Traws Pharma, Inc. (TRAW) Earnings Call Transcript & Summary

Good morning, and welcome to the Traws Pharma Investor Call on Bird Flu and COVID and Traws innovative small molecule product candidates. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be made available on the Traws' website following the conclusion of the event. Before we begin, on this slide, you'll see Traws' standard disclaimer language. Statements in this presentation and on this call may be forward-looking, including our plans, objectives and expectations for our antiviral pipeline programs. These matters involve risks and uncertainties, and the company's actual results may differ significantly due to a variety of factors that are discussed in detail in the company's SEC filings. And with that, I'd like to turn the call over to Dr. Werner Cautreels, Chief Executive Officer of Traws Pharma. Please go ahead, Werner.

Thank you, Tara, and good morning, everyone. I am Werner Cautreels, and I'm CEO of Traws Pharma. Welcome, everyone, to Traws' investor event, and thank you for joining us today. Today's event is an important event for Traws. We will discuss the unmet needs and the public health risk in bird flu and COVID, our 2 antiviral product candidates. Our 2 main speakers today are Dr. Robert Redfield and Dr. David Pauza. Dr. Redfield is our Chief Medical Officer, and previously was Director of the CDC. Dr. Pauza is our Chief Science Officer and will be presenting the data of the compound. Today also, our Executive Chairman, Dr. Iain Dukes, will be part of today's call, and some other members of the management team will be available also to take your questions and answer those questions. We believe that our antiviral compounds have the potential to be best-in-class compounds, as you will hear today. Our lead program is tivoxavir marboxil in development for bird flu. We will also introduce ratutrelvir in development for COVID. I'm now turning it over to Robert Redfield, who will start on the bird flu and medical need and public health.

Bird flu is a growing pandemic, as many of you know, particularly in the agricultural space, but it does have enormous pandemic potential if it learns how to eventually go human to human. Right now, we've had -- from 2019 to now, we've had over 150 million chickens and turkeys infected. It's now infecting over 40 million species in the United States, although it hasn't learned how to go mammal to mammal. It only seems to know how to go bird to bird. There's a small species barrier for it to eventually flip over to be able to infect humans. So far, we've had approximately 70 humans infected in the United States, all of them from bird to human with no evidence of human to human transmission, but the pandemic risk when this virus learns how they go human-to-human can be catastrophic. The human cases that have occurred, particularly in Southeast Asia have had greater than a 40% mortality. So this does pose an enormous potential pandemic risk. And if you look at what we're seeing right now, we're seeing a huge epidemic in the agricultural space, particularly in chickens and turkeys. It's also moved into dairy cattle. More recently, it's moved into pigs. And very recently, it's moved into sheep with this virus moving among those agricultural animals fairly efficiently, although it doesn't appear to be going mammal to mammal. It's going bird to mammal, bird to mammal, bird to mammal. Eventually, what one can see is there's occasionally cases of bird or dairy cow to human. And when that occurs, so far the human has not transmitted among other humans, but that's the real pandemic concern that eventually through changes in its amino acid sequences that it will learn how to go human to human. And when that occurs, it will cause a catastrophic bird flu pandemic. So when you look at right now, the issue with bird flu, clearly, one of the important things about the product that we're developing, it has a broad resistance profile against avian flu strains, including the strain of the Texas dairy worker, which is currently a prototype strain and the strain of the individual that eventually died of bird flu in the United States. It's a very good pharmacokinetic profile and that 1 dose will provide protection. We're probably up to 3 weeks. And it's also been shown to reduce disease and mortality in 3 accepted preclinical animal models. It is able to cause a massive reduction in virus replication in vivo in all 3 of these animal models. One dose is able to maintain a plasma level of above the EC90 for, as I mentioned, at least 3 weeks in our Phase I studies. And overall, it has an excellent tolerability profile, which will enable even higher concentrations to potentially be used to treat or prevent bird flu.

So good morning, everyone. I'm David Pauza. As Werner said, I'm the CSO, and I'll walk you through some of the current data that we've obtained to really pursue the application of this compound in the bird flu space. So several years ago, as we were beginning to worry about this problem, Dr. Redfield and I had spent a lot of time talking about the future pandemic potential of influenza, and we have been watching this for a long time. This compound, at that point in time, was then introduced into the Centers for Disease Control, who assayed the compound against a number of H5N1 type viruses that were circulating in nature in 2022, 2023. And on the right side, you see the EC50, or effective concentration 50%, in nanomolar for tivoxavir. And you see it's all sub-nanomolar concentrations against these H5N1s. So we knew we had a compound that was potent and it was going to be at least in the game for preventing a future H5N1 outbreak. Now, Dr. Redfield also mentioned the transmission of this virus from a cow to a dairy worker in Texas. We think that we are very fortunate in that instance that, that person did not subsequently transmit that virus to other humans. And the reason is because that the virus in the dairy worker evolved 9 unique mutations that were not present in the cow who infected him in the first place. Those mutations are all associated with increased deficiency of virus replication and increased transmissibility. And so I show in the -- you the map there to show you the distribution of these. Those are the unique ones that separated the virus in man from cow. So as soon as that virus got into the Texas dairy worker it started to adapt quickly. And that's the problem that will fuel any future pandemic outbreak. When we look at commonly used antiviral agents against -- that are used against seasonal flu, these were tested against the same Texas isolate, the A/Texas/37 isolate. So if we look at oseltamivir on the right, which is Tamiflu, against the -- an H1N1, which represents seasonal influenza, you see that the EC50 there is sub-nanomolar. If we look at that same compound against one of these H5N1s that I showed you on the previous slide, it would be a collection of those kind of wild viruses. It's already significantly less potent with a higher EC50 of 2.7. And then you go into this A/Texas strain and you get this remarkable problem of that A/Texas strain now as 530 EC50. Now we have to be careful because that Texas dairy worker was treated with Tamiflu, and this may be a resistant variant that emerged in him. But if he were to transmit that, he would be transmitting a completely Tamiflu-resistant virus. Baloxavir is another compound that has -- is available for seasonal flu. You could see it has a little bit about 1.5 nanomolar EC50 against H1N1 seasonal flu. It's fairly potent against a representative H5N1s in the wild collection, but it's extremely higher EC50 against the A/Texas strain. So while these antivirals will be used right now as the primary therapeutics for these viruses, you can see that they're unlikely to be highly effective in controlling this, especially after this virus begins to adapt in people. So we began the more serious investigation, the deeper investigation of the H5N1 by taking this virus, this A/Texas virus, and putting it into a mouse model. And we were one of the first groups that was able to do this because we had early access to the virus strain and vendors with the capability to do this at Biosafety Level 3. So infected mice through the intranasal route and treated them 1 time with our compound tivoxavir marboxil by oral route. So we're preserving as much as we can a mimic of the clinical experience. On the right side, in the top panel, you see that the vehicle control animals, shown in black, are all deceased by day 6. That's a very rapid killing in terms of most influenza strains. Commonly, when you work with an influenza strain in the mouse, you adapt it to the mouse first and then you study it. This is the human virus, just grown once to expand the virus and then put directly into mice. So there's no adaptation here. The treatment with tivoxavir marboxil called TRX-100 on this slide provided 100% protection and where all animals were surviving. On the lower part of that slide, you see a very typical marker for influenza, which is a rapid body weight loss shown for in black for the untreated animals, and in red, no body weight loss for our treated animal group. So in that initial animal study, tivoxavir marboxil is an outstanding antiviral. To go a little bit more into this, the 2 main things we're really looking at to evaluate any antiviral efficacy would be, number one, body weight, as I mentioned, and number two, how much virus is growing in the lung. Virus growing deep in the lung is the real challenge here and will be the real lethal mechanism of viruses like this. As you can see on the left, in the vehicle controlled animals, virus titers in the lung are very, very high, sometimes approaching 10 to the 9th. If you did this with a typical seasonal influenza virus, maybe the highest you would have in this experiment is about 10 to the 6 virus tighter. So you can already see quite easily that this virus is much more aggressive than a normal influenza. On the right side, we did the virus titration from animals that had been treated with tivoxavir marboxil, and you could see that all animals had virus levels below the lower limit of quantitation. So that's a stunning effect on the viremia. That means that we're close to 6 logs of virus reduction at minimum in this experiment and clearly demonstrated why these animals were surviving. Our next effort was to move this into ferrets. Ferrets are a commonly used strain of animals for looking at influenza outcomes doing therapy and vaccine development. So we took ferrets, we inoculated them with a lethal dose of this A/Texas virus. In this case, it was 1,000 infectious doses. And we treated them with 2 different dose levels. One dose level was equivalent by scaling to 120 milligrams dose given in humans, and the second dose was equivalent to a 240 milligrams in humans. The previous mouse experiment was done with 240 milligrams in humans equivalent. I've put these numbers on here, very importantly, to make a contrast with baloxavir, which baloxavir is an approved drug, and the label says that if you're 60 kilograms or less, you can treat with 40 milligrams. And if you're above 60 milligrams (sic) [ 60 kilograms ], you can treat with 80 milligrams. And you can see that those 2 approved dose levels are not very close to what we're looking at here. So we had 2 groups of animals. We treated them. We looked at our 3 indications; survival, body weight and virus burden. And we saw a pretty dramatic effect of the antiviral on these 3 endpoints. So in survival terms, all ferrets -- untreated ferrets were dead by day 4, again, a highly, highly lethal infection. The animals treated with the equivalent to 240 doses had 50% survival by day 14, and we saw what appears to be a dose effect -- dose response effect by a little bit lower survival in the 120-milligram equivalent group. So -- and in terms of body weight, you see the same thing. And so when we looked at these data carefully and said we got the first 2 criteria that we were looking at correct. We had an increase in survival, and we had a decrease in body weight loss. What about the viremia? And the viremia data from this ferret model are essentially stunning. You can see extremely high virus loads, now clearly in the 10 to the 9 range in some animals with a very large suppression of virus in the animals treated with either of the doses of tivoxavir marboxil. And the lower descriptors there, cranial, caudal, these describe portions of the lung that were sampled individually in this study. These animals were euthanized, and tissues were removed to perform these analyses. So by 3 days after infection, with a single treatment of tivoxavir marboxil, we got this result again showing the extraordinary antiviral efficacy. And I wanted to just show that in a different way. And so if we color code the regions of the lung to represent how much virus was measured in there, then we have the red and orange colors, meaning the highest viral load, and we get down to the blue, purple and pink, are the lower viral loads. So in the controls, you can see the lungs are massively attacked by this virus, extraordinary high virus loads and predictive of extreme lung damage, which is what we've seen in histology studies. In the dose equivalent to 120 milligrams in humans, we see a substantial reduction in the virus burden, and -- but that lower right lung still has some appreciable viremia in it. And that's telling us that this is the real side of attack of this virus. And a virus that grows like this in the lower lung is very dangerous. And on the far right side, you can see the animals treated with the equivalent to 240 milligrams, mostly pink lungs, which is what we're looking for and a little bit of virus still growing. So, again, we've met all the criteria that we established before, and we will repeat this experiment by going to the next higher dose level, which we think will be -- have a much bigger effect and still within our safety range. The final study that we've done is we've completed a study in nonhuman primates. These were in rhesus macaques, and they were infected and treated 12 hours later with, again, an oral dose of tivoxavir marboxil. We used the dose that was equivalent to 480 milligrams in a human, and we have 5 animals per group. Now this experiment turned out to be a nonlethal infection. And as I said, this was very early time with little experience of this virus in nonhuman primates. So the virus dose was probably a little low. We got a nonlethal infection, but it allowed us to explore the parameters, again, that were important to us. So we don't see the survival parameter, but we see the change in body weight and the change in lung viremia as again registering the substantial antiviral effect of this compound. So in terms of body weight, you could see that's a highly significant difference between animals that were treated, in animals that were untreated and with a very extraordinarily good p-value for especially for an animal study of this type. So there was a clear differentiation in terms of body weight. There was a clear -- even more clear differentiation in terms of lung viremia. So if color coated again the same way, and because of the virus dose, we didn't get up into the orange and red zone for virus burden in lung, but we got substantial virus replication in lung in the control animals compared to the treated animals, where we get all pink lungs, which remember, was what we wanted. So we've demonstrated the substantial impact of viremia and a highly significant impact on body weight loss, again, confirming the activity. So now we have 3 species with very similar, very significant data, telling us this antiviral is working. And maybe, Bob, you want to tell us -- well, I'll continue. So we've asked -- we asked ourselves what would we do then to go through and begin to characterize this in humans, and we've completed a Phase I study in humans, which was healthy volunteers looking at safety and tolerability, and the details of the study are outlined on this slide. We looked at participants that were 18 to 64 years of age, males and females. This is the pharmacokinetics result from that study. And I think we see a nice dose response in the pharmacokinetics of a single dose. And I want to keep emphasizing this that this antiviral is given one time when -- as soon as symptoms are apparent. And here in healthy volunteers, again, we gave only one time. And differently than the other products, I want to really emphasize the range of doses that were evaluated in this study. So the range of doses went up to 480 milligrams. Why? Because we believe these are the kind of doses that are going to be required to contain a highly aggressive human-adapted H5N1 virus. And here, I've shown you in dotted lines what it would take to control a seasonal influenza with this compound. And you can see that a single dose is going to give you good viral control out to about 3 weeks. And we haven't really done any more development to try to extend that, and there may be ways to even make that go farther. So 3 weeks control against a seasonal influenza, it may also control dairy workers and poultry workers from that initial transmission of it, of the bird flu into them. However, we know that high -- that we will require the high doses that will be necessary once this adapts to humans. So I think this is also a very encouraging data. And so the primary path for us to go forward is we want to apply this to bird flu. And we believe that bird flu represents an exceptional situation for 2 very important reasons. Dr. Redfield told you of the extraordinarily high lethality of this virus once it begins to spread among humans. We have about 30 years' experience with this virus, and when outbreaks have occurred, the lethality has been tremendous. Second, right now, there are very few cases of this in the U.S. So it would be impossible to do a clinical trial of human-adapted bird flu at the present time. But we believe that the risk is there, the threat is coming. And I would remind everybody that we're in the beginning of the South to North Bird migration, and there's a wave of bird flu coming with these wild birds as they travel north. So we have not seen the end of this. This is not like a seasonal flu, which will just be here for a few months. And veterinary epidemiologists have predicted that this influenza will circulate in domestic animals for at least 5 to 7 more years. So this is an exceptional situation, and we think that the FDA, so-called, animal rule is appropriate here because the animal rule is intended to allow studies where you demonstrate the efficacy of a compound in animal studies because it would be unethical or impractical to do these in humans. And so, as I said, exceptional pathogenicity, the fact that we can demonstrate this efficacy in animals, and we believe these are directly translatable to human beings and that we've already begun to accumulate the safety and pharmacokinetics in human beings. And we are prepared to respond to the FDA guidance concerning going forward. And so now I'm going to stop there, and now, we're going to transition to COVID, and I'd like to turn it back to Dr. Redfield.

I just want to emphasize that COVID continues to be a very significant cause of human disease in the United States today. It's going to be responsible for anywhere from probably 30,000 to 80,000 deaths per year. And this virus, unfortunately, is going to probably stay with us until the end of time. The vaccines that we have right now, they do not prevent infection. They do have an impact on hospitalization and death in individuals that are highly vulnerable. But again, they don't really have an impact on whether someone gets infected or not. And therefore, there's an enormous need to develop effective antiviral. And the virus does continue to mutate. And that means, again, makes the vaccines persistently less and less effective. When we look at why we really need better therapies for COVID, clearly, I talked about the decrease in the acceptance of the vaccine among the American public. Also the fact that the vaccine itself does not prevent against infection. It just modifies disease course. And again, the virus continues to evolve. And so there's a poor match between the vaccine and the circulating strains. It's an enormous clinical burden, as I mentioned, cause -- significant cause of premature death. And again, the economic burden is also substantial, particularly when you look at one of the consequences of COVID is that a significant percentage of people, and it's been estimated between 5% and maybe as high as 20% of individuals who develop COVID develop a prolonged syndrome post-COVID that we call long COVID, which has significant impact on those individuals' ability to work, et cetera. There's really limitations of the current antiviral that we have, Paxlovid. It works. It's an excellent drug. But the challenge with Paxlovid is it requires a PK enhancer, ritonavir, in order for it to get the levels that's needed to be efficacious. And that PK enhancer then makes it ineligible for people that are on blood thinners like Eliquis and many of the elderly that are on other drugs where there are drug-drug interactions so that they really can't take Paxlovid. Again, I will argue that COVID is now really pretty much established as a long-term public health challenge, in need of improved antiviral therapeutic products to help address this challenge. When you look at it, the threat to human health, as we've estimated, this is CDC's estimates, anywhere up to 7 million to 13 million infections, 2 million to 3 million people seeking outpatient visits, for 200,000 to 400,000 basically being hospitalized and CDC currently estimates 26,000 to 43,000 deaths to be attributed to COVID. When you look at the proposition that we currently have with our lead candidate, it has a broad, broad, broad resistant profile, which allows it to be active against a variety of the emergent variants and treatment against resistant strains that are currently resistant to the current Paxlovid-related products that the dose has a very favorable PK profile. It's estimated that it's about 13x the EC50 of the current Paxlovid. The data basically on drug metabolism is extremely, I think, exciting and distinguishes this product in that this drug can maintain the appropriate blood levels required independent of ritonavir, and therefore, makes it available to the high-risk patient population that Paxlovid currently is contraindicated in. It's got a very good safety profile in the Phase I studies that we've done up to 10 days and will allow one to design this drug as a 10-day therapeutic. Right now, ritonavir/Paxlovid is used as a short course of 5 days, and some of us see that, that is maybe one of the reasons why current COVID is associated with rebound in many of the patients that are treated, and also, as I mentioned, associated with a high penetration of long COVID. So we think that this product gives the potential for longer therapy, which we think will decrease rebound and potentially have an impact on the development of long COVID.

Okay. Thank you, Bob. So I'm going to take you now through the data package on the COVID-19 drug, ratutrelvir. It's a main protease inhibitor, as Dr. Redfield said, for a ritonavir-independent 10-day regimen. He'll explain the reasoning for these things as we go through. So ratutrelvir was compared using laboratory testing against a couple of other compounds. So nirmatrelvir is the protease inhibitor component of Paxlovid. And so when you test nirmatrelvir in the lab against a large number of SARS-COVID-2 variants, you can see the EC50 values there on the left panel. And in every case, ratutrelvir is more potent against the same virus tested at the same time. So these panels were commissioned by Traws Pharma and did the head-to-head testing. The ibuzatrelvir numbers are taken from the literature from a publication that's cited there. Ibuzatrelvir is the current ritonavir-independent corona -- Mpro inhibitor that Pfizer is developing, has in late-stage clinical trials, but it's important to note the potency differences here, more than 50x difference against the original COVID strain and really not a very potent drug against the viruses that we see there. So on the right-hand panel that I had taken again, those 3 compounds plus I've added ensitrelvir, which is the compound that is licensed in Japan and currently in clinical studies in the United States. And I've shown you the average EC50 across a number of strains. So nirmatrelvir, we looked at 9 strains that were tested, 23 EC50. Ensitrelvir is 69. For the 3 strains that I could find published, 123 for the ibuzatrelvir, and for our compound, 8.4, and that's tested against 18 different COVID strains. And so when we take an EC50 value, and then, we want to know what's the real threshold value we want to reach in the blood of individuals, what's our predicted window, then we usually multiply that value by 3, get a predicted EC90 value, and that's really what's important for dosing considerations and safety considerations. So you can see the EC90s there are quite substantial. So especially ensitrelvir, 207, and this ibuzatrelvir now 369 nanomolar in blood in order to reach efficacy levels compared to our compound, which is only 25 in order to reach the therapeutic level. So there's a substantial differentiation in terms of potency and efficacy. Now, a very important issue in antiviral treatment is always the evolution of drug resistance. And so here, I'm showing a little bit of information taking from the published literature, which now is beginning to reveal the frequency of nirmatrelvir resistance mutations in populations treated with Paxlovid. And you can see that we got up to 10% of participants in this one study had a Paxlovid resistance mutation already. So that's relatively high, and may indicate that the virus was incompletely suppressed in those individuals. In terms of ensitrelvir, which is shown in the middle panel, the main resistance mutation is this M49L. And you can see the 1 country in the world, which has licensed ensitrelvir, has a massive number of these mutations appearing. And in the U.S., where it's been used mostly in clinical trials, we're also seeing mutations appearing as well against ensitrelvir. In the right side, I gave you a table, which lists one by one all these amino acid changes in the protease gene, which are associated with resistance, and I have checked off which ones are found in nirmatrelvir clinical study and which ones are found in ensitrelvir clinical study. And then I've added the ones that we found in a laboratory study where we intentionally evolve the virus to be resistant to the drug. And you can see that there's very minimal overlap between our resistance pattern and the others. There's a little overlap between our compound and nirmatrelvir, zero overlap with the resistance pattern to ensitrelvir. So our unique pattern of drug resistance indicates that we may be effective against some of the variants that are appearing already, and these variants are continuing to spread in the population. To return to ratutrelvir, we want to show you some information -- direct information about the pharmacokinetics in our healthy volunteer study. And this -- I'm showing you the data for a once-daily dose of 600 milligrams of ratutrelvir. And again, importantly, once daily dose, taken for 10 days. And as you can see, if you plot the pharmacokinetics over a short number of hours, if you plot it for the dose on day 1 and the dose on day 10, the first and the last dose, you could see that there is not very much difference between the PK profile. That tells you we're not inducing the metabolism of the drug, which is the problem with others, where they had to introduce ritonavir. And we're not really accumulating the drug either. So in terms of antiviral, this is extraordinarily well-behaved drug. On the right side, I showed you the drug levels at 24 hours after each daily dose. And it's also important that these drug levels are very stable and very reproducible against -- across the whole profile of 10 days of treatment. And then we can summarize it all here. And I want to come back to this picture in just a moment because I want to put this into context of something that Dr. Redfield mentioned about long COVID. And we internally have long believed that you have to very effectively suppress this virus and suppress it for long enough to prevent viral rebound. And we had the concept for a long time that if people rebound, this is an indication they're going to have a susceptibility to long COVID. And now we're starting to see the first amounts of real data being released from other groups proving this point. So this group presented a poster at the CROI Meeting in 2025, demonstrating directly that there was -- if you have more symptoms of COVID or if you have slower decrease in viremia, you have a much higher risk of having long COVID. This risk is amplified in women. So it's true for everyone, but it's exacerbated in women. And it is the direct common sense view of this, right? If you don't get rid of the virus early and you let it linger, then bad things are going to happen. And so we're seeing the real data of the bad things. And Dr. Redfield has a lot of experience treating people with long COVID and tells us stories which are sometimes quite horrifying. Here's the additional look at the data provided by this group and identifying exactly the symptoms that are most associated with the risk of long COVID. And they are, again, what you might imagine, this brain fog, shortness of breath, GI symptom. And so these are all the things that tell you, you had a more intense infection and it lasted longer than it should have. And if you could reduce this viremia, accelerate the clearance of the virus, you're going to impact these factors, which are making you at risk for long COVID. So finally, just to conclude, I wanted to return back to the PK curve, and this needs just a little explanation because you see the peak on day 0 to 1 and another peak on 9 to 10. That's because those are the only 2 days where we take these samples over a short period of time. But you could see that, again, they look the similar, the first and last dose looks similar. The trough levels are very consistent, and we get a kind of free 2 days after the treatment, days 11, 12 still being in the zone of therapeutics. So remember, I told you that the EC90 was 25 nanomolar. You can see that where that positions on the curve. You can also see that our trough levels are 13x the EC50, which means we have plenty of room in there for viruses with unanticipated behavior. And we think it's a very important feature to put into this. The compounds that are using ritonavir are barely getting over the EC90 line with the metabolism inhibitor. We are comfortably above that by a very wide margin without any metabolism inhibitor. And we have extraordinary multiples up to our safety limit, our limit of exposure. So this is a safe, well-behaved drug doing everything we wanted it to do in terms of profile and volunteers, okay? And so just to conclude, we've shown for the coronavirus drug that we can have a very high safety and tolerability in human clinical trials. And we've also shown you data supporting its potency against a broad variety of Coronavirus strains, including the uniqueness of the drug resistance profile, which is another differentiator from the existing molecules. We are right now preparing to go into a pre-IND meeting with the FDA to align on what are the next steps. And we are pursuing the application and importance of this compound in the long COVID space. And now I'd like to turn this back to Werner, go ahead, for -- to -- sorry, to Iain for some final remarks.

Thank you, David, and thank you, both Dave and Bob. To conclude, we presented what I believe to be a compelling story for 2 best-in-class antiviral drugs that address critical threats to human health. First, the bird flu with tivoxavir marboxil. I think we've shown convincingly that we have a potent and broad resistance profile that include strange resistance to other agents. We've shown very good data in 3 well-accepted bird flu models that confirm the efficacy potential. In terms of human exposures, we have very favorable PK with plasma levels that are sustained for at least 3 weeks with good safety with the potential to go even longer with optimization of the formulation. Single-dose therapy provides the opportunity for bird flu treatment as well as prophylaxis, and we are progressing with discussions with the FDA along the animal rule for rapid approval of this drug. For COVID, for ratutrelvir, again, we've shown a very potent, broad resistance profile for our drug compared to gold standard drugs currently available or in development. We have a ritonavir-independent regimen, which mitigates drug-drug interaction limitations and opens the door to patients who cannot take Paxlovid. We are a single dose once a day, which shows favorable PK, but again, with good safety, allowing a 10-day dosing regimen. And that 10-day will allow for the prevention of both COVID rebound and long COVID. Next slide. So now I just want to give you a quick overview of our financials. The market potential and some milestones for the company. First, on the financials, our cash and cash equivalents and short-term investments, as of December 31, were $21.3 million. And our cash position is sufficient to support the planned operations into Q1 2026. As far as market potential is concerned, Dr. Redfield has described quite clearly the potential for both bird flu and for COVID. But if we just start with bird flu, if we were using the stockpile estimates, we would think between 300,000 and 600,000 doses would optimally need to be stockpiled to prevent pandemic threats. COVID, we have a potential best-in-class agent to replace existing therapies and prevent clinical rebound. And so guidance along the current sales of Paxlovid are reasonable, as we think about this agent. With respect to anticipated upcoming milestones, all the major milestones are in bird flu and have been summarized by Dave and Bob. But essentially, the first major update will be discussions with the FDA regarding the animal rule, and we expect to get feedback from the FDA in Q2 2025. We will also in parallel be finalizing formulations in CMC scale-up and finalizing also for development for bird flu and moving forward on a path to approval. For COVID, we'll be submitting a pre-IND meeting request to engage with the FDA to understand for milestones and endpoints for long COVID in this quarter. So at this point, I think I'll hand it over to Tara for Q&A. Tara?

[Operator Instructions] I'll now turn the call over to Bruce Mackle at LifeSci Advisors to moderate the session.

Thank you, Tara. So it looks like we have a few questions that have come in. First one, can you further clarify the process with FDA regarding the animal rule?

That's a question for David.

Yes. Thank you, Bruce. So the animal rule, to reiterate the important aspects, it is a mechanism to allow approval of drugs that cannot be effectively tested in human beings. And they can be tested for safety, but they can't be tested for efficacy because either the potential for risk is so high that you would never use a control group or the frequency of the disease is so low that you can't practically do the experiment. So we fit into both of those criteria, and we believe the animal rule is an appropriate path for us to address the FDA.

Thank you, David.

All right. Next question regarding the next steps for bird flu development. Can you just summarize and clarify those again in terms of the timing?

So this is David Pauza again. So we have submitted the pre-IND meeting request. And let me just clarify that. FDA accepts requests for a meeting under the pre-IND category, which may include just the discussion of the animal rule. So we will have that pre-IND meeting, and the important outcome will be their view about the applicability of animal rule for this program. And we are expecting that they have 30 days from the 21st of March in order to schedule this meeting and then probably something like 30 days after that to get to the meeting, and then, we should have feedback during that time from FDA about our status and what their concept of where we should go next.

Thank you, David.

Next one is for Dr. Redfield. I understand that you are still in active clinical practice. From your experience, what are the most important challenges with COVID patients?

Yes, I think it's really important to realize that this issue, what we call long COVID, is really a very significant clinical illness that some patients get post-COVID. And again, the estimates are as low as 5% and was as high as 20%, and in my own view, poses one of the largest economic burdens on the United States of the COVID pandemic. This long COVID can be quite significant and severe that I have a number of patients that as a consequence of long COVID have no longer been able to carry on their jobs. Many of them are quite successful leaders of companies, where they've just not been able to maintain their jobs, either because of significant cognitive dysfunction or because of extreme fatigability or, in some cases, a very unusual severe autonomic dysnomia, which they lose their ability to control their pulse and blood pressure. So they can only really maintain themselves that they're in the lying down position. It's a quite significant disease. And hopefully, the NIH and others will invest heavily in trying to develop therapies that will improve this condition. I do agree with what Dave proposed that one of the approaches is that this condition is exacerbated by prolonged viral replication that is probably not addressed by short-term treatment that is currently being done with Paxlovid, which is only 5 days. So we're hopeful that the approach that we're taking with a longer therapy for 10 days and even potential doing studies with our products that may even go out longer, where we may treat for 4 to 6, 8, 12 weeks to see if we can impact the occurrence of long COVID.

Thank you very much, Bob.

Next question here is can you describe the market outlook for bird flu and the market opportunity?

Dr. Redfield can come back to this in terms of like the stockpile.

Yes. I think the most -- I ran CDC, and of course, really important to the National Defense for is our stockpile, which Secretary Kennedy has just reprogrammed to go back to CDC to manage it. But my own view is there will be a high interest in trying to stockpile an effective antiviral for bird flu. And so that's why I gave the estimates of anywhere between 300 million and 600 million doses, I think, is probably what would be appropriate to anticipate for the stockpile to procure of an efficacious antiviral agent for bird flu.

Next question, how significant is the fact that ratutrelvir does not need the co-administration of ritonavir?

Yes. I think it's critically important. If you look at the people that will benefit from Paxlovid currently to prevent serious illness, hospitalization and death, those are individuals that we consider vulnerable. Now, probably the greatest vulnerability is this thing called age. Once you're greater than, say, 65, you're at high risk for bad outcome. And as I mentioned, unfortunately, COVID continues to have significant mortality in the United States with, I think, conservative estimates of at least 40,000 people planned to die this year. And the problem is that because of drug-drug interactions, Paxlovid is contraindicated in a significant number of the elderly that are at high risk for bad outcome. So a number of those individuals are not able to be treated with Paxlovid. The other issue that I would comment is that Paxlovid is a drug that ritonavir is a drug that has significant tolerability issues in patients and also is probably one of the reasons why Pfizer has limited the therapeutic course to 5 days. So I think it's quite significant limitations that Paxlovid has. And I probably think that's one of the reasons Pfizer has developed an alternative candidate themselves.

David, you have some additional comments?

Yes. I just wanted to comment on -- information released by Pfizer showed strong growth in request for treatment prescriptions, both in '23 and in '24 and a market for Paxlovid well north of $5 billion. And so, if we are leaving on the table, so to speak, about -- between 10% and 20% of people seeking prescriptions who have become ineligible, that's a substantial market that exists for a drug with properties of ratutrelvir.

Thank you, David.

Next question is, why do you think ratutrelvir is useful in addressing viral rebound and long COVID?

I think well -- yes, I think as Dave alluded to in one of the slides is really looking at the slope and decrease in viral replication in vivo. And it really has probably been underappreciated, the degree in which this virus replicates post-infection. And I think the new thinking that many of us had that are in this clinical space is this is a virus that's going to require much longer therapy to get down to viral clearance. And that may be -- initially, we were going to do 10 days, but as I have said, I can see that you might even design some long COVID studies where that's the outcome that you may go longer. It looks like if you don't treat somebody with anything, that the risk for the rebound is relatively low. If you do treat people with Paxlovid, the risk for rebound is much higher. And I suggest it's, again, that there's just incomplete viral suppression and viral persistence that's leading to this problem and the requirement for therapy to be repeated.

Thank you, Bob.

The next question, can you comment on the development of the compound in bird flu versus seasonal flu? And is there a certain link between these 2 developments?

Dave?

So throughout the presentation, we included data against showing efficacy against seasonal flu. We have a lot more of that information, which we didn't include today for time. For example, we've tested our compound against viruses that are resistant to baloxavir. And for the main resistance mutations to baloxavir, our compound is more effective. Baloxavir has a problem in the clinic in which it generates a high level of resistance mutations. So we're able to address that. We also have high potency against viruses that are resistant to Tamiflu/oseltamivir and very high potency against all seasonal flu strains that we've tested. And Bob's going to add something here.

I think it's important to look at just from a clinical perspective, when patients present with influenza. It's complicated because the clinical availability of timely, real-time antiviral testing isn't really there. So having an antiviral against influenza that, if you will, is really efficacious independent of baloxavir or Tamiflu resistance, which are becoming much more common now among circulated flus. I think we'll have a potential advantage in the marketplace. The second thing I want to just say, and it is speculative, but I want to put it out there. When you have a drug that has a pharmacokinetic profile where it can last, say, 3 weeks and its current data that we have, it does raise the possibility that this drug may also have efficacy, as Dave alluded to, among dairy workers and chicken workers and agricultural workers. It maybe have efficacy as a chemoprophylactic agent. I will remark as CDC Director, one of the things that I wanted to emphasize is that the current influenza vaccines at best are 50% efficacious. And frequently, they can be as low as 25% efficacious. They're also not efficacious among the patients frequently that you really want efficacy that is the old -- elderly, pregnancy, immunosuppression. So the potential, I think, for a safe, prolonged pharmacokinetic chemoprophylactic agent that actually could eventually maybe even replace the influenza vaccine marketplace, I think, is very real.

Thank you, Bob.

Next question, can you talk about potential prophylactic settings for TXM?

Bob?

Well, I think the question really will come down as we're already beginning to see more and more of the agricultural space is starting to screen agricultural workers for bird flu. And they are finding a number of individuals that have been infected, I think, and Dave may correct me, I think one of the studies that we reviewed was around 7% or 8% showed evidence of previous bird flu infection. So I do think that it's potentially very probable that the agricultural space may evolve from an occupational health perspective in looking at the use of chemoprophylaxis in agricultural workers, dairy farmers, chicken workers, turkey workers, but as I mentioned, unfortunately, this virus now has spread into pigs and it's spread into sheep.

Thank you, Bob?

Next question, can you comment on how the data from mice fared in nonhuman primate studies are predictive of human studies?

Dave?

Thank you. Yes, we're always careful about the translational relevance of data that we produce. So we look in mice quickly, that gives us a very quick and relatively inexpensive way to do a preliminary study, gives us a little information about dose, gives us a little information about how that antiviral is working. But then we really look to species like ferrets and nonhuman primates for really the final data that's going to stand up and really be proof of principle for this drug. And so we've been through 1 round of those animal studies already. We'll probably come back to them and refine the parameters and repeat that again. But, as I said, I think that the mouse was the introduction, the ferrets and the nonhuman primates really carry the weight of evidence, and we're very glad that the activity of the drug has held up well in all of those tests.

Thank you, Dave.

Great. Well, we're pushing up against an hour. So we're going to wrap here. I'm going to turn the call back over to Werner for closing comments.

Thanks, Bruce, and thanks, speakers, and answering those questions. It's my privilege to thank on behalf of the Traws team, all of you that have participated in this call today and having shown your interest in our company and the future of these very important new compounds. I believe this concludes the Traws' investor call. Back to Tara.

Great. Thank you, Werner. So this concludes today's event. You may now disconnect.