Biotech Values

[poorgradstudent]

Kinases:

I appreciate this post.

I’ve argued for a while that the kinase inhibitors were generally pretty unpredictable drugs – because they were too unspecific

I agree targeting the mutations and fusions appears to be a much more reliable strategy. I think our increased success rate (to date) of targeting mutations / fusions vs WT forms is largely due to our ignorance / inability to properly decipher the underlying biology. In that respect, mutations and fusions appear to prove better targets because the biology itself is giving us a bright, flashing signal rather than us having to dissect it.

In contrast, I would wager WT kinase targets (amplified or not) appear to prove less successful because judging the relevance / importance of one WT kinase versus another depends on our ability to decipher / weigh the biology... and we're not all that great at it yet.

For example, I don't think we ever had a convincing prospective reason (based on preclinical work) as to why a BTK inhibitor would prove clinically superior to PI3K or FLT inhibitors in the clinic... all had excitement surrounding them. We only know the increased relative importance of the BTK pathway in retrospect because the clinical results separated the winner from the losers.

Therefore, I don't think fusions / mutations necessarily make better, more impactful targets than WT kinases. I just think they help us skip a few steps that would normally unmask our ignorance.