Conference Transcript - CVKD 2025-09-30

Robert Bloom, Analyst — Managing Partner, Lithium Partners

All right. Hello, everyone. Thank you so much for joining us throughout the day here at the Lithium Partners Fall 2025 Investor Conference. Again, my name is Robert Bloom, Managing Partner here at Lithium Partners. Coming up next here, we have a presentation from Kadrenal Therapeutics, company trades under the ticker symbol CVKD on the NASDAQ. And presenting from the company is the Chief Medical Officer, Terry Ferguson. Terry, thanks so much for your participation in today's conference here. The floor is all yours.

Terry Ferguson, Other

Well, thank you, Robert. As Robert mentioned, I'm Terry Ferguson. I'm the chief medical officer at Cadrenal Therapeutics. At Cadrenal, we're focused on developing novel drugs to bridge gaps in anticoagulation. Anticoagulants are blood thinners to prevent heart attacks, strokes, and deaths for patients with a variety of cardiovascular conditions. Heart attacks and strokes are far and away the leading cause of death worldwide, and heart disease alone accounts for about one out of five deaths in the U.S. every year. Today, what I'm going to do is to first provide an overview of the company, second to give an update of our lead candidate to Carferin, a next-generation vitamin K antagonist for chronic use, and finally to highlight a recent exciting acquisition for Nexion, an IV factor 11a inhibitor for the acute care setting. This talk does include forward-looking statements, which should be considered with all appropriate caution. The oral anticoagulation market encompasses about $38 billion globally. The U.S. makes up about $20 billion of that. At Kadrenal, our primary focus is a segment of that market, specifically orphan and high-risk indications, which in the U.S. is about a $2 billion market. We're not going after venous thromboembolism and the broader world of atrial fibrillation. Those are both currently dominated by the DOACs, the direct oral anticoagulants. Three areas in particular are worth noting, areas where the DOACs have not really penetrated or where vitamin K antagonists like warfarin remain the standard of care. Those are ESKD, end-stage kidney disease, and atrial fibrillation, for which there is no clinically proven oral anticoagulant, left ventricular assist devices, which there is also no FDA-approved oral anticoagulant, and mechanical heart valves. Ticarfarin, our next-generation vitamin K antagonist, has orphan drug and or fast-track designation, and two out of three of these for ESKD, AFib, and left ventricular assist devices. Add to this the acute care setting that I'll be talking about in a bit for Fronexian, and you have a substantial potential market opportunity. The overall purpose of anticoagulant therapy in the first place is to prevent clot formation. These are commonly referred to as blood thinners. The clot-related things that you're trying to prevent are bad things like heart attacks, strokes, pulmonary embolism, vascular occlusion, all of which can result in death. When you give blood thinners, there's a therapeutic range, a sweet spot, if you will. Too little, and you don't prevent those clots or at higher risk for all those bad things. Too much, and you create a situation with a much higher risk of bleeding, which itself creates a whole other set of problems. Thus, there are serious consequences to poor control, and the higher the risk the patient, the worse those consequences are. The gaps that we're addressing at cadrenal are exactly those high-risk situations where current therapy does not give you good enough control. How long should a dog's legs be? Long enough to reach the ground. How much is enough anticoagulant therapy? Enough to prevent clots without excessive risk of bleeding. The areas that we are focusing on are exactly those areas where current therapies may not be good enough to give you the precise control that's necessary. Our lead compound is tacarfrin, a novel vitamin K antagonist like warfarin, but with an important difference. Unlike warfarin, tacarfrin is not metabolized by the hepatic cytochrome P450 system. What this means is more predictable drug levels and a much lower chance of the sort of drug-drug interactions that plague warfarin. Moreover, as I'll show in a second, tacarfrin levels, unlike warfarin, are not affected by poor kidney function. The result is an opportunity to address gaps in chronic vitamin K antagonist therapy in areas where the DOACs are ineffective or completely unproven. Also, Frenexion, a very recent acquisition, is a potent fast-on, fast-off small molecule factor XIa antagonist. It's differentiated from all the other factor XIa's in development because it's given intravenously and is the only one being developed for acute care applications. This is an overview of our current development pipeline. Ticarfarin has already been studied in 11 clinical trials with over 1,000 patients treated. Our lead indication is ESKD and atrial fibrillation. We already have orphan drug designation from the FDA, that means seven years of exclusivity following approval, along with fast-track designation for ESKD and AFib. Tocarfrin, in this circumstance, is phase 2-3 ready. We have drug product manufactured and available. And there is an additional phase 2 study planned in dialysis patients that I'll be discussing in just a few minutes. Ticarphorin also has orphan drug designation for patients with implanted left ventricular assist devices, another high-risk population, and we have an ongoing collaboration with Abbott, the maker of the HeartMate-3, the only commercial left ventricular assist device in use. Fronexion, which we recently acquired is a little earlier on in its development, but still has two completed phase one studies in humans. The current ultimate target indication for frunexion is for complex cardiac surgery, yet another circumstance where precise control of anticoagulation is absolutely necessary. Let me dive a little deeper into the tocarferin program. The largest study with tocarferin is the EMBRACE-AC study. EMBRACE-AC compared to carfarin to warfarin in a more general population of 607 patients with indications for anticoagulant therapy. An important caveat in this study was that this was intensively managed warfarin with INR measurements every week and dose adjustments guided by a central committee rather than at the site. The primary endpoint was the quality of coagulation control, expressed as the time in therapeutic range, TTR for short, for that particular patient. Overall, tacharfarine was every bit as good as and numerically better than intensively managed warfarin, with no thrombotic events and a very low incidence of bleeding. Importantly, in patients with abnormal warfarin metabolism and in patients taking drugs that interfered with warfarin, decarfarin appeared better. This highlighted opportunities to improve the reliability of warfarin, maybe not in the general population, but in circumstances where more precise control was needed, where warfarin could not perform optimally, precisely the sort of gaps we're targeting with decarfarin. Kidney disease is another area where anticoagulation management can be problematic, since many of the drugs used as anticoagulants are excreted via the kidney. This study compared warfarin and tacharferin levels in normal and in patients with stage 4 kidney disease, which is severe kidney dysfunction but not quite severe enough to need dialysis. As shown, warfarin levels expressed as either the area under the curve or the T1 half were substantially higher in patients with severe kidney disease, while in ticarphorin they were unaffected. And this highlights the need for a better form of therapy in patients with severe kidney disease. I'd mentioned a planned phase 2 study in dialysis patients. One of the biggest problems with anticoagulation in dialysis patients is making sure that the use of anticoagulants doesn't interfere with the regular dialysis sessions, and there's a very high risk of bleeding in dialysis patients. This study is designed as an open-label study in 25 to 30 patients with specific attention to patients starting on dialysis who already have indications for anticoagulant therapy, including atrial fibrillation. The overarching goal of this trial is to de-risk the subsequent registration study and ensure the safe use of anticoagulants in these patients and streamline the process of the trial to optimize coagulation management in the study and hopefully require fewer patients, less time and cost, and a higher probability of success. I'd point out that in current practice, not all dialysis patients for anticoagulant therapy are getting it because of their very high bleeding risk, and despite their much higher risk of heart attack, stroke, and death in patients initiating dialysis. Here we have an important therapeutic gap addressable by tocarferin. I'd like to spend a few minutes on the Frenexian program. There's been recent intense interest in the world of factor XI inhibitors. This is because factor XI plays a very unique role in clot formation. In hemostasis, which is your ability to form a clot in response to injury and minimize blood loss, factor XI plays a minor role. In contrast, for pathological clot formation, like a heart attack or a stroke, factor XI plays is a very fundamental role. Thus, the excitement about the factor XI inhibitors is that there is an opportunity to achieve sort of the holy grail of antithrombotic therapy, preventing pathological clot formation without increasing the risk of bleeding. As mentioned, there are a lot of factor XI inhibitors currently in development. Franexian, with its fast-on, fast-off pharmacokinetics, is the only one being developed for acute care indications. Those pharmacokinetic characteristics are ideally suited for exactly those kinds of application, acute care use in the hospital where precise control is needed on a minute-to-minute basis. All of the other factor 11s out there are intended for chronic use. Now, taking a step back and looking at our overall development plans and investment highlights for CADRENAL. These are our near-term clinical development timelines. As mentioned, our lead program is tacharfrin for end-stage kidney disease and plus atrial fibrillation. The phase two trial I mentioned is intended to de-risk the subsequent registration trial. The phase two study is scheduled to begin enrollment in the first part of 2026. the registration study will follow in 2027. I should point out that there's an additional LVAD phase 2 study targeted for later in 2026. Shifting gears and having recently acquired for Nexion, our primary goal for 2026 is to optimize the formulation with our ultimate clinical target of complex cardiac surgery. And as shown on the bottom, there are a number of key near-term milestones that will validate our progress towards these goals. In summary, both ticarfarin and fornexion target gaps in current antithrombotic care. Ticarfarin in chronic care, fornexion in acute care. Ticarfarin is the only vitamin K antagonist in late-stage development worldwide and meaningfully differentiated from warfarin by its metabolism. them. Fornexion, by virtue of its fast-on, fast-off pharmacokinetics, is the only small molecule factor XI inhibitor in development for acute care applications. Both of these have clearly identified paths forward in addressing substantial market opportunities. We have a very experienced leadership team and board, and it's been an honor to share this update on behalf of all of us at Cadrenal. We remain firmly committed to moving the needle and improving the standards of anticoagulation management. Thank you for your attention. Here's my contact information for our CEO, our CFO, and myself. Thank you, Robert. Let me turn it back to

Robert Bloom, Analyst — Managing Partner, Lithium Partners

you. Fantastic. Thank you so much, Terry, for the presentation. Thank you to everybody here for watching. If you do have any questions, as Terry just indicated, contact information is on the screen here uh for himself and members of the team similarly if i can be of assistance on the investor relations side either scheduling a meeting with the company or answering additional questions my email is bloom blum at lithiumpartners.com to learn more about lithium make sure to visit our website and stay connected with us as well as the company on linkedin on future events such as today's uh discussion here hope you have a great rest of the conference here thank you everyone thank you again terry thanks