Thank you Alan!
Maybe a discussion of the "mild Cushing's" opportunity warrants a BSR update.
I follow CORT quite closely and while I had heard Joe talk about early/mild Cushing's and the "much bigger market" discussion, I did not realize that there was pretty compelling proof of concept that even a dirty drug like Mife shows a clear benefit.
I would guess even most of the big boys are in dark (including the only recent smart money holder like Consonance). Yes there are tons of small independent investigator trials that we have all heard about, but what is different here is that even with only a high single digit subjects (with a benign adrenal mass), you can show a clear effect on insulin resistance. Also what is different is that there are several small studies that show the same effect. Lastly when you add up all the subjects in these small studies, you end up with total treated subjects that is not that far from the treated arm of the P3 !! All this makes Relacorliant in "mild Cushing's" have a decent chance of success (IMHO better than 60%)...versus a speculative shot in the dark (which is what I had thought).
As for market size, I fell off my chair when I read in the paper you posted that "10% of the elderly population has an ‘adrenal incidentaloma’, up to 20% of these show low-grade autonomous cortisol secretion and 60% of patients with autonomous cortisol secretion have insulin resistance." That arithmetically end up being 1-2% of elderly population as the total addressable market, which is way way bigger than what I would have guessed. Moreover, as you pointed out, all the talk about competition from new Keto like drugs and generic Mife is irrelevant in this population as the side-effects of those agents renders them unsuitable in for an older population with a mild disease burden.
One addl feedback from an academic endo doc. He said that one of the unsaid killer problem with Mife / Kormlyn in treating Cushing's is that it increases blood cortisol levels. Every Endo is in their training and in their practice diagnoses endocrinological disease by looking a hormonal abnormality in the patient. Treatment is a medical intervention that offset the hormonal abnormality and that improves the clinical symptoms. Kormlyn does something very different -- it results in a higher amount of cortisol in the test, and thus exacerbates the very hormonal abnormality that defines Cushing's syndrome. This is a bit like driving a car for the first time in UK. You need to learn to view the wrong side of the road as being the correct side. Now once a doc has experience with Kormlyn and sees benefit in the patient he can unlearn all that he is taught -- but unfortunately most Docs are way busy and/ or unwilling to learn something so different. Hence why the uptake was so slow and why even 10 yrs later it is still growing.
Anyway, I pass the above on and it might be helpful in understanding why even today there is so much skepticism about market size, etc. Good news is none of the above problem that limited Kormlyn uptake (along with side effects and abortion drug baggage) applies to Relacorliant. Unlike Kormlyn, Rela does not increase cortisol levels and has none of the side-effect / baggage. And when you add the "mild-Cushing's" opportunity to the mix, it becomes even more compelling.
Lastly one can make a strong case (IMHO) that Corcept should forget about oncology (i.e. license out those indications) and just focus on Cushing's and metabolic indications (starting w anti-psy wt gain). Those are low hanging fruit with a much higher chance of success and little competition. Let the big boys play the hype and sequencing / combo battles in the Oncology space......use the cash from licensing the oncology indication to buyback more of the stock and accelerate the metabolic applications.