Abstract: SA-PO0821
Topologically Engineered, Superdimeric α-CD19 x α-CD20 Bispecific Antibodies with Dual Enhanced Fc Domains: New Class of Natural Killer (NK)/Monocyte Engagers for Deep B Cell Depletion in Lupus Nephritis
Session Information
- Glomerular Management: Real-World Lessons and Emerging Therapies
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Capon, Daniel J, Hinge Bio, Inc., Burlingame, California, United States
- Lewis, Gavin M, Hinge Bio, Inc., Burlingame, California, United States
- Troitskaya, Larisa, Hinge Bio, Inc., Burlingame, California, United States
- Fomin, Marina E, Hinge Bio, Inc., Burlingame, California, United States
- Law, Brian, Hinge Bio, Inc., Burlingame, California, United States
- Frank, Brendon, Hinge Bio, Inc., Burlingame, California, United States
- Chan, Lap Shun Nelson, Hinge Bio, Inc., Burlingame, California, United States
- Edman, Ursula, Hinge Bio, Inc., Burlingame, California, United States
- Chapin, Steven J, Hinge Bio, Inc., Burlingame, California, United States
- Gefter, Malcolm L, Hinge Bio, Inc., Burlingame, California, United States
- Punnonen, Juha, Hinge Bio, Inc., Burlingame, California, United States
Background
The dramatic efficacy of anti-CD19 CAR-T in systemic lupus erythematosus (SLE) (N Engl J Med 2024 Feb 22;390(8):687-700) has opened up the possibility that autoimmune responses underlying LN may be reset leading to durable remissions. Given the challenges of CAR-T at large scale there is interest in safe and scalable NK/monocyte engagers capable of deep depletion of autoantibody producing B cells.
Methods
We describe GEM-DIMERTM technology, allowing us to engineer superdimeric, tetrahedral antibodies demonstrating bispecific binding to target cells and cooperative binding to recombinant Fcγ receptors expressed on cells. These include NK/monocyte engagers (i.e., CD16a engagers) comprising two α-CD19 (huFMC63) and two α-CD20 (rituximab) targeting domains, and two Fc domains incorporating S239D/I332E mutations that enhance Fcγ receptor binding.
Results
HB2198 demonstrated robust depletion of human B cells in cultures of whole blood or PBMCs, including PBMCs derived from SLE patients. HB2198 also demonstrated potent antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, direct cell killing activity, and macrophage mediated antibody-dependent cellular phagocytosis in the presence of physiological human IgG levels. Treatment of cynomolgus monkeys with HB2198 resulted in >99% depletion of circulating B cells within 1-3 days and remodeling of the B cell compartment as evidenced by a durable shift in proportions of naïve and memory B cells.
Conclusion
Our findings demonstrate the potential of HB2198 as an improved, off-the shelf treatment for LN, SLE and related diseases via deep and broad depletion of both CD19+ and CD20+ cells. First-in-human trials are anticipated in 2025.
GEM-DIMERTM technology used to create clinical candidate HB2198
Funding
- Commercial Support – Hinge Bio, Inc.