Viridian Presents Positive Clinical Data from Ongoing VRDN-001 Phase 1/2 Trial in Active Thyroid Eye Disease (TED) Patients

Viridian Therapeutics presented positive proof-of-concept data from the 10 mg/kg cohort in its ongoing phase 1/2 clinical trial of VRDN-001, an anti-IGF-1R antibody, in patients with active thyroid eye disease (TED). These data, as well as new in vitro data further characterizing and differentiating the pharmacological profile of VRDN-001, were included as part of three late-breaking poster presentations at the American Thyroid Association (ATA) 91st annual meeting. The abstract describing new in vitro data on the distinct anti-IGF-1R profile of VRDN-001 was also selected as an oral highlighted late breaking presentation. The three posters are available on the Viridian website (click here).

“Patients suffering from TED would benefit from additional therapeutic options,” said Raymond Douglas, MD, PhD, director of the Orbital and Thyroid Eye Disease Program, Cedars-Sinai Medical Center and an investigator in the VRDN-001 trial. “The rapid and near complete resolution of key signs and symptoms of TED in the majority of patients at six weeks following two infusions of 10 mg/kg VRDN-001 in a cohort of patients with active TED suggests VRDN-001, with further study, may provide an important new option for TED patients.”

ATA Poster #535: VRDN-001, a Full Antagonist Antibody to the Insulin-Like Growth Factor Receptor-1 (IGF-1R) for Thyroid Eye Disease (TED): Phase 1/2 Proof of Concept in Patients with TED

Poster #535 presents proof-of-concept data from the first cohort of patients with active TED treated in the ongoing phase 1/2 clinical trial. In this cohort, a total of 8 patients were randomized to receive two infusions of 10 mg/kg dose of VRDN-001 or placebo intravenously; 6 patients received VRDN-001 and 2 patients received placebo. In patients receiving VRDN-001, proptosis response was achieved by 83% of patients, with a mean reduction of 2.4 mm from baseline. Clinical Activity Score (CAS) of 0 or 1 was achieved by 83% of patients, with a mean reduction of 4.3 points from baseline. Complete resolution of diplopia was achieved by 75% of patients who presented with diplopia at baseline. VRDN-001 demonstrated a favorable safety and tolerability profile with no reported SAEs, no hyperglycemia, and no infusion reactions.

Poster #535 was authored by Shoaib Ugradar, UCLA Stein Eye Institute, Barrett Katz, Viridian Therapeutics, Denis O’Shaughnessy, Viridian Therapeutics, Rochelle Summerfelt, Viridian Therapeutics, Angela She, Viridian Therapeutics, and Raymond Douglas, Cedars Sinai Medical Center.

ATA Poster #568: VRDN-001, A Potent and Selective Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antagonist Antibody for Thyroid Eye Disease (TED): Phase 1 Safety and Pharmacodynamic Results in Healthy Volunteers

Poster #568 presents full safety and pharmacodynamic data from the completed healthy volunteer portion of the ongoing phase 1/2 trial of VRDN-001. A total of 13 subjects were randomized to receive two infusions of either 3, 10, or 20 mg/kg dose of VRDN-001 or placebo. Twelve subjects completed the trial; one of the subjects in the 20 mg/kg group withdrew for personal reasons after the first infusion and was followed through Day 35.

Plasma levels of IGF-1, a biomarker for IGF-1R antagonism, increased five- to seven-fold above baseline indicating maximal target engagement at all doses. All doses studied were generally safe and well tolerated, with no cases of hearing impairment or treatment related hyperglycemia and no infusion reactions.

Poster #568 was authored by Angela She, Barrett Katz, Rochelle Summerfelt, Denis O’Shaughnessy, Brent Dickinson, Kelly Foster, and Vahe Bedian of Viridian Therapeutics

ATA Poster #132: VRDN-001, a Full Antagonist Antibody to the Insulin-Like Growth Factor-1 Receptor (IGF-1R) in Development for Thyroid Eye Disease (TED), Binds to a Distinct Epitope from Teprotumumab

Poster #132 presents preclinical data from in vitro studies of VRDN-001.The data show that VRDN-001 binds the same region of the IGF-1R as teprotumumab but engages a distinct epitope. This difference in binding translated to differences in functional effects: unlike the anti-IGF-1R antibody teprotumumab, which incompletely antagonized IGF-1R function, VRDN-001 fully antagonized ligand binding, receptor autophosphorylation, and downstream signaling.  

These pharmacological differences may provide a mechanistic basis for the initial data reported from the ongoing VRDN-001 phase 1/2 study, including the pharmacodynamic responses in the healthy volunteer cohort presented in Poster #568 and favorable clinical responses seen in TED patients as presented in Poster #535.

Poster #132 was authored by Yang Zhao, Jordan Tsai, Rachel Newell, and Vahe Bedian of Viridian Therapeutics.

Upcoming Clinical Milestones for the Ongoing VRDN-001 Phase 1/2 Proof-of-Concept Trial

The company remains on track to present additional updates from the VRDN-001 phase 1/2 study this quarter. These updates will include topline data for the 20 mg/kg cohort of the ongoing phase 1/2 trial of VRDN-001 in TED, followed later this quarter by topline data from the currently enrolling 3 mg/kg cohort.

This ongoing trial is evaluating two infusions of VRDN-001, 3 weeks apart, with efficacy measured 6 weeks after the first dose. Each dose is evaluated in a cohort of eight patients, randomized so that six patients receive VRDN-001 and two patients receive placebo. The first cohort evaluated a dose of 10 mg/kg, with initial clinical data reported on August 15, 2022. The company expects to initiate the pivotal program for VRDN-001 by the end of 2022.

This quarter the company also will report final pharmacokinetic and pharmacodynamic data from Viridian’s first-in-human trial of VRDN-002, a half-life extended IGF-1R antibody, which build upon the recently presented interim results. The company expects data from a proof-of-concept trial of subcutaneously administered VRDN-002 in the second half of 2023.