Slide 1: Safety, Efficacy, and Quality of Life Outcomes of Subcutaneous Lonigutamab: Week 12 Results
Safety, Efficacy, and Quality of Life Outcomes of Subcutaneous Lonigutamab (Anti–IGF-1R): Week 12 Results from a Phase 1/2 Proof of Concept Study in Patients with Thyroid Eye Disease Shoaib Ugradar1, David A. Kostick2, Jane Spadaro3, Dinesh Selva4, Jean-Louis deSousa5, Krishna Tumuluri6, Jwu Jin Kho
Slide 2: Financial Disclosure
FINANCIAL DISCLOSURE I/All authors have had the following financial relationships with ineligible companies in the past 24 months: Name Company Relationship type Ended/not ended Shoaib Ugradar ACELYRIN, INC. Consultant/Advisor No (not ended) Shoaib Ugradar Viridian Therapeutics Consultant/Advisor No
Slide 3: Background
Background 〉 Thyroid eye disease (TED) is a chronic, debilitating, and in the most severe cases, vision-threatening condition driven by aberrant stimulation of the IGF-1R pathway1,2 〉 IGF-1R is a clinically validated therapeutic target in TED1-3 ACELYRIN-commissioned figure 〉 Despite treatment advan
Slide 4: Lonigutamab mechanism of action
Lonigutamab mechanism of action 〉 Lonigutamab is a novel, high-affinity, subcutaneously administered, anti–IGF-1R monoclonal antibody with a unique noncompetitive mechanism of action1,2 Noncompetitive Homeostatic circulating 1 IGF-1 binding with IGF-1 Lonigutamab Potential Therapeutic Benefits of Lo
Slide 5: Phase 1/2 study design
Phase 1/2 study design NCT056834961 Data through week 12 presented for Key eligibility criteria 40 mg Q3W, 50 mg Q4W, and 50 mg load + 25 mg QW 〉 Proptosis ≥3 mm above normal range in the study eye Lonigutamab 〉 CAS ≥4 (using a 7-item scale) for the 40 mg Q3W 40 mg Q3W Off-treatment follow-up most s
Slide 6: Demographics and baseline characteristics
Demographics and baseline characteristics Lonigutamab Lonigutamab Lonigutamab Placebo (40 mg Q3W) (50 mg Q4W) (50 mg load + 25 mg QW) n=2 n=6 n=8 n=8 Age, mean (SD), years 49.5 (12.0) 43.8 (13.7) 45.6 (11.4) 42.1 (13.2) Female, n (%) 2 (100.0) 5 (83.3) 3 (37.5) 5 (62.5) White, n (%) 1 (50.0) 5 (83.3
Slide 7: Proptosis response
Proptosis response (≥2-mm reduction in the study eye) 50% of patients in the 40 mg Q3W group achieved a proptosis 63% of patients in the 50 mg load + 25 mg QW group response within 3 weeks, which was maintained through achieved a proptosis response within 6 weeks, which was week 12 (off treatment) m
Slide 8: CAS improvement
CAS improvement (≥2-point reduction) 100% of patients in the 40 mg Q3W group achieved a 88% of patients in the 50 mg load + 25 mg QW group achieved a clinically meaningful improvement in CAS at week 6, which clinically meaningful improvement in CAS at week 6, which was maintained through week 12 (of
Slide 9: Diplopia response in patients with baseline diplopia
Diplopia response in patients with baseline diplopia >0 (Improvement in ≥1 Bahn-Gorman grade) Clinically meaningful diplopia response in the 40 mg Q3W 50% of patients in the 50 mg load + 25 mg QW group group at week 3 was maintained through achieved clinically meaningful diplopia responses at week 4
Slide 10: GO-QoL Mean Change from Baseline
Graves’ Ophthalmopathy Quality of Life (≥6-point improvement is considered clinically meaningful1; higher scores indicate better health) Patients in the 40 mg Q3W group reported improved quality of life Patients in the 50 mg load + 25 mg QW group reported improved within 3 weeks, which was maintaine
Slide 11: GO-QoL subdomains: visual functioning and appearance
Graves’ Ophthalmopathy Quality of Life (Visual functioning and appearance subdomains; higher scores indicate better health) 40 mg Q3W 50 mg Q4W 50 mg load + 25 mg QW (n=6) (n=8)a (n=8) 35 31.3 35 35 27.7 30 30 25.0 30 GO-QoL Mean Change GO-QoL Mean Change GO-QoL Mean Change 23.9 25 25 22.1 25 from B
Slide 12: Summary of efficacy data at week 12
Summary of efficacy data at week 12 40 mg Q3Wa 50 mg Q4W 50 mg load + 25 mg QW Proptosis CAS Proptosis CAS Proptosis CAS 50% response 100% ≥2-point 25% response 63% ≥2-point 63% response 100% ≥2-point ≥2 mm improvement ≥2 mm improvement ≥2 mm improvement −1.5 mm mean 67% CAS 0/1 −1.4 mm mean 50% CAS
Slide 13: Overall summary of TEAEs
Overall summary of TEAEs 〉 All events were mild or Lonigutamab Lonigutamab Lonigutamab Placebo (50 mg load + moderate in severity, with no (40 mg Q3W) (50 mg Q4W) n=2 25 mg QW) grade ≥3 or serious TEAEs n (%) n=6 n=8 n=8 〉 Injection-site reactions Any TEAEs 2 (100.0) 4 (66.7) 6 (75.0) 8 (100.0) (ery
Slide 14: Summary and conclusions
Summary and conclusions Lonigutamab, a high-affinity, next-generation, subcutaneously administered anti–IGF-1R monoclonal antibody with a noncompetitive binding mechanism, demonstrated proof of concept for clinical efficacy in patients with TED Efficacy summary 〉 Clinical data suggest that optimal c