DAY ONE - May 27-28, 2015
7:45 am Registration / Continental Breakfast
8:30 am Chairperson's Opening Remarks
E. Mitchell Seymour, Ph.D., RAC., Director, Founder, R&D Advisors LLC, Faculty, University of Michigan Institute for Clinical and Health Research
8:35 am Drug Discovery and Selection in Drug Repurposing
The value of repurposing therapeutic drugs for new indications is compelling and well documented. However, there is a myriad of technologies that can provide insight into drug-target-disease connectivity. In this presentation we will discuss and compare bottom-up and top-down approaches to discovering new drug—disease pathway and network biology. We will also discuss the criteria one must apply in order to determine if the repurposed drug candidate will be submitted for an IND evaluation.
Stephen Naylor, Ph.D., Chairman & CEO, MaiHealth Inc.
9:05 am A Knowledge-Based Approach to Drug Repositioning
Pharmaceutical companies are continually seeking new avenues to increase revenues. One such avenue that has seen a significant increase in activity in recent years is drug repositioning, in which companies seek new indications for existing drugs or late stage clinical assets. One of the most profitable outcomes of repositioning is to successfully reposition a drug for new indications. Most often this is done by serendipity, an observation of a side effect of a clinical trial, or intimate knowledge of a particular disease. A more systematic, science driven approach is desirable. Using a variety of Thomson Reuters’ databases we have developed a knowledge based approach to repositioning which combines target and pathway driven bioinformatics techniques with analysis of molecular descriptors and clinical trial information to identify new indications for existing compounds. These compounds are further analyzed for their ability to be best or first in class based on scientific, business and clinical criteria. In the present talk, the drug repositioning pipeline will be described and its utility will be demonstrated on several examples.
Alexander Ivliev, Ph.D., Senior Scientist, Thomson Reuters Life Sciences
9:35 am The Myths and Realities of Repositioning
One view is that repositioning is easy, quick, and cheap. And a lot of it certainly is, but it is very likely to lead to failures. What are the usual myths surrounding repositioning, and where are the opportunities? Financial, patent, and real-world impact cases will be discussed.
Aris Persidis, Ph.D., President, Biovista
10:05 Refreshment Break
10:35 am The Discontinued Drug Database: An Annotated Corpus to Identify Repurposing Candidates
The Discontinued Drug and Candidate Database (DDCD) is being developed a reference tool to facilitate the identification of potential repurposing candidates. It collates comprehensive information on pharmaceutically active compounds that have been discontinued from development, or have been pulled from the market. In addition to all identifiable "hard" data (such as chemical structure, INN names and/or research codes, pharmacological activities, key literature and patent references) for which extensive web references are to be provided, the DDCD will contain a wealth of "soft" context-based information such as developer statements and analyst assessments.
Hermann Mucke, Ph.D., Chief Executive, H.M. Pharma Consultancy
11:05 am Curing Rare Diseases: Patient-driven Therapies & Multi-partner Collaborations
Out of 8000 rare diseases, only 200 have a cure today. Healx Ltd, a Cambridge-based startup (UK), addresses this gap by applying a patient-driven drug development model. Healx combines cutting-edge computational techniques from Cambridge University with world-leading biomedical expertise. This allows to identify novel therapeutic solutions for rare diseases by shortlisting effective drug repositioning candidates. Experimental validation and co-development of therapies are performed hand in hand with patient groups and charities, placing them at the heart of the discussion. This alternative model will be illustrated with the NGLY1 disorder, involving private-public partnerships with 7 different organisations, which are spread over multiple cities in both Europe and the United States.
Tim Guilliams, Ph.D., Chief Executive, Healx
11:35 am Drug Repurposing Successes in Cancer are (Too) Rare: Causes and Potential Solutions
Drug repurposing successes in oncology are rare despite strong evidence supporting numerous drugs. Two non-profit organizations (NPOs), the Anticancer Fund and GlobalCures, joined forces to identify and implement solutions to improve the success rate. The main reason for a limited success is the unlikely return on investment (ROI) for drugs with the strongest evidence for an anticancer effect. Many issues originate from this simple fact. As a consequence, companies interested in drug repurposing must complexify the drug development process to secure intellectual property (IP) and likelihood of ROI. NPOs - who consider drug repurposing as a rapid way to offer additional therapeutic options to patients - see their efforts limited by a lack of experience in drug development and by limited financial resources. Regulators neither have experience nor propose a regulatory framework to manage application for approval of a new indication when the applicant is not the drug company. In addition to new incentives for drug developers, promotion of a drug development mindset in NPOs, exploring alternative ways of funding non-commercial trials and use of drug combinations are amongst the simplest solutions to address the problem and ultimately increase the success rate in the interest of patients and societies.
Gauthier Bouche, MD, Medical Director, Anticancer Fund
12:05 pm Luncheon
1:15 pm Development of a Novel Treatment for Non-Muscle Invasive Bladder Cancer
Ciclopirox olamine is contained within several topical drug products to treat fungal and yeast infections of the skin. Ciclopirox has also shown anticancer activity in vitro and in vivo in preclinical models of blood as well as solid tumor cancers. The drug has also been evaluated in acute myeloid leukemia patients following oral administration. Dr. Weir and his team are developing a patented prodrug of ciclopirox for systemic administration in the treatment of non-muscle invasive bladder cancer. Systemic administration of ciclopirox prodrug selectively delivers ciclopirox to the entire urinary tract. They’ve demonstrated proof of principle in vitro and in in vivo preclinical models of non-muscle invasive and muscle invasive bladder cancer. As a result, they are moving forward with IND-enabling activities with a goal of initiating bladder cancer clinical proof of concept trials in 2016. In this presentation, Dr. Weir will discuss pharmacokinetics, drug metabolism, in vitro and in vivo proof of principle as well as mechanism of action.
Scott Weir, PharmD, Ph.D., Director, Institute for Advancing Medical Innovation, Associate Director, Translational Research, University of Kansas Cancer Center, Professor, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center
1:45 pm CureAccelerator™: How A Global “Repurposing Research” Platform Can Drive More Treatments to the World's Unsolved Diseases
More than 7,000 “unsolved diseases” have no fully effective treatment, affecting more than 500 million people worldwide. CureAccelerator is the world’s first open-access, online platform dedicated to Repurposing Research – the quest to create new medical treatments from existing therapies, to drive more treatments more quickly to more patients. This presentation will describe how this innovative IT platform, funded with a grant from the Robert Wood Johnson Foundation, will enable funders, clinicians, researchers, academia, the biomedical industry and patient groups to collaborate far more efficiently, to accelerate the pace of repurposing research.
Bruce Bloom, DDS, JD, President and Chief Science Officer, Cures Within Reach
2:15 pm Drug Repositioning in Primary Care and Specialty Care: Commercial Successes in the Osteoarthritis and Rheumatoid Arthritis Disease Areas
Both osteoarthritis and rheumatoid arthritis continue to have gaps in the therapy, whether it is life-threatening NSAID-induced GI ulcers or less than optimal pain and inflammation relief for the millions of patients that suffer from the daily restrictions these diseases create. In these disease areas, Horizon Pharma has been able to successfully reposition known molecules to help patients and physicians in both Primary Care and Specialty Care settings. Despite many challenges encountered in the development, regulatory and commercial development of DUEXIS® and RAYOS®, the products have been successfully commercialized and provide examples of repositioning molecules to address unmet medical needs for patients. A brief history of these products will be shared to highlight the pre- and post-launch milestones.
Roy Anderson, Group VP of Marketing Strategy and Commercial Development, Horizon Pharma plc
2:45 pm Identification of Host-directed Antimicrobial Drugs
Antibiotic resistance remains a growing concern on a global scale. Targeting the host cell, but not the pathogen, can provide effective therapies and potentially circumvent the problem of antibiotic resistance. Moreover, developing novel ways to combat infections by intracellular pathogens through repurposing of FDA-approved drugs becomes an attractive approach in the light of the currently unmet need for novel anti-infectives.
Daniel M. Czyz, Ph.D., Postdoctoral Scholar/Crosson Lab, Department of Biochemistry & Molecular Biology, University of Chicago
3:15 pm Refreshment Break
3:45 Repurposing a NCE in an Orphan Indication
Financial and design obstacles impede many compounds’ paths to development. Transparency Life Sciences has created a drug development platform that allows for the cost-effective repurposing and repositioning of drug assets through the use of crowdsourced protocol design, intensive use of telemonitoring, and full data transparency. In this talk, CEO Tomasz Sablinski will discuss a current collaboration with Auven Therapeutics and Mt. Sinai School of Medicine. TLS is helping to repurpose Kiacta®, currently in a phase III trial in AA amyloidosis, for sarcoidosis. He will demonstrate how the TLS platform has catalyzed an innovative trial design and created new potential value for the compound, with the goal of providing a new therapeutic option for patients in need of new treatments for sarcoidosis.
Tomasz Sablinski, MD, Ph.D., Chief Executive Officer, Transparency Life Sciences
4:15 pm End-of-Day Panel Session
This session brings together the day's speakers for an informal question/answer period with our chairperson as well as the audience. This is a great opportunity to ask additional questions of the day's speakers. It also allows for an open dialogue between audience and speakers.
5:00 End of Day's Sessions
DAY TWO - May 28, 2015
7:45 am Continental Breakfast
8:30 am Chairperson's Opening Remarks
Bruce Bloom, DDS, JD, President and Chief Science Officer, Cures Within Reach
8:35 am A Major Global Drug Repositioning Initiative in Parkinson’s Disease
Drug repositioning represents one of The Cure Parkinson's Trust's major therapeutic initiatives. They have found a variety of innovative ways to select drug candidates, and to prioritize which enters clinical trials. Over the past 3 years, 72 drug candidates in Phase II-IV (drawn from many therapeutic areas, and involving > 40 pharmaceutical and biotechnology companies and 63 compelling biological targets) were initially assessed in high detail for their potential as disease-modifying treatments for Parkinson’s disease (PD). A committee of 12 global experts in PD, and who cover a range of appropriate neurological, pharmaceutical, genetic, biochemical, PK, BBB, safety and toxicology skills & experience, meet regularly to assess and prioritize these drugs, and choose which should enter Phase II proof of concept trials conducted across a network of specialist neurology hospitals around the world. To date, 17 of these drugs have successfully been prioritized to move into trials, the first of which enjoyed highly original and clinically encouraging results which were published in the Journal of Clinical Investigation. The committee has requested additional preclinical or safety studies on many of the other drugs proposed, and we anticipate many of these will soon also be prioritized to enter PD trials. We commend this unique approach for any therapeutic area wishing to conduct multiple simultaneous drug repositioning trials straddling a large number of different, highly promising biological targets.
Dr. Richard Wyse, Director of Research and Development, The Cure Parkinson's Trust
9:05 am Massive Parallelization of Repositioning in Orphan Drug Discovery
In this presentation, Dr. Gibson will discuss the following:
- Rationale for target agnostic approaches for orphan drug discovery
- Rational for drug repurposing in orphan drug discovery
- Description of our target agnostic massively-parallel assay for orphan diseases
- Preliminary reports of our successes in using this approach
Chris Gibson, Ph.D., MD, Chief Executive Officer, Recursion Pharmaceuticals
9:35 am High Fidelity Drug Repurposing Screen Using a New Computational Method
The number of failed and shelved drugs, whose safety is known, are growing every year. In parallel with this, the number of new targets is constantly growing. The technology to evaluate or re-evaluate new diseases, new targets, new pathways, and new functions continues to evolve so that research-led-repositioning rather than random screening is now a viable strategic model for rapid drug development. Efficient in-silico approaches may provide invaluable information on molecular mechanisms underlying drug action, drug side effects and repositioning. However existing in-silico approaches have limitations, including prominent false positives and limited target coverage. To overcome these challenges, we have developed a new drug repurposing method called "RepurposeVS" that combines ligand-and target-phenotypes properties to predict the best matched drug-target pairs, and potential molecular mechanistic pathways. Validity of the method will be discussed at the conference.
Sivanesan Dakshanamurthy, Ph.D., Associate Professor of Oncology, Clinical & Experimental Therapeutics Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center
10:05 Refreshment Break
10:30 am Academic Medicine - Challenge and Opportunity From the Frontline of Repurposing Research
Repurposing research is prevalent in academic medical centers often fits regulatory definitions that require an Investigative New Drug (IND) submission to FDA. Companies interested in academic research findings may also prefer that these trials were conducted under an IND. This talk will describe the regulatory challenges and opportunities in an academic environment and how they impact academic-industry alliances and translational potential.
E. Mitchell Seymour, Ph.D., RAC., Director, Founder, R&D Advisors LLC, Faculty, University of Michigan Institute for Clinical and Health Research
11:00 am The Role of Non-profits in the Hunt for New Drugs for Dementia
Drug repurposing offers a unique space that non-profit organizations can work in. There is evidence that many currently used drugs may be helpful in dementia. Non-profits can drive consensus exercises to identify leading targets to take to trials. Collaborative funding can enable clinical trials of repurposed agents. In this presentation, Dr. Pickett will talk through examples in Alzheimer’s Disease and other dementias, mainly with a UK focus.
James Pickett, Ph.D., Head of Research, Alzheimer's Society
11:30 am Drug Repositioning in Rare Diseases: Optimizing Patients Drug Access
SOM Biotech owns a virtual screening in-silico technology able to identify new activities of already know drugs which has enabled them to develop a property library of products that have reached clinical or approved status. Dr. Insa will present the case study of SOM0226, a repositioned product for the prevention and treatment of Transthyretin Amyloidosis (ATTR) which has jumped to Phase 2 proof of concepts in just two years after its discovery and is four times more potent/active than the most advanced new chemical entity (Tafamidis).Also, the case of SOM3355 for the treatment of chorea in Huntington patients will be discussed; a repurposed product with a better safety and compliance than the gold standard (Tetrabenazine).
Raul Insa, MD, Ph.D., MBA, Founder and CEO, SOM Biotech
12:00 pm Luncheon
1:00 pm Repurposing Non-antimicrobial Drugs for Treatment of Bacterial Infections
Among the most important scientific achievements in history has been the discovery and development of antibiotics. Unfortunately, antimicrobials currently used in the healthcare system are losing the battle in the fight against multidrug-resistant pathogens (MDRP). Thus there is an unmet need for strategic development of novel antimicrobials to address this burgeoning global health challenge. One strategy that warrants special attention as a unique method for identifying new antimicrobials is drug repurposing. Several approved drugs have been successfully repurposed as anti-infective agents especially to treat parasitic and protozoal diseases. However, to date, not a single drug has been successfully repurposed for use as an antibacterial. The presentation will discuss the challenges associated with repurposing approved drugs as antibacterials and potential uses of approved drugs that can be further explored to develop these existing drugs as novel therapeutics to treat MDRP. The final segment of the presentation will focus on our attempts in repurposing approved and abandoned drugs for the treatment and prevention of bacterial infections.
Mohamed Seleem, BVMS, MVSc, PhD., Assistant Professor of Microbiology, Department of Comparative Pathobiology, Purdue University School of Veterinary Medicine
1:30 pm Drug Repositioning in the Era of Precision Medicine
This presentation will focus on NuMedii’s general approach towards the discovery of new therapeutic uses for existing drugs. While the business models for repurposing marketed drugs versus repositioning of proprietary shelved assets remain distinct, each with their unique opportunities and challenges, much of the underlying big data content and computational approaches used to identify lead assets in a given therapeutic area of interest remain constant. This talk will provide a high level overview of some of the tools we have deployed for systematic drug repositioning. A couple of use cases will be presented describing the specific use of chemogenomics, systems biology and knowledge-based methodologies to identify new drugs/targets in Inflammatory Bowel Disease and Psoriasis.
Craig Webb, Ph.D., Chief Scientific Officer, NuMedii
2:00 pm Updates on the NCATS New Therapeutic Uses Program
Discovering New Therapeutic Uses for Existing Molecules (New Therapeutic Uses) is a collaborative program designed to develop partnerships between pharmaceutical companies and the biomedical research community to advance therapeutics development. Using assets that already have cleared several key steps in the development process gives scientists nationwide a strong starting point to contribute their unique expertise and accelerate the pace of therapeutics development. In June 2013, NCATS announced the first projects awarded through this program. In this presentation, you will hear an update on the program and some of the challenges and lessons learned.
Christine Colvis, Ph.D., Director, Drug Development Partnership Programs, National Center for Advancing Translational Sciences (NCATS), NIH
2:30 pm End-of-Day Panel Session
This session brings together the day's speakers for an informal question/answer period with our chairperson as well as the audience. This is a great opportunity to ask additional questions of the day's speakers. It also allows for an open dialogue between audience and speakers.
3:15 pm End of Conference