Slide 1: ATTRibute-CM Phase 3 Topline Results
ATTRibute-CM Phase 3 Topline Results July 17, 2023 1
Slide 2: Forward-Looking Statements and Disclaimer
Forward-Looking Statements and Disclaimer 2 The presentation at the call may contain forward-looking statements. Statements made or presented at the call may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of
Slide 3: Discussion topics
Discussion topics Q&A Session 5 Introduction & Overview 1 Neil Kumar, PhD Chief Executive Officer ATTRibute-CM Phase 3 Topline Results 2 Jonathan Fox, MD, PhD Chief Medical Officer, Cardiorenal Next Steps 3 Uma Sinha, PhD Chief Scientific Officer Commercial Launch Plans 4 Matt Outten, MBA Chief Comm
Slide 4: A sincere thank you to patients, families, and collaborators
4 4 A sincere THANK YOU to patients and families, advocates, physicians, clinical research staff, and collaborating research partners (acoramidis for ATTR-CM)
Slide 5: Program context
ATTR-CM Idea Phase 3 Achondroplasia Idea Phase 3 LGMD2i Idea ADH1 Idea Phase 3 CAH Idea Program context 5
Slide 6: Acoramidis designed to achieve maximal stabilization and preserve native TTR
Acoramidis was designed to achieve maximal stabilization and preserve native TTR TTR = Transthyretin; ATTR-CM = TTR amyloid cardiomyopathy. 1Hammarstrom, P et al., PNAS. 2002;99:16427-16432. 2Damy, T., et al., Eur J Heart Fail. 2021;23(2):277-285. 3Coelho, T. et al., Neurology. 2012;79:785–792. 4Ber
Slide 7: Acoramidis is a next generation stabilizer maximizing potency
Acoramidis is a next generation stabilizer that employs multiple strategies to maximize potency 7 Native TTR circulates in blood as a tetramer Dissociation into monomers initiates pathogenesis Monomers aggregate, causing disease Acoramidis was designed to mimic protective T119M mutation. Acoramidis
Slide 8: Data supporting more potent TTR stabilization
Data supporting more potent TTR stabilization 8 Near-Complete TTR Stabilization2 at target trough clinical concentrations Rapid, durable increases in serum TTR an in vivo marker of native tetramer stability Superior Binding to TTR in vitro1 facilitated by enthalpic interactions Tafamidis 20 mg Tafam
Slide 9: Unprecedented and consistent benefit on survival and morbidity
Unprecedented and consistent benefit on survival and morbidity Achieve statistical significance on primary endpoint:p-value <0.04 Primary endpoint met (p<0.0001) Unprecedented survival: Highest ever 30-month survival rate on drug (>80%) with clinically meaningful separation from placebo 81% 30-month
Slide 10: Discussion topics
Discussion topics Q&A Session 5 Introduction & Overview 1 Neil Kumar, PhD Chief Executive Officer ATTRibute-CM Phase 3 Topline Results 2 Jonathan Fox, MD, PhD Chief Medical Officer, Cardiorenal Next Steps 3 Uma Sinha, PhD Chief Scientific Officer Commercial Launch Plans 4 Matt Outten, MBA Chief Comm
Slide 11: ATTRibute-CM study design
ATTRibute-CM study design1,2 Screening and randomization Open-label extension 30-month primary endpoint3: Hierarchical analysis consisting of all-cause mortality, cumulative frequency of CVH, change from baseline in NT-proBNP, and change from baseline in 6MWD Efficacy assessment included 611 partici
Slide 12: Highly statistically significant result on primary and select secondary endpoints
Hierarchical analysis consisting of: All-cause mortality2 Cumulative frequency of CVH Change from baseline in NT-proBNP Change from baseline in 6MWD p<0.0001 Win Ratio 1.8 Cumulative frequency of CVH3 p<0.0001 Change from baseline in 6MWD4 p<0.0001 Change from baseline in KCCQ-OS4 p<0.0001 Change fr
Slide 13: No safety signals of potential clinical concern identified
No safety signals of potential clinical concern identified 13 Any treatment-emergent adverse events (TEAEs) 413 (98.1%) 206 (97.6%) TEAE with fatal outcome 60 (14.3%) 36 (17.1%) TEAE leading to hospitalization 212 (50.4%) 128 (60.7%) TEAE leading to study drug discontinuation 39 (9.3%) 18 (8.5%) Any
Slide 14: Exploratory post hoc analysis: serum TTR levels
Exploratory post hoc analysis: serum TTR levels Serum TTR Level Mean Change from Baseline1 (mg/dL) +42% Placebo + Tafamidis2 35 Placebo 100 Acoramidis 234 N = 14 1Mean change from baseline in serum TTR at Month 30 in mITT population. 2Mean exposure on tafamidis = 11 months in mITT population. Acoram
Slide 15: Exploratory post hoc analysis: median NT-proBNP
Exploratory post hoc analysis: median NT-proBNP NT-proBNP Level Median Change from Baseline1 (pg/mL) Placebo + Tafamidis2 35 Placebo 98 Acoramidis 232 N = 15 1Median change from baseline in NT-proBNP at Month 30 in mITT population. 2Mean exposure on tafamidis = 11 months in mITT population. Acoramid
Slide 16: Summary of topline results
Summary of topline results 16 Unprecedented 30-month survival of >80% for a targeted intervention in ATTR-CM Achieved primary endpoint with highly statistically significant result with Win Ratio of 1.8 6.4% ARR & 25% RRR in all-cause mortality 50% RRR for cumulative frequency of CVH Well-tolerated w
Slide 17: Discussion topics
Discussion topics Q&A Session 5 Introduction & Overview 1 Neil Kumar, PhD Chief Executive Officer ATTRibute-CM Phase 3 Topline Results 2 Jonathan Fox, MD, PhD Chief Medical Officer, Cardiorenal Next Steps 3 Uma Sinha, PhD Chief Scientific Officer Commercial Launch Plans 4 Matt Outten, MBA Chief Comm
Slide 18: First regulatory submission planned for year-end 2023
First regulatory submission planned for year-end 2023 Present ATTRibute-CM Primary Results European Society of Cardiology 2023 August 27th, 2023 File New Drug Application (NDA) with FDA End of 2023 Submit additional regulatory filings (EMA & others) 2024 Execute lifecycle management Initiate primary
Slide 19: Discussion topics
Discussion topics Q&A Session 5 Introduction & Overview 1 Neil Kumar, PhD Chief Executive Officer ATTRibute-CM Phase 3 Topline Results 2 Jonathan Fox, MD, PhD Chief Medical Officer, Cardiorenal Next Steps 3 Uma Sinha, PhD Chief Scientific Officer Commercial Launch Plans 4 Matt Outten, MBA Chief Comm
Slide 20: Commercial launch plans
Commercial launch plans 20 We have a world-class commercial team and we are prepared to go to market 20+ FTEs (Pharmacyclics, Vertex, and Schering Plough alumni) and a distinctive commercial advisory board, inclusive of Fred Hassan, Jennifer Cook and Jim Robinson Have initiated discussions with key
Slide 21: ATTRibute-CM Phase 3 Topline Results Q&A Session
ATTRibute-CM Phase 3 Topline Results Q&A Session 21