Genascence Announces Positive 12-Month Safety and Biomarker Data for GNSC-001 Gene Therapy in Knee Osteoarthritis Trial

PALO ALTO, Calif. – May 12, 2025 – Genascence Corporation, a clinical-stage biotechnology company focused on AAV gene therapy for musculoskeletal diseases, today announced positive 12-month safety and biomarker results from its Phase 1b DONATELLO clinical trial evaluating GNSC-001, a potential first-in-class AAV-based gene therapy for knee osteoarthritis (OA).

The 12-month analysis confirmed the study met its primary endpoint, demonstrating continued safety and tolerability across all tested doses of this AAV therapy. It also achieved a key secondary endpoint, showing sustained expression of IL-1 receptor antagonist (IL-1Ra) in the synovial fluid, building on previously reported six-month data. GNSC-001 is a genetic medicine that utilizes an adeno-associated viral (AAV) vector to express an optimized human IL-1Ra, a naturally occurring protein that blocks interleukin-1 (IL-1) signaling—a key driver of OA’s inflammation, pain, and cartilage destruction. Delivered via a single intra-articular injection, this AAV gene therapy aims to provide long-term IL-1 inhibition.

The FDA granted GNSC-001 Fast Track designation in Q4 2024, and Genascence recently had a successful meeting with the FDA regarding the design of its Phase 2b/3 clinical trial, focused on efficacy, which is planned to initiate in 2026. This next phase will further evaluate the potential of GNSC-001 as an AAV-delivered solution for OA.

Thomas Chalberg, Ph.D., Genascence CEO, highlighted the debilitating nature of OA and the limitations of current treatments, stating that the 12-month data supports GNSC-001’s potential to transform the OA treatment paradigm as an AAV gene therapy. CSO Annahita Keravala, Ph.D., added that GNSC-001 is the first IL-1 inhibitor to show sustained therapeutic levels of IL-1Ra after a single administration, suggesting a potentially disease-modifying benefit for knee OA, a condition currently lacking such treatments. The consistent performance of this AAV construct is very encouraging. Lisa Kadyk, Ph.D., CIRM Fellow, praised the innovative approach of this AAV gene therapy and its potential for a more effective, long-term treatment.

The Phase 1b DONATELLO study (NCT05835895) was a double-blind, placebo-controlled, dose-ranging trial that evaluated the safety, tolerability, and pharmacodynamics of a single intra-articular injection of GNSC-001 in 67 participants with knee OA across 10 U.S. centers. Through 12 months, GNSC-001 was well-tolerated with no treatment-related deaths, serious adverse events (SAEs), or AE-related withdrawals. The study demonstrated that mean IL-1Ra expression reached and remained above target therapeutic levels in multiple arms throughout the 12-month follow-up, reinforcing the promise of this AAV-mediated approach.

Osteoarthritis of the knee affects over 30 million Americans, causing pain, cartilage destruction, and loss of function, with no current therapies to alter or slow its progression. The positive 12-month data from the DONATELLO trial represents a significant step forward in developing a potential disease-modifying AAV gene therapy for this prevalent condition.