Slides
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ELEVATE IPF Phase 2b Topline Results December 2024
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Important Information The following presentation, including any printed or electronic copy of these slides, the talks given by the presenters, the information communicated during any delivery of the presentation and any question-and-answer session and any document or material distributed at or in connection with the presentation (together, the "Presentation"), has been prepared by PureTech Health plc (the "Company"). The information in the Presentation is not intended to form the basis of any contract. 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3 Bharatt Chowrira, PhD, JD Chief Executive Officer Eric Elenko, PhD Co-founder & President Camilla Graham, MD, MPH Vice President, Medical Affairs
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Deupirfenidone for IPF >232,000 patients in the US & the EU51 4 1 GlobalData Epidemiology and Market Size Search, EU5=United Kingdom, France, Germany, Italy and Spain; 2 Barratt SL, Creamer A, Hayton C, Chaudhuri N. Idiopathic Pulmonary Fibrosis (IPF): An Overview. J Clin Med. 2018 Aug 6;7(8):201; 3 Fisher, M., Nathan, S. D., Hill, C., Marshall, J., Dejonckheere, F., Thuresson, P., & Maher, T. M. (2017). Predicting Life Expectancy for Pirfenidone in Idiopathic Pulmonary Fibrosis. Journal of Managed Care & Specialty Pharmacy, 23(3-b Suppl), S17–S24. https://doi.org/10.18553/jmcp.2017.23.3-b.s17; 4 ESBRIET (pirfenidone) and OFEV (nintedanib) were approved in 2014; 5 Rubino C. M., Bhavnani S. M., Ambrose P. G., Forrest A., Loutit J. S. Effect of food and antacids on the pharmacokinetics of pirfenidone in older healthy adults. Pulmonary Pharmacology & Therapeutics. 2009 Aug;22(4):279-285; 6 Belhassen, M., Dalon, F., Nolin, M., & Van Ganse, E. (2021). Comparative outcomes in patients receiving pirfenidone or nintedanibfor idiopathic pulmonary fibrosis. Respiratory research, 22(1), 135. 2 standard-of-care treatments4 proven to slow disease progression, but have significant side effects, including nausea, vomiting and diarrhea,5,6 which impact patients’ ability to remain on treatment / tolerate an efficacious dose Idiopathic Pulmonary Fibrosis ▶ Life threatening, debilitating disease ▶ Scarring of the lungs, leading to shortness of breath and loss of lung function 2 Unknown cause Life expectancy 2 – 5 years3 Without treatmentWith treatment Life expectancy 4.5 - 7.5 years3
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Currently Approved Treatments are Efficacious but have Challenges 3 out of 4 patients never start treatment1 5 1 Dempsey TM, Payne S, Sangaralingham L, Yao X, Shah ND, Limper AH. Adoption of the Antifibrotic Medications Pirfenidone and Nintedanib for Patients with Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2021 Jul;18(7):1121-1128; 2 Based on 2022 ESBRIET® and OFEV® total WW sales; Ofev sales are inclusive of SSc-ILD, PF-ILD and IPF indications. 13.2% (73.6%) 13.2% pirfenidone nintedanib Nearly 75% of patients never receive antifibrotic therapy Only ~25% of US patients are on FDA approved drugs …of which >40% eventually discontinue antifibrotic therapy 42.8% 10.5% 21.2% 0% 10% 20% 30% 40% 50% Experienced nausea, diarrhea, or myalgias Switched to the other antifibrotic Discontinued therapy Despite drawbacks, both branded drugs achieved blockbuster status ($4B+)2
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Remarkable Efficacy and Favorable Tolerability Demonstrated in Phase 2b Study Results support advancing program 6 PIRFENIDONE DEUPIRFENIDONE Hydrogen Deuterium
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Remarkable Efficacy and Favorable Tolerability Demonstrated in Phase 2b Study Results support advancing program 7 ELEVATE Phase 2b Summary Primary and the key secondary efficacy endpoints achieved Favorable tolerability demonstrated Continued development supported PIRFENIDONE Hydrogen Deuterium DEUPIRFENIDONE
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1:1:1:1 Placebo TID (N=60) Deupirfenidone 550 mg TID (N=60) Pirfenidone 801 mg TID (N=60) Deupirfenidone 825 mg TID (N=60) N=240 ELEVATE: Global, Phase 2b, Multicenter, Randomized, Double- blind Clinical Trial 8 26 Weeks of Double-Blind Study Treatment (Part A) V3 W4 V2 D1 V4 W8 V5 W12 V6 W16 V7 W20 V8 W26 Deupirfenidone 550 mg TID (n=60) Deupirfenidone 825 mg TID (n=60) Pirfenidone 801 mg TID (n=60) Placebo (n=60) Open Label Extension (Part B) Deupirfenidone 550 mg TID Deupirfenidone 825 mg TID Deupirfenidone 825 mg TID Deupirfenidone 550 mg TID Deupirfenidone 825 mg TID Deupirfenidone 550 mg TID Screening (≤ 28 days) V1 Primary Efficacy Endpoint Rate of decline in FVC over 26 weeks Key Secondary Efficacy Endpoint Change in FVC % predicted from baseline to Week 26
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257 patients were recruited from 87 sites across 14 countries 9 United States 54 Patients Mexico 10 Patients Colombia 3 Patients Chile 20 Patients Argentina 37 Patients South Africa 17 Patients India 26 Patients Malaysia 12 Patients Philippines 2 Patients South Korea 38 Patients Thailand 4 Patients Greece 8 Patients Romania 6 Patients Georgia 20 Patients KEY DEMOGRAPHIC STATISTICS ▶ Median age: 72 years, 13.6% ≥ 80 years ▶ 71.2% Male, 28.8% Female ▶ 63% White or Caucasian, 33.5% Asian, 1.6% Black or African American, 1.9% Other ▶ 26.1% Hispanic or Latino ELEVATE: Global, Phase 2b, Multicenter, Randomized, Double- blind Clinical Trial
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ELEVATE Pre-defined Statistics Approach Commonly used Bayesian1 and frequentist analyses were applied 10 1 Bayesian is a method that has been used by large pharmaceutical companies in the IPF space. The FDA has also acknowledged the benefits of this approach. Frequentist Analysis Used for Primary and Key Secondary Endpoints Bayesian Statistics Used for Primary and Key Secondary Endpoints Efficacy Analyses Used a Random Coefficient Regression Model with Repeated Measures
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11 Efficacy analyses used a random coefficient regression model with absolute FVC or FVCpp including baseline as response variable and week, treatment (placebo, pirfenidone, deupirfenidone pooled arm) and interaction between week and treatment as fixed effect. The analyses were performed based on the predefined Full Analysis Set; Change from baseline FVC is not adjusted for patient characteristics such as height, age, race, or sex. TID = 3 times per day Summary of Change from Baseline in Forced Vital Capacity (FVC) over 26 Weeks by Bayesian Analysis Posterior Probability Posterior Mean (SE) Change from Baseline in FVC (mL) over 26 Weeks 98.5% -110.7 -48.4 -160 -140 -120 -100 -80 -60 -40 -20 0 20 Placebo TID (N=65) Deupirfenidone TID Pooled (N=128) Summary of Change from Baseline in Forced Vital Capacity % Predicted (FVCpp) over 26 Weeks by Bayesian Analysis Posterior Probability Posterior Mean (SE) Change from Baseline in FVCpp over 26 Weeks 99.6% -3.27 -1.10 -5 -4 -3 -2 -1 0 1 Placebo TID (N=65) Deupirfenidone TID Pooled (N=128) ELEVATE Achieved Primary and Key Secondary Endpoints
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Deupirfenidone Demonstrated Potential to Serve as a New Standard-of-Care Treatment for IPF 12 Efficacy analyses used a random coefficient regression model with absolute FVC or FVCpp including baseline as response variable and week, treatment and interaction between week and treatment as fixed effect. The analyses were performed based on the predefined Full Analysis Set. p values are two-sided and have not been corrected for multiplicity/ Note: Change from baseline FVC is not adjusted for patient characteristics such as height, age, race, or sex. TID = 3 times per day Statistically Significant Summary of Change from Baseline in Forced Vital Capacity (FVC) over 26 Weeks by Frequentist Analysis 0.43 0.02 0.13P-Value Adjusted Mean (SE) Change from Baseline in FVC (mL) over 26 Weeks -112.5 -80.7 -21.5 -51.6 -160 -140 -120 -100 -80 -60 -40 -20 0 20 Placebo TID (N=65) Deupirfenidone 550 mg TID (N=65) Deupirfenidone 825 mg TID (N=63) Pirfenidone 801 mg TID (N=61) Summary of Change from Baseline in Forced Vital Capacity % Predicted (FVCpp) over 26 Weeks by Frequentist Analysis 0.18 0.01 0.11P-Value -3.43 -1.81 -0.43 -1.46 -5 -4 -3 -2 -1 0 1 Placebo TID (N=65) Deupirfenidone 550 mg TID (N=65) Deupirfenidone 825 mg TID (N=63) Pirfenidone 801 mg TID (N=61) Adjusted Mean (SE) Change from Baseline in FVCpp over 26 Weeks
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Patients on Deupirfenidone 825 mg Approached the Level of Natural Decline Seen in Healthy Adults >60 Years Over 6 Months 13 1 Reflects outputs obtained via frequentist analysis; 2 FVC decline at 6 months was estimated assuming linear decline over time.Valenzuela, C., Bonella, F., Moor, C.,Weimann, G., Miede, C., Stowasser, S., Maher, T. (2024). Decline in forced vital capacity (FVC) in subjects with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) compared with healthy references. Poster presented at the European Respiratory Society International Congress, Vienna, Austria;and Luoto, J., Pihlsgård, M., Wollmer, P., & Elmståhl, S. (2019). Relative and absolute lung functionchange in a general population aged60-102 years. The European Respiratory Journal, 53(3), 1701812. https://doi.org/10.1183/13993003.01812-2017; FVC = forced vital capacity; Change from baseline FVC is not adjusted for patient characteristics such as height, age, race, or sex. ELEVATE Deupirfenidone 825 mg in IPF Patients1Population Healthy Adults Aged >60 Years2 FVC Decline Over 26 Weeks -21.5 mL -15 to -25 mL ELEVATE Placebo in IPF Patients1 -112.5 mL Placebo Healthy AdultsDeupirfenidone
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Deupirfenidone 825 mg Had ~50% Greater Effect Size Compared to Pirfenidone in the ELEVATE Trial 14FVC = forced vital capacity; Change from baseline FVC is not adjusted for patient characteristics such as height, age, race, or sex; FVCpp = percent predicted forced vital capacity 54.1% 57.4% 80.9% 87.5% 28.3% 47.2% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% FVC FVCpp Treatment Effect from Change in FVC Across Arms Pirfenidone 801 mg TID (N=63) Deupirfenidone 825 mg TID (N=64) Deupirfenidone 550 mg TID (N=65)
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SOC/PT Placebo TID (N=65) n (%) Pirfenidone 801 mg TID (N=63) n (%) Deupirfenidone 550 mg TID (N=65) n (%) Deupirfenidone 825 mg TID (N=64) n (%) Gastrointestinal disorders 16 (24.6) 33 (52.4) 23 (35.4) 34 (53.1) Nausea 5 (7.7) 17 (27.0) 11 (16.9) 13 (20.3) Dyspepsia 2 (3.1) 14 (22.2) 8 (12.3) 9 (14.1) Diarrhea 6 (9.2) 7 (11.1) 7 (10.8) 5 (7.8) Abdominal pain 3 (4.6) 5 (7.9) 4 (6.2) 9 (14.1) Constipation 1 (1.5) 4 (6.3) 1 (1.5) 3 (4.7) Vomiting 0 (0) 2 (3.2) 5 (7.7) 1 (1.6) Deupirfenidone Had Favorable Tolerability on Key GI-related AEs 15SOC/PT = System Organ Class / Preferred Term; GI = gastrointestinal
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Deupirfenidone Slowed Lung Function Decline in IPF and Achieved Primary and Key Secondary Endpoints 16 Efficacy: ELEVATE met both the primary and the key secondary efficacy endpoints Tolerability: Both doses of deupirfenidone demonstrated favorable tolerability Strength of deupirfenidone 825 mg: Decline in lung function with deupirfenidone 825 mg TID as monotherapy approached natural lung function decline expected in healthy older adults Committed to continued development of deupirfenidone through engagement with regulatory authorities and further data dissemination in upcoming forums
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Accelerating Momentum & Delivering Results Key milestones in the last 2 years 17 Note: Certain third-party trademarks are included here; PureTech does not claim any rights to any third-party trademarks. COBENFY (xanomeline and trospium chloride) is indicated for the treatment of schizophrenia in adults. For Important Safety Information, see U.S. Full Prescribing Information, including Patient Information on COBENFY.com. Following the acquisition of Karuna, KarXTis now under the stewardship of Bristol Myers Squibb and will be marketed as Cobenfy. BMS/Karuna received FDA Approval for Cobenfy PureTech’s Founded Entity Vedanta Biosciences initiated Phase 3 trial of VE303 PureTech completes successful Phase 2b trial of deupirfenidone in IPF PureTech’s Founded Entity Karuna Therapeutics acquired by BMS for $14B PureTech and Royalty Pharma entered into Cobenfy (KarXT) royalty transaction for up to $500M PureTech launches Founded Entity Seaport Therapeutics; $325M raised in 6 monthsPureTech’s LYT-200 granted Orphan Drug and Fast Track Designations
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Well-positioned to Maximize Patient Benefit & Shareholder Value 18 1 The percentage includes number of successful trials out of all trials run for all therapeutic candidates advanced through at least Phase 1 by PureTech or its Founded Entities from 2009 onward; 2 As of March 22, 2023, PureTech has sold its right to receive a 3% royalty from Karuna to Royalty Pharma on net sales up to $2 billion annually, after which threshold PureTech will receive 67% of the royalty payments and Royalty Pharma will receive 33%. Additionally, under its license agreement with Karuna/BMS, PureTech retains the right to receive milestone payments upon the achievement of certain regulatory approvals; 3 As of June 30, 2024. PureTech Level Cash, cash equivalents and short-term investments is a Non-IFRS measure. Robust Portfolio • Steady cadence of near and long-term catalyst across programs • Cobenfy up to $400M milestones2 • Cobenfy 2% royalties on annual net sales >$2B2 • Potential additional milestones and royalties from other Founded Entities • Potential future capital inflows from Founded Entity monetization events • $400.6 million as of June 30, 2024 3 with at least 3 years operational runway Recurring Capital Inflows Strong Balance Sheet Equity Stakes Proven Track Record • 80% clinical trial success rate1 • Self-funded with disciplined capital allocation