Pillar 1 - FTO (new thread), page-301

I have shared your concerns with Pillar one and have came to my own conclusion.

There is absolute reason to believe that just because something works in a rodent model, it may not translate into human efficacy. However, I believe this is when you are taking a 'new' drug from preclinical (in vitro), to in vivo mouse models, and then into humans. By new, I am referring to a pharmacological substance that has not yet been tested in humans. In most cases, there is little known of how a 'new' drug will perform in humans and so, testing in animals is largely recommended from a business as well as patient perspective to establish safety and mechanistic paramaters for drugs in development (1,2).

We all know that bisantrene is not a new drug. There is a extensive amount of safety and pharmacokinetic data available that supports its use in humans as well as data that demonstrates its efficacy; in fact, efficacy in population subgroups that may also overexpress FTO (breast / AML). Particularly obese women (a known group with increased breast cancer risk) with breast cancer who are more likely to overexpress estrogen and thus FTO (3). Also, the mRNA system has been around for millions of years and "the basic mechanisms governing the operation are based on the same methods and available resources" (4). Hence, while I am conscious of the limitations of rodent models, I am confident that because bisantrene has already shown to be safe, tolerable, and efficacious in human studies, it is substantially more advanced than a 'new' drug moving through development and the risk for Pillar one is thus reduced.

All IMO - DYOR

1. https://www.sciencedirect.com/science/article/pii/S2307502314000022
2. http://www.animalresearch.info/en/drug-development/
3. https://pubmed.ncbi.nlm.nih.gov/32089015/
4. https://www.eurekalert.org/pub_releases/2014-11/cfgr-ham111914.php