On August 15, 2017 Sierra Oncology, Inc. (NASDAQ: SRRA), a clinical stage drug development company focused on advancing next generation DNA Damage Response (DDR) therapeutics for the treatment of patients with cancer, reported it has established a DDR Advisory Committee composed of leading experts in this emerging field of cancer drug development (Press release, ProNAi Therapeutics, AUG 15, 2017, View Source [SID1234520254]). The DDR Advisory Committee will advise Sierra’s management as it advances its DDR oriented development programs and seeks to maximize the potential clinical and commercial deployment of its drug candidates.
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"A growing body of research has established that the DDR network is essential for cancer cell survival and adaptation. As such it presents fertile ground for generating innovative approaches to treat various cancers. To capitalize on this rapidly advancing and evolving science, we are collaborating closely with Cancer Research UK and the Institute of Cancer Research, institutions that are pioneers in DDR and the originators of our lead DDR asset, SRA737, which targets Chk1, a critical DDR regulator," said Dr. Nick Glover, President and CEO of Sierra Oncology. "We believe the formation of our new DDR Advisory Committee, represented by leading experts in DDR biology, chemistry and medicine, will further strengthen our ability to remain at the forefront of this field and demonstrates our commitment to this promising new area in cancer treatment."
Sierra Oncology’s DDR Advisory Committee consists of:
Eric J. Brown, PhD, Associate Professor of Cancer Biology at the Perelman School of Medicine of the University of Pennsylvania.
Karlene Cimprich, PhD, Vice Chair and Professor of Chemical and Systems Biology at the Stanford University School of Medicine.
Alan D. D’Andrea, MD, Fuller-American Cancer Society Professor of Radiation Oncology at Harvard Medical School and the Director of the Center for DNA Damage and Repair at the Dana-Farber Cancer Institute.
Alan R. Eastman, PhD, Professor at the Geisel School of Medicine at Dartmouth and the founding Director of the Molecular Therapeutics Research Program of the Norris Cotton Cancer Center at Dartmouth.
Michelle D. Garrett, PhD, Professor of Cancer Therapeutics in the School of Biosciences at the University of Kent and Visiting Professor of Cancer Therapeutics at the Institute of Cancer Research, London, UK.
Thomas Helleday, PhD, The Torsten and Ragnar Söderberg Professor of Translational Medicine and Chemical Biology at Karolinska Institutet, Stockholm, Sweden.
Leonard Post, PhD, Chief Scientific Officer of Vivace Therapeutics.
"We aim to maintain a leading position in the clinical translation of DDR science and view this team as integral to that objective. Members of our DDR Advisory Committee were selected to add specific expertise that will provide the company with complementary, well-rounded guidance and strategic advice," added Dr. Christian Hassig, Senior Vice President, Research of Sierra Oncology. "As we advance our pipeline, a thorough understanding of emerging DDR biology will inform our clinical strategies and help maximize the potential clinical opportunities for our assets."
About Sierra’s DDR Advisory Committee members:
Eric J. Brown, PhD, Associate Professor of Cancer Biology at the Perelman School of Medicine at the University of Pennsylvania.
Dr. Brown’s laboratory at the University of Pennsylvania examines how signaling maintains genome stability during DNA synthesis and how this function is essential to cancer cells. His laboratory was the first to report that oncogenic stress is sufficient to cause selective sensitivity to ATR inhibition. Dr. Brown’s laboratory is currently identifying predictive biomarkers of therapeutic benefit and the mechanisms of action of these drugs through a combination of genome-wide breakpoint mapping and replication fork proteomics. In collaboration with clinical researchers, these biomarkers of response will be exploited in current and future clinical trials. Collectively, the Brown laboratory seeks both to define the mechanisms of action of ATR/Chk1 inhibitors and to identify their optimal uses in cancer therapies.
Dr. Brown received his BA (Genetics) from the University of California at Berkeley (1989) and his PhD (Immunology)
from Harvard University (1996). He performed his doctoral research with Dr. Stuart Schreiber at Harvard University, where he purified and cloned the mammalian target of rapamycin (mTOR). In his postdoctoral research in Dr. David Baltimore’s laboratory at the California Institute of Technology, Dr. Brown investigated the impact of ATR suppression on genome stability and checkpoint signaling in response to replication stress.
Karlene Cimprich, PhD, Vice Chair and Professor, Department of Chemical and Systems Biology at the Stanford University School of Medicine.
The Cimprich lab is focused on understanding how cells maintain genomic stability, with an emphasis on the DNA damage response. These include effects on DNA repair, transcription, and DNA replication, as well as cell cycle arrest, apoptosis, and senescence. The lab is particularly interested in understanding how DNA damage is identified and resolved during DNA replication, when the genome is particularly vulnerable due to stalling of the replication fork at naturally arising and induced DNA lesions, structures or protein-DNA complexes. Dr. Cimprich’s research has evaluated the role of proteins, including Chk1 and Cdc7, in replication fork collapse.
Dr. Cimprich received her BS, from the University of Notre Dame, Chemistry (1989) and her PhD from Harvard University, Chemistry (1994). She was a Postdoctoral Fellow in the Department of Chemistry and Chemical Biology, Harvard University in the laboratory of Dr. Stuart Schreiber. Dr. Cimprich is a AAAS fellow and a recipient of the Kimmel Scholar Award, Burroughs Wellcome New Investigator Award, and the Ellison Senior Scholar Award.
Alan D. D’Andrea, MD, Fuller-American Cancer Society Professor of Radiation Oncology at Harvard Medical School and the Director of the Center for DNA Damage and Repair at the Dana-Farber Cancer Institute.
Dr. D’Andrea is internationally known for his research in the area of DNA damage and DNA repair. Through his work on DNA repair biomarkers, Dr. D’Andrea participates in a wide range of clinical trials, largely focused on ovarian, breast, prostate, and bladder cancers. His research has focused on the molecular cause of leukemia for many years and he also investigates the pathogenesis of Fanconi anemia DNA repair pathway, a human genetic disease characterized by bone marrow failure and AML in children. Dr. D’Andrea has previously published on the correlation between DNA repair deficient pathways and Chk1 inhibition.
Dr. D’Andrea received his MD from Harvard Medical School in 1983. He completed his residency in Pediatrics at Children’s Hospital of Philadelphia, and a fellowship in hematology-oncology at DFCI and Children’s Hospital, Boston. Dr. D’Andrea also completed a research fellowship at the Whitehead Institute of Biomedical Research at MIT where he cloned the receptor for erythropoietin while working in the laboratory of Harvey Lodish. Dr. D’Andrea joined the staff at DFCI in 1990 and in 2017 he became the Director of the Susan Smith Center for Women’s Cancer at the DFCI. A recipient of numerous academic awards, Dr. D’Andrea is a former Stohlman Scholar of the Leukemia and Lymphoma Society, and serves on their Medical and Scientific Advisory Board.
Alan R. Eastman, PhD, Professor at the Geisel School of Medicine at Dartmouth and the founding Director of the Molecular Therapeutics Research Program of the Norris Cotton Cancer Center at Dartmouth.
Dr. Eastman’s research has concentrated in the area of preclinical cancer chemotherapy through early phase clinical trials. His initial research focused primarily on the mechanism of action of cisplatin which led to analysis of the resulting cell cycle perturbation and the identification of apoptosis as an end point. These two areas, apoptosis and cell cycle checkpoint regulation, continue today with the overall goal of bringing new drugs and new strategies to clinical trials. Dr. Eastman has published extensively on Chk1 inhibition as well as Cdc7 inhibition and their respective mechanisms of action. Further, Dr. Eastman has participated in Chk1 inhibitor clinical trials.
Dr. Eastman received his BTech from Brunel University, London (1972) and his PhD from the Chester Beatty Research Institute, University of London (1975). In 1989, he joined the faculty at the Geisel School of Medicine at Dartmouth where he has been a professor since 1992. In 1993, he was the founding Director of the Molecular Therapeutics Research Program of the Norris Cotton Cancer Center at Dartmouth, an NCI-designated comprehensive cancer center, and he continues in this role today. Prior to this, he took a position in 1983 as associate professor at the Eppley Institute for Research in Cancer, University of Nebraska Medical Center.
Michelle D. Garrett, PhD, Professor of Cancer Therapeutics in the School of Biosciences at the University of Kent and Visiting Professor of Cancer Therapeutics at the Institute of Cancer Research, London, UK.
Dr. Garrett’s current research is focused on understanding the molecular and cellular effects of drugs that target cell signaling pathways and the cell division cycle. This research includes Chk1 inhibitors such as SRA737 and other functionally related drugs. One of the long-term aims of this work is to identify biomarkers for both patient stratification and drug-target engagement for these drugs in the clinic. Dr. Garrett is a co-inventor of SRA737 and related compounds.
Dr. Garrett received her undergraduate degree from the University of Leeds, UK (1987) and her PhD from The Institute of Cancer Research (ICR), London, UK (1991). She undertook post-doctoral research at Yale Medical School, USA and then in 1994 joined Onyx Pharmaceuticals, California, USA, where she was involved in the discovery of small molecule drugs targeting the cell cycle. This included the CDK4 inhibitor project, which went on to deliver Ibrance (Palbociclib) now a registered treatment for breast cancer. In 1999, Dr. Garrett returned to the ICR where she went on to become a Reader in Cancer Therapeutics and Head of Biology for the CRUK Cancer Therapeutics Unit. In September 2014, she joined the School of Biosciences at the University of Kent and currently has three cancer drugs in the clinic.
Thomas Helleday, PhD, The Torsten and Ragnar Söderberg Professor of Translational Medicine and Chemical Biology at Karolinska Institutet, Stockholm, Sweden.
Professor Helleday heads a large multidisciplinary translational research group at Karolinska Institute focusing on understanding basic DNA repair and DNA-damage and developing novel drugs for anti-cancer treatments. The group was first to demonstrate a novel concept for treating cancer called "synthetic lethality" established by the selective killing of BRCA1 or BRCA2 mutated breast and ovarian cancers by PARP inhibitors (now EMA/FDA approved). The research covers both basic and translational work including academic-driven clinical trials, based on basic science findings in his laboratory. Dr. Helleday has published extensively on the ATR/Chk1 pathway, and has established a cancer specific synthetic lethal relationship between ATR and Chk1 inhibition.
Professor Helleday received a degree in molecular biology (1995) and in Business Administration and Economics (1996) from the Stockholm University. He received a PhD from Stockholm University in 1999 for his studies on homologous recombination in mammalian cells. Professor Helleday has been awarded numerous eminent international grants and awards in recognition of his research accomplishments including the Eppendorf-Nature Young European Investigator Award (2005) for outstanding contribution within the field of biomedical science by the journal Nature and two prestigious ERC advanced grants (2010 and 2016).
Leonard Post, PhD, Chief Scientific Officer of Vivace Therapeutics.
Dr. Post is Chief Scientific Officer of Vivace Therapeutics and also serves as an advisor to numerous biotechnology companies and to venture investors. Until July 2016, he was Chief Scientific Officer of BioMarin Pharmaceuticals, and before that was CSO and co-founder of LEAD Therapeutics which was acquired by BioMarin in 2010. His work in DNA repair involved the discovery of the PARP inhibitor talazoparib at LEAD and its development into Phase 3 at BioMarin.
Talazoparib is currently being tested in EMBRACA, a Phase III clinical study in gBRCA+ locally advanced and/or metastatic breast cancer. From 2000-2006, he was Senior Vice President of Research and Development at Onyx Pharmaceuticals, during the clinical development of Nexavar from IND through NDA approval. Prior to Onyx, he was at Parke-Davis Pharmaceutical where he was VP of Discovery Research; and before that at The Upjohn Company in several positions. Dr. Post is currently a member of the board of directors of Viralytics, an ASX-listed company; and of private companies Orphagen Pharmaceuticals, Fedora Pharmaceuticals and Oxyrane Ltd.
Dr. Post received a Bachelor of Science in Chemistry from the University of Michigan and a PhD in Biochemistry from the University of Wisconsin, Madison after which he performed a Postdoctoral Fellowship in Virology at the University of Chicago. From 1993 to June 2000, he served as Adjunct Professor in the Department of Microbiology and Immunology at the University of Michigan.