Past Quadrant Talks
Lars Knutsen, Discovery Pharma Consulting
“The importance of enantiomers for the antimalarial mefloquine”
Tuesday, July 16, 2013, 10—11 am
UCSF Mission Bay, Byers Hall, Room 212
Mefloquine is a racemic antimalarial drug utilized extensively by the US military in combat zones but has been dogged by a range of side effects including documented deaths. Neuropsychiatric effects are reported, and the FDA product guide states it can cause mental health problems, including anxiety, hallucinations, depression, unusual behavior, and suicidal ideations, among others. Investigations at Cerebrus (Vernalis) in the UK revealed that these side-effects reside in a single enantiomer, which is a potent adenosine A1 and A2A receptor antagonist.
The drug was originally discovered by Walter Reed, a US Army research institute shortly after the Vietnam War, when at one stage 1% of US combat troops were succumbing to malaria each day. The first reported trials of mefloquine were in prisoners at Correctional Centers in Illinois and Maryland in the mid-1970s, and the urgency for approval of an effective antimalarial meant that phase III safety and tolerability trials were abbreviated or avoided. With a mean elimination plasma half-life of between 2 – 4 weeks, the up to 11-17% of travelers who are incapacitated to some degree by serious adverse events from drug ingestion cannot recover rapidly.
Our research at Vernalis indicated that the enantiomer structures were mis-assigned in the 1970s (Carroll, F. I.; Blackwell, J.T. J. Med. Chem., 1974, 17, 210) adding some confusion to this field. Mefloquine and its (-)-enantiomer (WR 187164C; CEB-1097) exhibit potent binding at recombinant human adenosine A1 and A2A receptor receptors. This latter compound was subjected to multiple rounds of iterative optimization and drug design paradigms by a interdisciplinary team of scientists which eventually resulted in the drug candidate V2006, a selective adenosine A2A antagonist which showed proof of concept on phase II clinical trials in Parkinson’s Disease, in collaboration with Biogen. This A2A antagonist drug class has potential as disease-modifying neuroprotective agents.
Lars J.S. Knutsen began his research career at Glaxo Group research, Ware, UK after completing his MA in Chemistry at Oxford. At Glaxo he completed his Ph.D. in C-Nucleoside Medicinal Chemistry, joining Novo Nordisk in 1986. There, he led two CNS projects, identifying anticonvulsant GABA uptake inhibitor Tiagabine™ and NNC 21-0136, an adenosine agonist stroke drug candidate. At Vernalis, UK from 1997–2001 he initiated two projects leading to clinically investigated drugs, adenosine A2A antagonist V2006/BIIB014 for Parkinson’s Disease and a CB1 antagonist for obesity. Lars then joined Ionix Pharmaceuticals, the UK’s first pain-focused Biotech in Cambridge, UK as Director of Chemistry, and after the sale of that company he moved to Cephalon’s US Medicinal Chemistry group as the company’s first Distinguished Scientist in late 2005, where he invented CEP-26401 (Irdabisant), a novel histamine H3 antagonist now in clinical trials. Lars lectures widely on drug discovery, has published 45 papers, holds 29 patents, is an Adjunct Professor at Drexel University College of Medicine and serves on the Science Advisory Board of The Charcot Marie Tooth Foundation (www.cmtausa.org). He runs Discovery Pharma Consulting LLC, a drug R&D and Expert Witness consulting company in West Chester, PA, USA (www.discoverypharm.com) and is a founder and acting CEO of the start-up company, Requis Pharmaceuticals Inc.
Ron Newbold, VP and Head, Strategic Research Partnerships within External R&D Innovation, Pfizer Worldwide Research and Development
“Innovating within Pharma: the role of strategic partnerships with academia”
Thursday, June 27, 2013, noon—1 pm
UCSF Mission Bay, Byers Hall, Room 212
[ slides ]
Ron will describe the importance that Pfizer places on working with academic partners to advance early stage discovery. He will also discuss how Pfizer identifies and establishes these partnerships and in turn the best ways for academics to find ways to engage Pfizer.
Dr. Ron Newbold is Head, Strategic Research Partnerships within External R&D Innovation. Ron and his group support established Worldwide Research & Development alliances with numerous universities and biotechnology companies. The mission of the External R&D organization is to strengthen Pfizer’s access to cutting edge science at institutions in the US and Europe in alignment with the needs of Pfizer’s research units. Ron’s group also has responsibility for the activities of The Pfizer Incubator and for Pfizer’s global scouting activities.
Ron brings to Pfizer significant experience in external partnering in the life sciences field from his previous activities in large pharma as well as entrepreneurial start-up experience with three early-stage biotech companies. After receiving his PhD in organic chemistry from the University of Rochester and a postdoctoral fellowship with Nobel Laureate E.J. Corey at Harvard University, he joined Merck where he founded and led their Strategic Research Initiatives licensing team from 1996-2004. Ron earned an MBA from Columbia Business School in 2003.
Following 14 years with Merck, Ron led business development for Sentigen Biosciences (founded by 2004 Nobel Laureate Richard Axel of Columbia University); Celldex Therapeutics (a spin-out from Medarex); and Auspex Pharmaceuticals, where he served as chief business officer, prior to joining Pfizer in 2010.
Spiros Liras, VP of Chemistry and Head, Cardiovascular Metabolic and Endocrine Diseases Medicinal Chemistry, Pfizer Worldwide Research and Development
“Opioid receptor antagonists for neuropsychiatric disorders”
Tuesday, June 11, 2013
UCSF Mission Bay, Byers Hall, Room 212
Opioid ligands of the three receptor subtypes mu, delta, and kappa have been implicated in the modulation of several disease states of the central nervous system spanning from addiction and pain, to depression and bipolar disorder. The design, synthesis and pharmacological evaluation of selective mu, delta and kappa opioid antagonists will be presented.
Spiros Liras is the head of the Cardiovascular Metabolic and Endocrine Diseases (CVMED) medicinal chemistry department at Pfizer Worldwide Research and Development. His current research interests include tissue targeting and discovery of orally active peptides as therapeutics for diabetes II and cardiovascular disease. Prior to joining CVMED, Spiros was Senior Director of medicinal chemistry in Neuroscience at Pfizer. In Neuroscience Spiros was involved in research aiming to deliver treatments for addiction, depression, schizophrenia, cognition and Alzheimer’s disease. Spiros obtained a Ph.D. in organic chemistry in 1989 from Iowa State University where he developed methods for the synthesis of anthracyclines and studied silicon radical mediated cyclizations and unusual patterns of the Diels-Alder reaction. Subsequently, Spiros joined the group of Professor Stephen F. Martin at the University of Texas at Austin as a postdoctoral fellow. At Texas Spiros completed the total synthesis of several natural products including members of the ergot alkaloid family, zaragozic acid, and developed methods for the synthesis of peptidomimetics. Spiros is the author or coauthor for more than 50 publications and patents.
Gary Woodnutt, VP, Open Innovation, Biotherapeutics R&D, Pfizer
“Bioactive peptides: a rising star in therapeutic options”
Tuesday, November 27, 2012
UCSF Mission Bay, Genentech Hall, Room N-114
Peptides are ideally suited for interaction with many therapeutic targets. Good affinity combined with excellent selectivity provide certain advantages over small molecule competition. The smaller size of peptides and the ability to generate selective agonists has the potential to develop distinct treatment options in comparison with antibodies and other macromolecules. However the exploitation of peptide families for therapy has been limited by their short half life in the body. Recent technologies enabling structural modification, conjugation simplicity and/or improved delivery have significantly reduced issues over peptide stability and elimination. The challenge now is to identify those areas where peptides can truly demonstrate distinct differentiation from other treatment modalities and continue to gain momentum as an important therapeutic option.
Gary Woodnutt has worked extensively in small molecule and protein discovery and development in multiple therapeutic areas. He joined CovX in 2006 to oversee the biology efforts in early stage discovery and development of peptide based therapies for oncology and metabolic disease and, as part of Pfizer, has been extensively involved in expanding the potential utility of peptide conjugates by the development of bifunctional technology. Currently vice-president of Open Innovation, he continues to expand collaborative links with academia and biotechnology companies.
Tony Wood, Pfizer
“A next-generation reverse transcriptase inhibitor for drug-resistant HIV”
Monday, July 16, 2012
UCSF Mission Bay, Byers Hall, room 212
Dr. Tony Wood will cover the use of structure based design and molecule quality criteria in drug design.
Tony was appointed Head of Worldwide Medicinal Chemistry at Pfizer in October 2008. Prior to this he was Head of Chemistry and Exploratory Medicinal Sciences in Sandwich from Feb 2007 and Head of Chemistry from April 2004. Tony joined Pfizer as a Scientist in the Department of Discovery Chemistry at Sandwich in 1992. Over the period of the next 8 years he made a number of contributions to the delivery of development candidates in various projects from within the Sexual Health, Urology, and Gastrointestinal Therapeutic Areas. He was appointed to the post of Manager in 1999 with responsibility for Anti-Infectives Chemistry and played a leading role in the discovery of Maraviroc, a CCR5 antagonist for the treatment of HIV, for which he was awarded the RSC Malcolm Campbell Prize in 2005, and was a co-recipient of the ACS Heroes of Chemistry Prize, the Prix Galien USA and Scrip Awards in 2008 and the PhRMA Discoverers Award in 2010. This period of time also saw Tony leading the team that discovered Lersivirine a new non cross resistant non nucleoside reverse transcriptase inhibitor that is currently in Phase II. In recognition of these achievements Tony was awarded the UCB Ehrlich Prize for excellence in medicinal chemistry by the EFMC in 2010.
Tony received his BSc in 1987 and PhD in 1990 in chemistry from the University of Newcastle upon Tyne, before completing post-doctoral studies with Professor Steven Ley, FRS at Imperial College in London working on the total synthesis of azadirachtin, one of the most complex molecules ever to have been synthesized, and a project that has only recently been completed.
Tony has active interests in many areas of medicinal chemistry and has held positions on a number of UK funding council review boards such as the BBSRC and EPSRC. He was elected to EPSRC Council in 2010. Tony is also co-editor in chief of the new RSC journal, Medicinal Chemistry Communications, and was editor of volume 41 of Annual Reports in Medicinal Chemistry in 2006. Tony is an author or inventor on more than 50 scientific publications and patents and has given invited lectures at a number of International Conferences on Medicinal Chemistry. Lastly, Tony is a Visiting Professor at the University of Newcastle upon Tyne.
David Lawson, Procter & Gamble
“Life science innovations and delighting the consumer: perspectives from a consumer goods company”
Wednesday, July 11, 2012
UCSF Mission Bay, Byers Hall, room 212
Innovation is the key driving force behind the success of many Procter and Gamble products. What is not so obvious to the consumer is the level of science and diversity of technologies that are combined to deliver new innovative products. Advances in life sciences particularly in systems biology, understanding of the microbiome and new life science platforms for renewable and sustainable materials are all active projects within P&G. Through strategic partnerships with many outside companies in the Bay Area, P&G is looking to further drive innovation and will provide an overview of these transformative technology platforms and the impact they will have in developing new products to delight the worlds’ consumers.
David Lawson received his BSc. in Zoology from the University of Glasgow in Scotland and a MSc, in Tropical Medicine from Salford University, England. He then went on to complete a PhD in Molecular Biology from the Max-Planck Institute in Tuebingen, Germany. He started with Procter & Gamble in Schwalbach, Germany in 1992 with responsibility for regulatory affairs for food and beverage products in Europe before managing the product development activities for the Pringles snack food business within Europe. In 2001 he transferred to Procter & Gamble’s headquarters in Cincinnati, USA and was responsible for developing research partnership collaborations between P&G and other companies in the food and beverage area. From 2004, David was the Associate Director for Global Health Care Connect + Develop identifying new technologies and collaboration opportunities for P&G’s Health Care businesses with particular focus on research programs including prevention and intervention therapies for respiratory care, water purification, in-home diagnostics and new over-the-counter treatments for gastrointestinal ailments.
As of June 2011, David is the Open Innovation Manager for all P&G’s R&D activities in the Silicon Valley based out of San Francisco seeking collaborations and innovations is as diverse areas as renewable materials, systems biology, smart products and advanced materials among others.
Leo Bonilla, Allan Kuchinsky and Anya Tsalenko.
Leo Bonilla, Allan Kuchinsky and Anya Tsalenko, Agilent Technologies
“A pathway-level view of multi-omics data and its use in translational research”
Wednesday, June 13, 2012
UCSF Mission Bay, Byers Hall, room 212
The presentation will consist of two inter-related talks. The first, by Leo Bonilla, articulates the broader context of Agilent’s integrated biology strategy and solutions. One such Open Source informatics tool, being prototyped at Agilent’s central research laboratories, is described in the subsequent talk by Anya Tsalenko and Allan Kuchinsky.
Towards a pathway-level view of multi-omics data and its use in translational research
Speaker: Leo Bonilla
This presentation will focus on the issues and informatics approaches surrounding the integration of multi-omics datasets and their integrated pathway-level representation to provide improved biological context in the study human disease, including cancer. Examples from the published literature will be discussed to illustrate challenges and solutions, with a special focus on the use of semi-quantitative techniques to generate actionable hypothesis for further experimentation or target/biomarker verification. Platform-specific workflows involving genomic, metabolomic and proteomic techniques will also be presented, including the use of Open Source informatics tools for data analysis and integration.
Leo Bonilla, PhD, is currently a Market Director of Life Science Research/Integrated Biology at Agilent Technologies in Santa Clara, CA. Prior to joining Agilent, Dr. Bonilla was a Principal Scientist in the Molecular Sciences Department at Amgen Inc (Seattle, WA) where he led a small team focused on the discovery and development of pharmacodydamic markers using mass-spectrometry based techniques (e.g., phosphoproteomics, selected reaction monitoring (SRM)). He was also founding Director of the BRIMS Center in Cambridge, MA, for the development and promotion of comprehensive, integrated, and robust mass spectrometry (MS)-based workflows that link early-stage discovery to next-stage quantitative verification of protein, peptide and small molecule biomarkers.
ENViz: a Cytoscape plugin for integrative statistical analysis and visualization of sample-matched data sets with multiple data types
Speakers: Allan Kuchinsky and Anya Tsalenko
Modern genomic, metabolomics, and proteomic assays produce multiplexed measurements that characterize molecular composition and biological activity from complimentary angles. Integrative analysis of such measurements remains a challenge to life science and biomedical researchers. We present ENViz: an enrichment network approach to jointly analyzing sample-matched datasets (e.g. gene expression and metabolites or miRNA) and systematic annotations (e.g. pathways and GO), implemented as a plugin to the Cytoscape network biology software platform. EMViz visualizes results of enrichment analysis as a Cytoscape network that can be navigated to show data overlaid on pathways and GO hierarchies.
Allan Kuchinsky is a Senior Research Scientist at Agilent Laboratories, the central research organization of Agilent Technologies. Allan works on visualization and analysis of biomolecular networks through prototyping of biological network visualization tools and their usage in collaborations with external biomedical researchers. Allan is a technical contributor to the Cytoscape software platform and has long-standing collaborations with the Gladstone Institute of Cardiovascular Disease and the UCSF Resource for Biocomputing, Visualization, and Informatics. Prior to Agilent, Allan worked on audio/video information retrieval systems, user interface and collaboration support systems, integrated circuit computer-aided design tools, and production/inventory control systems at Hewlett Packard.
Anya Tsalenko, PhD, is a Senior Research Scientist at Agilent Laboratories. As part of the Agilent Laboratories research team, Anya is working on developing state of the art bio-molecular measurements, as well as developing analysis and visualization tools for extracting the most accurate and complete biological interpretation of these measurements. Anya has co-authored more than 30 publications in peer reviewed journals. Prior to Agilent, Anya did a postdoc in the Department of Human Genetics at the University of Chicago. Anya has a PhD in Mathematics from Stanford Universit, and an MS in Mathematics from Moscow State University.
David Hepworth, Senior Director of Medicinal Chemistry, Cardiovascular and Metabolic Diseases, Pfizer
“Drug discovery case histories”
Thursday, April 19, 2012
UCSF Mission Bay, Byers Hall, room 212
The presentation will describe the discovery of several clinical candidates from my Pfizer career with a focus on the optimization of pharmacokinetic properties.
- BA and DPhil Oxford University, UK
- Postdoc at The Scripps Research Institute, La Jolla
- 1999-2007 – Associate Director of Medicinal Chemistry, Pfizer Sandwich Laboratories, UK
- 2007-2012 – Senior Director of Medicinal Chemistry, Pfizer Groton Labs
- 2012-present – Senior Director of Medicinal Chemistry, Pfizer Cambridge Labs
- Involved in the discovery of >12 drug candidates that have advanced to clinical trials across several disease areas
- Author or inventor on >35 papers and patent applications
Kenneth Wertman, Sanofi US
“Escaping the privileged classes: a biased walk in chemical space”
Wednesday, April 4, 2012
UCSF Mission Bay, Genentech Hall, room N114
The Sanofi Combinatorial Technologies Center is located in Tucson, Arizona, and serves as lead discovery engine with emphasis on novel classes of small molecule leads. Cross functional teams, composed of chemists, biologists, informaticians, and pharmocologists, operate in a project-centric network where processes and capabilities are optimized for high volume chemical space exploration. Our group has a dual mission: creating a novel, proprietary screening collection of drug-like molecules and identifying the value of these chemotypes through a variety of screening approaches. The presentation will summarize our capabilities and strategies and describe our interest in developing collaborative relationships of mutual benefit.
Kenneth F. Wertman earned a PhD in molecular and cellular biology from the University of Arizona in Tucson. He received his postdoctoral research training at Massachusetts Institute of Technology in Cambridge, Massachusetts. Dr. Wertman subsequently took employment at Genentech in South San Francisco, and later, in the Department of Molecular and Cellular Biology at the University of California, Berkeley.
Dr. Wertman returned to Arizona in 1992 to join the Selectide Corporation, a founding biotech company in the then newly invented field of combinatorial chemistry. During the subsequent ten years of innovation, application and maturation, combinatorial chemistry became a productive centerpiece in the industry’s early drug discovery toolbox; and Selectide became a strategic element with the world’s third largest pharmaceutical corporation, sanofi-aventis. Through these years Dr. Wertman has served the sanofi-aventis Tucson organization in a variety of capacities, including the establishment and leadership of laboratories for gene cloning/expression, drug discovery/optimization, chemical library production, and scientific portfolio management.
Dr. Wertman is presently the scientific director of the Tucson Research Center, and director of the Tucson component of the Lead Generation and Candidate Realization Platform of Sanofi.
Erik Wong, AstraZeneca
“CNS therapeutics in the post-patent cliff era: where are the innovations to drive drug discovery?”
Tuesday, March 27, 2012
UCSF Mission Bay, Helen Diller Bldg., room 160
Most CNS disorders are highly complex and polygenetic diseases. For example, in psychiatry, beyond the monoamine transport inhibitors for depression and dopaminergic antagonists for schizophrenia, well-meaning efforts over the last 20 years to identify “magic bullets” have met with disappointment. As a consequence, major pharmaceutical companies are exiting from CNS drug discovery, with a dire outcome for patients. This seminar will address a number of challenges that conspire to generate high failure rates for CNS drug discovery. The talk will also discuss some solutions to address the above challenges.
Dr. Wong received his PhD from the Medical Research Council, National Institute for Medical Research, London, UK.He has spent over 20 years in drug discovery and development, with particular focus on novel agents for psychiatric disorders. He has recruited and led several multi-disciplinary drug discovery teams at Merck Research Laboratory, Roche Bioscience, Pharmacia and Pfizer Inc., leading to late stage clinical development and launches, e.g. MK-801, reboxetine, asenapine, quetiapine. He is the author of over 100 peer-reviewed research publications. From 1998 to 2004, Dr. Wong was an adjunct professor of Psychiatry at Michigan State University.
Dr. Wong joined AstraZeneca Pharmaceuticals in 2007.He is currently the Director of External Science for the CNS/Pain Control Research Area, in Wilmington, Delaware, USA. In this role, he is responsible for evaluation and execution of research alliances to identify new therapeutic approaches for CNS research disorders.
Eric Whitters, Novartis Diagnostics
“The future of diagnostics—detecting, preventing, and predicting disease”
Tuesday, February 28, 2012
Room N114, Genentech Hall, UCSF Mission Bay
Diagnostics inform decision making across the entire healthcare spectrum. Yet although they may influence as much as 60-70 percent of health care decision-making, they comprise less than 5 percent of total hospital and Medicare costs. Eric Whitters, VP of Global R&D at Novartis Diagnostics, based in Emeryville, will discuss where diagnostics are heading, and how tools that detect, prevent, and predict disease impact clinical decision-making. Some of the areas where Eric will focus include:
- Major forces contributing to advancement of diagnostics such as access to genomic information, understanding of biological pathways, demand for rational data, and need for cost-effective treatments.
- Evolution of diagnostics in the areas of immunoassays, molecular diagnostics, and cell biology.
- Role of emerging technologies in reshaping the medical field including allergy diagnostics, serology testing, and electronic biosensors for near-patient testing for blood screening and vaccines.
Eric Whitters serves as the global head of research and development at Novartis Diagnostics. He leads a dynamic research team responsible for current investigations in neurodegenerative diseases, infectious disease immunochemistry and vaccine development. His current focus is the identification of emerging technologies and unique biomarkers that will foster the growth of Novartis Diagnostics. Eric also oversees the development of new diagnostic tests in the areas of infectious disease, prenatal health, and transfusion medicine that build on Novartis Diagnostics’ expertise in blood screening.
Eric joined Novartis Vaccines and Diagnostics after 13 years within the diagnostics industry where he held increasing roles in research & development for Diagnostic Product Corporation and later the Siemens Healthcare business. During this time, Eric led a multifaceted team responsible for the launch of over 100 new diagnostic products on the IMMULITE platform into the clinical world.
After a successful R&D career, Eric explored additional opportunities in the Siemens Healthcare world, serving in the management of Clinical Affairs, Regulatory Affairs and Technical Operations. During this time he led a team that successfully validated, submitted and registered several PMA assays in the United States as well as multiple 510(k) assays.
Eric received his Ph.D. in microbiology from the University of Illinois at Champaign.
Anabella Villalobos, Pfizer
“Exploiting a more polar property space in the design of brain-penetrant molecules”
Wednesday, January 25, 2012
Room N114, Genentech Hall, UCSF Mission Bay
In our efforts to increase the survival of drug candidates, we undertook a detailed study of the chemical space for Central Nervous System (CNS) molecules. Ultimately, we were interested in optimizing the number of design cycles and in vivo toxicology testing needed to advance candidates from idea to proof of concept clinical studies. We focused on understanding the relationships between physicochemical properties, in vitro absorption, distribution, metabolism, and excretion (ADME) and safety attributes, and binding efficiencies for over 200 marketed CNS drugs and Pfizer CNS candidates. This analysis together with medicinal chemistry knowledge was used to create and validate a prospective design tool which used an overall desirability score for drug-likeness. The novel CNS multi-parameter optimization desirability (CNS MPO Desirability) algorithm, based on six physicochemical parameters, showed that 74% of marketed CNS drugs displayed a high desirability score (>4, using a scale of 0-6). In addition, a relationship between an increasing desirability score and alignment of key in vitro ADME and safety attributes was seen in the marketed CNS drug set, the Pfizer candidate set, and a Pfizer proprietary diversity set. The CNS MPO Desirability score is thus an algorithm in the medicinal chemistry toolbox that may be used prospectively at the design stage to accelerate the identification of compounds with increased probability of success. Furthermore, application of this tool to new clinical drug candidates has challenged the long-held notion that CNS molecules need to be highly lipophilic with low polar surface area, moving the CNS design field in a new direction.
Anabella Villalobos is currently the head of Neuroscience and Antibody Directed Conjugate Medicinal Chemistry at Pfizer Worldwide Research and Development, Groton Laboratories. Anabella obtained her B.S. in Chemistry at the University of Panama and her Ph.D. in Medicinal Chemistry at the University of Kansas where she was a Fulbright-Hayes fellow. After two years as a National Institutes of Health Postdoctoral Fellow at Yale University in synthetic organic chemistry, Anabella joined the Groton Laboratories at Pfizer in 1989. Among Anabella’s accomplishments are her contributions to the Acetylcholinesterase Inhibitor program leading to the design and discovery of CP-118,954 (icopezil) which was advanced to Phase II clinical trials in Alzheimer’s disease. This candidate became part of the agreement that led to the successful co-promotion of Aricept by Pfizer and Eisai. Anabella has significant drug discovery and development experience and has led multidisciplinary teams that have taken development candidates into Phase I and Phase II studies for Alzheimer’s disease, stroke, and sleep disorders. She is the author of multiple publications and patents.
Jennifer Liras, Pfizer
“The evolving strategy for human brain penetration predictions: from preclinical pharmacokinetics to PBPK modeling”
Tuesday, December 6, 2011
Room 160, Helen Diller Cancer Center, UCSF Mission Bay
The blood-brain barrier has represented a significant challenge to the development of central nervous system therapeutics. This is due to a barrier which not only has very tight junctions, but also a system to pump out and metabolize xenobiotics. Assays and strategies have been developed, and they are now successfully employed to identify small molecule candidates that are actively effluxed from the brain. Strict avoidance of molecules with these properties is a strategy which is both useful and limiting. The talk will present a retrospective analysis of a preclinical screening algorithm and efforts toward a more enabling strategy employing a physiological based pharmacokinetic (PBPK) model of transport at the blood-brain and blood-cerebral spinal fluid (CSF) barrier.
Dr. Jennifer Liras is Senior Director of Neuroscience Pharmacokinetic, Dynamics and Metabolism (PDM). She has 14 years experience leading scientists responsible for characterizing and optimizing the pharmacokinetic properties of large and small molecule drugs in several Therapeutic Areas, working in her tenure at Pfizer in Cardiovascular Metabolic and Endocrine Diseases, Antibacterials, Immunology, Oncology and Neuroscience. She was the leader of the first group within Pfizer PDM specifically dedicated to the early characterization and optimization of Biotherapeutics and helped PDM to establish an external scientific presence in this field. She also gained experience with regulatory and development aspects of the pharmaceutical business as a core member of early clinical development teams and through management the biologics GLP bioanalytical function within PDM. She currently leads the Neuroscience PDM group and her scientific interests include advancing the capabilities of PDM to quantitatively predict the brain penetration of transported small molecules and increasing our ability to target centrally mediated pharmacology with biologics. Jenny received a Ph.D. in organic chemistry in 1995 from The University of Texas at Austin and conducted her postdoctoral research in enzymology at Brandeis University.
Don Ganem, Novartis
“Reflections on a year in the biotech/pharma industry after 30 years at UCSF”
Tuesday, November 29, 2011
Byers Auditorium, Genentech Hall, UCSF Mission Bay
Don will reflect on how industry differs from the academy, what about academic research leadership is transferrable to industry and what is not, what Industry can usefully learn from the academic model of research and vice versa, and how graduate education in science should change if we really want to promote translation of biologic discoveries to the clinic – and if we want to better prepare students for careers in biotech.
Dr. Don Ganem is Global Head of Infectious Disease Research and VP of the Novartis Institutes for Biomedical Research. Prior to joining Novartis, Dr. Ganem was a Professor of Microbiology/Immunology and Medicine at the University of California, San Francisco, where he was also an Investigator of the Howard Hughes Medical Institute. His research focuses on the replication and pathogenesis of human viral pathogens, including hepatitis B virus and human herpesvirus 8, the causative agent of Kaposi’s sarcoma. His clinical interests include chronic viral infections and hospital-acquired infections with multi-resistant bacterial pathogens.
Dr. Ganem is a member of the National Academy of Sciences, the Institute of Medicine, the American Academy of Arts and Sciences, and the American Academy of Microbiology. He received his B.A. and M.D. degrees from Harvard University, and underwent postgraduate clinical and scientific training at the Brigham and Women’s Hospital and UCSF.
Alex Shoemaker, Abbott
“The discovery and development of the PARP inhibitor veliparib”
Thursday, November 17, 2011
Room 212, Byers Hall, UCSF Mission Bay
Alex Shoemaker will discuss the discovery and development status of the PARP inhibitor veliparib (ABT-888) as a novel therapeutic agent in oncology. His presentation will highlight key aspects of the scientific rationale for the utilization of PARP inhibitors and important questions being addressed in clinical studies.
Alex Shoemaker, Ph.D., is an Associate Director in the Global Pharmaceutical Research and Development division of Abbott Laboratories. He currently heads a drug discovery team responsible for the discovery of small molecule inhibitors of novel targets in oncology as well as translational medicine research in support of the veliparib program. Previously, he led pharmacology efforts in support of Abbott’s Bcl-2 inhibitor program as well as other small molecule and biologics programs. Alex obtained his Ph.D. in genetics from the University of Wisconsin-Madison and conducted postdoctoral studies at the Ludwig Institute of Cancer Research (San Diego) where he studied the genetics of DNA repair and modifiers of cancer syndromes in mice.
Tim Rolph, Pfizer
“Developing glucokinase activators for the treatment of type 2 diabetes”
Wednesday, October 12, 2011
Room N114, Genentech Hall, UCSF Mission Bay
Tim Rolph will describe the discovery and clinical evaluation of two distinct glucokinase activators. One targets discrete activation of the pancreatic enzyme with minimal activity against the liver and hypothalamic enzymes. The other targets activation of liver glucokinase without systemic exposure to maximally suppress hepatic glucose output with minimal hypoglycemia, offering an insulin sparing alternative to patients for whom metformin is unsuitable.
Tim’s other research interests include the regulation of muscle growth and metabolism, anti-parasitic vaccines and parasiticides, as well as anti-infective chemotherapy.
Tim Rolph is Vice President of Pfizer Worldwide Research & Development (WRD) and Chief Scientific Officer of Cardiovascular Metabolic & Endocrine Disease (CVMED) Research at the company’s Cambridge South Laboratories. Prior to being appointed to this role in 2009, Tim had been Head of Research at PGRD’s Groton Laboratories, since February 2007.
Tim joined Pfizer in 1994 in Animal Health Biology at Pfizer’s Sandwich laboratory in the UK. In this role, he was instrumental in expanding the Animal Health group’s portfolio to include companion animal medicines. In 1997, Tim moved to Human Health Discovery, leading Anti-Infectives discovery at Sandwich during which period MaravirocTM, the first in class CCR5 antagonist for HIV, was discovered. He subsequently became Head of Discovery Biology in 1999, then Head of Discovery in 2004. He received a BSc in biochemistry from Queen Elizabeth College at the University of London, and a D. Phil. from the Faculty of Clinical Medicine at Oxford University, where he trained in metabolism during the era of Krebs, Newsholme and Williamson.
Spiros Liras, Pfizer
“Phosphodiesterase inhibitors as treatments for psychiatric and neurodegenerative diseases”
Tuesday, July 19, 2011
Room 106, Stanley Hall, UC Berkeley
Spiros Liras will discuss the design and synthesis of novel PDE-10 and PDE-9 inhibitors as potential treatments for schizophrenia and Alzheimer’s disease. His presentation will highlight the application of structure based drug design and the evolution of medicinal chemistry design principles for effective targeting of the central compartment.
Spiros Liras, PhD, is the head of the Cardiovascular Metabolic and Endocrine Diseases (CVMED) medicinal chemistry department at Pfizer Worldwide Research and Development. His current research interests include tissue targeting and discovery of orally active peptides as therapeutics for diabetes II and cardiovascular disease. Prior, he was Sr. Director of medicinal chemistry in Neuroscience at Pfizer where he was involved in research aiming to deliver treatments for addiction, depression, schizophrenia, cognition and Alzheimer’s disease. Spiros obtained a Ph.D. in organic chemistry in 1989 from Iowa State University and was a postdoc at UT Austin where he completed the total synthesis of several natural products including members of the ergot alkaloid family, zaragozic acid, and developed methods for the synthesis of peptidomimetics.
John Dunlop, Pfizer
“The evolution of neuroscience research at Pfizer”
Tuesday, June 28, 2011
Room 212, Byers Hall, UCSF Mission Bay
John Dunlop will explore collaborative opportunities in Psychiatry and Neurodegeneration. In this presentation, he will provide an overview of the Pfizer Neuroscience strategy and organization and emphasize a number of key areas of basic research where opportunities for external collaboration exist.
John Dunlop, PhD, responsible for overseeing preclinical drug discovery efforts in the areas of Neurology and Psychiatry for Pfizer Worldwide R&D, will provide an overview of the Pfizer Neuroscience strategy and organization and emphasize a number of key areas of basic research where opportunities for external collaboration exist. John joined Pfizer as part of the Wyeth integration in late 2009 as Executive Director in the Neuroscience Research Unit and Head of its Enabling Technology Department, supporting efforts in drug discovery in Neuro-degenerative and Psychiatric diseases and Autism. John obtained a PhD in Neurochemistry from the University of St. Andrews, in Scotland, UK. Upon completion of his PhD studies John joined Wyeth Research UK.
David Price, Pfizer
“The discovery of maraviroc for the treatment of HIV”
Tuesday, June 7, 2011
Room 106, Stanley Hall, UC Berkeley
Selzentry™/Celsentri® (maraviroc) is a rare example of a genetically validated molecular target and chemistry matter derived from high throughput screening delivering a clinical candidate that has subsequently been approved. The talk details the evolution of the screening paradigm and how challenges of pharmacokinetics and safety shaped the medicinal chemistry thinking and drug design. In particular overcoming cardiovascular safety linked with binding to the hERG ion channel and development of high throughput screens for this effect is highlighted.
David Price, PhD, is the Senior Director, Cardiovascular Metabolic and Endocrine Diseases at Pfizer, where he works to open up alternative approaches to small molecules and manages a number of collaborations investigating the utility of modalities outside of traditional small molecules. David previously worked in anti- infectives and delivered 2 compounds into development: the first, maraviroc, is now approved and the second is in Phase IIb trials. David has also worked in library design and during his time in the Allergy and Respiratory group his work yielded a clinical candidate currently in Phase II trials. David is the recipient of many honors including the ACS award for “Hero of Chemistry” (2008) and the winner of the UK/USA Prix Galien award (2009). David completed his graduate studies at the University of Nottingham and postdoctoral work at Colorado State University.