Day 1 | Day 2 | Short Courses | Download Brochure
TUESDAY, NOVEMBER 3
7:30 Continental Breakfast Breakout Discussion Sessions
8:30 Chairperson’s Remarks
Sriram Balasubramanian, Ph.D., Director, Translational Research, Pharmacyclics, Inc.
8:40 Discovery of SB939, an HDAC Inhibitor with Class-Leading Properties
Haishan Wang, Ph.D., Group Leader, Chemistry Discovery, S*BIO Pte Ltd.
Discovery of SB939, an HDAC inhibitor with a best-in-class profile, will be described, supported by recent clinical data. After extensive SAR studies and optimization of in vitro properties, PK/PD and in vivo efficacy studies, SB939 emerged as a lead candidate with properties suitable for once daily oral dosing. Potent tumor growth inhibition in a range of xenograft models have been shown, with advantage over the agents currently in clinical trials. SB939 is currently being tested in both hematological and solid tumor patients. Preliminary data show that the superior preclinical profile is translated to the clinic.
9:10 Belinostat: A Pan HDAC Inhibitor with Clinical Potential in Both Hematological Malignancies and Solid Tumors
Steven Butcher, Chief Operating Officer, TopoTarget A/S
Richard Penson, Massachusetts General Hospital
Belinostat has demonstrated activity in lymphoma and leukemia patients and in certain solid tumor types. Monotherapy efficacy forms the basis for the recent initiation of the first pivotal trial using belinostat in PTCL. Combination of belinostat with 5-FU (BelFU) has also demonstrated encouraging clinical effects in patients that might be identified by a blood cell-based biomarker for efficacy. Clinical data using full dose combination of belinostat with carboplatin and paclitaxel demonstrates the therapeutic potential of this combination for the treatment of platinum-resistant ovarian cancers and solid tumors.
9:40 Networking Coffee Break in the Exhibit Hall
10:40 HDAC Inhibitor Entinostat Sensitizes ERa-negative MDA-MB-231 Tumors to Respond to Aromatase Inhibitor Letrozole
Angela Brodie, Ph.D., Professor of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine
Aromatase inhibitors (AIs) are providing a significant benefit to most patients with breast cancer but are ineffective in hormone receptor-negative tumors, which comprise of approximately 25% of breast cancers and tend to be more aggressive. The discovery of recruitment of histone deacetylase (HDAC) enzymes in cancer provides a rationale for inhibition of HDAC activity to release transcriptional repression as a potential therapeutic strategy. The objective of this study was to extend the advantages of endocrine therapy to patients with estrogen receptor-negative (ER-) tumors by combining treatment with an HDAC inhibitor. Our results provide the basis for possible use of AIs in combination with HDAC inhibitors for the treatment of ER- tumors. This could open a new avenue for the management of ER- breast cancer.
11:10 JNJ-26481585 – Development of a Novel Second Generation Oral Pan-HDAC Inhibitor for Anti-Cancer Therapy
Janna Sand-Dejmek, M.D, Ph.D., Senior Scientist, Oncology Biomarkers, Ortho Biotech Oncology Research & Development
The second-generation HDAC inhibitor JNJ-26481585 shows preclinical activity against a wide range of hematological and solid tumors. It induces acetylation of both HDAC1 (histones) and HDAC6 substrates (tubulin) at nano-molar concentrations in human tumor cells. It inhibits tumor cell proliferation, impairs angiogenesis and induces widespread apoptosis in a number of cell lines and in vivo models regardless of p53 and ras mutational status. JNJ-26481585, which is currently in Phase I clinical trials, is a promising “second generation” HDAC inhibitor for a broad spectrum of human solid and hematological malignancies.
11:40 A Clinical Update on the Development of Panobinostat
Samit Hirawat, M.D., Executive Director, Oncology Clinical Development, Novartis Pharmaceuticals Corporation
Panobinostat (LBH589) is a deacetylase inhibitor (DACi) belonging to novel cinnamic hydroxamic acid class of compounds. It is a highly potent pan-DAC inhibitor (pan-DACi) that has shown anti-tumor activity in patients with Hodgkin’s lymphoma, multiple myeloma, acute myeloid leukemia, prostate cancer, breast cancer etc as a single agent or in combination with other anticancer agents. Panobinostat is formulated as an oral capsule and a solution for intravenous (i.v.) injection. Both the oral and i.v. formulations are currently being investigated in ongoing phase I and phase II studies in advanced solid tumors and hematological malignancies.
12:10 pm Improving Outcomes for Lung Cancer with HDAC Inhibitors
Suresh Ramalingam, M.D., Associate Professor of Hematology-Oncology, Emory University School of Medicine
Platinum-based chemotherapy is the mainstay of treatment of advanced non-small cell lung cancer. HDAC inhibitors have modest activity as monotherapy in thoracic malignancies, but possess properties that are attractive for combining them with other standard therapies. We have developed a novel regimen of vorinostat in combination with a platinum-based chemotherapy regimen, based on favorable preclinical interactions. Proof of principle for the use of this approach has now been established in a placebo-controlled randomized study in advanced NSCLC.
12:40 Close of Conference
Day 1 | Day 2 | Short Courses