Pipeline & Programs
Advancing a PIPELINE of GEM-DIMER™ antibodies to treat severe diseases with significant unmet patient needs.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which the immune system attacks healthy tissue, causing widespread inflammation across the skin, joints, kidneys, and other organs. SLE disproportionately affects women, who account for approximately 90% of cases, and is most commonly diagnosed between 15 and 45 years of age.
Lupus nephritis
Lupus nephritis (LN) is a common organ-specific manifestation of SLE, affecting approximately 50% of patients. LN occurs when inflammation targets the kidneys, which can lead to irreversible organ damage and end stage renal disease. SLE patients without LN are classified as having extrarenal lupus (ERL).
LEAD PROGRAM
HB2198
Hinge Bio’s lead program, HB2198, is a bispecific anti-CD19/anti-CD20 GEM-DIMER™ antibody with two Fc domains, both of which are enhanced for potent binding to Fc gamma receptors on immune effector cells. Combining bivalent targeting of both CD19 and CD20 with dual enhanced Fc domains, HB2198 broadly targets B cells while engaging natural killer cells and tissue-resident macrophages, maximizing both comprehensive targeting and immune effector mechanisms. In vivo preclinical studies have demonstrated rapid and deep depletion of both peripheral and tissue-resident B cells, including memory B cells.
The therapeutic goal of HB2198 is to induce remission and possibly a cure in patients with B cell-mediated autoimmune diseases by rapidly depleting their autoantibody-producing B cells, with the safety, accessibility, and cost benefits of an off-the-shelf antibody-based therapeutic.
- Antibody-dependent cellular cytotoxicity (ADCC)
- Antibody-dependent cellular phagocytosis (ADCP)
- Complement-dependent cytotoxicity (CDC)
- Direct B cell killing
B CELL DEPLETION
B cells comprise a diverse and central component of the adaptive immune system, spanning early progenitors through antibody-secreting plasma cells. CD19 and CD20 are clinically validated targets with demonstrated therapeutic impact across autoimmune diseases and B cell malignancies.
Dual targeting of CD19 and CD20 offers the potential for broader and deeper B cell depletion than single-target approaches. CD19 expression is generally maintained on plasmablasts, a population that expands in certain autoimmune diseases and during disease flares. CD20 is expressed at high density on mature B cells, enabling efficient antibody binding and immune-mediated depletion. Additionally, a subset of pathogenic CD20⁺ T cells has been identified in autoimmune inflammation and described across multiple publications, representing a population that CD20-directed approaches can capture but CD19-only approaches would miss. Importantly, HB2198 is the only antibody-based therapy combining dual CD19/CD20 targeting with dual enhanced Fc technology, potentially enabling greater effector cell engagement than other approaches in the class.
