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

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

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

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

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 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

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

SunStone: A Study of Obexelimab in Patients with Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=190 | Recruiting | Sponsor: Zenas BioPharma (USA), LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

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

Enrollment open • CNS Disorders • Multiple Sclerosis

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

New P2 trial • CNS Disorders • Multiple Sclerosis

SunStone: A Study of Obexelimab in Patients With Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=190 | Not yet recruiting | Sponsor: Zenas BioPharma (USA), LLC

New P2 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

POPULATION PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSES OF OBEXELIMAB IN HEALTHY VOLUNTEERS AND IN PATIENTS WITH RHEUMATOID ARTHRITIS OR IgG4-RELATED DISEASE (EULAR 2024) - "The population PK analysis of obexelimab demonstrates the ethnic insensitivity of obexelimab PK. Optimal PK, robust RO and PD following 250 mg SC weekly further supports clinical development of obexelimab to treat B-cell mediated autoimmune diseases."

Clinical • PK/PD data • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD19

OBEXELIMAB INHIBITS BCR SIGNALLING AND PATHOGENIC B CELL CHEMOTAXIS IN PATIENTS WITH IGG4-RELATED DISEASE (EULAR 2024) - "Collectively, these gene expression and chromatin accessibility data suggest that obexelimab has a broad inhibitory effect on B cells consistent with the role of phosphoinositides in regulating the cellular and activation mechanisms in B cells. Paired with the previous published data demonstrating interference with BCR signalling, obexelimab likely dampens crosslinked BCR-induced BTK phosphorylation in antigen-experienced B cell subsets from IgG4-RD patients and impacts phosphoinositide mediated B cell migration. Together, these two mechanisms may eliminate the potential of pathogenic, self-reactive B cells to respond to self-antigen, migrate out of secondary lymphoid organs, and infiltrate inflamed tissues."

Clinical • IO biomarker • Inflammation • CD27

Obexelimab in IgG4-related disease: B-cell inhibition as a novel therapeutic approach. (PubMed, Lancet Rheumatol) - No abstract available

Journal • Inflammation

Evaluation of the safety, efficacy, and mechanism of action of obexelimab for the treatment of patients with IgG4-related disease: an open-label, single-arm, single centre, phase 2 pilot trial. (PubMed, Lancet Rheumatol) - P2 | "All patients except for one had clinical responses to obexelimab treatment. Both reductions in circulating B cells without evidence of apoptosis during obexelimab treatment and their rapid rebound after treatment discontinuation suggest that obexelimab might lead to B-cell sequestration in lymphoid organs or the bone marrow. These results support the continued development of obexelimab for the treatment of IgG4-related disease."

Journal • P2 data • Allergy • CNS Disorders • Dermatology • Immunology • Infectious Disease • Inflammation • Musculoskeletal Diseases • Rheumatology • CD19 • CD4 • FCGR2B

IgG4-related disease: A proteiform pathology with frequent chest manifestations (PubMed, Rev Mal Respir) - "Substantial progress has been made over recent years in understanding IgG4-RD pathophysiology, and personalized patient care seems to be an achievable medium-term goal."

Journal • Review • Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pancreatitis • Pulmonary Disease • Respiratory Diseases • BTK • SLAMF7

A Study of Obexelimab in Patients With Warm Autoimmune Hemolytic Anemia (SApHiAre) (clinicaltrials.gov) - P3 | N=134 | Recruiting | Sponsor: Zenas BioPharma (USA), LLC | Trial completion date: Dec 2027 ➔ Jun 2026 | Initiation date: Jun 2023 ➔ Sep 2023

Trial completion date • Trial initiation date • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

Obexelimab Inhibits B Cell Activation and May Interfere with B Cell Chemotaxis in IgG4-Related Disease (ACR Convergence 2023) - "Collectively, these chromatin accessibility and transcriptromic data suggest that reciprocal changes in PIP3 and PI(3,4)P2 dependent events induced by obexelimab on B cells alter B cell activation and migration. Paired with the previous published data demonstrating attenuation of BCR signalling, obexelimab not only reduces PIP3-dependent BCR-induced BTK activation in B cells from IgG4-RD patients but could also enhance PI(3,4 )P2 phosphoinositide-mediated B cell migration, possibly causing sequestration of B cells. Together, these two mechanisms may eliminate the potential of pathogenic, self-reactive B cells to respond to self-antigen, migrate out of secondary lymphoid organs, and infiltrate inflamed tissues."

IO biomarker • Inflammation • CD27

Population Pharmacokinetic and Pharmacodynamic Analyses of Obexelimab in Healthy Volunteers and in Patients with Rheumatoid Arthritis or IgG4-Related Diseases (ACR Convergence 2023) - "The population PK analysis of obexelimab demonstrates the ethnic insensitivity of obexelimab PK. Robust RO and PD following 250 mg SC weekly further supports clinical development of obexelimab to treat B-cell mediated autoimmune diseases."

Clinical • PK/PD data • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD19

Antibody based therapeutics for autoimmune hemolytic anemia. (PubMed, Expert Opin Biol Ther) - "The anti-CD20 rituximab, which targets Ab production by B-cells, induces 80% of response in warm type AIHA (wAIHA) and 50-60% in cold agglutinin disease (CAD). Other B-cell targeting MoAbs including ianalumab, povetacicept, and obexelimab are under active study. The anti-CD38 MoAb daratumumab has been used in several reports to target long-lived plasma-cells responsible of AIHA relapse, being effective even in multi-refractory cases. Anti-complement MoAbs will soon change treatment paradigm in CAD; the anti-C1s sutimlimab rapidly increased Hb in more than 80% of cases. Finally, MoAbs inhibiting the neonatal Fc receptor (FcRn), such as nipocalimab, can reduce the half-life of the pathogenic autoAbs, representing a promising treatment for wAIHA...Thus, combination with B-cell/plasma cell targeting drugs will deserve to be explored. On the other hand, their rapid efficacy should be exploited for the acute AIHA phase."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

A Study of Obexelimab in Patients With Warm Autoimmune Hemolytic Anemia (SApHiAre) (clinicaltrials.gov) - P3 | N=134 | Recruiting | Sponsor: Zenas BioPharma (USA), LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology