Gnti-148: an allogeneic islet-specific engineered treg for treating T1D

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Gentibio, Inc. $1,066,332 on August 24, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to develop GNTI-148, an allogeneic islet-specific engineered regulatory T cell therapy for treating newly diagnosed type 1 diabetes.

GNTI-148 is designed to restore immune tolerance and preserve pancreatic islet function in newly diagnosed T1D patients with the goal of halting disease progression. The therapy builds on Gentibio's proprietary platform featuring stable FOXP3 expression, pancreatic islet-specific targeting, and tunable IL-2 signaling via a chemically inducible signaling complex. By integrating hypoimmune engineering technology, GNTI-148 can be delivered as an off-the-shelf allogeneic product, offering the durable efficacy of autologous therapies at lower cost and greater accessibility through allogeneic scalability.

Work is performed in Cambridge, Massachusetts. The period of performance runs through July 31, 2028. This is a Phase II SBIR award. The funding supports proof-of-concept, safety and toxicology, and technical development studies to validate GNTI-148 functionality, safety, and product feasibility.

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease that affects approximately 1.3 million adults and 200,000 children in the united states, with incidence rising annually. Standard therapies, including insulin replacement and immunomodulators such as teplizumab, provide partial disease management but do not achieve durable modification and are associated with long-term risk for complications. Thus, a cure remains a critically unmet medical need. Regulatory T cell (TREG) therapy represents a promising approach to restore immune tolerance and preserve pancreatic islet function in newly diagnosed patients. However, prior clinical experience has been constrained by limited stability, persistence, specificity, and accessibility of TREG products. In this phase II sbir proposal, gentibio will develop gnti-148 to treat patients with newly diagnosed T1D and aim to halt disease progression. Gnti-148 is built on a proprietary platform that ensures stable FOXP3 expression, pancreatic islet-specific targeting, and tunable IL-2 signaling via a chemically inducible signaling complex (CISC) used in our clinical-stage autologous product gnti-122. By integrating gentibio's novel hypoimmune engineering technology to overcome host immune rejection, gnti-148 can be delivered as an allogeneic, off-the-shelf engtreg product for durable treatment of recently diagnosed T1D patients. Gnti-148 is designed with the durable efficacy of autologous therapies while offering a cost-effective solution for broader and more accessible clinical use, enabled by the scalability of allogeneic therapies. Importantly, IT mirrors the convenience of biologics while offering potential for more durable insulin-independence and improved clinical outcomes. Through a combination of proof-of-concept, safety/TOX, and technical development studies, this proposal will validate gnti-148 functionality, safety, and product feasibility, and DE-risks clinical translation to position IT as a transformative, accessible therapy for patients with recently diagnosed T1D. As a precision- engineered, off-the-shelf cell therapy, gnti-148 can transform the treatment paradigm of T1D through immune regulation and protecting pancreatic islets.