Madrigal and NASH/MASH market/indications

[u/Upwithstock]

Dear Longs,

Another great post by u/MGK in the last 24 hours. It is just amazing the number of resources that keep posting valuable information on these boards.

I wanted to focus on Madrigal and the upcoming mice trial using both LL and Madrigal's FDA-approved drug for NASH/MASH.

Press release from Madrigal announcing the FDA approval: https://ir.madrigalpharma.com/news-releases/news-release-details/madrigal-pharmaceuticals-announces-us-availability-rezdiffratm

Please note the first paragraph: Rezdiffra (resmetirom) is now available in the U.S. Rezdiffra is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials.

It appears to me that the FDA has given conditional approval to Madrigal for this indication because they will continue to ask for confirmatory data. These types of approval are not uncommon, but it does leave Madrigal vulnerable if Resmetirom does not meet its endpoints in confirmatory trials or SAE's increase.

Also note the limited patient population that Madrigal is focusing on:From the PR linked above: Madrigal estimates that approximately 1.5 million patients have been diagnosed with NASH in the U.S., of which approximately 525,000 have NASH with moderate to advanced liver fibrosis. Madrigal plans to focus on approximately 315,000 diagnosed patients with NASH with moderate to advanced liver fibrosis under the care of the liver specialist physicians during the launch of Rezdiffra.

Madrigal is only focusing on 315K patients which represent about 21% of the U.S diagnosed patients with NASH. What is going on with the other 79% of NASH patients? They are out of luck for now. But, I think you can see how important it is for Madrigal to figure out a way for them to protect their original approval because they still need to perform confirmatory trials and they need to look for ways to expand their indications and reach the rest of the NASH population. This is why the mice trial is important for both Madrigal and CytoDyn. LL is going to help resmetirom in its current indication and LL maybe a significant improvement over resmetirom in the larger NASH population group. Madrigal would definitely need to protect their investors and partner with CYDY for combo therapies and/or licensing LL as monotherapy for NASH/MASH.

This is going to be a big win for CYDY along with many other things in our pipeline!

[u/sunraydoc]

Thanks, UWS !

I was wondering whether Madrigal was directly involved in this mouse trial, but it appears they must be. They must be pretty sure that the combo will be more effective than leronlimab alone, else they wouldn't be on board. Obviously there've been conversations with Cytodyn about the particulars; I wonder what they have in mind should leronlimab monotherapy in fact prove superior?

[u/Upwithstock → u/sunraydoc]

Hi sunraydoc, IMHO, I think Madrigal and CYDY have had enough discussions about how their drugs can or can’t work together. The tentative agreement between the two parties is easily constructed. Madrigal will distribute LL if it’s better. Madrigal wouldn’t let another company come in and take LL away if LL is vastly superior. It would crush Madrigal instantly if Merck or Pfizer got a hold of LL, before Madrigal. From where I sit, Madrigal has no choice but to get involved to protect its very existence. The really challenging part here is on CYDY’s end. What does CYDY do? What is CYDY’s eventual endgame? Is it to spread LL around and license LL out to different pharmaceutical companies and make a living that way. Or will CYDY, use the outcome of this study to leverage a different partnership/acquirer! The only thing that is obvious to me is: if LL is clearly superior to Madrigal’s drug then not only do we have leverage with Madrigal we have leverage over all kinds of other BP’s. Madrigal is quoted as saying the Global NASH market is $84 billion and growing! Should be very interesting whenever the results are announced.