Puretech Health Plc · LSE:PRTC
Puretech Health — Technical Presentation (October 2025)
39 slides from Puretech Health's technical presentation, October 2025
Slide 1: Deupirfenidone Program Supplemental Slides
Deupirfenidone Program Supplemental Slides
Slide 2: Table of Contents
Table of Contents Deupirfenidone Executive Summary Disease Overview Unmet Need in IPF Deupirfenidone Overview Introduction Preclinical Data Phase 1 Data Phase 2b ELEVATE Data Deupirfenidone Differentiation Historical IPF Trial Failures and PureTech Differentiation Deupirfenidon
Slide 3: Deupirfenidone (LYT-100): Potential New Standard-of-care for IPF and other PPFs
Deupirfenidone (LYT-100): Potential New Standard-of-care (SOC) for IPF and other PPFs Lung Disease Debilitating, fatal disease; current SOC agents cannot be taken in high with High doses due to poor tolerability, resulting in suboptimal efficacy Patient Need Ideal Treatment Stabilization of lung fun
Slide 4: Accelerating Program Advancement for Patients in Need
Accelerating Program Advancement for Patients in Need December 2024 Successful completion of Phase 2b trial Open label extension (OLE) ongoing March 2025 140 patients continued in the OLE 85 patients received at least 52 weeks of treatment to date1 Additional data from Phase 2b to be present
Slide 5: Unmet Needs in IPF
Unmet Needs in IPF bad : BURETECH = o GIVING LIFE TO SCIENCE”
Slide 6: Idiopathic Pulmonary Fibrosis (IPF) Overview
Idiopathic Pulmonary Fibrosis (IPF) Overview IPF is a progressive and fatal disease with a significantly unaddressed patient population >232,000 ~2-5 years IPF patients in the US & EU51 Involves scarring of the lungs, leading Life expectancy of IPF to shortness of breath and loss of lung without tre
Slide 7: Efficacy is the Key Prescribing Focus in IPF
Efficacy is the Key Prescribing Focus in IPF The majority of respondents prioritize efficacy (over safety/tolerability) in trying to optimize therapy for IPF patients, regardless of practice setting (2025 analysis) Recognizing the Tradeoffs Between Efficacy and Safety/Tolerability, If I Have to Choo
Slide 8: Stabilization of Lung Function is the Ideal Treatment Goal in IPF
Stabilization of Lung Function is the Ideal Treatment Goal in IPF Pulmonologists and patients seek improved efficacy without sacrificing tolerability1 Change in Forced Vital Capacity (FVC) Over 52 Weeks 100 Change in Forced Vital Capacity (FVC) from Baseline 80 Natural lung function decline (~-50 mL
Slide 9: Dose-limiting Tolerability Challenges Have Prevented Patients on SOC from Achieving Greater Efficacy
Dose-limiting Tolerability Challenges Have Prevented Patients on SOC from Achieving Greater Efficacy Natural Lung Function Decline Expected in Healthy Older Adults1 Commonly Reported Side Pirfenidone Nintedanib Effects with Use of Label2 Label3 Current Antifibrotics* (N=623) (N=723) Nausea 36% 24% I
Slide 10: Introduction to Deupirfenidone
Introduction to Deupirfenidone 10
Slide 11: Deupirfenidone Is a Novel Compound with the Potential to Become the Next Standard-of-care Treatment in IPF
Deupirfenidone Is a Novel Compound with the Potential to Become the Next Standard-of-care Treatment in IPF STRUCTURE OVERVIEW DEUTERIUM SUBSTITUTION ▶ Leverages clinically validated pirfenidone1 New chemical entity with potential for improved efficacy without with strategically sacrificing tolerabil
Slide 12: Preclinical Data
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Slide 13: Deupirfenidone: Preclinical POC Demonstrates Anti-inflammatory & Anti-fibrotic Pharmacology
Deupirfenidone: Preclinical POC Demonstrates Anti- inflammatory & Anti-fibrotic Pharmacology PRECLINICAL PLASMA IN VITRO REDUCTION OF TGF-Β CONCENTRATIONS OF TNFΑ WITH INDUCED SOLUBLE COLLAGEN DEUPIRFENIDONE VERSUS CONTROL PRODUCTION (MOUSE FIBROBLASTS) minutes of oral pretreatment , pg/mL TGF-β Deu
Slide 14: Deupirfenidone Preserves Pharmacologic Effect of Pirfenidone
Deupirfenidone Preserves Pharmacologic Effect of Pirfenidone Preclinical data shows improved anti-inflammatory and anti-fibrotic activity vs pirfenidone A B Vehicle Plasma TNF-α concentration, pg/mL Pirfenidone, 100mg/kg Plasma II-6 concentration, pg/mL Deupirfenidone, 100mg/kg Reduction in LPS-stim
Slide 15: Phase 2b ELEVATE Data
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Slide 16: ELEVATE Trial Demonstrated Unprecedented Efficacy for Deupirfenidone 825 mg TID
ELEVATE Trial Demonstrated Unprecedented Efficacy for Deupirfenidone 825 mg TID POTENTIAL FOR LUNG ENHANCED EFFICACY DURABLE EFFICACY SUPPORTING FUNCTION VERSUS CURRENT RESPONSE OUT TO 52 PHARMACOKINETIC (PK) STABILIZATION STANDARD OF CARE WEEKS DATA Deupirfenidone 825 mg TID Deupirfenidone 825 mg T
Slide 17: ELEVATE: Global, Phase 2b, Multicenter, Randomized, Double-blind Clinical Trial
ELEVATE: Global, Phase 2b, Multicenter, Randomized, Double- blind Clinical Trial 26 Weeks of Double-Blind Study Treatment Open Label Extension Screening (Part A) (Part B) (≤ 28 days) V2 V3 V4 V5 V6 V7 V8 D1 W4 W8 W12 W16 W20 W26 Deupirfenidone Deupirfenidone 550 mg TID Deupirfenidone 550 mg TID 550
Slide 18: ELEVATE: Global, Phase 2b, Multicenter, Randomized, Double-blind Clinical Trial
ELEVATE: Global, Phase 2b, Multicenter, Randomized, Double- blind Clinical Trial 257 patients were recruited from 87 sites across 14 countries KEY DEMOGRAPHIC STATISTICS Romania Georgia South Korea ▶ Median age: 72 years, 6 Patients 20 Patients 38 Patients 13.6% ≥ 80 years United States ▶ 71.2% Male
Slide 19: Overview of ELEVATE Statistical Approach
Overview of ELEVATE Statistical Approach Commonly used Bayesian1 and frequentist analyses were applied ▶ We obtained FVC data per patient over time, BAYESIAN STATISTICS commonly referred to as observed data Used for Primary and Key Secondary Endpoints ▶ Observed data doesn’t account for missing data
Slide 20: ELEVATE Achieved Primary and Key Secondary Endpoints
ELEVATE Achieved Primary and Key Secondary Endpoints Posterior Mean (SE) Change from Baseline in FVC (mL) over 26 Weeks Posterior Mean (SE) Change from Baseline in FVCpp over 26 Weeks Change from Baseline in Forced Vital Capacity (FVC) over 26 Change from Baseline in Forced Vital Capacity % Predicte
Slide 21: Deupirfenidone Demonstrated Potential to Serve as a New Standard-of-Care Treatment for IPF
Deupirfenidone Demonstrated Potential to Serve as a New Standard-of-Care Treatment for IPF Adjusted Mean (SE) Change from Baseline in FVC (mL) over 26 Weeks Change from Baseline in Forced Vital Capacity (FVC) over 26 Change from Baseline in Forced Vital Capacity % Predicted Adjusted Mean (SE) Change
Slide 22: Deupirfenidone 825 mg TID Preserved Lung Function; Rate of Decline Similar to Healthy Older Adults
Deupirfenidone 825 mg TID Preserved Lung Function; Rate of Decline Similar to Healthy Older Adults Change from Baseline in Forced Vital Capacity (FVC) Over 26 Weeks (mL) 0 -20 -21.5 mL -15 to -25 mL -40 -60 FVC decline for deupirfenidone 825 mg TID at 26 weeks -80 in ELEVATE approached the level of
Slide 23: Deupirfenidone Demonstrated a Clear Dose-dependent Effect
Deupirfenidone Demonstrated a Clear Dose-dependent Effect Change from baseline in FVC and FVCpp (Mixed Model Repeated Measure with Random Slope Regression) Adjusted Mean (SE) Change from Baseline in Forced Vital Adjusted Mean (SE) Change from Baseline in Forced Vital Capacity Capacity (FVC) Over Tim
Slide 24: Versus Placebo, Deupirfenidone 825 mg TID Had ~50% Greater Effect Size than Pirfenidone
Versus Placebo, Deupirfenidone 825 mg TID Had ~50% Greater Effect Size than Pirfenidone in ELEVATE Trial Treatment Effect from Change in Forced Vital Capacity (FVC) and Percent Predicted Forced Vital Capacity (FVCpp) Across Arms 90% 87.5% 80.9% 80% 70% 57.4% 60% 54.1% 50% 47.2% 40% 28.3% 30% 20% 10%
Slide 25: PK Analysis From ELEVATE Showed Deupirfenidone 825 mg TID Has ~50% Greater Exposure than Pirfenidone
PK Analysis From ELEVATE Showed That Deupirfenidone 825 mg TID Has ~50% Greater Exposure than Pirfenidone Analysis of Estimated AUC for Deupirfenidone ELEVATE PK Summary and Pirfenidone Deupirfenidone 550 mg Deupirfenidone 825 mg ▶ Deupirfenidone 825 mg TID had TID vs. Pirfenidone TID vs. Pirfenidon
Slide 26: Deupirfenidone Had Favorable Tolerability in ELEVATE Trial
Deupirfenidone Had Favorable Tolerability in ELEVATE Trial Summary of Most Common (≥5% in Any Treatment Group) TEAEs by SOC, PT, and Treatment Group (Safety Set) Placebo Pirfenidone Deupirfenidone Deupirfenidone TID 801 mg TID 550 mg TID 825 mg TID SOC/PT (N=65) (N=63) (N=65) (N=64) n (%) n (%) n (%
Slide 27: Deupirfenidone's Favorable Tolerability Profile Allows for Higher Drug Exposure and Greater Efficacy
Deupirfenidone’s Favorable Tolerability Profile Allows for Higher Drug Exposure and Greater Efficacy Favorable Higher Deuteration PK Greater Tolerability Dose & Higher Differentiation Efficacy Profile Exposure 27
Slide 28: >90% of Patients Opted to Enroll in the Ongoing Open-label Extension
>90% of Patients Opted to Enroll in the Ongoing Open-label Extension 26 Weeks of Double-Blind Study Treatment Open Label Extension Screening (Part A) (Part B) (≤ 28 days) V2 V3 V4 V5 V6 V7 V8 D1 W4 W8 W12 W16 W20 W26 Deupirfenidone Deupirfenidone 550 mg TID Deupirfenidone 550 mg TID 550 mg TID N=257
Slide 29: Preliminary Open Label Extension Data Demonstrate Strong and Durable Efficacy over at Least 52 Weeks
Preliminary Open Label Extension Data Demonstrate Strong and Durable Efficacy with Deupirfenidone 825 mg TID over at Least 52 Weeks Change in Forced Vital Capacity (FVC) Over 52 Weeks -30 mL to -50 mL1 50 Healthy Older Adults 0 Expected natural lung function decline Change in FVC from Baseline (mL)
Slide 30: Preliminary 52-week Data Reaffirm Potential for Deupirfenidone to Become a New Standard of Care for IPF
Preliminary 52-week Data (Part A + Part B) Reaffirm Potential for Deupirfenidone to Become a New Standard of Care for IPF FVC Change from Baseline Over 52 Weeks Indirect comparison; not based on head-to-head data1 HEALTHY OLDER ADULTS INVESTIGATIONAL IPF AGENTS Expected natural lung function Deupirf
Slide 31: Deupirfenidone Has Demonstrated Potential for Best-in-class Efficacy
Deupirfenidone Has Demonstrated Potential for Best-in-class Efficacy FVC Relative Benefit Over Placebo Indirect comparison. Not based on head-to-head data Deupirfenidone 825 mg (Ph 2b ELEVATE IPF 26 weeks) no background 81% Deupirfenidone 825 mg (Ph 2b ELEVATE IPF OLE 52 weeks*) no background 84% Pi
Slide 32: Historical IPF Trial Failures & PureTech Differentiation
Historical IPF Trial Failures & PureTech Differentiation 32
Slide 33: Deupirfenidone Differentiates from Other IPF Programs
Deupirfenidone Differentiates from Other IPF Programs Observations From IPF Trial Failures Deupirfenidone Differentiation Idiopathic Nature of Evaluating a new mechanism of action for an Deupirfenidone builds on >10 years of established Disease idiopathic disease is inherently risky human efficacy a
Slide 34: Commercial Opportunity
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Slide 35: Deupirfenidone Has the Potential to be Best-in-class in IPF
Deupirfenidone Has the Potential to be Best-in-class in IPF Strong data package as a Why Deupirfenidone? monotherapy; first therapy to show potential lung function normalization in IPF Broad potential to be the new SOC for IPF patients Best-in-class efficacy: first and only IPF treatment to sh
Slide 36: Deupirfenidone Has the Potential to Be Used Across Multiple Patient Segments
Deupirfenidone Has the Potential to Be Used Across Multiple Patient Segments Potential to capture patients currently on SOC (~25%) AND expand to those who never start (~75%) Patients Who Never Start Treatment ~75% Tolerability risks outweigh modest efficacy benefits, discouraging patients from ever
Slide 37: ELEVATE Data Suggests Multi-billion Dollar Revenue Potential
ELEVATE Data Suggests Multi-billion Dollar Revenue Potential The ELEVATE data for 825 mg TID are a “home run” scenario for deupirfenidone as defined by stakeholder market research Potential for ▶ Versus placebo, 825 mg TID dose showed 50% better efficacy than pirfenidone Best-in-Class ▶ Stabilizatio
Slide 38: IPF Market Has the Potential for Substantial Market Growth
IPF Market Has the Potential for Substantial Market Growth Global IPF Market: • Despite only ~25% of IPF patients ever starting therapy4, >$5B >$10B SOC agents have achieved blockbuster status • Expected market growth in coming years is driven by: >$5B 1) Increased patient uptake & adherence via the
Slide 39: Potential to Expand into Other Progressive, Fibrotic Diseases with High Unmet Need
Potential to Expand into Other Progressive, Fibrotic Diseases with High Unmet Need Progressive pulmonary fibrosis (PPF), also termed progressive fibrotic ILD (PF-ILD), is estimated to affect ~675,000 patients in the US and EU5 CURRENT ADDRESSABLE MARKET: FUTURE ADDRESSABLE MARKETS: US AND EU5 >232,0
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