Expression of the therapeutic gene, IL-1Ra, was sustained out to 12-month timepoint, reaching target levels

GNSC-001 is designed to offer long-term, sustained IL-1 inhibition following a single injection into affected joint; IL-1 is a key mediator involved in pathogenesis of OA

Company completed successful meeting with FDA on Phase 2b/3 study design; preparing to transition to late-stage development

Genascence Corporation (“Genascence”), a clinical-stage biotechnology company revolutionizing the treatment of prevalent musculoskeletal diseases with gene therapy, today announced positive 12-month safety and biomarker results from the Phase 1b DONATELLO clinical trial evaluating GNSC-001, a potential first-in-class gene therapy blocking interleukin 1 (IL-1) for the treatment of knee osteoarthritis (OA). Results from the 12-month analysis showed the study met the primary endpoint, demonstrating continued safety and tolerability across all doses tested, as well as the key secondary endpoint showing sustained IL-1Ra expression in synovial fluid, building on data reported through the six-month visit.

GNSC-001 is a genetic medicine – a recombinant adeno-associated viral vector expressing an optimized human interleukin-1 receptor antagonist (IL-1Ra), a naturally occurring protein that blocks IL-1 signaling. IL-1 is considered one of the key mediators involved in the pathogenesis of OA, causing inflammation, joint pain, and cartilage destruction. GNSC-001 is designed to offer long-term, sustained inhibition of IL-1 following a single intra-articular injection into the affected joint.

The U.S. Food and Drug Administration (FDA) granted GNSC-001 Fast Track designation in the fourth quarter of 2024. Genascence recently completed a successful meeting with the FDA on the design of the Phase 2b/3 clinical trial of GNSC-001 focused on clinical efficacy and plans to initiate the Phase 2b/3 study in 2026.

“Osteoarthritis is incapacitating, causing years of pain and disability for people living with the disease. Current treatment options are limited to managing pain and do not treat the underlying disease itself,” said Thomas Chalberg, Ph.D., founder and CEO of Genascence. “The 12-month safety and sustained IL-1Ra expression data affirms the promise of GNSC-001 to potentially transform the treatment paradigm for OA. We are pleased by the successful meeting with the FDA, and look forward to initiating the study, transitioning GNSC-001 to late-stage clinical development so we can bring a new treatment option to people suffering from this disabling disease.”

“GNSC-001 is the first IL-1 inhibitor that has been shown to generate IL-1Ra expression levels that reach and maintain therapeutic thresholds long-term following a single administration,” said Annahita Keravala, Ph.D., chief scientific officer (CSO) of Genascence. “Results from the DONATELLO clinical trial suggest that our novel therapeutic approach, a local gene therapy can potentially have therapeutic benefit in knee OA, a disease for which there are no treatments beyond management of symptoms. This would be transformative for people suffering from this debilitating condition, and thus warrants further development.”

"These results from the DONATELLO trial reflect the kind of innovation CIRM was created to support,” said Lisa Kadyk, Ph.D., CIRM Fellow, Clinical Development at the California Institute for Regenerative Medicine (CIRM), which supported the DONATELLO clinical trial with a $12 million award. “By harnessing the power of gene therapy, GNSC-001 represents a novel and potentially disease-modifying approach to treating osteoarthritis. We are encouraged by the 12-month safety and biomarker data and proud to have supported this important step toward a more effective, long-term treatment for people living with knee OA."

Dr. Keravala will present data from the six-month interim analysis of the DONATELLO clinical trial at the 28^th Annual American Society of Gene and Cell Therapy (ASGCT) 2025 Annual Meeting, being held May 13-17, 2025 in New Orleans, LA and virtually. The poster presentation details are provided below.

Title: A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Phase 1b Study Evaluating Safety, Tolerability, and Pharmacodynamics of a Local AAV-Mediated Anti-Interluekin-1 Gene Therapy in Subjects with Knee Osteoarthritis: 6-Month Interim Results

Date/Time: Thursday, May 15, 2025, 5:30-7:00 pm CT

Location: Poster Hall

Abstract Number: AMA616

Poster Number: 1849

Abstracts can be found at https://annualmeeting.asgct.org/.

About the DONATELLO Clinical Trial

The DONATELLO Phase 1b clinical trial (NCT05835895) is a double-blind, placebo-controlled dose-ranging study designed to evaluate the safety, tolerability, and pharmacodynamics of a single intra-articular injection of GNSC-001 in patients with OA of the knee. The study enrolled 67 participants with OA at 10 centers across the U.S. The first five groups were randomized to receive GNSC-001 at doses of 110¹² vg or 110¹³ vg, with or without a short course of oral steroids for immune-conditioning, or a placebo (saline) injection. The trial was expanded to enroll an additional, non-randomized arm. In this arm, pre-treatment synovial fluid sampling was required for entry, and subjects received 110¹³ vg GNSC-001 with an abbreviated three-day course of oral steroids plus a local, intra-articular steroid injection.

Data and Safety Summary

The primary endpoints of the DONATELLO clinical trial are safety and tolerability. Through 12 months of follow-up, data show that GNSC-001 was well tolerated, with no treatment-emergent or treatment-related deaths, serious adverse events (SAEs), or adverse event (AE)-related withdrawals reported. The most common target knee AEs included arthralgia, joint swelling, and joint effusion.

The study’s secondary endpoints include expression levels of interleukin-1 receptor antagonist (IL-1Ra) in synovial fluid at Month 12, as well as change from baseline to Month 12. Results revealed that mean expression of IL-1Ra reached target therapeutic levels in multiple arms of the study and remained above the target threshold throughout the 12-month follow up period. Immune-conditioning with a short course of steroids generally supported higher levels of prolonged IL-1Ra expression.

The DONATELLO clinical trial was supported by a $12 million award from the California Institute for Regenerative Medicine (CLIN2-14265).

About Osteoarthritis (OA) of the Knee

Osteoarthritis (OA) is a progressive joint disease that is a leading cause of disability. It is characterized by destruction of cartilage and structural changes in bone within the joint, which contribute to pain and loss of joint function. Osteoarthritis affects more than 30 million Americans and is increasing as a result of the aging population and increasing prevalence of obesity. Osteoarthritis represents a major economic burden, owing to direct medical costs and loss of productivity. Each year, millions of patients are treated for knee OA with NSAIDs, opioids, and steroid injections into the knee to manage their knee pain. There are no currently available therapies known to alter or slow down OA progression.

About Genascence Corporation

Genascence, a clinical-stage biotechnology company revolutionizing the treatment of prevalent musculoskeletal diseases with gene therapy, is developing life-changing treatments for highly prevalent conditions affecting millions of people. The company was founded in 2017 with technology licensed from three leading U.S. research institutions: Mayo Clinic, University of Florida, and NYU Langone Health. Headquartered in Palo Alto, California, Genascence’s founders and leadership team have deep experience in the design, development, and manufacturing of successful gene therapies and biological medicines. For more information, please visit www.genascence.com.

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