WALTHAM, Mass., Dec. 1, 2011 /PRNewswire/ -- Syndax Pharmaceuticals, Inc., a clinical-stage epigenetics oncology company, announced today that multiple data presentations from phase 2 clinical trials with entinostat in combination and as a single agent will be made at upcoming scientific conferences.
San Antonio Breast Cancer Symposium
Data from ENCORE 301, a multicenter, randomized, double-blind, placebo-controlled, phase 2 study of exemestane with and without entinostat in 130 postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer, will be presented in a poster discussion at the San Antonio Breast Cancer Symposium taking place December 6 to 10 in San Antonio, Texas. Denise A. Yardley, MD, breast program leader, senior investigator at the Sarah Cannon Research Institute and principal investigator of the study, will present the data which will include an update on overall survival.
Presentation Date/Time: Wednesday, December 7 from 5:00 PM - 7:00 PM
Poster Title: Entinostat, a Novel Histone Deacetylase Inhibitor, Added to Exemestane Improves PFS in Advanced Breast Cancer in a Randomized, Phase II, Double-Blind Study
Session: POSTER DISCUSSION I: Endocrine Resistance
Abstract Number: PD01-04
Location: Ballroom A
American Society of Hematology Annual Meeting and Exposition
Data from ENGAGE 501, a multicenter, phase 2 study entinostat, a novel, oral small molecule inhibitor of class I histone deacetylases, in patients with relapsed or refractory Hodgkin's lymphoma will be presented at the American Society of Hematology Annual Meeting and Exposition in San Diego on December 11 from 6:00 PM to 8:00 PM. Details on this presentation and additional data presentations are below:
Presentation Date/Time: Sunday, December 11 from 6:00 PM - 8:00 PM
Poster Title: The HDAC Inhibitor Entinostat (SNDX-275) Induces Clinical Responses in Patients with Relapsed and Refractory Hodgkin's Lymphoma: Results of ENGAGE-501 Multicenter Phase 2 Study
Program/Session: Oral and Poster Abstracts, 624. Lymphoma- Therapy with Biologic Agents, excluding Pre-Clinical Models: Poster II
Abstract Number: 2715
Presentation Date/Time: Saturday, December 10, 2011: 5:30 PM-7:30 PM
Poster Title: HDAC and LSD1 Inhibitors Synergize to Induce Cell Death in Acute Leukemia Cells
Program/Session: Oral and Poster Abstracts, 604. Molecular Pharmacology, Drug Resistance: Poster I
Abstract Number: 1427
Location: Hall GH (San Diego Convention Center)
Presentation Date/Time: Monday, December 12 from 6:00 PM - 8:00 PM
Poster Title: Entinostat, a Novel Histone Deacetylase (HiDAC) Inhibitor Enhances the Anti-Tumor Activity of Bortezomib (BTZ) in Rituximab-Chemotherapy Sensitive and Resistant Lymphoma Cell Lines
Program/Session: Oral and Poster Abstracts, 625. Lymphoma - Pre-Clinical - Chemotherapy and Biologic Agents: Poster III
Abstract Number: 3734
Location: Hall GH (San Diego Convention Center)
Breast Cancer and Hormone Therapy
Annually about 207,000 women have breast cancer in the United States and about 20,000 of them have metastatic breast cancer (MBC). Approximately 70 percent of women with breast cancer have ER+ breast cancer. Blocking estrogen activity with aromatase inhibitors represents an effective treatment for most ER+ MBC patients, however acquired drug resistance to aromatase inhibitors leads to disease progression requiring less effective, more toxic chemotherapies.(1) Delaying resistance and disease progression represents a significant unmet need that could prolong survival while decreasing health care costs associated with chemotherapy and hospitalization.
Hodgkin's lymphoma (HL) is a cancer of lymph tissue found in the lymph nodes, spleen, liver, bone marrow, and other sites. It is most common among people ages 15 - 35 and 50 - 70. Although the cause is not known, past infection with the Epstein-Barr virus (EBV) is thought to contribute to some cases and patients with HIV infection are more at risk than the general population. It is estimated that 8,830 people in the US will be diagnosed with and 1,300 will die of the disease in 2011, with the prognosis of patients with relapsed HL being particularly poor. HDACi have shown promise in treating this disease. Preclinical studies have identified at least three complementary mechanisms to explain how HDACi may be effective in the treatment of HL (Buglio, Blood 2008): induction of apoptosis, regulation of cytokines and chemokines and alterations of cancer/testis antigens (Jona et al., Exp Hematol. 2011).
Syndax's lead product entinostat is a novel, oral small molecule inhibitor of class I histone deacetylases, key enzymes that alter the structure of chromatin to control gene expression. Entinostat is differentiated from other members of the class through its unique selectivity profile, pharmacokinetic properties and safety profile. Entinostat has been studied in more than 600 cancer patients where objective tumor responses have been observed in both solid and hematologic malignancies.
Breast cancer animal models demonstrated that resistance to aromatase inhibitors occurs through up-regulation of growth factor signaling pathways and down-regulation of estrogen receptor-alpha (ERa). Entinostat effectively down-regulates growth factor signaling in breast cancer cells where these pathways are active. Entinostat also up-regulates the expression of ER in breast cancer cells which have negligible or undetectable levels of ER. The ability to target multiple mechanisms of resistance establishes entinostat as a promising candidate for preventing and overcoming aromatase inhibitor resistance through epigenetic modulation. In pre-clinical testing entinostat induced tumor regression when combined with an aromatase inhibitor after the development of hormone resistance.
Additional phase 2 studies with entinostat have demonstrated promising results in combination with the EGFR-TKI erlotinib (ENCORE 401) and DNA methyltransfer inhibitor azacitidine in non-small cell lung cancer). Results from the ENCORE clinical program have provided the basis for moving entinostat in pivotal, phase 3 testing across a platform of breast and lung cancer indications.
Syndax Pharmaceuticals, Inc. is a Waltham, MA-based, late-stage, oncology-focused pharmaceutical company. The company 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. Syndax has worldwide rights to develop and commercialize entinostat which has shown promise in randomized clinical trials in solid tumors. Syndax is backed by top-tier Venture Capital firms: Domain Associates, MPM Capital, Avalon, Pappas and Forward Ventures. Formed in 2005, Syndax's intellectual property is based on work from scientific founder Ronald Evans, Ph.D., 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. For more information please visit www.syndax.com.
(1) Hurvitz, S, Pietras, R. Rational Management of Endocrine Resistance in Breast Cancer, Cancer, 2385- 2397 (2008).
E. Blair Schoeb
Syndax Pharmaceuticals, Inc
|SOURCE Syndax Pharmaceuticals, Inc.|
Copyright©2010 PR Newswire.
All rights reserved