*INVITE* KOL Call Fri 11am >> TTRacking ALNY TTR Outlook Post CARDIO-TTRansform

研报英文原文证据摘录

*INVITE* KOL Call Fri 11am >> TTRacking ALNY TTR Outlook Post CARDIO-TTRansform

bo n = 202) which included all the patients who had undergone randomization, received at least one

dose of acoramidis or placebo, had at least one efficacy evaluation after baseline, and had eGFR >30 ml/min/1.73 m2

. c. Reported baseline and mortality data from HELIOS-B omit one patient in the placebo group (originally N = 329) who was randomized but withdrew before dosing

Source: Jefferies Research and Company Data

Exhibit 3 - Endpoint Comparison in ATTR-CM Trials

ATTR-ACT APOLLO-B ATTRibute-CM HELIOS-B CARDIO-TTRansform TRITON-CM

Company Pfizer Alnylam BridgeBio Alnylam Ionis / AstraZeneca Alnylam

Clinical Trial NCT01994889 NCT03997383 NCT03860935 NCT04153149 NCT04136171 NCT07052903

Therapy Tafamidis Patisiran Acoramidis Vutrisiran Eplontersen Nucresiran

Enrollment period Dec 2013 - Aug 2015 Oct 2019 – May 2021 Apr 2019 - Oct 2020 Dec 2019 - Aug 2021 Mar 2020 - Jul 2023 Jul 2025 - ongoing

Primary efficacy

endpoint/s Four-step hierarchical: first death

from any cause, followed by CV-

related hospitalizations, then Composite of all-cause mortality

Two-step hierarchical: All-cause change from baseline in NT- and recurrent cardiovascular

mortality followed by frequency Change from baseline at Month proBNP, then change from Composite of all-cause death Composite of CV death and events (CV hospitalizations and

of CV-related hospitalizations 12 in 6-MWT baseline in 6MWT distance and recurrent CV events recurrent CV events urgent HF visits)

Statistical method

for primary efficacy

endpoint Stratified Wilcoxon rank-sum Modified Andersen-Gill model

test; stratified Hodges–Lehmann Recurrent events Andersen Gill Recurrent events Andersen Gill with robust variance estimator