Genprex Collaborators Present Positive Preclinical Data on Diabetes Gene Therapy at the ASGCT 28th Annual Meeting
- Successful demonstration of improved glucose tolerance and reduced insulin requirements in NHP trials
- Therapy shows potential as a curative treatment for both Type 1 and Type 2 diabetes
- Effective immunosuppression protocol identified to prevent anti-viral immunity
- Longer immunosuppression may be required than initially planned (beyond 3 months)
- Anti-viral immune response can degrade improvement in glucose tolerance
- Still in preclinical stage, requiring more studies before human trials
Insights
Genprex's gene therapy shows promising results in diabetes primate models, though immunosuppression challenges remain before human trials.
Genprex's diabetes gene therapy candidate, GPX-002, is showing promising preclinical results in non-human primates (NHPs). The therapy uses a novel approach involving adeno-associated virus (rAAV) to deliver Pdx1 and MafA genes directly into the pancreatic duct, effectively converting alpha cells into insulin-secreting beta-like cells. This represents a potentially transformative approach to diabetes treatment.
The data presented at the ASGCT meeting demonstrates that one month after treatment, the NHPs showed improved glucose tolerance and reduced insulin requirements - key metrics for diabetes therapy efficacy. The most significant scientific challenge identified in the study involves managing the immune response. While the therapy shows efficacy, researchers found that a three-month immunosuppression regimen (combining rituximab, rapamycin, and steroids) was insufficient, as discontinuation led to anti-viral immune responses that degraded therapeutic benefits.
What's particularly noteworthy is that this approach targets both Type 1 and Type 2 diabetes, potentially addressing a massive patient population. The research remains firmly in the preclinical stage with ongoing studies examining viral efficacy after a longer six-month immunosuppression period. The immunosuppression requirement presents a significant translational hurdle that must be overcome before human trials, as long-term immunosuppression carries substantial risks. The need for direct pancreatic duct infusion via laparotomy (surgical incision) also presents procedural complexity that could limit clinical application if not simplified.
While these results demonstrate proof-of-concept in primates - a critical step beyond previous mouse models - Genprex still faces a lengthy development pathway before potential FDA submission, with no human trial timeline yet announced.
Novel Gene Therapy is Addressing Both Type 1 and Type 2 Diabetes
"We are pleased with the preclinical studies evaluating our novel gene therapy in diabetes, and we are proud to have been selected to present this data before an audience of innovators in cell and gene therapy," said Ryan Confer, President and Chief Executive Officer at Genprex. "We believe GPX-002 offers a promising opportunity for curative therapy in diabetes, which could impact the millions of patients suffering from this debilitating disease."
The oral presentation details for the Genprex-supported abstract:
Abstract Title: Immune Modulation Sustains Alpha Cell Reprogramming and Mitigates Immune Responses to AAV in a Diabetic Non-Human Primate Model
Session Title: Challenges in Immunological Responses to Therapeutic Interventions
Presenter: Hannah Rinehardt, MD, University of Pittsburgh Medical Center
Presentation Date: May 16, 2025
Presentation Time: 4:15 – 4:30 p.m. CT
Location: Room 278-282
In the oral presentation, Dr. Rinehardt discussed GPX-002, the diabetes gene therapy, which uses intraductal infusion of recombinant adeno-associated virus (rAAV) to deliver the Pdx1 and MafA genes. The gene therapy converts alpha cells into beta-like cells that secrete insulin physiologically, reversing diabetes in mouse models, where immunosuppression was not necessary. Researchers evaluated the immune response to direct infusion of rAAV into the pancreatic duct of Non-Human Primates (NHPs) with streptozotocin-induced diabetes and evaluated how to best manage immune responses.
Diabetes was induced with streptozotocin (STZ) in cynomolgus macaques, a type of NHP. NHPs received retrograde intraductal infusion of rAAV via laparotomy for precise delivery to the pancreas. rAAV capsids were chosen based on tropism for endocrine cells, and pre-existing neutralizing antibody titers (NAbs) were negative. Blood work, including serum C peptide and IV glucose tolerance tests, were serially obtained to monitor therapeutic efficacy. Immune response monitoring was performed for up to 4 months post-infusion and included serial NAbs, ELISpot assays, and immunophenotyping. Pancreatic tissues were analyzed using IHC and RNA-scope for beta cell markers, as well as single-cell RNA transcriptomics.
Expression of viral proteins occurs for a limited period of time after rAAV infection, since the infection doesn't produce new AAV virus. One-month post-infusion, NHPs showed improved glucose tolerance and reduced insulin requirements. In the following months, using steroid-sparing regimens, increases in pancreatic B and T lymphocyte populations were noted on scRNA sequencing. Temporary immunosuppression (IS), using a combination of rituximab, rapamycin, and steroids for a 3-month course is largely effective at preventing anti-viral immunity. However, discontinuation of IS at 3 months post-infusion led to an immune response afterwards, indicating that IS in NHPs may need to be continued longer.
In conclusion, the novel rAAV gene therapy demonstrated that infusion of rAAV directly into the pancreatic duct of NHPs improves glucose tolerance but induces an anti-viral immune response which can degrade the improvement in glucose tolerance. The anti-viral immune response in NHPs can be largely prevented by administration of a multi-agent IS that leads to sustained therapeutic effects.
Researchers are continuing preclinical studies of GPX-002 therapy in NHP models of both Type 1 and Type 2 diabetes to generate additional data, and present studies are evaluating viral efficacy after six months of immunosuppression.
For more in-depth preclinical data supporting GPX-002, please review Genprex's Corporate Presentation.
About GPX-002
GPX-002, which has been exclusively licensed from the University of
About Genprex, Inc.
Genprex, Inc. is a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes. Genprex's 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. Genprex works with world-class institutions and collaborators to develop drug candidates to further its pipeline of gene therapies in order to provide novel treatment approaches. Genprex's oncology program utilizes its systemic, non-viral Oncoprex® Delivery System which encapsulates the gene-expressing plasmids using lipid-based nanoparticles in a lipoplex form. The resultant product is administered intravenously, where it is taken up by tumor cells that then express tumor suppressor proteins that were deficient in the tumor. The Company's lead product candidate, Reqorsa® Gene Therapy (quaratusugene ozeplasmid), is being evaluated in two clinical trials as a treatment for NSCLC and SCLC. Each of Genprex's lung cancer clinical programs has received a Fast Track Designation from the FDA for the treatment of that patient population, and Genprex's SCLC program has received an FDA Orphan Drug Designation. Genprex's diabetes gene therapy approach is comprised of a novel infusion process that uses an AAV vector to deliver Pdx1 and MafA genes directly to the pancreas. In models of Type 1 diabetes, GPX-002 transforms alpha cells in the pancreas into functional beta-like cells, which can produce insulin but may be distinct enough from beta cells to evade the body's immune system. In a similar approach for Type 2 diabetes, where autoimmunity is not at play, GPX-002 is believed to rejuvenate and replenish exhausted beta cells.
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Cautionary Language Concerning Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are made on the basis of the current beliefs, expectations and assumptions of management, are not guarantees of performance and are subject to significant risks and uncertainty. These forward-looking statements should, therefore, be considered in light of various important factors, including those set forth in Genprex's reports that it files from time to time with the Securities and Exchange Commission and which you should review, including those statements under "Item 1A – Risk Factors" in Genprex's Annual Report on Form 10-K for the year ended December 31, 2024.
Because forward-looking statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Genprex's ability to advance the clinical development, manufacturing and commercialization of its product candidates in accordance with projected timelines and specifications; the timing and success of Genprex's clinical trials and regulatory approvals, including but not limited to, the Company's beliefs about the anticipated effects of GPX-002 and its potential as a therapeutic approach; the effect of Genprex's product candidates, alone and in combination with other therapies, on cancer and diabetes; the effects of any strategic research and development prioritization initiatives, and any other strategic alternatives or other efforts that Genprex takes or may take in the future that are aimed at optimizing and re-focusing Genprex's diabetes, oncology and/or other clinical development programs including prioritization of resources, and the extent to which Genprex is able to implement such efforts and initiatives successfully to achieve the desired and intended results thereof; Genprex's future growth and financial status, including Genprex's ability to maintain compliance with the continued listing requirements of The Nasdaq Capital Market and to continue as a going concern and to obtain capital to meet its long-term liquidity needs on acceptable terms, or at all; Genprex's commercial and strategic partnerships, including those with its third party vendors, suppliers and manufacturers and their ability to successfully perform and scale up the manufacture of its product candidates; and Genprex's intellectual property and licenses.
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