Tenax Therapeutics, Inc. 12th Annual Cantor Fitzgerald Global Healthcare Conference

Okay, great. Thanks. Yeah, a little bit of a surprise. Half an hour before we talked to put what we view as the full analysis of the study out in front of the public. on August 10, we had been unblinded for a handful of days. We saw the result. We needed to get it out there. The information we shared brought up a lot of good questions, and so we aim to answer those now. The ESC late breaker, not quite 2 weeks ago now, answered a lot of questions, too. Really, it was just before that we received the full stat package. So, we're happy to get it out there and answer a lot of questions. Our view overall is that you can't run from it or avoid it.

The primary endpoint missed statistical significance, but there is an enormous amount of very clear information, and a lot of it is now with the public, that will help guide us to the right patients who respond with an improved Six-Minute Walk Test to levosimendan. There is also, in the data that people will see in much more detail than before, a clear indication that in this very complicated patient population who have volume overload on both sides of the heart, we have a drug that is active as a biventricular drug. The NT-proBNP decrease magnitude is so great that it sort of led us to say, "Why is it greater than PERSIST? Why is it greater than HELP?" And the answer is in the echo data, and basically the overloaded left ventricle that defines HFpEF and the overloaded right ventricle that needs to be targeted in any PH patient.

They are both putting out less NT-proBNP. That is our conclusion. The pulmonary artery pressure is coming down at a very impressive rate. And both of these things happen across the population. So what the full data reveal, of course, is still that patients who do not have much room to improve when they enter the study do not improve much. It also will answer a lot of questions about the safety of the population overall. A lot of misinterpretation was made because of the initial way that we broke that data down by quartiles, and I think the data today shows there is an improvement in every quartile among the patients on levosimendan. There is not some harm being done, and that word just does not apply to our trial.

What looks like a worsening to some is simply the placebo effect in the third and fourth quartiles and a reducing effect of levosimendan on those patients who, again, they just have less room to improve. But across those quartiles or frankly, any of the pre-specified populations, we see NT-proBNP coming down, and we see right ventricular systolic pressure or pulmonary artery pressure coming down in the population. So an ideal drug would address both sides of the heart, and it would provide some support to the right side of the heart. And we also see in the echo data that is out now, I think it is slide 18, that basically at a stat sig level, every parameter among I think 25 or 30 on that page is going the right direction and is not crossing the line of identity. Two of them are not stat sig.

The echo data also supports that the calcium sensitization mechanism of the drug is helping these patients. The NT-proBNP coming down so much is showing that cardiac wall stress, likely on both sides, is coming down. And we see the pulmonary pressure dropping at a level that would get a Group 1 drug approved. So that tells us that in the top-line review, we are right. We need to avoid patients who do not have much room to improve, but that is who we will enroll in LEVEL-2. When you see a result like that, you say, "What happened? The drug did not work," or, "The trial failed.

Yeah. The drug is working more effectively biologically than we thought it would. The primary endpoint missed because, and there are a couple of good slides to walk through here, a great number of patients who walk too far at baseline were enrolled in the trial. We did not, three-quarters of the way through enrollment, start getting nervous about this and say, "Wait a minute. We have got all these people walking 400 meters. Why are there so many 50 and 40-year-olds in our trial?" These were not concerns. Patients with a 10% improvement who walk 450 meters walk 45 meters further. What you see in our data is that those patients in that fourth quartile on placebo, they walk, I think, 15 meters further. It is not a huge improvement, but it is not really good for the primary endpoint.

That is what we learned from the trial, that we really did not appreciate the degree to which a patient's baseline health status would limit their improvement, as shown in the Six-Minute Walk Test. There have not been trials that instructed us that that would be the case above 400 meters. We also know that from HELP, the wedge pressure in patients with really high wedge pressure comes down a lot. Some of them walk a lot further when that happens. So we now know what we did not know during the enrollment, that those patients are simply not going to reveal treatment benefit. Their NT-proBNP comes down, their pressures come down. Their profile in terms of their safety, whether they are above or below the median, is the same.

And that is another thing that is in the data that we put out today that I think was a legitimate reaction to the quartile walk data. The question comes up, well, if you only treat half of that population a second time, are we going to see a lot more of the? And the analysis is there and the answer is no. Treatment emergent adverse events are basically the same across the group. That is very reassuring. We probably should talk about safety as soon as we open our mouths to talk about this study, but it is foremost, but it is very encouraging.

Right. Okay, let me comment on it as I go through, right? How do you reconcile, you missed on primary endpoint. You're really excited about these pre-specified endpoints that are biological. These are important endpoints. You see a big translation to walk, but you still missed, right? Let me jump forward. I have to put this up there. People remember the LS mean is the per SAP way of analyzing the primary endpoint. The mean data is there below it. It shows the treatment difference of 8 meters. And then this really is the raw data averaged for investors. What we showed on the 10th was the LS means. You basically see a theoretical result that adjusts for a lot of things with the LS means. The FDA is going to require an LS means.