Slide 1: Obexelimab, a B-cell inhibitor, in IgG4-Related Disease: Results from the Phase 3 INDIGO Trial
ACTRIMS 2026 Presentation #800 Obexelimab, a B-cell inhibitor, in IgG4- Related Disease: Results from the Phase 3 INDIGO Trial Emanuel Della-Torre¹, Matthew C Baker², Wen Zhang³, Cory A. Perugino⁴, Guy Katz⁴, Yoshiya Tanaka⁵, Arezou Khosroshahi⁶, Alexander Kleger⁷, Nicolas Schleinitz⁸, Fernando Mart
Slide 2: Disclosures
Disclosures Obexelimab is an investigational medicine and has not been approved by any regulatory authority for the treatment of IgG4-related disease. Emanuel Della Torre Amgen, Zenas BioPharma, Sanofi, Matthew Baker Amgen, Eli Lilly, Gilead, BeOne Medicines, Zenas BioPharma, Sanofi, argenx, Neurocr
Slide 3: Background and need for novel treatment strategies
Background and need for novel treatment strategies • IgG4-related disease is a chronic relapsing systemic disease • Glucocorticoids (GCs) are effective but associated with cumulative toxicity • B-cell depletion works but comes with relevant limitations
Slide 4: Background and need for novel treatment strategies
Background and need for novel treatment strategies • IgG4-related disease is a chronic relapsing systemic disease • Glucocorticoids (GCs) are effective but associated with cumulative toxicity • B-cell depletion works but comes with relevant limitations 1. Prolonged immunosuppression 2. Hypogammaglob
Slide 5: Obexelimab and B-cell inhibition
Obexelimab and B-cell inhibition • Humanized bifunctional monoclonal antibody • Co-engagement of CD19 and FcγRIIb1,2 • B-cell inhibition with no antibody or complement dependent cytotoxicity3,4 • Reversible partial B-cell reduction3,4 1. Chu SY et al. Mol Immunol. 2008;45:3926–3933. 2. Horton HM et
Slide 6: The INDIGO trial
The INDIGO trial • Double-blind, randomized, placebo-controlled trial (NCT05662241) • To evaluate the efficacy and safety of obexelimab, administered subcutaneously, in maintaining IgG4-related disease remission
Slide 7: The INDIGO trial – Study Design
The INDIGO trial – Study Design • Double-blind, randomized, placebo-controlled trial (NCT05662241) • To evaluate the efficacy and safety of obexelimab, administered subcutaneously, in maintaining IgG4-related disease remission Screening RCP OLP Inclusion Day 1 Week 8 Week 52 • Adults with IgG4-RD (A
Slide 8: Endpoints
Endpoints Primary Endpoint Time to first IgG4-RD flare requiring initiation of rescue therapy, in the opinion of the investigator and confirmed by the AC. IgG4-RD = IgG4-related disease; AC = adjudication committee.
Slide 9: Endpoints
Endpoints Key Secondary Endpoints 1 Time to first investigator-determined flare requiring initiation of rescue therapy 2 Number of investigator- and AC-determined flares requiring initiation of rescue therapy · No AC-determined flare Proportion of patients achieving complete 3 · No treatment for fla
Slide 10: Flare assessment and adjudication
Flare assessment and adjudication • Organ-specific flare criteria developed by an international expert panel • Flare criteria included detection of subclinical/asymptomatic disease activity • Imaging at Week 52 • Flare determinations underwent blinded independent adjudication, with majority-vote con
Slide 11: The largest clinical trial in IgG4-RD
The largest clinical trial in IgG4-RD • 194 patients enrolled from 15 countries across 114 sites: the largest clinical trial in IgG4-RD conducted to date reflecting the full disease spectrum 15 Countries EAST ASIA • China • Japan • Rep. of Korea • Taiwan EUROPE • France • Germany • Italy • Poland •
Slide 12: Trial disposition
Trial disposition Assessed for Eligibility (Screened) N = 287 Screening Failure: n = 93 (32.4%) · Inclusion/Exclusion Criteria n = 91 · Other: n = 2 Randomized (1:1) n = 194 (67.6%) Obexelimab Placebo n = 97 n = 97 Discontinued RCP: n = 12 (12.4%) Discontinued RCP: n = 10 · Adverse event: n = 6 (10.
Slide 13: Baseline demographics
Baseline demographics Obexelimab Placebo Characteristic (N=97) (N=97) Age — yr 59.6 ± 13.4 58.7 ± 12.0 Male sex, n (%) 65 (67.0) 64 (66.0) Race, n (%) Asian 59 (60.8) 51 (52.6) White 27 (27.8) 39 (40.2) Other 11 (11.3) 7 (7.2) Region, n (%) Asia 51 (52.6) 48 (49.5) US/Canada 24 (24.7) 16 (16.5) Euro
Slide 14: Clinical characteristics
Clinical characteristics Obexelimab Placebo Characteristic (N=97) (N=97) IgG4-related disease manifestation Recurrent — no. (%) 64 (66.0) 65 (67.0) Newly diagnosed — no. (%) 33 (34.0) 32 (33.0) Number of organs involved — no. (%) 1 6 (6.2) 7 (7.2) 2–4 59 (60.8) 58 (59.8) >4 32 (33.0) 32 (33.0) Most
Slide 15: Results
Results
Slide 16: Results – Obexelimab reduced the risk of IgG4-RD flares
Results – Obexelimab reduced the risk of IgG4-RD flares 1.0 PRIMARY ENDPOINT 0.9 0.8 Obexelimab Probability of No Flare 73.2% of patients receiving obexelimab remained flare-free through Week 52 0.7 • Flares occurred in 26/97 patients 0.6 receiving obexelimab (26.8%) and Placebo 53/97 receiving plac
Slide 17: Results – Obexelimab met all Key Secondary Endpoints
Results – Obexelimab met all Key Secondary Endpoints SECONDARY ENDPOINTS Obexelimab Placebo Time to first investigator-determined flare (Patients Annualized rate of adjudicated flares requiring with ≥1 flare) rescue therapy (Flares/yr) Obexelimab 26.8% Obexelimab 0.34/yr Placebo 57.7% Placebo 0.70/y
Slide 18: Results – Glucocorticoid Toxicity Index
Results – Glucocorticoid Toxicity Index Proportion of Patients With ≥20- or ≥30-Point GTI-CWS at Week 52 Glucocorticoid Toxicity Index - Cumulative Worsening Score* P = 0.0135 P = 0.0090 61.2% (49.99; 71.56)* • GTI-CWS assesses accumulated 49.4% glucocorticoid-related toxicity over (38.39; 60.48)* 4
Slide 19: Results – Sustained effect of Obexelimab on Serum IgG4
Results – Sustained effect of Obexelimab on Serum IgG4 Serum IgG4 levels decline after GC induction was sustained through Week 52 with obexelimab but increase above baseline with placebo 700 600 Placebo 500 Mean IgG4 (mg/dL) 400 300 200 Obexelimab 100 0 0 1-2 4 12 Week 32 52 No of participants Obexe
Slide 20: Results – B cells remained above LLN through Week 52
Results – B cells remained above LLN through Week 52 Mean CD20+ B-cell counts decline after GC induction was sustained through Week 52 and remained above the LLN during obexelimab treatment 600 Mean CD20+ 400 Cells/µL Placebo 200 (LLN) 74 cells/µL Obexelimab 0 0 1-2 4 12 Week 32 52 No of participant
Slide 21: Results – Adverse Events
Results – Adverse Events Obexelimab Placebo (N=97) (N=97) Patients with ≥1 AE 95 (97.9%) 93 (95.9%) Patients with ≥1 SAE 10 (10.3%) 18 (18.6%) Patients with ≥1 Grade ≥3 AE 11 (11.3%) 23 (23.7%) Patients with AE leading to discontinuation of treatment 9 (9.3%) 3 (3.1%) Selected Treatment-emergent AEs
Slide 22: Conclusions
Conclusions 1. Obexelimab significantly reduced the risk of IgG4-RD flare requiring rescue therapy versus placebo through Week 52. 2. Obexelimab reduced cumulative glucocorticoid rescue use and was associated with less glucocorticoid toxicity worsening versus placebo. 3. Obexelimab was generally wel
Slide 23: Conclusions
Conclusions 1. Obexelimab significantly reduced the risk of IgG4-RD flare requiring rescue therapy versus placebo through Week 52. 2. Obexelimab reduced cumulative glucocorticoid rescue use and was associated with less glucocorticoid toxicity worsening versus placebo. 3. Obexelimab was generally wel
Slide 24: The New England Journal of Medicine: Obexelimab for the Treatment of IgG4-Related Disease
The NEW ENGLAND JOURNAL of MEDICINE ORIGINAL ARTICLE Obexelimab for the Treatment of IgG4-Related Disease E. Della-Torre, M.C. Baker, W. Zhang,‘ C.A. Perugino,’ G. Katz,° Y. Tanaka,‘ A. Khosroshahi,’ A. Kleger,® N. Schleinitz,? F. Martinez-Valle,!° H. Schulze-Koops,!! S. Nakayamada,° V. Rebours,'? K