Arrow Therapeutics Limited Corporate Presentation 2007 1 Arrow - - PowerPoint PPT Presentation

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Arrow Therapeutics Limited Corporate Presentation 2007 1 Arrow - - PowerPoint PPT Presentation

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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

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Arrow Therapeutics Limited

Corporate Presentation 2007

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Arrow Therapeutic Areas – Clinical 2006

Respiratory Syncytial Virus RSV604 First in class therapeutic

  • Large unmet medical need
  • Significant market potential
  • Little competition
  • Simple virology

Hepatitis C A-831 Novel NS5a inhibitor

  • Large unmet medical need
  • Significant market potential
  • Competitive but NS5a not
  • Complex virology
  • Need potency to avoid resistance
  • Window of opportunity
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RSV Programme

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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
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RSV market potential

RSV Therapeutic BROAD MARKET $900m - $1,250m per year (2015)

Potential for prophylaxis $?m per year Immuno- compromised $5-50m per year

Infants $650-850m per year

Elderly $220m per year COPD / Asthma $380m per year

$200 - $3,000 per treatment ‘Synagis’ prophylaxis ~$1bn sales (2005)

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RSV604

  • Novel inhibitor of RSV
  • Broad spectrum activity, subtypes

and >50 clinical strains

  • Slow onset of resistance and no

cross resistance observed with known inhibitors

  • Novel mode of action, targeting

essential replication complex

N H N O N H N H O F

  • S-(-)- “active enantiomer”
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Day 2 Day 6 RSV RSV + RSV604 10 µM Day 2 Day 6 RSV RSV + RSV604 2 µM RSV604 IC50 0.9 µM IC90 1.8 µM

Proof of Concept – in vitro

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Clinical Trial Strategy

Complete Arrow Phase I Oral/SAD NF Complete NVS Phase I iv/SAD NF Winter 2008-2010 NVS Phase III Infants Winter 2007/8 NVS Phase III ICP IND being updated, scheduled NVS Phase II ICP POC Complete Arrow Phase II Pilot SCT Complete Arrow Ph 1 MAD Complete Arrow Ph 1 SAD

Status Responsible Clinical trial

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200 400 600 800 1000 4 8 12 16 20 24 Time (h) A -6 0 4 4 4 C o n c e n tr a ti o n (n g / m L ) 600&450 300mg 150mg IC90 IC50

200 400 600 800 1000 1200 1400 1600 192 196 200 204

Time (h)

600&450mg 300mg 150mg IC90 IC50

Human PK Day 1 Day 7

RSV604 Phase I summary

  • No Serious Adverse Events
  • No ‘probably’ drug-related adverse events
  • No ECG, telemetry, vital signs adverse findings
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Placebo 5 days Placebo 5 days Oral RSV604 5 days Oral RSV604 5 days

Days of study 2 7 3 8 4 5 6 1

Screen, diagnose, recruit

Primary endpoint: decrease in RSV by qPCR vs Placebo

RSV604 Pilot POC Study – CP204

Design: 6 patients RSV604 open label – Safety – PK of RSV604 and con meds – Antiviral activity (qPCR)

  • Placebo-controlled study
  • 22pts even number on drug

and placebo

  • Total of 27 pts in 27 clinical

trial centres US/EU/Aus.

  • Results presented this week
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DFCI 05-310

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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
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Hepatitis C

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Slow disease progression Asymptomatic for decades Liver cirrhosis and cancer

Pipeline – HCV – Epidemiology

WHO: “VIRAL TIME BOMB” WHO: “VIRAL TIME BOMB”

Still major route in Developing countries Major current route in US/EU/Japan Perinatal

Infected Blood and Blood Products

170 million infected worldwide

3-4m US 5-10m EU ~2m JP 3-4m new infections per annum

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Pipeline – HCV – Current Treatments

Significant medical need for more effective therapy with reduced side effects Significant medical need for more effective therapy with reduced side effects Current standard of care:

Serious Side Effects: Depression, neutropenia, headaches, Haemolytic anaemia, fatigue, nausea, others birth defects, others

Combined sales > $2 billion

  • ral

ribavirin Pegylated Interferon (weekly subcutaneous injection) +

+

Genotype 1: 48 week therapy 40-50% SVR

Genotype 1 most important >70% in US/EU. Growing pool of non-responders

Current efficacy:

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Pipeline – HCV - Genomic organisation

Bartenschlager & Lohmann http://www.med.uni-heidelberg.de/hyg/hyg5/EN/HCV.HTM http://euhcvdb.ibcp.fr/euHCVdb/jsp/map_p.jsp

Arrow’s target

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NS5a target

  • Essential for replicon activity
  • 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 NS5a focus: dual approach with two chemotypes

  • T. L. Tellinghuisen, J. Marcotrigiano and C. M. Rice

Nature 435, 374-379

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A-831

√√

< 5 fold 1b/1a

A-831 HCV Std.

Novel/ <10 steps 4ug/ml (30mg/kg) 9.87ug/ml liver F 25% 0.4ug/ml (30mg/kg) 19.9ug/ml liver F 25% 50 fold 500nM NS5a 6 steps

√√ √√ √√ √√

Mechanism/ Synthesis Second Species PK Rat PK (Cmax, F) TI (replicon) Replicon 1b

PO v IV

1 10 100 1000 10000 100000 500 1000 Time (mins) Conc (ng/mL) IV (0.5 mg/kg) PO 5 mg/kg PO 25 mg/kg

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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

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Arrow today

CHEMISTRY 24 BIOLOGY 14 DEVELOPMENT 9 FINANCE & FACILITIES 5

  • BUS. DEV

2 CEO

Strong research based on industry experienced senior management and staff, mixed 50:50 with junior staff from good academic labs across EU. Development team from GSK, Roche with experience

  • f taking multiple drugs through development

Management team with experience of successful drug development and marketing as well as biotech business creation 57 employees in total Central London based: 30,000 sq ft of purpose fitted laboratories and office space

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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