Replies to post #247273 on Biotech Values

[dewophile]

If memory serves (I don’t have search capability on this site) many years ago you posted about how investable rare conditions are after blockbuster sales were reported for a drug with a very small indication (I want to say novoseven). So this would represent a 180 on your part.
Maybe I’m remembering wrong.
Anyway the upside w targeted therapies is the high hit rate in development. Obviously you have to think through the commercial viability ahead of time. At 300k + a course there often is room for profit , but not in the billions like some of the other indications you cite

[DewDiligence]

The APGN program about which I just posted (#msg-172051157) is an instance of the kind of fragmentation you addressed in your post.

Soft-tissue sarcoma (STS) is itself quite rare, and DDLPS is one of several STS subtypes. Even if APGN's program is successful (and that's a very big if), the addressable market for the drug will be tiny, and the average patient time on drug is going to be relatively short.

[vinmantoo]

First, yes I am aware that heterogeneity exists and the impact of clonal evolution under selective pressure.

The key word here is "relatively." And yes, while there are few broad tumor types that have a single driver (like CML), there are many molecularly defined subsets of tumors that are driven predominantly (but perhaps not completely) by a single targetable mutation (ALK, ROS1, EGFR, etc in NSCLC).

You said it yourself but don't seem to follow your own advice. Only a FEW tumor types have broad drivers. The reality is even in most of those, you can't treat the tumor by just blocking a single driver, at least for long as resistance arises.

But you are making my argument from an investment standpoint for me. Okay so a particular combination will work for the 0.5% x 0.5% of patients who carry both actionable mutations. Do I want to be involved from an investment standpoint in the development of such combinations? No. Great for patients, not great for investments.

This is a straw man argument with based on your made up and absurdly low numbers.

I am not arguing at all about the value of precision medicine for patients, I am only making the point that as the molecular pathophysiology of cancers is further dissected, treatments will become increasingly targeted to smaller populations. Either a) the populations become so small that the company will never make money or b) therapies will become so extravagantly expensive that nobody will be able to get them anyway.

This is in contrast to inherently highly polygenic diseases like RA, ulcerative colitis, or multiple sclerosis, where they are so highly variable that precision medicine just doesn't really work yet (and will not for the next several decades). Thus they are still a viable investment because the drugs that come out can treat broad populations. Companies researching diseases of consumption like NASH and obesity also remain highly investable due to the size of these populations and the fact that precision medicine is largely irrelevant in this space, with the exception of the small population of patients with strong genetic drivers of liver disease or obesity.

You don't seem to grasp that RA and ulcerative colitis already have very good treatments. Why aren't you arguing that it is foolish to look for newer and more effective treatments? As far as NASH, that is a relatively new and understudied disease, especially compared to oncology, whose mechanism is not understood. Why in the world would you place faith in that as an investment opportunity?

Good luck to you.