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Obsidian Therapeutics Presents Data Demonstrating Regulation of Protein Activity with its Next-Generation CAR-T Platform at Keystone Symposium on Emerging Cellular Therapies
[February 13, 2018]

Obsidian Therapeutics Presents Data Demonstrating Regulation of Protein Activity with its Next-Generation CAR-T Platform at Keystone Symposium on Emerging Cellular Therapies


Obsidian Therapeutics, Inc., a biotechnology company dedicated to the development of next-generation cell and gene therapies with pharmacologic operating systems, today announced the presentation of preclinical data on its technology platform and applications at the Keystone Symposium on Emerging Cellular Therapies, to be held February 11-15, 2018 in Keystone, Colorado. The presentation includes initial in vivo proof of concept data demonstrating Obsidian's strategy for precise pharmacologic control of cell therapy by employing destabilizing domains (DDs), which are small, fully-human protein domains that confer conditional stability to a fused payload protein.

"We are excited to present data on our platform and our first series of applications to the scientific community, as we have seen precise and robust control of gene expression using our technology in vitro and in vivo," said Dr. Steve Shamah, PhD, Senior Vice President and Head of Research for Obsidian, who presented the poster at the Keystone Symposium. "We are also sharing our first data on fully human approaches to engineering immune cells with pharmacologic operating systems. These data are foundational to our goal of putting control of CAR-T and other cell therapies in the hands of clinicians and patients, thereby enabling safer, more effective cancer treatments."

The Keystone presentation describes the successful implementation of DD technology in engineered primary human T cells and demonstrates ligand-controlled regulation of cytokine protein expression in vitro and in vivo to enhance CAR-T function. These dta demonstrate the feasibility of exogenous control over transgene-derived protein expression in primary human T cells for the development of next-generation CAR-T cell products with enhanced efficacy and more favorable safety profiles. Data presented at the meeting include:

  • Destabilizing domain (DD) technology enabled titratable and reversible regulation of protein levels in preclinical studies, using FDA-approved small-molecule drugs as pharmacologic regulators.
  • The studies demonstrated small-molecule control of DD-mbIL15 and DD-IL12 "cassettes" in human T cells in vitro.
  • Systemic IL12 levels from transduced T cells were regulated in vivo with pulsatile dosing and precise dose-response.
  • A range of DD variants were used in the studies, with performance characteristics matched to specific applications.
  • These studies represent in vivo proof of concept for the ability to create next-generation CAR-T cell products that provide precise control over transgene-derived protein expression, with the potential to offer enhanced efficacy and more favorable safety profiles.

About Destabilizing Domains

Obsidian uses Destabilizing Domains (DDs) to enable pharmacologic regulation of protein activity for next-generation cell and gene therapies. Obsidian's 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, Obsidian's 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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