All right. Hello, everyone. Welcome back. Up next here, we have the Cadrenal Therapeutics fireside chat. Again, my name is Robert Blum, Managing Partner at Lytham Partners , and today I'll be moderating a Q&A discussion with Quang Pham, Cadrenal's Chairman and CEO, and Matt Boxer, the Co-Founder of Veralox and the VLX-1005, as well as acting Chief Scientific Officer of Cadrenal. As a reminder, Cadrenal trades under the ticker symbol CVKD on the Nasdaq. First off, Quang, Matt, thanks so much for joining us today.
Thank you, Robert, and Lytham Partners for hosting the fireside chat once again this year, the start of 2026.
Fantastic. Well, let's get started here. Quang, I'm going to start off with you. You know, again, for those not familiar with Cadrenal, provide a high-level overview of how Cadrenal is positioning itself around sort of "bridging critical gaps in anticoagulation for rare and high-risk patients," and maybe provide briefly an overview of the three distinct programs you have.
Yeah, I'm glad to do that, Robert. Yeah, Cadrenal, we are focusing on those areas, like you said, in anticoagulation where the prevalent or the big DOACs, direct oral anticoagulants like Eliquis and Xarelto, have entered the market about 15 years ago. Before that, the warfarin, the vitamin K antagonist, has been around since the mid-1950s. So what has happened since the DOACs have entered the market is they've taken over the large thrombosis indications, venous thrombosis, pulmonary embolism, and so forth. Where the gaps are is where kidney-impaired patients, like those with end-stage renal disease and atrial fibrillations, that's where our lead program in phase 3, Tecarfarin, has orphan drug designations for end-stage renal plus AFib, as well as for patients with implanted left ventricular assist device. So now you have 70 years since warfarin was introduced.
It's still being used in areas where the DOACs are either contraindicated or not used, and those primarily are those with implanted medical devices like mechanical heart valves and LVADs, so that's one area we're focused on with our Lead program. We also just acquired VLX-1005 from Matt's company, Veralox, where he was the Co-Founder, and we're very excited about that. The program just completed a phase two, and so we are looking at the data set and preparing to interact with the FDA, and that indicates for HIT, heparin-induced thrombocytopenia, and so we're very excited about that program, and then later in 2025, in the fall, we acquired a phase two candidate called Fruinexian, and that's a short-acting factor XI for cardiovascular surgery and kind of fast on, fast off.
And so in summary, where we are filling the gaps are the old warfarin drugs being used off and on label in mechanical heart valves, LVADs, and other uses. We're looking at gaps in kidney-impaired patients with AFib. We're looking at HIT, which VLX-1005 has Orphan and Fast Track, and with Fruinexian in this short-acting Factor XI. Just a quick note about the Factor XI, a lot of exciting news has come out. We're still waiting for the first Factor XI to be approved, and as the DOACs enter into the generic phase here in the next few years, one big news did come out just before the holidays was that Andexxa, the reversal agent, as you know, most of these anticoagulants or blood thinners should have, or like warfarin and Tecarfarin, have reversibility, but Andexxa, the reversal agent for DOACs, has been pulled from the market.
Healthcare providers have expressed concern about that lack of reversibility. That's where the general anticoagulation market, that's where Cadrenal fits in with our three programs.
Fantastic. Matt, with your participation here today, you know I really want to maybe spend the bulk of our time discussing VLX-1005. And maybe first off, Matt, provide us with a brief overview of your background for those that may not be familiar.
Sure. Thanks, Robert. So I'm a chemist by training, so I received a PhD from the University of Chicago, NIH Postdoctoral Fellowship, where I was a medicinal chemistry group leader working in early-stage drug discovery for almost a decade. And during that time, I became really excited about the opportunity to develop drugs into and through the clinic. And I thought the best opportunity would be to form a company. And so I co-founded Veralox Therapeutics. After co-founding, we raised venture capital with some great investors and took the asset VLX-1005 all the way through IND filing phase one and phase two clinical trials. Now I'm really excited that this asset is in the hands of some great and experienced drug developers here at Cadrenal and excited to join the team and continue its development.
All right. Very good. So Matt, you've built VLX-1005 around 12-LOX . Can you take us back to sort of the origin of that insight? How did you and your team come to focus on 12-LOX and what convinced you that immune-mediated platelet activation was the right place to intervene rather than downstream clot formation?
Yeah, sure. Sure. So while I was at NIH, one of the Co-Founders at Veralox , Dave Maloney, and his team were working on novel 12-lipoxygenase 12-LOX inhibitors. They had instituted a really novel screening paradigm to identify first-in-class selective inhibitors of the enzyme, which had never been discovered before. Around that time, 12-LOX , the role of 12-LOX in Fcγ RIIa-mediated and immunoinflammatory pathways was evolving. And through ongoing collaboration and 12-LOX ' role in platelet activation was clearly emerging. And this was really exciting for the team. And we knew that intervening upstream of clot formation was really going to be a game-changing approach to HIT and other immunoinflammatory pathways.
And so one of the analogies we like to use is that this approach of targeting 12-LOX upstream in the cascade is akin to plugging the leak on a boat versus bailing out water on a sinking ship, which is really the mechanism of action for a lot of the drugs used in this clotting cascade, particularly within HIT. So really altogether, we knew we had something really novel and really exciting, and we were motivated to keep developing VLX-1005. And that's why I formed Veralox and now excited again to have this in the hands of Cadrenal to continue development.
All right. Very good. Great analogy there. There are obviously many thrombotic and inflammatory conditions where platelet activation plays a role. Why did you choose HIT as the first clinical indication for a 12-LOX inhibitor, and what made it the clearest proof of concept opportunity from both a clinical and regulatory standpoint?
Yeah, sure. Sure. So we chose HIT, I'd say, largely because of a really clear mechanistic tie-in for VLX- 1005 and 12-LOX within that disease. So we knew 12-LOX was becoming, you know, it was emerging as a key mediator of platelet activation. And it was just downstream of the platelet surface receptor FcγRIIa , which I mentioned previously. And that HIT, the disease, is characterized by an activation through that FcγRIIa receptor. The pathogenesis of HIT and the role of FcγRIIa in 12-LOX lined up so well that we knew we had that mechanistic tie-in. As we looked further into the disease, we saw a huge unmet need. So the vast majority of clinicians we talked to as we were exploring our approach felt the current therapeutics did not work well in this disease.
I think the high morbidity and mortality currently with current treatments on the market exemplified that there was this high unmet need. Additionally, with HIT being a rare disease, we felt strongly we could obtain Orphan Drug Designation, which we did receive. Then we also obtained Fast Track Designation, which gave our assets advantages from a regulatory standpoint. Really just everything lined up in terms of a novel mechanism of action, then a clear tie-in with HIT, and then some regulatory advantages and really got us excited to develop this asset for HIT.
You know, maybe, Matt, for those in the audience who may be less familiar, you know, can you briefly explain what heparin-induced thrombocytopenia is and why it's such a serious complication?
Yeah, absolutely, so HIT is characterized by an immune reaction to heparin, so patients that receive heparin for extended times, typically during surgery, they will develop antibodies that complex with the heparin and PF4, platelet factor 4, which is a platelet-derived protein. This complex then activates FcγRIIa receptor on the platelets. This platelet activation leads to the consumption of platelets, which is the thrombocytopenia in the disease name, and it's the pathogenesis of the clotting, so paradoxically, these patients that were on heparin for anticoagulation end up with extensive clotting stemming from the reaction to heparin, and so all of this leads to thrombosis, ischemia, amputations, organ failure, and a high mortality rate, so the current approved treatments, as I alluded to earlier, inhibit the clotting cascade, and with patients already on low platelet counts, these drugs can actually exacerbate this bleeding.
And so that's why we're really excited because, again, we're targeting the pathogenesis with hopefully a lower bleeding diathesis, and we can inhibit the activation of platelets that are contributing to the disease progression.
You know, and maybe you mentioned sort of the orphan drug designations there. You know, help us understand why, despite this being considered a rare disease, HIT represents a meaningful and underserved market opportunity in anticoagulation.
Yeah. Yeah, so the current treatments come with the issues that I mentioned. And because of this, there's actually a lot of off-label use in this disease. And so clinicians are searching for an effective treatment for HIT that doesn't come with this bleeding risk. And with heparin continuing as cardiovascular surgeries rise in the U.S., there's, you know, 50,000 confirmed new HIT patients every year in the U.S. alone. We see HIT, obviously, across the globe as well. And because of this, we see a really underserved market with a high unmet need, which really, really gives us a lot of opportunity.
All right. And then these designations, talk about how they sort of help to accelerate development and maybe de-risk some of the capital requirements over the next 24 months or so.
Yeah, sure. So Orphan Drug Designation and Fast Track together really compress the timelines and de-risk capital. So Orphan Drug Designation allows smaller, more flexible trials and does provide tax credits, fee waivers, and market exclusivity. This all lowers total development costs and can improve probability-adjusted returns in the end. Fast Track Designation adds speed to the development process. It enables earlier, more frequent FDA interactions, rolling submissions, and faster resolution of any development questions we may have. Overall, it just reduces execution risk between these key milestones as we continue development.
All right. Very good. You mentioned at the beginning sort of why you pursued HIT, but how do you think about the broader applicability of 12-LOX inhibition? Are there other immune-mediated or thrombo-inflammatory diseases where this mechanism could meaningfully change outcomes?
Yeah, so we've certainly largely been focused on HIT initially, and it's still early days for these additional opportunities, but the application in sparing beta cells in type 1 diabetes is something we're interested in. There's some earlier work in the role and the involvement of 12-LOX in diabetes, so that's something where type 1 diabetes, that's something we're interested in, but these are preclinical discovery stages, but we do have a suite of additional 12-LOX inhibitors, novel composition of matter, and we're really excited about having significant opportunity in these other immunoinflammatory diseases that need either an IV or oral administration and the potential for chronic dosing with these new inhibitors.
All right. Fantastic. Well, thank you so much for that overview there. Matt, Quang , let's maybe come back to you here for a moment. With the addition of Fruinexian, as you mentioned, and VLX-1005, in addition to Tecarfarin, right, Cadrenal now really spans acute immune-mediated platelet activation, acute care coagulation. You know, from your perspective, how do these two assets together shape Cadrenal's really sort of identity and long-term strategy? And what excites you most about how they could ultimately change anticoagulation care?
Robert, I think what we are excited about is providing patients with potentially two therapeutics to offset what have been long-standing drugs that have been used in anticoagulation. Like I mentioned earlier, warfarin started using warfarin in the early 1950s. Heparin was from the 1930s. So when you look at vitamin K antagonist class warfarin, Tecarfarin is also a vitamin K antagonist. The main difference is the metabolism and kidney-friendly. What we want to provide to those patients who I think are stuck on warfarin is they cannot use the DOACs. They are warfarin for life in certain situations.
I think there have been so many advances scientifically in the medically implanted devices, mechanical heart valves, other heart valves, and the left ventricular assist device that these patients, we believe, deserve an alternative vitamin K antagonist where the Factor XIs aren't being tested and the DOACs have either not been tested or have failed. So that's on the Tecarfarin side. When you talk about heparin, it's widely used in cardiac surgery. What we're trying to do is what Matt and his team has done so well at Veralox and taking it through phase two is to provide these patients who unfortunately get HIT and get sent over to hematology the ability to get something quickly to make sure that they don't suffer without a relieving therapeutic.
Looking at the big picture, we believe we fit in very well in our mission of providing anticoagulation therapy in areas where Warfarin, DOACs, factor XIs, and even in HIT, there's no treatment. As mentioned, we have Orphan and Fast Track for both of our lead programs, VLX-1005, as well as Tecarfarin.
All right. Very good. You know, your investor deck there references, I think it's combined $3 billion in peak annual revenue opportunity across these targeted indications. I don't know if you're able to choose a favorite child here, but which program do you believe sort of provides the, or maybe it's programs provide the primary value inflection driver over the next three to five years and why?
Well, you know, we believe the latest is the greatest, and so there's a reason in the timing of acquiring VLX-1005, exciting news about the phase 2 data that's being analyzed and about to be published and announced, the excitement around the investigators, certainly VLX-1005, then Tecarfarin, Fruinexian and the Factor XIs as a whole, as any new drugs in a new class that's yet to be approved, we're patiently looking at the program for Fruinexian as well, but I can just say that VLX-1005, Tecarfarin and Fruinexian in that order because we are very excited with our latest acquisition.
All right. Very good. For investors out there following, talk about maybe some of the key upcoming milestones folks should be looking out for.
Certainly, as I mentioned, phase two has been wrapped up, the database lock. Our team's been speaking with the primary investigators as well as leading HIT thought leaders through introductions via Matt Boxer and the Veralox team. We're excited about that data being analyzed and published very soon. Obviously, the CMC portion of VLX-1005 is being worked on right now. Interaction with the FDA is upcoming as well later this quarter. As far as Tecarfarin, we mentioned last year that we have a drug product ready for the trial. Upcoming FDA interaction is always critical. We are aware of certain potential delays, as mentioned in the media about the January 30th. We're going as fast as we can with our clinical, medical, and regulatory teams in pushing those two programs forward here as we start 2026.
All right. Very good. Maybe in the final moments we have here, Quang, if we're sitting here five years from now, what do you hope clinicians and patients are saying about Cadrenal's impact on anticoagulation care?
Robert, very excited entering 2026. I would say in five years, patients, number one, would say Cadrenal focus on two areas that the bigger pharma, bigger companies, for any reason, did not develop drugs for their needs. That's for HIT patients, patients with ESKD, end-stage kidney disease and atrial fibrillation, and patients with advanced mechanical heart valves. That Cadrenal provided two very important drugs to treat patients in that category. And lastly, we're very excited about what Matt mentioned just a few minutes ago, the oral applications for our 12-LOX inhibitors and that there is an oral chronic medication in phase two, later development for other conditions for the 12-LOX program.
All right. Fantastic. Well, we will leave it there. Quang, Matt, thank you so much for your time today. I want to obviously thank everyone here as well for watching. If there are any questions or perhaps you'd like to schedule a call or a meeting with Cadrenal here, feel free to send me an email. That's blum@Lythampartners.com. So again, thank you guys so much for your participation in the summit here today. I hope you guys have a great rest of your day.
Thank you.
Thanks.
Quang, Matt, thank you very much for the time today and your participation in the summit. Again, quick reminder, all the webcasts will be available to watch on demand after the summit. Okay. We're going to end the summit here today with a special guest as Thomas Flaten, Senior Research Analyst of Lake Street Capital Markets, moderates a fireside chat with Josh Disbrow, the CEO of Aytu BioPharma. Please stick around. We will be right back.