Seeking Alpha hatchet job, page-118

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Invest31415

Yesterday, 8:49 AM

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Let’s just say several of your points are inaccurate. To name some:

(1) CHF primary endpoint: indeed was not reached (p value 0.4). I’m not sure you fully understand the meaning of statistical noise. Treating this 1.2 ratio (in a band of 0.8-1.7) as a clear indication that recurrent HF-MACE events occur significantly more in the treatment arm is just bad science. The p value simply tells you there was no significant effect. What you see as slight separation in the graph is measured on very few patients, and again, was not significant.

(2) Since you are so sure and knowing, could you please explain exactly what happens in slide 22 (the primary outcome slide)? What is exactly measured there? Can you trace it to how many HF-MACE events happened in each arm?

(3) Your mITT claims are simply one big wrong misunderstanding and mess. Really, the answer was in front of your eyes and you blindly missed it. The trial started with 565 patients. I’m guessing not 566, since at the end that was the exact number. Now… in the VERY SAME slide you have shown it says clearly: “28 randomized but not treated”. Do you understand this?? Let me explain: it means that for some reason not related to the trial but to the clinical decision of the physician deciding for the patient, the treatment was not given, not the real one and not the sham one. Why? Maybe physician decided it is too risky to inject directly to their hearts. Hence , these patients CAN NOT be part of the statistics. Clear now? I will leave you with the drill of subtracting 28 from 565.

(4) The secondary analysis and additional analysis : I agree some of those were not specifically stated such as the 3 point MACE and also the average no. of ischemic admissions per patient year. Some were stated: mortality, and MI or Stroke. The general point here is to first see what the data says. Some numbers were astonishing in their p values and strength. 60% reductions in MI & Stroke events and related admissions in both class II and III, and 60% reduction in CV death for stage II. I don’t think they have seen an increase in deaths in stage III patients as you speculate. Had it been something like that, they would have had to report it. I simply think it was not statistically significant simply due to need of larger numbers for stage III (as the effect is smaller there). Now… can you please show me ANY CHF trial you know of in the last 20 years that reduced MI & Strokes by 60% (the p value is very high for this effect)?? A single shot?? Reducing 60%?? Any CHF trial you know that reduced CV death by 60% (for stage II patients)?? A single example?? You know what, find me one that does it with just 30%. I’ll be waiting here for an answer. So presenting this as “failed” is really …I would say … weird.

(5) Will the FDA approve CHF with this trial?? I also find it unlikely, knowing the FDA. However, if there’s a case to “Bend the rules” it’s this one. Very significant results, with clear clinical benefit, touching the crown jewels of MI, Stroke and CV deaths with astonishing 60% reductions. Will the FDA decide to wait say 4-5 years for this to happen? Or will it allow something while forcing strict confirmatory in parallel? Or will it allow a confirmatory and accelerated approval upon initial interim (much before trial ends)? I’m not as sure as you are about it. Also, what about Japan? What about China?

(6) Partner: the CHF results are screaming for a partner. By now it is KNOWN this works. It may need more confirmation for FDA, but it works. This is a goldmine waiting for the CHF big pharmas (in particular I think Novartis and Astra). I have seen mega deals done on much less than this promise. You are betting against THAT??? Well… again… I think a questionable decision.

(7) I still think there are many hidden gems in the CHF trial to be revealed with the full analysis of the trial. Let’s see it all. Exact breakdown to all types of admissions, their lengths, severity, let’s see the full LV echo data, let’s see the biomarkers data. Since we have seen a huge effect on ischemic MACE I expect more numbers to show improvements. Let’s wait and see. In this casino of what else is there in the trial data that can surprise us, I’m not sure the bets are that there’s nothing there. For example, my bet (Against yours): we will see significant numbers in the LV echo data (because that was shown very nicely in the phase 2).

(8) ARDS:

the trial was stopped. It was not because there was no signal at all… It was since the trial seemed to not be able to reach a strong enough p value for the signal. We know there’s some trend at least, since we know the trial passed the previous DSMB check. So… the story is that since mortality rates and ICU protocols were changed so much in the last months for ARDS, that the trial was not powered correctly. However – What happened here? A year ago did anyone dream of ARDS?? No… So MESO got a big phase 2 trial (let’s call it phase 2, cause that’s what it will be used for) for almost free, for a new indication. Collecting extremely valuable information. Gaining a huge potential partner along the road (Novartis). You call that a failure?... I wonder. What if in the analysis on the whole patients there are clear positive signals? Say shorter admissions, better survival at longer than 30 days, shorter time to extubation, etc? Are you positively sure this won’t happen, BEFORE you have seen the data analyzed?? And knowing there are simply 2-3 months to wait for some initial analysis?? Are you sure there will be NOTHING there to make Novartis take the deal? Conduct a phase 3 ARDS trial? And pay milestone money? I guess I am less decisive about that.

(9) GvHD: Again, are you sure the appeal process is doomed?... When Jakafi, the current SoC has such terrible side effects and shows less efficacy? And … was approved based on a single arm trial on 50 patients? … And the 9-1 ODAC?? You really are 100% positive there’s no chance for the appeal?? I guess I have my doubts compared with you.

(10) CLBP: So you estimate it is a complete failure, only since the results were delayed. It could be the case, but really nice signals in the phase 2 trials, a year with covid and delays everywhere… I’m waiting for the results, then I’ll decide about it. It’s really a 50/50 call right now. Delays may pull you to one side, and the past trials pull to the other. You do realize that anything in this trial that makes Grunenthal conduct a phase 3 in the EU means milestone money, right??

So to summarize: I think you were completely mistaken in some of your points, and completely one sided on the others. The truth here, is that there are many hints for strong signals in several indications. Yes, things will be slower than expected, and overall MESO will have to compromise for deals on projects once thought to be projects to be fully owned. To me, MESO took a hit from an AMGN behemoth potential of say ~100B$ valuations (if all went clear cut) to much lower valuations. Hard to estimate now, but let’s say ~10B$. (both estimations for long term, several years). So it took a giant hit in potential, but still … so much of it still with us…

GLTA