veligrotug (VRDN-001) / Sanofi, Viridian Therap, Zenas BioPharma, AbbVie, ZAI Lab - LARVOL DELTA

THRIVE-2 Phase 3 Trial of Veligrotug (VRDN-001) in Chronic Thyroid Eye Disease (TED): Efficacy and Safety at 15 Weeks (AACE 2025) - "TED remains a condition with significant unmet needs, particularly in the chronic phase, where treatment options are limited. IGF-1R antagonism has emerged as a key therapeutic approach, addressing inflammation and proptosis."

Clinical • P3 data • Inflammation • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease

Efficacy and Safety of Veligrotug (VRDN-001), a Full Antagonist Monoclonal Antibody to IGF-1 Receptor, in Active Thyroid Eye Disease (TED): THRIVE Phase 3 Topline Results (AACE 2025) - "Veligrotug, a full antagonist monoclonal antibody to the IGF-1 receptor (IGF-1R), is an investigational treatment for thyroid eye disease (TED). Clinical and preclinical evidence indicate a central role for IGF-1R antagonism in reducing the inflammation and proptosis that occur in TED."

Clinical • P3 data • P3 data: top line • Inflammation • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease • IGF1

Viridian Therapeutics Announces Positive Long-Term Durability Data from the Veligrotug Phase 3 THRIVE Clinical Trial in Patients with Active Thyroid Eye Disease (TED) (Businesswire) - P3 | N=154 | THRIVE (NCT05176639) | Sponsor: Viridian Therapeutics, Inc. | "70% of veligrotug patients (21/30) in THRIVE, who were proptosis responders at week 15 and continued follow-up to the end of the study at week 52, maintained their proptosis response. Maintenance of response is defined as responders at week 15 who still had at least a 2-millimeter (mm) reduction in proptosis compared to baseline at week 52, without worsening in the fellow eye (≥2 mm increase), as measured by exophthalmometry. There were no changes to the safety profile in the follow-up period. The vast majority of adverse events reported at the week 15 primary analysis had resolved by week 52....We continue to make great progress towards submitting the BLA in the second half of this year and preparing for a potential launch in 2026."

FDA filing • Launch US • P3 data • Thyroid Eye Disease

Viridian Therapeutics Receives FDA Breakthrough Therapy Designation for Veligrotug for the Treatment of Thyroid Eye Disease (TED) (Businesswire) - "Viridian Therapeutics...announced that the United States Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to veligrotug ('veli'), the company’s lead anti-insulin-like growth factor-1 receptor (IGF-1R) drug candidate for the treatment of TED....Breakthrough Therapy Designation request based on veligrotug’s (i) consistent and robust improvement and resolution of diplopia in chronic TED, and (ii) rapid onset of proptosis response. Veligrotug met all of its primary and secondary endpoints in the pivotal THRIVE and THRIVE-2 clinical trials in active and chronic TED."

Breakthrough therapy • Thyroid Eye Disease

Efficacy and Safety of Veligrotug (VRDN-001), a Full Antagonist Monoclonal Antibody to IGF-1 Receptor, in Active Thyroid Eye Disease (TED): THRIVE Phase 3 Topline Results (ESPE-ESE 2025) - P3 | "Topline results from the THRIVE phase 3 trial show 5 IV infusions of 10 mg/kg veligrotug were well tolerated and led to significant and clinically meaningful improvements in proptosis, CAS, and diplopia at 15 weeks. Additional follow-up through 52 weeks is ongoing."

Clinical • P3 data • P3 data: top line • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease • IGF1

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

THRIVE-2 Phase 3 Trial of Veligrotug (VRDN-001) in Chronic Thyroid Eye Disease (TED): Efficacy and Safety at 15 Weeks (ESPE-ESE 2025) - P3 | "THRIVE-2, which assessed 5 IV infusions of veli vs placebo, is the first RCT in chronic TED to show statistically significant improvement not only in proptosis, but also in diplopia, with a generally well-tolerated safety profile. Results suggest the promising potential of veli in chronic TED. Follow-up through 52 weeks is ongoing."

Clinical • P3 data • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease

THRIVE-2 Phase 3 Trial of Veligrotug (VRDN-001) in Chronic Thyroid Eye Disease (TED): Efficacy and Safety at 15 Weeks (ENDO 2025) - P3 | "THRIVE-2, which assessed 5 IV infusions of veli vs placebo, is the first RCT in chronic TED to show statistically significant improvement not only in proptosis, but also in subjective diplopia, with a generally well-tolerated safety profile. Results suggest the promising potential of veli in chronic TED. Follow-up through 52 weeks is ongoing.*."

Clinical • P3 data • Inflammation • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease

Efficacy and Safety of Veligrotug (VRDN-001), a Full Antagonist Monoclonal Antibody to IGF-1 Receptor, in Active Thyroid Eye Disease (TED): THRIVE Phase 3 Topline Results (ENDO 2025) - P3 | "Topline results from the THRIVE phase 3 trial show 5 IV infusions of 10 mg/kg veligrotug were well tolerated and led to significant and clinically meaningful improvements in proptosis, CAS, and diplopia at 15 weeks. Additional follow-up through 52 weeks is ongoing.*. .*"

Clinical • P3 data • P3 data: top line • Inflammation • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease • IGF1

Study of ZB001 in Chinese Patients With Thyroid Eye Disease (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Zenas BioPharma (USA), LLC | Active, not recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Apr 2024 | Trial primary completion date: Oct 2024 ➔ Apr 2024

Trial completion • Trial completion date • Trial primary completion date • Ophthalmology • Thyroid Eye Disease • IGF1

VRDN-001-302: An Open-label Study for Non-responders of VRDN-001-101 and VRDN-001-301 (OLE) (clinicaltrials.gov) - P3 | N=143 | Active, not recruiting | Sponsor: Viridian Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2026 ➔ Jul 2025

Enrollment closed • Trial completion date • Ophthalmology • Thyroid Eye Disease

STRIVE: A Randomized, Controlled, Safety and Tolerability Study of VRDN-001 in Participants with Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=231 | Active, not recruiting | Sponsor: Viridian Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Ophthalmology • Thyroid Eye Disease

Veligrotug (VRDN-001), a Full Antagonist Monoclonal Antibody to IGF-1 Receptor, in Active Thyroid Eye Disease (TED): THRIVE Phase 3 Efficacy and Safety Topline Results (ARVO 2025) - P3 | "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • P3 data • P3 data: top line • Ocular Inflammation • Ophthalmology • IGF1

Viridian Therapeutics Highlights Recent Progress and Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "TED Portfolio Progress: Veligrotug:...BLA submission is on track for the second half of 2025, with an MAA submission to the European Medicines Agency expected in the first half of 2026."

EMA filing • FDA filing • Thyroid Eye Disease

Reduced Proptosis and Muscle/Fat Volume by MRI/CT in a Proof-of-Concept Study in TED Shows Potential for Disease-Modifying Effects of VRDN-001, a Targeted TED Therapy (ATA 2024) - "In this small number of patients with active TED, MRI/CT analysis shows potential for a disease-modifying effect of VRDN-001, with reductions of EOM and OF associated with improvements in proptosis at 6 weeks that continued through 12 weeks (9 weeks beyond last treatment)."

Immunology • Ophthalmology • Thyroid Eye Disease • IGF1

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

THRIVE Phase 3 Trial of VRDN-001 in Active Thyroid Eye Disease (TED): Next Generation Insulin-like Growth Factor-1 Receptor Blockade (ATA 2024) - "Topline results from THRIVE, a double-masked, placebo-controlled phase 3 registrational trial, will provide an initial view on the clinical safety and efficacy outcomes of a full treatment course (5 IV infusions) of VRDN-001 in active TED."

Late-breaking abstract • P3 data • 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

An Efficacy, Safety, and Tolerability Study of Veligrotug (VRDN-001), in Participants with Chronic Thyroid Eye Disease (TED) (THRIVE-2) (clinicaltrials.gov) - P3 | N=188 | Active, not recruiting | Sponsor: Viridian Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Ophthalmology • Thyroid Eye Disease

VRDN-001, a Targeted TED Therapy: Disease-Modifying Effects on Proptosis and Muscle/Fat Volume by MRI/CT in a Proof-of-Concept Study in TED (AAO 2024) - "Mean changes from baseline at 6 weeks for VRDN-001 versus placebo were −4.6 mm versus −0.2 mm for proptosis, −31% versus −10% for EOM and −19% versus −2% for OF; changes at 12 weeks were −5.9 mm versus −0.1 mm for proptosis, −37% versus −17% for EOM and −37% versus 0% for OF. Conclusion In this small number of patients with TED, MRI/CT analysis shows potential for a disease-modifying effect of VRDN-001, with reductions of EOM and OF associated with improvements in proptosis at 6 weeks that continued through 12 weeks (9 weeks beyond last treatment)."

Ophthalmology

Viridian Therapeutics to Webcast VRDN-001 Phase 3 THRIVE Topline Results on September 10, 2024 (Businesswire) - "Viridian Therapeutics...will host a conference call and webcast to report topline data for the THRIVE phase 3 clinical trial, evaluating VRDN-001 in patients with active TED, on Tuesday, September 10, 2024 at 8:00am ET."

P3 data: top line • Thyroid Eye Disease

Viridian Therapeutics Announces Completion of THRIVE-2 Enrollment for VRDN-001 in Patients with Chronic Thyroid Eye Disease (TED) (Businesswire) - "Viridian Therapeutics...announced that enrollment is complete in THRIVE-2, its phase 3 clinical trial for VRDN-001 in patients with chronic TED. THRIVE-2 enrolled 188 patients globally and exceeded the enrollment target of 159 patients due to patient demand. Approximately 40% of the enrolled patients were from US sites. Topline data from THRIVE-2 is on track for readout by year-end 2024....Topline data for THRIVE is on track for readout in September 2024."

Enrollment status • P2 data • P3 data: top line • Thyroid Eye Disease

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

A Randomized, Active Controlled, Safety and Tolerability Study of VRDN-001 in Participants With Thyroid Eye Disease (TED) (clinicaltrials.gov) - P3 | N=212 | Recruiting | Sponsor: Viridian Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Ophthalmology • Thyroid Eye Disease