Viridian Therapeutics, Inc. announced positive topline clinical data from the third, low dose cohort in its ongoing Phase 1/2 clinical trial of VRDN-001, an anti-insulin-like growth factor 1 receptor (IGF-1R) antibody, in patients with active thyroid eye disease (TED). The Company believes this data further validate the differentiated and potentially best-in-class clinical activity of VRDN-001. The data also support the planned dosing interval for Viridian’s VRDN-002 and VRDN-003 subcutaneous programs of up to once monthly.

VRDN-001 – Phase 1/2 proof-of-concept trial: The proof-of-concept portion of this double-blind, placebo-controlled Phase 1/2 trial evaluated two infusions of VRDN-001 administered intravenously, three weeks apart, with efficacy measured six weeks after the first dose. VRDN-001 was evaluated at doses of 3, 10, and 20 mg/kg, with each cohort designed to include six patients randomized to drug, and two patients randomized to placebo. The Company previously announced positive results from the first two dose cohorts, which demonstrated a favorable safety profile.

The third cohort evaluated a VRDN-001 dose of 3 mg/kg with 6-week data announced today. In the 3 mg/kg dose cohort, nine patients were randomized to receive VRDN-001 to enable all consented patients who were eligible following screening to participate in the trial, and two patients were randomized to receive placebo. One patient receiving placebo discontinued in the trial prior to the 6-week evaluation.

VRDN-001 – Safety data: VRDN-001 was generally safe and well-tolerated by all patients treated in the three dose cohorts. There were no reported serious adverse events (SAEs), no discontinuations, and no infusion reactions in patients treated with VRDN-001 as of December 19, 2022, the most recent cut-off date for follow-up observation. The safety and tolerability profile at the 3 mg/kg dose level was generally consistent with previously reported results.

VRDN-001 – Clinical activity data: All VRDN-001 treated patients (n=21) in the 3 mg/kg (n=9), 10 mg/kg (n=6) and 20 mg/kg (n=6) cohorts were treated for two full cycles and were evaluated for changes in proptosis, clinical activity score (CAS) and diplopia. Improvement in proptosis and CAS was generally consistent across the three cohorts. A preliminary analysis of systemic IGF-1 levels, a biomarker for target engagement, shows a similar increase was also observed across the three cohorts.

The following activity was observed in the 3mg/kg cohort (n=9) and across all three dose groups (n=21) at week 6: Subcutaneous program: The Company believes that data from the 3 mg/kg dose cohort of VRDN-001 validate a low volume, subcutaneous product profile for the Company’s next-generation half-life extended anti-IGF-1R antibodies VRDN-002 and VRDN-003. VRDN-002 is a novel anti-IGF-1R monoclonal antibody that incorporates half-life extension technology. The Company previously reported that VRDN-002 demonstrated a half-life up to 43 days in healthy volunteers, supporting administration as a low-volume, subcutaneous injection up to once-monthly.

VRDN-003 is an anti-IGF-1R monoclonal antibody with the same amino acid sequence as VRDN-001, except for the addition of the half-life extension technology that is incorporated in VRDN-002. The company’s updated pharmacokinetic (PK) modeling support feasibility of ongoing development of a self-administered pen for subcutaneous administration, and a planned dosing interval of up to once-monthly for VRDN-002 and VRDN-003.