Arrow Therapeutics Limited Corporate Presentation 2007 1
Arrow Therapeutic Areas – Clinical 2006 Hepatitis C Respiratory Syncytial Virus A-831 Novel NS5a inhibitor RSV604 First in class therapeutic • Large unmet medical need • Large unmet medical need • Significant market potential • Significant market potential • Competitive but NS5a not • Little competition • Complex virology • Simple virology • Need potency to avoid resistance • Window of opportunity 2
3 RSV Programme
RSV Overview • Seasonal virus – winter season • The cause of 20% of all lower respiratory tract infections • Serious threat where compromised immune systems – 10% of stem cell patients contract RSV � 50% develop pneumonia � 45%-80% die • >2% of infants under 2 years of age hospitalised with RSV • RSV cause exacerbations in COPD & asthma sufferers • Leading cause of morbidity and mortality in elderly 4
RSV market potential Infants $650-850m per year ‘Synagis’ prophylaxis ~$1bn sales RSV Therapeutic (2005) COPD / BROAD MARKET Asthma Potential for $380m prophylaxis $900m - $1,250m per year $?m per year (2015) per year Elderly $220m $200 - $3,000 per year per treatment Immuno- compromised $5-50m per year 5
RSV604 • Novel inhibitor of RSV O H N • Broad spectrum activity, subtypes H N and >50 clinical strains H F N N O • Slow onset of resistance and no cross resistance observed with known inhibitors • Novel mode of action, targeting •S-(-)- “active enantiomer” essential replication complex 6
Proof of Concept – in vitro Day 2 Day 6 Day 2 Day 6 RSV RSV RSV RSV + + RSV604 RSV604 10 µM 2 µM RSV604 IC50 0.9 µM IC90 1.8 µM 7
Clinical Trial Strategy Clinical trial Responsible Status Ph 1 SAD Arrow Complete Ph 1 MAD Arrow Complete Phase II Pilot SCT Arrow Complete Phase I Oral/SAD NF Arrow Complete Phase I iv/SAD NF NVS Complete Phase II ICP POC NVS IND being updated, scheduled Phase III ICP NVS Winter 2007/8 Phase III Infants NVS Winter 2008-2010 8
RSV604 Phase I summary • No Serious Adverse Events • No ‘probably’ drug-related adverse events • No ECG, telemetry, vital signs adverse findings Human PK Day 1 Day 7 1600 A -6 0 4 4 4 C o n c e n tr a ti o n (n g / m L ) 1000 1400 800 600&450 1200 600&450mg 300mg 1000 600 300mg 150mg 800 150mg 400 IC90 IC90 600 IC50 IC50 200 400 200 0 0 0 4 8 12 16 20 24 192 196 200 204 Time (h) Time (h) 9
RSV604 Pilot POC Study – CP204 Screen, diagnose, recruit Design: 6 patients RSV604 open label Days of study – Safety 1 2 3 4 5 6 7 8 – PK of RSV604 and con Oral RSV604 5 days meds Oral RSV604 5 days – Antiviral activity (qPCR) • Placebo-controlled study Placebo 5 days Placebo 5 days • 22pts even number on drug and placebo • Total of 27 pts in 27 clinical trial centres US/EU/Aus. Primary endpoint: decrease in RSV • Results presented this week by qPCR vs Placebo 10
11 DFCI 05-310
Novartis Deal • On signing (received) - $10 million – Pre-commercial milestones – Sales related milestones • Total upfront plus milestones = $217 million • Arrow will receive royalties appropriate for a Phase II compound • Novartis fund all development costs • Follow-ups not included other than limited right of negotiation 12
13 Hepatitis C
Pipeline – HCV – Epidemiology Infected Blood and Blood Products Still major route in Major current route in Perinatal Developing countries US/EU/Japan 170 million infected worldwide WHO: WHO: Slow disease progression “VIRAL TIME “VIRAL TIME 5-10m EU Asymptomatic for decades BOMB” BOMB” 3-4m US Liver cirrhosis and cancer ~2m JP 3-4m new infections per annum 14
Pipeline – HCV – Current Treatments Current standard of care: Pegylated Interferon oral (weekly subcutaneous injection) ribavirin + Combined sales > $2 billion + Serious Side Effects : Depression, neutropenia, headaches, Haemolytic anaemia, fatigue, nausea, others birth defects, others Current efficacy: Genotype 1: 48 week therapy 40-50% SVR Genotype 1 most important >70% in US/EU. Growing pool of non-responders Significant medical need for more effective therapy with reduced side effects Significant medical need for more effective therapy with reduced side effects 15
Pipeline – HCV - Genomic organisation Arrow’s target Bartenschlager & Lohmann http://www.med.uni-heidelberg.de/hyg/hyg5/EN/HCV.HTM http://euhcvdb.ibcp.fr/euHCVdb/jsp/map_p.jsp 16
NS5a target NS5a focus : dual approach with two • Essential for replicon activity chemotypes • N terminal half is well conserved across genotypes & structure available for domain 1 • No known human homologues suggesting virus specific activity would be possible • Key to virus control of host cell response – a double hit •T. L. Tellinghuisen, J. Marcotrigiano and C. M. Rice Nature 435, 374-379 17
A-831 Rat PK Mechanism/ Replicon TI Second 1b/1a 1b (replicon) Species PK (Cmax, F) Synthesis 4ug/ml 0.4ug/ml (30mg/kg) (30mg/kg) Novel/ HCV 500nM < 5 fold 50 fold 19.9ug/ml liver 9.87ug/ml liver <10 steps Std. F 25% F 25% NS5a √√ √√ √√ √√ √√ A-831 6 steps PO v IV 100000 10000 Conc (ng/mL) IV (0.5 mg/kg) 1000 PO 5 mg/kg 100 PO 25 mg/kg 10 1 0 500 1000 Time (mins) 18
HCV Summary • Multiple programs: – Novel NS5a programs (2 programs) • Clinical Candidate (A-831 selected Q4 2005) SAD study complete entering MAD study • Pre-clincal candidate A-689 from second series selected – Polymerase program • 2007Objectives: – Second NS5a development series to Phase 1 Q4 ‘07 – A-831 POC Q3 • Strategy – Parallel evaluation of two NS5a series – Ideal for combinations 19
Arrow today CEO Management team with experience of successful drug development and BUS. DEV 2 marketing as well as biotech business FINANCE creation & FACILITIES 5 Development team from GSK, Roche with experience DEVELOPMENT 9 of taking multiple drugs through development BIOLOGY 14 Strong research based on industry experienced senior management and staff, mixed 50:50 with CHEMISTRY 24 junior staff from good academic labs across EU. 57 employees in total Central London based: 30,000 sq ft of purpose fitted laboratories and office space 20
Conclusions • Leadership position in RSV therapeutics – Collaboration with Novartis – Most advanced anti-viral therapy in development • Multiple novel HCV programs first entering the clinic 2006 – Two novel NS5a programs – A non-nucleoside polymerase program • Proven anti-viral research engine 21
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