Selective Estrogen Receptor Covalent Antagonist (SERCA) inactivates both wild-type and mutant ERα
Cambridge, Mass., December 6, 2017 — 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 that company scientists are presenting data from preclinical studies involving H3B-6545, an oral, selective small molecule covalent antagonist of wild-type and mutant Estrogen Receptor (ERα) at the 40th Annual San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX. The data will be shared in a poster presentation.
The poster, presented by Manav Korpal, Ph.D., is titled “Development of a first-in-class oral selective ERα covalent antagonist (SERCA) for the treatment of ERαWT and ERαMUT breast cancer” and is taking place in the following session:
Session: Poster Session 1: Treatment: New Drugs and Treatment Strategies (5:00 PM – 7:00 PM)
Date/Time: Wednesday, December 6, 2017, 5:00 PM
Room: Hall 1
“We are encouraged by the initial results that H3B-6545 demonstrated over the current standard of care agents in preclinical models,” said Markus Warmuth, M.D., President and CEO, H3 Biomedicines. “At H3, our research in breast cancer seeks to advance the understanding of this debilitating illness and work towards discovering novel treatments for those affected by the disease.”
The poster presented at SABCS demonstrated that H3B-6545 has a unique mode of ERα antagonism and exhibits superior preclinical anti-tumor activity to fulvestrant in the MCF-7 xenograft model with once daily oral dosing, achieving maximal antitumor activity at doses >10x below the maximum tolerated dose in mice. In addition, H3B-6545 demonstrated superior preclinical anti-tumor activity to both tamoxifen and fulvestrant in patient derived xenograft models of breast cancer carrying estrogen receptor mutations. Based on these results, in September, 2017, H3B-6545 entered into a Phase 1 multi-center, open-label study to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of the compound in women with ER-positive, Her2-negative metastatic breast cancer. Please refer to www.clinicaltrials.gov for additional clinical trial information.
“The results from the preclinical models indicate a new mode of inhibition, covalent antagonism of ERα, is potent in in vitro and in vivo models of breast cancer,” said Pete Smith, Ph.D., Chief Scientific Officer, H3 Biomedicine. “The fact that current ER-directed therapies are only partially effective in the ERα mutant setting, and that a significant proportion of resistant breast cancer metastases continue to remain dependent on ERα signaling for growth/survival, highlights the critical need to develop the next generation of ERα antagonists that can overcome aberrant ERα activity.”
H3B-6545 is an orally bioavailable, potent and selective small molecule modulator of wild-type and mutant Estrogen Receptor (ERα). 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, pharmacokinetics, pharmacodynamics 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.