It's my pleasure to introduce the next presenting company, which is Aardvark Therapeutics, traded on the NASDAQ under the ticker symbol AARD. This is a recent IPO. My name is Raghuram Selvaraju. I'm a senior healthcare equity research analyst and managing director here at Wainwright. It's my pleasure to introduce, presenting on behalf of Aardvark, Bryan Jones, Chief Operating Officer. Bryan?
Come on. Okay. As Raghuram said, we just had IPO in February of this year. We have about $150 million in the bank right now. This should get us out to 2027 as our projected runway. What I'm going to talk about is I'm going to talk about three different indications. I'll talk about Prader-Willi, hypothalamic obesity, and then general obesity. The sort of theme throughout all of these that I'm going to be talking about is the difference between hunger and appetite, and then how our drug can actually address the hunger axis of the calorie intake for people. This is our management team now. We just announced a press release yesterday where we added four new members to our senior management team, so we'll be updating that. I brought Danny with me. This is his first day. He's our new Chief Commercial Officer.
People will be glad to introduce himself to them. What we're talking about is we're talking about the difference between hunger and appetite. The difference here is really key and fundamental to what we're doing. Hunger is a penalty avoidance pathway. This is the pain you get when you don't eat and when you don't consume calories. Whereas appetite is reward-based. It's the pleasure in eating. This is really important because our calorie intake as human beings, it's really the integration of these two signals. They're wired differently in your brain. They're controlled differently, and you respond to them differently. Normally, when you eat food, you release a hormone called cholecystokinin, or CCK, that binds to your vagus nerve, and it sends a signal to your brain that says, "Hey, you should not be hungry anymore.
You just ate a meal. After you eat that meal, your body then starts secreting a hormone called ghrelin, and that goes up, and after a few hours, it gets to a high level, and you're now hungry again. You are doing this cycle all day long, and that is why you have a meal cycle and a calorie intake. This happens through the gut-brain axis. Whereas the GLP-1s, these are an injectable, so you get systemic wide. It crosses the blood-brain barrier. This impacts your reward-based system. This is why you like to eat. I do not know if you have talked to other people that are on GLP-1s, but what you will find is what they will tell you is they sit down to a meal, they look at the food, and they go, that does not sound very good. They lose that pleasure in life of eating.
Some people don't do that, but most people do. In fact, the discontinuation rate from GLP-1s is quite high because of this sort of nausea-like symptom of food just not looking good and not enjoying life. The next one here. I'm going to talk about two different sets of indications. The first one we're looking at is restoring a dysfunctional hunger signal. These are indications where we think CCK is broken, and therefore this hunger signal is not being processed correctly because that CCK is no longer there. The two indications are Prader-Willi and hypothalamic obesity. I'll come back to this in a minute to explain more about why we think those are going to work. As opposed to general obesity, where one of the biggest things you need to do is you need to diet, but it's hard to diet because you get hungry.
If you can suppress hunger in an obese patient that's trying to diet, they can lose weight. That's really the fundamental things that we're trying to do with our company. Just to look at our pipeline, the Prader-Willi syndrome, we are actually in the current process of doing a pivotal phase three trial that has started. It's rolling patients. We will be starting two other trials, one in hypothalamic obesity and one in general obesity this year. Those should read out in 2025. Or 2026, sorry, it is 2025 now. Let me start with hyperphagia and Prader-Willi. The market is pretty well known. There are about 20,000-25,000 people in the United States that have this. Soleno just released their product, ViCat. They've announced pricing of about $450,000 a year. You can see this is a multi-billion dollar potential market opportunity.
I want to talk a little bit about Prader-Willi for a second and what is it beyond hyperphagia. Prader-Willi is a genetic chromosome abnormality. These patients are similar to what Down syndrome kids look like. They tend to be shorter stature. They are excess fat compared to their lean body mass. They have a lot of other symptoms. They have a lot of arthritis-like symptoms, joint pain. They have severe constipation. Of course, they have a lot of behavioral issues, mainly associated with the hyperphagia, as well as they tend to be developmentally delayed and maybe a little bit of autistic behaviors. It's really a broad syndrome. What we're really addressing is the hyperphagia. There's just not a cure for these patients as a chromosome abnormality. One of the things I told you about earlier was CCK.
Why do we think CCK will work in Prader-Willi? There's a couple of reasons for that. Number one, Prader-Willi patients are known to make CCK, but it gets stuck in their intra-endocrine cells that line their gut. When they eat food, they don't release it. They're not getting that signal that should suppress hunger. Why do we think that really is true? One of the major reasons, if you take and you knock out CCK in a rodent and you put them in a cage and give them unlimited food, like normally you do when you house rodents, they will eat themselves to death. They never get the signal that they've eaten. We're pretty convinced CCK is a fundamental pathway. In addition, CCK interacts with your gallbladder.
It is part of what stimulates the food passage after you eat. Normal passage is 24-36 hours. Prader-Willi patients is three to five days. They're very, very constipated. Very difficult for them to be treated. The other thing is CCK also impacts inflammation. We know that these patients have a lot of inflammation. Again, many of the things that activity of CCK correlate with the symptoms of Prader-Willi patients. We completed our phase I typical SADMAD study. Went up to 240 milligrams twice a day in these patients. The key point about the study is, number one, we had essentially no adverse events in phase I. Very, very clean profile. This makes a lot of sense because our drug is really a topical treatment for the gut. 99% of the drug stays in the gut. Less than 1% gets into the bloodstream.
The chance of side effects is very, very low because you're not getting exposure to other tissues. We've completed a phase two study. I'm going to show you that data here in just a second. As I mentioned before, our phase three is ongoing. We've discussed this with the FDA. This is potentially a single pivotal study. This is from our phase two study. There are actually two studies here. The one on the left, it's left, yeah, it's left here. The one on the left here, this is where we started out. We had 12 patients. They're at a fixed dose of 200 milligrams per day. The scale on the left is a hyperphagia questionnaire for clinical trials for HQCT. This is what the FDA considers the gold standard for approval.
What you can see here is we had a nine-point reduction that showed up in only two weeks. That reduction stayed good for a full 28 days, which was the limit of how long we could treat with the tox package we had when we started these studies. As soon as we take the patients off drug, within two weeks, their symptoms are starting to come back. This is very, very suggestive that the drug is doing what it's supposed to be doing. These are not placebo-controlled trials, full transparency, but the effect size here and the rebound is very consistent with the drug that's having activity. We then did a second cohort, basically a second new study where we dose escalated. In this case, we gave patients 400 for a week, 600 for a week, and then 800 milligrams twice a day for a week.
They're dose escalating. In this patient, we had four naive patients, and then we had two patients that were in the original study. The two patients we chose were our lowest responder, and then we chose a patient that was kind of a medium responder in the prior study. Both of those patients had better data in the second study when we dose escalated. You can see here, the turquoise line here is all the patients in the trial. Again, we saw the response similar to what we saw with the fixed dose cohort, but there were two patients that were particularly non-compliant with our study protocol. When we take those patients out, you even see a better response.
Really, the learnings from those, I'm going to talk about it on the next slide, really kind of impact the design of how we're going to do our phase three study. There is one other point I was going to make, but I've forgotten, so I'm going to move on. This is what we're looking at here. The bar graph on the left, this is the data from all the patients in the study. We saw a 30% reduction in the HQCT. If we take out the patients that we think violated the protocol and more consistent with the way our phase three study is going to be designed, we would have seen a 50% reduction. What have we learned that we're taking out to design for the phase three?
Number one, one of the patients that we took out, the mother was rating the patient at the beginning of the study, and the father was rating the patient at the end of the study. You can't have raters change because their scale, their absolute number is going to be different. In our phase three, we're insisting that one parent is committed to rating throughout this study. We also learned that really strictly controlling the environment is important. These patients don't travel well. They don't break the routine well. The other patient that violated the study went on two one-week vacations, including Disneyland, which is incredibly hard to control their food intake and their behavior. Really hard to measure. We're asking the patients during the phase three trial to please keep your routine for at least the duration of three months, right?
The third thing we found is that there are compounds that are given, antipsychotics like Risperdal, which actually stimulate severe hunger. They can conflict and confound the data. We are not allowing those patients into the trial. All the lowest responders in our phase two were ones that were on Risperdal. It is consistent with us. If we take those out and do that, then we will have better data. If you go on to our phase three design, this is what we are designing. We are doing a classic placebo-controlled trial, 45 patients per arm. Immediately following the active part of the trial, patients will be allowed to roll over into an open label extension. We will continue dosing patients until we file our NDA. One of the key measures of this trial that we have instituted is there is a problem with placebo effect in these studies.
This is a subjective scale. All the parents in the world know that you have to have a 13 to get into these studies. That's what every company has always done. What we did is we said, "Look, once you qualify for the study, we're going to measure your score at baseline. You're in the study. No matter what your score is, you're in the study." We talked with the FDA, and they agreed that only patients above 13 get included in this just to school analysis. Patients below 13 will still be evaluated, but they don't count toward our powering. We need to enroll 45 patients above 13 in each arm. We'll have an interim look to make sure we have enough patients. That's the powering of the trial.
We should be able to show we're looking for a difference of five, but we powered it for a standard deviation of six. We think we've overpowered this trial, but we want to make sure that we can see that difference. Now I'll go on. Any questions about that before I go on?
The two that discontinued? Yeah, the one patient had two different raters, right, which you're not supposed to do. The other patient had these vacations. They also got prescribed, that one patient got prescribed steroids by an outside investigator, which is also kind of a no-no. Yeah. Yeah. We left them in the protocol. That's why we have the dark turquoise line. We didn't want to hide the data, but we really think that data underrepresents the effect we were seeing. Right? Talk about hypothalamic obesity.
We think of Prader-Willi as genetic hypothalamic obesity, right? The signal, the CCK going to your hypothalamus to turn off your hunger signal, is defective. When people have a certain type of brain tumor, they do a craniopharyngioma surgery, about 50% of those patients now become hypothalamic obese patients, right? It's because the hypothalamus gets damaged during the surgery. Now the receiver of the signal is not functioning correctly. If we can stimulate more CCK to be made, we can increase the signal, and the receiver now can have a better response. That's the theory. There have been studies in the past where people have taken CCK and treated patients with hypothalamic obesity, and it looks to work. Unfortunately, when you give systemic CCK at high levels, it's very toxic.
What we're doing is just stimulating the normal CCK so we do not get those high levels. Just to let you know, there's about 5,000-10,000 of these patients in the United States. It tends to be more prevalent in Asia. We don't know why that is, but there's a lot more per capita patients in Asia. The hypothalamus, the control signal for hunger, is damaged in these patients. This is the whole mechanism. I'm going to skip over that. That's sort of the rationale behind that. We're starting that study. We're doing the final design right now. It should be starting that study soon. The last thing I want to talk about is ARD-201 for obesity. This is similar to the 101. I just want to be accurate about this so the nomenclature is good.
It has the same active ingredient as ARD-101. We have found, and I'm going to show you the data here, that if you add a DPP-4 inhibitor to it, you actually get a synergistic response on obesity, and you also get a more profound deepening of the metabolic benefits of losing weight when you put the combination together. We want to do a fixed dose combination as a separate product. The other benefit of that for us is that Prader-Willi patients die from gastroparesis. DPP-4 has a low incidence of gastroparesis, so you would not want to prescribe this drug to a Prader-Willi patient. It allows us to have a price differential between the two products. This is the combination data. What you can see here is that little gray line, that's sitagliptin by itself.
It's been known that if you go on sitagliptin, you might lose weight for a week or two, but you rebound quickly and forever that you're on it, you don't lose weight. The turquoise line is ARD-101 by itself. When you put the two together, you get a synergistic loss in weight, which is really pretty impressive. If you look at our clinical data, again, we're talking about hunger here. The data on the left is actually from a phase two trial in obese patients' placebo control, where we're asking a questionnaire. It's called the COEQ-10. It's a series of questions that talk about your hunger and your desire for food. On the hunger portion of this questionnaire, we were statistically significant reduction in hunger with only 20 patients. The other two domains in that COEQ-10 are about your desire, your cravings.
One is about your strength of your cravings. The other is about the frequency at which you have those cravings. We were almost statistically significant on both of those domains. The last domain, this is pretty interesting. It kind of distinguishes us from the GLP-1s. The last domain talks about how do you enjoy food. When you do decide to eat, does it taste good? Is it desirable? The GLP-1s do very poorly on that question. Ours was neutral. The patient said food's just as good as it always was. They can still eat, still enjoy their food, but they do not have to eat if they miss a meal. They do not have to eat if they are dieting, which is really the point here. The other thing about this is we actually have a really good big impact.
If you look here in the preclinical data on the left, the LDL and the HbA1c, these are metabolic parameters that are always improved when you lose weight, but the magnitude that we saw on these animals is greater than just the weight loss the animals exhibited. There is some kind of benefit of stimulating CCK in this way. On the right is data from our phase two trial. Just good to go back about our drug and the way it works. When you have a parameter that is out of whack, elevated LDL, elevated HbA1c, elevated glucose, inflammatory markers, our drug will suppress it back to baseline, but it does not suppress it below baseline. You give our drug to a normal weight animal, it will not become anorexic. It is pushing you back to where you are supposed to be, right?
In this data here, you're seeing in the clinical study, we had one patient that had elevated HbA1c. Normally, it takes three months to show a difference, but we were able to show a difference in one month, and that's a real difference. We had four patients that had elevated LDL. Both of the active patients had reduced LDL. Both of the placebo patients had no change. Again, very consistent, the drug is having a positive impact on the metabolic parameters associated with being overweight, beyond just the weight loss that you're seeing. Going here, this next trial is really designed as a proof of concept trial and a way of positioning ourselves on the market in order to design a phase three program for approval.
What we want to do here is, obviously, the first thing you do is you test your drug, ARD-201, versus placebo. It's pretty common. We also want to put a GLP-1 in this study so we can compare the magnitude of weight loss to a GLP-1. We want to do a combo of GLP-1 plus ARD-201. Because in our animal study, if you show that those are additive, that our drug can add benefit on top of the GLP-1 effect. Potentially in the future, what we could do is actually give ARD-201 plus a lower dose of GLP-1 that's below their side effects and keep them on the GLP-1 at a lower dose without all the nausea and the vomiting that happens to the high discontinuation rate.
Most importantly, what we want to do is once they've lost weight after about 12 weeks, we want to randomize the patients to placebo and to 201 because we believe what we can do is prevent the weight rebound that happens with these patients. As you know, 85% of patients that are on a GLP-1 or patients that are on a GLP-1 when they lose their weight will regain 85% of their weight within one year. This is actually the nemesis for every single diet in the history of the world, right? I personally have lost the same 25 pounds at least 20 times, and it always comes back. If I could have a drug that would keep it off, I would love it. This gives us a couple of different things. We think we'll preserve the lean body mass because we should not impact that.
We'll be able to show how we compare to GLP-1. We'll show if we're additive to a GLP-1, and we'll show if we can prevent the rebound. This will help us decide how we want to develop this drug in the future. Just to summarize, we're targeting hunger pathways, starting with pathways that are defective in the mechanism by which we're working, but then want to branch and expand our use of this product into other types of indications with hunger. We have data in the clinic, and we're in late stage with our one program. Any questions I can answer? Yes.
Within the real focus for all of the drugs that you really believe happens, what are some mechanisms? How do you see that with the accommodation for the GLP-1? How do you see it affected?
Yeah. What we in the literature, people have shown that CCK helps preserve lean body mass. In our clinical data, in our Prader-Willi, for example, we showed a decrease in body fat without a change in body mass. We think that we can help preserve the lean body mass. We do not have a ton of evidence in that yet, but we think that is a possibility, which is why we are going to be measuring that in that study.
Do you think some of these newer differentials seem like they are going to be a bit dramatic because the other parts of these that they are focused on, additives and that, why is that? Do you think they are competitive to you or?
They are completely different mechanisms. I think they are positive approaches to stimulating muscle. I do not think we are stimulating muscle as much as preserving what is there, right?
Anytime you do a rapid weight loss, you tend to lose some muscle. Even with just dieting, you rapidly diet. We just think we'll help preserve that lean body mass. Again, we have to prove that.
Do you think it's chronic therapy?
Our drug is definitely a chronic therapy. If you think about CCK, it's released every single time you eat. That means two, three, four times a day. You need to be stimulating it on a regular basis. Now, in our animal models, I would tell you that once a day seems to be enough. It's the way we dose. In Prader-Willi patients, we're going to do twice a day because they're very severely affected. We just want to make sure we get full coverage. It's quite a big dose, but you also have to remember when you eat, that drug is diluted.
It gets spread out through your digestive tract, and your digestive tract is very long. You have to have a lot of drug to make sure there's enough. The other thing that I point out is that intra-endocrine cells respond to food. If they responded to micromolar or nanomolar amounts of food, you would be bouncing off the walls every time you ate a meal. Their gain is turned way down, and they're not very responsive. You mentioned this is non-systemically employed. That's correct. About 1% of the drug. Mostly it is secreted into the feces.
I just wanted to ask about the current status of the regulatory outlook with respect to placebo-adjusted weight loss and what you consider to be the benchmark there. Historically, 5% placebo-adjusted weight loss has kind of been considered the benchmark. Have you seen any kind of change in the regulatory disposition as of late based on results from recent studies with competitor molecules, or do you see that 5% placebo-adjusted weight loss still remaining the benchmark from a regulatory standpoint?
The FDA actually just released guidance that 5% weight loss is the benchmark for approvability. The reason they did that is because 5% weight loss is where the maximum or the most of the benefit for your other health factors comes in. Losing beyond 5% is more cosmetic. The first 5% is the health. That is currently the regulatory benefit. We think that actually helps us because when we first were starting out talking about this program, everybody's going, "How do you compare to a GLP-1? How do you compare to a GLP-1?" That is not really relevant. The GLP-1s are fighting themselves.
We're talking about a different mechanism. It might be synergistic or a combination with those. We just got to get 5% and then show a better safety profile and a better impact on some of the other parameters of metabolic.