-A complete preclinical pharmacology package supporting development of GNTI-122 to first in human trials
Cambridge, Mass., March 22, 2024 – Gentibio, Inc., a biotherapeutics company developing engineered T regulatory (Treg) cells (EngTregs) therapies for autoimmune and auto-inflammatory diseases, today announced the publication of preclinical data for lead program, GNTI-122, for the treatment of newly diagnosed and at-risk Type 1 diabetes (T1D), in the peer-reviewed journal JCI Insights. GNTI-122 is an engineered autologous cell product derived from bulk CD4 T cells isolated from a patient’s peripheral blood. Through gene editing, 3 key pillars are engineered into the cell product; (i) stable FOXP3 expression, (ii) single antigen specificity through introduction of a TCR and (iii) a chemically inducible signaling complex (CISC) allowing the engineered cells to receive a specific and tunable IL-2 signal in response to low dose rapamycin. This unique engineering strategy for the GNTI-122 cell product overcomes key bottlenecks – scalability, specificity, and IL-2scarcity – in the development of Treg therapeutics to treat T1D and other chronic autoimmune diseases.
T1D, also known as juvenile diabetes, is an autoimmune disease caused by the immune system destroying the cells of the pancreas responsible for making insulin. The data in the publication entitled “GNTI-122, an autologous antigen-specific engineered regulatory T-cell therapy for type 1 diabetes,” demonstrated that the GNTI-122 cell production is scalable, and the resulting product has high purity that retains a stable regulatory phenotype and is activated by an islet-specific antigen expressed in beta cells. In an in vitro assay with effector T cells (Teffs) derived from patients with T1D, GNTI-122 demonstrated a mechanism of action through direct suppression of same antigen-specific Teffs and a broader mechanism of bystander and polyclonal suppression of Teffs of different islet antigen specificities. In a T1D mouse model, surrogate mouse engineered Tregs (mEngTregs) with stable FOXP3 expression and a mouse islet specific TCR, demonstrated long term suppression of pathogenic T cells attacking the pancreas, which reduced inflammation, protected insulin-producing islet beta cells, and mitigated the development of T1D. Importantly, inclusion of CISC in the human EngTregs provides access to two key levers of (i) facilitating production of a high purity cell product and (ii) improving in vivo persistence of adoptively transferred GNTI-122 through rapamycin dosing. Finally, the team used both in vitro and in vivo pharmacokinetic studies with rapamycin and GNTI-122 to support development of a translational model aimed at guiding future clinical dosing in T1D patients.
The combined data set presented in this publication established a strong preclinical pharmacology and translational package demonstrating the unique properties GNTI-122 and its potential in the treatment of T1D. “The preclinical data set summarized in this publication demonstrates that GNTI-122 has the potential to be a groundbreaking therapy in T1D. The Genti team is working hard to bring this innovative treatment to patients.” stated Tom Wickham, PhD, chief scientific officer.
About GentiBio, Inc.
GentiBio, Inc. is a biotherapeutics company co-founded by pioneers in Treg biology and immunology from Seattle Children’s Research Institute, Benaroya Research Institute, and MIGAL Galilee Research Institute to develop engineered regulatory T cells programmed to treat autoimmune and inflammatory diseases. GentiBio’s Series A financing was led by Matrix Capital Management with participation by Avidity Partners, JDRF T1D Fund, seed investors OrbiMed, RA Capital Management, Novartis Venture Fund, and Seattle Children’s Research Institute. GentiBio’s autologous and allogeneic engineered Tregs platforms integrate key technologies designed to successfully (re)establish immune tolerance and overcome major limitations in existing Treg therapeutics. GentiBio is at the forefront of leveraging a unique therapeutic modality that has the potential to address the fundamental cause of many diseases that result from overactivity and/or malfunctioning of the immune system. The company also has a collaboration with Bristol Myers Squibb for the development of Treg therapies for inflammatory bowel diseases. To learn more, visit www.gentibio.com
Company Contact:
Chuck Silberstein
Chief Financial Officer
chuck.silberstein@gentibio.com