obexelimab (ZB012) / Xencor, Zenas BioPharma, BMS, Royalty - LARVOL DELTA

Efficacy and Safety of Obexelimab to Treat IgG4-Related Disease: Protocol for a Global, Randomized, Placebo-Controlled Trial. (PubMed, Rheumatol Ther) - P3 | "The INDIGO trial achieved its global enrollment goal with 194 patients, making it the largest phase 3 trial in IgG4-RD to date and providing 90% power to detect a clinically meaningful reduction in flare risk. This trial will provide critical evidence on B-cell inhibition as a treatment strategy for IgG4-RD and assess obexelimab as a potential steroid-sparing option to address significant unmet needs of this patient population."

Clinical • Journal • Inflammation

Zenas BioPharma Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "Zenas expects to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in the second quarter of 2026 and a Marketing Authorization Application (MAA) to the EMA in the second half of 2026. The Company expects that full data from the INDIGO trial will be presented at a future medical meeting...Topline results of the Phase 2 SunStone trial in Systemic Lupus Erythematosus (SLE) expected 4Q 2026."

EMA filing • FDA filing • P2 data • P3 data • Immunology • Inflammation • Systemic Lupus Erythematosus

Week 12 Results from MoonStone, a Phase 2 Study of Obexelimab in Relapsing Multiple Sclerosis (ACTRIMS Forum 2026) - P2 | "At week 12, treatment with obexelimab resulted in a near complete suppression of the cumulative number of new GdE T1 lesions over weeks 8 and 12 compared with placebo, accompanied by reductions in new and/or enlarging T2-weighted lesions. No new safety concerns were observed during this study. These results provide the first clinical evidence of activity for obexelimab in RMS and support further investigation of this molecule as a novel B-cell inhibitor for the treatment of MS."

Late-breaking abstract • P2 data • CNS Disorders • Infectious Disease • Multiple Sclerosis

A randomized Phase 2 trial for Systemic Lupus Erythematosus is ongoing and Zenas expects to report topline results, including biomarker data from this trial in the fourth quarter of 2026. (GlobeNewswire)

Biomarker • P2 data • Systemic Lupus Erythematosus

Zenas BioPharma Announces Late-Breaking Platform Presentation of Results from Phase 2 MoonStone Trial of Obexelimab in Relapsing Multiple Sclerosis at ACTRIMS Forum 2026 (GlobeNewswire) - "Separately announced 24-week data support the robust and durable activity of obexelimab and further validate its unique inhibitory mechanism of action...Obexelimab met the primary endpoint, demonstrating a highly statistically significant 95% relative reduction in the cumulative number of new gadolinium (Gd)-enhancing (GdE) T1 hyperintense lesions over week 8 and week 12 compared with placebo (p=0.0009)...The adjusted mean number of new GdE T1 hyperintense lesions per scan was 0.01 (95% CI: 0.00, 0.06) in the obexelimab group compared to 0.23 (95% CI: 0.11, 0.51) with placebo."

Late-breaking abstract • P2 data • Multiple Sclerosis

Trials in Progress: Study Design of the Phase 2 MoonStone Trial of Obexelimab in Relapsing Multiple Sclerosis (ACTRIMS Forum 2026) - P2 | "The MoonStone trial is designed to evaluate the efficacy and safety of obexelimab, a novel B cell inhibitor, in RMS. Findings from this study will inform the potential role of this differentiated mechanism in MS treatment."

P2 data • CNS Disorders • Multiple Sclerosis • CD19 • NEFL

Zenas also expects to report topline results, including a biomarker analysis, of the obexelimab Phase 2 SunStone trial in SLE in the fourth quarter of 2026 (GlobeNewswire)

Biomarker • P2 data • Systemic Lupus Erythematosus

Zenas BioPharma Announces Positive Results from Phase 3 INDIGO Registrational Trial of Obexelimab in Immunoglobulin G4-Related Disease (IgG4-RD) (GlobeNewswire) - "Zenas anticipates submitting a Biologics License Application (BLA) to the FDA in the second quarter of 2026 and a Marketing Authorization Application (MAA) to the EMA in the second half of 2026...Obexelimab met the primary endpoint, demonstrating a highly statistically significant and clinically meaningful 56% reduction in the risk of IgG4-RD flare compared to placebo (Hazard Ratio 0.44, p=0.0005) during the 52-week randomized placebo-controlled period. Obexelimab also met and demonstrated highly statistically significant activity compared to placebo on all four key secondary endpoints...The Company expects that full data from the INDIGO trial will be presented at a future medical meeting..."

EMA filing • FDA filing • P3 data • Immunology • Inflammation

Management of Autoimmune Hemolytic Anemia (ASH 2025) - "For relapsed/refractory patients rituximab has become the preferred second line-therapy, comparing favorably with the traditional splenectomy, which has been progressively abandoned or moved to further lines along with classic immunosuppressors. Several novel treatments are in development for wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab)."

IO biomarker • Anemia • Autoimmune Hemolytic Anemia • Bone Marrow Transplantation • Hematological Disorders • Immunology • Infectious Disease • HP • SYK

Management of autoimmune hemolytic anemia. (PubMed, Hematology Am Soc Hematol Educ Program) - "Rituximab is now the preferred second-line option for relapsed/refractory patients, comparing favorably with the traditional splenectomy. The latter is increasingly reserved for later lines together with classic immunosuppressants. Several novel treatments are in development for refractory wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab)."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Bone Marrow Transplantation • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Transplantation • SYK

Obexelimab, a CD19 and FcγRIIb inhibitor of B cell function (GlobeNewswire) - "Systemic Lupus Erythematosus (SLE): Continued enrollment in the Phase 2 SunStone trial, a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of obexelimab in patients with SLE. Zenas expects to complete enrollment of the Phase 2 SunStone trial around year-end 2025 and report topline results in mid-2026."

Enrollment status • P2 data • Systemic Lupus Erythematosus

Effect of Obexelimab on the Production of Anti-Erythrocyte Autoantibodies in Vitro By Mitogen Stimulated Direct Anti-Globulin Test (MS-DAT) (ASH 2024) - "Rituximab reduced anti-RBC autoantibody production in vitro by 40%, while the isotype control had no effect.Conclusion : These preliminary results demonstrate an immunomodulatory effect of obexelimab on the production of anti-erythrocyte autoantibodies in vitro either in unstimulated or mitogen-stimulated wAIHA patient whole blood cultures. This work supports the ongoing Phase 2 study, evaluating the efficacy and safety of obexelimab in patients with wAIHA."

Preclinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • Rare Diseases • CD19

Evaluation of Obexelimab in Patients with Warm Autoimmune Hemolytic Anemia: Preliminary Results from an Open Label Phase 2 Study (ASH 2024) - P3 | "There were no discontinuations due to adverse events.Conclusions. Data from the ongoing study suggests that obexelimab administered SC is well-tolerated and may provide improvement in Hgb and other biomarkers of anemia in patients with primary wAIHA, who have failed at least one prior therapy."

Clinical • P2 data • Anemia • Autoimmune Hemolytic Anemia • Fatigue • Gastroenterology • Hematological Disorders • Hepatology • Immunology • Pulmonary Disease

Effect of Obexelimab Surrogate Monoclonal Antibody on Inhibition of Autoimmune Hemolytic Anemia (AIHA) Induction in Mice (ASH 2024) - "Most importantly, the mean levels of hemoglobin, a marker of anemia, were higher in XENP8206 treated disease mice when compared to levels in the PBS treated disease mice at weeks 11 and 12 (p<0.05). Taken together, the current study demonstrated in vivo pharmacological activities of obexelimab surrogate mAb XENP8206 in a relevant disease model and provide supportive scientific rationale for the development of obexelimab as a treatment for AIHA."

Preclinical • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • CD19 • CD21 • CD24 • CD93 • FAS • SDC1 • SPN

Zenas BioPharma Announces Positive Results from Phase 2 MoonStone Trial of Obexelimab in Relapsing Multiple Sclerosis (GlobeNewswire) - "Obexelimab met the primary endpoint, demonstrating a highly statistically significant 95% relative reduction in the cumulative number of new gadolinium (Gd)-enhancing (GdE) T1 hyperintense lesions over week 8 and week 12 compared with placebo (p=0.0009)....Near-complete suppression of new GdE T1 hyperintense lesions, which are markers of active inflammation, was observed with obexelimab by 8 weeks of treatment and was sustained through week 12....Zenas also expects to report topline results from...24-week MoonStone trial results in the first quarter of 2026."

P2 data • Multiple Sclerosis

New Developments in the Treatment of IgG4-Related Disease: A Comprehensive Clinical Approach. (PubMed, J Clin Med) - "Although rituximab has recently demonstrated efficacy in the treatment of IgG4-RD, no consensus exists regarding the optimal maintenance regimen. The emergence of new B-cell-targeted therapies and other immunomodulators represents a promising step toward more personalized treatment approaches. In this review, we provide an updated and integrative overview of the emerging treatment strategies for IgG4-RD, highlighting future directions towards individualized management."

Journal • Review • Immunology • Inflammation

Effect of obexelimab on the production of anti-RBC Ab and cytokines from patients with warm autoimmune hemolytic anemia. (PubMed, Blood Adv) - "Soluble receptor IL-2Ra was slightly reduced and APO-1/FAS was minimally increased in obexelimab (15 mcg/mL) treated PWM-stimulated blood cell cultures. Collectively, these findings support the notion that obexelimab exerts an immunomodulatory effect on RBC-specific autoantibody and cytokine production in wAIHA."

Journal • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • FAS • IFNG • IL10 • IL17A • IL2RA • TGFB1 • TNFA

Obexelimab, a CD19 and FcγRIIb inhibitor of B cell function (GlobeNewswire) - "Target enrollment of the INDIGO trial concluded in November 2024, and Zenas expects to report topline results around year-end 2025....Relapsing Multiple Sclerosis (RMS) Phase 2 MoonStone trial...Zenas expects to report results from this trial, including the 12-week primary endpoint results, early in the fourth quarter of 2025....Zenas expects to complete enrollment of the Phase 2 SunStone trial around year-end 2025 and report topline results in mid-2026."

P2 data • P3 data: top line • Multiple Sclerosis • Systemic Lupus Erythematosus

Zenas also announces $120.0 million private placement financing (GlobeNewswire) - "Upon closing of the Private Placement, Zenas expects that its cash, cash equivalents and investments will be sufficient to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2026, and assuming receipt of the potential $75 million milestone from Royalty Pharma for the defined success criteria in the Phase 3 INDIGO trial, into the first quarter of 2027."

Financing • Immunology

INDIGO: A Phase 3 Study of Obexelimab in Patients With IgG4-Related Disease (clinicaltrials.gov) - P3 | N=194 | Active, not recruiting | Sponsor: Zenas BioPharma (USA), LLC | Trial completion date: Dec 2027 ➔ Feb 2029

Trial completion date • Inflammation

CD19 and FcγRIIb co-engagement inhibits processes essential to T cell-dependent B-cell responses. (PubMed, J Immunol) - "Treatment after GC onset resulted in dissolution of the GC. Collectively, these data demonstrate that CD19/FcγRIIb co-engagement effectively suppresses processes essential to support T cell-dependent B-cell responses, which is consistent with the proposed mechanism of action of obexelimab."

Journal • IL2RA

Royalty Pharma and Zenas BioPharma Enter Into Obexelimab Funding Agreement for Up to $300 Million (The Manila Times) - "Initial $75 million to fund the potential U.S. commercial launch of obexelimab for the treatment of IgG4-Related Disease; Additional $150 million associated with the upcoming results of the obexelimab Phase 3 INDIGO trial and FDA approval for the treatment of IgG4-Related Disease."

Financing • Immunology

Pharmacokinetics, Receptor Occupancy, and Pharmacodynamics of Obexelimab Following Intravenous Administration in Adult Healthy Volunteers and in Patients With Rheumatoid Arthritis. (PubMed, Clin Pharmacol Drug Dev) - "Obexelimab was generally well-tolerated, primarily mild-to-moderate gastrointestinal events occurring more frequently than with placebo. These results support further development of obexelimab for autoimmune disorders."

Journal • PK/PD data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD20 • CD86

A Study of Obexelimab in Patients With Relapsing Multiple Sclerosis (MoonStone) (clinicaltrials.gov) - P2 | N=93 | Active, not recruiting | Sponsor: Zenas BioPharma (USA), LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

Zenas BioPharma Reports First Quarter 2025 Financial Results and Provides Corporate Updates (GlobeNewswire) - "Topline results from pivotal Phase 3 INDIGO trial in Immunoglobulin G4-Related Disease expected around year-end 2025; Phase 2 MoonStone trial in Relapsing Multiple Sclerosis enrollment concluding; topline results expected early in the fourth quarter 2025; Enrollment of Phase 2 SunStone trial in Systemic Lupus Erythematosus expected to be completed by year-end 2025; topline results expected mid-2026."

P2 data • P3 data: top line • Trial status • Immunology • Multiple Sclerosis • Systemic Lupus Erythematosus