Drug Repositioning InformaticsDeveloping Information Analytics & Search Solutions To Identify, Evaluate and Exploit New Opportunities For Drug RepositioningNick BrownInformatics Programme ManagerNew Opportunities
Our CompanyHealthcare For PeopleAs one of the world’s leading pharmaceutical companies, our business is providing innovative, effective medicines that make a real difference to patients. We focus our skills and resources on six important areas of healthcare, which include some of the world’s most serious illnesses. Cardiovascular Gastrointestinal Neuroscience Respiratory & inflammation Infection Cancer
New OpportunitiesThe Other Disease Areas...New Opportunities is a fully virtualized R&D unit that brings medicines to patients in disease areas where AstraZeneca is not currently conducting research.Our current interests are in ophthalmology, wound‐healing, bone disorders, dermatology, women’s health, critical care, auditory disorders and regenerative medicine.We are always seeking New Opportunities by In‐licensing promising late stage assets to strengthen our pipeline Out‐licensing and co‐development models for internal candidate drugs Testing and adding value to our compounds through in vivo and clinical models Forming partnerships with external companies with expertise in specific diseases
External PartnershipsRecent SuccessIn 2009, we signed a deal with Alcon, experts in ophthalmology and in 2011, we signed a deal with Galderma, experts in dermatology. Partnering with world‐leaders is the most efficient and effective way to unlock the potential of our compounds in these rapidly evolving disease areas.
Drug RepositioningDefinitions...Repositioning, Reprofiling, Repurposing, Recycling...We simply look to systematically consider alternative disease indications for all of our drugs and compounds, from early discovery to late stage development compounds, even considering life cycle management opportunities.We do this through the gathering of different types of information, informatic analyses, scientific testing and prioritizing our options for a considered portfolio. Today I will describe some of these approaches.
Structure-Based RepositioningPredictive ModellingWe have experimented with a variety of in‐silico modelling approaches (Bayesian, QSAR, Random Forest) to identify novel indications for screening our early Discovery compound library based on structure alone. positive negativeWe hope to start to use such approaches in earnest to develop new R&D programmes with a longer term approach to diseases of unmet patient needs. Always interested in hearing additional approaches that have the ability to profile entire compound libraries.
Launched Drug RepositioningLife-Cycle Management IndicationsOne of the easiest opportunities to reposition is with existing, launched drugs, leveraging literature, clinical and mechanistic information. ▪ Xylocaine (lidocaine) – many literature and medical sources described the potential for this anesthetic, reformulated for migraine. This has now been tested in clinical trials as a nasal spray for migraine.▪ Atacand (candesartan) and similar compounds have the potential to be useful in hypertension, alcoholic liver disease and aortic valve stenosis. These are also undergoing clinical testing.Where compounds have been launched, there is a lot of information that can be gathered from conference and grants, as well as web‐sources and forums to provide possible clues to consider further new indications.
Mechanistic RepositioningBuilding The FoundationIn 2008, we negotiated, licensed and indexed >50 million scientific abstracts. Our systems use these & aggregated competitive intelligence systems on the fly Identify Find Alerts & Trends Capture Ideas Collaborators Repositioning to Breaking For Our & Companies Opportunities Information Prioritisation SOLR Web Services Clinical Trials Publications Patents News Congress Data Grants PhD theses PhD Unstructured Scientific Abstracts Structured Comp IntelWe then leverage tools like Pipeline Pilot to build prototypes rapidly
Mechanistic RepositioningUnderlying ConceptWe systematically process every disease against every mechanism, finding potential hotspots that we should investigate further. Potential Potential Disease terms Mechanism of Actions Mechanism of Actions Disease terms Biological Rational Competitive RationalUsing a variety of statistical approaches, we can identify new opportunities for our existing compounds or in‐licensing opportunities for external compounds.
Asset Repositioning MatrixStitching Information TogetherUsing this approach, we have identified hundreds of opportunities that connect druggable target mechanisms to disease indications. e.g. Neglected Tropical DiseaseHaving evaluated some hits pre‐clinically , we have our first human study this year. As well as single hits, we also identifies themes for potential franchises, such as ophthalmology and dermatology, where we seek world leaders to partner with
Matrix ReloadedExtending The SourcesAs the system was developed to handle millions of datapoints, from different data slices, we have started to add additional data from a variety of sources Biological Potential & Target Efficacy Competitor Landscape & Patent Position Safety & Adverse Events Consideration Patient & Genetic Rationale Tissue & Cell RationalOnly in combination, can we utilize this information to have a prioritized view of our assets and those potential repositioning opportunities we should progress further to evaluation.
Web 2.0 RepositioningUsing The Power of PeopleAs a small team, we are unable to triage every potential opportunity, but by building an intranet based approach, scientists from across AZ can curate potential hits as well as submit their own ideas in one system. Reject hypothesis Second Opinion Evaluate Pre‐Clinically Submit New IdeaThis also helps to actively consider repositioning opportunities from one disease area into another existing AZ disease area, as well as those that we consider in New Opportunities.
Influencing R&D SearchAccessing our internal contentOver the past 6 months, I have been working with a team in AstraZeneca (and external company) to develop new platforms for searching internal R&D content and surfacing it in bespoke business applications. By standardizing our internal AZ vocabularies and auto‐tagging our rich, internal document sources, we have been able to identify around 1700 files that contain potential new indications that have been hypothesized over the past 10 years.We aim to increase access to this R&D content, through improved information policies and knowledge management systems but also by driving it through demonstrating clear, unequivocal business benefits such as this.
Repositioning By FunctionLeveraging how our drugs workUnderstanding mechanisms and targets is not sufficient. Working with our scientists, we have recognised that the best repositioning successes are done by truly understanding how the drugs operate. No target is involved !For example heart failure / angina hypertension Stroke / aneurysms e.g. lowers blood AZ compounds pressure retinopathy nephropathy dementiaWe have interviewed over 100 scientists to collate information about our drugs systematically into a single location and biological process maps
Biological Process MappingCapturing AZ KnowledgeWe capture information around where and how the drugs work, down to the level of the cell, tissue and pathophysiological changes leading to outcomes.
Consortium Model ?We can’t do this alone...Whilst we can map our own existing AZ development compounds and drugs, we are working with Thomson Reuters (GeneGO) to launch a new consortiumMetaMiner Mechanism of Action (MMMOA) consortium Commencing July 2011 Mapping bioprocess maps for FDA approved drugs over 3 years Manually curated maps, supported by scientific evidenceBenefits ? We are aiming to use this in conjunction with internal approaches to facilitate our drug repositioning and drug combination initiativesInterested ? Get in touch… Contact Nick Brown (AZ), Caroline Hellawell (AZ), or Rob Greenwood (Thomson Reuters)
New Opportunities - Virtual iMED100% ExternalisationWith no R&D of our own, New Opportunities always looks to consider the external world as its laboratory, working with leaders in any field.We are always interested to work with people on repositioning systems, computational approaches, disease models, licensing compounds, collaborative development opportunities…
Understanding New Disease Areas Finding Key Opinion Leaders & Experts Of course, to rapidly understand new disease areas, we try to work with leading experts. To find them, we built KOL Miner (with OpenQ) – a system that analyses the 50M scientific documents on the fly and finds people & companies in seconds.Top KOLs in GABA across the world. Top 10 KOLs working with leptocytes in GABA field. It also creates interaction maps and timeline views, that enable us to figure out who is key, who are rising stars and who has the largest sphere of influence. This also allows us to rapidly find companies to test our new hypotheses with.
Evaluating Our HypothesesFinding The Right CROAs well as working with leading academic experts, we work with many CROs to test ourideas pre‐clinically. We use a private version of the Assay Depot marketplace to findservices and screens. The private marketplace acts as a single source of information aboutinternal and external services, and can enable us to easily chat with new CROs about whatmodels they have, how much they cost and what parameters we are planning to evaluate.Service marketplace and communication channel for 4000+ CROs The marketplace helps standardize information about in vivo models that have previously been difficult to compare directly.
New OpportunitiesPlease come and talk to us !Hopefully today I have provided a brief overview of how we use a virtual function in a pharmaceutical company to repositioning our portfolio and evaluate these.If you would like to work together or want to discuss anything further please get in touch. email@example.com Any Questions…
AcknowledgementsNone of this possible without the help ofEd Holbrook (AstraZeneca) and some of our collaborators I can nameMark Robertson (AstraZeneca) Graham Cox (Tessella)Caroline Hellawell (AstraZeneca) Jerry Campbell (Tessella)Johanna Sagemark (AstraZeneca) Jamie Kincaid (Accelrys)Jane Escott (AstraZeneca) Alex Benn (Accelrys)Marcus Bjäreland (AstraZeneca) Julie Bryant (GeneGO)Ian Barrett (AstraZeneca) Svetlana Bureeva (GeneGO)Amy McDonough (AstraZeneca) Ruben Jimenez (OpenQ)Graeme Wilkinson (AstraZeneca) Otavio Freire (OpenQ)Hitesh Sanganee (AstraZeneca) Kevin Lustig (AssayDepot)Elaine Anderson (AstraZeneca) Corey Jacklin (AssayDepot)Lisa Taylor (AstraZeneca)
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