All right. Hello, everyone, and welcome back. For the next Fireside Chat webcast, we welcome Cadrenal Therapeutics, who trades under the ticker CVKD on the Nasdaq, and joining us today from the company is their Chief Executive Officer, Quang Pham. Quang, welcome.
Robert, thank you. And Happy New Year. And thank you to Lytham Partners for having us back to kick off the year.
Absolutely. Thanks so much for your participation. Let's dive right in. I want to start off with sort of, you know, how you came to Cadrenal. It's, I think, a fascinating story and one that I think really drives your why.
I think, looking back, you know, I had a stint in the Marines after college. And my first job in the pharmaceutical industry actually was to sell Prilosec, a blockbuster, as you know. But the other drug that I don't talk about a lot, but I reflect back now that taught me a lot about cardiology and cardiovascular spaces is called Plendil, a calcium channel blocker. So I did begin my pharmaceutical career promoting a cardiovascular drug, an antihypertensive drug. Fast forward, I've been an entrepreneur since 2000 with venture-backed pharma space, pharma marketing. But in 2000, my late father passed away from a stroke. And he was at that time on Coumadin. And so that always stuck in the back of my mind as I came across tecarfarin a number of years later and that I learned it was also a vitamin K antagonist.
And it kind of intrigued me that in this modern day, we have great new inventions, great new drugs such as Eliquis and Xarelto. But that, you know, despite all of these years, warfarin, Coumadin, now generic warfarin, is still being used. So I was fascinated by tecarfarin, the potential that it had, and began working on it in 2017. And so now it's going on eight years now working on tecarfarin because I believe in it. I believe in that, you know, patients who are dependent on warfarin that can't take Eliquis and Xarelto deserve the industry to investigate and find a way to bring a new drug that could displace warfarin, which was once deemed the most dangerous drug in America due to numerous interactions and variability.
So my sole mission and our teams and our investor has been to focus on tecarfarin to get it into patients in 2025 with the lead identification of a rare condition, advanced heart failure patients who are on the left ventricular assist device, also known as LVADs. And at this point in time, the only LVAD, it's a good one. The only LVAD available in the United States is the one made by Abbott HeartMate 3. So it's a journey going on a decade. And I think we're making great progress. I'll take, you know, another minute here to talk about the market conditions. I think going on two or three years now, we hear every year the market is tough for biotech companies, biopharma, for cardiovascular. I don't care about the conditions because the patients don't care about the conditions. They have no control over it.
We have no control of it. We just keep going forward, and we have been able to find the right investors, the right partners, and the right management team to keep tecarfarin going forward with the orphan drug designation a year ago this spring and our conversations with Abbott, the world leader in the LVAD market.
I think that's well said, and again, a fascinating background that sort of brought you to Cadrenal here. Yeah, I want to come back to the broader sort of anticoagulation therapies out there. Most folks probably have family members that are on drugs, and you mentioned, I think, a couple of maybe Eliquis, Xarelto. You know, these are multi-billion dollar drugs in the anticoagulation space here, but talk about why tecarfarin plays such a potentially pivotal role in this broader anticoagulation landscape.
I know you bet, Robert. A lot of people are on drugs. I think, like you say, a lot of people are on medication because cardiovascular disease remains the world's number one killer, a very elusive killer that's been kind of ignored. It's a chronic, kills the most people in the world, including the United States. It's the most under-invested category. It's the largest and most under-invested category. You do have drugs like Eliquis and Xarelto, and they're used to treat the large anticoagulation categories like atrial fibrillation, venous thrombosis. What we found out, and the research has found out, is that that's great.
But those with the rare cardiovascular conditions. And I'll start with the first one that we received from the FDA, which was end-stage kidney disease with AFib, atrial fibrillation. And that the drugs that I mentioned, they're called direct oral anticoagulants, DOACs, the Factor Xa inhibitors. They're not being used there. They haven't worked in these rare cardiovascular conditions. And so we went out and got the orphan drug designation for ESKD plus AFib. Then we saw that LVAD patients through a member on our advisory board suggested that we look at that. So when we look at the LVAD space, we see advanced heart failure patients. The drugs such as the DOACs have been tried, and they were unsuccessful. And that warfarin is being used, and it's not even on label. There is no alternative medication.
I think in this modern age, when you see dozens of drugs in antihypertension, you see dozens of drugs in anti-diabetes, you have hundreds of drugs in oncology, and you have no approved drug for LVAD patients for anticoagulation. We saw as a great opportunity. I think looking at the data from tecarfarin, and I think the data will show that it is a very effective vitamin K antagonist. The metabolism is different than warfarin. It bypasses the P450. The most important difference that we saw was that it produced better anticoagulation and that chronic kidney disease and chronic kidney impairment did not affect the metabolism of tecarfarin as it did in warfarin in one of our head-to-head trials. Why that's important, Robert, is that most advanced heart failure patients have chronic kidney disease.
And so we believe that tecarfarin could potentially be successful and very important for LVAD patients in that providing effective anticoagulation, less side effects, and that those with kidney impairment could also benefit. And so I think those three give us great confidence in our discussions with Abbott and our discussions with our investigators, our discussions with the LVAD thought leaders, and with the FDA.
You know, I think there's been a lot of new findings, right, sort of published this last year in peer-reviewed journals, independent of anything Cadrenal was really working on, right, that discussed a number of different data points. But one in particular was sort of this time in therapeutic range or TTR and sort of the management of quality and the LVAD patient clinical outcomes. You know, what did this study highlight? And maybe you can discuss the co-author of the study, Dr. Mandeep Mehra's role in the industry.
Dr. Mandeep Mehra is, in my opinion, the foremost expert in the LVAD space as well as anticoagulation for LVAD patients. He led a study called the ARES study, which completed about 18 months ago, and it's been published in peer-reviewed journals to show that patients no longer need aspirin, the removal of aspirin from the anticoagulation regimen of warfarin and aspirin. That was tremendous for LVAD patients. But also that sub-analyses of the ARES study have shown and will be published that the higher time spent in the time in therapeutic range for these patients led to less bleeding, less bleeding for these LVAD patients, meaning less trips and less complications. They are very sick already, multiple concomitant diseases, advanced heart failure, getting an LVAD implanted. Now they have to deal with such risks as lower time in therapeutic range and bleeding from using warfarin.
And I think removing the aspirin was a major milestone for the space. And so Dr. Mehra has been very helpful in helping us look at that data, but also guiding us along, you know, with our team on how to come up with this LVAD protocol. And I think we have publicly stated that we had a meeting with the FDA and continue to be in dialogue to finalize the protocol so that we can begin a study in 2025. I think at the higher level, important groups such as the Anticoagulation Forum have talked about the importance of monitoring. And I think the public may or may not know that in 2010, the beginning of the new Factor X Inhibitors, starting with Pradaxa, came to the market.
And then there were no longer requirements for testing of the International Normalized Ratio, the INR, basically the standard globally for 60 years before that to measure the effectiveness of warfarin and the anticoagulation. So overnight, no more testing required for this new class of drug. As a result, they are now one of the top groups of drugs that lead patients to go to the ER from bleeding. And so when you don't have monitoring, certainly it's more convenient for providers. Certainly it's more convenient for the patients and their caretakers.
But the oversight is that nobody knows the effectiveness of anticoagulation until there's a bleeding. When they're over-anticoagulated, there's no adjustment, and then they end up in the ER. So I think those are the consequences of non-monitoring. So I think with tecarfarin, there will be monitoring. But it's important. You want to monitor these patients who are very sick to make sure they're properly anticoagulated.
All right. Let's thank you for that. Let's dive into LVADs a little bit more detail here, help viewers understand sort of the broader landscape. You've mentioned Abbott on a number of occasions, you know, but who are some of the other sort of the key players in this market on the device side in particular?
I think everybody knows that the HeartMate 3 is a very good LVAD. It's the world leader, and it's the only LVAD available in the United States. And that's the, you know, that's the territory, the market that we're focused on in doing the trial and getting tecarfarin approved here with the lead indication. There are trials underway with a number of smaller private and public companies investigating different types of LVADs, smaller, more effective, different pumps. But, you know, as far as Cadrenal and tecarfarin, the trial will be in newly implanted patients with LVADs. And as I mentioned it twice already, it will be patients only implanted with the HeartMate 3 because none of the other LVADs are expected to be reviewed or approved in the next three to five years, if not longer.
Let's talk maybe a little bit more about sort of that relationship that you have here with Abbott.
Yeah, let me, sure. I think I forgot to mention also is that there will be need for anticoagulation with the vitamin K antagonist. But if there's a desire to have tecarfarin in the regimen of those future LVADs, should they be approved, is that a trial will be necessary for the compatibility, the hemodynamic compatibility of the new LVADs with tecarfarin.
All right, so it sounds like a pretty close relationship there going on with Abbott. I'm sure something that, you know, everyone is paying attention to here. You know, just, you know, given timing here, let's sort of move on beyond LVADs. You mentioned a little bit earlier there end-stage kidney disease with AFib. Talk about some of the other rare cardiovascular conditions and how Tecarfarin addresses some of these unmet needs.
Yeah, so there in the last 24 months, there have been a number of articles in peer-reviewed journals highlighting the whole oral anticoagulation space, you know, starting with the only one available until 2010, warfarin. Brand name was Coumadin until it ran off patent, which was promoted by Bristol Myers Squibb, who then rolled out apixaban, which is Eliquis, which was the number three DOAC or Factor Xa inhibitor after Xarelto, rivaroxaban, and then edoxaban. So basically came out by Daiichi Sankyo. So when the journals looked back, there seemed to be a gap in four areas of where the DOACs are being used and warfarin's being used either because of necessity or just purely off-label. In the case of the LVAD, that was one area that was identified.
Another huge area where there's no innovation are the mechanical heart valve patients, of which there are over 500,000 in the United States alone that are chronically dependent on warfarin post-implant. The Factor Xa have been tried, and they just simply don't work in those patients, and trials have been terminated early. I think beyond the LVADs and mechanical heart valves, other areas of either rare cardiovascular condition. Let me just be clear, the mechanical heart valves is not considered a rare cardiovascular condition. The other areas where warfarin's being used by necessity or there's no alternative are rheumatic heart disease with AFib, as well as APS, autoimmune condition where the antibodies are overproduced and there's a risk for clotting. Those are the four areas of unmet need in anticoagulation.
There's been a lot in the news, in the journals about the Factor XIs, and there are a number of them that are in the phase III, which should be reading out here over the next 24 to 36 months. But there are a number of them in there anywhere from small molecules, from big pharma to smaller mid-sized pharma to private companies, and also antibodies. And dosing goes anywhere from daily to weekly to monthly. And so those, I think in general, that's the whole anticoagulation, oral and by injection.
You know, I guess as we sort of look to 2025 here, you know, you've talked about a phase III pivotal trial with LVAD patients. In terms of sort of the, we'll call it the operational readiness activities, supply chain, et cetera, where does everything sit on that side of the equation?
Yeah, you know, we are pushing forward, making a lot of progress with the drug product on the CMC manufacturing side. We will have the drug ready this year. Obviously, the conversation with the FDA continues, and we hope to finalize the protocol. And, you know, our top priority is to enroll and dose a patient in 2025. We remain singularly focused on that.
And as you know, as I said before, despite the difficulties of the financial markets, you know, patients, they still need the drug. They still need, you know, not just our drug, but in other rare cardiovascular conditions and other rare diseases around the world, and especially here in the United States. We, on the manufacturing side, on the IND sponsoring side, we have to just keep going despite whatever headwinds, whatever experts say. I think we've proven that over the last few months with our advances in the regulatory category with tecarfarin, but also in the financial sector with our fundraising.
You know, I think something that we haven't hit on yet, but I think it's important for everyone that may not be familiar is the orphan drug designation. I think it was in April of this last year that you received orphan drug designation for patients with LVADs. Maybe just talk about what that means and also sort of the ODD and fast track for ESKD and AFib.
Yeah, so I think one thing about government oversight, and I think the U.S. Congress and a number of patient groups and providers, I think over 30 years ago, Congress passed the Orphan Drug Act, and in summary, you know, I think when we look at business and big companies and big pharma and big categories and billion-dollar blockbusters, well, the Orphan Drug Act was designed to incentivize and encourage small companies and large companies, but, you know, smart companies like tecarfarin, like Cadrenal when we were private and when we became public to pursue pharmaceutical therapies to treat patients in rare diseases that affect less than 200,000 patients in the U.S., and in return, once approved, the drug and the sponsor will get seven years of exclusivity in the United States and 10 years in the EU.
Also, some other advantages, the waiver of the PDUFA fee and other, you know, incentives. But I think it's important for the rare disease patients to know that, you know, Congress did act, the industry did act, I think did act. And I think it's our job as manufacturers to continue to pursue these, you know, smaller patient populations to make sure that they're not ignored, they're not, you know, being overlooked, they're not given a 70-year-old drug like warfarin that began its life as a rat poison.
Let's look to 2025. I think we've hit on most of the key, but maybe help kind of summarize some of the key milestones that people should expect from Cadrenal here.
Well, I think, you know, anytime you begin a year, the planning has been done. It comes down to execution. And I think number one is solidifying and getting the protocol agreed upon with the agency. You know, number two is also getting the operational support, as you mentioned, in place, procedures, SOP, the manufacturing has to be in place. And I think also last but not least, the financial backing to lead to a, you know, beginning and execution of a successful trial. Those four pillars.
Excellent. Well, look, thank you so much, Quang, for the time here today. Greatly appreciate it. I want to remind everyone that if you'd like to coordinate a meeting and I can be helpful, certainly want to do that. You can send me an email, Blum, B-L-U-M, at lythampartners.com or reach out to the company here as well directly. Quang, again, thank you so much for your time today.
Thank you, Robert. Thank you to Lytham Partners, and thank you to all of our investors to date, and feel free to reach out to myself or our CFO, Matthew Szot, via our website.
Fantastic. Well, thanks so much again. We have a few more presentations and fireside chats coming up next, so please don't go anywhere. Thank you all very much.