BridGene’s IMTAC ™ Small Molecule Discovery Platform Featured in Multiple Presentations at 2021 AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics

San Jose, CA, October 7, 2021BridGene Biosciences, Inc., a biotechnology company using a unique chemoproteomic technology to discover and develop small molecules for high value, traditionally undruggable targets, disclosed today research findings from five scientific  presentations at the 2021 AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics. The presentations detail the company’s proprietary small molecule discovery platform, IMTACTM (Isobaric Mass Tagged Affinity Characterization) and its use in BridGene’s latest discovery of therapeutic candidates and the identification of new targets for approved small-molecule drugs.

The conference begins today, October 7, 2021, and runs through October 10, 2021.

“We are excited to have multiple poster presentations during this year’s AACR-NCI-EORTC illustrating how BridGene is bringing game-changing capabilities to drug discovery and development,” stated Ping Cao, Ph.D., Co-Founder and CEO of BridGene Biosciences. “This is among the most prominent scientific gatherings addressing drug discovery and molecular targets. Overall, our presentations describe our IMTACTM platform technology and its capabilities, the discovery of novel small-molecule inhibitors for undruggable targets, and the identification of previously unknown targets for approved small-molecule drugs.”

The full poster presentations are available on the AACR website at https://www.aacr.org/meeting/aacr-nci-eortc-international-conference-on-molecular-targets-and-cancer-therapeutics/ . The highlights from the presentations are as follows:

Presentation: A chemoproteomic platform for identifying small-molecule modulators of protein-protein interactions, discovering new cancer targets, and revealing previously unknown targets for well-known drugs

  • IMTACTM has the potential to redefine precision medicine, discover new drugs and new targets, and identify new indications for known drugs.
  • Using the IMTACTM platform, BridGene discovered small-molecule ligands for several “hard-to-drug” targets and oncogenic mutations, including GTPases (e.g., RhoA), transcription factors (e.g., TEAD), splicing factors (e.g., SRSF1), epigenetic modulators (e.g., WDR5), and E3 ligases.
  • IMTACTM ‘s proteome-wide profiling capability enabled BridGene to reveal, for the first time, new targets for well-known drugs.
  • Combining IMTACTM screening with phenotypic screening uncovered new/unknown targets that drive certain disease phenotypic changes.

Presentation: Identification of previously unknown targets for approved small-molecule drugs using chemoproteomic platform IMTAC™

  • BridGene’s IMTACTM profiling is a powerful approach for generating comprehensive target maps for small-molecule drugs, both covalent and non-covalent ones.
  • IMTACTM used on different cells leads to the identification of different sets of protein targets
  • Known kinase targets and previously unknown non-kinase targets were identified for ibrutinib and sunitinib using IMTACTM
  • A non-kinase target TEX264 of sunitinib was identified by IMTACTM, creating new opportunity for cancer treatments.

Presentation: Discovery and development of novel covalent inhibitors of the YAP-TEAD transcription activity

  • BridGene is developing covalent, small-molecule TEAD inhibitors to treat mesothelioma, glioblastoma, liposarcoma, pancreatic and other types of cancer.
  • BridGene used the IMTACTM platform to screen its unique covalent library against live-cell proteomes and identified three distinct series of hits (MCS Tanimoto Coefficients at ~0.3 between any two series) for TEAD proteins with nanomolar affinity and high proteomic selectivity.
  • Multiple, novel, and potent small-molecule TEAD inhibitors were obtained with good druggability.
  • BridGene’s TEAD inhibitors 1) exhibited anti-proliferative properties against NF2- deficient mesothelioma cell lines (NCI-H226, NF2-/-) with low nM IC50’s; 2) demonstrated the potential to disrupt TEAD-YAP protein-protein interaction in cells in an ELISA assay, 3) showed  single-digit nM potency in disrupting TEAD downstream gene expression in MCF7-TEAD1 luciferase reporter cells.
  • With high potency and proteomic selectivity, BridGene believes these TEAD inhibitors could function as single-agent therapies or work in combination with other agents to treat multiple cancers.

Abstract Title: Discovery of a covalent inhibitor for an oncogenic mutant RhoAY42C

  • Inhibiting the RhoA protein is believed to offer a promising approach to the treatment of diffuse gastric cancer (DGC) that harbors CDH1 mutation/deletion. The Cancer Genome Atlas (TCGA) study shows that ~1% DGC patients harbor the oncogenic mutant RhoAY42C.
  • BridGene screened its proprietary covalent library against RhoAY42C in live cells through IMTAC target focused screening to detect covalent ligands of the mutant RhoAY42C.
  • A pilot screening successfully identified a covalent ligand of RhoAY42C, BGS1933. Mass spec analysis confirmed the covalent modification of Cys42 in RhoA by BGS1933.  
  • BGS1933 shows inhibition of CCK-81 cell growth, a cell line containing RhoAY42C mutation.
  • SAR is underway to further improve its potency and selectivity towards RhoA Y42C.
  • The discovery of a covalent inhibitor of RhoAY42C could allow BridGene to validate the protein’s role in DGC and facilitate the development of new first-in-class targeted therapies for the treatment of gastric cancer.

Presentation: Discovery of novel small-molecule inhibitors for an epigenetic modulator WDR5

  • BridGene used the IMTACTM platform to screen its unique covalent library against live-cell proteomes and discovered small-molecule ligands for WDR5. WDR5 is a widely expressed protein and an increasingly attractive therapeutic target for many types of cancer.
  • Preliminary characterization of the “hit” compound, BGS1989, showed that it interacts with WDR5 in a dose-dependent manner, and has the ability to inhibit MLL1 methyltransferase activity at low µM potency.
  • After one round of chemical optimization, researchers identified an improved inhibitor, BGS2597 with nM potency against WDR5. Work is underway to delineate which WDR5 functions are modulated by BGS2597 and improve its activity and selectivity for WDR5.
  • The WDR5 inhibitor discovered using IMTAC platform provides an excellent starting point for the development of new drugs targeting WDR5-dependent cancers.

About AACR

The American Association for Cancer Research (AACR) is the first and largest cancer research organization dedicated to accelerating the conquest of cancer. Through its programs and services, the AACR fosters research in cancer and related biomedical science; accelerates the dissemination of new research findings among scientists and others dedicated to the conquest of cancer; promotes science education and training; and advances the understanding of cancer etiology, prevention, diagnosis, and treatment throughout the world.

About BridGene Biosciences

BridGene is a biotechnology company focused on discovering and developing innovative small molecules that drug traditionally undruggable targets, providing new paths to treat diseases. By using its proprietary chemoproteomic platform, IMTAC™, BridGene is able to screen small molecules against all proteins in live cells to discover drug candidates for high value and previously undruggable targets. For this purpose, BridGene takes advantage of its proprietary, diverse library of tagged, drug-like small molecules. The ultimate goal is to enable breakthrough small-molecule drug discovery and to expand the mechanisms to treat diseases, with targets previously inaccessible to small molecules. BridGene can perform IMTAC screening for both covalent and non-covalent molecules and discover new targets for disease treatments by deconvoluting phenotypic screening hits, setting the company apart from its peers. The company is advancing a diversified pipeline of first-in-class drugs for targets in multiple disease areas. For more information, visit http://bridgenebio.com/.

Contact

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