Can you tell us a bit about your practise and research interests?

One of the concerns about APOLLO-B that became more prominent after the acromidis readout is that the standard of care has notably evolved over the last few years, so the expected decline in the control arm would be more similar to the ATTRibute trial for acromidis vs the ATTR-ACT trial for tafamidis arm back in 2018. What are your thoughts on that?

Can you talk a bit more about how people are diagnosed with ATTR-CM nowadays compared to before 2019? I understand their are echocardiograms, tracers, but I guess I'm just wondering what are the chances of a misdiagnosis?

In your opinion, why do you think acromidis failed their phase 2? 

so ATTRibute-CM allowed NYHA class 1-3 in their trials, and I believe about 29 % of patients fell into that category, where as APOLLO-B excludes class 3 and 4 patients in their trial. Do you think the bias towards healthier patients would affect their chances of hitting the 6MWT primary?

APOLLO-B study includes patients who are on tafamidis for more than 6 months who show evidence of disease progression. What are your thoughts on that, and do you think those would affect the outcome vs treatment naive patients?

Kind of a follow-up, do you know what would be classified as evidence of disease progression, given that this is an elderly population with an average age in the wild type in the mid 70s? Like are they using echocardiograms to verify this?

I've heard from other KOLs that the % of patients who are wild type is about 90% and could be as high as 95% vs those who are hereditary. So the vast majority of patients on APOLLO-B should be expected to be wt. Is that a fair assessment?

About the MoA, I think there is a general perception that RNA silencing is more potent than stabilizers. Do you have any opinion on that, agree or disagree?

Are you familiar with Ionis' Eptonlersen? Antisense drug. Do you have any thoughts on how that stacks up against patisiran?

Can you talk a bit about reimbursement for tafamidis and any challenges you've seen?

Discussing the secondary endpoints for a bit, how meaningful do you think KCCQ is, especially since it seems a bit subjective? And I guess the follow-up to that is, is it fair to say that mortality and the 6MWT are the key metrics to watch for when this reads out?

If you were to rate your confidence in APOLLO-B having a positive readout at 6MWT, what would you rank it and why?

The speed of deterioration - how does it differ between placebo and treatment arms?