Slide 1: Primary Results from the Phase 2 Randomized, Placebo-Controlled Trial of Coramitug in ATTR-CM
PRIMARY RESULTS FROM THE PHASE 2 RANDOMIZED, PLACEBO CONTROLLED, BLINDED TRIAL OF THE MONOCLONAL ANTIBODY CORAMITUG IN TRANSTHYRETIN AMYLOID CARDIOMYOPATHY (ATTR-CM) Marianna Fontana,1 Pablo Garcia-Pavia,2 Martha Grogan,3 Sanjiv J Shah,4 Mads D M Engelmann,5 G Kees Hovingh,5 Arnt V Kristen,6 Michell
Slide 2: Disclosures
DISCLOSURES https://sciencehub.novonordisk.com/aha2025/fontana.html Prof Fontana reports consultancy for Alexion/Caelum Biosciences, Alnylam, AstraZeneca, Attralus, Bayer, BridgeBio/Eidos, Cardior, Intellia Therapeutics, Ionis Pharmaceuticals, Janssen Pharmaceuticals, Lexeo Therapeutics, MyCardium A
Slide 3: ATTR-CM Is Caused by Amyloid Deposition in the Myocardium
ATTR-CM IS CAUSED BY AMYLOID DEPOSITION IN THE MYOCARDIUM ATTR-CM is a progressive and fatal condition that results from accumulation of wild type or variant TTR amyloid fibrils in the heart.1 The disease leads to hospitalizations and reduced survival with progressive heart failure and arrhythmias,
Slide 4: From Changes in Amyloid Load to Changes in Patient Outcomes
FROM CHANGES IN AMYLOID LOAD TO CHANGES IN PATIENT OUTCOMES NT-proBNP Troponin I 6MWT CMR KCCQ-CSS Reduction in Changes in Changes in amyloid load structure and patients’ (as observed by function Changes in prognosis CMR, PET or (assessed by biomarkers, 6MWT, bone echocardiography functional scores
Slide 5: Coramitug Is Designed to Target Misfolded TTR
CORAMITUG IS DESIGNED TO TARGET MISFOLDED TTR • Coramitug is a humanized monoclonal antibody designed to bind specifically to a unique epitope exposed on misfolded monomeric and aggregated forms of TTR • It does not bind to native tetrameric TTR1 • Binding inhibits the formation of new TTR amyloid f
Slide 6: Antibody-Dependent In Vitro Phagocytosis of TTR Amyloid by Murine Coramitug
ANTIBODY-DEPENDENT IN VITRO PHAGOCYTOSIS OF TTR AMYLOID BY THE MURINE FORM OF CORAMITUG1,2 Control IgG Murine coramitug IgG, immunoglobulin G. 6 1. Suhr O et al. AAN 2021 Virtual Annual Meeting (oral presentation); 2. Higaki JN et al. Amyloid 2016;23:86–97.
Slide 7: Antibody-Dependent In Vitro Phagocytosis of TTR Amyloid by Murine Coramitug
ANTIBODY-DEPENDENT IN VITRO PHAGOCYTOSIS OF TTR AMYLOID BY THE MURINE FORM OF CORAMITUG1,2 Phagocyte Phagocyte TTR amyloid TTR amyloid Control IgG Murine coramitug IgG, immunoglobulin G; TTR, transthyretin. 7 1. Suhr O et al. AAN 2021 Virtual Annual Meeting (oral presentation); 2. Higaki JN et al.
Slide 8: Trial Design
TRIAL DESIGN Global, phase 2, randomized, multicenter, double-blind dose finding and safety trial Trial time frame Inclusion criteria Primary endpoints: Changes from baseline to 2022–2024 • Hereditary or wild-type ATTR-CM week 52 in NT-proBNP and 6MWT Patient recruitment • NYHA class II or III Secon
Slide 9: Baseline Characteristics
BASELINE CHARACTERISTICS Demographics and clinical characteristics were balanced across arms (N=104) Placebo Coramitug 10 mg/kg Coramitug 60 mg/kg (n=35) (n=34) (n=35) Median age, years (IQR) 78.0 (74.0, 82.0) 78.0 (72.0, 81.0) 76.0 (71.0, 80.0) Male sex, n (%) 34 (97.1) 29 (85.3) 34 (97.1) vATTR am
Slide 10: Primary Endpoints
PRIMARY ENDPOINTS • From baseline to week 52, coramitug 60 mg/kg statistically significantly reduced NT-proBNP levels compared with placebo (–48%; 95% CI: –65%, –22%; p=0.0017) • The change in 6MWT from baseline to week 52 was not statistically significantly different from placebo with either dose 6
Slide 11: Structural and Functional Remodeling by Echocardiography
STRUCTURAL AND FUNCTIONAL REMODELING BY ECHOCARDIOGRAPHY Left and right ventricular function LV, left ventricular; RV, right ventricular. 11
Slide 12: Structural and Functional Remodeling by Echocardiography
STRUCTURAL AND FUNCTIONAL REMODELING BY ECHOCARDIOGRAPHY Diastolic function and estimated pulmonary pressures 12
Slide 13: Safety
SAFETY Coramitug was associated with no apparent drug-related serious AEs Placebo Coramitug 10 mg/kg Coramitug 60 mg/kg (n=35) (n=34) (n=35) N (%) Events Ratea N (%) Events Ratea N (%) Events Ratea Any AEb 33 (94.3) 316 760.7 32 (94.1) 266 657.0 33 (94.3) 224 524.4 AE occurring in >15% of participan
Slide 14: Conclusions
CONCLUSIONS https://sciencehub.novonordisk.com/aha2025/fontana.html • In this randomized phase 2 study, treatment with the humanized monoclonal antibody coramitug at a dose of 60 mg/kg resulted in a statistically significant reduction in NT-proBNP compared with placebo over 52 weeks as well as a red
Slide 15: Thank You
Thank you to the patients, their families, investigators, study staff and collaborators for their participation in the trial THANK YOU #AHA25
Slide 16: Coramitug, a Humanized Monoclonal Antibody for ATTR-CM: Phase 2 Trial Publication
Coramitug, a Humanized Monoclonal Antibody for the Treatment of Transthyretin Amyloid Cardiomyopathy: a Phase 2, Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial Marianna Fontana; Pablo Garcia-Pavia; Martha Grogan; Sanjiv J. Shah; Mads D.M. Engelmann; G. Kees Hovingh; Arnt V. Kristen;