All right, hello, everyone. Thank you for joining us throughout the day here at the Lytham Partners Fall 2024 Investor Conference. Once again, my name is Robert Blum, Managing Partner of Lytham Partners, and during this webcast here, we welcome Cadrenal Therapeutics, ticker symbol of CVHD on the Nasdaq, and joining us today from the company, the Chief Medical Officer, Dr. Douglas Losordo. For this webcast, we're gonna do this a little bit more of a fireside chat presentation style. So, we'll dive into questions just in a moment here. Before we begin, though, I wanna just remind everyone that management is available for one-on-one meetings throughout the conference here.
If you've not already scheduled your one-on-one meeting and would like to do so, you can send me an email, that's Blum, B-L-U-M, @lythampartners.com, or you can visit the landing page for the conference. That's lythampartners.com/fall2024. From there, you can click on the investor registration button to make your one-on-one selection. So Doug, welcome, and thank you once again for your participation.
Thank you, Robert. It's a pleasure to be here.
Great. Let's start off. Maybe for those that are not you know sort of intimately familiar with Cadrenal, give us a little bit of background, and then, you know, let's really then dive into tecarfarin and sort of the why. So please proceed.
Sure. Great, that's a great place to start, Robert, and thank you. Well, you know, the story is actually relatively simple. Cadrenal is a company that was formed with one purpose, and that purpose is to bring a better blood thinner to the market. And specifically, the aim of the company is to advance a drug called tecarfarin, to put it in the hands of patients and doctors to replace a very old and very tough-to-use drug called warfarin. A lot of people know about warfarin. The story of warfarin is interesting in that it was a drug discovered in mold that was growing in hay that was being fed to cows, and the cows were bleeding to death.
And so that's how scientists at the University of Wisconsin discovered that there was a mold in the hay that was making this drug that prevented blood clotting. So it was an accidental discovery, and that drug came to the market in the nineteen fifties. Unbelievably, and unlike any other situation in medicine that I can think of, this is the only drug that does what warfarin does, that is, to thin the blood by inhibiting vitamin K-dependent clotting factors. One drug. Now, think about it. Think if there was only penicillin, one antibiotic. You know, what if there was only one statin, the original statin, Mevacor? You know, you can't think of any other situation in medicine where an important drug, an important pathway, is only addressed with one drug, but this is it.
And so this company was formed because tecarfarin was specifically designed to solve the problems of warfarin, and the problem of warfarin is its metabolism, which is very unstable, and it's unstable because of genetic variability, drug-drug interactions, and so forth. And so I can tell you, as a practicing cardiologist, I, there was only one drug I hated writing prescriptions for, and that was warfarin, because I knew that it was so fragile in terms of its metabolism, that a lot of bad things can happen, and they do happen. And so tecarfarin was designed to solve the problems of warfarin, and it's our mission to get it to the market. How was that?
I think that's good background. So let's talk about, you know, sort of. You've talked about the importance and sort of the design here. Let's talk about maybe some of the comparisons, you know, as you know, talk about what's been done in the past, tecarfarin versus warfarin.
Yeah, very important to go through this because if people, you know, start to do some research on tecarfarin, they're gonna see that there have been some clinical trials done and so forth, and here's where it's very important to understand the data extremely well. So tecarfarin versus warfarin, honestly, in my view, it's not a fair fight. Tecarfarin was tested in a clinical trial of over 600 patients, head-to-head, double-blind, and in spite of the fact that the deck was stacked against tecarfarin by virtue of this study design, when one looked directly at the data that was measured, the quality, if you will, of anticoagulation measured in that study, tecarfarin won by a statistically significant margin. So that's the headline.
Now, the backstory is that when that study was done, which is almost twenty years ago, the study design was set up, really, as I said, stacking the deck against tecarfarin so that the primary analysis, the one that was, you know, sort of reported in that, in that manuscript, indicated that while tecarfarin was numerically better, it wasn't statistically better. But that's a by-product of the fact that the statistical design, and actually the overall conduct of this study, almost made it impossible for tecarfarin to win. I can explain in a little bit more detail if you think I should.
Yeah, no, I yeah, please, 'cause I think this is an important part of the conversation-
Yeah
... please do.
So the study design was set up so that dosing of the drugs was controlled by, let's call it a central committee, a central dosing committee. Now, needless to say, that's not how things work in the clinic. Nevertheless, that was the design used in the study, and what that resulted in was a time in therapeutic range. So what's time in therapeutic range or TTR? That is, if you measure the INR, that's the measurement of blood thinning that you get from a vitamin K antagonist like tecarfarin. If you measure the INR 10 times, and it's in the target range seven times, then your TTR is 70%, which is 70% of the time you're right where you need to be.
Now, in the clinic, and you can look historically over fifty years of warfarin use, the average time in therapeutic range for warfarin runs around 40% or 50%. In the clinical study that I was just mentioning, it was running 70%. So right there, you know, you've created a study design that is the opposite of a real-world comparison. You're creating a false benefit for warfarin by dosing the patients by virtue of a remote committee that's looking over every single dose, versus what happens in a clinic that results in a much lower time in therapeutic range. And so now that's part one.
Part two is the statistical design contained a, I would call it, an anomaly, and that anomaly is that there was a method that resulted in the insertion of data points to fill in blanks where there was missing data. I don't really understand the rationale for that, but that method, called imputation, also contributed to the, I would say, falsely elevated performance of warfarin. In spite of the central planning committee approach, with dosing adjustment by a remote committee, in spite of that, when one looked only at the actually measured INR values to calculate the TTR, tecarfarin won by a statistically significant margin. So we know that the drug works better. That's why the company was formed.
And honestly, that's why we are so passionate about getting this drug in the hands of doctors and patients, because Warfarin is just such a hard drug to use, and the consequences of its difficulty are very severe events: bleeding, thrombosis, hemorrhage, hospitalizations, you name it. It is a minefield. And that was really most elegantly shown recently in a clinical trial in patients with left ventricular assist devices, LVADs, just published at the end of last year. Over 600 patients, randomized, double-blind, placebo-controlled, and what that study showed was that the time in therapeutic range, TTR, and bad events in LVAD patients was extremely powerful statistically. So if your TTR is low, your chance of having a hemorrhage is high, and the opposite is true.
Now, the problem that was revealed by that study was that even in places where LVADs are being implanted, so top medical centers in the country, the average TTR in that study was 56%, way below the target of 70%. When we saw that data and started speaking to the investigators that were involved in that program, we realized that this was absolutely the perfect opportunity to finally get tecarfarin on the market, because now we had very recent data showing the failure of warfarin and the consequences of the failure of warfarin in terms of a very high hemorrhage rate.
And so that's why we're actively pursuing this pathway, to get warfarin versus tecarfarin tested in LVAD patients, because to us, that's a very high probability of success, and finally get this drug onto the market where it can be used and prevent a lot of the bad things that happen as a result of, warfarin's challenges.
That, that's a nice segue, which is in August, so just, you know, a little over a month ago here now, you announced that you were in discussions with Abbott about sort of a planned pivotal study of tecarfarin in patients with recently implanted LVADs. Expand upon that announcement and, you know, and sort of why Abbott would be an ideal potential partner here?
Yeah. Yeah, so thanks for bringing that up, you know, and I, and I have to say that, you know, if you look around the landscape of companies that are doing things in medicine, drug device companies, there's a lot of great companies out there, no question about it. A lot of high-quality, motivated organizations that want to do good for patients, and I would put Abbott at the top of that list. And if you need evidence of that, take a look at the study that I just mentioned that they performed. It was a study, that six hundred-plus patient study. The whole purpose of that study was to see if aspirin was a benefit to patients who had an LVAD. Now, look, aspirin's a generic drug. Abbott doesn't control aspirin.
It's part of the standard of care for just about anybody with cardiovascular disease, but they asked a really important question, and why'd they ask it? Why did they spend millions of dollars to get that question answered? Because they want better outcomes for their patients, and they found out that aspirin actually doesn't help patients with LVADs. And so, a better vitamin K antagonist in patients with LVADs, Abbott immediately became interested and wanted to talk to us about what we're doing. And really, again, they're not, they're not really a pharmaceutical company, they're a device company, but they're in the business of making people better, and they're, they're in the business of making their patients, that is, the patients that get one of their LVADs better. They happen to be the world leader in LVADs.
In fact, the HeartMate 3, which is what their most recent device is called, is really the only LVAD being implanted in the United States right now, and it's the world leader. They're also the world leader in a lot of other medical devices, but as far as LVADs go, they've got the best device on the planet by a long shot. But, you know, they're not resting on their laurels. They want to see how they can improve outcomes. And I think they saw that the results of that study that I mentioned, in which they proved that aspirin wasn't needed, but they also provided evidence of how poorly warfarin serves those patients.
When they saw that data and realized there was no other option in terms of a vitamin K antagonist for the LVAD patients, and they heard that there was another option, that's where their interest came in. And so, yes, we're actively speaking to them about how we can work together to make this program a success and get our drug out there to serve these patients. Excuse me.
That, that's very helpful. In terms of... Let's talk about the market opportunity, maybe specifically surrounding LVADs. You just said Abbott is sort of the worldwide leader. I think you said almost, you know, exclusively, you know, the main player here in the United States. Talk a little bit about the market opportunity and how tecarfarin might fit in there.
You know, it's a really interesting point that you raise. You know, the LVAD market is relatively circumscribed. There are approximately, let's say, 14-15 thousand LVADs walking around the United States right now. It's about triple that number worldwide. And the rate of implants is actually going up, so that prevalent population will go up. But here's the really interesting point: If you look at all the things that warfarin is used for right now, many of them, including LVADs, and other indications, are so-called off-label indications. That is, they've never been tested or proven in a clinical study to work, but it's all that doctors had, and so that's what's used.
So when I think about the future of vitamin K antagonist, and I just, you know, put my doctor hat back on and think to myself, geez, you know, if somebody did a study, I was still practicing and writing warfarin prescriptions, and somebody did a study and found that there was another vitamin K antagonist out there that was better and safer than warfarin in LVADs, and I had a patient that came in that needed a vitamin K antagonist anticoagulant, what would I do? And, well, I can tell you what I would do. If I knew there was a better alternative out there that, you know, was a more stable drug, easier to control, et cetera, et cetera, that's what I would... You know, I would write the prescription for that drug.
Now, putting my drug developer hat back on, suffice it to say that LVAD is going to be, you know, our lead indication, but it's not gonna be our only indication. There are many things that we can and will pursue where Warfarin is still the only show in town, if you will. Once we displace it in one indication, it will become easier and easier to displace Warfarin and really finally retire that drug. That's the ultimate goal, is to get rid of that bad, terrible drug. Now, look, Warfarin played its place, don't get me wrong, but the time has come for it to really retire.
All right. That's helpful. Let's talk about the regulatory pathway. Phase 3 ready, orphan drug designation. There was an announcement here over the last month or so, talking about a Type B meeting that you're having with the FDA. I'm sure there are certain things that you're not able to share, but to the extent that you can provide a generalized understanding of, you know... Well, walk us through kind of what these-
Sure. Yeah, absolutely. Absolutely. So, a Type B meeting, for those who aren't familiar with the nomenclature, is a pivotal meeting with the FDA, where you're talking about a program that is at a critical juncture. And so in our case, that means the design and agreement with the agency on a design that, you know, if the study is successful and meets its endpoints, that you're ready to file an NDA. So that was the purpose of that meeting, was to reach an agreement with the agency on all the steps that we had to take that would get us to an NDA filing at the end of the study.
I've submitted, at this point in my career, too many meeting requests to even count, but I can tell you that, you know, you always get back some early comments from the agency, and the preliminary comments that we got back from the agency on this program were the most benign I've ever received in my entire career. So that was really nice because they agreed with us on the vast majority of things that we were talking about. And, you know, look, that's because they're familiar with the drug. It's been in large studies, they know the safety of the drug, and I think they kind of know that it needs to get out to the market, and so they've been, I can say, very collaborative over the years, not only with us, but with prior sponsors.
One area that they wanted more information was our approach to the primary endpoint, so we'll provide them some additional information, have a follow-up conversation, and then we'll be ready to finalize our protocol, and submit that, and get the study up and running.
Fantastic. We're sort of closing in on the hour here. Maybe just some final takeaways for investors to really pull away from this conversation, but just the opportunity in general, and again, this is an investor conference.
Sure! No, look, I mean, this is an easy conversation, too. So if you think about the advances in anticoagulation in the last couple of decades, you know, I'll just use Eliquis as an example. Eliquis is a great drug, don't get me wrong, but, you know, Eliquis and all the other drugs of that class were developed in-house at pharmaceutical companies. And so there was really no investor opportunity to take advantage of that new technology, right? It was all done... Now, sure, if you bought stock in Bristol Myers Squibb, you know, you made some money there, presumably, with the advent of these drugs, but not the kind of leverage that one would have as an investor when you're helping to bring forward a drug in a small company like Cadrenal, where that is the main purpose of the company.
If you know, if you kind of look at the company profile right now, and you think about the economics of what a new successful anticoagulant would be, you know, it to some investors, that leverage might seem like a big opportunity. Certainly, you know, for us, those of us that came into this company very early, we saw the opportunity to do something remarkable for patients that really was long overdue, that is, to bring this better blood thinner to the market and get rid of an old drug that, you know, really is past its heyday. You know, I think the stars are really aligned here with a good drug that we know a lot about.
We know it's better than what's out there, and now we found an indication that I think can very efficiently get us to a filing.
That's fantastic. Doug, we'll go ahead and leave it there. I'm always appreciative of the time that you give to us here and the knowledge that you sort of share with us and investors. Before we do wrap things up, I just want to again, once, remind everyone, if you'd like to schedule a one-on-one meeting with management, either throughout the conference here or even afterwards, you can send me an email. That's Blum, B-L-U-M, @lythampartners.com, or again, visit the landing page for the conference website, Lytham Partners-