Slide 1: Preliminary Safety and Efficacy of Subcutaneous Lonigutamab in Thyroid Eye Disease
Preliminary Safety and Efficacy of Subcutaneous Lonigutamab (Anti–IGF-1R) From a Phase 1/2 Proof of Concept Study in Patients with Thyroid Eye Disease S h o a i b U g r a d a r 1, D a v i d A . K o s t i c k 2, J a n e S p a d a r o 3, A n i t a G r o v e r 4, S o J u n g I m m 4, S a r a h C h e s
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 Shoaib Ugradar has received consulting fees from ACELYRIN, INC., Amgen, Lassen T
Slide 3: Background: Thyroid Eye Disease
BACKGROUND: THYROID EYE DISEASE Thyroid eye disease (TED) is a chronic, debilitating, vision-threatening condition1,2 › Characterized by progressive inflammation resulting from aberrant stimulation of IGF-1R/TSHR signaling1,2 Proptosis Limitations of available therapies: Redness Jonathan Trobe, M.D.
Slide 4: Background: Lonigutamab
BACKGROUND: LONIGUTAMAB The Molecule Lonigutamab is a high-affinity, humanized, anti–IGF-1R monoclonal antibody1 › High binding affinity (30 pM)2 › Unique binding epitope peripheral to the IGF-1 binding site2 › Efficient receptor internalization within minutes1 Objective: To provide proof of concept
Slide 5: Phase 1/2 Study Design
PHA SE 1 /2 STU DY DESI GN NCT05683496 Key Eligibility Criteria Efficacy Endpoints • Proptosis ≥3 mm above normal range in the study eye • Proptosis response (≥2-mm reduction) • CAS ≥4 (using a 7-item scale) for the most severely affected • CAS MCID (≥2-point improvement) eye • Diplopia response (im
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: Cohort 1
PROPTOSIS RESPONSE: COHORT 1 Treatment period through week 6 / off-treatment through week 12 50% of patients achieved a proptosis response within 3 weeks after a single 40-mg SC injection, which was maintained through week 12 (off-treatment) Proptosis Response Proptosis Mean Change from Baseline (de
Slide 8: Diplopia and CAS: Cohort 1
DIPLOPIA AND CAS: COHORT 1 Treatment period through week 6 / off-treatment through week 12 100% of patients achieved a clinically meaningful Clinically meaningful diplopia response at week 3 improvement in CAS at week 6, which was was maintained through week 12 (off-treatment) maintained through wee
Slide 9: Proptosis Response: Cohort 2
PROPTOSIS RESPONSE: COHORT 2 67% of patients achieved a proptosis response within 4 weeks Proptosis Response 80 (defined as a ≥2-mm reduction in proptosis) Proptosis Responders, % 70 67 67 60 50 Lonigutamab (50 mg loading dose 40 followed by 25 mg QW; n=6) 30 Lonigutamab 50 mg 20 Lonigutamab 25 mg 1
Slide 10: Diplopia and CAS: Cohort 2
DIPLOPIA AND CAS: COHORT 2 Clinically meaningful diplopia responses 83% of patients achieved a clinically meaningful within 4 weeks improvement in CAS within 4 weeks Diplopia Response in Patients with Baseline Diplopia CAS Improvement, MCID >0 (a ≥2-point reduction is considered clinically meaningfu
Slide 11: Safety: Cohorts 1 and 2
SAFETY: COHORTS 1 AND 2 No audiology changes, no hyperglycemia events, and no serious adverse events Placebo Lonigutamab Lonigutamab • Most events were mild in severity, with (Cohort 1: (Cohort 2: 50 mg no serious TEAEs (Cohort 1) 40 mg Q3W) load, 25 mg QW) n=2 n (%) 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 achieved early clinical responses across manifestations of disease – Responses were maintained through the time points e
Slide 13: Backup
BACKUP
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 Responders at Week 6 100 100 Cohort 1: Placeboa 80 Cohort 1: Lonigutamab 83 Responders, % (40 mg Q3W) Cohort 2: Lonigutamab 60 67 (50 mg load, 25 mg QW) 50 40 40 20 25 0 0 0 0 Pro