Corporate Presentation November A world-class allergy and asthma specialty biopharma business

Transcription

1 Corporate Presentation November 2015 A world-class allergy and asthma specialty biopharma business

2 Disclaimer 2 Neither this presentation nor any verbal communication shall constitute, or form part of, any offer, invitation or inducement to any person to underwrite, subscribe for, or otherwise acquire or dispose of, any shares or other securities in Circassia Pharmaceuticals plc ( Circassia ). Forward-looking statements This presentation and information communicated verbally to you may contain certain projections and other forward-looking statements with respect to the financial condition, results of operations, businesses and prospects of Circassia. The use of terms such as may, will, should, expect, anticipate, project, estimate, intend, continue, target or believe and similar expressions (or the negatives thereof) are generally intended to identify forward-looking statements. These statements are based on current expectations and involve risk and uncertainty because they relate to events and depend upon circumstances that may or may not occur in the future. There are a number of factors which could cause actual results or developments to differ materially from those expressed or implied by these forward-looking statements. Any of the assumptions underlying these forward-looking statements could prove inaccurate or incorrect and therefore any results contemplated in the forward-looking statements may not actually be achieved. Nothing contained in this presentation or communicated verbally should be construed as a profit forecast or profit estimate. Investors or other recipients are cautioned not to place undue reliance on any forward-looking statements contained herein. Circassia undertakes no obligation to update or revise (publicly or otherwise) any forward-looking statement, whether as a result of new information, future events or other circumstances.

3 Circassia overview Building an allergy & asthma champion 3 Strong broad-based specialty biopharma business 2 currently marketed products sold to allergy / asthma specialists 12 products in development for allergy, asthma and COPD Lead allergy candidate in phase III (data expected Q2 2016) Lead asthma product filed Q Potential for 8 product launches by end 2021 Commercial infrastructure focused on allergy / asthma specialists Focused commercialization strategy Direct to specialists in key markets and partner in primary care Scalable infrastructure to optimize launch of lead allergy product and broader portfolio Strong growth platform Immediate revenues, near-term pipeline and high-value specialty products Novel short-course immunotherapies have potential to revolutionize multi-$bn allergy market Fully funded to deliver pipeline ( 209.3m cash 1 at 30 September 2015) 1 Cash, cash equivalents and short-term bank deposits (unaudited)

4 Circassia s strategy Building a self-sustaining specialty biopharma company 4 Deliver the pipeline Market specialty products Independently in N America and major EU markets Partnerships elsewhere Build broad and balanced portfolio

5 Strong, deep and balanced pipeline 5 Product NIOX MINO NIOX VERO Launched Launched PSX1001* Flixotide substitute UK 1 approval UK 1 launch EU 1 launch PX1439* Serevent substitute UK filing UK launch EU launch PSX2005 Seretide substitute Cat SPIRE PSX1050* Flovent substitute Grass SPIRE House Dust Mite SPIRE PSX3001 Novel triple presentation Ragweed SPIRE Partnered timelines not disclosed publicly PK study Ph III data UK filing EU / US filing Ph II data UK launch Ph III data EU / US launch EU / US filing Ph II data EU launch EU / US launch Ph III data EU / US filing Ph III data Ph III data US filing EU / US launch US filing US filing US launc US launc US launc PSX1002 Novel LAMA formulation Ph II data Ph III data US filing Pipeline does not show earlier-stage programmes: Birch SPIRE, Japanese cedar SPIRE, Alternaria SPIRE and home use NIOX device *Partnered 1 Approval / launch reflects estimates of MHRA review and decentralized procedure timelines only All timelines are forward-looking projections that involve risks and uncertainties please see the disclaimer on slide 2 for further details

6 Focused commercialization strategy Targeting direct sales in US & major EU markets 6 Circassia US & EU commercial operations Corporate administration (Finance, HR, IT) Business analytics Compliance (legal, regulatory) Market access Medical affairs Marketing Sales Supply chain / distribution Direct sales force Allergists KOLs Asthma specialists Top prescribers primary care Partner elsewhere Outside US and Europe Primary care Partner sales force Primary care

7 7 1 Marketed products 2 Asthma / COPD pipeline 3 Novel allergy immunotherapies 4 Summary

8 Products marketed around the world Direct sales infrastructure in US and EU s largest allergy market 8 Direct sales targeting allergy / asthma specialists in key markets Opportunity to expand in EU Broad international distribution network Novel products Direct sales Distributors

9 Leadership in FeNO asthma management Meeting key clinical need in major therapeutic market 9 Only point-of-care device available across major markets to measure FeNO to assist diagnosis and management of asthma Strong IP with 72 granted patents in US, EU & Japan with protection currently to 2026 Asthma is one of largest healthcare burdens 25 million asthmatics in US 14 million physician office / 1.8 million ER visits in US with asthma as primary diagnosis >$50bn medical cost of asthma in US in 2007 Clinical evidence shows FeNO measurement improves asthma management Improves diagnosis Improves determination of inhaled steroid responsiveness Improves control through tailoring inhaled steroid use Improves monitoring of treatment compliance Potential to reduce exacerbations Extensive big pharma use in asthma clinical studies Validates the importance of FeNO in asthma Helps establish FeNO in market and train physicians in use of products

10 Next generation roll-out underway Product improvements offer major opportunity 10 Transition to next generation product provides major opportunity NIOX MINO EU 2004, US 2008, China 2010, Japan 2013 For ages 4+ in EU; 7+ in US 10 second test; 90 second result Monitor lasts 3 years or 3,000 tests Limited portability NIOX VERO EU 2013, US 2014, Japan 2015, China 2015 For ages 4+ EU; 7+ in US Fully portable; enhanced screen interface 6 and 10 second test; ~60 second result Monitor lasts 5 years or 15,000 tests Long-term upside potential from home use device currently in planning

11 Endorsement from key organizations Included in ATS treatment guidelines and NICE recommendation 11

12 Potential to accelerate growth Foundations in place to boost NIOX sales positioned for growth Significant progress in establishing new market category and changing existing paradigm FeNO accepted by KOLs and specialists Number of major guidelines include FeNO Scientific evidence / publications support use of FeNO Reimbursement established (64% US coverage; targeting 75% by 2016) Next generation NIOX VERO device offers significant improvements over predecessor NIOX VERO US and Japanese launches H Chinese NIOX VERO launch H2 2015

13 Significant market opportunity Ideal fit with Circassia s commercialization strategy 13 Robust global revenue growth US specialist opportunity 18% CAGR over last 5 years Q revenues 13.6m $190m Direct sales force KOLs 30% growth vs Q US primary care opportunity Allergists Asthma specialists Targeting strong full year growth $610m Partner sales force Top prescribers primary care Primary care

14 14 1 Marketed products 2 Asthma / COPD pipeline 3 Novel allergy immunotherapies 4 Summary

15 Near-term pipeline & longer-term novel formulations 15 Focus on pmdi market segment Directly substitutable products No requirement for significant commercial infrastructure Limited development Rapid route to market; near-term revenue Challenging to achieve for respiratory products Non-substitutable competitors require promotion Device types pmdi DPI Direct sales force Significant pricing potential 73.5% of pre-entry brand price for first to market generic in US during exclusivity % of pre-entry brand price for only on market generic in US 1 KOLs Novel combinations / products Longer more extensive development Majority of market in primary care Circassia to target allergy / asthma specialists Partner for phase III and targeting primary care Partner sales force Allergists Primary care Asthma specialists Top prescribers primary care 1 Bureau of Economics, Federal Trade Commission, Working Paper No 317. The effect of generic drug competition on generic drug prices during the Hatch-Waxman 180-day exclusivity period. April 2013.

16 Novel technology provides sophisticated API control 16 Technology #1 Technology controls Significant potential benefits Engineered API Technology #2 Size Shape Aerodynamics Surface properties Manufacturability Product stability Product performance Directly substitutable products Potential first to market with unique combination of therapeutic equivalence, all strengths, similar device, same formulation & costeffective Novel products Optimized combinations and novel formulations Established at commercial scale in cgmp compliant FDA-approved facilities Broad IP protecting apparatus to 2022 in US & 2019 in EU; patents pending will extend product and process protection to 2030 in US and 2028 in EU

17 Lead product filed in EU Collaboration with Mylan PSX1001 Flixotide substitute (EU) PSX1050 Flovent substitute (US) 17 EU filing Mylan collaboration Product candidate targeting substitution for GSK s Flixotide pmdi (Flovent pmdi in US) Filing validated and under assessment Q Review under EU orally inhaled products guidelines that allow approval based on in vitro equivalence data only Decentralized procedure - MHRA reviewing file Decision on first approval anticipated H File in EU and retain marketing rights in certain territories Full rights retained in China, South America, Middle East and Africa Mylan has marketing rights in agreement territory 1 FDA guidelines require PK and PD studies in US Technology validation by leading company Estimated $930m originator sales ($680m in US; $250m ex-us) 1 USA, Canada, Australia and New Zealand, India, Japan, Europe (including the EU and EFTA states (Iceland, Liechtenstein, Norway and Switzerland)), Turkey, Russia and CIS Originator sales estimate based on GSK Annual Reports 2011 and 2014 and selected IMS data 2011 and 2012

18 Strong pipeline of follow-up products PX1439 Serevent substitute PSX2005 Seretide substitute 18 Serevent pmdi substitute Stability batches in place Estimated originator sales $60m 1 Partnered in UK / Ireland Seretide pmdi substitute Global rights retained Initial registration batches in place Originator sales estimated $1.8bn 1 Targeting UK filings by end H Originator sales estimates based on GSK Annual Reports 2011 and 2014 and selected IMS data 2011 and 2012

19 Longer-term high value novel products PSX1002 Novel LAMA formulation 19 Optimized glycopyrronium bromide formulation Potential Spiriva competitor targeting predicted >$3bn 1 opportunity Compelling phase IIa results Significant efficacy vs placebo 1 Respiratory Market 2025: Taking A Deep Breath And A Deep Dive Jefferies 2013 Equity Research

20 Significant potential benefits for combination products PSX3001 Novel triple presentation 20 Engineered mono blend 2+1 formulation LAMA LABA ICS LAMA LABA ICS Triple combination ICS + LABA/LAMA 1 targeting emerging ~$8bn 2 market opportunity Entered clinic H single-dose / repeat-dose 38-subject study Results expected Q Inhaled corticosteroid (ICS) / long-acting beta agonist (LABA) / long-acting muscarinic antagonist (LAMA) 2 Respiratory Market 2025: Taking A Deep Breath And A Deep Dive Jefferies 2013 Equity Research

21 Approach exploits market dynamics Opportunity to capture modest share of significant markets 21 Global key inhaled maintenance respiratory market 1 (excludes ICS monotherapy market: >US$2bn in 2014) Monotherapy ICS PSX1001 / PSX 1050 targeting Flixotide / Flovent substitution Triple fixed dose combination PSX3001 Monotherapy LAMA PSX1002 Monotherapy LABA PSX1439 targeting Serevent substituion LABA/ICS PSX2005 targeting Seretide substitution Potential near-term approvals with high value follow up products 1 Respiratory Market 2025: Taking A Deep Breath And A Deep Dive Jefferies 2013 Equity Research

22 22 1 Marketed products 2 Asthma / COPD pipeline 3 Novel allergy immunotherapies 4 Summary

23 Allergic rhinitis is a global healthcare problem Affects 10-20% of global population 23 Allergic diseases affect over 1 billion people worldwide 3 Allergic rhinitis is the world s most prevalent chronic non-communicable disease 3 Allergy is medical condition with greatest impact on work productivity in US 4 Allergy is a precursor of asthma; treatment with immunotherapy halts allergic march Rank Allergen USA Skin prick test positive (% Popl n ) (million) 1 1 House dust mite Perennial rye Short ragweed Cockroach Bermuda grass Cat Source: Arbes et al. J Allergy Clin Immunol Aug;116(2): Rank Allergen Europe Skin prick test positive (% Popl n ) (million) 2 1 House dust mite Grass pollen Cat Birch pollen Mould Olive pollen 3 11 Source: Bousquet et al. Allergy. 2007: 62: Targeted by Circassia Future potential targets Immunotherapy is the only way to treat the underlying disease 1 US Census Bureau, World Bank, EAACI Global Atlas of Allergy Gemson & Eng, August 2004

24 Moderate to severe allergy is inadequately addressed by current therapies 24 Allergen avoidance: not feasible in majority of cases Symptomatic drugs: (anti-histamines, nasal corticosteroids etc) limited efficacy Prescription market estimated at approximately $7bn 1 Whole allergen immunotherapy Subcutaneous immunotherapy (SCIT) Sublingual immunotherapy (SLIT) Targets cause of allergy leading to tolerance of allergens Reduces allergic march to asthma Provided by allergy / asthma specialists Allergen injected Lengthy treatment 3-5yrs Poor patient adherence Non-standardized dosing High frequency of side effects including potential for anaphylaxis Total 5 year cost: ~$3,600 $6,000* Allergen under the tongue Lengthy treatment 1-3yrs Low adherence (7% complete 3yrs 2 ) US requires EpiPen prescription High frequency of side effects including potential for anaphylaxis Total 1 year cost: $1,400 - $2,700** Total 3 year cost: ~$9,000** Majority of allergic rhinitis patients consulting a GP have moderate to severe symptoms 3 1 Bloomberg 2 J Allergy Clin Immunol Aug;132(2): e2. doi: /j.jaci Epub 2013 May 3 Bousquet et al. J Allergy Clin Immunol Jan;117(1): * Based on Circassia s estimates ** Based on Merck/ALK and Stallergenes published US prices for SLIT treatments

25 Proprietary ToleroMune technology Designed to treat underlying disease with minimal side-effects 25 ToleroMune identifies T-cell epitopes Short linear stretches of amino acids in allergen sequence Binds to antigen presenting cells to induce regulatory T cells Identified from blood of allergic individuals Whole allergen SPIREs Synthetic Peptide Immuno-Regulatory Epitopes Short treatment designed to provide efficacy without the safety issues Regulatory T cells down-regulate allergic response Lack of B-cell epitopes avoids cross-linking of mast cells eliminating early response / no need to dose escalate Synthetic manufacture no extraction from whole allergens Broadly applicable across range of allergies Allergens already identified; no research required Final product is a room temperature stable, lyophilized vial containing a mix of 7 peptides for injection T cell epitopes selected Modern, synthetic, rationally-designed pharmaceuticals

26 Technology validated with clinical proof-ofconcept in four programs 26 Development stage Key findings Cat SPIRE Phase III field study (n = 1,409) Proof-of-concept in multiple products Grass SPIRE Phase IIb study (n = 282) Short-course treatment Efficacy persists over time House dust mite SPIRE Phase IIb study (n = 172) Enhanced efficacy in more symptomatic subjects Ragweed SPIRE Phase IIb study (n = 280) Safety profile similar to placebo Birch SPIRE, Japanese cedar SPIRE and Alternaria SPIRE in earlier stage development

27 Cat SPIRE phase IIb Proof-of-concept Skin prick +ve cat: US: 17% 1 (53m) EU: 8-10% 2 (30-37m) 27 Randomised, placebo-controlled parallel group chamber study Commercial-scale room-temperature stable formulation 202 subjects randomised 2 dosing regimens and placebo Primary objective: evaluate efficacy in cat allergic subjects following cat allergen challenge Subjects in chamber 3 hours per day for 4 days at baseline and at post-treatment challenge Controlled levels of cat dander (similar to house that has a cat) Symptoms recorded every 30 minutes Exposure chamber Toronto Comparison of symptom scores at challenge 5 months after starting treatment to baseline 1 Arbes et al. J Allergy Clin Immunol Aug;116(2): Bousquet et al. Allergy. 2007: 62: 301-9

28 Cat SPIRE phase IIb (n=202) Confirmed efficacy 28 Total Rhinoconjunctivitis Symptoms Score ( TRSS ) Patient self-rated scores used as primary efficacy measure Scoring system required by regulators Used for approval of intranasal steroids, antihistamines etc Scores measured on 4-point rating scale 0: absent 1: mild, barely noticeable 2: moderate, annoying / troublesome 3: severe, incapacitating SPIRE studies use 8 symptoms = 24-point scale; cat SPIRE used sneezing & runny / blocked / itchy nose & itchy / watery / red / sore eyes Overall TRSS improvement of 2.1 vs. placebo (p = 0.05) TRSS score of 8 could be 8 mild / barely noticeable scores TRSS score of 12 could be 4 mild / barely noticeable and 4 moderate / annoying scores Note: Based on non-asthmatic subjects

29 Cat SPIRE phase IIb Sustained benefit at 1 and 2 years with no additional dosing 29 1 year follow-up study: efficacy enhanced over time 2 years follow-up study: efficacy persists at 2 years Overall TRSS improvement of 3.9 vs. placebo (p = 0.01) Overall TRSS improvement of 3.9 vs. placebo (p = 0.13) Secondary endpoint: TRSS improvement at end of day 4: 5.1 vs. placebo (p=0.02) Tolerance persists at least 2 years without further dosing Published: J Allergy Clin Immunol Jan;131(1):103-9.e1-7 / Clin Exp Allergy May;45(5): doi: /cea.12488

30 Cat SPIRE represents therapeutic step change More effective and more convenient 30 Product / Study 3 Treatment Difference Active vs. Placebo TRSS Cat SPIRE chamber study 1 4 doses 4 weeks apart 3.9 ALK-Abelló Grazax pivotal field study 2 (licensed in Europe) SLIT tablets Stallergenes Oralair grass field study 2 (licensed in Europe) SLIT tablets Daily 16 weeks before and during season Daily 16 weeks before and during season Allergy Therapeutics Pollinex Quattro grass field study 2 (filed Germany in 2009, not yet approved) adjuvanted whole allergen IT GSK fluticasone furoate perennial rhinitis field study 2 intranasal steroid 4 administrations 1 week apart 1.1 Once daily for 4 weeks 0.86 Sanofi fexofenadine cat chamber study 2 antihistamine 180 mg 2 hours before chamber (ie pre-symptoms) Based on the 4 x 6 nmol dose of cat SPIRE in CP005A 2 Source: Summary of product characteristics for each product, except i) Fexofenadine: Ann Allergy Asthma Immunol Feb;96(2): and ii) Pollinex Quattro: EAACI XXVIII Congress 2009 Poster presentation 3 TRSS scoring ranges from points for these studies

31 Cat SPIRE phase III on track to report Q Multi-year follow up initiated 31 Screening Cat SPIRE phase III: recruitment complete Period 1 Period 2 Study Medication Administration (every 4 weeks ± 2days) End of Dosing Assessment (2 wks ± days since last dose) Visit 1A 1B/C 2A 2B 3A.3H 3I 1,409 cat-allergic subjects in North America, EU and Russia Baseline TRSS 10 Primary endpoint 1 year after start dosing Single phase III & supporting studies sufficient for registration Pediatric safety study on track to complete H A 4B 4C 4D 4E 4F 5 Baseline Allergy Evaluation x3 wks Period 3 (Post Administration Collection) PAC1 x3 wks PAC2 x3 wks PAC3 x3 wks 2 5 year follow-up on track: 329 subjects enrolled* Randomisation Follow-Up (3-10 days after PAC3) Week Year 2 Year 3 Year 4 Year 5 Reporting of Health Economics (Subjects) Quarterly Visits to confirm and evaluate Safety Information (Sites) Annual Allergy Evaluation* Annual Allergy Evaluation* Annual Allergy Evaluation* Annual Allergy Evaluation* * Timed to occur annually after Baseline Allergy Evaluation Period in CP007 *At 28 July 2015

32 HDM SPIRE phase IIb (n=172) Efficacy demonstrated at 1 year Skin prick +ve HDM: US: 28% 1 (86m) EU: 22% 2 (82m) 32 Overall TRSS improvement of 2.8 vs. placebo (p = 0.02) at one year Increasing symptom severity Excellent data similar to cat SPIRE at 1 year Treatment effect maintained in more symptomatic subjects 1 Arbes et al. J Allergy Clin Immunol Aug;116(2): Bousquet et al. Allergy. 2007: 62: Selected for oral presentation at AAAAI 2014

33 HDM SPIRE phase IIb 2 year follow-up study Improvement maintained; enhanced effect in more symptomatic 33 Matched subjects at year 1 and 2 Subjects with baseline TRSS >12 Overall TRSS improvement of 1.4 vs placebo at two years Overall TRSS improvement of 3.0 vs. placebo Overall TRSS improvement of 1.4 vs placebo at one year Symptom improvement sustained at same level in same patients

34 Grass SPIRE phase IIb (n=282) Efficacy demonstrated after first grass season Skin prick +ve grass: US: 27% 1 (84m) EU: 17% 2 (63m) 34 Subjects with mean baseline TRSS 8 Subjects with mean baseline TRSS 12 Overall TRSS improvement of 1.6 vs. placebo (p = 0.035) Overall TRSS improvement of 2.0 vs. placebo (p = 0.040) Increasing treatment effect over time Enhanced efficacy in the more symptomatic 1 Arbes et al. J Allergy Clin Immunol Aug;116(2): (Perennial rye) 2 Bousquet et al. Allergy. 2007: 62: (Grass pollen)

35 Grass SPIRE phase IIb long-term follow-up Symptom improvement confirmed in same subjects 35 Matched subjects (8 x 6 nmol group) TRSS -5.0 vs. placebo (p = 0.004) Matched subjects (4 x 12 nmol group) TRSS -4.5 vs. placebo (p = 0.008) TRSS -2.9 vs. placebo (p = 0.075) TRSS -3.4 vs. placebo (p = 0.033) TRSS -4.0 vs. placebo (p = 0.016) TRSS -4.1 vs. placebo (p = 0.010) Initial treatment effect maintained after three grass pollen seasons despite no further doses

36 Ragweed SPIRE phase IIb (n=275) Proof-of-concept demonstrated (2011) Skin prick +ve ragweed: US: 26% 1 (82m) 36 Subjects with mean baseline TRSS 8 Subjects with mean baseline TRSS 12 Overall TRSS improvement of 1.7 vs. placebo (p = 0.066) Overall TRSS improvement of 2.9 vs. placebo (p = 0.044) Stronger efficacy in more symptomatic subjects 1 Arbes et al. J Allergy Clin Immunol Aug;116(2): J. Allergy Clin. Immunol Feb 129, Issue 2, Supplement, Page AB368

37 Mean change in TRSS (baseline minus follow-up) Ragweed SPIRE phase IIb Comparison treatment effect 2014 vs 2011 study (mean baseline TRSS 12) 2011 (mean baseline TRSS 12) Overall TRSS improvement 1.2 vs. placebo (p = 0.149) Overall TRSS improvement 2.9 vs. placebo (p = 0.044) Marked placebo response 28 of 70 placebo-treated subjects (40%) had >25% reduction in symptom score Greater placebo effect in 2014 study vs 2011 study on days 3 & 4

38 Ragweed SPIRE phase IIb (2014) Field score endpoint 38 Mean change in Combined Score from preseason to peak season Mean Combined Score and mean ragweed pollen count Placebo 8 x 12 nmol ITT population Mean change in CS p value vs placebo Field endpoint: combined TRSS (0-24 scale) and rescue medication use (RMS) score (0-3 scale) - Combined Score = (TRSS / 8) + (RMS); 0-6 scale Treatment effect 33% vs placebo - FDA requires at least 15% treatment effect 1 - World Allergy Organization: at least 20% treatment effect clinically meaningful 1 With upper bound of 95% confidence interval minimum10%

39 Potential to revolutionize immunotherapy market 39 Key characteristics Current immunotherapy Subcutaneous Sublingual Short course immunotherapy giving clearly superior efficacy Efficacy for at least a year with single course Two year follow-up data encouraging¹ Very good safety and well-tolerated Safety profile similar to placebo No patients with anaphylaxis Standardized dose No need for dose escalation No need for doses tailored to individual patients State-of-the-art synthetic production process No natural whole allergen No potency variation between vials Patient-friendly administration Silicon crystals 1 Demonstrated for cat SPIRE, HDM SPIRE and grass SPIRE

40 Full global rights retained Ideal fit with focused commercialization strategy 40 Commercialization strategy US cat SPIRE target population Independent in key markets Cat-allergic individuals ~24 million 1 Scalable infrastructure in place Train on cat SPIRE in preparation for launch Build relationships with allergists early Map out customers & key accounts in advance Current sales support field force build well ahead of launch Consulting a specialist Offered IT ~1.3 million ~1.0 million Secondary focus Patients not offered IT Target steeper sales curve with higher peak Sales force plan Primary focus Patients declining IT 100 in N America initially targeting 3,500 specialists 90 in EU targeting high prescribers among 6,600 specialists Subsequently target other high prescribers Selected ENT physicians Special interest primary care physicians Partner in other markets Accept IT (~378k) Complete IT (~60k) Secondary focus Patients failing to complete IT 1 Kantar Health Quantitative Cat Allergy Report 2010

41 Multiple studies demonstrate significant market opportunity 41 Selected sizing and pricing studies US market research for cat SPIRE (Kantar / 2010) 93 allergists, 82 PCPs, 8 payers US opportunity: $ billion peak annual sales Opportunity for cat SPIRE Illustrative peak sales of c.$ mm for US and EU US pricing research for cat SPIRE (Bridgehead / 2011) 101 allergists, 105 patients, 35 payers Supports pricing of $2,000-3,000 EU market & pricing research for cat SPIRE (PRMA / 2011) 27 specialists, 28 PCPs, 27 payers Supports Grazax as the likely benchmark US market overview for 4 lead SPIRE products (LEK / 2009) $2.6bn opportunity in US US and European research for 4 lead SPIREs (GfK / 2014) $2,600 pricing in US US: 200,000 x $2,600 = $520mm Equals 5 of 34 new cat allergy patients / month already coming to allergist US pricing: Supported by third-party research EU: 5 0,000 x $1,500 ( 1,100) = $75mm 1.5 million patients in EU already on allergy immunotherapy EU pricing: Discount to Grazax cost of k over 3+ years Consistent assessment of commercial opportunity

42 42 1 Marketed products 2 Asthma / COPD pipeline 3 Novel allergy immunotherapies 4 Summary

43 Strong newsflow 43 News Date* Description Grass SPIRE support study H1 15 Observational study (TG003) reports (n=102) Grass SPIRE phase II results H1 15 Phase II controlled asthmatic study (TG004) reports (n=54) NIOX MINO / NIOX VERO sales data H2 15 Interim results with H1 15 sales results Flixotide substitute approval outcome 1 H2 15 MHRA response to filing 1 Cat SPIRE safety study complete H2 15 Pilot pediatric safety study (CP009) completes (n 12) Ragweed SPIRE phase IIb complete H2 15 Phase IIb follow-up field study (TR006A) completes (n=249) HDM SPIRE study recruitment H2 15 Complete phase IIb field study (TH005) recruitment (n=660) Serevent substitute filing H1 16 EU decentralized procedure filing to MHRA Flixotide substitute launch 1 (if approved) H1 16 UK launch 1 (if approved) Seretide substitute filing H1 16 EU decentralized procedure filing in UK NIOX MINO / NIOX VERO sales data H1 16 Year end results with FY 15 sales Cat SPIRE phase III results H1 16 Phase III study (CATALYST) reports (n=1,409) Grass SPIRE recruitment campaign H1 16 Campaign starts for registration study Triple combination study results H1 16 Repeat dose study reports (n=38) NIOX MINO / NIOX VERO sales data H2 16 Interim results with H1 16 sales results Cat SPIRE filing H2 16 File for marketing approval Birch SPIRE study results H2 16 Study reports following birch pollen season (n=64) *To be included in announcements as appropriate and in-line with financial calendar including half-year / full-year results 1 Approval / launch reflects estimate of MHRA review timelines only

44 Delivering on our strategy 44 Delivering the pipeline Flixotide substitute approval anticipated H Two regulatory filings anticipated by end H On track to report cat SPIRE phase III in Q Strong clinical progress in multiple late-stage allergy programmes Commercializing products independently in key markets Direct sales targeting allergy / asthma specialists in US and Germany Scalable infrastructure to optimize first allergy product launch Market access and payor expertise in place Leverageable across broader portfolio Building broad and balanced portfolio Pipeline of 12 products in development for allergy, asthma and COPD Potential for 8 product launches by end 2021 World-class allergy & asthma specialty biopharma business fully funded to deliver portfolio

45 A world-class specialty biopharma business 45 Marketed products Direct sales in US and Germany Broad international distribution network Strong pipeline Direct sales Distributors

46 Contact us Office Investors Financial and Corporate Communications Circassia Northbrook House Robert Robinson Avenue Oxford Science Park Oxford OX4 4GA United Kingdom W: E: Steven Harris, CEO Julien Cotta, CFO T: +44 (0) FTI Consulting 200 Aldersgate Aldersgate Street London EC1A 4HD United Kingdom T: +44 (0) E:

47 Financial highlights For the six months ended 30 June 2015 (unaudited) 47 Raised gross proceeds of 275m Acquisition of Prosonix completed on 15 June Acquisition of Aerocrine completed on 18 June (92.6% shares purchased; increased to 97.2% on 2 July) Consideration for Aerocrine 138.3m Consideration for Prosonix 100.0m (of which 30.0m contingent on lead product UK approval) Aerocrine loan 28.7m repaid to lenders (OrbiMed/Novo) on 29 June Deal costs 12.8m Loss for the financial period 21.7m (H1 2014: 16.2m) Cash at 30 June m (31 December m) Cash acquired with businesses 37.7m Contingent 30.0m payment expected by year end Fully funded to deliver pipeline