Core Viewpoint - Genprex, Inc. is advancing its diabetes gene therapy candidate GPX-002, which shows promise in treating both Type 1 and Type 2 diabetes, as evidenced by positive preclinical data presented at the ASGCT Annual Meeting [1][2]. Group 1: Research and Development - GPX-002 utilizes recombinant adeno-associated virus (rAAV) to deliver Pdx1 and MafA genes, converting alpha cells into beta-like cells that secrete insulin, effectively reversing diabetes in mouse models without the need for immunosuppression [2][3]. - The therapy has been tested in cynomolgus macaques with streptozotocin-induced diabetes, demonstrating improved glucose tolerance and reduced insulin requirements one month post-infusion [4][5]. - Ongoing preclinical studies are evaluating the long-term efficacy of GPX-002 after six months of immunosuppression in non-human primate models for both Type 1 and Type 2 diabetes [6]. Group 2: Presentation Details - The oral presentation at the ASGCT Annual Meeting was titled "Immune Modulation Sustains Alpha Cell Reprogramming and Mitigates Immune Responses to AAV in a Diabetic Non-Human Primate Model," presented by Dr. Hannah Rinehardt [2]. - The presentation highlighted the challenges of managing immune responses to the therapy, indicating that temporary immunosuppression can effectively prevent anti-viral immunity but may need to be extended beyond three months [4][5]. Group 3: Company Overview - Genprex, Inc. is a clinical-stage gene therapy company focused on developing innovative therapies for cancer and diabetes, utilizing advanced technologies to deliver disease-fighting genes [8]. - The company’s approach for diabetes involves a novel infusion process using an AAV vector to directly administer therapeutic genes into the pancreas, with the potential for routine endoscopic procedures in humans [7][8].

Clinical Trials - The company is currently enrolling patients in the Phase 2a expansion portion of the Acclaim-1 clinical trial, which combines REQORSA and AstraZeneca's Tagrisso for late-stage NSCLC patients [120]. - The recommended Phase 2 dose (RP2D) of REQORSA in the Acclaim-1 trial is determined to be 0.12 mg/kg, which is twice the highest dose level delivered in previous trials [120]. - The Phase 2a expansion portion of the Acclaim-1 trial is expected to enroll approximately 33 patients who have progressed on Tagrisso or Tagrisso-containing regimens [120]. - The FDA has granted Fast Track Designation for the Acclaim-1 treatment combination of REQORSA and Tagrisso in NSCLC patients [121]. - The Acclaim-3 clinical trial is currently enrolling patients using a combination of REQORSA and Genentech's Tecentriq for extensive stage small cell lung cancer (ES-SCLC) [124]. - The RP2D of REQORSA in the Acclaim-3 trial is also set at 0.12 mg/kg, based on safety data showing no dose limiting toxicities [124]. - The Acclaim-3 trial aims to enroll approximately 50 patients across 10 to 15 U.S. sites, with a primary endpoint of determining the 18-week progression-free survival rate [124]. - The Acclaim-3 clinical trial has received FDA Fast Track Designation and Orphan Drug Designation for the patient population [125]. - The company expects interim enrollment of the Phase 2a expansion portion of the Acclaim-1 trial to be completed by the end of 2025 [153]. Financial Performance - Research and development (R&D) expense for Q1 2025 was $2,539,993, a decrease of 22% from $3,274,380 in Q1 2024, primarily due to the closure of the Acclaim-2 clinical trial and a reduction in R&D staff from 15 to 9 employees [143]. - General and administrative (G&A) expense for Q1 2025 was $1,429,299, down 47% from $2,719,667 in Q1 2024, attributed to expense reduction strategies and a decrease in G&A staff from 11 to 6 employees [144]. - Net loss for Q1 2025 was $3,964,601, a reduction of 34% compared to $5,968,869 in Q1 2024, mainly due to decreased clinical and manufacturing expenses and overall staff reduction from 26 to 15 employees [147]. - As of March 31, 2025, the company had an accumulated deficit of $158,764,044, having never generated revenue from product sales since inception [148]. - In 2024, the company sold 5,366,503 shares of common stock for net proceeds of $6.3 million and completed a registered direct offering for approximately $5.8 million [149]. - During the three months ended March 31, 2025, the company sold 13,278,666 shares of common stock for gross proceeds of approximately $6.2 million, resulting in net proceeds of $6,028,103 after offering expenses [150]. - Net cash used in operating activities decreased by $1,136,466, or 21%, from $5,297,891 in Q1 2024 to $4,161,425 in Q1 2025, primarily due to the closure of the Acclaim-2 clinical trial and expense reduction strategies [156]. - Net cash provided by financing activities was $6,028,103 for the three months ended March 31, 2025, a decrease of $765,096 compared to $6,793,199 in Q1 2024 [158]. - The company had no net cash provided by or used in investing activities for the three months ended March 31, 2025, compared to a net cash outflow of $15,822 in Q1 2024 [157]. Strategic Focus - The company has entered into a sponsored research agreement with MD Anderson to support further preclinical studies of TUSC2 and other tumor suppressor genes [119]. - The company is focusing on optimizing and re-focusing its diabetes and oncology clinical development programs to enhance the likelihood of success [116]. - The company is currently developing GPX-002 for both Type 1 and Type 2 diabetes, with preclinical studies ongoing at the University of Pittsburgh [126]. - The company plans to seek further regulatory guidance from the FDA on IND-enabling studies in the second half of 2025 [126]. - A new sponsored research agreement with the University of Pittsburgh was established in May 2025 to study Type 1 and Type 2 diabetes in animal models [126]. - The company is exploring a non-viral lipid nanoparticle delivery system for multiple treatments [126]. - The company has implemented strategies to optimize clinical and research programs and is considering various strategic alternatives to enhance stockholder value [138]. - The company anticipates needing to raise additional capital to fund future operations, including ongoing clinical trials, as it does not expect to generate revenue from product sales in the near term [153]. - The company estimates it can fund its current operations and planned clinical trial activities through the end of the second quarter of 2025 [154]. - The company may seek additional capital through strategic collaborations or transactions, but there is uncertainty regarding its ability to maintain liquidity over the next 12 months [153]. - The company has utilized all available capacity under the current prospectus supplement for the 2023 ATM Facility as of the filing date of the Quarterly Report [153].

Core Viewpoint - Genprex, Inc. has announced a new Sponsored Research Agreement (SRA) with the University of Pittsburgh to further study its gene therapy GPX-002 for Type 1 and Type 2 diabetes in animal models, following the completion of a previous two-year agreement [1][2]. Company Overview - Genprex, Inc. is a clinical-stage gene therapy company focused on developing therapies for cancer and diabetes, utilizing innovative technologies to deliver disease-fighting genes [5][6]. - The company’s lead product candidate, Reqorsa® Gene Therapy, is under evaluation in clinical trials for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) [5]. Research and Development - The new SRA with the University of Pittsburgh will sponsor preclinical studies of GPX-002, which has shown promising results in reducing insulin requirements and improving glucose tolerance in animal models of diabetes [2][3]. - GPX-002 employs an adeno-associated virus (AAV) vector to deliver Pdx1 and MafA genes directly to the pancreas, aiming to transform alpha cells into functional beta-like cells in Type 1 diabetes and rejuvenate exhausted beta cells in Type 2 diabetes [3][6]. Market Context - As of 2024, approximately 38.4 million Americans have diabetes, with 10% having Type 1 diabetes and 90-95% having Type 2 diabetes. The global diabetes population is projected to rise from 537 million in 2021 to 783 million by 2045 [4]. - Diabetes caused over 6.7 million deaths globally in 2021 and resulted in approximately $966 billion in health expenditures, reflecting a significant increase over the past fifteen years [4].

Core Viewpoint - Genprex, Inc. announced positive preclinical data for Reqorsa® Gene Therapy, demonstrating its robust anti-tumor effects in KRASG12C mutant non-small cell lung cancer (NSCLC), both alone and in combination with LUMAKRAS® [1][2]. Group 1: Preclinical Data Presentation - The positive preclinical data was presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting, highlighting the therapeutic potential of REQORSA in treating Ras inhibitor resistant lung cancer [1][2]. - The poster titled "Overcoming sotorasib acquired resistance in KRASG12C mutant NSCLC by TUSC2 gene therapy" showcased that TUSC2 gene therapy effectively overcomes acquired resistance to sotorasib in mouse xenografts [3]. Group 2: Efficacy of Reqorsa - TUSC2 transfection significantly reduced colony formation and increased apoptosis in acquired resistance cell lines, indicating strong anti-tumor efficacy [3]. - REQORSA alone showed a strong anti-tumor effect on TC314AR PDXs, while sotorasib alone exhibited no significant activity [3]. - A synergistic effect was observed when combining REQORSA with sotorasib, enhancing tumor control compared to either treatment alone [3]. Group 3: Technology and Delivery System - Reqorsa consists of a plasmid containing the TUSC2 gene encapsulated in non-viral lipid-based nanoparticles, specifically targeting cancer cells while minimizing uptake by normal tissue [5]. - Laboratory studies indicated that the uptake of TUSC2 in tumor cells after REQORSA treatment was 10 to 33 times higher than in normal cells [5]. Group 4: Company Overview - Genprex, Inc. is a clinical-stage gene therapy company focused on developing therapies for cancer and diabetes, utilizing its Oncoprex® Delivery System for gene administration [6][7]. - The company is advancing its pipeline of gene therapies and has received Fast Track Designation from the FDA for its lung cancer clinical programs [7].

Core Viewpoint - Genprex, Inc. has announced the presentation of positive preclinical data for its diabetes gene therapy candidate GPX-002 at the upcoming ASGCT Annual Meeting, highlighting the potential of gene therapy as a curative treatment for diabetes [1][2]. Group 1: Research and Development - The oral presentation will focus on the immune modulation and reprogramming of alpha cells to beta-like cells in a diabetic non-human primate model, showcasing the effectiveness of the rAAV gene therapy approach [3]. - The study demonstrated that retrograde intraductal infusion of rAAV6 can convert alpha cells into insulin-secreting beta-like cells, reversing diabetes in mouse models [4]. - One month post-infusion, non-human primates exhibited improved glucose tolerance and reduced insulin requirements, indicating the therapy's durable effects [5]. Group 2: Immune Response Management - The research evaluated the immune response to direct infusion of rAAV into the pancreatic duct and how to manage potential anti-viral immunity, which can hinder gene therapy success [4][5]. - Temporary immunosuppression using a combination of rituximab, rapamycin, and steroids was largely effective in preventing anti-viral immune responses, allowing sustained therapeutic effects [6]. Group 3: Product Overview - GPX-002 is being developed for both Type 1 and Type 2 diabetes, utilizing an AAV vector to deliver Pdx1 and MafA genes directly into the pancreatic duct [7]. - In Type 1 diabetes, GPX-002 aims to transform alpha cells into functional beta-like cells, while in Type 2 diabetes, it is believed to rejuvenate exhausted beta cells [7]. Group 4: Company Background - Genprex, Inc. is a clinical-stage gene therapy company focused on developing therapies for cancer and diabetes, collaborating with leading institutions to advance its drug candidates [8].

Core Viewpoint - Genprex, Inc. has signed an exclusive patent license agreement with NYU Langone Health for Reqorsa® Gene Therapy, which is being investigated as a treatment for mesothelioma, thereby expanding its oncology portfolio and clinical development pipeline [1][2]. Company Overview - Genprex, Inc. is a clinical-stage gene therapy company focused on developing therapies for cancer and diabetes, utilizing its Oncoprex® Delivery System to administer disease-fighting genes [8][9]. - The company collaborates with leading research institutions to advance its gene therapy candidates [8]. Product Details - Reqorsa® Gene Therapy (quaratusugene ozeplasmid) is designed to deliver the TUSC2 gene to cancer cells, with studies showing a 10 to 33 times higher uptake in tumor cells compared to normal cells [7][9]. - The therapy has demonstrated significant decreases in cell proliferation and invasion, along with increased apoptosis in malignant pleural mesothelioma cell lines [4]. Research and Development - Positive preclinical data for Reqorsa was presented at the 2024 EORTC-NCI-AACR Symposium, indicating its potential effectiveness against mesothelioma [2][4]. - Genprex has established a Mesothelioma Clinical Advisory Board to support its preclinical oncology program, consisting of four renowned researchers [5]. Market Context - Mesothelioma is a rare cancer with approximately 3,000 new cases diagnosed annually in the U.S., primarily affecting the pleura, which accounts for 80-90% of cases [6]. - The life expectancy for pleural mesothelioma is around 18 months, with a 3-year survival rate of 23% for treated patients [6].

Core Viewpoint - Genprex, Inc. has been selected to present its Acclaim-3 Phase 1/2 clinical trial design for Reqorsa Gene Therapy in combination with Tecentriq at the 2025 ASCO Annual Meeting, highlighting its commitment to advancing cancer treatment options [1][2]. Company Overview - Genprex, Inc. is a clinical-stage gene therapy company focused on developing therapies for cancer and diabetes, utilizing innovative technologies to deliver disease-fighting genes [3]. - The company's lead product candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), is under evaluation for treating non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) [3]. - Genprex's oncology program employs a non-viral Oncoprex Delivery System, which uses lipid-based nanoparticles to encapsulate gene-expressing plasmids for intravenous administration [3]. Clinical Trial Details - The Acclaim-3 clinical trial will evaluate the combination of Reqorsa Gene Therapy and Tecentriq as maintenance therapy for extensive stage small cell lung cancer (ES-SCLC) [1][2]. - The trial design will be presented in a poster session on May 31, 2025, by Dr. Bo Wang [2]. Regulatory Designations - Genprex's lung cancer clinical programs have received Fast Track Designation from the FDA, and the SCLC program has also received Orphan Drug Designation [3].

Core Viewpoint - Genprex, Inc. announced the publication of positive preclinical data on its lead drug candidate, Reqorsa® Gene Therapy, for treating KRASG12C mutant non-small cell lung cancer (NSCLC) [1][2][3] Group 1: Research and Development - The abstract detailing the preclinical data was published in the online Proceedings supplement of Cancer Research [1] - The data will be presented at the 2025 AACR Annual Meeting, highlighting advances in cancer treatment [2][3] - The study demonstrated that TUSC2 gene therapy (REQORSA) effectively overcomes acquired resistance to sotorasib in KRASG12C mutant NSCLC mouse xenografts [4][5][6] Group 2: Mechanism and Efficacy - Acquired resistance to Lumakras® (sotorasib) presents a significant challenge in treating KRASG12C mutant NSCLC, necessitating alternative strategies [4] - TUSC2 gene therapy exhibits multifunctional activity, inhibiting downstream signaling pathways, inducing tumor cell death, and activating immune responses [4][5] - REQORSA alone showed significant antitumor efficacy, and a synergistic effect was observed when combined with sotorasib [5][6] Group 3: Product Information - Reqorsa® Gene Therapy consists of a plasmid containing the TUSC2 gene encapsulated in non-viral lipid-based nanoparticles [7] - The therapy is designed to specifically target cancer cells while minimizing uptake by normal tissue, with laboratory studies showing 10 to 33 times greater uptake in tumor cells compared to normal cells [8] Group 4: Company Overview - Genprex, Inc. is focused on developing gene therapies for cancer and diabetes, utilizing its Oncoprex® Delivery System [9] - The company’s lead product candidate, Reqorsa, is currently being evaluated in clinical trials for NSCLC and small cell lung cancer (SCLC) [9]

Clinical Trials and Research - The company is developing REQORSA® gene therapy for Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC), with a recommended Phase 2 dose of 0.12 mg/kg established after the Phase 1 trial [486]. - In the Phase 1 portion of the Acclaim-1 trial, one patient achieved a partial remission after 47 courses of treatment, demonstrating prolonged progression-free survival (PFS) of approximately 35 months [486]. - The Acclaim-1 trial is expected to enroll approximately 33 patients who have progressed on Tagrisso or Tagrisso-containing regimens, with an interim analysis planned after treating 19 patients [486]. - The FDA has granted Fast Track Designation for the combination of REQORSA and Tagrisso in NSCLC patients who have progressed on Tagrisso treatment [487]. - The Acclaim-3 trial is currently enrolling patients, with an expected enrollment of approximately 50 patients, focusing on the 18-week progression-free survival rate as a primary endpoint [491]. - The Acclaim-2 trial has been closed due to slow enrollment, with no patients currently receiving study treatment [490]. - The company is collaborating with MD Anderson to identify biomarkers that may enhance patient screening and enrollment for clinical trials [485]. - The company plans to complete interim enrollment of the Phase 2a expansion portion of the Acclaim-1 trial by the end of 2025 [523]. - The company may face delays in clinical trials due to various factors, including competition for patients and transitions to new third-party CDMOs [524]. Financial Performance - Research and development (R&D) expenses decreased by $7,081,159, or 40%, to $10,535,446 for the year ended December 31, 2024, compared to $17,616,605 in 2023 [509]. - General and administrative (G&A) expenses decreased by $2,793,257, or 21%, to $10,632,028 for the year ended December 31, 2024, compared to $13,425,285 in 2023 [510]. - Net loss for the fiscal year ended December 31, 2024, was $21,111,163, a decrease of $9,749,298, or 32%, from a net loss of $30,860,461 in 2023 [513]. - As of December 31, 2024, the accumulated deficit was $154,799,443, with no revenue generated from product sales since inception [515]. - Cash balance as of December 31, 2024, was $1,601,660, with subsequent net proceeds of approximately $6.0 million received through the ATM Agreement [522]. - Net cash used in operating activities decreased by $7,589,515, or 31%, from $24,738,603 in 2023 to $17,149,088 in 2024 due to expense reduction strategies [529]. - Net cash provided by investing activities changed from a net cash used of $71,214 in 2023 to a net cash provided of $1,166 in 2024, resulting in a net change of $72,380 [530]. - Net cash provided by financing activities increased by $1,418,576, or 13%, from $10,593,377 in 2023 to $12,011,953 in 2024, attributed to differences in capital raising activities [531]. - The net decrease in cash for the year ended December 31, 2024, was $5,135,969, compared to a decrease of $14,216,440 in 2023 [529]. Future Outlook and Funding - The company expects to fund operations through equity offerings, ATM drawdowns, and potential debt financing, anticipating the need for additional capital to support ongoing clinical trials [523]. - R&D expenses are expected to increase in the future as the company advances product candidates through clinical trials and expands research programs [504]. - The company anticipates needing additional fundraising activities and cash on hand by the second quarter of 2025 to meet fixed cash obligations related to clinical studies [526]. - The company expects insufficient cash to cover ongoing clinical trials and research and development programs through fiscal year 2025 without raising additional working capital [526]. - Future capital requirements will depend on various factors, including development costs, manufacturing expenses, and costs associated with being a public company [528]. - The company may need to use liquidity for acquisitions or additional capital to fund newly acquired operations, which could lead to dilution for existing security holders [527]. - The company has ongoing obligations related to the Acclaim clinical trials, which may require adjustments to its operating plan if cash is insufficient [526]. - The company reduced headcount in R&D from 16 employees at December 31, 2023, to 10 employees at December 31, 2024, as part of expense reduction strategies [509]. - The company has reduced its workforce from 28 employees at December 31, 2023, to 16 employees at December 31, 2024, as part of its expense reduction strategies [529].

Core Viewpoint - Genprex, Inc. announced positive preclinical data for its lead drug candidate, Reqorsa® Gene Therapy, targeting KRASG12C mutant non-small cell lung cancer (NSCLC), which may provide a new treatment option for patients resistant to Ras inhibitors [1][2]. Group 1: Research and Development - The upcoming presentation at the 2025 American Association for Cancer Research (AACR) Annual Meeting will showcase preclinical data on Reqorsa® Gene Therapy [1]. - The study focuses on overcoming acquired resistance to sotorasib (Lumakras®), the first FDA-approved KRAS inhibitor, in KRASG12C mutant NSCLC [3]. - TUSC2, the active component in Reqorsa, has shown multifunctional activity, including inhibiting cancer cell growth and activating immune responses [3][4]. Group 2: Clinical Efficacy - TUSC2 transfection significantly reduced colony formation and increased apoptosis in acquired resistance (AR) cell lines [4]. - Reqorsa demonstrated a strong antitumor effect in mouse xenografts and patient-derived xenograft (PDX) models, outperforming sotorasib alone [4][5]. - A synergistic effect was observed when combining Reqorsa with sotorasib in treating TC314AR PDX tumors [4]. Group 3: Product Information - Reqorsa (quaratusugene ozeplasmid) is a gene therapy that delivers the TUSC2 gene using a non-viral lipid-based nanoparticle system, specifically targeting cancer cells [6][8]. - Laboratory studies indicate that TUSC2 uptake in tumor cells is significantly higher than in normal cells, ranging from 10 to 33 times [7]. Group 4: Company Overview - Genprex, Inc. is a clinical-stage gene therapy company focused on developing therapies for cancer and diabetes, utilizing its Oncoprex® Delivery System [8]. - The company is advancing its pipeline of gene therapies and has received Fast Track Designation from the FDA for its lung cancer programs [8].