Obsidian Therapeutics, Inc., a biotechnology company developing cell therapies with pharmacologic operating systems, today announced the presentation of preclinical data demonstrating fine-tuned regulation of cytokine production and CAR-T function using Destabilizing Domains (DDs) paired with FDA-approved small molecule drugs. Obsidian will reveal a suite of novel human DDs and showcase their application in CAR-T therapy at the Society for Immunotherapy of Cancers (SITC) 33rd Annual Meeting in Washington, DC, November 7-11, 2018.
DDs are small, fully-human protein domains that confer conditional stability to a fused payload protein. These regulated cassettes can be readily added to a cell or gene therapy product. CAR-T cells are engineered to find and destroy tumor cells and can be armed with powerful cytokines, such as IL12 and IL15, to further enhance anti-tumor immunity. However, these potent immune modulators require precise control to optimize their therapeutic benefit.
Pharmacologic regulation of CAR-T therapies is a critical next step in the advancement of adoptive immunotherapy for cancer, said Steve Shamah, Ph.D., Senior Vice President and Head of Research for Obsidian, who will present one of the posters at SITCs 33rd Annual Meeting. By designing pharmacologic operating systems that use FDA-approved small molecules for regulation, we believe we have opened a new set of opportunities for next-generation cell therapies.
Highlights of the two preclinical presentations describing Obsidians enhanced CAR-T therapies include:
Abstract Number P271: Titratable and reversible regulation of IL12 or IL15 with FDA-approved drugs for enhanced CAR-T therapy Presenter: Steve Shamah, Ph.D. Date and Time: Friday, November 9, from 12:45 “ 2:15 pm and 6:30 “ 8 pm
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- Our discovery process yields a wide array of fully human DD variants with performance characteristics that can be matched to specific applications.
- We have achieved titratable, fine-tuned regulation of IL12 and IL15 in human T cells in vitro and in vivo with clinically translatable DDs and FDA-approved drugs.
Abstract Number P238: Regulation of in vivo anti-tumor activity of adoptively transferred CAR-T cells using FDA-approved small molecule drugs Presenter: Jennifer Gori, Ph.D., Associate Director, Head of In Vivo Pharmacology, Obsidian Date and Time: Saturday, November 10, from 12:20 “ 1:50 pm and 7:00 “ 8:30 pm
- DDs provide small molecule regulation of CAR expression and activity in T cells.
- We have demonstrated on-demand anti-tumor activity of a clinically translatable DD-CAR in T cells with drug dosing in vivo.
These studies show Obsidians ability to achieve precise kinetic and dose-responsive control over transgene-derived protein expression, fueling the development of CAR-T cell therapies that are potentially safer and more efficacious.
About Destabilizing Domains
Obsidian uses Destabilizing Domains (DDs) to enable pharmacologic regulation of protein activity for next-generation cell and gene therapies. Obsidians DDs are small, fully-human protein domains that confer conditional stability to a fused payload protein. In the absence of a specific small-molecule ligand, the fusion protein is rapidly degraded, whereas in the presence of the ligand the fusion protein becomes stable and functional. Obsidian uses this approach to equip engineered cells with controllable functions that can be precisely tuned by the administration of non-immunosuppressive, small-molecule medicines that are readily available and dispensed by the treating physician.
About Obsidian Therapeutics
Obsidian Therapeutics is a biotechnology company developing next-generation cell and gene therapies with pharmacologic operating systems. Based upon founding work on destabilizing domains by Professor Thomas Wandless, a leading researcher in chemical and systems biology, Obsidians lead programs are CAR-T products that incorporate controllable functions for enhanced safety and efficacy. Obsidian was founded in 2015 by Atlas Venture and is funded by a strong syndicate of venture investors. The company is headquartered in Cambridge, Massachusetts. Please visit www.obsidiantx.com.
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Kathryn Morris, 914-204-6412