IN8bio (NASDAQ:INAB) outlined new preclinical and clinical data across its gamma-delta T-cell platforms during a company R&D presentation, highlighting a CD19-directed T-cell engager program for autoimmune disease and updated findings from its glioblastoma cell therapy programs.
William Ho, IN8bio’s CEO and co-founder, said the clinical-stage biotechnology company is focused on developing gamma-delta T cells for autoimmune disease and oncology. Ho described gamma-delta T cells as a small but potentially influential part of the immune system, comprising about 1% to 5% of the white blood cell population, and said the company believes they can coordinate broader immune responses without some of the liabilities associated with CD3-directed approaches.
INB-619 Designed as a Pan-Gamma-Delta T-Cell Engager
Rochlin said INB-619 includes three components: a CD19 targeting domain, a pan-gamma-delta T-cell binding domain designed to activate multiple gamma-delta T-cell compartments, and an undisclosed gamma-delta T-cell expansion domain. She said the CD19 domain could be swapped for other targets, though the presentation focused on CD19.
In preclinical experiments, Rochlin said INB-619 eliminated CD19-expressing Nalm-6 cells in culture while maintaining the broader immune cell population. She also said the engager expanded Vδ1, Vδ2 and other gamma-delta T-cell subtypes, with expansion decreasing after target cells were eliminated, which the company characterized as controlled rather than runaway activation.
In lupus donor samples, Rochlin said INB-619 drove B-cell depletion by day four and day six that was comparable to commercial CD19 and CD20 engagers blinatumomab and mosunetuzumab. She said INB-619 did not broadly expand CD4 or CD8 alpha-beta T-cell compartments in those experiments, and showed lower levels of cytokines including IL-6, IL-10, IL-17 and TNF-alpha versus the comparator engagers.
Rochlin said the company is now evaluating INB-619 in multiple animal models and expects to release animal data later this year. During the Q&A session, she said the first target in those studies is B-cell depletion, while also evaluating gamma-delta T cells and cytokine responses.
Glioblastoma Program Shows Longer PFS in Repeat-Dose Patients
The company also reviewed data from its glioblastoma programs, INB-200 and INB-400. These programs use an autologous, genetically modified gamma-delta T-cell therapy designed to resist temozolomide chemotherapy and be delivered directly into the brain during maintenance therapy after surgery, radiation and chemotherapy.
Dr. David Reardon, head of neuro-oncology at Dana-Farber, described glioblastoma as an incurable and “essentially universally fatal” cancer, with the current standard of care based on surgery, radiation and temozolomide remaining largely unchanged since 2005. He said median overall survival with that standard regimen is just under 15 months, and said many prior Phase 3 studies in glioblastoma have failed because therapies do not reach the tumor effectively, particularly the infiltrating edge protected by the blood-brain barrier.
Rochlin said IN8bio has treated 17 patients across the Phase 1 and Phase 2 programs, with no major toxicities, no ICANS and no cytokine release syndrome reported, despite direct dosing into the brain. She said repeat-dose patients, combining those who received three or six doses, had median progression-free survival of 13 months and median overall survival of 17.2 months as of the company’s data cut. By comparison, she said a control group of enrolled patients who received standard of care but not IN8bio’s cells had median PFS of 6.6 months and median OS of 13.2 months, while the historical Stupp regimen showed median PFS of 6.9 months and median OS of 14.6 months.
Rochlin said the company observed statistically significant separation in Kaplan-Meier curves for progression-free survival and overall survival, though she also noted the data will be updated at ASCO. She said immune analyses showed repeat dosing helped sustain peripheral gamma-delta T-cell levels, which correlated with overall survival in the company’s analysis.
Single-Cell Tumor Analysis Points to Immune Changes
Rochlin also discussed exploratory single-cell and AI-based tumor mapping analyses of glioblastoma samples. She said IN8bio observed evidence that treatment turned a “cold” tumor microenvironment “hot,” including increased immune cell infiltration, reduced cell proliferation and reduced granulocytes and neutrophils in treated tumors.
In one analysis, she said treated tumor samples showed an 18-fold increase in CD8 T cells, a 24% decrease in tumor burden, an 82% reduction in Ki-67 cell proliferation and a 90% reduction in granulocytes. Rochlin said the findings are intended to help inform future trial design and understand mechanisms of response, resistance and escape.
Cash Runway and Regulatory Plans
Patrick McCall, IN8bio’s chief financial officer, said the company had approximately $21.1 million in cash as of March 31, which he said provides runway into the second quarter of 2027. McCall said a potential $20.1 million second close from a prior financing is tied to animal data from the T-cell engager program and could extend the company through the IND for INB-619 and through 2027.
McCall said IN8bio expects to present additional long-term follow-up from the glioblastoma program at ASCO and at another medical meeting later in the year. Ho said the company also plans to engage with the FDA in the second half of the year to discuss a potential regulatory path for the glioblastoma program, including whether an accelerated approval pathway could be feasible.
During the Q&A session, Reardon called the glioblastoma data “quite compelling” and said progression-free survival exceeding predicted overall survival is meaningful in the context of the disease. He said larger studies will be needed to validate the results and said an appropriate randomized control cohort would likely be important for the FDA.
About IN8bio (NASDAQ:INAB)
IN8bio is a clinical-stage biopharmaceutical company developing γδ T cell therapeutic and γδ T cell engager (TCE) product candidates to address unmet medical needs. γδ T cells are
a specialized population of T cells that possess unique properties, including the ability to differentiate between healthy and diseased tissue. The Company’s lead programs consist of INB-100, an allogeneic γδ T cell candidate for adult patients with high-risk
leukemias undergoing haploidentical stem cell transplantation.
