Genprex Collaborators to Present Positive Preclinical Data on Diabetes Gene Therapy at the ASGCT 28th Annual Meeting

Rhea-AI Summary

Genprex announced that its research collaborators will present positive preclinical data for their diabetes gene therapy drug candidate GPX-002 at the ASGCT 28th Annual Meeting in New Orleans this May.

The research focuses on a novel gene therapy using recombinant adeno-associated virus (rAAV) to treat diabetes mellitus. Key findings show that retrograde intraductal infusion of rAAV6 successfully delivered Pdx1 and MafA genes, converting alpha cells into insulin-secreting beta-like cells.

Testing on non-human primates demonstrated:

• Improved glucose tolerance and reduced insulin needs one month post-infusion
• Durable effects using AAV6 capsid with endocrine-specific promoters
• Successful immune response management using temporary immunosuppression
• Sustained therapeutic effects even after stopping immunosuppression

The research represents a potential breakthrough in diabetes treatment, with results showing sustained therapeutic effects without long-term immunosuppression requirements.

Positive

• Positive preclinical data for GPX-002 diabetes gene therapy showing improved glucose tolerance in non-human primates
• Selection to present at ASGCT's Annual Meeting validates the diabetes program's potential
• Demonstrated durable therapeutic effects using AAV6 capsid with endocrine-specific promoters
• Successful immune response management achieved through temporary immunosuppression
• Sustained therapeutic effects observed even after discontinuation of immunosuppression

Negative

• Still in preclinical stage, indicating long pathway to potential commercialization
• Requires immunosuppression therapy for effectiveness, which could limit patient eligibility
• Potential immune response challenges to AAV delivery system

Novel Gene Therapy Program Offers a Promising Opportunity for Curative Therapy in Diabetes

AUSTIN, Texas, April 29, 2025 /PRNewswire/ -- Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, today announced that its research collaborators have been selected to present at the upcoming American Society of Gene and Cell Therapy's (ASGCT) 28^th Annual Meeting being held May 13-17, 2025 in New Orleans, Louisiana. The collaborators will present positive preclinical data and research from studies of GPX-002, the Company's diabetes gene therapy drug candidate.

"We are proud of the preclinical data supporting our novel gene therapy program for diabetes, and we believe selection to present our program at one of the premier events in cell and gene therapy provides another point of validation for our diabetes program," said Ryan Confer, President and Chief Executive Officer at Genprex. "We look forward to sharing our GPX-002 data with industry leaders engaged in advancing the latest scientific research and new technologies."

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

The featured Genprex-supported abstract to be presented for oral presentation at the ASGCT 28^th Annual Meeting:

Gene therapy using recombinant adeno-associated virus (rAAV) offers a promising opportunity for curative therapy in diabetes mellitus. Retrograde intraductal infusion of rAAV6 to deliver Pdx1 and MafA, converting alpha cells into beta-like cells that secrete insulin physiologically, reverses diabetes in mouse models. Little is known about the direct infusion of AAV into the pancreatic duct for gene therapy in non-human primates (NHPs). In clinical trials, anti-viral immunity to AAV can be a barrier to successful gene therapy. Researchers evaluated the immune response to direct infusion of rAAV into the pancreatic duct of NHPs with streptozotocin-induced diabetes and evaluated how to best manage immune responses.

Diabetes was induced with streptozotocin (STZ) in cynomolgus macaques. 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.

One-month post-infusion, NHPs showed improved glucose tolerance and reduced insulin requirements. The AAV6 capsid with endocrine-specific promoters driving Pdx1 and MafA showed durable effects. ELISpot-positive cytotoxic T cells and neutralizing antibodies developed when steroids were absent. With steroid-sparing regimens, 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. Despite complete IS discontinuation at 3 months post-infusion, meaningful anti-viral immune response was not mounted up to one month after IS withdrawal as evidenced by low NAb titers and negative ELISpot analysis. Additionally, rAAV gene therapy in these animals remained effective and glucose tolerance continued improving in the absence of immunosuppression.

In conclusion, researchers developed a novel rAAV gene therapy approach and demonstrated that infusion of rAAV directly into the pancreatic duct of NHPs induces an anti-viral immune response. The anti-viral immune response in NHPs can be largely prevented by administration of a multi-agent IS and can allow for sustained therapeutic effects.

About GPX-002
GPX-002, which has been exclusively licensed from the University of Pittsburgh, is currently being developed using the same construct for the treatment of both Type 1 diabetes (T1D) and Type 2 diabetes (T2D). The same general novel approach is used in each of T1D and T2D 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. In T1D, GPX-002 is designed to work by transforming alpha cells in the pancreas into functional beta-like cells, which can produce insulin but may be distinct enough from beta cells to evade the body's immune system. In vivo, preclinical studies show that GPX-002 restored normal blood glucose levels for an extended period of time in T1D mouse models. In T2D, where autoimmunity is not at play, GPX-002 is believed to rejuvenate and replenish exhausted beta cells.

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.

Interested investors and shareholders are encouraged to sign up for press releases and industry updates by visiting the Company Website, registering for Email Alerts and by following Genprex on Twitter, Facebook and LinkedIn.

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, 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.

These forward-looking statements should not be relied upon as predictions of future events and Genprex cannot assure you that the events or circumstances discussed or reflected in these statements will be achieved or will occur. If such forward-looking statements prove to be inaccurate, the inaccuracy may be material. You should not regard these statements as a representation or warranty by Genprex or any other person that Genprex will achieve its objectives and plans in any specified timeframe, or at all. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Genprex disclaims any obligation to publicly update or release any revisions to these forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release or to reflect the occurrence of unanticipated events, except as required by law.

Genprex, Inc.
(877) 774-GNPX (4679)

GNPX Investor Relations
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FAQ

What are the key findings of Genprex (GNPX) diabetes gene therapy presented at ASGCT 2025?

The preclinical data shows improved glucose tolerance and reduced insulin requirements in non-human primates one month after treatment with GPX-002. The therapy demonstrated durable effects using AAV6 capsid with endocrine-specific promoters driving Pdx1 and MafA genes.

How does Genprex (GNPX) GPX-002 gene therapy work for diabetes treatment?

GPX-002 uses recombinant adeno-associated virus (rAAV) delivered through retrograde intraductal infusion to convert alpha cells into beta-like cells that secrete insulin physiologically, potentially offering a curative therapy for diabetes.

When will Genprex (GNPX) present their diabetes gene therapy data at ASGCT 2025?

The presentation will be given by Dr. Hannah Rinehardt from University of Pittsburgh Medical Center on May 16, 2025, at 4:15 PM CT in Room 278-282 during the 'Challenges in Immunological Responses to Therapeutic Interventions' session.

What are the immunosuppression results for Genprex (GNPX) diabetes gene therapy?

A 3-month combination therapy of rituximab, rapamycin, and steroids effectively prevented anti-viral immunity. After discontinuing immunosuppression, the therapy remained effective with continued glucose tolerance improvement and low immune response.

How long do the effects of Genprex (GNPX) GPX-002 diabetes treatment last?

The preclinical data shows that the therapeutic effects were durable and continued improving even after stopping immunosuppression at 3 months, with sustained benefits observed up to 4 months post-infusion in non-human primates.