Open Innovation Alliances in Drug Repositioning

Transcription

1 Open Innovation Alliances in Drug Repositioning Dr Hitesh Sanganee AstraZeneca New Opportunities imed KDDF Drug Repositioning Conference 29 th November 2012

2 AstraZeneca is a global innovation-driven, prescription-based biopharmaceutical business 57,000 employees, 14 principle research centres 26 Supply & Manufacturing sites Extensive sales and marketing networks worldwide Neuroscience Disorders of the CNS are a significant disease burden worldwide. Gastro-intestinal 10-20% of adults suffer from Gastro-Oesophageal Reflux Disease. Oncology Cancer claims over 7m lives each year. Respiratory Chronic Obstructive Pulmonary Disease (COPD) is the 4 th leading cause of death worldwide and around 300m people suffer from asthma. Infection Escalating antibiotic resistance and increased risk of serious infections. Cardiovascular 17 million people die from CV disease each year.

3 Despite our heavy investment, collaboration is essential for delivery of new medicines We employ over 11,000 people in R&D and last year invested $5 billion. We have 14 principal research centres in eight countries. But we can be stronger still by working with partners who add complementary knowledge and skills. Academia Biopharma Government Patients Increase probability of delivering innovative medicines November 2012 Open Innovation Alliances in Drug Repositioning

4 We need scientific experts across the value chain Research Development Commercialisation Find the Target Find the Molecule Translate to man (preclinical) Translate to man (clinical) Deliver to Patient Finding the Target Finding the Molecule Pre-Clinical Clinical Deliver to the Patient Basic Biology Disease specialists Bioscientists informaticians Medicinal chemists Bioscientists DMPK Disease experts Disease models Toxicologists Statisticians Clinicians Statisticians Regulatory Trial delivery Regulatory Real World Evidence Patient Safety November 2012 Open Innovation Alliances in Drug Repositioning

5 AstraZeneca New Opportunities imed Drug repositioning is central to our operating model Given focus on new disease areas much of the potential will exist externally. Opportunities could range from product in-licensing to strategic acquisitions. Many of our internal drug candidates may have utility in other diseases in addition to their initially evaluated indications. Selective evaluation of these will enable a higher probability of success per asset and /or inform early LCM. Leveraging known targets to provide longer term POC options. (opportunistic) Access external opportunities Drug candidate repositioning Research stage collaborations to access novel biology External alliances to deliver all activities 5 November 2012 Open Innovation Alliances in Drug Repositioning

6 Drug repositioning adding sustainable value? Has the potential to reduce costs and timelines......and has been successful... viagra Angina to male sexual dysfunction......and on to pulmonary hypertension Revatio From hypertension to male pattern baldness Rogaine Cymbalta Nature Reviews Drug Disc, 3, , 2004 From morning sickness to multiple myeloma Thalomide From depression to fibromyalgia but requires a constant flow of new ideas to remain successful Where do these new ideas come from? 6 November 2012 Open Innovation Alliances in Drug Repositioning

7 The New Opportunities repositioning process Aligning the best assets with the best ideas Pool of development compounds: AstraZeneca small molecules & MedImmune biologics E.g., Consider patent life SAD & MAD complete Platform of evidence - preferably efficacy in patients Not previously deprioritized by New Opportunities Disease terms Mechanism of Actions Asset substrate Define Compound Criteria Linking target to disease New Ideas! Example include. A discontinued CV drug in PoC for glaucoma 7

8 What is Open Innovation? Open Innovation by Henry Chesbrough In his 2003 book Open Innovation: The New Imperative for Creating and Profiting from Technology, Henry Chesbrough defined Open Innovation as a paradigm that assumes that firms can and should use external ideas as well as internal ideas, and internal and external paths to market. 8 November 2012 Open Innovation Alliances in Drug Repositioning

9 Open Innovation versus Closed Innovation From Closed to Open Model Closed Traditional System Out Licensing How We Innovate Open Open System Has the Potential to Drive Additional Value $ Universities Suppliers Partners $ Back-up Molecules $ New Indications for Development Program $ Outside Technologies $ Issues with the How Current We Operate SystemToday The current environment limits testing of a molecule to one or maybe a few indications Limited resource and expertise forces big pharma to focus only on a few diseases The molecules full potential is not explored $$$$$ Fully explore the potential of each molecule in a timely manner Leverage expertise of special external groups Little expenditure in resources and upfront investment 9 November 2012 Open Innovation Alliances in Drug Repositioning

10 Alliance Management The Art of Working Together 10 November 2012 Open Innovation Alliances in Drug Repositioning

11 Two Aspects of Successful Alliance Management Process and behavioral disciplines Alliance Management Process for the entire alliance lifecycle Process Behavior Behavioral skills and discipline to ensure a collaborative spirit and the ability to proactively and diplomatically manage challenges 11 November 2012 Open Innovation Alliances in Drug Repositioning

12 AstraZeneca s Externalization Strategy Alliance Management is a Key Success Factor The contributions of partnerships to AstraZeneca s portfolio is expected to increase from currently 40% to 60% in the near-term Alliance Management is recognized as a critical success factor for delivering maximal deal value and ensuring the positioning as a partner-of-choice AstraZeneca has established an Alliance Management Center of Excellence and the corporate alliance database has grown beyond 1000 agreements Novel alliance models based on the principles of Open Innovation are being pioneered 12 November 2012 Open Innovation Alliances in Drug Repositioning

13 Alliance Management Life-Cycle Investing time upfront for long-term success Negotiation Phase Launch Phase Manage Phase Implementation Matters Transition to normal business Deliver expected value from Alliance Full-time Alliance Manager Accountable for the overall Alliance health 90 day Kick-off plan Team building Establish Alliance goals and objectives Alignment of Incentives Scorecard & Health Check Continuous improvement culture 13 November 2012 Open Innovation Alliances in Drug Repositioning

14 Open Innovation vs. Traditional Alliances A Comparison 14 November 2012 Open Innovation Alliances in Drug Repositioning

15 Open Innovation Alliances Multi-party Alliances 15 November 2012 Open Innovation Alliances in Drug Repositioning

16 Open Innovation Alliance Models Virtual imed New Opportunities Forms Alliances to Explore Utility of Existing Drug Candidates in New Disease Areas Academic partnerships Development Compound Tool Box AZ Development Compounds Information archive Know-how Dec, 2011 MRC May, 2012 NCATS Next steps... MRC committed up to 10M to fund studies on AZ compounds Proposals received in 8 week call period from 37 UK institutions Proposals span core and adjacent/white space indications Multiple preclinical and clinical collaborative projects to be funded NIH New Therapeutics for Existing Molecules Initiative announced May 2012 Up to $20M in 1 st year; Eight partners Request for Proposals in June, 2012 Clinical projects Evaluating models for broader open innovation Evaluating opportunities with endowments, emerging markets, and foundations Strategic partnerships with biotech and/or pharma e.g Alcon, Galderma 16 November 2012 Open Innovation Alliances in Drug Repositioning

17 AstraZeneca/Medical Research Council Alliance MRC UK Academia 22 compounds >100 clinical and pre-clinical proposals from 37 UK institutions Proposals submitted on all compounds & across a broad span of disease areas MRC will provide funding up to 10M New Opportunities Neuroscience Resp. & Inflamm. Oncology CV & GI Infection

18 AstraZeneca/Medical Research Council Alliance Groundbreaking Initiative for Discovery of New Medicines Tripartite alliance between AstraZeneca, UK Medical Research Council and UK Researchers/Academic Institutions to explore the utility of existing AstraZeneca compounds in new indications of high unmet need. 18 November 2012 Open Innovation Alliances in Drug Repositioning

19 How do we drive the academic response? high quality of compounds and information shared is essential AZD4017 Summary (11 beta) Hydroxysteroid dehydrogenase 1 inhibitor AZD4017 is a potent, selective, orally bio available, 11bHSD1 inhibitor that has been studied in healthy human volunteers and abdominally obese patients Mechanism of Action 11-beta Hydroxysteroid Dehydrogenase Type1Inhibitor Cannabinoid CB1 receptor Agonist DGAT Inhibitor EGFR Tyrosine Kinase Inhibitor Code Number AZD4017 AZD1704 AZD7687 AZD4769 Safety, tolerability and adverse events Pre-clinical pharmacology One and 3 month toxicology studies have been performed in rat and cynomologus monkeys. AZD4017 has been studied in healthy human volunteers and abdominally obese patients and is tolerated when given in single doses up to 1500mg and in multiple doses up to 900mg for periods of up to 9 days. The most commonly reported AEs amongst healthy volunteers were gastrointestinal disorders and headache and were of mild to moderate intensity. The most commonly reported adverse events in patients were hematoma after biopsy and headache and were all mild in intensity. Efficacy of AZD4017 has been established in mouse, rat and dog models. Endothelin A receptor antagonist GABAA ion channel stimulator GABABR1 receptor agonist Glucokinase activator GSK3b Inhibitor MAPK14 (p38) tyrosine kinase inhibitor Matrix Metallopeptidase (MMP) 13 Inhibitor Matrix metallopeptidase 9 12 (MMP9 MMP12) inhibitor Metabotropic Glutamate Receptor 2 Positive Allosteric Modulator mtor Serine/Threonine Kinase (mtorc1/2) Inhibitor ZD4054 AZD7325 AZD3355 AZD1656 AZD1080 AZD6703 AZD6605 AZD1236 AZD8529 AZD8055 Clinical studies Exclusions /restrictions to future studies Other relevant information Proof of mechanism studies have been conducted in abdominally obese patients. A Ph2a proof of principle study, of 28 days duration, is currently being conducted in patients with raised intra ocular pressure. Women of child bearing potential and children should be excluded as the necessary preclinical studies to support administration to these individuals are not currently available. Pre clinical studies indicate the need for monitoring liver enzymes in clinical studies. Opportunities in diabetes patients or in glaucoma/raised intra ocular pressure would not be considered at this time. Muscarinic M1 Receptor Agonist Myeloperoxidase (MPO) inhibitor Neurokinin Receptor NK3 Antagonist P2X7 Antagonist PPARA Agonist Src tyrosine kinase inhibitor TRPV1 Ion channel Inhibitor δ Opioid receptor agonist AZD6088 AZD5904 AZD2624 Probe AZD4619 AZD0530 AZD1386 AZD November 2012 Open Innovation Alliances in Drug Repositioning

20 MRC Made Funding Decision in Oct November 2012 Open Innovation Alliances in Drug Repositioning

21 NIH/NCATS Alliance Discovering New Therapeutic Uses for Existing Molecules Discovering New Therapeutic Uses for Existing Molecules is a collaborative pilot program designed to develop partnerships between pharmaceutical companies and the biomedical research community to advance therapeutic development. This innovative program matches researchers with a selection of molecular compounds from industry to test ideas for new therapeutic uses, with the ultimate goal of identifying promising new treatments for patients. Pharma partners providing access to a total of 58 compounds: AstraZeneca, Abbott, Bristol-Myers Squibb Company, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceutical, Pfizer, and Sanofi. In the fiscal year 2013, NCATS will provide up to $20 million to fund two- to three-year staged, cooperative agreement research grants 21 September 2012 NIH Alliance Wegner & Prothmann New Opportunities

22 NIH Alliance AZ s Compound List Code Number AZD1981 AZD2423 ZD4054. zibotentan AZD3355 AZD7325 AZD1656 MEDI-2338 AZD1236 AZD5904 AZD0328 AZD7268 AZD9056 AZD0530 AZD2171 Mechanism of Action Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)/DP2 antagonist Chemokine (C-C motif) receptor 2 (CCR2) antagonist Endothelin receptor A (ET A ) antagonist γ-aminobutyric acid B receptor (GABA-B) agonist γ-aminobutyric acid A receptor alpha 2 (GABA-A alpha 2) agonist Glucokinase (GK) activator Interleukin 18 (IL-18) antibody Matrix metalloproteinase 9 and 12 (MMP-9 12 inhibitor) Myeloperoxidase (MPO) inhibitor Nicotinic acetylcholine receptor, a7 (a7nachr) agonist δ Opioid receptor agonist Purinergic receptor (P2X) ligand-gated ion channel, 7 (P2X 7 ) antagonist Src tyrosine kinase inhibitor Vascular endothelial growth factor receptor (VEGF) inhibitor 22 September 2012 NIH Alliance Wegner & Prothmann New Opportunities

23 Example Data 23 September 2012 NIH Alliance Wegner & Prothmann New Opportunities

24 Overall Process 24 September 2012 NIH Alliance Wegner & Prothmann New Opportunities

25 Summary AstraZeneca is globally pioneering novel alliance models based on the principles of Open Innovation Open innovation enhances drug repositioning activities by utilizing ideas and knowledge of multiple partners Alliance Management is a key success factor for AZ and we are spearheading a process to efficiently manage these activities and are positioning ourselves as a partner-of-choice Open innovation activity with NIH and MRC have delivered novel ideas for molecules and both programs are progressing, further underling the value of open innovation. 25 November 2012 Open Innovation Alliances in Drug Repositioning