasmid that expresses a tumor suppressor gene named TUSC2.
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”).
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-1 and our Acclaim-2 clinical trials, and we expect that we have sufficient cash to cover these requirements.
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.
The decrease of $25,671,485, or 100%, in net cash provided by financing activities was primarily due to the $25,000,000 registered direct offering in February 2021 and there were no comparable capital raising activities throughout the year ended December 31, 2022.
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.
Our accrued expenses are dependent, in part, upon the receipt of timely and accurate reporting from contract research organizations ("CROs") and other third-party service providers. To date, there have been no material differences from our accrued expenses to actual expenses.
Our accrued expenses are dependent, in part, upon the receipt of timely and accurate reporting from contract research organizations (“CROs”) and other third-party service providers.
GPX-002 is designed to work by transforming alpha cells in the pancreas into functional beta-like cells, which can produce insulin but are distinct enough from beta cells to evade the body’s immune system. GPX-003 is believed to work by replenishing and rejuvenating the beta cells that make insulin.
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.
The increase of 3,075,652, or 15%, in net loss was primarily due to the expansion of our personnel and our clinical and manufacturing programs to support our Acclaim-1 and Acclaim-2 clinical trials. 82 Liquidity and Capital Resources From inception through December 31, 2022, we have never generated revenue from product sales and have incurred net losses in each year.
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.
The TUSC2 gene 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 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”).
In August 2022, we entered into a one-year sponsored research agreement with the University of Pittsburgh for the use of GPX-003 in a non-human primate (“NHP”) model in Type 2 diabetes and we expect data from this study to be reported by the end of 2023.
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.
The Acclaim-1 trial uses a combination of REQORSA and AstraZeneca PLC’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® in patients with late-stage NSCLC that has activating epidermal growth factor receptor (“EGFR”) mutations and progression after treatment with Tagrisso.
Research and development ("R&D") expense was $11,510,074 for the year ended December 31, 2022 as compared to $8,970,865 for the year ended December 31, 2021.
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.
General and Administrative Expense. General and administrative ("G&A") expense for the year ended December 31, 2022 was $12,295,070 as compared to $11,676,703 for the year ended December 31, 2021.
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.
We will then proceed into the dose expansion portion of the trial. We expect enrollment in the Phase 1 dose escalation portion of the Acclaim-2 trial to be completed by the end of 2023 after which we will move into the dose expansion portion of the trial.
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.
Furthermore, we cannot guarantee future results, events, levels of activity, performance, or achievements. Overview We are a clinical stage gene therapy company pioneering the development of gene-based therapies for large patient populations with unmet medical needs. Our oncology platform utilizes our non-viral ONCOPREX® Nanoparticle Delivery System.
Furthermore, we cannot guarantee future results, events, levels of activity, performance, or achievements. All amounts in this report are in United States (“U.S.”) dollars, unless otherwise noted. Overview We are a clinical stage gene therapy company pioneering the development of gene-based therapies for large patient populations with unmet medical needs.
We do not expect our operations will require significant increases in our short-term cash needs. 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.
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.
See “Note 10 – Subsequent Events – March 2023 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. See “Note 9 – Subsequent Events – March 2024 Registered Direct Offering” to the Financial Statements included in this Annual Report on Form 10-K.
We expect our research and development expenses to increase in the future as we continue to advance our current clinical trials, and advance additional current and future product candidates into and through clinical trials, as we pursue regulatory approval of our current and potential product candidates in the United States and Europe, and as we 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) 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.
Subsequent to year-end 2022, on March 1, 2023, we raised approximately $3.6 million in net proceeds in a registered direct offering pursuant to which we sold 3,809,524 shares of common stock and a like number of warrants.
On March 1, 2023, we completed a registered direct offering in which we sold 95,239 shares of our common stock and warrants to purchase 95,239 shares of our common stock to an accredited healthcare-focused institutional investor for aggregate net proceeds of approximately $3.6 million.
We believe REQORSA’s unique attributes position REQORSA to provide treatment for patients with NSCLC, SCLC, and possibly other cancers, and that it can improve on current therapies. Acclaim – 1: We currently are enrolling and treating patients in the Phase 1 dose escalation portion of our Phase 1/2 Acclaim-1 clinical trial.
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.
The following table sets forth the primary sources and uses of cash for the years ended December 31, 2022 and 2021: Years Ended December 31, 2022 2021 Net cash used in operating activities $ (17,778,964 ) $ (14,284,924 ) Net cash provided (used) in investing activities 97,731 (83,796 ) Net cash provided in financing activities 6,426 25,677,911 Net (decrease) increase in cash and cash equivalents (17,674,807 ) 11,309,191 83 Short Term Cash Requirements We believe that our existing cash is sufficient to fund our expected short-term needs.
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.
This increase of $2,539,209, or 28%, is primarily due to (i) advancements and expansions in our manufacturing programs, including manufacturing and testing of our drug product, for our Acclaim-1 and Acclaim-2 clinical trials, (ii) increased usage of third-parties, including CROs, to manage and maintain our Acclaim-1 and Acclaim-2 clinical trials, and (iii) increase in R&D personnel to support our manufacturing and pre-clinical and clinical programs.
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.
Cash used in investing activities Net cash provided by investing activities was $97,731 for the year ended on December 31, 2022 and net cash used in investment activities was $83,796 for the year ended December 31, 2021.
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.
The increase of $3,041, or 13%, in depreciation was primarily due to the timing of purchases of computer equipment for new employees. Net Loss . We had a net loss of $23,740,621, for the fiscal year ended December 31, 2022 compared to a net loss of $20,664,969 for the fiscal year ended December 31, 2021.
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.
The increase of $618,367, or 5% is primarily due to an increase in G&A headcount and associated accruals from 7 full-time G&A employees on December 31, 2021 to 10 full-time G&A employees on December 31, 2022. Interest Income. Interest income was $90,098 and $5,133 for the years ended December 31, 2022 and 2021, respectively.
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.
The statistically significant study results showed the treated animals had decreased insulin requirements, increased c-peptide levels, and improved glucose tolerance compared to baseline. JOBS Act On April 5, 2012, the JOBS Act was enacted.
The statistically significant study results showed the treated animals had decreased insulin requirements, increased c-peptide levels, and improved glucose tolerance compared to baseline. In April 2023, the Company hosted a Key Opinion Leader virtual event entitled “Novel Gene Therapy to Treat Type 1 Diabetes,” which discussed preclinical data reported at ATTD 2023 supporting gene therapy to treat Type 1 diabetes.
Delays in the conduct of our trials could result in utilizing our capital resources sooner without advancing our clinical trials as anticipated.
We also have experienced delays in clinical trial enrollment as a result of competition for patients and additional time required in connection with our transition to the new third party CDMO and the manufacture of final drug product. Delays in the conduct of our trials could result in utilizing our capital resources sooner without advancing our clinical trials as anticipated.
As of December 31, 2022 we had sold 3,886 shares of our common stock for net proceeds to us totaling $4,532. During January 2023, we issued an additional 53,592 shares of company stock for aggregate net proceeds of $78,355 under the 2022 ATM facility. As of December 31, 2022, we had $20,954,069 in cash.
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).
Enrollment in the Acclaim-3 clinical trial is expected to commence by the end of the third quarter 2023.
Enrollment in the Acclaim-3 clinical trial is expected to be completed during the second half of 2024 after which we expect to commence the Phase 2 portion of the Acclaim-3 trial in the second half of 2024.
The increase of $3,494,040, or 24%, in net cash used in operating activities in 2022 was primarily due to us increasing our headcount from 15 full-time employees on December 31, 2021 to 25 full-time employees on December 31, 2022, advancing our manufacturing programs, and the launch and continuing operations of our Acclaim-1 and Acclaim-2 clinical trials.
The increase of $7,117,105, or 40%, in net cash used in operating activities in 2023 was primarily due to us advancing our manufacturing programs to support enrollment of patients in our Acclaim-1 and Acclaim-2 clinical trials in the year ended December 31, 2023 compared to December 31, 2022 when our Acclaim-1 and Acclaim-2 clinical trials were initiated but enrolling patients at the slower, safety-oriented, Phase 1 portion per their respective protocols.
There was no interest expense for the years ended December 31, 2022 and 2021 because we satisfied all debt obligations and repaid all short-term loans prior to 2019. As of December 31, 2022, we had no outstanding debt. Depreciation Expense. Depreciation expense was $25,575 and $22,534 for the years ended December 31, 2022 and 2021, respectively.
As 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 .
Removed
Using this system, plasmids containing tumor suppressor genes, which are deleted early in the development of cancer, are encapsulated within lipid nanoparticles and administered intravenously to the patient to re-express the deleted tumor suppressor genes.
Added
Our oncology platform utilizes our systemic, non-viral ONCOPREX® Delivery System which uses lipid-based nanoparticles in a lipoplex form to deliver tumor suppressor gene-expressing plasmids to cancer cells. The product is administered intravenously, where it is taken up by tumor cells that then express tumor suppressor proteins that were deficient in the tumor.
Removed
In August 2022, the Acclaim-1 Safety Review Committee (“Acclaim-1 SRC”) approved escalating the dose from 0.06 mg/kg in the first cohort of patients to 0.09 mg/kg in the second cohort of patients and in December 2022, the SRC approved escalating the dose from 0.09 mg/kg in the second cohort to 0.12 mg/kg in the third and final cohort.
Added
Following the May 2023 completion of the Phase 1 dose escalation portion of the study, the Acclaim-1 Safety Review Committee (“Acclaim-1 SRC”) approved advancement from the Phase 1 dose escalation portion to the Phase 2a expansion portion of the study.
Removed
We are thus enrolling and treating patients at the 0.12 mg/kg dose level. We expect enrollment in the dose escalation portion of the study to be completed in the next several days following the filing of this Annual Report.
Added
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.
Removed
After completion of enrollment and cycle one of treatment for the remaining untreated patients, the Acclaim-1 SRC will meet and establish the maximum tolerated dose ("MTD") or recommended Phase 2 dose ("RP2D"). We will then proceed into the dose expansion portion of the study.
Added
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.
Removed
The dose expansion portion of Acclaim-2 is a Phase 2 study and the dose expansion portion of Acclaim-1 will be considered a Phase 2 study upon the filing with the FDA of an upcoming protocol amendment.
Added
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.
Removed
We expect to dose the first patient in Acclaim-3 by the end of the third quarter of 2023. Patients will be treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced.
Added
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.
Removed
We expect to finalize our constructs and meet with the FDA before the end of 2023 to obtain their guidance on the toxicology studies that we plan to conduct.
Added
The expansion portion of both the Acclaim-1 and Acclaim-2 trials are Phase 2 studies.
Removed
Section 107 of the JOBS Act provides that an “emerging growth company” can take advantage of the extended transition period provided in Section 7(a)(2)(B) of the Securities Act for complying with new or revised accounting standards. In other words, an “emerging growth company” can delay the adoption of certain accounting standards until those standards would otherwise apply to private companies.
Added
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.
Removed
Although we are currently an emerging growth company, we have irrevocably elected not to avail ourselves of this extended transition period and, as a result, we will adopt new or revised accounting standards on the relevant dates on which adoption of such standards is required for other public companies.
Added
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.
Removed
We have implemented all new accounting pronouncements that are in effect and may affect our financial statements, and we do not believe that there are any other new accounting pronouncements that have been issued that would have a material impact on our financial position or results of operations.
Added
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.
Removed
Notwithstanding the foregoing, subject to certain conditions set forth in the JOBS Act, as an “emerging growth company,” we intend to rely on certain exemptions, including, without limitation, the exemption from the requirements (i) to provide an auditor’s attestation report on our system of internal controls over financial reporting pursuant to Section 404(b) of the Sarbanes-Oxley Act, and (ii) to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements, known as the auditor discussion and analysis.
Added
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.
Removed
We expect that our eligibility to qualify as an “emerging growth company” will end on December 31, 2023, the last day of our fiscal year following the fifth anniversary of the date of our initial public offering.

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