Ann: Biotech Showcase 2022 Presentation, page-14

@dachopper
You are absolutely correct, this is because the NYHA classification is very subjective. See below of an extract from an article:

"The survey of cardiologists showed no consistent method for assessing NYHA class and a literature survey showed that 99% of research papers do not reference or describe their methods for assigning NYHA classes. The interoperator variability study showed only 54% concordance between the two cardiologists."

However, no one can miss diabetic/ischemic classification; furthermore, there seems to be a bidirectional link between diabetes and heart-failure. exert from this article write: "People who have Type 2 diabetes, characterized by elevated blood sugar levels, are two to four times more likely to develop heart failure than someone without diabetes. But heart failure, a condition in which the heart fails to efficiently pump oxygenated blood through the body, also is a risk factor for diabetes"

I also agree with you that our target population for the next trial should be 1) CRP >2 (inflammation), 2) NYHA class II - III (but the study will enriched for class II, as many class III patients have too much scare tissues already in the heart) 3) diabetic/ischemic patients (either as an inclusion criteria OR as a pre-specified subpopulation)

Ideally we would ignore class III patients, but since it is so difficult to discern between class II & III, it is wiser to include both into the next trial, whatever the next trial may be (either another phase 3; or a phase 4 (slim chance)- if we get Accelerated Approval for the diabetic/ischemic group).

The meeting with the FDA will be interesting, because if we have to wait for another phase 3 trial, that's at least 4-5 years before we see any results, during which more patients would have died from HF.