VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor for Thyroid Eye Disease (TED): Phase 1/2 Clinical Study in Patients

Clinical and preclinical evidence confirms IGF-1R antagonism reduces TED-related inflammation and proptosis. VRDN- 001, a full antagonist antibody to IGF-1R, is being evaluated in a phase 1/2 double-masked, randomized clinical trial (NCT05176639) at 3, 10, or 20 mg/kg administered intravenously. Results from the first cohort of TED patients are presented here.

Tuesday, March 14th: 7:30 - 7:45 am VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor for Thyroid Eye Disease (TED): Phase 1/2 Clinical Study in Patients Raymond Douglas 1, Kimberley Cockerham 2, Roger Turbin 3, Rosa Tang 4, Navdeep Nijhawan 5, Shoaib Ugradar 1, Denis O’Shaughnessy 6, Rochelle Summerfelt 6, Angela She 6, Barrett Katz 6 Cedars Sinai Medical Center, 2 Senta Clinic, 3 Rutgers New Jersey Medical School - Department of Ophthalmology & Visual Science, 4 Eye Wellness Center– Neuro-Eye Clinical Trials, Inc., 5 Oshawa Clinic, 6 Viridian Therapeutics Inc. 1 Introduction: Clinical and preclinical evidence confirms IGF-1R antagonism reduces TED-related inflammation and proptosis. VRDN001, a full antagonist antibody to IGF-1R, is being evaluated in a phase 1/2 double-masked, randomized clinical trial (NCT05176639) at 3, 10, or 20 mg/kg administered intravenously. Results from the first cohort of TED patients are presented here. Methods: Adults with active moderate-to-severe TED with clinical activity score (CAS) ≥4 were randomized to 2 infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo (3:1). Safety, tolerability, and efficacy through 6 weeks were assessed. Endpoints included overall responder rate (% of subjects with ≥2 mm reduction in proptosis and ≥2 point reduction in CAS), proptosis responder rate (% of subjects with ≥2 mm reduction), change from baseline in proptosis and CAS, proportion of subjects with CAS decrease to 0 or 1, and diplopia resolution. Results: Baseline characteristics were similar between VRDN-001 (n=6) and placebo (n=2). After 2 infusions, the overall responder rate was 83% (5/6; VRDN-001) vs. 0% (0/2; placebo). Proptosis responder rate was 83% (5/6; VRDN-001) vs. 50% (1/2; placebo). Proptosis decreased by 2.4 mm (VRDN-001) vs. 1.0 mm (placebo) and CAS decreased by 4.3 (VRDN-001) vs. 1.5 (placebo). CAS decreased to 0 or 1 for 83% (5/6; VRDN-001) vs. 0% (0/2; placebo). In patients presenting with diplopia, complete resolution occurred for 75% (3/4; VRDN-001) vs. 0% (0/1; placebo). One case of transient hearing impairment was reported that resolved by next visit, with normal audiometry. No serious AEs, hyperglycemia, or infusion reactions occurred. Conclusions: Two infusions of 10 mg/kg VRDN-001 led to rapid, clinically meaningful improvement across all efficacy measures at 6 weeks in TED patients, surpassing results at the same timepoint from prior RCTs of other anti-IGF-1R antibodies. Results from the additional 3 mg/kg and 20 mg/kg cohorts may extend these findings and define potential VRDN-001 treatment regimens. References: None provided. Abstract Type: Clinical Trial Keywords: Graves' disease, Neuro-ophth & systemic disease (eg. MS, MG, thyroid), Orbit/ocular pathology Financial Disclosures: Raymond Douglas: Raymond Douglas is a consultant and research investigator for Horizon Therapeutics and Viridian Therapeutics.; Kimberley Cockerham: Kimberly Cockerham serves on the medical advisory board and is a research investigator for Viridian Therapeutics; and serves on the medical advisory board, has received honoraria, and is a research investigator for Horizon Therapeutics.; Roger Turbin: Roger Turbin is a research investigator for Viridian Therapeutics and has received honoraria from Horizon Therapeutics.; Rosa Tang: Rosa Tang is a research investigator and consultant for Viridian Therapeutics; is a research investigator for Horizon Therapeutics; has received honoraria from EMD Serono; and is a consultant for Alexion Pharmaceuticals.; Navdeep Nijhawan: Navdeep Nijhawan is a research investigator for Viridian Therapeutics.; Shoaib Ugradar: Shoaib Ugradar is a consultant for Viridian Therapeutics.; Denis O’Shaughnessy: Denis O’Shaughnessy is an employee of Viridian Therapeutics Inc.; Rochelle Summerfelt: Rochelle Summerfelt is an employee of Viridian Therapeutics Inc.; Angela She: Angela She is an employee of Viridian Therapeutics Inc.; Barrett Katz: Barrett Katz is an employee of Viridian Therapeutics Inc. Grant Support: None. Contact Information: None provided. 2023 Annual Meeting Syllabus | 381