class war Why does Promis promote the idea that 310 is in the same class as aducanumab?
Aducanumab was not designed for the job, rather it was a natural molecule discovered to have some benefit in one human population. It doesn't bind to an epitope constrained by misfolding, like PMN 310s HHQK, rather it gloms onto fibrils, soluble or not, and has some affinity for oligomers correlating negatively with size i.e., not to monomers and not significantly to dimers. So while PMN 310 is a genuine ABO-specific drug, aducanumab is really a plaque drug rebranded from ACH for the ABO hypothesis.
Is there so much overlap on oligomers that Promis can’t credibly dump the class adjective? Not to me, it looks like orders of magnitude difference in useful (LMW oligomer) binding once adcuanumab’s preferential binding to HMW oligomers plus toxicity arising from fibril binding binding are considered.
Cashman et al have written excellent papers highlighting the differences, but those are for peer review not financial markets so they don’t make any attempt to quantify how much better PMN could perform than the competition in the real world. Our consultant management has then compounded the marketing differentiation problem with their “best in class” mantra.
Aducanumab’s binding characteristics are complex and still being defined as the drug came first and the explanation later, opposite PMN’s synthetic approach. A new paper on aducanumab’s binding is coming out Feb 24 and one from 2020 is not yet available free, but we still have the one from 2018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913127/ which would have been a reference for Cashman et al in thier 2019 paper available on our website. So there is not a lot of mystery to aducanumab’s failure, the mystery is our marketing.