Table of Contents As filed with the Securities and Exchange Commission on November 26, 2025 Registration No. 333-291722 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Amendment No. 1 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 GENPREX, INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) Delaware 2834 90-0772347 (Primary Standard Industrial Classification Code Number) (I.R.S. Employer Identifi ...

Core Viewpoint - Genprex, Inc. announced the publication of data from its Acclaim-1 Phase 1 clinical trial of Reqorsa Gene Therapy in combination with Tagrisso for advanced non-small cell lung cancer, highlighting promising safety and early efficacy results [1][2][3]. Group 1: Clinical Trial Details - The Acclaim-1 trial is an open-label, multi-center Phase 1/2 study evaluating Reqorsa in combination with osimertinib in patients with late-stage NSCLC who have progressed after osimertinib treatment [2][3]. - The trial's dose escalation portion primarily assessed safety, establishing a Recommended Phase 2 Dose (RP2D) of 0.12 mg/kg with no Dose Limiting Toxicities (DLTs) reported [3][8]. Group 2: Patient Outcomes - Among the 12 patients treated, three experienced prolonged time to progression, including one with a continuing partial response after 47 cycles over 32 months [4][5]. - Specific patient outcomes included one patient achieving partial remission after extensive prior treatments and continuing treatment for over three years [5][6]. Group 3: Safety Profile - Reqorsa administration was generally well tolerated, with no DLTs and manageable infusion-related reactions similar to those seen with antibody treatments [8][10]. - Symptoms from infusion-related reactions were effectively managed with prophylactic medications [8]. Group 4: Company Overview - Genprex, Inc. focuses on developing gene therapies for cancer and diabetes, utilizing a non-viral Oncoprex Delivery System to administer disease-fighting genes [9][10]. - The company's lead product, Reqorsa, is under evaluation for NSCLC and small cell lung cancer (SCLC), with both programs receiving Fast Track Designation from the FDA [10].

Table of Contents As filed with the Securities and Exchange Commission on November 21, 2025 Registration No. 333- (State or other jurisdiction of incorporation or organization) (Primary Standard Industrial Classification Code Number) Delaware 2834 90-0772347 (I.R.S. Employer Identification Number) UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 GENPREX, INC. (Exact name of registrant as specified in its charter) Copies ...

Core Insights - Genprex, Inc. has added Gabrail Cancer Center in Canton, Ohio, as a new clinical trial site for its Acclaim-1 and Acclaim-3 clinical trials studying Reqorsa® Gene Therapy for lung cancer [1][2] - The company aims to expand its reach and expedite patient enrollment in these trials, which have received FDA Fast Track Designation [1][4] Acclaim-1 Clinical Trial - Acclaim-1 is a Phase 1/2 clinical trial evaluating the combination of Reqorsa and AstraZeneca's Tagrisso® for late-stage non-small cell lung cancer (NSCLC) patients with activating EGFR mutations [2][4] - The Phase 1 portion showed that Reqorsa was well tolerated with no dose-limiting toxicities, and early signs of efficacy were observed [3][4] - The trial plans to enroll approximately 33 patients, with an interim analysis expected after treating 19 patients, anticipated to be completed in the first half of 2026 [4] Acclaim-3 Clinical Trial - Acclaim-3 is a Phase 1/2 clinical trial evaluating the combination of Reqorsa and Genentech's Tecentriq® as maintenance therapy for extensive stage small cell lung cancer (ES-SCLC) [5][7] - The Phase 2 expansion is expected to enroll around 50 patients, with the primary endpoint being the 18-week progression-free survival rate [7] - An interim analysis will be conducted after the 25th patient reaches 18 weeks of follow-up, with completion of enrollment for this analysis also expected in the first half of 2026 [7] Company Overview - Genprex, Inc. is focused on developing gene therapies for cancer and diabetes, utilizing its Oncoprex® Delivery System to administer disease-fighting genes [8][9] - The company's lead product candidate, Reqorsa, is being evaluated in two clinical trials for NSCLC and SCLC, both of which have received FDA Fast Track Designation [9]

Core Insights - Premarket trading is showing notable activity with significant price movements indicating potential trading opportunities before the market opens [1] Premarket Gainers - Olema Pharmaceuticals, Inc. (OLMA) has seen a substantial increase of 213%, trading at $26.68 - Diginex Limited (DGNX) is up 12%, currently priced at $15.25 - Gorilla Technology Group Inc. (GRRR) has risen by 11%, trading at $14.05 - Amer Sports, Inc. (AS) is up 9%, priced at $33.47 - Click Holdings Limited (CLIK) has increased by 9%, trading at $7.38 - Beamr Imaging Ltd. (BMR) is up 9%, currently at $2.14 - James Hardie Industries plc (JHX) has risen by 8%, trading at $18.22 - Arvinas, Inc. (ARVN) is up 8%, priced at $12.00 - Axalta Coating Systems Ltd. (AXTA) has increased by 7%, trading at $30.28 - Genprex, Inc. (GNPX) is up 6%, currently at $4.31 [3] Premarket Losers - LifeMD, Inc. (LFMD) has decreased by 22%, trading at $3.65 - Alpha Technology Group Limited (ATGL) is down 21%, currently priced at $17.00 - Intellinetics, Inc. (INLX) has fallen by 19%, trading at $7.25 - Energizer Holdings, Inc. (ENR) is down 16%, priced at $20.00 - Invivyd, Inc. (IVVD) has decreased by 14%, currently at $2.42 - BellRing Brands, Inc. (BRBR) is down 12%, trading at $22.30 - Sadot Group Inc. (SDOT) has fallen by 9%, currently priced at $3.99 - CEVA, Inc. (CEVA) is down 8%, trading at $21.60 - Helmerich & Payne, Inc. (HP) has decreased by 7%, currently at $25.44 - Opendoor Technologies Inc. (OPEN) is down 5%, trading at $7.39 [4]

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[145] - 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[145] - Three patients in the Phase 1 portion of the Acclaim-1 trial experienced prolonged progression-free survival (PFS), with one patient maintaining a partial remission for approximately 39 months[145] - The Acclaim-2 trial, which involved REQORSA and Merck's Keytruda, has been closed due to slow enrollment and competition for eligible patients[148] - The Phase 2 expansion portion of the Acclaim-3 trial is expected to enroll approximately 50 patients, with a primary endpoint of determining the 18-week progression-free survival rate[149] - The FDA has granted Fast Track Designation for the Acclaim-1 treatment combination of REQORSA and Tagrisso in NSCLC patients who have progressed on Tagrisso treatment[146] - The Acclaim-3 trial has also received FDA Fast Track Designation and Orphan Drug Designation for the patient population with extensive stage small cell lung cancer[150] - The company is collaborating with MD Anderson to discover and develop biomarkers to select the patient population most likely to respond to REQORSA[144] - The company has experienced delays in clinical trial enrollment due to competition for patients and disruptions caused by the COVID-19 pandemic[194] - The company expects interim enrollment for the Phase 2a expansion of the Acclaim-1 trial and the Phase 2 dose expansion of the Acclaim-3 trial to be completed in the first half of 2026[193] Research and Development - The ONCOPREX Delivery System is designed to deliver tumor suppressor genes to cancer cells, with the potential to combat multiple types of cancer[142] - The company is in early stages of discovery programs to identify other cancer candidates using the ONCOPREX Delivery System[144] - The company has licensed multiple gene therapy technologies for Type 1 and Type 2 diabetes from the University of Pittsburgh, utilizing an adeno-associated virus vector containing the Pdx1 and MafA genes[151] - GPX-002 is being developed for both Type 1 and Type 2 diabetes, with preclinical studies showing decreased insulin requirements and improved glucose tolerance in treated non-human primate models[152] - The company submitted a request to the FDA in December 2023 for guidance on nonclinical studies needed for an Investigational New Drug application, with plans to initiate research in Type 2 diabetes animal models by the end of 2025[151] - The new sponsored research agreement with the University of Pittsburgh includes a revised research plan for Type 1 and Type 2 diabetes, incorporating the latest technologies acquired in 2023[151] - The company is working on regulatory and clinical strategic planning for its diabetes gene therapy products, aiming for IND-enabling studies by the end of 2025[151] Financial Performance - An equity line of credit agreement was established with Lincoln Park Capital Fund, allowing the company to sell up to $12.5 million in common stock over 24 months, with net proceeds of approximately $2.9 million from sales in Q3 2025[153] - A reverse stock split was approved at a ratio of one-for-fifty, effective October 21, 2025, to adjust share prices[155] - The company completed two registered direct offerings in October 2025, raising approximately $2.5 million and $3.1 million in net proceeds, respectively, from the sales of common stock[156][157] - The company has filed a prospectus supplement for up to $11.495 million of common stock under the 2023 ATM Facility, selling 242,537 shares for aggregate net proceeds of $1,006,740 since October 1, 2025[158] - The company has a full valuation allowance on deferred tax assets due to a history of operating losses since inception, with cumulative net operating losses recorded from April 1, 2009, to September 30, 2025[165] - Research and development (R&D) expense for Q3 2025 was $2,192,881, a decrease of $563,200 or 20% compared to Q3 2024[176] - R&D expense for the nine months ended September 30, 2025 was $7,232,370, a decrease of $464,613 or 6% compared to the same period in 2024[177] - General and administrative (G&A) expense for Q3 2025 was $1,153,032, a decrease of $413,053 or 26% compared to Q3 2024[178] - G&A expense for the nine months ended September 30, 2025 was $4,764,617, a decrease of $4,370,608 or 48% compared to the same period in 2024[179] - Net loss for Q3 2025 was $3,799,240, a decrease of $516,747 or 12% compared to Q3 2024[184] - Net loss for the nine months ended September 30, 2025 was $12,438,742, a decrease of $4,341,960 or 26% compared to the same period in 2024[185] - As of September 30, 2025, the accumulated deficit was $167,238,185[187] - The company sold 338,811 shares of common stock for gross proceeds of approximately $7.2 million during the nine months ended September 30, 2025[189] - The company entered into an equity line of credit purchase agreement with Lincoln Park for up to $12.5 million[190] - As of September 30, 2025, the company had $1,103,315 in cash and cash equivalents[192] - The company does not expect to generate revenue from product sales until successful development and regulatory approval of its product candidates, which may take several years[193] - The company anticipates needing to raise additional capital to fund operations, including ongoing clinical trials, with uncertainty regarding its ability to maintain liquidity over the next 12 months[193] - Net cash used in operating activities decreased by $2,840,198, or 20%, from $14,053,136 in 2024 to $11,212,938 in 2025, primarily due to the closure of the Acclaim-2 trial and expense reduction strategies[196] - The company had no net cash provided by investing activities in 2025, compared to $774,645 in 2024, due to timing associated with patent prosecution costs[197] - Net cash provided by financing activities increased by $2,685,450, from $8,029,143 in 2024 to $10,714,593 in 2025, due to higher amounts raised from capital raising activities[198] - The overall headcount of the company reduced from nineteen employees in 2024 to thirteen employees in 2025, contributing to decreased operating expenses[196] - There is substantial doubt regarding the company's ability to continue as a going concern due to recurring losses and the need for additional financing[193]

Core Points - Genprex, Inc. has announced a registered direct offering of 377,780 shares of common stock at a price of $9.00 per share, with potential additional gross proceeds of up to $6.6 million from short-term warrants [1][2] - The offering is expected to close around October 29, 2025, subject to customary closing conditions [1] - H.C. Wainwright & Co. is acting as the exclusive placement agent for this offering [2] Financial Details - The gross proceeds from the offering are anticipated to be approximately $3.4 million before deducting fees and expenses [2] - The short-term warrants will allow the purchase of up to 755,560 shares at an exercise price of $8.75 per share, which will be immediately exercisable [1][2] Regulatory Information - The shares are being offered under a "shelf" registration statement that was declared effective by the SEC on June 9, 2023 [3] - The unregistered warrants and underlying shares are being offered in a private placement and have not been registered under the Securities Act [4] Company Overview - Genprex, Inc. is a clinical-stage gene therapy company focused on developing therapies for cancer and diabetes [6] - The company's lead product candidate, Reqorsa® Gene Therapy, is being evaluated in clinical trials for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) [7] - Genprex's diabetes gene therapy approach aims to transform pancreatic alpha cells into functional beta-like cells to produce insulin [7]

Core Insights - Genprex, Inc. announced positive preclinical data for Reqorsa® Gene Therapy targeting ALK-EML4 positive non-small cell lung cancer (NSCLC) [1][3][4] - The data was presented at the 2025 AACR-NCI-EORTC International Conference, highlighting the potential of Reqorsa in combination with Alectinib to improve treatment outcomes [2][3] Company Overview - Genprex is a clinical-stage gene therapy company focused on developing therapies for cancer and diabetes, utilizing innovative technologies to deliver disease-fighting genes [7][9] - The company's lead product, Reqorsa, is designed to deliver the TUSC2 gene specifically to cancer cells while minimizing effects on normal tissues [6][9] Research Findings - Preclinical studies demonstrated that Reqorsa can upregulate the tumor suppressor gene TUSC2, inducing apoptosis in ALK+ NSCLC cells, including those resistant to Alectinib [4][6] - The combination of Reqorsa and Alectinib resulted in longer survival rates in mouse models compared to control groups, supporting the potential for clinical trials in ALK-positive lung cancer [3][4] Clinical Development - Reqorsa is currently being evaluated in two clinical trials for NSCLC and small cell lung cancer (SCLC), both of which have received Fast Track Designation from the FDA [9] - The SCLC program has also received Orphan Drug Designation from the FDA, indicating its potential to address unmet medical needs [9]

Core Points - Genprex, Inc. has announced a registered direct offering of 243,622 shares of common stock at a price of $11.21 per share, with expected gross proceeds of approximately $2.7 million [1][2] - The company will also issue unregistered short-term warrants to purchase up to 487,244 shares at an exercise price of $11.00 per share, potentially adding up to $5.4 million in gross proceeds if fully exercised [1][2] - The offering is expected to close around October 24, 2025, pending customary closing conditions [1] Financial Details - The gross proceeds from the offering are estimated at $2.7 million before deducting fees and expenses [2] - If the short-term warrants are fully exercised, the additional gross proceeds could reach approximately $5.4 million [2] Regulatory Information - The shares are being offered under a "shelf" registration statement declared effective by the SEC on June 9, 2023 [3] - The unregistered warrants and underlying shares are offered in a private placement and have not been registered under the Securities Act [4] Company Overview - Genprex, Inc. is a clinical-stage gene therapy company focused on developing therapies for cancer and diabetes [6] - The company's lead product candidate, Reqorsa® Gene Therapy, is in clinical trials for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) [7] - Genprex's diabetes gene therapy approach aims to transform pancreatic alpha cells into functional beta-like cells to produce insulin [7]

Core Insights - Genprex, Inc. announced positive preclinical data for its Reqorsa® Gene Therapy, indicating its potential effectiveness in treating ALK-EML4 positive non-small cell lung cancer (NSCLC) [1][2] - The therapy demonstrated a 79% tumor shrinkage rate, outperforming alectinib, which showed a 60% reduction [7] Company Overview - Genprex is a clinical-stage gene therapy company focused on developing therapies for cancer and diabetes, utilizing its Oncoprex® Delivery System to administer gene therapies [10] - The lead product candidate, Reqorsa® Gene Therapy (quaratusugene ozeplasmid), is currently being evaluated in clinical trials for NSCLC and small cell lung cancer (SCLC) [10] Research Findings - Preclinical studies showed that Reqorsa can induce apoptosis in ALK+ NSCLC cell lines and patient-derived organoids, leading to significant tumor reduction [6][8] - The combination of Reqorsa and alectinib resulted in a 23% improved outcome compared to alectinib alone, suggesting its potential as a companion drug for advanced disease [7] Upcoming Presentations - Positive preclinical data will be presented at the 2025 AACR-NCI-EROTC International Conference on Molecular Targets and Cancer Therapeutics, highlighting the efficacy of Reqorsa in NSCLC [1][3]