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H3 Biomedicine Preclinical Proof-of-Concept Data on First-in-Class Spliceosome-Modulator Therapy for Genomically Identified Patients with Hematological Cancers Published in Nature MedicineH3 Biomedicine Inc., a clinical stage biopharmaceutical company specializing in the discovery and development of next generation cancer therapies using its data science and precision chemistry product engine, today announced publication of the discovery and preclinical characterization of H3B-8800, its oral, first-in-class modulator of the SF3b spliceosome complex. The publication highlights the significant anti-tumor activity of H3B-8800 in several in vivo models, including patient-derived xenografts (PDX) of hematological malignancies with recurrent mutations in RNA splicing factor genes that comprise the spliceosome. The H3B-8800 data generated by H3 Biomedicine scientists and collaborators appear in the most recent issue of Nature Medicine and can be accessed online at https://www.nature.com/articles/nm.4493. (Seiler M. et al, "H3B-8800, an orally available small molecule splicing modulator, induces lethality in spliceosome-mutant cancers"). RNA splicing is the biological process by which pre-cursor messenger RNA (pre-mRNA) is edited into a mature mRNA. Splicing factors are proteins that carry out the editing process which is catalyzed by the core spliceosome complex. Mutations in genes encoding for certain of these RNA splicing factors that form the spliceosome are among the most common mutations found in patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) and Chronic Lymphocytic Leukemia (CLL), and occur in subsets of patients with solid tumors. Despite the high prevalence of these mutations in cancer, no known spliceosome mutation-targeting cancer therapies are approved currently. Based on the promising preclinical data in the publication, H3 is currently evaluating H3B-8800 in a Phase 1 clinical trial for patients with AML, MDS and CMML identified by certain splicing factor mutations, and expects to present initial clinical data from this ongoing study in 2018. In 2017, H3B-8800 was granted orphan drug designations for AML and CMML. "The significant anti-tumor activity shown in this publication demonstrates preclinical proof-of-concept of H3B-8800 in seeral hematological cancers of high unmet medical need," said Peter Smith (News - Alert), Ph.D., Chief Scientific Officer of H3 Biomedicine, Inc. "No therapies currently exist to affect mutations in the spliceosome in cancers, and H3B-8800 is the first known investigational therapy to modulate and target cancer cells with mutated genes in this complex. The discovery of H3B-8800 highlights the power of the H3 Biomedicine product engine to create highly differentiated investigational therapies to address molecular traits driving cancers in subsets of patients." The Nature Medicine publication outlines the discovery process led by H3 Biomedicine scientists to create and characterize a highly potent, selective, oral, first-in-class modulator of the SF3b complex to target cancer cells with mutations in RNA splicing factor genes. Data highlights of the publication include:
H3B-8800 is one of three investigational therapies of H3 Biomedicine in clinical trials. The two additional investigational therapies include:
Portions of the work described in the Nature Medicine publication were originally presented at the 2016 American Society of Hematology (ASH) Meeting by lead author Silvia Buonamici, Ph.D., Executive Director, Target (News - Alert) Biology and Translational Research, H3 Biomedicine. About H3B-8800 H3B-8800 is a potent, selective, and orally bioavailable small molecule modulator of wild-type and mutant SF3b complex, a key component of the spliceosome. Recurrent heterozygous mutations in several core members (SF3B1, U2AF1, SRSF2, ZRSR2) of the spliceosome have been identified in both hematological malignancies, including myelodysplastic syndrome, acute myelogenous leukemia and chronic lymphocytic leukemia, as well as solid tumors such as skin, lung, breast and pancreatic cancers. Preclinical data indicates that H3B-8800 modulates RNA splicing and shows preferential anti-tumor activity in a range of spliceosome mutant cancer models. H3 is conducting initial clinical development in patients with hematological malignancies (including MDS, AML, and CMML) that may carry mutations in the core spliceosome genes to assess the safety and preliminary efficacy of H3B-8800. About H3 Biomedicine H3 Biomedicine is a Cambridge, Massachusetts-based biopharmaceutical company combining long-term vision with operational excellence and specializing in the discovery and development of precision oncology treatments. Using modern synthetic chemistry, chemical biology, and human genetics, the company seeks to bring the next generation of cancer treatments to market with the goal of improving the lives of patients. H3 was established as a subsidiary of Eisai's U.S. pharmaceutical operation, Eisai Inc. which provided essential research funding and access to global pharmaceutical capabilities and resources. For more information, please visit www.h3biomedicine.com.
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