Genprex’s Gene Therapy Shows Promise in Overcoming Lung Cancer Resistance—Implications for Investors

Genprex, Inc. (NASDAQ: GPA) has taken a significant step forward in its quest to combat treatment-resistant lung cancer. The company’s research collaborators recently published an abstract in the Cancer Research supplement, detailing preclinical data on Reqorsa® Gene Therapy as a potential solution to acquired resistance in KRASG12C mutant non-small cell lung cancer (NSCLC). The findings, presented at the 2025 AACR Annual Meeting, highlight Reqorsa’s ability to overcome resistance to sotorasib (Lumakras®), the first FDA-approved KRAS inhibitor. For investors, this breakthrough underscores Genprex’s potential to address a critical unmet need in oncology, with implications for clinical development and market positioning.

The Problem of Acquired Resistance in KRAS-Targeted Therapies

KRAS mutations, particularly the G12C variant, are present in approximately 13% of NSCLC cases, making it a high-priority target for drug development. Sotorasib, developed by Amgen (NASDAQ: AMGN), became the first therapy to gain FDA approval for KRASG12C-positive NSCLC in 2021. However, acquired resistance (AR) to sotorasib often emerges within months of treatment, limiting long-term efficacy. Genprex’s study directly addresses this issue, demonstrating that its TUSC2 gene therapy could restore sensitivity to sotorasib or act as a standalone treatment in resistant tumors.

Key Findings from the AACR Study

The abstract, titled “Overcoming sotorasib acquired resistance in KRASG12C mutant NSCLC by TUSC2 gene therapy,” revealed several critical insights:
1. In Vitro Efficacy: TUSC2 transfection reduced colony formation in sotorasib-resistant cell lines and increased apoptosis.
2. In Vivo Synergy: In mouse xenograft models, Reqorsa alone suppressed tumor growth in resistant tumors (H23AR and TC314AR PDX models), while combining it with sotorasib produced a synergistic antitumor effect.
3. Targeted Delivery: Genprex’s Oncoprex® Delivery System ensures TUSC2 preferentially targets cancer cells, with uptake in tumors being 10–33 times higher than in normal cells, minimizing off-target toxicity.

A Technology Advantage: The Oncoprex® Delivery System

The Oncoprex® platform, a non-viral lipid-based nanoparticle system, is central to Genprex’s competitive edge. Unlike viral vectors, which can trigger immune responses or have limited scalability, Oncoprex® leverages the negative surface charge of cancer cells to achieve precise delivery. This specificity reduces side effects and supports systemic administration, a key advantage over localized therapies.

Regulatory Momentum and Clinical Pipeline

Genprex’s lung cancer programs have already secured critical regulatory milestones:
- FDA Fast Track Designation for Reqorsa in NSCLC and small cell lung cancer (SCLC).
- Orphan Drug Designation for the SCLC program, granting market exclusivity and potential tax incentives.

The company is advancing Reqorsa through clinical trials, with the AACR data bolstering its case for combination therapy trials alongside sotorasib. Should these trials succeed, Genprex could position itself as a partner to companies like Amgen, expanding its revenue potential through licensing or co-development agreements.

Market Opportunity and Investment Considerations

The global KRAS inhibitor market is projected to grow at a CAGR of 12.3% through 2030, driven by rising NSCLC incidence and the need for effective resistance management. Genprex’s focus on genetically defined subsets (KRASG12C mutations) aligns with the trend toward precision oncology, where therapies targeting specific genetic markers command premium pricing.

Investors should note that Genprex is still in the pre-commercialization phase, with success contingent on clinical trial outcomes. However, the AACR data and FDA designations reduce execution risk, while the combination therapy approach creates a pathway to faster regulatory approval. Competitors like Mirati Therapeutics (NASDAQ: MRTX) and Turning Point Therapeutics (NASDAQ: TPTX) are also pursuing KRASG12C therapies, but Genprex’s gene therapy platform offers a unique mechanism to address resistance—a critical differentiator.

Conclusion: A High-Reward, High-Impact Play in Oncology

Genprex’s recent preclinical data marks a pivotal step toward addressing one of the most pressing challenges in lung cancer treatment: acquired resistance. The synergy observed in combination with sotorasib, coupled with the targeted delivery of TUSC2, positions Reqorsa as a potential cornerstone therapy for a subset of NSCLC patients. With FDA Fast Track status and a clear clinical path forward, Genprex is well-positioned to capitalize on a market expected to exceed $2.5 billion by 2030 (Grand View Research).

For investors, Genprex represents a high-risk, high-reward opportunity. While clinical trial outcomes remain uncertain, the AACR findings and the company’s proprietary delivery system suggest a robust scientific foundation. Should Reqorsa succeed in late-stage trials, its potential as a standalone or combination therapy could drive significant revenue growth, particularly in the lucrative precision oncology space. For now, the stock’s valuation—currently trading at $X.XX—appears undervalued relative to its addressable market and technological innovation.

Disclosure: The author holds no positions in Genprex or related companies.