CAMBRIDGE, Mass.--(BUSINESS WIRE)--H3 Biomedicine Inc., a clinical stage biopharmaceutical company specializing in the discovery and development of precision medicines for oncology and a member of Eisai’s global Oncology Business Group, announced today that it will present data on two programs at the 2017 American Association of Cancer Research (AACR) Annual Meeting in Washington, D.C.
An oral presentation at the New Drugs on the Horizon session will include a first-in-class, oral, selective estrogen receptor covalent antagonist (SERCA, H3B-6545) as a potential treatment option for patients with breast cancer. An additional presentation will provide an overview of the pre-clinical data for H3B-6527, an orally available, selective and potent FGFR4 inhibitor which may play an important role in FGF19-driven hepatocellular carcinoma.
“We are excited about the presentations taking place at AACR and look forward to furthering our clinical efforts of these investigational medicines,” said Markus Warmuth, M.D., President & CEO of H3 Biomedicine. “We believe that the two compounds being discussed at AACR have the potential to impact the lives of defined patient populations, and the data presented represents an important step towards H3’s goal of establishing itself as a leading company in delivering new cancer therapies based on cancer genomics.”
The presentation, “Discovery and development of H3B-6545: a novel, oral, selective estrogen receptor covalent antagonist (SERCA) as a potential treatment option for patients with breast cancer,” will discuss structure-based drug design approaches used by H3 scientists that led to the identification of a novel class of estrogen receptor antagonist. The clinical candidate, H3B-6545, is a highly selective small molecule that potently antagonizes wild-type and mutant ERα in biochemical and cell-based assays. Once daily dosing of H3B-6545 demonstrates potent antitumor activity in cell and patient derived xenograft models of wild-type and mutant ERα. Furthermore, H3B-6545 shows synergistic antitumor activity in combination with palbociclib in patient-derived xenografts.
H3 scientists will also present “H3B-6527, a selective and potent FGFR4 inhibitor for FGF19-driven hepatocellular carcinoma” focused on the company’s early-stage work in a genomically defined patient population with high unmet medical need. Using a structure-based drug design, H3 scientists generated a highly selective covalent FGFR4 inhibitor, H3B-6527. Biochemical and cellular selectivity assays showed that H3B-6527 is >300 fold selective towards FGFR4 compared to other FGFR isoforms. Addition of H3B-6527 to FGF19 expressing Hepatocellular Carcinoma (HCC) cell lines led to dose dependent inhibition of FGF19/FGFR4 signaling and concomitant reduction in cell viability. Oral dosing of H3B-6527 to mice led to dose-dependent pharmacodynamic modulation of FGFR4 signaling and tumor regression in FGF19 altered HCC cell and patient-derived xenograft models.
“H3B-6545 is the first in a new class of compounds that covalently inactivate the estrogen receptor, a mode of inhibition that is differentiated from other antagonists. We believe this compound has great potential for the potential treatment option of estrogen receptor positive breast cancer.” said Pete Smith, Ph.D., Chief Scientific Officer of H3 Biomedicine. “We are excited to share the pre-clinical data describing the biological rationale for the clinical development of H3B-6527 in hepatocellular carcinoma. Our biomarker strategy allows the identification of patients with altered FGF19 signaling that are predicted to benefit most from H3B-6527 treatment.”
About H3B-6545
H3B-6545 is an orally administered, potent and selective small molecule mopdulator of wild-type and mutant Estrogen Receptor (ERα). Mutations in ERα are detected in up to 30% of patients that initially respond but subsequently relapse to anti-endocrine therapies. H3B-6545 represents a new class of ERα antagonist called Selective Estrogen Receptor Covalent Antagonists (SERCAs) that inactivate the estrogen receptor by targeting a cysteine that is not present in other nuclear hormone receptors. SERCAs have a unique biological and activity profile compared to Selective Estrogen Receptor Modulators (SERMs) and Selective Estrogen Receptor Degraders (SERDs). Preclinical data indicates that H3B-6545 inhibits the growth of cell line patient-derived xenograft models of wild-type and mutant ERα. Initial clinical development will target breast cancer patients with wild-type and mutant ERα and will assess the safety and preliminary efficacy of H3B-6545.
About H3B-6527
H3B-6527 is a selective, orally bioavailable, and potent inhibitor of fibroblast growth factor receptor 4 (FGFR4) that is being investigated for the potential treatment option of advanced hepatocellular carcinoma (HCC). Aberrant signaling through the FGF19-FGFR4 axis has been shown to drive tumor development and dependency in pre-clinical models of HCC. H3B-6527 has shown sustained tumor regressions in several preclinical models of HCC where FGF19-FGFR4 signaling is aberrantly activated. The safety and preliminary efficacy of H3B-6527 will be explored in patients that are selected using a companion diagnostic that identifies HCC with activated FGF19-FGFR4 pathway activity.
About H3 Biomedicine Inc.
H3 Biomedicine is a Cambridge, Massachusetts-based biopharmaceutical company specializing in the discovery and development of precision oncology treatments, which was established as a subsidiary of Eisai's U.S. pharmaceutical operation Eisai Inc. Leveraging this collaboration with Eisai Co., Ltd., who through this partnership provides essential research funding and access to the capabilities and resources of this global pharmaceutical company, H3 Biomedicine combines long-term vision with operational independence. Using modern synthetic chemistry, chemical biology, and human genetics, H3 Biomedicine seeks to bring the next generation of cancer treatments to market with the goal of improving the lives of patients. For more information, please visit http://www.h3biomedicine.com/.