September 5, 2017
Cambridge, MA — 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, today announced dose administration for the first patient in a Phase 1, open-label, dose-escalation and expansion study of single agent H3B-6545, an orally bioavailable, potent and selective small molecule antagonist of wild-type and mutant Estrogen Receptor (ERα). Preclinical data indicates H3B-6545 inhibits the growth of cell line and patient-derived xenograft models of wild-type and mutant ERα.
“The initiation of this study represents a significant milestone for our company, as it marks the third program from our portfolio to enter the clinic in the past 12 months,” said Peter Smith, Ph.D., CSO of H3 Biomedicine. “Through this study, we anticipate creating significant clinical data to guide our future development plans for this first in class covalent antagonist of the estrogen receptor. The program highlights H3’s strong work in cancer genomics and drug development.”
H3B-6545 represents a new class of ERα antagonists discovered by H3 Biomedicine scientists called “Selective Estrogen Receptor Covalent Antagonists” (SERCAs). SERCAs inactivate the estrogen receptor by targeting a cysteine that is not present in the majority of other nuclear hormone receptors. SERCAs have a unique biological activity profile compared to Selective Estrogen Receptor Modulators (SERMs) and Selective Estrogen Receptor Degraders (SERDs).
“We are looking forward to working with H3 Biomedicine on this new class of Selective Estrogen Receptor Covalent Antagonists,” said Erika Hamilton, M.D., BRE 287 study chair and Director, Breast & Gynecologic Cancer Research, Sarah Cannon Research Institute. “The preclinical data of this first-in-human drug support a unique biologic and activity profile. We look forward to the continued study of this novel agent and hope to find additional opportunities to overcome established patterns of drug resistance.”
The purpose of the Phase 1 multi-center, open-label study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of H3B-6545 in women with ER-positive, Her2-negative breast cancer. H3B-6545 will be administered daily as a single agent dosed orally on a 28-day cycle. The first portion of the study includes a dose-escalation phase, in which cohorts of patients will receive ascending oral doses of H3B-6545 to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose based on safety and tolerability. The second portion of the study is a dose expansion phase where patients will receive H3B-6545 to further evaluate the safety, tolerability and clinical activity of the recommended Phase 2 dose. Please refer to www.clinicaltrials.gov for additional clinical trial information.
“We are thrilled to be working with Dr. Hamilton, one of the leaders in the breast cancer arena, and a world-class study team at Sarah Cannon Research Institute,” said Markus Warmuth, M.D., President and CEO of H3 Biomedicine. “The fact that Sarah Cannon enrolled this first patient well ahead of previously announced expectations speaks to the interest in this drug held by patients and investigators alike.”
H3B-6545 is an orally bioavailable, potent and selective small molecule modulator 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. Current endocrine therapies are only partially effective in the ERα mutant setting and a significant proportion of endocrine-therapy resistant breast cancer metastases continue to remain dependent on ERα signaling for growth/survival indicating a critical need to develop the next generation of ERα antagonists. Scientists at H3 Biomedicine have discovered a new class of ERα antagonists 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 H3B-6545 inhibits the growth of cell line and patient-derived xenograft models of wild-type and mutant ERα with improved activity over standard-of-care therapies. 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 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 www.h3biomedicine.com.