Press Release: Syndax Pharmaceuticals, Inc. Licenses Selective Histone Deacetylase Inhibitor MS-275

Syndax Pharmaceuticals, Inc. Licenses Selective Histone Deacetylase Inhibitor MS-275 Clinical oncology compound already tested in over 200 patients WALTHAM, Mass. - Syndax Pharmaceuticals, Inc. announced today that it has entered into an exclusive licensing agreement with Bayer Schering Pharma AG for the acquisition of worldwide rights to the selective histone deacetylase inhibitor (HDACi) MS-275, which becomes known as SNDX-275. Under the terms of the agreement, Syndax will develop and commercialize the compound, while Bayer Schering Pharma will receive upfront and milestone payments. The HDACi becomes Syndax’s lead product candidate to be developed in combination with other oncology therapies. Financial terms of the agreement were not announced. According to Syndax president and chief executive officer, Joanna Horobin, M.D., “The successful in-licensing of SNDX-275, which has already demonstrated safety, tolerability, and clinical activity, catapults Syndax forward as an oncology drug development company. There is clinical evidence of the drug’s potential to treat a variety of tumor types in optimized, mechanistically driven combinations with other known cancer therapies. Based on data from 200 patients across various doses and tumor types, we plan to initiate Phase 2 trials in certain hematological and solid tumor indications where there are significant unmet medical needs and where an accelerated approval may be possible.” Dr. Horobin added that additional clinical trials with SNDX-275 are expected to begin in late 2007. Syndax also intends to continue the collaboration with the National Cancer Institute previously established by Schering AG, now Bayer Schering Pharma AG. “The huge potential for HDAC inhibitors to change the traditional approach of rotating cancer patients through different and increasingly toxic cycles of drug treatment was singularly attractive to the venture capital syndicate that recently invested $40 million in Syndax. We believe that the ability of HDAC inhibitors to biochemically restore drug targets is a powerful strategy to improve and extend the lives of cancer patients by re-sensitizing tumors to more desirable and less toxic therapies,” noted Kim Kamdar, Ph.D., member, Syndax Board of Directors, and principal, Domain Associates. ”I am very excited that Syndax has licensed this selective HDACi from Bayer Schering Pharma AG. The clinical results with SNDX-275 in combination with azacitidine are quite encouraging. I look forward to working with the Syndax team in the development of this promising molecule,” said Dr. Steven Gore, associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, who has been investigating SNDX-275 in combination with the DNA methyl transferase inhibitor azacitidine. Role of HDAC inhibitors in cancer Genes that regulate cell growth are frequently silenced in cancer cells due to over-expression or improper targeting of chromatin modifying enzymes. Among these enzymes are histone deacetylases (HDACs). The acetylation state of histones determines in part whether the chromatin is “open”, allowing gene expression or “closed”, prohibiting gene expression. Several HDACs can be over-expressed in tumor cells, upsetting the balance of gene expression such that levels of the proteins encoded by these genes are reduced. In addition, some cancers arise though genetic alterations that lead to the expression of fusion proteins that recruit HDACs to the wrong genomic location, also resulting in the silencing of genes normally involved in cell growth. Changes in chromatin structure have been shown to affect some of the gene products, which are important targets for cancer therapy. Preclinical studies have demonstrated that HDAC inhibition can synergize with and significantly enhance the therapeutic efficacy of a broad range of anti-cancer agents, potentially even restoring the sensitivity of tumor cells to these agents. These findings highlight the exciting potential for HDAC inhibitors in combination with existing oncology drugs to regulate gene expression and lower apoptotic thresholds. About SNDX-275, an oral HDAC Inhibitor SNDX-275 (formerly known as MS-275) is an orally bioavailable, highly selective class I, histone deacetylase inhibitor with a long half-life that allows weekly dosing. Having been evaluated in over 200 cancer patients, SNDX-275 is one of the most clinically advanced class I selective HDAC inhibitors. In Phase 1 clinical trials, SNDX-275 was associated with responses in both hematologic and solid tumors over a range of doses. In those studies, SNDX-275 was generally well tolerated at the dose and regimen selected for evaluation in Phase 2 clinical trials, which will assess the safety and efficacy of SNDX-275 in combination with other cancer agents. About Syndax Syndax Pharmaceuticals, Inc. is a Waltham, MA-based, oncology-focused biopharmaceutical company, with a lead product candidate, SNDX-275, expected to enter Phase 2 clinical trials in 2007. Syndax is building a portfolio of new oncology products to extend and improve the lives of patients by developing and commercializing novel cancer therapies in optimized, mechanistically driven combination regimens. Formed in 2005, the company's intellectual property is based on work from scientific founder Ronald Evans, PhD, recipient of the 2004 Albert Lasker Prize for Basic Medical Research, a Member of the National Academy of Sciences, a professor at the Salk Institute for Biological Studies and a Howard Hughes Medical Institute Investigator. Syndax recently closed a $40 million Series A financing co-led by Domain Associates and MPM Capital, with participation from Avalon Ventures, Forward Ventures, and Pappas Ventures.