The Zoom Q&A in-interface at the bottom of your screen. With that, Doug, I'll turn it over to you.
Thank you very much, Alex, and it's a pleasure to be here today. Thank you for the invitation. I'm pleased to be speaking about Cadrenal Therapeutics and our upcoming efforts to improve outcomes in patients with cardiovascular conditions who require chronic anticoagulation therapy. First, the usual forward-looking statements must be recognized. Cadrenal Therapeutics is a late-stage development company, which has already achieved multiple orphan drug and fast track designations for its chosen indications. We're developing a drug called tecarfarin, which is a novel oral reversible vitamin K antagonist anticoagulant to prevent heart attacks, strokes, and deaths due to blood clots in patients with certain cardiovascular conditions. Our lead indication is in patients with left ventricular assist devices or LVADs.
These patients are implanted with a heart pump because of severe heart failure, and available evidence shows that the currently available anticoagulant, warfarin, is not doing a sufficient job, so there's a significant unmet need for these very sick patients. Other indications in our pipeline include those with end-stage kidney disease and atrial fibrillation, for which we have an orphan drug designation and a fast track designation. And others that we're contemplating include patients with mechanical heart valves, with difficult-to-control anticoagulation due to certain genetic variants that they possess. Interestingly, tecarfarin is the only anticoagulant currently in development for patients with left ventricular assist devices. And in addition, the other rare cardiovascular conditions that we are pursuing are also unique to tecarfarin or our pursuit of developing our drug for these indications. How does tecarfarin compare to what's already out there on the market?
Well, the direct oral anticoagulants, such as Eliquis, have been shown to work in broad settings, like healthy patients with atrial fibrillation. But in the patients that we're interested in, those with cardiovascular conditions that require a left ventricular assist device, or patients with end-stage kidney disease, with atrial fibrillation, or those with mechanical heart valves, those indications are not being pursued by the direct oral anticoagulants, or DOACs, or they've been initially tested and have failed quickly. Why do we think tecarfarin is better? Well, unlike warfarin, the only currently available vitamin K antagonist or VKA, tecarfarin is metabolized through a different pathway, which is much different than the warfarin pathway.
In fact, tecarfarin was specifically designed to leverage a more abundant and more reliable metabolism pathway so that its metabolism would be stable, whereas warfarin's is notoriously unstable, resulting in very challenging levels of anticoagulation in terms of control. We see tecarfarin as a new weapon in our war against warfarin, which we see as one of the most dangerous drugs in America. Tecarfarin has an opportunity to fill a market void in a number of chronic anticoagulation conditions, and therefore improve the lives of patients and actually ease the work of the healthcare providers who are struggling to control anticoagulation with warfarin. What's the overall prospect for tecarfarin? Well, there's a high level of unmet need. No anticoagulation therapy is indicated for these patients with implanted cardiovascular devices, like left ventricular assist devices or mechanical heart valves or other rare CV conditions.
So we have a really unique opportunity to provide a first-ever FDA label indication for these important conditions and these patients suffering with this unmet need. The mechanism of action of tecarfarin is well known. Vitamin K antagonism has been shown to be valuable in a variety of settings. The problem is that the only available vitamin K antagonist right now is warfarin, which is very challenging to use because of its metabolic pathway. Warfarin was an accidentally discovered compound, whereas tecarfarin was a specifically designed compound, designed to retain the value of a vitamin K antagonist pathway, but to avoid the unstable metabolism that warfarin suffers under. We have extensive safety data from 11 clinical trials in over 1,000 patients that demonstrates that our drug is safe and has the promise of being more effective than warfarin in these various indications.
Because of the indications that we're pursuing, such as the left ventricular assist device, there are some interesting, unique business development opportunities, for us in terms of interacting with the manufacturers of the left ventricular assist devices. We've also been recognized by FDA as providing a potentially useful alternative to warfarin, and have been awarded orphan drug designations and fast track designations to enable us to accelerate our path to approval. Because of the above, we have a very interesting scenario where one might predict that the uptake of our drug as the first ever label indication for these conditions could be fairly rapid, and our pricing under orphan designation could be favorable.
We are advantaged by a management team that has extensive experience in drug development, and a board of directors that also is extremely experienced and has helped to guide the company in its initial phases in its first 18 months of existence. We're also benefited by a renowned scientific advisory board with really household names in the fields of cardiovascular drug development, nephrology, and anticoagulation. The problem we're seeking to solve is that certain cardiovascular conditions lack effective, proven anticoagulation. Warfarin is not approved for many of the rare cardiovascular conditions for which it is prescribed. It's prescribed off-label, and clinicians are hesitant to prescribe the DOACs and Eliquis more broadly, especially given the negative evidence in clinical trials that have been conducted.
Warfarin in the LVAD patient population has been shown to have a high frequency of hemorrhagic events, despite very careful monitoring at top-flight medical centers. The drug is just very hard to use in those patients. The unstable metabolism due to drug-drug interactions and genetic variability of the elimination pathway make it a challenging drug to control. In addition, patients with late stage heart failure have a significant prevalence of renal dysfunction, making warfarin even tougher to use. The same is true in the setting of end-stage kidney disease with atrial fibrillation. Those patients already have a high risk of bleeding due to dialysis, dialysis-induced platelet dysfunction, and the stability of warfarin in those patients has been shown to be very low, with time in therapeutic range below 50% in many clinical studies. Drug-drug interactions in these patients with multiple comorbidities are well known.
On the right side of this chart, the DOACs have been shown to have many challenges, including the cost and time of reversal in these sick patients with LVADs, LVAD patients being excluded from approval studies, and the DOACs, in fact, are not part of the guidelines for LVAD patients. Similarly, in the end-stage kidney disease population, there's limited head-to-head evidence, and what evidence there is, is not very promising for the DOACs. The LVADs are a increasing population, in the United States and around the world. The devices that are out there now, and in particular, the HeartMate 3, which is the leading device, has been shown to be far superior to previously used devices, and the use of the device is increasing as a result of its established efficacy.
A recent publication, however, highlighted the inadequacy of the currently available vitamin K antagonist, warfarin, for anticoagulation in LVAD patients. Time in therapeutic range is targeted at 70%. However, in this clinical study conducted at top medical centers around the country and around the world, was only able to achieve a time in therapeutic range of around 56%, well below the target. As you can see from this graphic, a low time in therapeutic range was associated with a significantly increased risk of major hemorrhagic events. So the inadequacy of warfarin, the only currently available vitamin K antagonist, translates into poor outcomes in LVAD patients, and our program intends to solve that problem by using a more reliable, more stable vitamin K antagonist. Indeed, tecarfarin was designed specifically to solve the warfarin metabolism problem....
The warfarin metabolism problem results from the fact that it is primarily metabolized by the cytochrome P450 pathway, which is fairly limited in expression, genetically variable, and highly used. Many drugs compete for this pathway, so many, many drug-drug interactions. In contrast, the metabolism pathway used by tecarfarin is the human carboxyl esterase 2 pathway, which is abundantly expressed, not used by many drugs, and although there is genetic variability, that genetic variability has never been shown to result in any clinically meaningful change in drug metabolism. Therefore, we believe that tecarfarin will result in a superior, stable level of anticoagulation, making patients safer and making the prescription of tecarfarin a much more straightforward situation for practitioners.
As I've mentioned, there are several indications that we are pursuing, which in aggregate, and these are not all the potential possibilities, but in aggregate, we think there's a very significant market to improve vitamin K antagonist-based anticoagulation with a significant market potential. Because of the prior work that's been done on tecarfarin, we are in the very interesting position of being able to pursue pivotal stage programs in multiple indications. Because of the safety database that already exists and the evidence for bioactivity and efficacy of this drug, we're able to design single pivotal studies for multiple indications, which will accelerate our path to approval. Financially, we have a very simple cap table. We have a significant insider ownership, meaning that our interests and those of investors are highly aligned.
We have no debt, and our operating expenses at the present time are very modest, as you can see here. To summarize, why Cadrenal now, in fact, why Tecarfarin now? Well, tecarfarin is targeted for indications where it is now clear from data that warfarin fails to achieve sufficiently stable anticoagulation. DOACs have not been shown to benefit. And so we're pursuing unmet needs where a vitamin K antagonist is required, but where the currently available vitamin K antagonist is not doing a sufficient job. Mechanism of action of tecarfarin is well-established, and its safety track record is also well-established.
We have some interesting business development opportunities because of the indications that we are pursuing, and we have regulatory pathways that we've started to leverage, that are available to us because of our desire to fill these unmet needs in specific orphan-sized populations. We think there's a very nice commercial market opportunity here because of our opportunistic strategy to fill unmet needs in these rare cardiovascular conditions. That's the end of the formal presentation, and I'll be happy to entertain any questions at this point.
Great, thank you very much for sharing this story with us. Maybe we could start things off with a couple of your recent announcements. You recently issued a release on data from the Abbott-sponsored clinical study. What did that data demonstrate, and, you know, what's the impact on the program overall?
Right, that's a very important point, so thanks for raising that, Alex. So Abbott sponsored a study, which was, you know, I would say, typical of Abbott, which seems to be a company that always tries to do the right thing and improve the lives of their patients. They sponsored a study to see if aspirin was really required for LVAD patients, and I'll fast-forward. That study showed not only is aspirin not advantageous, but actually may be harmful to LVAD patients. You know, as you probably know, aspirin is used widely in patients with cardiovascular disease, but in this particular case, thanks to this diligent work by Abbott, we learned that aspirin is not helpful.
But a side effect of that study actually was showing that even at the best medical centers around the country and around the world, watching over warfarin-based anticoagulation very diligently, the levels of anticoagulation, the quality of anticoagulation, was far from optimal. And associated with that, poor level of anticoagulation were bad outcomes for the patients. That is to say, patients suffered from an excess of hemorrhages because warfarin was not able to achieve a sufficiently stable level of anticoagulation. Please proceed.
Yeah, no, I, and I understand it firsthand. I have one family member who takes daily aspirin, and another one who's on warfarin. And I think you, you know, you've shown also in the slides that certainly, you know, safety improves, quality of life improves. Is this true generally for patients across the cardiovascular condition, or is it really only LVAD that you've been showing these outcomes?
That's a great, a great point. So as I mentioned, or I alluded to, the mechanism of vitamin K antagonism-based anticoagulation is very, very important. As the DOACs started to become available, there was a, maybe a sense that warfarin was just gonna go away, that vitamin K antagonist-based anticoagulation was gonna go away because the DOACs, you know, the Eliquis class of drugs, were so good, so easy to use. It turns out, however, that the mechanism of vitamin K antagonism for anticoagulation is very important for certain patients, LVADs being one example, but patients with mechanical heart valves, patients with end-stage renal disease, patients with certain, autoimmune diseases, such as antiphospholipid syndrome. All these patients are not benefited actually by the DOACs, and so the multiple pathway mechanism of anticoagulation that results from vitamin K antagonism is required.
The problem is that the only available drug to pursue that pathway of anticoagulation is a very hard-to-manage drug, not because of vitamin K antagonism, but because the metabolism of warfarin is so unreliable. And so a very clever medicinal chemist was really looking for drugs to improve and landed on warfarin as a drug that had, you know, so many Achilles' heels in terms of the molecular structure. He knew he could fix it, and he did. He fixed the vitamin K antagonist warfarin, maintained that beneficial pathway of anticoagulation, but was able to engineer a new metabolism pathway, so the anticoagulation pathway could be leveraged without the baggage of unstable metabolism, and that's tecarfarin.
Great context. Thank you very much. You know, also on the more recent side, I think you've announced some collaboration, discussions, or, you know, partnerships, and could you talk about, you know, what some of the next steps there are, and you know, how they kind of help with furthering the commercialization of the business?
Sure, absolutely. So, you know, we issued a press release that we've been in conversations with Abbott. Of course, Abbott is a great company, as I mentioned, that really always seems to me strives to do the right thing for its patients. They've developed an amazing left ventricular assist device. When they learned that we were trying to develop an anticoagulant to help those patients, we started a conversation with them to see if there was a way that we could work together, and that conversation has continued. You know, so I would just say at this point, we're in a very nice conversation with Abbott to see how we can work with each other to improve the lives of patients with LVADs. And we're very excited about that. Obviously, it's a great company, which we're very excited to work with.
Thank you. And so of the, the programs that you're targeting, the three programs, is there one that you consider, you know, the lead program? And, and if so, you know, could you help us understand that?
Sure. Well, the other LVAD program is the lead, and it's. I can explain that to you, I think pretty easily. We're advantaged in pursuing an improvement in anticoagulation in LVAD patients by this very recently completed study that's Abbott-sponsored, looking at the elimination of aspirin. But the great thing about that study is it was a large study of over 600 patients, looked very closely at the levels of anticoagulation. So it's very recent data that the most recent, and by far and away, the best heart pump, which shows the importance of the quality of anticoagulation yielded by the vitamin K antagonist. So the timing for us was irresistible, frankly, to see this data come out, to show how our drug, by yielding better quality anticoagulation, could help these patients.
It's easy to translate an improvement in the quality of anticoagulation yielded by the vitamin K antagonist and to reduce hemorrhage in these patients. So that made study design for us very straightforward. And so the design and execution of that study, especially, you know, having a recent study in that population has some practical implications in terms of speed of enrollment, site identification, and so forth, that really make it an irresistible target. Not to say that the other indications that I mentioned, end-stage kidney disease with AFib, heart valve patients, autoimmune diseases, all those things are important because the available vitamin K antagonist warfarin falls short in all of those indications. But the LVAD, I think, gives us some advantages from a practical standpoint of being able to execute a study most efficiently.
That's great. Thank you for sharing. And that sort of leads into my next question, which is, could you talk about, you know, some of the advanced preparations for your upcoming clinical trial? You know, what goes into making that successful? And you, I think, you've touched on a little bit, site selection, different things, but for folks, you know, newer to the process, would love to hear more.
Yeah, I'm glad you raised that because there's two sides to this coin. One is the site prep is really preparation for the study, but the other part of it, of course, is preparing for success. And that means, you know, you imagine, as we do, that our study is gonna show that tecarfarin is a better option for these patients. So then it's an educational aspect to this, of really being prepared for the community at large to understand the importance of the quality of anticoagulation that's yielded by the vitamin K antagonist, and to really prepare the world, if you will, the prescribing community, for the fact that there's gonna be a better option out there that will make their patients' lives better. So it's two aspects of it.
One is, you know, really being prepared to... I would, you know, people talk about first patient in a study. I always think about the last patient out of the study. That's the goal, right? Is to get that study completed and get the data as efficiently as you can. And then being prepared for the positive outcome and really get the community to understand, you know, what we in the company are very excited about because we know how the drug works. So, so we're very excited about the fact that we, with a successful study behind us, that we're gonna make people's lives better, the LVAD patients then and beyond, make their lives better, and actually make the prescribing community's life a lot easier because this more stable drug.
That makes sense. And so I guess at this point in the, you know, the upcoming clinical trial, the study planning process, do you have a sense of, you know, timelines for readouts and next steps, or is it a bit too premature at this point?
Yeah, I always hesitate to you know, define timelines at this stage. I will say that we're going to have a conversation with the FDA very soon to reach an agreement on our study design, and that will allow us to lay out the timelines very, very clearly, right? Once we know that we've reached agreement with the agency on sample size, endpoint timing, and so forth, then the rest is really relatively straightforward to lay out. So I probably have to you know, hold off. You know, I think we're probably thinking about a little over, from start to finish, a little over 2 years from first patient to data. But again, that's dependent on our agreement with the agency.
Great context. Thank you. And, you know, as we are coming up against time, maybe we could just end by summarizing, you know, for investors who might be looking across cardiovascular opportunities, you know, maybe what do you like most about Cadrenal and think, you know, is the best value proposition for the street right now?
Well, you know, the thing that attracted me to the company was the fact that, as a cardiologist, I wrote a lot of prescriptions for warfarin. It was one of the prescriptions I disliked writing the most because it was such a tough drug to use and to control. So when I looked at the data on tecarfarin, I thought to myself, really, I thought, "Why is this drug not in the toolkit of prescribers right now?" We're talking about very discrete indications
but I do think we're in a position to really do something important, which is to leverage this very important pathway for anticoagulation, that is vitamin K antagonism, with a much better and more straightforward drug to use. And that's just gonna mean better outcomes for patients, fewer adverse events for patients. So that's what we're excited about, is that broad impact of this drug, leveraging a good pathway and getting rid of a tough drug that is warfarin.
Makes sense. Well, thank you very much, Dr. Losordo. With that, we are at time, so I'd like to thank you for sharing this story, and also thank everybody listening for spending time with us today.
Thanks a lot, Alex. Appreciate it.
Take care.