Hinge Bio Initiates First-in-Human Trial of HB2198, Novel Dual-Target B Cell Depleting Therapy for Autoimmune Diseases
Key Insights
Hinge Bio (search) has successfully dosed the first participants in a Phase 1 clinical trial of HB2198, a novel multispecific antibody targeting both CD19 (search) and CD20 (search) for B cell depletion in autoimmune diseases (search).
The company has initiated two separate Phase 1 trials: one evaluating safety and tolerability in healthy volunteers and another screening patients with systemic lupus erythematosus (search).
HB2198 aims to achieve immunological remission through rapid and deep B cell depletion without T cell activation, potentially offering improved safety compared to CAR-T or T cell engager approaches.
Hinge Bio (search), a privately-held clinical-stage biotechnology company, has announced the successful dosing of the first participants in its Phase 1 clinical trial of HB2198, marking a significant milestone in the development of novel B cell depleting therapies for autoimmune diseases (search). The company's lead multispecific product candidate targets both CD19 (search) and CD20 (search) with enhanced dual Fc domains, representing a new approach to treating B cell-mediated autoimmune disorders (search).
Dual Phase 1 Trial Strategy
Hinge Bio (search) has initiated two separate Phase 1 clinical trials of HB2198. The first is a dose-escalation trial assessing safety, tolerability, pharmacokinetics and pharmacodynamic activity in healthy volunteers, while a second Phase 1 trial evaluating HB2198 in patients with Systemic Lupus Erythematosus (search) (SLE (search)) is currently open to screening.
"The Phase 1 healthy volunteer population allows us to dose escalate efficiently, and importantly, evaluates the potential safety advantages of HB2198 and supports expansion into additional B cell-mediated autoimmune diseases (search) beyond SLE (search)," said Paul Brunetta, M.D., Chief Medical Officer at Hinge Bio (search).
Mechanism and Therapeutic Goals
HB2198 is designed to treat B cell-mediated autoimmune disorders (search) by targeting both CD19 (search) and CD20 (search) with enhanced engagement of immune effector cells without activating T cells. This approach aims to address the safety limitations of current therapeutic strategies.
"With HB2198, our therapeutic goal is to achieve immunological remission through rapid and deep B cell depletion without T cell activation and associated cytokine release, thereby providing clinical efficacy with a better safety profile versus CAR-T or T cell engager approaches," Dr. Brunetta explained.
Preclinical Foundation
Preclinical studies have demonstrated robust and deep B cell depletion in both blood and tissues, which supported the clinical evaluation of HB2198 at the planned dose levels and regimens. The studies showed potent depletion of both peripheral and tissue resident B cells in vivo with a promising safety profile.
Emerging clinical evidence supports the concept that deeper tissue B cell depletion associates with greater efficacy for patients living with a variety of autoimmune disorders. HB2198 seeks to achieve an immunological remission through rapid and deep B cell depletion in both peripheral blood and lymphoid tissues, without the challenges and toxicities associated with CAR-T or T cell engagers.
GEM-DIMER Platform Technology
HB2198 is developed from Hinge Bio (search)'s proprietary GEM-DIMER™ platform, which enables the creation of multivalent, multi-specific antibody-based therapeutics designed for enhanced biological activity and unique functionality. The platform is being leveraged to address problems of inadequate efficacy, resistance, and side effects in autoimmunity, inflammatory disease, cancer, and other diseases.
Clinical Significance and Future Outlook
"This first-in-human dosing marks a significant milestone for Hinge Bio (search) and our mission to develop innovative therapies to improve the lives of patients suffering from Lupus (search) and other B cell-mediated diseases with high unmet medical need," said Chief Executive Officer Barry Selick, Ph.D.
The therapeutic goal of HB2198 is to provide the safety, convenience, accessibility, and cost benefits of an off-the-shelf antibody-based therapeutic that can be administered in an outpatient setting. The company believes this approach will provide meaningful benefits to patients compared to existing treatment options.
Hinge Bio (search) is advancing a pipeline of programs with an initial focus on autoimmune disease, positioning HB2198 as a potential breakthrough therapy for patients with B cell-mediated autoimmune disorders (search) who currently face limited treatment options.