All right. Good morning, everyone.
First, likewise.
I'm Adi. I'm on the SMID cap Biotech team here at Evercore, and pleased to host AN2 Therapeutics CEO Eric Easom with me. One of the questions we have been starting our conversations with is, as 2025 comes to an end, maybe recap the year. You had a big pivot this year, how that has reshaped AN2, and what you are focused on now.
Yeah. No, thanks for having me. So 2025 was a big transition year, as you say. We had a phase III readout of our lead compound, epetraborole, for nontuberculous mycobacteria lung disease caused by MAC. And so the phase III readout in May. And unfortunately, it didn't give us a signal like we had seen in phase II. But what it did do is create a lot of learnings for us that kind of paves a future path forward, still in NTM, that I'll talk more about in a bit. But in the previous year, in 2024, we had already we're a boron chemistry platform company and had already made an expansion of our therapeutic focus to oncology. And so we have two oncology programs that are slated to go into development in the very near- term. And we'll talk more about those two.
We also entered the clinic with a novel compound and mechanism for Chagas disease, a parasitic infection that you don't hear too often on this stage, but very important disease, and so we have that, so basically in a number of other opportunities that we're looking at, so I think we've got lots of opportunity. We had cash flow to see these through, so cash into early 2028, and a pretty compact team and able to see that out, so it really shaped kind of the future for the company.
Great. So as you suggested, there was a pipeline overview. Maybe we can start by looking at the oncology programs, highlight those, and then we will move to the infectious disease. So can you discuss the pipeline assets you have in the oncology?
Sure. So we have two oncology, two leading ones that are going to enter development, as I mentioned. Both of these are really powered and enabled by our boron chemistry platform. So we do a lot of chemistry biology. We've got two decades of experience in that. And so the first one is ENPP1 inhibitor. So this is an innate immune response for tumors. And so cancer hijacks the signaling pathway for the STING pathway. And so by blocking ENPP1, you restore and kind of turn, essentially, cold tumors hot. It also prevents metastasis. So a lot of this biology has been worked out over the last five years. And we understand it a lot better. It gets around the issues that we're seeing with STING. We're overactivating the immune system and things like that. So we're really excited.
The biology on ENPP1 also is more broad to other therapeutic areas, which we can talk about later, too, so the first one is that. The second one is a very validated target, PI3K alpha. There's lots of compounds, so there's kind of the first generation of alpelisib and these that has a major side effect in that it causes hyperglycemia. Patients can't stay on it long. Second generations have tried to come up with pan inhibitors that hit all the mutations but are wild-type sparing, companies like Relay and Scorpion, but they really are kinase-centric and don't really hit helicase that hard, so we truly have pan mutant wild-type sparing compounds with very large margins over the wild-type, and so we're very excited. We think that there's lots of breast cancer franchises and companies that'll be interested in that.
We also have boron chemistry, which doesn't have a lot of freedom to operate. There's a lot of crowded IP space around that. So there's a couple of advantages. But mainly, it's the target product profile. So those are the two lead compounds.
Great. So using the platform chemistry that you have, what would be the main points of differentiation between the compounds that you develop for these two targets versus what maybe are in the field?
Yeah. So for example, ENPP1, it's an ideal target for boron. Boron's not the solution for everything, but certainly, it hits novel targets that haven't been achieved. But in this instance, we get it's a perfect target. So we're able to get highly potent compounds, highly selective, with good PK, good essentially exposure in different tissues around the body. So we're able to come up with top inhibitors versus other chemistries that are used to hit this target are things like metal chelators and other chemistries that have problems, PK problems, other issues. So we think we will certainly have a best-of-class molecule there with that. For PI3K, boron binds in different locations and other compounds, which we believe is leading to selectivity that we're seeing. So a highly differentiated selectivity profile.
These aren't hitting novel targets like we see in both of our infectious diseases or unknown targets to drugs in humans. These are known but highly differentiated.
Got it. So before we move to infectious disease, what are the key steps between now and getting those first cancer programs into the clinic? And roughly, how should we think about the timing?
Yeah. It'll pick up now. I mean, I think we've moved very efficiently through the research phase because the chemistry was very amenable to the boron chemistry approach. But preclinical, we think it'll take six to nine months, and then we could be in the clinic. So this will move into something really important and serious in the short- term.
Great. And a question which I asked before when we were discussing, how should we think of any preclinical data that might come out? Should we expect something in 2026?
Yeah. Sorry, I missed that. I think for ENPP1, for example, in our corporate deck, we don't have the luxury of waiting on meetings for a year. So we're presenting some of the data around that. So we have incredible animal data. We have synergy with checkpoint inhibitors. They should be synergies with other DNA damaging agents. So a lot of our data, pretty extraordinary data, is we're starting to share in our corporate decks. For PI3K, the same thing. We've got a profile compound that has a 40-fold margin over 1047, one of the key kinase mutations, 10-15-fold for the helicase. And just to contrast that, like Relay has a 10-12X for kinase and a 3X for helicase. So we can hammer the target much harder, we believe, with this kind of a profile.
Great. Great.
That data is out there. We'll be sharing more proactively than just waiting on ASCO to come around.
Okay. Great. So much to look forward to. So shifting to infectious disease, so how would you rank the Chagas, melioidosis, and abscessus today in terms of strategic priority and potential value?
Yeah. So I think of it this way. We're just now gearing up this IIT for Mycobacterium abscessus. This is another one of the many bugs that make up NTM lung disease. And there's approximately 15,000 patients in the U.S. and globally. So it's a $1 billion-plus market just in the U.S. alone. And it's a known market. There's no drugs approved by the FDA for this. Most patients have to have two, three IV-only antibiotics administered daily, if you can imagine. So this is similar to cancer or oncology therapy. There's very limited oral agents available. So epetraborole is an oral agent. And we have tons of enabling data from our phase III trial. We were gearing up to file an NDA as quickly as possible.
So we believe that this study will be phase III enabling and really move the needle based on the outcome of the study one way or the other. So that we think of very highly. Chagas disease is different. There's no real uniform cure for chronic Chagas disease. So this is a parasite that goes into people's hearts and GI tract and causes aortic aneurysms, heart failure, serious complications in about 30% of the patients. When I give you the next number, it'll be more shocking. There's like seven to 10 million people with Chagas disease that have parasites in their heart. So most people don't know much in this country or the developed world because it's primarily a Latin America disease. But it's kind of hit a viral moment in the U.S. where there's lots of kissing bugs that are infected in the U.S.
There's more than 300,000 cases in the U.S. There's more than 100,000 in Europe and other places like Japan. So it's a commercial market that has to be developed, but the need could not be greater. We have a compound that cures non-human primates of a natural infection that are living in Texas, infected in Texas. So it's 100% curative in these monkey models. It's a novel target. We also discovered another trypanosome drug called acoziborole for African sleeping sickness, which none of you ever want to get because it goes into your brain. But that's before the EMA and is expected to get approved in the next three months. So that's a single oral dose cure. So we believe this is going to technically work. We have proof of concept already in these NHPs, which is not a model.
That's a market, but it has to be developed. But that's a $1 billion-plus market, we think of that. Melioidosis is different. It's more of a kind of a global health play, but it has a high mortality. We had 40% death. We ran a 200-patient observational trial, had 40% of the patients die in 90 days. So highly lethal bacterial infection. And so that's a government priority in terms of biothreats. It's potentially eligible for PRV. It'll be funded non-dilutively. So it's something part of our global health mission more than anything, but it's an important program.
Great. So just going over these programs for the abscessus program, what does a realistic path look like? You have an investigator-initiated work ongoing. And so from there to a clear registration, what would that look like?
Yeah. So this is not a typical IIT. I think it's going to be. We haven't disclosed too many details, but it's going to be a pretty significant, like 90-patient trial that's going to be proof of concept in patients and will support a phase III initiation. So I think we're, and it's also led by the top investigators in the world in this field. So it's a pretty exciting thing for us. It also is being, because it's an IIT, run by those investigators. So it frees up a lot of our resources to focus on a lot of big pipeline projects that we have beyond that.
Great. Great. And one of the things you mentioned for Chagas was that you have very strong non-human primate data.
Yeah.
Right. Can you share how you'll move to phase I and what you'll be looking there to move further into phase II? Because as the monkey data is very strong. Discuss the clinical path there.
Yeah. I should emphasize it because the monkey data, Merck and Eisai had compounds that went in the clinic for Chagas. Both of those failed in the clinic, and when you test those in this monkey, it's not a model. It's a real infection with an immune system that works just like humans. It completely shows that those would have failed in that, and we're 100% curative. We publish these data. So really, it's about PK/PD in the phase I and safety. So we're well into the phase I. I mean, we're already into the multiple ascending dose and things like this. So as long as we have a dose that hits the right PK parameters, then this is a truly transformative potential oral therapy for this terrible disease.
Got it. So you've leaned a lot on partnerships and non-dilutive funding.
No.
How should we think about the balance between the partnered versus wholly owned programs? And I think you touched on the cash runway a little bit, but can you just discuss that again?
Yeah. I mean, we're innovators at heart. We're a boron chemistry platform company and want to innovate and develop our own drugs. But we can't do it all. And so I think we have part of the non-dilutive is we do a lot of global health. We just signed an agreement with GSK and Gates on tuberculosis, the next generation TB, which, by the way, is the same mechanism as epetraborole for abscessus. So this is the third or fourth deal we've done with GSK around these sorts of things. So there's a lot of confidence around that. But you're going to see from us that we can't do all these things. So there's other indications and things where we can have a chance to partner, bring in real cash, non-dilutive cash, not just the global health deal. And that will help our runway too.
So we'll develop what we can, but what's beyond our capabilities now, we'll partner those and try to leverage and accelerate. But you can see from our pipeline, we've got four things I've told you about. There's another three or four that are very exciting. And I think so we don't have to hit on one of them. We're a pretty small cap biotech right now. We're recovering from this phase III, but we just need to stick the landing on one of these, not all four or five, to do this. So I'm feeling very confident and lots of conviction around our potential.
Great. So you're looking ahead at 2026. It would be hard to pick, but maybe what are the most exciting milestones or catalysts to look forward to?
Yeah. It's interesting. I was at a CEO conference recently, and the Regeneron CEO was saying, "We don't focus necessarily because none of us are smart enough to pick the winners." And that's my experience throughout my whole career. You think it's this, and it'll be something completely out of left field that hits. So I think we're pursuing all these. We're able to get a lot of leverage across some of these programs too with IITs and things like that. But we're going to have the abscessus trial start up. And through most of enrollment in 2026, we're going to have the Chagas phase I complete soon and initiate the phase II. We've got our two cancer programs going into development. And then we've got another three or four tricks up our sleeve.
So we've got a lot coming down in 2026 that I think will show great progress and also show this idea of having multiple chances here to win.
Got it. So one thing you mentioned was that you won't be waiting for any conferences to share more and more preclinical data from the cancer side of the pipeline. As the Chagas completes the phase I, should we be expecting data release from that before it moves on to phase II?
Yeah. I mean, we'll give top-line results probably in a press release. But with that one, we will probably present at a conference in the fall, is the plan. But that's, and we're planning on the phase II and starting that.
Okay. Okay. Great. Great. That brings us to almost the end of our time as well. Thank you so much.
Thank you.
Yeah. Great discussing.
Pleasure being here.