GNSC-001 / Genascence - LARVOL DELTA

Genascence Announces U.S. Food and Drug Administration Grants Regenerative Medicine Advanced Therapy Designation to GNSC-001 for Knee Osteoarthritis (OA) (Businesswire) - "Genascence Corporation...announced that the U.S. Food and Drug Administration (FDA) has granted the Regenerative Medicine Advanced Therapy (RMAT) designation to GNSC-001, a potential first-in-class gene therapy blocking interleukin 1 (IL-1) for the treatment of knee osteoarthritis (OA)."

FDA event • Osteoarthritis • Rheumatology

A Phase 1b, Randomized, Double-Blinded, Placebo-Controlled Dose Ranging Study to Evaluate the Safety, Tolerability and Pharmacodynamics of a Single Intra-articular Injection of GNSC-001 Gene Therapy in Subjects with Osteoarthritis of the Knee (DONATELLO): 6-month Interim Results (EULAR 2025) - P1 | "Groups 1 and 3 received 60 mg oral prednisone for 7 days, starting Day -1 and tapering for 6 weeks. From Phase 1b DONATELLO 6-month data: GNSC-001 was generally safe and well tolerated with no treatment-related SAEs The majority of TEAEs were mild/ moderate with similar rates in randomized groups Open-label Group 6 had a higher TKAE rate; it was unclear if this was patient-factor related with SF aspiration required at entry, or steroid regimen-related. • Peristent IL-1Ra transgene expression was evident in SF, all groups had levels higher than BL and PBO Higher expression was associated with short courses of steroid immune-conditioning Mean IL-1Ra levels were sustained above target levels in most groups through Month 6 12 month data is awaited"

Clinical • Gene therapy • P1 data • PK/PD data • Gene Therapies • Immunology • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology

A phase 1 clinical trial shows safe, sustained, AAV-mediated expression of IL-1Ra in the human osteoarthritic knee joint. (PubMed, Sci Transl Med) - "Therefore, we found that intra-articular gene therapy with sc-rAAV2.5IL-1Ra was safe. The sustained increase in local IL-1Ra in human knee joints supports the further clinical examination of this therapy to provide therapeutic benefit in OA."

Journal • P1 data • Gene Therapies • Immunology • Osteoarthritis • Pain • Rheumatology • IL1R1

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 (ASGCT 2025) - "The trial was expanded to include a non-randomized open-label arm- Group 6 (n=14) that received GNSC-001 1×1013 vg with a local steroid injection plus an abbreviated course of oral steroids (IC- IA+oral); specifically, 80 mg IA methylprednisolone, and 60 mg oral prednisone on Day -1 for 3 days. GNSC-001 is thus of potential therapeutic benefit in knee OA, a previously undruggable disease, and warrants further development. Disease Focus of Abstract:Arthritis"

Clinical • Gene therapy • P1 data • PK/PD data • Developmental Disorders • Gene Therapies • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Genascence Phase 1b DONATELLO Trial Evaluating Potential First-in-Class Gene Therapy for Knee Osteoarthritis (OA) Meets Primary Endpoint Showing GNSC-001 Was Safe and Well Tolerated Across Multiple Dosing Arms (Businesswire) - P1b | N=67 | DONATELLO (NCT05835895) | Sponsor: Genascence Corporation | "Genascence Corporation...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...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...Dr. Keravala will present data from the six-month interim analysis of the DONATELLO clinical trial at the 28th....(ASGCT) 2025 Annual Meeting..."

New P2/3 trial • P1 data • Osteoarthritis

Genascence Announces Six-Month Results from Phase 1b DONATELLO Trial Indicating GNSC-001 Was Safe and Well Tolerated Across Multiple Dosing Arms (PRNewswire) - P1 | N=67 | DONATELLO (NCT05835895) | Sponsor: Genascence Corporation | "Genascence Corporation...today announced positive interim safety and biomarker results from the Phase 1b DONATELLO clinical trial evaluating GNSC-001....Data from the six-month analysis demonstrated acceptable safety and tolerability across all doses tested, along with encouraging biomarker data....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....Twelve-month data from DONATELLO are expected in the second quarter of 2025."

P1 data • Osteoarthritis

DONATELLO: Safety and Pharmacodynamics of GNSC-001 Intra-articular Injection for Knee Osteoarthritis (clinicaltrials.gov) - P1 | N=67 | Active, not recruiting | Sponsor: Genascence Corporation | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene therapy • Gene Therapies • Immunology • Osteoarthritis • Pain • Rheumatology

DONATELLO: Safety and Pharmacodynamics of GNSC-001 Intra-articular Injection for Knee Osteoarthritis (clinicaltrials.gov) - P1 | N=65 | Recruiting | Sponsor: Genascence Corporation | N=50 ➔ 65 | Trial completion date: Jan 2028 ➔ May 2029 | Trial primary completion date: Jan 2025 ➔ May 2025

Enrollment change • Gene therapy • Trial completion date • Trial primary completion date • Gene Therapies • Immunology • Osteoarthritis • Pain • Rheumatology

Genascence Announces Initiation of Phase 1b Clinical Trial of GNSC-001 Gene Therapy for Knee Osteoarthritis (OA) (PRNewswire) - "Genascence Corporation...today announced the initiation of its Phase 1b clinical trial of GNSC-001 for the treatment of knee osteoarthritis (OA) (DONATELLO). The study is now actively enrolling at ten clinical centers throughout the United States. A total of approximately 50 patients will participate, with trial enrollment expected to complete in the first quarter of 2024....Initial six-month data of the DONATELLO clinical trial are expected in the fourth quarter of 2024."

Enrollment status • P1 data • Trial status • CNS Disorders • Osteoarthritis • Pain

DONATELLO: Safety and Pharmacodynamics of GNSC-001 Intra-articular Injection for Knee Osteoarthritis (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Genascence Corporation

Gene therapy • Trial completion date • Trial primary completion date • Gene Therapies • Immunology • Osteoarthritis • Pain • Rheumatology

DONATELLO: Safety and Pharmacodynamics of GNSC-001 Intra-articular Injection for Knee Osteoarthritis (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Genascence Corporation | Phase classification: P1b ➔ P1

Gene therapy • Phase classification • Gene Therapies • Immunology • Osteoarthritis • Pain • Rheumatology

Genascence to Present Full Data from Phase 1 Clinical Trial on GNSC-001, Company's Lead Program in Osteoarthritis, at European Society of Gene & Cell Therapy 30th Annual Congress (PRNewswire) - P1 | N=9 | NCT02790723 | "Genascence Corporation...today announced that data from the Phase 1 clinical trial of GNSC-001 for the treatment of osteoarthritis (OA) demonstrated that it was safe and well tolerated. The study findings also showed that a single intra-articular injection of GNSC resulted in elevated interleukin-1 receptor antagonist (IL-1Ra) expression over baseline in synovial fluid for the length of the 12-month study. Additionally, treatment with GNSC-001 showed a trend in improvement of pain and function scores in all study participants, with a limited amount of disease progression in this first-in-human study. These data will be delivered in a poster presentation at the European American Society of Gene & Cell Therapy's (ESGCT) 30th Annual Congress being held October 24-27, 2023, in Brussels, Belgium."

P1 data • CNS Disorders • Osteoarthritis • Pain

DONATELLO: Safety and Pharmacodynamics of GNSC-001 Intra-articular Injection for Knee Osteoarthritis (clinicaltrials.gov) - P1b | N=50 | Recruiting | Sponsor: Genascence Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Gene therapy • Gene Therapies • Immunology • Osteoarthritis • Pain • Rheumatology

DONATELLO: Safety and Pharmacodynamics of GNSC-001 Intra-articular Injection for Knee Osteoarthritis (clinicaltrials.gov) - P1b | N=50 | Not yet recruiting | Sponsor: Genascence Corporation

Gene therapy • New P1 trial • Gene Therapies • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Genascence Receives $11.6 Million Award From California Institute for Regenerative Medicine to Help Advance its Lead Gene Therapy Program in Knee Osteoarthritis (Yahoo News) - "Genascence Corporation...today announced it has been awarded $11.6 million over four years from the California Institute for Regenerative Medicine (CIRM). The funding will be used to support Genascence's Phase 1b clinical trial of GNSC-001 in knee osteoarthritis (OA), as well as phase-appropriate manufacturing activities."

Financing • CNS Disorders • Osteoarthritis • Pain

Genascence Announces Data From Phase 1 Clinical Trial on GNSC-001, Company's Lead Program in Osteoarthritis, Presented at American Society of Gene & Cell Therapy 25th Annual Meeting (PRNewswire) - P1 | N=9 | NCT02790723 | Sponsor: Mayo Clinic | "Genascence Corporation...announced that additional safety data from the Phase 1 clinical trial of GNSC-001 for the treatment of osteoarthritis (OA), including 12-month follow-up on all subjects, demonstrated that it was safe and well tolerated. These data will be delivered in a poster presentation today at the American Society of Gene & Cell Therapy's (ASGCT) 25th Annual Meeting being held virtually and in-person May 16-19, 2022, in Washington, D.C....Results showed that intra-articular injection of GNSC-001 produced no severe adverse events....Clinical trial participants developed various degrees of anti-AAV neutralizing antibodies after injection of GNSC-001, as seen in preclinical studies....Injection of GNSC-001 was associated with increased concentrations of IL-1Ra in synovial fluid, which remained elevated after 12 months of follow up. Pain and function scores improved following injection of GNSC-001."

P1 data • CNS Disorders • Immunology • Osteoarthritis • Pain

Genascence Announces First Close in Series A Financing led by Pacira BioSciences and Expands Board of Directors and Scientific Advisory Board (PRNewswire) - "Genascence Corporation...announced it has completed the first closing in a Series A financing led by Pacira BioSciences, Inc., totaling $10.5 million. Additional investors included Polymerase Capital, DeepWork Capital, and University of Florida Research Foundation. Proceeds of the financing will be used to accelerate clinical development of GNSC-001, the company's lead program in osteoarthritis (OA)....In addition, the company announced that additional data from the Phase 1 clinical trial of GNSC-001 for the treatment of osteoarthritis (OA), including 12-month follow up on all subjects, will be presented in a poster session at the upcoming American Society of Gene & Cell Therapy's (ASGCT) 25th Annual Meeting being held virtually and in-person May 16-19, 2022, in Washington, D.C."

Financing • P1 data • Immunology • Osteoarthritis

AAVIL-1Ra: Safety of Intra-Articular Sc-rAAV2.5IL-1Ra in Subjects With Moderate Knee OA (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Mayo Clinic | Active, not recruiting ➔ Completed

Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

AAVIL-1Ra: Safety of Intra-Articular Sc-rAAV2.5IL-1Ra in Subjects With Moderate Knee OA (clinicaltrials.gov) - P1; N=9; Active, not recruiting; Sponsor: Mayo Clinic; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2022 ➔ Mar 2022; Trial primary completion date: Dec 2021 ➔ Mar 2022

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology • MRI

Genascence Announces Completion of Dosing and Interim Safety Data for Phase 1 Clinical Trial of GNSC-001 in Osteoarthritis (PRNewswire) - P1, N=9; NCT02790723; Sponsor: Mayo Clinic; "Genascence Corporation...today announced that dosing across all three cohorts has been completed in the Phase 1 clinical trial of GNSC-001 for the treatment of osteoarthritis (OA)....Initial data from the Phase 1 Study will be presented at the American Society of Gene and Cell Therapy's (ASGCT) 24th Annual Meeting taking place May 11-14, 2021 in virtual format....Interim safety data results show that GNSC-001 was safe and well tolerated, with adverse events being absent (8/9) or mild/moderate (1/9) in all treated subjects...Following the Phase 1 trial, Genascence plans to initiate a Phase 2 trial to further evaluate the safety and efficacy of GNSC-001 in osteoarthritis. Genascence has filed a company-sponsored IND for the Phase 2 study, which has been cleared by US FDA."

Enrollment closed • IND • New P2 trial • P1 data • Osteoarthritis • Pain