Slide 1: Preliminary Safety, Efficacy, and Quality of Life Outcomes of Subcutaneous Lonigutamab
Preliminary Safety, Efficacy, and Quality of Life Outcomes of Subcutaneous Lonigutamab (Anti–Insulin-Like Growth Factor 1 Receptor [IGF-1R]) from a Phase 1/2 Proof of Concept Study in Patients with Thyroid Eye Disease Jwu Jin Khong1, David A. Kostick2, Jane Spadaro3, Anita Grover4, So Jung Imm4, Sar
Slide 2: Disclosures
Disclosures • This study is sponsored by ACELYRIN, INC. Lonigutamab is an investigational therapy not approved by any regulatory authority • All authors met the ICMJE authorship criteria and had full access to relevant data • Jwu Jin Khong has received consulting fees from ACELYRIN, INC., and Amgen;
Slide 3: Background: Thyroid Eye Disease
Background: Thyroid Eye Disease Proptosis Redness Thyroid eye disease (TED) is a chronic, debilitating, and vision-threatening condition1,2 › Characterized by progressive inflammation resulting from aberrant stimulation of IGF-1R/TSHR signaling1,2 Jonathan Trobe, M.D. - University of Michigan Kellog
Slide 4: Background: Lonigutamab
Background: Lonigutamab Lonigutamab is a high-affinity (30-pM binding affinity), humanized, anti–IGF-1R monoclonal antibody1,2 Unique Binding Epitope2 IGF-1R Internalization1,2 Maintains circulating IGF-1 levels closer to homeostatic range Peripheral to IGF-1 binding site; does not compete with IGF-
Slide 5: Phase 1/2 Study Design
Phase 1/2 Study Design NCT056834961 Cohort 1 Lonigutamab Key Eligibility Criteria 40 mg Q3W 6 Week Treatment • Proptosis ≥3 mm above normal Post-treatment follow-up Placebo-Controlled range in the study eye Placebo (n=8) • CAS ≥4 (using a 7-item scale) for the most severely affected eye Cohort 2 12
Slide 6: Demographics and Baseline Characteristics
Demographics and Baseline Characteristics Placebo Lonigutamab Lonigutamab (Cohort 1) (Cohort 1: 40 mg Q3W) (Cohort 2: 50 mg load, 25 mg QW) n=2 n=6 n=6 Age, mean (SD), years 49.5 (12.0) 43.8 (13.7) 43.3 (13.3) Female, n (%) 2 (100.0) 5 (83.3) 4 (66.7) White, n (%) 1 (50.0) 5 (83.3) 2 (33.3) BMI, mea
Slide 7: Proptosis Response
Proptosis Response ≥2-mm Reduction in Proptosis Cohort 1 Cohort 2 50% of patients achieved a proptosis response within 3 67% of patients achieved a proptosis response weeks after a single 40 mg SC injection, which was within 4 weeks maintained through week 12 (off-treatment) 80 80 70 70 67 67 Propto
Slide 8: Diplopia Response in Patients with Baseline Diplopia >0
Diplopia Response in Patients with Baseline Diplopia >0 Improvement in ≥1 Bahn-Gorman Grade Cohort 1 Cohort 2 Clinically meaningful diplopia response at Clinically meaningful diplopia responses week 3 was maintained through week 12 within 4 weeks (off-treatment) 50 50 Diplopia Responders, % 40 Diplo
Slide 9: CAS Improvement, MCID
CAS Improvement, MCID ≥2-Point Reduction Is Considered Clinically Meaningful Cohort 1 Cohort 2 100% of patients achieved a clinically meaningful improvement 83% of patients achieved a clinically meaningful in CAS at week 6, which was maintained through week 12 improvement in CAS within 4 weeks (off-
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 Cohort 1 Cohort 2 Patients reported improved quality of life within 3 weeks Patients reported improved quality of life at week 4 after a single 40 mg SC injection, w
Slide 11: Safety: Cohorts 1 and 2
Safety: Cohorts 1 and 2 No audiology changes, no hyperglycemia events, and no serious adverse events Lonigutamab Lonigutamab • Most events were mild in Placebo (Cohort 1: (Cohort 2: 50 mg severity, with no serious TEAEs (Cohort 1) 40 mg Q3W) load, 25 mg QW) n (%) n=2 n=6 n=6 • Injection-site reactio
Slide 12: Conclusions
Conclusions • These findings with lonigutamab represent the first reported proof-of-concept results of a subcutaneous anti–IGF-1R agent in patients with TED • Patients in cohort 1 (40 mg Q3W) achieved early clinical responses across manifestations of disease – Responses were maintained through the t
Slide 13: Backup
Backup 13
Slide 14: Responses at Week 6: Cohorts 1 and 2
Responses at Week 6: Cohorts 1 and 2 Clinically meaningful results with lonigutamab across cohorts Cohort 1 and Cohort 2 Responses at Week 6 100 Cohort 1: Placeboa 100 25 Cohort 1: Lonigutamab GO-QoL Mean Change 80 20 (40 mg Q3W) 83 21.1 Responders, % 15 from Baseline Cohort 2: Lonigutamab 60 67 10