Metagenomi’s Dual-Component AAV Gene Editing Therapy MGX-001 Demonstrates Curative FVIII Activity in Non-Human Primates

EMERYVILLE, Calif. — November 11, 2025 — Metagenomi, Inc., an in vivo genome editing company, today reported compelling new dose range finding data for its AAV gene editing program, MGX-001, for Hemophilia A. The data, derived from non-human primate (NHP) studies, demonstrated the potential for MGX-001 to achieve curative Factor VIII (FVIII) activity, supporting a best-in-class, one-and-done clinical development strategy.

Best-in-Class Efficacy with Dual AAV and LNP Delivery

MGX-001 is a sophisticated, dual-component genetic medicine. It utilizes an adeno-associated virus (AAV) vector to deliver the genetic template—a B-domain deleted human FVIII gene—and a proprietary lipid nanoparticle (LNP) to deliver the MG29-1 nuclease mRNA and guide RNA. This combined AAV-LNP approach enables the endogenous production of FVIII, restoring the body’s natural ability to regulate hemostasis for a potentially lifelong cure.

Jian Irish, Ph.D., M.B.A., President and CEO of Metagenomi, noted that the results build upon prior studies: “The data demonstrated clear dose-dependent activity across both the AAV and LNP components of MGX-001, resulting in therapeutically relevant FVIII activity in each animal treated in all but the lowest AAV dose. This new data builds upon an earlier study demonstrating durable and stable FVIII activity in NHPs over an approximately 19-month study, giving us confidence that our novel AAV-based approach has the potential to be a curative, one-and-done treatment.”

Dose Range Findings Confirm Curative Potential

The NHP dose range finding study successfully established a clinical dose regimen. A functional cure is generally defined as FVIII levels of 50% to 150% of normal human levels.

• Dose Dependency: FVIII activity was shown to be dependent on both the AAV and LNP dose. Therapeutically relevant levels were achieved across the five highest AAV dose cohorts.
• Curative Levels Achieved: At a fixed LNP dose and a variable AAV dose (ranging from 1.6e12 to 4e13 vg/kg), MGX-001 achieved average per-cohort FVIII activity between 49% and 81%.
• Proposed Clinical Dose: The proposed clinical regimen (AAV at 5e12 vg/kg and LNP at 0.6 mg/kg) achieved an average FVIII activity of 49%.

The treatment was generally well tolerated, with no animal exceeding the maximum acceptable level of 150% FVIII activity, demonstrating appropriate regulation of the therapeutic gene. Furthermore, this AAV gene editing therapy showed no identifiable off-target editing in preclinical assays.

Advancing to the Clinic

Glenn F. Pierce, M.D., Ph.D., a leading expert and former hemophilia A patient, underscored the significance of the results: “The MGX-001 AAV approach represents a potential paradigm shift for the treatment of hemophilia A patients who, even with currently approved therapies, are subject to rare but serious spontaneous bleeding events… The impact that a potential one-and-done curative treatment can have is enabling a new standard of life with a hemophilia-free mindset.”

Metagenomi is leveraging these preclinical results in regulatory discussions and expects to hold a Pre-IND regulatory meeting in Q4 2025. Investigational New Drug (IND) and Clinical Trial Application (CTA) submissions are expected in Q4 2026 to advance this promising AAV gene editing treatment into human trials.