Genprex’s Reqorsa Gene Therapy Shows Promise in Overcoming Cancer Drug Resistance

The fight against lung cancer just got a new weapon. Genprex, a clinical-stage gene therapy company, recently announced breakthrough preclinical data for its lead candidate, Reqorsa (quaratusugene ozeplasmid), at the 2025 American Association for Cancer Research (AACR) Annual Meeting. The therapy demonstrated remarkable efficacy in overcoming resistance to sotorasib (Lumakras®), a targeted treatment for KRASG12C-mutant non-small cell lung cancer (NSCLC). These findings, paired with ongoing clinical trials, position Reqorsa as a potential game-changer in oncology.

Preclinical Breakthrough: Overcoming Drug Resistance

The AACR study, titled “Overcoming sotorasib acquired resistance in KRASG12C mutant NSCLC by TUSC2 gene therapy,” tested Reqorsa in models of tumors resistant to sotorasib. Key results include:
- Single-agent efficacy: Reqorsa significantly inhibited tumor growth in sotorasib-resistant xenograft and patient-derived xenograft (PDX) models. In the H23AR model, Reqorsa outperformed sotorasib, which showed no activity in these resistant tumors.
- Synergy with sotorasib: A combination of Reqorsa and sotorasib produced a synergistic antitumor effect in TC314AR PDX models, reducing tumor viability further than either treatment alone.
- Mechanistic insights: Reqorsa re-expressed the TUSC2 tumor suppressor gene, inducing apoptosis (programmed cell death) and suppressing colony formation in resistant cancer cells.

The Science Behind Reqorsa’s Success

Reqorsa’s mechanism hinges on its non-viral Oncoprex® Delivery System, which uses positively charged lipoplexes to target negatively charged tumor cells. This system achieves 10–33 times higher TUSC2 uptake in tumor cells compared to normal cells, minimizing side effects and maximizing therapeutic impact. TUSC2 re-expression disrupts key survival pathways in cancer cells, including MAPK and mTOR, while also promoting immunogenic cell death—a dual attack on tumors.

Clinical Pipeline Momentum

The preclinical success has spurred Genprex to advance Reqorsa into pivotal trials:
- Acclaim-3 Phase 1/2 trial: Presented at the 2025 American Society of Clinical Oncology (ASCO) meeting, this study evaluates Reqorsa in combination with atezolizumab (Tecentriq®) as maintenance therapy for extensive-stage small cell lung cancer (ES-SCLC). ES-SCLC has a median survival of just 9–12 months, underscoring the urgent need for new treatments.
- Regulatory tailwinds: Reqorsa’s NSCLC and SCLC programs hold FDA Fast Track Designations, with SCLC also receiving Orphan Drug Designation—a status that grants market exclusivity and financial incentives.

Market Opportunity and Risks

KRASG12C mutations drive 12–15% of NSCLC cases, a population with limited options after resistance develops to targeted therapies like sotorasib. The global lung cancer market is projected to exceed $25 billion by 2030, with gene therapies like Reqorsa poised to capture a significant share.

However, risks remain:
- Clinical trial execution: Success in preclinical models does not guarantee human results.
- Manufacturing scalability: Genprex relies on third-party partners for drug production, raising potential bottlenecks.
- Competitive landscape: Other therapies, including Amgen’s KRAS G12C inhibitors, are in late-stage development.

Conclusion: A Promising Play in Oncology Innovation

Genprex’s Reqorsa represents a critical advancement in tackling drug resistance, a major hurdle in cancer treatment. The preclinical data, combined with strategic clinical trials and regulatory support, suggest strong potential for Reqorsa to carve out a niche in lung cancer therapy.

With its targeted delivery system and dual antitumor/immunomodulatory effects, Reqorsa could address a $25 billion market while meeting urgent unmet needs. Investors should monitor Acclaim-3 trial updates and FDA interactions closely. While risks exist, the science underpinning Reqorsa—and its ability to synergize with existing therapies—paints a compelling picture for long-term value creation in this high-growth therapeutic space.

For now, Genprex’s journey from lab to clinic continues—a journey that could redefine how we treat one of the world’s deadliest cancers.