XPose Therapeutics embarks on the discovery and development of novel oncology medicines targeting DNA Damage Response with non-dilutive funding from NCI

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XPose Therapeutics is leveraging 3D structures of molecular fragments bound to drug targets to develop specific therapeutics

We are bringing our extensive team training in some of the best research laboratories with pioneering experience in drug discovery; crystallography and structural biochemistry; and biology of DNA-binding and DNA repair proteins to a pipeline of DDR therapeutics

The modulation of DNA Damage Response (DDR) proteins is an emerging path to develop novel oncology therapeutics. XPose Therapeutics (XPose) is using a unique hit-to-lead approach to rapidly identify and build novel, target-specific DDR modulators. Our strategy starts with experimental poses of molecular fragments bound to DDR targets in 3D crystal structures, determined by high-throughput protein X-ray crystallography (hence XPose). Our lead target is a base excision repair DDR enzyme implicated in multiple cancers. Numerous inhibitors of this target have been identified previously by conventional methods like high-throughput screening, computational screening and pharmacophore modeling of commercially available molecules. However, no drugs are yet on the market. This limited progress reflects key drawbacks in the current inhibitors. The development of a successful selective inhibitor will find therapeutic use for several cancers, with the potential to be employed in synthetic lethality and combination therapy paradigms. XPose has identified a collection of novel fragment hits, distinct from other molecules for this target, and solely owns and controls all chemical matter IP. The XPose DDR target pipeline is being bolstered with additional targets, for which the same approach to generate hits and accelerate early discovery of novel chemical matter will be applied.

“XPose Therapeutics, Inc. is in a breakthrough position to pursue drug discovery and development on our lead target,” said Patricia Pellicena, PhD, VP of Biochemical and Cellular Pharmacology at XPose.

“This NCI-supported non-dilutive grant funding via an SBIR Phase I award will help us ramp up efforts on advancing the lead target program and provides a significant boost on top of the acceptance of XPose into the Berkeley SkyDeck HotDesk (Incubator) program in the Spring 2020 session. And to meet our growing needs, we are also excited about taking up residence in new laboratory space at MBC BioLabs in San Carlos, which excels in bringing state-of-the-art equipment, infrastructure and services to the local startup community,” said Debanu Das, PhD, Co-Founder and CEO of XPose.

About XPose
With help from QB3, San Francisco Bay Area-based XPose Therapeutics was founded in Fall 2019 by seasoned scientists, entrepreneurs and professionals in drug discovery, structural biology, chemistry and target biology to leverage a cutting-edge approach using experimental information on 3D protein-ligand interactions as a starting point to discover and develop target-specific small molecule cancer therapeutics for undruggable targets. The XPose focus is on DNA Damage Repair (DDR) proteins and their demonstrated roles in cancer. The compounds we discover and develop can be deployed in a multi-pronged approach across two modalities: monotherapy involving enzyme inhibition, synthetic lethality or targeted-protein degradation; and combination therapy with other genotoxins and cytostatics, thereby providing a significantly large therapeutic landscape to help a wide variety of patients.

Disclaimer
XPose Therapeutics is supported by the National Cancer Institute of the National Institutes of Health (NIH) under Award Number R43CA254552, The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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