ACELYRIN (SLRN) Study Update summary

Introduction and background

• Lonigutamab is a next-generation subcutaneous anti-IGF-1R therapy under development for thyroid eye disease (TED), aiming to address unmet needs in this chronic, vision-threatening autoimmune condition with significant quality-of-life impact.

• Current treatments, such as teprotumumab, are limited by IV administration, safety concerns, and incomplete long-term durability.

• Lonigutamab is designed for self-administration, potentially enabling broader and more flexible treatment.

• TED affects over 100,000 people in the US, causing proptosis, diplopia, and risk of blindness, with a significant unmet need for safer, more effective, and convenient therapies.

Study design and clinical program

• Two global, double-masked, placebo-controlled Phase III trials (LONGITUDE-1 and LONGITUDE-2) will enroll about 350 patients, with top-line data expected in 2H 2026.

• Trials feature broad inclusion criteria, including prior teprotumumab responders, patients with longer disease duration, and those with age-appropriate hearing loss.

• Both studies use a 100 mg loading dose followed by 50 mg every two weeks, aiming for a Cmin above 3 μg/mL to optimize efficacy and safety.

• Primary endpoint is proptosis response rate (≥2 mm reduction) at week 24; secondary endpoints include CAS, diplopia, and GO-QOL, with optional MRIs.

• All patients cross over to active drug after 24 weeks, ensuring at least 28 weeks of lonigutamab exposure and up to 52 weeks of individualized, long-term treatment.

Key clinical results and efficacy

• Subcutaneous lonigutamab demonstrated robust efficacy at lower plasma exposures compared to IV anti-IGF-1R agents.

• 63% proptosis response (≥2 mm), 100% CAS response (≥2 points), 50% diplopia response, and up to 27.7-point GO-QOL improvement at week 12 with optimal dosing.

• Mean proptosis reduction was -1.9 mm, with rapid onset of effect as early as week 4–6 and sustained responses through week 12.

• Efficacy is comparable to IV anti-IGF-1R agents, with the convenience of subcutaneous administration.

• Maintaining Cmin above 3 μg/mL is critical for sustained efficacy; less frequent dosing led to suboptimal responses.