Phase 1 Safety and Pharmacodynamic Results of VRDN-001, a Full Antagonist Antibody to the Insulin-Like Growth Factor-1 Receptor (IGF-1R) in Development for Thyroid Eye Disease (TED) (P3-9.007)

Abstract

<h3>Objective:</h3> Report the interim safety and pharmacodynamic (PD) results for healthy volunteers from a phase 1/2 clinical trial (NCT05176639) evaluating VRDN-001 intravenously administered at 3–20 mg/kg. <h3>Background:</h3> Clinical and preclinical studies have confirmed insulin-like growth factor-1 receptor (IGF-1R) antagonism can reduce the inflammation and proptosis that occur in Thyroid Eye Disease (TED). VRDN-001, a full antagonist antibody to the IGF-1R, is under development for the treatment of TED. <h3>Design/Methods:</h3> Adult healthy volunteers were randomized 3:1 to receive 2 intravenous infusions 3 weeks apart of either placebo or 3, 10, or 20 mg/kg VRDN-001. PD parameters (IGF-1 serum levels) and adverse events (AEs) were assessed up to 50 days. <h3>Results:</h3> Thirteen participants received VRDN-001 3 mg/kg (n=3), 10 mg/kg (n=3), 20 mg/kg (n=4), or placebo (n=3). Mean age was 49 years (range: 25–73) and 5 were female. All VRDN-001 doses elicited rapid, sustained, and similar increases in IGF-1 serum levels, a biomarker for IGF-1R inhibition. Following the first infusion, IGF-1 increased within a day, reaching 3–5-fold above baseline by Day 8. Increases were sustained until the second infusion, and then further increased to 5–7-fold above baseline (&gt;500 ng/mL), and sustained through Day 50. No increases in serum IGF-1 occurred for placebo. Eleven of the 13 participants experienced 19 AEs (16 mild and 3 moderate). Transient hypotension (10 mg/kg group) and muscle spasm (placebo group) were the only AEs to be deemed treatment-related by the masked investigator. No treatment-related hyperglycemia or hearing impairment was observed. <h3>Conclusions:</h3> VRDN-001 administered to healthy volunteers at 3–20 mg/kg indicated maximal target engagement at all doses and was generally safe and well-tolerated, with no observed treatment-related hyperglycemia or hearing impairment. Results from the ongoing evaluation of VRDN-001 dosed at 3–20 mg/kg in TED patients will further inform potential treatment regimens. <b>Disclosure:</b> Dr. She has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. She has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Dianthus Therapeutics. Dr. She has stock in Viridian Therapeutics. Dr. Katz has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. Katz has received stock or an ownership interest from Viridian Therapeutics. Mrs. Summerfelt has received personal compensation for serving as an employee of Viridian Therapeutics. An immediate family member of Mrs. Summerfelt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Viridian Therapeutics. Mrs. Summerfelt has stock in Viridian Therapeutics. Dr. Oshaughnessy has received personal compensation for serving as an employee of viridian therapeutics. Dr. Oshaughnessy has stock in viridian therapeutics. Mr. Dickinson has nothing to disclose. Dr. Foster has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. Bedian has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. Bedian has received personal compensation for serving as an employee of Dianthus Therapeutics. Dr. Bedian has stock in Viridian Therapeutics. Dr. Bedian has stock in Astria Therapeutics.