Hello, and welcome to the Life Science Investor Forum. On behalf of OTC Markets and our co-host, Zacks Small Cap Research, we are very pleased you have joined us. The next presentation of the day is from Cadrenal Therapeutics. Their session will be moderated by David Bautz, Senior Equity Analyst with Zacks Small Cap Research. Please note you may submit questions for the presenter. You can also view a company's availability for a one-on-one meeting by clicking Book a Meeting. At this point, I'm very pleased to welcome Quang Pham, Chairman and Chief Executive Officer of Cadrenal Therapeutics, which trades on the Nasdaq under the symbol CVKD. Welcome, Quang and David.
Great. All right, let's dive in. The, obviously the big news recently was the company's in-licensing of CAD-1005, which looks like it's ready to move into phase III development. While you were evaluating this compound for potential in-licensing opportunities, what were the specific elements in the data package that convinced you that this asset was worth going after?
Yeah, great question, David. We're very excited. CAD-1005 was formerly known there in the internet world among researchers and hematologists and cardiologists and cardiac surgeons as VLX-1005 for Veralox Therapeutics' lead asset. Veralox Therapeutics and its researchers and management team did a wonderful job of getting 1005, which now we are referring to as CAD-1005 under Cadrenal. We actually acquired the asset along with another asset, an oral agent in the 12-LOX category, which is in the preclinical. The lead asset, CAD-1005, is phase II complete. It is an IV solution, acute hospital therapy for patients with suspected or confirmed HIT, which is HIT, heparin-induced thrombocytopenia.
HIT is in the world of, I'll give you what would be an example of a HIT patient. Somebody goes in for a heart surgery, cardiac surgery, is given heparin, the most widely used anticoagulant or blood thinner via IV in the hospital setting to protect the patient from getting blood clots. A small amount of patients have this immune reaction. You go in, getting cardiac surgery, you know, heart surgery, getting heparin, everything's going well, you're coming out, and all of a sudden you have this reaction. It causes your platelets to drop just, it's called heparin-induced thrombocytopenia, then you're gonna develop blood clots. You're developing blood clots from taking heparin, which is supposed to designed to keep you from getting blood clots.
The patient's in extreme critical care in the ICU. We, you know, tested the drug in these patients, and what we found out when we started looking at Veralox last year to acquire the VLX-1005, was that thrombotic events in the arm with 1005 was tremendous in reducing the number of thrombotic events. Now, the study, the phase II, was not designed for statistical significance, but the signal was very promising.
Based on that and based on the safety of the two phase I's and the preclinical modeling, not only in HIT, but in obesity and type 1 and type 2 diabetes, we made the decision to acquire and take the data package to the FDA, and the FDA scheduled a phase II meeting for us for Cadrenal, our CAD-1005, for HIT. You know, the drug also has Orphan Drug status as well as Fast Track.
Excellent. All right. Why don't you walk us through the mechanism of action for the drugs. I know it works differently from what else is out there. Maybe how it addresses the actual underlying biology of the disease.
Yes. I'll make it so the investors and other interested parties can get this, and you know, obviously questions and inquiries for a deeper scientific dive is always available with our medical team. Basically in the world of anticoagulation, you started with warfarin as an oral for general thrombosis. Then in about 15 years ago, the world of Factor Xa came into existence. The Eliquis, Xarelto, they're both all oral chronic. In the hospital setting, it's heparin, and there are two other agents that are used, argatroban and bivalirudin. What happens is when they're giving heparin and they develop HIT, these patients are given argatroban or bivalirudin, which is only going to treat, you know, the clot. It does not treat the underlying platelet activation. The technology, the platform is called 12-lipoxygenase inhibition.
About a decade ago, about six to eight companies globally tried to develop 12-LOX for a number of different indications, and 1005 is the only one that made it into the clinic. It works in HIT in terms of platelet activation and without increasing bleeding to help the patients recover. That's how, you know, whereas the other two drugs just basically try to stop the clots after they form. One drug, our drug is the underlying, the other one is basically the symptoms or the after effect of HIT. That's the major difference.
It is also found that 12-LOX inhibition is also, you know, helpful in the underlying causes of, like I said, in the preclinical setting, the scientific researcher also saw effectiveness in type 1 diabetes, type 2, and also the inflammatory consequences of obesity. We're very excited about that. There's been publication about the effects on obesity and type two diabetes in the preclinical setting that we're about to share. The research has been completed and has been published. This is the first time that we're going to publicize it because Veralox did not do it because they were busy with other strategic priorities towards the second half of 2025. We're very excited. As you know previously, we've been a company focused on the, what we call cardiorenal, right?
Cardiovascular and renal. Our previous lead asset was tecarfarin, a vitamin K antagonist like warfarin, which had potentially a better profile and efficacy than warfarin as that cleared through the kidneys. That has also Orphan Drug and Fast Track from the FDA for patients on end-stage kidney disease, stage 5 or about to get on dialysis, who also could have concomitant atrial fibrillation or irregular heartbeat. When we came across 1005, we thought the reduction in thrombotic events, which, you know, as I mentioned, we've been in front of the FDA, and we know that events really is what, at the end of the day, it's not marker, it's not, you know, other signals.
It does reduce events and eventually, you know, prevent mortality from these events, strokes, heart attack, thrombosis formation, PEs, pulmonary embolism, and those kind of things that are associated with thrombosis. I must say that, you know, we disclosed that the study's original primary endpoint was the rate of platelet count recovery, which at the time, Veralox a scientist had informed me that at that time in the literature, that was from the HIT experts globally, that the thought was that if they could accelerate, you know, the rate of platelet recovery, they put that in the primary endpoint, and the thrombotic events is the secondary.
As it turned out, the thrombotic events looked very promising, but the rate of recovery in the primary event was the same between 1005 and in the other arm where, you know, placebo was used on, you know, on the background of argatroban or bivalirudin, the other two anticoagulants to prevent clots.
Okay. To kind of follow up on those results there from that phase II study, so what was the safety like for the compound?
The safety for the two phase I and the phase II, no extra bleeding. I think that's, you know, usually the number one concern is when you're taking an anticoagulant, whether IV or oral, chronically or in acute setting, if you're preventing blood clots, hopefully the trade-off is not, you're not getting a ton of bleeding. In this case, the drug has shown to be very safe in the two phase I and the phase II. We're very pleased about that.
Excellent. Yeah. You mentioned that, the lead indication will be HIT.
Yes.
There are other indications that the drug might be used for. What is it about HIT that kind of makes it the most compelling initial indication to go after?
Well, number one, HIT is deadly, HIT is serious, and there's a great unmet need for that. Once again, it's in a setting where, you know, it's cardiac surgery turned into hematology. Somewhere there, you know, based on our experience with end-stage kidney disease dialysis patients who are under the care of nephrologists, once they develop atrial fibrillation or irregular heartbeat, now they're under the care of electrophysiologist, a specialty under cardiology. When we bring that experience in not only in the tecarfarin, as well as the other drug that we acquired last year called frunexian, which is a acute setting Factor XIa, you know, in the phase II ready. We saw that it's a unique challenge of going from cardiac surgery, ICU, and then all of a sudden the care goes over to the hematologist.
From our experience, we always felt thrombotic events have always been our experience with the FDA. HIT was chosen by the Veralox investors and management team because one, it was a great unmet need. Two, the FDA had designated the drug an Orphan Drug as well as gave it Fast Track and also orphan status in the EU. That was number one. Two, the promising reduction in thrombotic events. Now they chose HIT obviously because it's manageable. As you know, the anticoagulant world, whether it's acute or chronic or oral, is vast. There are pockets of unmet need, and clearly HIT has been without a new drug for decades.
Yeah, absolutely. In thinking about the phase III program, like what do you see as how are you going to design that? What are the outcomes going to be for that trial, and other parameters for that phase III study?
Yeah. Based on our extensive interactions with the FDA in anticoagulation in the space, we went in with the reduction in thrombotic event as the primary endpoint. It's a therapy of seven to 14 days, dose BID, and also, you know, the will be powered for superiority over the other arm. Once again, in the background, the inclusion criteria, you know, was either they had to be on bivalirudin or argatroban, the other two hospital-based anticoagulant. It's gonna be expanded even more. We're gonna share that in the near future here, the whole trial design as proposed by us. Obviously, we're gonna go into the meeting that we have already stated, you know, later this quarter to discuss with the agency.
Okay.
Which should be a you know size of under 200. Primary endpoint will be reduction in thrombotic events with this powered for superiority versus placebo in the background of bivalirudin, argatroban, and possibly other anticoagulation agents.
Okay. If the study's successful, if the drug eventually gets approved, is this something that's gonna replace the current therapies, or is it gonna be used in conjunction with them?
In conjunction with.
Okay. All right.
Once again, the other therapies are reactive. You know, you get HIT, and then the other therapy is to prevent additional clots. This is, you know, to treat the thrombus, the platelet activation, and it's the underlying cause of HIT as the reaction to heparin.
Okay.
It's a very rare immune reaction, and so both drugs are used differently, but overall, the safety and recovery of the patient in the hospital is at the top of priorities for, you know, the hematologist and the cardiac surgeon, the cardiologists who are taking care of these patients.
Okay. As far as the phase III—
I'm sorry, a 30-day follow-up. Yeah.
Okay. I was just gonna say, as far as the phase III design goes, what do you think is the most important part of your trial design that's gonna help maximize, the probability of success for that trial?
Well, I think there are several factors. You know, we as a company, as a team, we go into phase III designs with the protocol and stats plan for success, obviously, based on the previous track record of the drug candidate. In this case, it's 1005. Certainly inclusion, exclusion criteria are very, very important. The selectivity of the sites that see HIT patients, but can also, these academic centers, who can also enroll patients in the study is always critical in the academic setting. I would say those two are at the very top of the priorities for us as we look into this trial.
Excellent. You did mention that you will be meeting with the FDA. Can you talk a little bit more about that, and then kind of what the purpose of that meeting is for?
Yeah. You know, we asked for a meeting with the FDA, and the FDA, I guess we've already publicized it's an end- of- phase II meeting, which they've already got the data, and we've already released the top-line data, obviously. It will be discussed in detail at an upcoming conference, and, you know, there are other publication consideration for our academic consultants and advisors to the company. That's, you know, that's the industry, right? It's exciting scientific funding and findings. You know, a company like ours and most public companies, there are needs to be published. I mean, the research will need to be published, but we need to publicize the data.
We try to find a balance of getting the data out for investors, but also respect the academic need for publication in peer-reviewed journals and presenting it for the first time in detail at specialty conferences, obviously, that relates to HIT or hematology. I think those are important consideration. I think we're very excited about an acute treatment potentially for this orphan indication of seven to 14 days, and also a 30-day follow-up to get them out of the hospital. It's different than what we've been working on before. Longer trials, bigger trials, and one-year follow-up. We're excited about all those things.
I just wanna re-emphasize how dangerous HIT is and how deadly it is. It's something that's, you know, could take on and rapidly advance. You know, we're excited about, you know, getting this drug, getting in sync, getting guidance from the agency, and then getting investors to back it. Veralox, the previous R&D holder, had a very good track record of attracting investors to get it through phase II. The end-of-phase II meeting, the purpose is to go over the phase II trial, but the purpose also is the path forward. You know, what are we thinking about primary endpoint for the phase III, including, you know, exclusion criteria, and also, you know, follow-ups, powering, and the stats plan. That's, you know, that's pretty much, you know, by definition, by the regs, that's what an EOP or end of phase II meeting is.
Yeah. Do you have a general idea of timelines as far as, you know, when the study may start, and then, enrollment timeframe?
Yeah. We, you know, we're looking. I think we've already stated publicly, looking to start the study in the first quarter, have all the preparations done at the end of this year. You know, obviously, you know, that's depending on the outcome and the guidance we get from the agency and, you know, we never count our chickens before they hatch, and neither none of our peers do either. We go in with the best preparation, the best powering of the study, you know, the best data that we can get. I think we get, like our peers, the best KOL, the best care provider that are on the front lines, the ones that see HIT patients and know how dire, what a dire need it is to have a new therapy. That's we're gonna put a very good team and a good plan forward to interact with the agency.
Okay.
We're very bullish on the drug, on the process. You know, the investors wanna see that, right? Everybody wants to see the guidance to make sure that, you know, the trial is feasible and fundable.
Yeah. That's a good segue to talk about financing a little bit. What should investors think about, you know, how the funding strategy is for this phase III program?
Well, it's like I said, the trial should be about 24 months, and it's gonna cost about $35 million-$40 million. That's what we're estimating based on what we are preparing to speak with the agency about. You know, obviously there's other costs, including CMC. There are other costs, you know, there could be other requirements to do additional phase I study. But you know, we're very pleased with the safety track record of the drug. Others, you know, actually to run it, you know, you need people, you need smart people, and you need very good partners to run the trial.
What I think when you look at a drug that's potentially $850 million with Orphan Drug status and Fast Track, and that's just the markets in the U.S. and in the EU for a condition that really screams for a new therapy that really help people stay alive, you know. I mean, once again, I just wanna remind interested parties that are watching, you know, you have a patient that goes in for cardiac surgery thinking, you know, whether it's a transplant valve or something, and you're expecting a good outcome. We have very good cardiac surgeons in this country. We have very good hospitals. We have very good medical device companies that support those kind of operations. But they're using a drug that's, I think was invented in the 1930s, okay.
There's been no replacement for it, heparin. The other drug, like I said, we mentioned earlier, ticagrelor as an oral anticoagulant that, you know, the sister of heparin is warfarin. It was around when President Eisenhower was in office in the 1950s. They're giving, you know, the IV heparin and, like, once again, you know, unfortunately a small number of patients develop this immune reaction, and they end up getting clots from the drug that they're taking to prevent it. It's a paradox. So far there's been no solution. You know, we're very excited always to work on, you know, two of our drug candidates have Orphan Drug Designations.
I mean, the U.S. Congress and the FDA recognized and passed that Orphan Drug Act over, you know, three decades ago for this purpose, so that drug companies like ours can focus and have some protection for the investment and the time to get therapies for populations under 200,000 that are affected in the United States.
Yeah, absolutely. HIT is definitely a place that, or an indication that needs new drugs for sure. Lastly, because you mentioned it earlier that CAD-1005 has other potential uses, so maybe you could go over what you're most excited about after HIT for this drug.
Yeah. One of the investors in Veralox was the T1D Fund. That's one of the early preclinical, you know, signals that Veralox that we're uncovering based on, like I said, we've been focused on HIT, but these are other publications that have really been publicized. The other one is reducing the inflammatory effects of obesity. You know, we have, like I said, it's been published, it just hasn't been publicized. We're excited about, you know, starting to talk about that. The focus operationally financing for the company is around HIT. In a phase II meeting coming up.
The purpose of talking and sharing the data on obesity, on type 1, type 2 diabetes, there's so many global partners and, you know, small cap, middle cap companies working in these big disease area. I think researchers are looking for combinations. We just, you know, we wanna share that information for potential developers and partners. You know, it is not a reality to try to do a phase III concurrently with another phase III for a size of company at this stage. We just wanna share the findings, the great clinical, preclinical work that the Veralox team did, and now that we own those assets, we wanna share that so researchers at other companies can see the potential of 12-LOX inhibition.
Yeah. Absolutely. All right, last question. Looking ahead, say three years into the future, what does success look like for Cadrenal and maybe frame for CAD-1005?
You know, I think success for Cadrenal would be, we would have already applied, you know, submit an NDA with a Fast Track, and the drug's approved in three years, within three years. That's for the IV. Our CAD 1005, but it's the beachhead for 12-LOX inhibition as a platform. Hopefully by that time, our oral series, CAD- 2000, you know, is in at least phase III for a chronic larger indication. That would be a huge win.
Whether it's with a partner, or, you know, out licensed to do those bigger indications I talked about, type 1, type 2 diabetes as well as, some having a play in helping patients with obesity and dealing with issues and the consequences of obesity, will be a huge win if we can find a partner to help develop that while we focus on HIT.
Yeah. Well, that sounds great. Quang, thanks again for joining us. We really appreciate the overview.
Thank you, David, and thank you for the OTC Markets. Good to be back on.
All right.