Genascence Announces Six-Month Results from Phase 1b DONATELLO Trial Indicating GNSC-001 Was Safe and Well Tolerated Across Multiple Dosing Arms

Mean IL-1Ra expression reached and maintained target levels in synovial fluid throughout six-month follow-up period

Immune-conditioning with short steroid course supported higher levels of transgene expression

Results will guide design of Phase 2 study and discussion with regulatory authorities

PALO ALTO, Calif., Jan. 9, 2025 /PRNewswire/ -- Genascence Corporation ("Genascence"), a clinical-stage biotechnology company revolutionizing the treatment of prevalent musculoskeletal diseases with gene therapy, today announced positive interim safety and biomarker results from the Phase 1b DONATELLO clinical trial evaluating GNSC-001. GNSC-001 is an investigational AAV gene therapy product for knee osteoarthritis (OA) that encodes interleukin 1 receptor antagonist (IL-1Ra), a potent inhibitor of interleukin 1 (IL-1). Data from the six-month analysis demonstrated acceptable safety and tolerability across all doses tested, along with encouraging biomarker data.

"These six-month interim results mark a critical milestone in our mission to transform the treatment paradigm for osteoarthritis," said Jeymi Tambiah, M.D., chief medical officer of Genascence. "The safety profile and sustained IL-1Ra expression data underscore the promise of GNSC-001 as a potential one-time gene therapy for this debilitating condition. The results from DONATELLO will guide discussions with regulatory authorities as Genascence prepares to initiate a Phase 2 trial focused on clinical efficacy."

"The ability to locally and sustainably inhibit IL-1 activity in the joint has been a long-standing goal in osteoarthritis research," said Annahita Keravala, Ph.D., chief scientific officer of Genascence. "GNSC-001 is the first IL-1 inhibitor that has been shown to generate IL-1Ra expression levels that reach and maintain therapeutic thresholds in the synovial fluid long-term following a single administration. This highlights the potential of our gene therapy approach to address a key mediator of inflammation and disease progression in osteoarthritis and offers hope for a transformative treatment option for patients."

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 1x10¹² vg or 1x10¹³ 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 1x10¹³ vg GNSC-001 with an abbreviated three-day course of oral steroids plus a local, intra-articular steroid injection.

The six-month interim analysis will help guide the selection of the optimal dose of GNSC-001 as well as immune-conditioning regimens for future studies designed to evaluate clinical efficacy. Twelve-month data from DONATELLO are expected in the second quarter of 2025.

Data and Safety Summary
The primary endpoints of the DONATELLO clinical trial are safety and tolerability. Through six 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 6, as well as change from baseline to Month 6. The interim 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 six-month follow up period. Immune-conditioning with a short course of steroids generally supported higher levels of prolonged IL-1Ra expression.

About GNSC-001
GNSC-001 is a genetic medicine – a recombinant adeno-associated viral vector expressing an optimized form of IL-1Ra, a naturally occurring protein that blocks interleukin-1 (IL-1) signaling. IL-1 is considered one of the key mediators involved in the pathogenesis of OA, causing inflammation, joint pain, as well as cartilage destruction. GNSC-001 is designed to offer long-term, sustained inhibition of IL-1 following a single injection into the affected joint. GNSC-001 has received Fast Track Designation with the U.S. Food and Drug Administration.

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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