June 26, 2018

7:45 am Continental Breakfast/Registration

8:25 am Chairperson's Opening Remarks

Aris Persidis, Ph.D., President, Biovista

8:30 am The Drug Repurposing Hub: A Community Resource for Indication Discovery
A longstanding obstacle to drug repurposing is the lack of a comprehensive library of clinical compounds suitable for testing. To address this challenge, we developed the Drug Repurposing Hub, a hand-curated physical and online collection of more than 5,000 compounds. This talk will describe the development of this new resource and current efforts to test drugs across multiple cellular assays.
Steven Corsello, MD, Postdoctoral Fellow, Broad Institute, Instructor in Medicine, Dana-Farber Cancer Institute

9:00 am Leveraging Human Genetics to Repurpose Drugs: Lessons Learned
Last year Dr. Lavieri presented an overview of how we are using the data housed within BioVU, a DNA biobank linked to a de-identified version of Vanderbilt University Medical Center’s electronic health record system, to generate hypotheses for drug repurposing projects. This year, he will share information on the four phase II studies their team is launching this year, and he also will also share lessons learned from several projects that did not advance to clinical development.
Robert R. Lavieri, Ph.D., Project Manager, Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center

9:30 am The Application of Cognitive Tools to Accelerate Drug Repurposing for Parkinson’s Disease
Currently no disease-modifying compounds exist for Parkinson’s disease, and drug repurposing offers the promise of finding a safe cure faster. The Watson team rank ordered over 600 drug candidates for likelihood of treating Parkinson’s disease based on their ability to reduce the aggregation and/or toxicity of the protein alpha-synuclein. The team then generated & evaluated hypotheses by providing rationale for the links between top drug candidates, alpha-synuclein, and Parkinson’s disease. This enabled the start of lab validation efforts to evaluate drugs for repurposing for L-Dopa-induced dyskinesia.
W. Scott Spangler, Chief Data Scientist, Distinguished Engineer, IBM Watson Health

10:00 am Refreshment/Networking Break

10:30 am Systematic Drug (Re)Purposing by Triangulating Insights from Unstructured and Structured Data Using Machine Learning
Through a case study, Qrativ (joint venture between Mayo Clinic and nference) will describe how its software platform Darwin.ai can be used to extract and triangulate insights from unstructured data (e.g. text...) and structured data (e.g. genome sequencing, real world evidence...) in order to systematically identify drug (re)purposing opportunities.
Agustin J. Lopez Marquez, Vice President, Business Development and Marketing, nference, Qrativ 

11:00 am Using Artificial Intelligence to Identify Potential Drug Repurposing Opportunities
BenevolentBio is focused on AI technology in the bioscience industries. The initial focus has been on human health – generating new ideas that have the potential to improve the lives of millions and deliver better medicines to patients faster in currently overlooked areas such as orphan diseases and rare cancers. We apply our AI to radically improve the efficiency of drug development, produce better target selection, optimize compounds and draw previously impossible insights from hundreds of millions of associations between biologically meaningful entities and unstructured text. We have developed a significant pipeline of drug candidate programs ranging from early-stage discovery assets to Phase IIb clinical development assets and are working with major pharmaceutical groups to license compounds and develop drugs. We also work closely with charities and other funders, especially in rare disease areas.
Bryn Williams Jones, Director of Exploratory Research, Benevolent AI

11:30 am Repositioning is Easy - Or Is It? The impact of AI on Future Progress
There are several easy and quick and cheap ways to do repositioning. They generate results of variable quality and confidence, as the compromise for being quick/easy/cheap. Big healthcare data has the potential to help do repositioning very well, but not all approaches, including different AIs, are the same. Examples of matching the right repositioning problem with the right AI solution will be shared, including Biovista's Project Prodigy AI.
Aris Persidis, Ph.D., President, Biovista

12:00 pm Luncheon

1:00 pm Panel Session: Artificial Intelligence in Drug Repurposing - Opportunities and Challenges

Chair: Dr. Bruce Bloom, President & Chief Science Officer, Cures Within Reach

1:45 pm The Power of Passion: How a Cancer Not-for-Profit has Moved the Needle for the Treatment of Blood Cancers
The Leukemia & Lymphoma Society (LLS) was founded in 1949 with the goal of curing leukemia.  Today, with annual revenues of $400 million, LLS has been instrumental in developing some of the most innovative cancer treatments in history, including targeted therapies like the tyrosine kinase inhibitors and CAR-T cell immunotherapy.  This talk will describe the research funding approaches utilized by LLS, its investment in both academic and private sector research – including efforts in drug repurposing - and the results obtained.
Lou DeGennaro, Ph.D., President & CEO, The Leukemia and Lymphoma Society

2:15 pm A Systems Biology Driven Repositioning Strategy Identifies Digoxin for Treating Groups 3 and 4 Medulloblastoma
Medulloblastoma is the most common malignant brain tumor of childhood, treatments are sorely needed both to improve survival and reduce treatment related complications. Its sub-types, Groups 3 and 4, an unmet medical need, represent a particular challenge due to their intra-group heterogeneity, which limits the options for "rational" targeted therapies. We report a systems biology driven strategy that combines data from multiple genomic and epigenomic sources to construct novel driver signaling networks to accelerate the discovery of new treatments for cancers. From over 1,300 known drug candidates studied, we identified five members of the cardiac glycoside family potentially inhibit the growth of Groups 3 and 4 medulloblastoma, and subsequently confirmed digoxin, one of the five cardiac glycosides, with in vitro and in vivo studies.
Stephen Wong, Ph.D., P.E., Chief Research Information Officer and Professor and Chair, Department of Systems Medicine and Bioengineering, Houston Methodist 

2:45 pm Nutraceuticals as Repositioning Agents: Rapid Acceleration from Bench to Clinical Trial
Nutraceuticals or dietary supplements are regulated compounds with demonstrated bioactivity. Leveraging existing government regulations and data highlighting safety and efficacy, nutraceuticals can be repurposed for several clinical indications. This talk will focus on strategies to rapidly move nutraceuticals from bench to bedside and will discuss how a novel avocado-derived lipid was quickly moved into a Phase I trail.
Paul Spagnuolo, Ph.D., Associate Professor, Department of Food Science, University of Guelph

3:15 pm Refreshment Break

4:15 pm Application of In Silico Proteome Screening to Discover a Drug’s Polypharmacology to Facilitate Drug Repurposing
In this presentation, Dr. Shahani will discuss the following:
♦ Polypharmacology and its importance in drug discovery and particularly drug repositioning 
♦ Technical overview of Cyclica’s in silico Proteome Screening approach and the data it generates
♦ Data from repurposing study of FDA approved drugs for treatment of Systemic scleroderma
♦ Additional data from separate study exploring the repurposing of an anti-clotting agent for treatment of cancer in combination with statin drugs
Vijay Shahani, Ph.D., Senior Solution Scientist, CyclicaRx

4:45 pm End of Day's Sessions

June 27, 2018

8:00 am Continental Breakfast

8:40 am Chairperson's Opening Remarks

Dr. Bruce Bloom, President & Chief Science Officer, Cures Within Reach

8:45 am A Systems Medicine Approach to Drug Repurposing
The REPO-TRIAL investigates an unconventional strategy to improve the efficacy and precision of drug repurposing trials. Instead of applying classical disease definitions based on symptoms or organs, REPO-TRIAL uses a systems medicine based in-silico approach that identifies mechanistically related disease phenotypes and, as a result, a virtual patient cohort. Research animal use will be kept to a minimum by applying a preclinical randomised confirmatory trial (pRCTs) concept, preclinical systematic reviews, and meta-analyses facilitated by our open access pre-clinicaltrials.org platform. Selected results will be validated via high precision clinical trials in patients with cerebro-cardiovascular phenotypes stratified using an exclusive mechanistic biomarker panel. We thus innovate two biomedical product classes, drugs and diagnostics. REPO-TRIAL commenced in February 2018, and will conclude in January 2023.
Hermann Mucke, Ph.D., Principal, H.M. Pharma Consultancy

9:15 am Big Data-based Drug Repurposing Strategy: Special Focus on Brain Ischemia
In this presentation, Dr. Casas will present her team's innovative in-silico based approach to improve the efficacy and precision of drug repurposing trials. This systems medicine-based in-silico approach identifies mechanistically related disease phenotypes followed by later validation of this in-silico drug repurposing approach via pre-clinical experimentation and clinical trials. Their approach has been validated in one of the highest prevalence unmet medical needs, brain ischemia. Surprisingly, her team finds that sGC, an hitherto exclusive cardiovascular target, is closely linked to neurological disorders, an application that has so far not been explored clinically. Indeed, we repurposed apo-sGC activators for ischemic stroke suggesting this drug class as a possible first-in-class neuroprotective therapy for stroke.
Ana Casas Guijarro, Ph.D., Department of Pharmacology and Personalised Medicine, Maastricht University

9:45 am Drug Repurposing Using Drosophila Screens and Informatics
Starting with a drosophila RNAi screen to identify genes associated with disease phenotype, the talk will outline an approach that analyzes a heterogeneous network of proteins, diseases and drugs to identify drugs that can be repurposed for the disease. An application of the approach to repurpose drugs for pain will be discussed.
Kas Subramanian, Ph.D., Vice President & Head of Bioinformatics, Syngene International

10:15 am Refreshment Break

10:45 am Repurposing Low-dose Methotrexate for the Treatment of Myeloproliferative Disease
We have previously found that low doses of the generic rheumatology drug methotrexate acts as a JAK/STAT pathway inhibitor. As such, MTX potentially represents a low cost treatment for diseases caused by over activation of the JAK/STAT pathway such as the myelproliferative blood cancers polycythemia vera and essential thrombocytosis. However, moving from preclinical and case study data to human clinical trials has proven to be far more difficult than originally imagined - even for the repurposing of a safe, low cost and widely available drug such as MTX. We have now partnered with a blood cancer charity to gain access to clinical trials unit expertise and a generics drug manufacturer to obtain orphan drug designation for this disease / drug combination. My talk will describe the scientific background to this story and will detail the hurdles we have faced, the solutions we have found and the prospects for repurposing success we anticipate.
Martin Zeidler, Ph.D., Reader, Cellular Signaling, Department of Biomedical Science, The University of Sheffield

11:15 am Expanding the Impact of Repurposing Research
Repurposing research is a growing and critical part of therapy discovery. Repurposing research can quickly provide affordable "new" therapies, with comparably lower research costs. Many repurposing research successes are patient driven and/or physician discovered, and new bioinformatics, phenotypic screening and global information sharing are further driving purposeful repurposing research opportunities. Cures Within Reach and our many industry, academic, philanthropic, clinical and advocacy partners are leading this Repurposing Research Revolution, and together we are developing new financial and collaborative initiatives to continue this growth. This presentation will focus on the future of repurposing research and how every stakeholder group must play a role.
Dr. Bruce Bloom, President & Chief Science Officer, Cures Within Reach
Clare Thibodeaux, Ph.D., Director of Scientific Affairs, Cures Within Reach

11:55 am Luncheon

1:00 pm Open Innovation - A Driver for Drug Repositioning
In this presentation, Dr. Hayes will discuss the rational for repositioning. He will also delve into the various features of AstraZeneca's Open Innovation program which supports repositioning efforts. Lastly, he will discuss ongoing internal and collaborative case studies.
David Hayes, Ph.D., Director, Translational Research Science, AstraZeneca

1:30 pm New Financing Approaches To Re-purposing Clinical Trials
Pharmaceutical companies invest heavily in new drug development. This can be a boon for patients suffering from a myriad of diseases and afflictions. However they are also focused on generating a profit for their stakeholders. Much of their research is focused on drugs with potential for sizable profits. Where does that leave rare diseases with small patient populations and limited profit potential? Payer-private financing is an alternative approach that matches private investors with healthcare payers to fund re-purposing research on already approved medications towards new areas such as rare diseases. Learn about the opportunities and challenges this new funding model presents.
David McKie, VP of Marketing Operations, Medidata Solutions

2:00 pm Using AI to Repurpose Drugs in Rare Diseases: The Fragile X Example

Michale Bouskila-Chubb, Ph.D., MBA, Head of Business Development, Healx

2:30 pm Repositioning, How to Get Value Outside of the Orphan Arena
The critical challenge in drug repurposing has been to redefine the key drivers for success, as investors are looking for more with less: a straightforward definition of the repositioning art. Among the new and exciting tools to be used and discussed in Dr. Marin's talk, OP2 is using in silico development, in a much broader sense than just molecule designing, as we are using AI to generate data before clinical development, a way to rethink the role of regulatory affairs, speed up marketing approval and market access and increase value for stakeholders.
Fred Marin, Pharm.D., Co-Founder and CEO, OP2 Drugs SAS

3:00 pm End of Conference