IN8bio, Inc. presented compelling preclinical data for its novel gamma-delta T cell engager INB-619 at the 2025 American College of Rheumatology Convergence Meeting in Chicago, demonstrating the therapy's potential to transform autoimmune disease treatment through safer and more effective B cell depletion.
Breakthrough T Cell Engager Technology
INB-619 represents a potential first-in-class, CD19-targeted, pan-gamma delta T cell engager designed to activate and expand both major gamma-delta T cell subsets, V-delta-1 and V-delta-2. In preclinical systemic lupus erythematosus donor models, the therapy achieved complete elimination of B cells with efficacy equivalent to approved CD19 and CD20 engagers, including the FDA-approved compounds blinatumomab and mosunetuzumab.
The data demonstrated minimal secretion of adverse cytokines such as IL-6, a validated biomarker for cytokine release syndrome, at concentrations multiples lower than currently marketed compounds tested. This cytokine-sparing profile could allow for higher doses and deeper B cell depletion than has been observed with other protein engagers to date.
Enhanced Safety Profile Through Novel Mechanism
Unlike conventional T cell engagers that activate the CD3 receptor and can trigger potentially lethal toxicities including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, INB-619 uniquely targets through the gamma-delta T cell receptor and does not require CD3 engagement. This mechanism significantly reduces the potential for toxicities from cytokines or cellular exhaustion.
INB-619 selectively expanded gamma-delta T cells from both SLE and healthy donors without activating CD4+ or CD8+ alpha-beta T cells, supporting the potential for an improved safety and tolerability profile. The therapy's unique ability to expand gamma-delta T cells in vivo allows it to overcome the low baseline gamma-delta T cell counts that have limited other gamma-delta T cell engager technologies in development.
Clinical Implications for Autoimmune Disease
"These results demonstrate IN8bio's unique know-how and capabilities with gamma-delta T cell biology," said William Ho, CEO and Co-Founder of IN8bio. "INB-619 is a gamma-delta T cell engager with innovative properties fully developed in-house. We achieved deep, consistent B cell depletion, independent of starting gamma-delta T cell levels, with a potentially superior safety profile compared with existing T cell engagers."
The results highlight INB-619's potential to transform the treatment of autoimmune diseases by harnessing the unique properties of gamma-delta T cells to safely and precisely eliminate pathogenic B cells and drive immune reset. By engaging both circulating and tissue-resident gamma-delta T cells, INB-619 could enable more durable immune modulation in complex autoimmune diseases.
Robust Preclinical Performance
The data demonstrated robust, dose-dependent B cell killing and gamma-delta T cell expansion while maintaining a favorable cytokine profile consistent with the unique biology of gamma-delta T cells. Gamma-delta T cells are specialized immune cells capable of potent killing activity with low or no cytokine release, making them particularly attractive for therapeutic applications.
INB-619 achieved robust gamma-delta T cell expansion and complete B cell depletion across both healthy donor samples and those with active systemic lupus erythematosus disease, demonstrating consistent efficacy regardless of disease state. This pan-gamma-delta T cell expansion leads to deep B cell depletion, a key therapeutic goal in B cell-driven autoimmune disorders such as SLE.
