VRDN-003 / Viridian Therap - LARVOL DELTA

Viridian Therapeutics Highlights Recent Progress and Reports First Quarter 2025 Financial Results (Businesswire) - "Biologics License Application (BLA) submission for veligrotug on track for second half 2025 with potential for U.S. launch in 2026; preparatory commercial activities underway; REVEAL-1 and REVEAL-2, phase 3 clinical trials assessing VRDN-003 in active and chronic thyroid eye disease (TED), are on track for topline data in the first half of 2026....VRDN-008, a bispecific neonatal Fc receptor (FcRn) inhibitor with an extended half-life, on track for an Investigational New Drug (IND) submission for year-end 2025."

FDA filing • IND • Launch US • P3 data: top line • Ophthalmology • Thyroid Eye Disease

REVEAL-2: An Efficacy, Safety, and Tolerability Study of VRDN-003 in Participants with Chronic Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=195 | Recruiting | Sponsor: Viridian Therapeutics, Inc. | N=126 ➔ 195

Enrollment change • Ophthalmology • Thyroid Eye Disease

REVEAL-1: An Efficacy, Safety, and Tolerability Study of VRDN-003 in Participants with Active Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=117 | Recruiting | Sponsor: Viridian Therapeutics, Inc. | N=84 ➔ 117

Enrollment change • Ophthalmology • Thyroid Eye Disease

A Safety and Tolerability Study of VRDN-003 in Participants with Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=284 | Recruiting | Sponsor: Viridian Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Ophthalmology • Thyroid Eye Disease

A Safety and Tolerability Study of VRDN-003 in Participants with Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=284 | Not yet recruiting | Sponsor: Viridian Therapeutics, Inc.

New P3 trial • Ophthalmology • Thyroid Eye Disease

Viridian Therapeutics Highlights 2025 Corporate Priorities Following Positive Phase 3 Topline Data in Thyroid Eye Disease (Businesswire) - "Our BLA and early commercial preparations are well underway, and we are on track to submit the BLA in the second half of this year. The results of THRIVE and THRIVE-2 give us even higher conviction that our subcutaneous VRDN-003 program will deliver positive topline data in the first half of 2026, which would enable a BLA submission for VRDN-003 in the second half of 2026...Topline data for both REVEAL-1 and REVEAL-2 remains on track for the first half of 2026, which would enable a BLA submission by year-end 2026."

FDA filing • P3 data: top line • Thyroid Eye Disease

Subcutaneous Administration of VRDN-003, a Next-Generation Full Antagonist Antibody to IGF-1R, in Patients With Thyroid Eye Disease (TED): Two Randomized Placebo-Controlled Clinical Studies (REVEAL-1 and REVEAL-2) (ATA 2024) - "Objective: VRDN-001 and VRDN-003 are full antagonist antibodies to the IGF-1 receptor (IGF-1R). VRDN-003 is in development as a sub-cutaneous treatment for TED with the goal of reducing the treatment burden currently associated with IV infusions. The REVEAL-1 and REVEAL-2 randomized, double-masked, placebo-controlled trials will be the first to assess subcutaneous VRDN-003 in patients with TED."

Clinical • Ophthalmology • Thyroid Eye Disease • IGF1

REVEAL-2: An Efficacy, Safety, and Tolerability Study of VRDN-003 in Participants with Chronic Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=126 | Recruiting | Sponsor: Viridian Therapeutics, Inc.

New P3 trial • Ophthalmology • Thyroid Eye Disease

REVEAL-1: An Efficacy, Safety, and Tolerability Study of VRDN-003 in Participants with Active Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=84 | Recruiting | Sponsor: Viridian Therapeutics, Inc.

New P3 trial • Ophthalmology • Thyroid Eye Disease

Subcutaneous VRDN-003 vs. VRDN-001, Full Antagonist Antibodies to IGF-1R for TED: Phase 1 Safety/PK/PD Studies (AAO 2024) - "Conclusion At two dose levels, a single dose of VRDN-003 was well tolerated, had four to five times longer half-life than VRDN-001 and demonstrated sustained increases in IGF-1 levels. Safety and efficacy of VRDN-003 SC will be assessed in clinical studies enrolling patients with TED."

Clinical • P1 data • PK/PD data • Ocular Inflammation • Ophthalmology • IGF1

VRDN-003, a Full Antagonist Antibody to IGF-1R for Thyroid Eye Disease (TED): Phase 1 Results Show Potential for Subcutaneous Administration (ETA 2024) - "These results show the potential for VRDN-003 SC dosing regimens. A single dose of VRDN-003 was well tolerated with an extended half-life 4–5 times longer than that of its parent molecule, VRDN-001. Safety and efficacy of VRDN-003 SC are planned to be further assessed in clinical studies enrolling patients with TED."

P1 data • CNS Disorders • Insomnia • Ophthalmology • Sleep Disorder • Thyroid Eye Disease

Emerging therapies in the medical management of thyroid eye disease. (PubMed, Front Ophthalmol (Lausanne)) - "Teprotumumab - an anti-IGF-1R monoclonal antibody that has recently emerged as a first-line therapy for active, moderate-to-severe TED - has demonstrated statistically significant improvements in proptosis, diplopia, clinical activity score, and quality of life compared to placebo. Currently under investigation are several other agents, with varying administration modalities, that aim to inhibit IGF-1R: VRDN-001 (intravenous), VRDN-002 or VRDN-003 (subcutaneous), lonigutamab (subcutaneous), and linsitinib (oral). Tocilizumab, a monoclonal antibody of interleukin 6, has played a role in the management of multiple autoimmune and inflammatory conditions and may offer promise in TED...Among the agents under investigation that aim to decrease ocular morbidity associated with TED are agents that IGF-1R, interleukin 6, and the neonatal Fc receptor. The management of TED continues to expand with novel immunologic approaches for disease therapy."

Journal • Review • Endocrine Disorders • Grave’s Disease • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease • IL6

Viridian Therapeutics Announces Details of Subcutaneous VRDN-003 Phase 3 Clinical Program for Patients with Active and Chronic Moderate-to-Severe Thyroid Eye Disease (Businesswire) - "Viridian Therapeutics, Inc...today reported details of its plans to initiate a phase 3 clinical trial program for its SC VRDN-003 product candidate for patients with moderate-to-severe TED....Viridian is planning to initiate two randomized, double-masked, placebo-controlled phase 3 clinical trials designed to evaluate the efficacy and safety of subcutaneously administered VRDN-003 in patients with active and chronic TED, named REVEAL-1 and REVEAL-2, respectively. These clinical trials are expected to initiate in August 2024....Viridian anticipates topline data for both clinical trials to be available in the first half of 2026 and to file a BLA by the end of 2026."

Clinical protocol • FDA approval • New P3 trial • P3 data • Ophthalmology • Thyroid Eye Disease

VRDN-003, a Full Antagonist Antibody to the IGF-1 Receptor for Thyroid Eye Disease (TED): Safety and Pharmacokinetic Results of Subcutaneous Administration in Healthy Volunteers (ENDO 2024) - "A single dose of VRDN-003 administered IV or SC to HVs was well tolerated and showed favorable PK for SC administration including a half-life of 40-50 days, 4-5 times longer than its parent molecule, VRDN-001. These results show the potential for VRDN-003 SC dosing regimens with the goal of reducing the treatment burden associated with achieving IGF-1R blockade in TED. Safety and efficacy of VRDN-003 SC will be further assessed in planned clinical studies enrolling patients with TED.Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation."

Clinical • PK/PD data • CNS Disorders • Insomnia • Ophthalmology • Sleep Disorder • Thyroid Eye Disease • IGF1

Antagonist Properties of VRDN-003, a Next-Generation, Half-Life Extended Antibody to IGF-1 Receptor for TED (AAO 2023) - "In addition, both antibodies provided similar and near-complete inhibition of IGF-1–induced phosphorylation of IGF-1R (proximal signaling) and phosphorylation of AKT (distal signaling) with IC50s of 0.1-0.2 nM. Conclusion Given that VRDN-001 and VRDN-003 antagonist properties are the same, VRDN-003 has potential for similar clinical effect to that previously observed with VRDN-001."

Ophthalmology • IGF1

VRDN-003, a Novel Half-Life Extended IGF-1 Receptor Antibody for TED: Preclinical PK and Human PK Modeling (AAO 2023) - "In human PK modeling, SC dosing of VRDN-003 either once or twice a month produced drug concentrations in the range of those achieved with VRDN-001 IV administration at 3 mg/kg or 10 mg/kg every 3 weeks. Conclusion These results suggest VRDN-003 may provide a low-volume, SC injection option for patients with TED, with similar clinical effect to that observed with IV infusion of VRDN-001."

Preclinical • Ophthalmology • IGF1

Design and Preclinical Characterization of VRDN-003, a Next-Generation, Half-life Extended Antibody to IGF-1 Receptor in Development for Thyroid Eye Disease (TED) (ARVO 2023) - "VRDN-001 is a full antagonist antibody to IGF-1R with subnanomolar affinity; VRDN-003 is a next-generation, half-life extended version of VRDN-001 designed to enable subcutaneous administration via a fixed-dose patient-controlled pen. In addition, VRDN-003 has been modified to last longer in the body so that it can be given at home by a self-administered injection under the skin. If proven to be safe and effective in people, VRDN-003 could become a more convenient, self-administered treatment option for TED patients."

Preclinical • Ocular Inflammation • Ophthalmology • IGF1

Preclinical Pharmacokinetics of VRDN-003, A Next-Generation Half-life Extended Antibody to the IGF-1 Receptor for Thyroid Eye Disease (ARVO 2023) - "Our preclinical study in monkeys, which metabolize drugs similar to humans, showed that a dose of VRDN-003 lasted approximately twice as long as a dose of VRDN-001, whether injected under the skin or given as an intravenous infusion. If proven safe and effective in people, VRDN-003 has the potential to become a more convenient, self-administered treatment option for TED patients."

PK/PD data • Preclinical • Ocular Inflammation • Ophthalmology • IGF1