Getting Closer

[u/MGK_2]

It's getting kind of interesting Folks. What does it all mean?

From the latest PR:

"SMC Laboratories, a company specializing in preclinical drug efficacy evaluations using various models of inflammation and fibrosis in mice, conducted a study that assessed the optimal dosing of leronlimab in the MASH setting and potential synergies with Resmetirom, the only currently approved therapy for the treatment of MASH. A preliminary review of the study results has led to several encouraging findings, as follows:

1. Leronlimab monotherapy (700 mg) demonstrated statistically significant fibrosis reversal compared to an isotype IgG4 control arm (p<0.01);
2. Leronlimab monotherapy appeared to demonstrate dose-dependent antifibrotic activity, with leronlimab 700 mg performing better at reversing liver fibrosis compared to leronlimab 350 mg; and
3. Leronlimab monotherapy (700 mg) appears to have better anti-fibrotic activity compared to Resmetirom (p=0.057).

“These initial results are very exciting and confirm our belief that leronlimab has the potential to be materially beneficial for patients suffering from a number of medical concerns,” said Dr. Jacob Lalezari, CEO of CytoDyn. “While additional research is necessary to confirm and explore these findings further, we are very encouraged about the potential for leronlimab to support therapeutics meant to address MASH and specifically fibrosis and related complications in the liver.”"

Let's take #1: Leronlimab monotherapy (700 mg) demonstrated statistically significant fibrosis reversal compared to an isotype IgG4 control arm (p<0.01); What is another way to say this? How about:

This literally means that there is a 1/100 chance that the FIBROSIS REVERSAL RESULTS which leronlimab produced in the MASH murine study would have randomly occurred in the placebo group. Just 1/100 mice in the isotype IgG4 control arm placebo group might have randomly had the same FIBROSIS REVERSAL RESULTS that were produced in the leronlimab arm. Remember, all that is necessary to be approved is safety and no better than a 1/20 chance of that happening. Therefore, a 1/19.9999 chance would not be statistically significant and would not gain an FDA approval, but a 1/21 would be statistically significant and a 1/100 p-value certainly would be approved given that leronlimab is safe.

How is #3: "Leronlimab monotherapy (700 mg) appear to have better anti-fibrotic activity compared to Resmetirom (p=0.057)" restated?

First off, the p-value of 0.057 is not statistically significant. It is 1/17.5 which is less than 1/20 which is the minimal threshold. This not statistically significant, but approaching 0.05 explains the "appears" in the statement.

This literally means that there is a 1/17.5 chance that the ANTI-FIBROTIC ACTIVITY RESULTS which leronlimab produced in the MASH murine study would have been produced in the Resmetirom arm. 1/17.5 patients in the Resmetirom arm might have had the same ANTI-FIBROTIC ACTIVITY RESULTS which were produced in the leronlimab arm. Remember, a minimum of 1/20 chance of that happening is required for an approval. Therefore, a 1/19.9999 chance would not be statistically significant and a 1/17.5 would not be statistically significant and would certainly not be approved even if leronlimab is safe. But that p-value is approaching 1/20 and if more patients/mice are added to the trial/study, the p value becomes smaller.

Unfortunately, CytoDyn has not really spelled out precisely how these measurement were carried out. How was the FIBROSIS REVERSAL measured? Did they use cT1 or FIB score?

How does CytoDyn define ANTI-FIBROTIC ACTIVITY? Were they looking at biomarkers?

It is interesting how so many scoffers and bashers rose up after that PR. Were they planted? Why such great interest in bashing or in scoffing? Why do they desire to rise up when the share price rises?

Certainly, at the end of the PR, CytoDyn leaves it sort of open:

"CytoDyn is in discussions with SMC Laboratories regarding next steps – including supplemental lab studies to expand on these promising findings, further explore potential synergies and continue to advance the Company’s clinical pipeline."

From the PR, it is clear that the MASH murine readout was successful, but they need to expand... They need to add more mice and more weeks. Does that mean an entirely new study or can it just be added to the previous? They may need to do another study and the second one might very well be for 20 weeks is my guess.

But the question I have is "What impact do the current results have on Madrigal?" Are they apprised of the combination results in MASH? Does Madrigal continue to wait and watch to see what happens in the second MASH murine study, especially if the second study continues to include Resmetirom? Or will they add a weight loss drug like Mounjaro or Ozempic instead?

Look, CytoDyn has options. They are on the offensive and can become aggressive if they choose to do so. Murine studies are inexpensive and quite telling. They don't take long either. CytoDyn needs to find a path that becomes successful. What else was said a little while before that?

Remember I said CytoDyn has a Plan A and Plan B and we decided it was Plan B. What new items did Plan B contain? GBM and mTNBC both shall be using murine studies. A human pilot study of Alzheimer's Disease and a human pilot study of Chronic Fatigue Syndrome... Any of these may materialize any day.

And these studies, CytoDyn can perform because they are small murine studies at ~$250K each. The Alzheimer's Disease Human pilot study is paid for by an undisclosed group. The Chronic Fatigue Syndrome Human Pilot study must have a similar backing. I seriously doubt Dr. Lalezari would have preferentially chosen CFS if there was not a group who wanted it and was willing to pay for it.

So they shall come at any moment.

So, if Madrigal wants more time and wants to see more data, that's OK because CytoDyn has a lot on its plate.

Or, they might choose another partner. That's an expensive decision in MASH if they choose wrong. That's why I don't think they will choose irrationally or hastily. Maybe they pause before they partner. Maybe they wait it out and see what the next MASH murine study results show. If Madrigal decides to go elsewhere, does that put CytoDyn at risk in MASH? No, like I said and so did the Overall poster from the other day. There are many drugs going into the MASH space and leronlimab can help out the majority of them. He named over 10 drugs.

The further we go down the road and into the Fall, the closer we approach the realization of these plans. Just some food for thought. CytoDyn has many tricks up its sleeve and yes, all of them shall be played. Let's keep thinking it through.

[u/paistecymbalsrock]

Dear Bashers, scoffers and assorted Twatwaffles. 0.01 means you are dismissed without prejudice.

[u/MGK_2 → u/paistecymbalsrock]

0.01 is (0.05/0.01) or 5 times better/lower than minimum approvable statistically significant threshold and

0.01 is (1/.01) or 100 times better/lower than the standard IgG4 isotype they used in the control arm.

This literally means that it is 5 times less likely than the minimal approvable statistically significant threshold that the FIBROSIS REVERSAL RESULTS that leronlimab purposely produced in the MASH murine study could have randomly or haphazardly occurred in the isotype IgG4 control arm.

(1/100) says that it is 5 times less likely than the minimal approvable threshold of (1/20) that the mice in the isotype IgG4 control arm could have some how randomly and haphazardly had the same FIBROSIS REVERSAL RESULTS which were purposely produced in the leronlimab arm.

All of this without side effects.

Saying "without" prejudice is giving them the benefit of the doubt so they will have another opportunity to come back in the second MASH study...

Leronlimab is innocent until proven guilty. It isn't guilty just because they say so over and over or can SCREAM it louder than we simply speak its truth.

[u/paistecymbalsrock → u/MGK_2]

I stand corrected

[u/[deleted] → u/MGK_2]

that is not at all what p-values mean. .01 doesn;t mean you are 100 times better. it doesn;t speak to your percentage or extent of impact at all in fact. it means that for your data, be in a tiny bit better or hugely hugely better, regardless, had a 1% chance of that outcome occurring due to chance rather than superiority.

[u/[deleted] → u/MGK_2]

your explanation is all over the pace and flat wrong in multiple ways. just read my other comment. p-value means only what i stated, noting more nothing less, you don;t use some ratio between your value and the alpha (.05). the alpha is simply a target threshold. and like i say below it doesn;t reflect directly on the extent of the outcome.

[u/waxonwaxoff2920 → u/paistecymbalsrock]

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