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

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

IgG4-related disease: lessons from the first 20 years. (PubMed, Rheumatology (Oxford)) - "Both glucocorticoids and B cell depletion are effective at inducing remission in IgG4-RD in most patients. The optimal approach to the use of these agents is now being defined in clinical trials."

Journal • Review • Endocrine Disorders • Fibrosis • Immunology • Inflammation • Oncology • Pancreatitis • Rheumatology

Zenas BioPharma Announces Key 2024 Accomplishments and 2025 Business Objectives to Support the Global Development and Commercialization of Therapies for Autoimmune Diseases (GlobeNewswire) - "Topline results from Phase 2 Trial in Relapsing Multiple Sclerosis (MoonStone) expected in third quarter 2025; Topline results from pivotal Phase 3 Trial in Immunoglobulin G4-Related Disease (INDIGO) expected year-end 2025; Enrollment of Phase 2 Trial in Systemic Lupus Erythematosus (SunStone) expected to be completed in 2025..."

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

SunStone: A Study of Obexelimab in Patients with Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=190 | Recruiting | Sponsor: Zenas BioPharma (USA), LLC | Trial completion date: Mar 2026 ➔ Sep 2026 | Trial primary completion date: Nov 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

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 | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2026 ➔ Dec 2027

Enrollment closed • Trial completion date • Inflammation

A Study of Obexelimab in Patients With Warm Autoimmune Hemolytic Anemia (SApHiAre) (clinicaltrials.gov) - P3 | N=134 | Active, not recruiting | Sponsor: Zenas BioPharma (USA), LLC | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2026 ➔ Jun 2026

Enrollment closed • Trial primary completion date • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Pharmacokinetics, Pharmacodynamics, Bioavailability, and Immunogenicity of Obexelimab Following Subcutaneous Administration in Healthy Japanese and Non-Japanese Volunteers. (PubMed, Adv Ther) - P1 | "Obexelimab SC administration demonstrated favorable bioavailability, was well-tolerated, and showed no clinically meaningful ethnic differences in PK/PD. These results support further clinical development of SC obexelimab to treat B-cell mediated autoimmune diseases."

Journal • PK/PD data • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus • CD19

Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy. (PubMed, Transfus Med Hemother) - "Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter...Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan)...Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging. This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Oncology • Rare Diseases • Thrombosis • Transplantation

A Population Modeling and Simulation of the Effect of Obexelimab Exposure on the QTc Interval in Healthy Volunteers and Patients with Rheumatoid Arthritis or IgG4-Related Disease (ACR Convergence 2024) - "A linear model form was adequate to predict obexelimab concentration-induced changes in QTc. Obexelimab did not produce any clinically relevant effect on electrocardiographic QTc interval in healthy volunteers, RA or IgG4-RD patients."

Clinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD19