Conference Transcript - ANTX 2026-06-04

Operator

Good afternoon and welcome to the Jefferies Global Healthcare Conference. My name is Nick Becora with the Jefferies Investment Banking Team and it is my pleasure to introduce Eric Esam, CEO of AN2 Therapeutics.

Eric Easom, CEO

Thank you very much. Glad to be here today. So, get started. Forward-looking statements. I'll be talking about things that have forward-looking statements.

Operator

So, please take that into account.

Eric Easom, CEO

All right. So just to introduce AN2 Therapeutics. So we are a boron chemistry company. We do R&D internally and develop our own pipeline. So we have a broad pipeline. We have three clinical stage assets now that are in phase two proof of concept study. Two of those do not have any FDA-approved drugs for the indications, and so I'm going to kind of go through those. The immediate projects we're working on are polycythemia of error, our PV, and we're going to go into depth a lot about each one of these, but PV is kind of our latest addition to the pipeline, and there's a lot of excitement and potential around that program. Mycobacterium abscesses is a non-tuberculous mycobacterium kind of teria family of diseases. And there are no FDA approved drugs for that. So we have an oral project that I'll also be speaking about. And then the third one is for Chagas disease. And this is a parasitic infection where parasites go into your muscle tissue, most particularly the heart and cause quite a bit of cardiac issues in patients. And we'll talk about that as well. We put out a press release this morning about our phase one data and also efficacy data in non-human primates, which is quite exciting and moving forward into phase two. So near term, we're going to have data on all three of these programs. programs, and we'll be sharing that as soon as the fourth quarter of this year and throughout next year on all these programs. And then we have a number of research programs that are driven, again, by our boron chemistry internal capabilities. And we have two oncology programs, one in PI3 kinase, and then one in ENPP1. So I'm going to go through all of these here today. So in terms of milestones that are coming forward, so with PV, we're in the process of getting a phase two study off the ground. And we'll be initiating that in the third quarter of this year. And then we'll have data later this year and primarily into next year where we'll really have a lot of proof of concept. in an open-label, multi-part study. This is a big market opportunity. It's already a, you know, well-validated market with other competitive drugs, and so we'll talk about how we position into that in a bit. For mycobacterium abscesses, so this is an infection, a bacterial infection, chronically in the lungs, and so we have initiated a Phase II IIT study with a number of prominent key opinion leaders in the U.S., and we expect data next year. So this is a fairly large, it's orphaned, but in terms of large market potential opportunity here, there's 15,000 patients in the U.S., you know, 50 kind of in major markets. And so we'll go through some of the detail, but we've got lots of readouts here on that. And then Chagas disease, we just this morning put out a press release with our phase one data showing, you know, good PK and safety profile that supports phase two studies. Importantly, we also put out non-human primate data, which get naturally infected. And so this is about as close to proof of concept as you could get. And so we're excited about that. We'll be starting a phase two later this year. And we'll have top-line data around third quarter of next year. And there's 10 million Chagas patients in the world with parasites, you know, in their heart muscles. So you can imagine this is a really bad disease. There's no FDA-approved treatment for this. And in the U.S., there's about 300,000 estimated patients, potentially much higher. We don't really measure it and don't know. These are projections. the vector that transmittance here in the United States. So I'll go through a lot more details, but it's much more common than you think. And then we have the two cancer projects, which I'll spend a little less time and focus more on the clinical for today. All right. So for PV, we are studying our drug oral petroboral. So this is in the process of starting a phase two, which we intend to get going in the third quarter. It's an oral treatment. It's targeting red blood cells only. So it's very specific to red blood cells. And we have a lot of clinical and preclinical data that enable this. And I'll go through that in a bit. But that really shows that, you know, we've got lots of data that has potential. And we're going to run this study to show that in PV patients, you know, we believe we'll get the same effect. So the goal of treatment, so with PV, there's two primary goals. These patients have essentially excess red blood cells, and your blood coagulates and thickens and causes the potential for thrombotic events. And so there's two kind of known clinical measures that physicians try to control in patients. One of those is hematocrit. So being able to control the amount of red blood cells that a patient has is one of the critical parameters that increases the risk or decreases, in the case of you can control it, potential thrombotic events, which is the real risk to patients. Also, they, you know, they have other symptoms. They have, you know, enlarged spleens and other fatigue associated with the treatments because oftentimes the treatments are front-line therapy as phlebotomies and other agents that cause off-target, cytoreductive agents that cause off-target activities. So you want to alleviate symptoms and ultimately to reduce the risk of some kind of a thrombotic event stroke, et cetera. This is the high risk for patients. So patients have mutations in JAK kinase, which basically signal to progenitor cells to produce a lot more red blood cells than are necessary. And so that's the fundamental cause of this. So by having a red cell targeted therapy that doesn't, you know, it's not a broad side or reductive agent that reduces red cells, white cells, much like an oncology type of agent, then you can treat the disease potentially without having all the side effects and have a much better quality of life for patients. Currently, they use phlebotomy or bloodletting frequently in patients. So patients that we'll be studying in our trial have at least three phlebotomies every 24 weeks. So it's pretty common, so you're taking multiple phlebotomies, and then they use low-dose aspirin to control platelet production, which is the other high risk besides somatocrit, so those are the two kind of clinical therapies that are used. And then cytoreductive agents, as I've said, they use hydroxyurea and other agents to try to control the red blood cells, but the issues oftentimes are you hit other cells besides just the red cells. All right, so as I mentioned, we have lots of enabling data. So these data are from a petroboral. We studied it in non-tuberculous mycobacteria patients, and you can see that hematocrit, But EBO is the blue or dark line, 500 milligrams once a day. And the red line is basically background therapy or placebo. And so you can see a nice reduction in hematocrit over the first four weeks, and then it kind of plateaus. And over the course of six months and even longer in these patients, there was over 100 patients, you get a 10%, 12% reduction in hematocrit. like four percentage points, and then as soon as you take therapy off, it returns to baseline. So this is kind of a, you know, shows the very specific nature. It's stepwise. This is kind of what you want to see in this type of patient. So patients who have high hematocrates, you know, the idea would be you'd phlebotomize them or reduce them to lower than 45%, which is kind of in the normal range, and then be able to maintain them rather than having to continuously do phlebotomies and reduce, and they're very fatigued, and then they eventually eat their way back up to high hematocrates, and then you have to phlebotomize them again over and over for the rest of their life, essentially, is how it's treated. So if you had a medication that could do this in a very controlled, targeted, red cell targeted way. So these are the enabling data from non-PV patients, and so the goal of our phase 2 study is to show that in PV patients we see a similar effect and that we can control hematocrit. We also have replicated these results in many other trials, so on the left-hand side you're seeing a one-month phase 1 study at multiple doses of a petroboral, so you get this kind of, you know, this is just kind of zeroing in on the first month, but you can see a nice, not really rapid drop like you might see with cytoreductive agents, but a good, you know, fairly rapid rate to get it under control. And then as soon as you take off the drug, you get a return back to baseline. On the right-hand side, these are long-term chronic tox studies in NHPs that were done. And so these doses are in doses for NHP, but for effect, one of the questions we always had was at high doses, so at 450 milligram per kilogram, you know, that's equivalent of 4,500 milligrams once a day oral. You know, it has the same shape, so there's not this bottomless, you know, drive hematocrit down, you know, too low. But here you're seeing, you know, maximum kind of a 6 percentage point, which is a pretty big drop in hematocrit, and then returning to baseline. And these are, you know, that was the no AL dose on this study.

Operator

So we've seen it repeated.

Eric Easom, CEO

In terms of specificity, so white blood cells, you know, a lot of these agents will also have effects on other cell lines. So you ideally wouldn't have that. You'd have a red cell specific, like a petroboral. So we see nothing in the same group of 105 patients in white blood cells compared to placebo. You see a slight mild increase in platelets, but nothing of concern here at all. So this is, again, the kind of profile you'd want to see. So, as I mentioned, there's two primary clinical pillars that physicians want to try to achieve to reduce the thrombotic event. One of those is hematocritic control below 45. The other is platelet reduction. So, you can see with current therapies, this was done in a large study, that less than, you know, 57% of patients after three months were not controlled with current therapy. So, you know, given that it's one of the most, you know, the biggest treatment goal and that you have 57% of patients are not well controlled, there's still a significant unmet need to try to control hematocrit in these patients. So that's why we need additional therapies to do this, like a Petroball, and having an oral red cell selective agent would be ideal that has minimal titration, so other drugs in this space have kind of onerous titration schedules. They're slow-acting, and they have ultimately tolerability and other issues. So there's a big need, I think, for more tools to help patients reduce the thrombotic risk, and that's where a petroboral would fit in. Okay, in terms of the study, we're doing the phase two. We'll have essentially three parts. So the sentinel group will start in the third quarter of this year. This is open label, both the sentinel and then this part one are open label. So the sentinel will look at 10 patients at a very low dose. So we've never dosed a PV patient. So we want to go in at a, we're dosing at 250 every other day just to look at safety, PK, make sure everything lines up. And then we'll enter into this dose titration where they would start at 250 once a day and then individually titrate patients to the control that they need. So if you need a little more, you could go to 500 once a day or 750 once a day. And we'll analyze all that data, and then ultimately we'll randomize patients in Part 2 to a placebo-controlled trial where we can incorporate more subjective measures like PROs that measure fatigue and other elements that come into play in addition to, you know, lowering phlebotomy needs for these phlebotomy-dependent patients. I should have mentioned, these are going to be phlebotomy-dependent patients that have three or more phlebotomies over the previous 24 weeks, and they can also be on a cytoreductive agent, and you would add a petroboral on top of that to show that we can control hematocrit. So we'll have data throughout, you know, later this year, potentially on the sentinel group. We may not see a lot of efficacy given the low dose, just because it's kind of a starting, but then really in the dose titration throughout the early part of 27 into mid-year, we'll have a lot of data coming out of that Part 1 open label that we'll be able to share. Okay, and I just covered the data kind of readouts there. So, all right, going to our next program. So mycobacterium obsesses is part of the non-tuberculous mycobacterium lung disease. So this is a chronic infection that essentially affects the bacteria that affects the lungs. It is a related bacteria to tuberculosis, which is transmitted human to human. Abscesses is an environmental pathogen that you pick up in soil. It's in hot water heaters, hot tubs. So that's where the exposure comes from. And ultimately, you have a much higher five-year mortality. It basically deteriorates the lung, lung function. They become very fibrotic in cavities and ultimately is detrimental to lung function. So it's chronic. It's very serious in patients. There's about 15,000 of NTM patients in the U.S. It's mainly older, mainly postmenopausal women, but also men can have it. They often have comorbidities with COPD and other kind of lung diseases. And there are no approved therapies from the FDA. And so the real catch here, I think, is that patients who have this, they end up having a lot of coughing, breathing difficulties. They're very fatigued, and, you know, it's just a race to kind of the bottom over time. And so basically old antibiotics are used, and it obsesses the drugs that work are IV antibiotics. So you have to take IV infusions every day, multiple drug cocktail. So it's, you know, think of like, you know, oncology type of a treatment. So the idea of having an oral therapy is kind of backbone to this regimen, and ultimately an all-oral regimen will be a huge advancement to patients and their quality of life, and hopefully you can kill the bacteria and get them back to normal. So a petroboral has shown great promise in this area, and particularly for abscesses. So we have, you know, it's a differentiated profile I've mentioned. And it's a novel mechanism, so there's no preexisting resistance. So many of these drugs have been used for decades, and patients have developed resistance. These patients are often, as I mentioned, treated for months and years on end, like multiple years. And so there's a real potential to develop multidrug resistance, which is why they're dosed in these cocktail combinations. So we think we have a good safety profile. oral would be great for patients. And so the trial we're running is an 84-patient trial. It's being run by the PI is Kevin Winthrop, which is one of the primary authors and world experts in this space out of Oregon Health Sciences and a number of other prominent physicians who also treat many patients in the U.S. We have microbiological and PRO endpoints, and we've done extensive kind of PKPD dose selection for this study. Oops. I'm kind of stuck on this slide here. Hang on.

Operator

Oh, there we go.

Eric Easom, CEO

Okay. So, you know, another important part is we've tested a number of preclinical isolates that It came from patients' lungs, and we look for, you know, how potent our petroboral is against these mycobacterium abscesses pathogens. And so you can see here we are really potent against, you know, over 100 isolates. It's got a really tight range. For those of you who have been following our story, we also did a MAC trial in really severe, advanced late-stage refractory MAC patients, and the MIC-90s in those cases were, you know, 16 and 32. So here we're over 250 times more potent against the bacteria, which is important in PKPD. The patients we're studying are naive, so they're going to have, you know, minimal cavities. We're doing all this, you know, in early-stage patients to really show the antibacterial effect, and then we would go into further studies. I may need some help on advancing the slide here too. Unless there's a, oh, here we go. So here I've got on the next two slides a number of animal studies. So we've done these with a researcher at Johns Hopkins. And we compare ourselves to imipenem, which is one of the IV-only antibiotics that is considered to be kind of the gold standard. And here you can see our oral drug, compared to control, which is shown in the green, is where we show efficacy that's similar or almost as good as the best drug that we have for this, which is this imipenem IV antibiotic, at two doses. And so this was super exciting to the researcher at Johns Hopkins because they've never really seen an oral drug to be as effective as their best drug they have for this disease and animal models. And on the next slide, there's one other oral drug that's in development now called amatocyclin. And so here you can see this drug has performed a phase two, shown very positive data, and is starting to be used more and more in abscesses patients. It's a drug by Paratek. And so you can see our drug in the same animal models is sidle versus a more static kind of profile in terms of bacterial killing. So we've got a very effective against a drug that's been shown to have very good phase two activity. So it gives us more confidence that our Phase II data will be on track. We're doing two dose groups in the Phase II study, so you can see here, and that will start, you know, it's already started. We've started dose, and we made an announcement in the first quarter, and we'll have data late next year for the study. And that's what I just mentioned there. So, okay, so the next one I really want to highlight is Chagas disease. So Chagas disease is a parasitic disease of muscle, but the muscle that gets you in trouble is the heart. So these parasites, you get bitten by a so-called kissing bug is the common name. The kissing bug transmits parasites. They go into your muscle, and they live silently. So this is really a silent killer of patients. They live in the heart for years and years, and they cause inflammation and fibrosis in the heart, and then you ultimately end up with heart failure in about 30% of the patients, or patients drop dead of an aortic aneurysm is kind of the endgame, and about 30% of patients have serious outcomes. It also affects the GI and other parts. So our drug, AN2-502998, is a drug we discovered. It's an oral therapy that's used. There's 10 million Chagas patients. There's not a drug approved by the FDA for chronic Chagas, and there's 300,000-plus patients, as I mentioned. So this is a real unmet need. Many people don't know this or they think of it as more of a global health issue, But it's really an entire Latin America or the Americans, including North America. And I'll show you some distribution. So this just shows kind of a patient heat map, if you will, or a map of where you see concentration of Chagas disease all over the United States. So this is where patients, you know, the estimates have come from. They're, you know, they're in the most populous states and also where there's a lot of Latinos, including California, Texas, Florida, the South. But the kissing bug vector, the other thing I want to mention is there's infected kissing bugs that exist pretty much from Indiana, across the U.S., and South. So the vector is right here in the United States. It's in Central America and South America. So it's a real serious problem. We have no idea really about transmission. It's not measured. We don't know that much about it, but we do estimate there's 300,000 in the U.S., a couple hundred thousand in Europe, in Spain, Portugal, places like this. Okay, so our drug, there's two drugs that are approved for more of an acute pediatric form of the disease. So when you first get bitten, you get kind of a mild flu-like disease. It's rarely, if ever, noticed and missed, and 99% of the patients have chronic form of disease that causes the serious heart. So these drugs can be used, but they're not very effective, and they have a lot of safety and tolerability issues in older patients. Our drug hits a novel mechanism of action, CPSF3. It's involved in mRNA processing. And so this is completely enabled by our boron chemistry. We have a sister drug that we were part of the discovery for another trypanosome disease called African sleeping sickness that just showed phase 3 data of 96% cure in patients with that disease and has been recommended recently by EMA for approval. So we know this mechanism works in trypanosome diseases and so forth. And importantly, and what we mentioned this morning, is we've run a third monkey study. So the one I'm showing here is two months of dosing. This was the first one we did. This was done at a prominent cancer facility in Texas. And they have primate colonies that they use for medical research. And here you can see the blue line is we were able to cure, parasite cure, or sterile cure, which is critical because if you don't kill all the parasites, they will recrudesce and come back for out to a year. And we even tracked these with our researcher, Rick Tarleton, at the University of Georgia for multiple years. So we know we cure these monkeys of parasite. The middle line there is benzinidazole. That's the one that's approved for acute disease. It doesn't work very well in this model, and it's similar results in human. And then you have pretty severe toxicity issues that make it almost impossible to treat patients. And then the bottom line is just there to show, so Esci Pharmaceuticals and also Merck had a compound similar to this, both failed in clinical trials, and you can readily see it in this monkey model. So this monkey model is not really a model. It's a natural infection by the kissing bug with genetically diverse parasites. And so we're able to cure. So we have high technical confidence. And the data we announced today was 28 days. So we planned a dose in the human study for that. And basically this just goes into more detail about the monkey model. All this is available in our corporate presentation. So I'm going to, for speed, skip forward a few slides here. So the other point that we try to make is that Chagas disease is, The closest example we can give is like hepatitis C. So hepatitis C in the United States was a major problem. About 30% of patients develop liver disease, liver transplants, liver failure, liver cancer they end up with. And so Chagas is about the same, except it's the heart, not the liver. It's smaller. It's about, you know, a tenth of the size, 300,000 versus 3 million. But as you may recall, the hepatitis C market was a $200 to $300 billion market. So we think we have a real opportunity here not only to help the 10 million patients with a drug that can actually cure the parasites and help the disease, but in the U.S. and in other major markets, there's a significant market opportunity that we're working on that is not really out there. So we've got the phase one data in the NHP we just announced today. We'll initiate a phase two later this year, and then we'll have top line around third quarter next year on this phase two study. So here, just to summarize, we've got three phase two programs that are going to read out data starting later this year and throughout next year. So we have a lot of value creation, a lot of risk mitigation, a lot of potential to help patients with really serious diseases. But because we're a boron platform and we follow a lot of biology, we've also got a couple of oncology programs I'll just quickly highlight. One's a PI3K alpha. We have our compounds that we are going to bring forward into development that we think are pan-mutant specific, more in the synovation kind of mode, if you think about it, versus a relay kind of compound that's kinase-centric. And then we have an ENPP-1 program for oncology. So I think I'm out of time, but I'll leave it there. But lots of good work going on, and we're excited about all of this.