Building a self-sustaining, world-class specialty biopharmaceutical
Transcrição
Building a self-sustaining, world-class specialty biopharmaceutical
Preliminary Results Presentation 11 March 2016 Building a self-sustaining, world-class specialty biopharmaceutical business Disclaimer 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. 2 Significant progress during 2015 Building a self-sustaining specialty biopharma company Delivering the pipeline In-house progress strongly complemented by acquisitions – Cat SPIRE on track to report phase III data Q2 2016 – Aerocrine brings specialty commercial infrastructure and products – Grass SPIRE registration study to begin H1 2016 – Prosonix broadens pipeline – House dust mite SPIRE field study fully recruited – £275 million fundraising for strategic acquisitions – Ragweed SPIRE follow-up demonstrates treatment effect – Funded to deliver: £203.8m cash at 31 December 2015 – Ragweed dose ranging study to begin H2 2016 – Flixotide® pMDI substitute approved in UK – Triple combination COPD treatment study to report Q2 2016 – NIOX® indication extension study to report H2 2016 Marketing specialty products − 32% NIOX® sales growth since acquisition − Next-generation NIOX VERO® launched in China − Commercial scale-up ahead of first allergy product launch: US sales team 65% expansion; further doubling by Q1 2017; European expansion underway 3 Building broad and balanced portfolio – Birch SPIRE moved into clinic; phase IIa study dosing complete – 3 asthma pMDI substitutes and 2 novel COPD formulations added to pipeline – Potential for 8 product launches by end 2021 Accelerating specialty commercial strategy Leveraging common commercial ‘backbone’ 4 NIOX® asthma management US specialist opportunity ~$190m KOLs SPIRE allergy immunotherapies Lead product illustrative peak sales >$500m Specialists COPD treatments; asthma therapy substitutes ~$11bn market; targeting ~$2.4bn originator sales Top prescribers primary care Primary care Strong, deep and balanced portfolio 5 Marketed, late-stage and longer-term products Product Research Preclinical Phase I Phase II Phase III / Substitute Filed / Approved Marketed NIOX MINO® NIOX VERO® Flixotide® substitute* Cat SPIRE Seretide® substitute Flovent® substitute* Serevent® substitute* Grass SPIRE House Dust Mite SPIRE Ragweed SPIRE LAMA novel formulation Birch SPIRE Triple combination *Partnered Pipeline does not include earlier stage programs: Japanese cedar SPIRE, Alternaria SPIRE, NIOX® home device 6 1 SPIRE allergy therapies 2 Respiratory pipeline 3 NIOX® asthma management 4 Commercial progress 5 Financial results 6 Summary Proprietary ToleroMune® technology Designed to treat underlying disease with minimal side-effects 7 Whole allergen 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 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 T cell epitopes selected Final product is room temperature stable, lyophilized vial of 7 peptides for injection Silicon crystals Broadly applicable across range of allergies – Allergens already identified; no research required Modern, synthetic, rationally-designed pharmaceuticals Skin prick +ve cat: US: 17%1 (53m) EU: 8-10%2 (30-37m) 8 Cat SPIRE phase IIb Strong treatment effect at 1 year; persists at 2 years Chamber study: 202 subjects randomized 1 year follow-up data Subjects challenged in chamber 3 hours per day for 4 days at baseline and post-treatment Controlled levels of dander (similar to house with cat) Primary efficacy measure based on patient-rated Total Rhinoconjunctivitis Symptom Score (TRSS) Overall TRSS improvement 3.9 vs. placebo (p = 0.01) Comparison of TRSS improvement from baseline post treatment vs placebo Scoring system required by regulators Measured on 4-point 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 1 Arbes et al. J Allergy Clin Immunol. 2005 Aug;116(2):377-83 2 Bousquet et al. Allergy. 2007: 62: 301-9 Published: J Allergy Clin Immunol. 2013 Jan;131(1):103-9.e1-7 Cat SPIRE phase III on track to report Q2 2016 Multi-year follow up recruitment ongoing 9 Phase III on track Period 1 Period 2 Screening 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 4A 4B 4C 4D 4E 4F 5 Period 3 (Post Administration Collection) Baseline Allergy Evaluation x3 wks PAC1 x3 wks PAC2 x3 wks Follow-Up (3-10 days after PAC3) Randomisation Week -8 -3 2–5 year follow-up on track: 424 subjects enrolled* PAC3 x3 wks 0 20-22 28 30 37-39 52-54 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 1 March 2016 CATALYST: designed to deliver Study design Primary endpoint fully powered: improvement in combined TRSS / rescue medication use one year after start of dosing vs placebo ― Recruitment 19% over target (n=1,409); retention rate on track ― Designed with 99% power vs placebo ― Powered for 25% improvement cf 40% day 4 symptom improvement in phase IIb; FDA requires at least 15% treatment effect* ― Assumed 50% greater variability than observational field study ― Powering sufficient if robust TRSS improvement alone with little or no rescue medication use Inclusion criteria minimize confounding factors ― Moderate to severe allergy: baseline TRSS ≥10 ― Subjects live with cat(s) in the home ― Centers in cold dry locations to minimize HDM * With upper bound of 95% confidence interval minimum10% 10 CATALYST: delivering commercial opportunity Broad range of supportive endpoints Secondary endpoints ― Total Rhinoconjunctivitis Symptom Score (TRSS) ― Rescue medication use ― Nasal symptoms ― Ocular symptoms ― Rhinoconjunctivitis quality of life ― # of days with no severe / moderate TRSS without rescue medication use Exploratory endpoints ― Health economic (work/school days lost; hospital/doctor visits; non-rescue medication treatment) ― Work place productivity & activity impairment/classroom impairment ― Pittsburgh sleep quality index ― Impression of change in rhinoconjunctivitis score ― Change in asthma control in asthmatics 11 Progress achieved across allergy portfolio 2015 progress Cat SPIRE pediatric study (n=15; aged 5-11 years) completed to support EU filing Ragweed SPIRE two-season follow-up study complete Ragweed SPIRE dose-ranging field study on track to initiate 2016 House dust mite SPIRE field study fully recruited (n=715); results expected H1 2017 Grass SPIRE registration study on track to begin H1 2016 Birch SPIRE clinical development initiated; dosing complete (n=64); results expected H2 2016 12 Ragweed SPIRE phase IIb two-season data Field study follow-up over additional pollen season Field study endpoints Field endpoint: combined TRSS (0 -24 scale) and rescue medication use (RMS) score (0-3 scale) - Combined Score = (TRSS / 8) + (RMS); 0-6 scale - Measured pre-season to peak & across whole season Treatment effect demonstrated vs placebo despite no further treatment - Improvement for all regimens pre- to peak season (1013%) and across whole season (15-21%) - Highest dose regimen achieved greatest effect across whole season (21%) Treatment effect considerations - FDA requires at least 15% treatment effect1 - World Allergy Organization: at least 20% treatment effect clinically meaningful 1 With upper bound of 95% confidence interval minimum10% Combined Score and ragweed pollen count 13 Large-scale studies on track to begin 2016 Grass SPIRE registration study Innovative design follows consultation with FDA and EMA ― Single field study: 8 x 6nmol vs placebo ― Positive safety study enables inclusion of controlled asthmatics ― Adaptive design allows mid-study powering adjustment ― Initial 400 subjects report combined score improvement ― Expansion cohort already recruited ― Further randomization ensures robust powering (expectation n=1,100) ― On track to initiate H1 2016 ― Results anticipated H2 2018 14 Ragweed SPIRE dose-ranging study Large-scale field study ― Results to date suggest optimal dose may not yet be reached ― Highest dose performed best in previous studies (2011 and 2014) ― Dose-ranging study comparing best performing dose to date (8 x 12nmol) with double dose ― Field study comparing improvement in combined symptom and rescue medication use vs placebo ― Recruitment target approximately 450 ― On track to initiate 2016 ― Dosing completion before 2017 season ― Results expected H1 2018 15 1 SPIRE allergy therapies 2 Respiratory pipeline 3 NIOX® asthma management 4 Commercial progress 5 Financial results 6 Summary Near-term pipeline & longer-term novel formulations 16 Device types Significant pricing potential Focus on pMDI market segment ‒ 73.5% of pre-entry brand price for first to market generic in US during exclusivity1 Directly substitutable products – Limited development pMDI ‒ 47.8% of pre-entry brand price for only on market generic in US1 DPI – Modest commercial infrastructure required – Challenging to achieve for respiratory products – Non-substitutable competitors require promotion Direct sales force Novel combinations / formulations KOLs − Longer and more extensive development − Majority of market in primary care Specialists − Circassia to target specialists − Partner for phase III and targeting primary care Top prescribers primary care Partner sales force 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. Primary care Novel technology controls API properties Technology controls ‒ Size Significant potential benefits Directly substitutable products ‒ Shape ‒ Surface properties ‒ Potential for first to market with therapeutic equivalence, all strengths, similar device and same formulation ‒ Manufacturability Novel products ‒ Aerodynamics ‒ Product stability ‒ Product performance Engineered API ‒ Optimized combinations and novel formulations 17 Lead product approved in UK Collaboration with Mylan Successful EU filing Flixotide® substitute (EU) Mylan collaboration Targets substitution of Flixotide® pMDI Mylan has marketing rights in major territories (inc US and EU)1 Decentralized procedure – UK Reference Member State Product confirmed approvable Nov 2015 Subsequently approved in all three strengths in Dec 2015 FDA guidelines require PK and PD studies in US Approval based on in vitro demonstration of equivalence only Estimated $820m originator sales (>60% US) 1 USA, Canada, Australia and New Zealand, India, 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, 2014 and 2015 and selected IMS data 2011 and 2012 Flovent® substitute (US) 18 Seretide® substitute targets $1.5bn originator Seretide® substitute Salmeterol (PSX2005 vs originator)* Fluticasone (PSX2005 vs originator)* Plasma concentration (pg / ml) by time (mins) [geometric means n≤75] Plasma concentration (pg / ml) by time (mins) [geometric means n≤75] Plasma concentration (pg / ml) by time (mins) [geometric means n≤75] *Preliminary non-QA results; low strength fluticasone administered via spacer AUC similar for salmeterol and fluticasone; Cmax similar for fluticasone (PSX2005 vs originator)* Data suggest formulation may contain insufficient salmeterol fine particles 19 Triple combination clinical development Engineered mono blend LAMA LABA Novel triple presentation 2+1 triple formulation ICS LAMA LABA ICS Triple combination1 clinical study initiated H2 2015 (n=38) Single-dose stage complete; repeat-dose near completion with results expected Q2 2016 1 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 20 21 1 SPIRE allergy therapies 2 Respiratory pipeline 3 NIOX® asthma management 4 Commercial progress 5 Financial results 6 Summary Leadership in FeNO asthma management Meeting key clinical need in major therapeutic market NIOX® is only point-of-care FeNO device available across major markets Clinical evidence shows FeNO measurement improves asthma management – – – – Improves diagnosis Improves determination of inhaled steroid responsiveness and control through tailoring use Improves monitoring of treatment compliance Potential to reduce exacerbations NIOX® sold direct to specialists in US & Germany; distributors elsewhere − Revenues from sale of devices and repeat tests Extensive big pharma use in clinical studies − Validates importance of FeNO; trains physicians; helps establish FeNO in market 22 Next generation roll-out underway Product improvements offer major opportunity 23 Transitioning to next generation Direct sales NIOX MINO® NIOX VERO® EU 2004, US 2008, China 2010, Japan 2013 EU 2013, US 2014, Japan 2015, China 2015 Ages 4+ in EU; 7+ in US Ages 4+ EU; 7+ in US 10 second test; 90 second result 6 and 10 second test; ~60 second result Monitor lasts 3 years or 3,000 tests Monitor lasts 5 years or 15,000 tests Limited portability Fully portable; enhanced interface Long-term upside potential from home use device currently in planning Distributors NIOX VERO® China launch August 2015 KOL and distributor meetings 24 Continuing strong growth Foundations in place to boost NIOX® sales Positioned for growth Expansion of US indication down to 4 years old – study underway Potential expansion into primary ciliary dyskinesia diagnosis − NIOX VERO® adapted for nasal sampling − Study planned with ethics approval pending Growing evidence of asthma misdiagnosis supports NIOX® − 53.5% over-diagnosis in recent childhood primary care study* − NICE reports 30% treated for asthma no longer have signs of condition NICE primary care implementation project March – Oct 2016 − To ensure smooth introduction of new asthma diagnosis / monitoring guideline − FeNO included in proposed guideline (target publication July 2017) *Br J Gen Pract 2016; DOI: 10.3399/bjgp16X683965 25 Strong performance since acquisition Ideal fit with Circassia’s commercialization strategy 26 US specialist opportunity Robust revenue growth 18% CAGR 2010-14 Direct sales force ~$190m Post acquisition (19/06/15) revenues £10.3m 32% growth vs same period 2014 KOLs Specialists US primary care opportunity Targeting continued strong growth Top prescribers primary care ~$610m Partner sales force Primary care 27 1 SPIRE allergy therapies 2 Respiratory pipeline 3 NIOX® asthma management 4 Commercial progress 5 Financial results 6 Summary Commercial infrastructure expansion Significant progress in 2015 US headquarters established in Chicago Recruited commercial leadership — Commercial operations, marketing, medical affairs, sales, supply/distribution Integrated Aerocrine organization — Direct sales in US and Germany Subsequent dramatic expansion — Commercial team now over 100-strong — Medical affairs across key territories — Reimbursement expertise established — Targeting >100-strong field team by Q1 2017 — EU direct sales territory review initiated — Discussions in France to establish direct presence 28 Commercial team enhancement 29 Realigned territories & focused target lists Significant growth in US sales force • More focused, smaller territories • Establishing Circassia presence in key US markets where Aerocrine was absent • Closer to key physicians Field Sales Team Revamped sales training Improved territory management tools • All sales training materials revised • Veeva CRM roll-out • On-boarded / retrained entire field sales team → improved consistency • Account profiling, call planning and promotional material delivery • Reorganized around clinical sell Updated incentive compensation • Aligned with growth strategy • Attractive to reward and retain top talent First US national sales meeting Dec 2015 Follows over 2,000 applications for 28 open positions 30 First global NIOX® brand campaign launched 31 Customer research in US and 3 EU countries resulted in compelling brand positioning — “FeNO by NIOX®” — objective measure for diagnosing and monitoring asthma — Engages in complexities of asthma management and clinical benefits of measuring airway inflammation by FeNO testing Research maps cat allergy ‘patient journey’ Physical, emotional and social suffering US / EU research with cat allergy sufferers confirms significant need for accessible long-term relief Cat allergy is physically draining and debilitating Cat allergy has a major impact on mood and emotions Embarrassment and guilt create self-imposed boundaries Patients cut social interactions and relationships affected “I want to have a life, I want go out and do things without living in fear I turn into a coughing, mucus building, walking, sneezing, coughing person that everyone runs from like Godzilla.” - Patient, Rapidfire, US “You feel empty, ill, tired, unmotivated and useless.” - Patient, Online Spotlight, Germany 32 Pricing and treatment research confirm major market opportunity Opportunity for cat SPIRE US cat SPIRE target population Cat-allergic individuals Illustrative peak sales of c.$500-700m for US and EU US: 200,000 x Equals 5 of 34 new cat allergy patients / month already coming to allergist EU: 50,000 $2,600 = $520mm Consulting a specialist Offered IT ~24 million1 ~1.3 million $1,500 (€1,100) = $75mm 1.5 million patients in EU already on allergy immunotherapy EU pricing: Discount to Grazax cost of €2.5-5.3k over 3+ years Secondary focus Patients not offered IT ~1.0 million Primary focus Patients declining IT US pricing: Supported by third-party research x 1 Kantar Health Quantitative Cat Allergy Report 2010 33 Accept IT (~378k) Complete IT (~60k) Secondary focus Patients failing to complete IT 34 1 SPIRE allergy therapies 2 Respiratory pipeline 3 NIOX® asthma management 4 Commercial progress 5 Financial results 6 Summary Financial highlights Year ended 31 December 2015 Raised £275m gross proceeds – – – – – – Acquisition of Prosonix completed 15 June Acquisition of Aerocrine completed 18 June (92.6% of shares; increased to 97.9% 31 Dec) 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) 29 June Deal costs £12.8m Loss for financial year £50.0m (2014: £35.1m) – H1 £21.7m (H1 2014: £16.2m) – H2 £28.3m (H2 2014: £18.9m) Cash at 31 December 2015 £203.8m (31 December 2014 £186.6m) – Cash acquired with businesses £37.7m – Contingent £30.0m payment paid January 2016 35 Income statement Year ended 31 December 2015 36 Research & development 37 Cat allergy immunotherapy – CP007 (phase III) recruitment complete Dec 2014 – 2–5 year follow up initiated 2014 HDM allergy treatment – Recruitment into TH005 (phase IIb field trial) Ragweed allergy therapy – Recruitment into TR006 (phase II) complete 2014 Birch and Japanese cedar allergy treatments – Birch allergy therapy first–in-human trial fully recruited Respiratory investment – Triple combination clinical study (first stage complete) – PK testing for Seretide® pMDI substitute 38 1 SPIRE allergy therapies 2 Respiratory pipeline 3 NIOX® asthma management 4 Commercial progress 5 Financial results 6 Summary Strong newsflow 39 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 H2’15 MHRA response to filing Cat SPIRE safety study complete H2‘15 Pilot pediatric safety study (CP009) completes (n=15) 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 (TH005) field study recruitment (n=715) NIOX MINO® / NIOX VERO® sales data H1’16 Year end results with H2’15 sales Cat SPIRE phase III results H1‘16 Phase III study (CATALYST) reports (n=1,409) Grass SPIRE registration study H1‘16 Recruitment starts for registration study (n=~1,500) 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 Ragweed SPIRE dose-ranging study H2’16 Phase IIb study initiation (n=~450) Birch SPIRE study results H2’16 Study reports following birch pollen season (n=64) NIOX® US label extension study H2’16 Completion of study in four to six year olds Cat SPIRE filing H2‘16 File for marketing approval HDM SPIRE study complete H1’17 Phase IIb field study (TH005) completes (n=715) Cat SPIRE two-five year follow-up H1’17 Phase III follow-up two year follow-up completes Seretide® pMDI substitute filing H2’17 Initial MAA filing *To be included in announcements as appropriate and in-line with financial calendar including half-year / full-year results Good strategic progress Building a self-sustaining specialty biopharma company Business built on three franchises leveraging common infrastructure − SPIRE immunotherapies targeting leading allergies − NIOX® market-leading asthma management products − Respiratory portfolio of particle-engineered asthma & COPD products − Franchises leverage novel technologies and out-sourced business model − Commercialization exploits common infrastructure focused on allergy / asthma specialists Strong and balanced growth platform − Cat allergy phase III data on track for Q2 2016 − Grass allergy registration study on track to begin H1 2016 − NIOX® products positioned for growth; 32% revenue growth since acquisition − Respiratory technology validated; lead product approved − Potential for 8 product launches by end 2021 − Funded to deliver (£203.8m cash1 at 31 December 2015) 1 Cash, cash equivalents and short-term bank deposits (unaudited) 40 Contact us Office Investors Financial and Corporate Communications Circassia Northbrook House Robert Robinson Avenue Oxford Science Park Oxford OX4 4GA United Kingdom Steven Harris, CEO Julien Cotta, CFO FTI Consulting 200 Aldersgate Aldersgate Street London EC1A 4HD United Kingdom W: www.circassia.com E: [email protected] T: +44 (0) 1865 405560 T: +44 (0) 20 3727 1000 E: [email protected]