Two compounds that hit targets that have not been in human drugs before, so that's really novel and interesting: one antibacterial and one antiparasitic. Recently we have also started work—not that recent, but over the last couple of years—in oncology, and I'm going to talk more about that. Boron chemistry, we think, allows, if you pick the right targets, to move very quickly. They have good drug-like properties, PK, all that. Another important feature is we're not in a really crowded IP space, so from an oncology point of view, where the competition's far greater than infectious diseases, it's a huge advantage. There's no issues with freedom to operate or anything like that. Not only is it, we think, sometimes a better approach scientifically, but also from an IP point of view. That's a little background.
Okay, perfect. I know we just last week had the phase III readout we were waiting for, for e petraborole oral antibiotic in refractory MAC NTM, and I think we'll come back to that. I wanted to start with the oral candidate you have for Chagas disease. That's AN2-502998. You can just call it 998. You know, an indication probably not on most investors' radar, but serious indication. Just tell us a bit about the disease, its status here in the U.S., how it's diagnosed, and things like that.
Yeah, happy to. We have this is a compound that started in phase I. We're going to be doing that in the second half of this year, so it's going to move relatively quickly. Chagas disease is something that, at least in the U.S., people don't know a whole lot about it, but it's a really serious infectious disease. It's throughout the Americas, and it's transmitted by an infected kissing bug, so a beetle-like bug that bites you, takes a blood meal while you're sleeping, usually on your face, deposits on your face, defecates, and you scratch, and the parasites go into the wound. Seven million people have this. They go into the muscles within your body and live for decades, and the muscles that cause problems are the heart.
About 30% of patients develop serious cardiac issues, something, you know, think serious heart failure, aortic aneurysms, because it's long-term inflammation in the heart. We have a drug that will cure, we believe, the disease for chronic Chagas. Most people don't realize they have Chagas. You have an acute fever and kind of mild flu-like symptoms, and it goes away after a week or so. Rarely is that ever detected, and it basically culminates when you end up in a cardiologist's office or you drop dead or something like this. It is a serious disease. There's over 300,000 patients in the United States alone. There's another 300,000 in Europe, Canada, anywhere where kind of Latin, Southern U.S. Americas have immigrated to Japan, Australia, etc. This is one of these where nobody's paying attention, but there's seven million people and not good drugs for it.
We think there's a really good commercial opportunity. There's also a good opportunity to do good for patients who suffer from this horrible disease. I mean, just to say, like in Brazil, where you've got out of the seven million, there's over a million cases. You know, Dr. Chagas was on the real note. That's how important this disease is in Latin America in pretty big economies. Anyway, we have a drug. It's an analog. We worked on lots of trypanosome diseases. We discovered, or were part of a team that discovered a single oral dose cure for human African trypanosomiasis, or sleeping sickness. It's a novel target. This is part of the boron chemistry. We found it through just science, phenotypic screening. That drug is a single oral cure. It's before the EMA now for approval.
We created another drug for cattle trypanosomosis that kills three million head of cattle in Africa per year. It's a single IM injection that's in development. So we know from the target, we know that it kills trypanosomes. It had 96%, 95%, 96% cure in sleeping sickness. And so in Chagas, we can cure naturally infected chronic non-human primates. So monkeys, they get infected in monkey colonies in Texas, at well-known cancer centers and other places. And so we've treated those. This is not a typical animal model where it's a, you know, somewhat flawed in which ways the immune system has been—it functions just like a human. Their immune system, the bugs know how to, parasites know how to hide out from the immune system, all the features, because they're a natural carrier of these things. So we're 100% curative in non-human primates. That's been published in Nature.
This is really an exciting story. We think that this in the U.S., you know, it's essentially like many HCV market, you know, Harvoni and Sovaldi were things. We've done a lot of work on pricing, payer, finding patients, but we think that's where it's going. We're excited about this drug. It's just now getting to the clinic, and we're going to move pretty quickly to get that to patients.
Okay, great. You said over 300,000 potentially in the U.S., so that would not qualify for orphan, but maybe do you go after the 30% with the cardiac effects? Maybe can you discuss a little bit more the market research? I think you have said you see this as a billion-dollar opportunity. Just how do you get to that kind of number?
Yeah, it does qualify for orphan. So it's already been pre-qualified. It's part of a neglected tropical disease voucher that's hard-coded in the Orphan Drug Act. This one doesn't expire like pediatric. It's eligible for a PRV, which is a nice bonus for us. It is that, and I think it's because there's just not many patients who are identified and treated in the United States today. Right now, because there's not really good—there's two drugs that are approved for acute Chagas for pediatric patients, which is almost never seen or treated because they don't detect it. We think it's fairly straightforward. There's a rapid serology diagnostic, multiple ones available in the United States. I've taken it. I went to Stanford, and they take a blood sample and, you know, send you the result in a day, just like any other.
I think it's a test-and-treat strategy. We know that people from Brazil, Bolivia, you know, there's certain geographies, Mexico, get this. And we think that it's just driving awareness around that. There's just never been a drug or any effort from companies to get behind something to create awareness of just know your status like HIV or anything else and treat, test and treat. That's how we will plan to drive it.
Okay, great. Maybe discuss the regulatory path. How do you—or is that to be determined? Have you had discussions with the FDA? When do you think you might be on market?
Yeah, so we haven't yet, but you know, our base assumption here is because of the high unmet need and seriousness of the disease, you know, we can do phase II and a single pivotal phase III trial. There's been several of these I should mention run. This is a really important point, is that Merck had a compound about a decade ago that failed in the clinic. Eisai, the big Japanese company, had a compound that failed, and then a nonprofit has had one that failed too. So there's been multiple trials. The investigator that has been involved in all those that's working with us, you know, she can recruit, she says, 100 patients per site in Bolivia and countries like that within a year. You know, these are pretty quick studies. Treatment will be, you know, one to two months.
Anyway, what I wanted to say was if you put those same Merck compounds, Eisai compounds into this non-human primate naturally infected chronic model, they fail. I mean, it's very predictable. They have very poor efficacy, maybe 10% cure versus 100% cure. I think that's—so we think we can move it pretty quickly. phase II is already being planned. The phase I will run now, just a standard sad mad trial in Australia. We're going to run phase II next year in Bolivia and countries in Latin America, but primarily in Bolivia. The phase III can start pretty quickly after that. It's not too far of a distance to get there.
Okay, great. I want to switch to IV of epetraborole for melioidosis. You have an NIH grant for that. I guess how far does that get you? What's the—any impact from the NIH budget cuts that you can foresee at this point? And what date are you going to announce this year?
Yeah, so I think—so melioidosis is another disease that most people have never heard of. It's caused by a gram-negative bacteria called Burkholderia pseudomallei. It's in the soil and water, and it's readily accessible to anybody that wanted to do bad things with it. We just are completing an observational trial with really the—there's very few drugs that work, but IV meropenem and IV ceftazidime are used. In the best conditions, we're seeing mortality rates at 90 days of greater than 40%, pushing 50% in patients. This is a very deadly disease. It is a national security threat for both soldiers, you know, our military, as well as U.S. citizens. Military get deployed in these areas, and they pick up the bug because they're really close to soil and water when they get dropped into the jungle of Asia or whatever.
There's a lot of publications about this. It exists in the United States. It's endemic in the Gulf region. If you're really, you know, digging wells or things like this, I mean, there's cases that crop up. It's in tropical areas. Anyway, I think because it's a national security and such a high risk, and those death rates or mortality rates I was mentioning are with the best drugs we have in good hospitals in Thailand. This is scary stuff, and it's not like anthrax where you can't get a hold of it. This you go on vacation and, you know, in Bangkok and get a soil sample, you can culture this stuff. It's readily accessible to people who want to do bad. We had an NIH contract of $18 million.
That takes us through—we're still working out the details—but through phase II proof of concept study, which we plan to start in the second half of this year. It'll take about a—it took us a year to recruit 200 patients in the observational trial. And we did the observational trial, by the way, with standard of care drugs because we really wanted to know what the mortality rates really were, what the patients were, and really to de-risk phase II so we knew how to enroll this and increase our chances of success. So our drug, epetraborole, works in all the animal models. It works extremely well compared to, you know, the current standards like ceftazidime and things like that. It's substantially better. We think it's got a really good shot to reduce mortality in patients, and we're anxious to try that.
I think because it's a national security, it's not a global health or other kind of thing like that. It's a serious issue for the United States military and government, and so therefore it hasn't been subjected to cuts.
Okay, great. Do you have a design already for phase II? i guess what's gating to starting that trial, and how quickly do you think you can enroll that?
Yeah, so we're just finishing up the—we're going to read out the observational trial, and then we've already manufactured IV drug, so all the drug product is done now. It's really a matter of getting kind of getting the final scope of that design done with the observational. There's no—I don't think there's any serious gating effect there.
Okay, but you'll speak to FDA, sounds like, after the—
Yeah.
Okay.
Yeah, and I mean, this commercially is not, you know, this is one where, you know, there's going to be sales in endemic countries, including the U.S. There's quite a bit of it in Australia, especially the Northern Territory, melioidosis. There's government stockpiling for biothreat reasons, which will have some revenue. We also think it'll get a PRV. You know, all those are nice to have, but mostly it's, you know, we want to help the terrible outcome of this disease.
Okay, great. Maybe so back to oral epetraborole . Last week you had the phase III readout for refractory MAC NTM, and you know, unfortunately, placebo kind of reared its ugly head, highly refractory pretreated patients. But how are you thinking about the oral formulation going forward, MAC NTM? Your press release cited abscesses. Just what are you thinking about there?
Yeah, I mean, I think, you know, when we started off, there's a huge need for new NTM drugs. There's only one FDA-approved drug. It's inhaled Arikayce liposomal amikacin, and it's really difficult for patients to take. And very few of them—or not very few, but, you know, 35%-40% of patients discontinue pretty quickly. But it works okay. We had a perfect plan. We're going to go in and do a study on top of background, just like Insmed did with Arikayce . Oral therapy, people prefer that over inhaled, and that was simple. All that was based on we're going to enroll similar kinds of patients that they did. What ended up is we missed the endpoint. We had a much more severe population.
You know, we started enrolling this trial in the pandemic and kind of post-pandemic and post-Arikayce being on the market for six years. We ended up with a really substantially more sick population in terms of long years of disease, lots of fibrocavitary, cavitary. You know, this is a—it's really, you know, pushing close to they have no options. It's almost salvage kind of therapy. I think, and what we saw in those patients is, you know, MIC levels that were eightfold higher than what we had anticipated, things like that. I think, you know, it was more the population than it was the drug, and it was hard to see a signal. We do see signals of effect. We had a very phase II data set.
We think that there are other less severe populations, and the one that we're probably most interested in is abscessus because our data is quite spectacular. We think it's more than 250-fold more potent in abscessus than MAC. There's plenty of patients. There's 15,000 abscessus patients in the U.S. There's 25,000 in Japan. There's a lot in Europe. You know, this is a therapy where this is a, you know, a multi-billion dollar market in and of itself, even though it's a small subset of NTM. Look for us to have some decisions about how we're going to proceed over the next months on that front. We're not done. We've got lots of enabling data, so we would be crazy not to continue to look at that potential for this drug.
Okay. Yeah, we definitely heard in our KOL calls the unmet need in abscesses. Most likely you'd pursue that non-dilutively. Is that the plan?
Yeah, there's some mechanism. You know, we really just want to get quick data to show efficacy. We really were swinging for the fences, I think, with phase II, three, and we had a very promising drug here. I think it took a long time, and the patients were really sick. We want to get fast data, and there's a couple of ways we think we can get that in the relatively short term.
Okay, and it's first line MAC NTM still potentially on the table, correct?
Yeah, absolutely. I mean, treatment naive MAC is, you know, there. I think that, you know, the MIC 90, I do not know if we have reported all this, but in these treatment refractory patients for patients who had never seen the drug at baseline, you know, the MIC 90, as I mentioned, was eightfold higher, but it was 32, which was on the high end of our dose. When we did this in panels across Japan and the U.S., it was MIC of four. As long as we have normal MICs, early stage disease, we think this is a very effective drug for this. We are going for the one where our data looks the best, I think, at first. Yeah.
Okay, great. I want a few minutes on the oncology programs you guys just announced last week. You have announced your first two targets. I'm sure there's more to come. I guess maybe just how does the boron platform play into these targets? Maybe you can just discuss the two targets that you have announced.
Yeah, so we've kind of been quietly working. We're primarily an infectious disease focused company, even though Anacor was, you know, anti-inflammatory was what we ended up getting bought by Pfizer from. This boron chemistry can apply to any target, but our expertise has been there. We were working on some viral targets and came across this novel exciting target in cancer called ENPP1, which basically turns a cold tumor hot and is involved in metastasizing of cancers and so forth. There was a pretty important publication that came out a couple of years ago out of Stanford that revealed this. It's a novel, you know, a lot of people have tried to activate innate immunity, and it's got some challenges, but this one seems to have a lot of promise. There's quite a few companies. It's early days.
The human efficacy is just starting to kind of come out from some of these. But the beauty here is that boron, our approach, is perfectly suited for this. We're able to make a lot of progress. So we've been working on this for a while and just revealed that we're working on it. I think there will be a lot of interest. You know, there's no public company that I'm aware of, although they might be working on this. I think we can come up with compounds that have, you know, extremely good potency, better than anything that's been published, but great PK. We'll have a best of class potential, and we're kind of right behind people who are getting clinical data, and we can be able to adjust very quickly. We're super excited about this target.
We're going to put it into development later this year. We're further along than probably a lot of people realize, and we can move quickly. I think, you know, that's the first target. We've also stepped into the very crowded but very interesting PI3Kα world. Lots of competition in cancer compared to ID. Again, we have a tool that nobody has. We're, you know, we're the first-generation compounds, you know, bound to the kind of the catalytic. These are allosteric. We're able to bind covalently to the target, which is quite unique. We also bind in a different location than Scorpion, Relay, a lot of those. The ultimate message on that one is we think that we're seeing that we can hit—there's three mutants that are really important: 1047, 545, 542. We can hit all of those.
It's a pan mutant, and everybody says they have wild type sparing, but, you know, the margins between hitting wild type, which causes a lot of the hyperglycemia and side effect profile that we're trying to avoid, are small. We can get, you know, a hundredfold on some of these more Loxo kind that has since passed, you know, Loxo is no longer, but a hundredfold there. We can get, you know, big margins also, more than 10-20 fold on 542, 545. If we can achieve that in a single molecule, which we have molecules that can achieve that in our hands, we think we can have best of class potential here and follow. The competition we see is Scorpion, Relay, you know, these that are out in front of us, but their profiles don't look like this either.
We are super—we think we can differentiate primarily because of chemistry. And then the other thing is IP. You know, there is a lot of overlapping structures amongst all these competitors, and freedom to operate becomes an issue. We do not have any of that concern. We are pretty—we think we can win there.
Okay.
We have a bunch of other projects behind that. We can create drugs, and we can create them against novel targets, not only first of class, but best of class. We have cash to get, you know, to take us into 2028. We got cash to do all of this within our existing runway. We believe we are going to have multiple ways to win as a company, even though we have just had this, you know, setback in NTM.
Yep. That was my last question. Thank you very much for that time. Thanks for joining us, Eric and Lucy. I was going to ask you about cash.
Yeah.