Disease Nonprofits Dive into Drug Development
Jennifer Couzin, Science
Finding a Cure
Mary Schwartz, Director, Pachonychia Congenita Project
An Alternative Model of IRB Review: The NCI Central IRB Initiative
Jacquelyn L. Goldberg, JD, Head, The NCI Central IRB Initiative
NIH Initiatives for Development of Rare Disease Therapies
Stephen C. Groft, PharmD, Director, Orphan Drug Office, NIH
Moving Translational Discoveries into the Clinic via Public and Private Sectors and NIH Lab Perspective
Douglas R. Lowy, MD, Director, Laboratory of Cellular Oncology, NCI
Developing Molecularly Targeted Therapies for Basal Cell Carcinoma - Stuck by the Hedgehog
Ivor Caro, MD, Medical Director, Dermatology, Genentech
Obstacles to Translation Conference
This Conference addressed the Obstacles that have prevented us from translating the spectacularly successful identification of gene defects in heritable skin disorders into molecularly targeted therapies. This lack of success is not unique to the skin community - those focused on extra-cutaneous systems have fared poorly as well. But the accessibility of the skin to the delivery of agents that might be too toxic for systemic use makes these diseases scientifically compelling targets, and the suffering wrought by these mutations makes them especially compelling medical targets.
The goals of the Conference were to identify the barriers and to emphasize strategies to surmount them - to set the course for discovery and development of molecularly targeted therapies that not only will improve the lives of these patients but also will serve as models for the next generation of therapies for more common, genetically more complex disorders. The four types of impediments to progress that we will discussed were:
- Obstacles to Identification and Production of Useful Molecules
- Obstacles to their Delivery and Immunologic Barriers to their Use
- Regulatory Obstacles
- Financial Obstacles
The Program was divided into an initial 8 sessions, each focused around major topics relevant to the development of molecularly targeted drugs for heritable skin diseases. The listed invited speakers each presented their comments, and these were followed by discussion by invited panelists and registrants. During the ninth session, all registrants and listed speakers/panelists were divided into working groups, each group charged with formulating plans for overcoming the previously identified and discussed Obstacles. The final session reported the deliberations of the Breakout groups. "Slides" from the presentations can be viewed by clicking on the links.
Ervin Epstein (UCSF); Barbara Gilchrest (Boston University); Leonard Milstone (Yale)
The black box of drug discovery and development - what goes on between having an idea and getting a new drug approved
Anthony Quinn (Roche)
Drug Development: Translational Research and Academic-Industry Collaboration
Seth Stevens (Amgen)
Obstacles to Translation: Financial Issues
Luke Envin (MPM Capital)
Obstacles and Dollars
Geert Cauwenbergh (Barrier Therapeutics)
Obstacles Conference
Lorne Taichman (Stony Brook)
Dermatology at Pfizer: Growing a Franchise
Howard Welgus (Pfizer)
Obstacles to Translation
Marlene Haffner (FDA)
Regulatory "Obstacles"
Jonathan Wilkin (formerly FDA)
Hedgehog Pathway Antagonists and Basal Cell Carcinoma
Fred de Sauvage (Genentech)
Drug Discovery Continuum
John Reed (Burnham Institute)
The development of therapies for ultra-orphan disorders: Challenges and successes in the development of enzyme replacement therapy for Mucopolysaccharidosis I
Emil Kakkis (BioMarin)
Developing Targeted Therapies for the Treatment of Solid Malignancy: Successes and Challenges
Mark Sliwkowski (Genentech)
Towards Enzyme Substitution Therapy of Transglutaminase 1 deficient Lamellar Ichthyosis
Heiko Traupe (University Hospital Muenster)
Obstacles to Therapy for Dystrophic Epidermolysis Bullosa
David Woodley (USC)
DNA Repair Protein Therapeutics
Dan Yarosh (AGI Dermatics)
Obstacles to Translation Conference
Joseph Carroll (SIRNA)
Use of Antisense Oligonucleotides for the Treatment of Inheritable Rare Disorders
Frank Bennett (Isis)
Overcoming obstacles to develop siRNA-based therapeutics for pachyonchia congenita
Roger Kaspar (Transderm)
Targeted Genome Modification Mediated by Triple Helix Formation
Peter Glazer (Yale)
Highly Efficient Endogenous Human Gene Modification Using Engineered Zinc Finger-Nucleases
Michael Holmes (Sangamo)
Gene Transfer for Genodermatoses
Paul Khavari (Stanford)
"A topical selection approach to improve long-term gene expression"
Jonathan Vogel (NCI)
Preclinical Models for Inherited Skin Diseases
Dennis Roop (Baylor)
Immunological Barriers in Molecular Therapy Targeted to Skin
Soosan Ghazizadeh (Columbia)
Hereditary Skin Disorders: Potential Targets for Gene-Based Therapies
Sherri Bale (GeneDx)
Cultural Disconnect - Academics vs Product Development
Eugene Bauer (Neosil)
NIH Initiatives that Promote Translation
Stephen Katz (NIH)
I. Obstacles to Drug Discovery
II. Obstacles to Translation of Promising Therapies
III. Obstacles in our Various Institutional Cultures
IV. Obstacles to Raising Necessary Money
Sherri Bale, PhD - President and Clinical Director, GeneDx
Eugene Bauer, MD - Chief Executive Officer, Neosil
Frank Bennett, PhD - Vice President of Antisense Research, Isis
John M. Carroll, PhD - Director, Dermatology, Sirna Therapeutics
Geert Cauwenbergh, PhD - Chairman and Chief Executive Officer, Barrier Therapeutics
Fred de Sauvage, PhD - Senior Director, Dept. of Molecular Biology, Genentech
Luke Evnin, PhD - General Partner, MPM Capital
Ervin Epstein, Jr., MD – Research Dermatologist, Clinical Professor, Dept. of Dermatology, University of California, San Francisco
Soosan Ghazizadeh, PhD - Assistant Professor, Dept. of Dermatology, Columbia University Medical Center
Barbara Gilchrest, MD - Professor and Chair, Dept. of Dermatology, Boston University School of Medicine
Peter Glazer, MD, PhD - Professor of Genetics and Chair, Dept. of Therapeutic Radiology, Yale
Marlene Haffner, MD, MPH - Director, Office of Orphan Products Development, US Food and Drug Administration, Rear Admiral, Adjunct Professor of Medicine, Uniformed Services University of the Health Sciences, US FDA, Office of Orphan Products Development
Mike Holmes, PhD - Director, Therapeutic Gene Modification, Sangamo BioSciences
Emil Kakkis, MD, PhD - Senior Vice President, Business Operations, BioMarin
Stephen Katz, MD - Director, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, NIH
Roger Kaspar, PhD - Founder and Chief Executive Officer, Transderm
Paul Khavari, MD, PhD - Carl J. Herzog Professor, Dept. of Dermatology Program in Epithelial Biology, Stanford University School of Medicine
Margaret Kripke, PhD - Executive Vice President, Chief Academic Officer, MD Anderson
Leonard Milstone, MD - Professor, Dept. of Dermatology, Yale
Anthony Quinn, MD, PhD - Vice President and Head of Discovery Medicine, Roche Palo Alto
John Reed, MD, PhD - President and Chief Executive Officer, Burnham Institute
Dennis Roop, PhD - Professor, Depts. of Molecular & Cellular Biology and Dermatology, Baylor
Mark Sliwkowski, PhD - Director, Staff Scientist, Molecular Oncology, Genentech
Seth Stevens, MD - Director, Global Medical Affairs, Amgen
Lorne Taichman, MD, PhD - Professor, Dept. of Oral Biology and Pathology, Stony Brook University
Heiko Traupe, MD - Associate Professor for Dermatology, Dept. of Dermatology, University Hospital Muenster
Jonathan Vogel, MD - Senior Investigator, NCI
Howard Welgus, MD - Vice President, Global Therapeutic Area Head, Dermatology, Ann Arbor, Therapeutic Area Head, Arthritis, Pfizer Global R&D
Jonathan Wilkin, MD - Formerly, Director, Division of Dermatologic and Dental Drug Products, FDA
Daniel B. Yarosh, PhD - President and Chairman, AGI Dermatics
The organizers of this Conference are Ervin
Epstein, Jr. (epsteine@derm.ucsf.edu),
UCSF; Barbara Gilchrest, Boston University; and Leonard Milstone, Yale.
Sponsors include AGI Dermatics, the American Academy
of Dermatology Association, the American Skin Association, the BCCNS Life
Support Network, DeBRA of America, F.I.R.S.T., Genentech, the National Institutes of Health, the Pachyonchia Project,
Pfizer, SIRNA Therapeutics, the Skin Cancer/Organ Transplant Program Project Grant, and
UCSF Department of Dermatology.
