Peer-reviewed results in Molecular Therapy Oncology show that disabling NRF2 resensitizes tumors to standard of care therapy and slows tumor growth in lung cancer models

CorriXR Therapeutics, Inc., an oncology-focused biotherapeutics company pioneering a novel gene editing platform to overcome drug resistance in solid tumors, today announced the publication of a manuscript in Molecular Therapy Oncology detailing results from a preclinical study evaluating CRISPR-directed gene editing for the treatment of squamous cell lung carcinoma (LUSC). The study was conducted in collaboration with scientists at ChristianaCare’s Gene Editing Institute (GEI).

“This foundational work strengthens CorriXR’s strategy of disrupting cancer cell survival pathways to restore sensitivity to standard therapies,” said Eric B. Kmiec, Ph.D., Founder and Chief Executive Officer of CorriXR Therapeutics and Executive Director of GEI. “These findings build on more than a decade of GEI research into NRF2, a master regulator of cellular stress responses and known driver of treatment resistance. We are encouraged by the consistency of results across in vitro human lung cancer models and our in vivo studies and are actively pursuing IND-enabling work to bring this promising approach to patients.”

Key findings from the study include:

• Restoration of chemosensitivity: Editing 20-40% of LUSC cells to disrupt NRF2 was sufficient to resensitize tumors to chemotherapy, resulting in significant reductions in tumor growth.
• Reduced cancer-driving signals: Edited tumors reduced NRF2 expression and downregulation of its downstream markers, demonstrating effective pathway disruption.
• No off-target editing above background: Unintended edits remained below 0.2% supporting the specificity and safety of the gene editing approach.
• Strong translational potential: The lipid nanoparticle (LNP) delivery system achieved robust editing in both engineered and patient-derived tumor models, reinforcing the feasibility of advancing towards clinical development.

“Treatment resistance remains one of the greatest challenges in oncology, and these data demonstrate that targeting NRF2 can meaningfully resensitize tumors with minimal off-target effects,” said Kelly Banas, Ph.D., lead author of the study and Associate Director of Research at GEI. “This approach has the potential to lower chemotherapy doses, reduce toxicity and help patients remain healthier throughout treatment.” Kmiec added, “Instead of creating entirely new drugs, we are using gene editing to make existing ones effective again.”

The study also highlights that the biology of NRF2 driven resistance extends beyond lung cancer. “While this work focused on LUSC, NRF2 overactivation drives treatment resistance across multiple solid tumors, including head and neck squamous cell carcinoma (HNSCC),“ said Kmiec. “These data indicate that CRISPR-enabled targeting of NRF2 may disrupt the tumor microenvironment and address a shared mechanism of therapeutic failure.”

LUSC is an aggressive form of non-small cell lung cancer (NSCLC), representing 20-30% of lung cancer cases and affecting an estimated 190,000 people annually in the U.S. Chemotherapy remains a cornerstone of care, but many patients develop resistance, leaving limited options beyond dose escalation, which increases toxicity and typically worsens quality of life. NRF2 overactivation is a well-established driver of this resistance across multiple solid tumors, including HNSCC, esophageal and liver cancers – representing a significant unmet medical need.

These findings provide a compelling foundation to advance CorriXR’s lead program for HNSCC, as well as the Company’s LUSC program, into clinical development. CorriXR and GEI are now independently validating results at commercial CROs, conducting the required safety and regulatory studies to support an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for approval of human trials, and are exploring partnerships to accelerate clinical translation.

The full publication: Functional characterization of tumor-specific CRISPR-directed gene editing as a combinatorial therapy for the treatment of solid tumors - ScienceDirect is available online in Molecular Therapy Oncology.

About CorriXR Therapeutics

CorriXR is developing genetic medicines to transform the treatment of solid tumors. The Company’s patented non-viral gene editing platform targets NRF2, a transcription factor controlling more than 200 genes that shape a pro-oncogenic tumor microenvironment and drive treatment resistance. Disruption of NRF2 resensitizes cancer cells to standard of care therapies, and is being developed as a monotherapy, or in combination with chemotherapy, radiotherapy, or immunotherapy. CorriXR's platform has potential applications across more than 30 types of squamous cell carcinomas by increasing treatment efficiency at lower doses, expanding patient eligibility, and reducing treatment-limiting toxicity — ultimately leading to improved patient outcomes. Learn more at www.corrixr.com.

About ChristianaCare Gene Editing Institute

ChristianaCare is one of the largest healthcare systems in the Mid-Atlantic region. Within its Helen F. Graham Cancer Center & Research Institute, ChristianaCare established the Gene Editing Institute in 2015 as a leading center for translational research in gene editing technologies. CorriXR is the inaugural biotech spin-out of ChristianaCare and the Gene Editing Institute, which served as the research and development engine behind CorriXR. This collaboration combines deep scientific expertise with direct access to clinical environments, enabling CorriXR to accelerate the development and commercialization of next-generation therapies. For more information, visit www.geneeditinginstitute.com.

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Instead of creating entirely new oncology drugs, we are using gene editing to make existing ones effective again.