DEFA14A: Genprex Advances Gene Therapies for Cancer & Diabetes

Genprex, Inc. reports significant progress in its oncology and diabetes gene therapy programs, including clinical trial advancements and intellectual property expansion, with key milestones expected in 2026.

Summary

• Achieved several key milestones in early 2025 across oncology and diabetes programs.
• Oncology program re-focused to expedite regulatory submissions for Reqorsa Gene Therapy (quaratusugene ozeplasmid), which holds FDA Fast Track Designation for both Acclaim-1 and Acclaim-3 indications, and Orphan Drug Designation for small cell lung cancer (SCLC).
• Acclaim-1 (late-stage non-small cell lung cancer with EGFR mutations): Currently enrolling and treating patients in Phase 2a expansion; Phase 1 showed Reqorsa was generally well tolerated with no dose limiting toxicities and early signs of efficacy, including prolonged progression-free survival and one partial response.
• Expect to complete Phase 2a expansion enrollment for interim analysis (19 patients) by the end of the first quarter of 2026 and report interim analysis in the first half of 2026.
• Acclaim-3 (extensive stage SCLC): Currently enrolling and treating patients in Phase 2 expansion; Phase 1 showed Reqorsa was generally well tolerated.
• Expect to complete enrollment of the first 25 patients for interim analysis in the Phase 2 expansion portion by the first quarter of 2026.
• Collaborating with MD Anderson Cancer Center to discover and utilize biomarkers to select patient populations most likely to respond to Reqorsa.
• Presented positive preclinical data for Reqorsa at the 2025 AACR annual meeting, demonstrating its effectiveness in overcoming sotorasib acquired resistance in KRASG12C mutant NSCLC mouse xenografts.
• Presented the Acclaim-3 clinical trial design at the 2025 ASCO Annual Meeting.
• Expanded intellectual property portfolio for Reqorsa with exclusive license agreements for potential treatment of mesothelioma (New York University Langone Health) and glioblastoma (UTHealth Houston).
• Signed a Sponsored Research Agreement (SRA) and an exclusive license agreement with the University of Michigan Rogel Cancer Center for Reqorsa in ALK-EML4 positive (ALK+) translocated lung cancer.
• Researching Reqorsa as a single agent drug, with positive preclinical data presented at the 2024 SITC Meeting showing increased immune response against tumors.
• Diabetes program (GPX-002) is being developed for both Type 1 and Type 2 diabetes, designed to transform alpha cells into functional beta-like cells (T1D) and rejuvenate exhausted beta cells (T2D).
• Preclinical studies show GPX-002 restored normal blood glucose levels for an extended period in T1D mouse models.
• Plan to seek FDA guidance on Investigational New Drug (IND)-enabling studies for GPX-002 in the second half of 2025.
• Advancing the diabetes program by researching a non-viral lipid nanoparticle delivery system for GPX-002, which could allow for re-dosing.
• Signed a new exclusive license agreement with the University of Pittsburgh (Pitt) for the diabetes gene therapy program, consolidating prior agreements.
• Signed a new SRA with Pitt to study GPX-002 in T1D and T2D in non-human primate (NHP) models.
• Formed Convergen Biotech, Inc., a wholly-owned subsidiary, to facilitate the separation of the diabetes program from the oncology program, aiming to enhance each program and potentially expedite clinical development.
• Successfully completed technology transfer of GPX-002 manufacturing process from Pitt to commercial CDMOs, enabling cGMP-compliant clinical scale production and accelerating manufacturing.
• Research collaborators presented positive preclinical data for GPX-002 at the 2025 ASGCT Annual Meeting, showing improved glucose tolerance and reduced insulin requirements in diabetic NHPs with immunosuppression.
• Collaborators presented positive preclinical data on GPX-002 at the 2025 American Diabetes Association's 85th Scientific Sessions, including proof-of-concept for a non-viral LNP delivery system and demonstration of alpha cell transdifferentiation to beta-like cells in NHPs.

Sentiment

Score: 8

Explanation: The filing presents a highly positive outlook, detailing significant progress in both oncology and diabetes programs, including promising clinical and preclinical data, expansion of intellectual property, strategic collaborations, and manufacturing advancements. The tone is confident and forward-looking, emphasizing value creation and a robust pipeline.

Positives

• Reqorsa Gene Therapy has FDA Fast Track Designation for both Acclaim-1 and Acclaim-3 indications, and Orphan Drug Designation for SCLC, indicating expedited development pathways.
• Acclaim-1 Phase 1 trial showed Reqorsa was generally well tolerated with no dose limiting toxicities and early signs of efficacy, including prolonged progression-free survival and one patient achieving a partial response.
• Positive preclinical data for Reqorsa demonstrated its ability to overcome sotorasib acquired resistance in KRASG12C mutant NSCLC, addressing a significant challenge in cancer treatment.
• Expanded intellectual property portfolio for Reqorsa through new exclusive license agreements for potential treatments in mesothelioma and glioblastoma, broadening its therapeutic scope.
• Secured new SRA and exclusive license for Reqorsa in ALK-EML4 positive lung cancer, further strengthening its position in targeted oncology.
• Positive preclinical data for Reqorsa as a single agent showed increased immune response against tumors, suggesting broader therapeutic potential.
• GPX-002 preclinical studies demonstrated restoration of normal blood glucose levels for an extended period in Type 1 diabetes mouse models.
• Successful technology transfer of GPX-002 manufacturing process to commercial CDMOs enables cGMP-compliant clinical scale production and accelerates manufacturing timelines.
• Positive preclinical data for GPX-002 in non-human primates showed improved glucose tolerance, reduced insulin requirements, and successful transdifferentiation of alpha cells to beta-like cells, with sustained glucose control.
• Initiation of research into a non-viral lipid nanoparticle delivery system for GPX-002 offers the significant benefit of potential re-dosing for patients.
• Formation of Convergen Biotech, Inc., a wholly-owned subsidiary, is expected to enhance and expedite the development of the diabetes program by allowing focused strategies and potentially attracting direct investment.

Risks

• Ability to advance the clinical development, manufacturing, and commercialization of product candidates in accordance with projected timelines and specifications.
• Timing and success of clinical trials, intended regulatory submissions, and any resulting regulatory approvals.
• Effectiveness of product candidates, alone and in combination with other therapies, on cancer and diabetes.
• Future growth and financial status, including ability to maintain compliance with Nasdaq listing requirements and to continue as a going concern.
• Ability to obtain capital to meet long-term liquidity needs on acceptable terms, or at all.
• Performance and scalability of commercial and strategic partnerships, including those with third-party vendors, suppliers, and manufacturers.
• Intellectual property and licenses, including their enforceability and scope.
• Current expectations, estimates, forecasts, and projections about the industry and markets in which the company operates may not be accurate.
• Actual results may differ materially from forward-looking statements due to inherent risks and uncertainties.

Future Outlook

Genprex is dedicated to transforming the lives of patients battling cancer and diabetes through pioneering gene therapies, believing in their innovative approaches to reintroduce tumor suppressor genes and revitalize insulin-producing cells. With multiple FDA Fast Track Designations and promising clinical trial results, the company positions itself at the forefront of medical advancements. Key milestones are anticipated in the second half of 2025 and beyond, including completing enrollment for Acclaim-1 and Acclaim-3 interim analyses by Q1 2026, reporting Acclaim-1 interim analysis in H1 2026, and seeking FDA guidance on IND-enabling studies for GPX-002 in H2 2025. The company expresses confidence in its technology achievements and believes it is at a momentous inflection point for achieving potentially value-creating milestones.

Management Comments

• I am extremely proud of the entire Genprex team as we have worked tirelessly to advance our pipeline assets in oncology and diabetes.
• I am enthusiastic about our future as we continue to advance our clinical development program while maintaining streamlined, focused strategies that are important to build value across the entire company.
• We continue to evaluate ways to optimize our clinical and research programs and operational strategies, as part of our ongoing prioritization initiative.
• Additionally, we are considering various strategic alternatives and opportunities to enhance stockholder value.
• Importantly, we remain focused on our mission, which guides, inspires and fuels everything that we do.
• I am proud of the fact that our team is off to such a strong start in 2025 by achieving several key milestones so far this year.
• We believe the expansion portion of this study will provide early insight into drug effectiveness and increase the likelihood of a successful randomized Phase 2b trial, which will follow the expansion portion study.
• We believe this research and collaboration position us as a leader in gene therapy and within the diabetes market.
• We believe this intended separation once complete will allow for the enhancement of each program by focusing on the needs of their respective markets and patients.
• We also believe this separation could expedite clinical development and enable greater opportunity for direct investment and strategic collaboration into the diabetes program.
• We believe we are the first and only company to be doing this type of research in the pancreatic duct using an LNP in place of a viral AAV construct.
• This research provides the proof of concept needed to move forward with additional studies, and it opens the door for a future second generation approach that would allow multiple dosing of patients.
• We have never had a time in our Company history where we have had such a robust pipeline.
• I am confident in the technology achievement we’ve made to date, and I believe we are at a momentous inflection point for Genprex as we execute our strategic plans for the company and achieve potentially value-creating milestones ahead of us.
• I am excited for Genprex’s future. I look forward to sharing our future success together.

Industry Context

The company operates in the cutting-edge fields of gene therapy for oncology and diabetes. Its focus on reintroducing tumor suppressor genes for cancer and revitalizing insulin-producing cells for diabetes aligns with broader industry trends seeking novel, targeted therapies for difficult-to-treat diseases. The exploration of non-viral delivery systems (lipid nanoparticles) for gene therapy is a significant trend aimed at overcoming limitations of viral vectors, such as immunogenicity and re-dosing challenges, positioning the company at the forefront of this innovation. Collaborations with major academic institutions like MD Anderson, NYU Langone Health, UTHealth Houston, University of Michigan, and University of Pittsburgh are common strategies in biotech for leveraging specialized research and accelerating drug development.

Comparison to Industry Standards

• Reqorsa's FDA Fast Track Designation for NSCLC and SCLC, and Orphan Drug Designation for SCLC, indicate recognition of unmet medical need, a common pathway for expedited development in the oncology space, similar to strategies employed by other biotech firms.
• The use of combination therapies (Reqorsa with Tagrisso or Tecentriq) is a standard approach in oncology to improve efficacy and overcome resistance, mirroring strategies employed by major pharmaceutical companies like AstraZeneca and Genentech (Roche).
• The preclinical data showing Reqorsa overcoming sotorasib acquired resistance in KRASG12C mutant NSCLC is significant, as acquired resistance is a major challenge in targeted cancer therapies, a problem many oncology companies are actively trying to solve.
• The development of GPX-002 for Type 1 and Type 2 diabetes, particularly the approach of transforming alpha cells into insulin-producing beta-like cells, represents a novel gene therapy strategy in diabetes, distinct from traditional insulin or GLP-1 based treatments offered by companies like Novo Nordisk or Eli Lilly.
• The exploration of non-viral lipid nanoparticle delivery systems for gene therapy, as opposed to traditional viral vectors (like AAV), positions the company alongside leading gene therapy developers who are also exploring next-generation delivery methods to improve safety, efficacy, and re-dosing potential.

Corporate Governance

Stakeholder Impact

• Shareholders: Potential for enhanced stockholder value through strategic alternatives, clinical development advancements, and achievement of value-creating milestones. Continued interest and support are recognized.
• Patients (Cancer & Diabetes): Development of pioneering gene therapies (Reqorsa and GPX-002) aimed at transforming lives, bringing hope, and improved outcomes for those battling cancer and diabetes.
• Employees: The entire team is recognized for working tirelessly to advance pipeline assets, indicating a dedicated and productive workforce.
• Academic Partners: Strong and ongoing collaborations with leading academic institutions (e.g., MD Anderson, NYU, UTHealth Houston, University of Michigan, University of Pittsburgh, Meharry Medical College) are crucial for research and development.
• CDMOs/Vendors: Successful technology transfer and ongoing strategic collaborations with contract development and manufacturing organizations and other vendors are vital for manufacturing and research.

Next Steps

• Complete Phase 2a expansion enrollment for Acclaim-1 interim analysis (19 patients) by the end of the first quarter of 2026.
• Report on Acclaim-1 interim analysis in the first half of 2026.
• Complete enrollment of the first 25 patients for interim analysis in the Phase 2 expansion portion of the Acclaim-3 study by the first quarter of 2026.
• Conduct a randomized Phase 2b trial for Acclaim-1 following the expansion portion study.
• Continue preclinical studies of GPX-002 in non-human primate models of both Type 1 and Type 2 diabetes to generate additional data.
• Seek FDA guidance for preclinical studies needed to file an Investigational New Drug (IND) application for GPX-002 in the second half of 2025.
• Initiate first-in-human studies for GPX-002.
• Further evaluate in vivo anti-tumor efficacy of REQORSA in malignant gliomas using mouse models.
• Continue exploring how REQORSA may be beneficial for patients with specific types of lung cancer, other cancers, and other diseases through strong partnerships with academic institutions and preclinical programs.
• Execute strategic plans for the company and achieve potentially value-creating milestones.

Key Dates

Recommendation

The filing details substantial progress across Genprex's oncology and diabetes gene therapy pipelines, including positive early clinical and preclinical data, multiple FDA designations (Fast Track, Orphan Drug), significant intellectual property expansion, and strategic moves like the formation of a subsidiary to optimize the diabetes program. The successful technology transfer for GPX-002 manufacturing is a critical de-risking step. The company is advancing towards key clinical milestones and IND filings, indicating a robust pipeline and potential for significant value creation. The exploration of non-viral delivery systems also positions the company at the forefront of gene therapy innovation. These developments suggest strong future potential for the company's therapeutic candidates, making it an attractive investment.

Keywords

Gene Therapy, Oncology, Diabetes, Lung Cancer, NSCLC, SCLC, Mesothelioma, Glioblastoma, Reqorsa, GPX-002, Clinical Trials, FDA Fast Track, Orphan Drug, Biomarkers, Preclinical Data, Intellectual Property, Biopharmaceutical, Biotechnology, Drug Development