Traws Pharma - Earnings Call - Q4 2024 & Study Update

Executive Summary

• Q4 2024 topline reflected a development-stage profile: minimal revenue ($56,000*) and negative EBITDA (-$5.28M*), while FY 2024 net loss was driven by non-cash acquired IPR&D ($117.5M) and warrant expense ($24.4M) from the December financing.
• Management prioritized bird flu (H5N1) as the lead program; positive animal-model and Phase 1 pharmacokinetic data for tivoxavir marboxil underpin a potential accelerated approval pathway under FDA’s Animal Rule, with an FDA meeting request submitted on March 21, 2025 .
• COVID candidate ratutrelvir showed Phase 1 PK supporting ritonavir-independent dosing and sustained exposure (≈13x EC50 at target dosing), advancing toward pre-IND engagement on Long COVID endpoints (Q2 2025) .
• Cash and equivalents were $21.3M at year-end, aided by the $20M initial tranche of a financing up to $72.6M, extending runway into Q1 2026; additional warrant exercises could add up to $52.6M contingent on specified data readouts.
• Near-term catalysts: FDA feedback on Animal Rule (Q2 2025), CMC/formulation progress, path-to-approval plan for bird flu, and COVID pre-IND request—likely to drive narrative and stock reaction as regulatory clarity and data milestones emerge.

What Went Well and What Went Wrong

What Went Well

• Tivoxavir marboxil delivered robust efficacy signals: single-dose protection across mice, ferret, and non-human primate models using the Texas dairy worker H5N1 strain, with lung viral clearance below quantitation thresholds and improved survival and body weight maintenance .
• Phase 1 PK supported single-dose exposure above EC90 for ~3 weeks with good tolerability, strengthening the case for prophylaxis/treatment and alignment with accelerated Animal Rule approval strategy .
• Financing brought in top-tier healthcare investors, extending cash runway and bolstering capacity to reach value-inflecting regulatory interactions and clinical plans; management emphasized strong progress and strategic focus on respiratory threats.

What Went Wrong

• Financials remain constrained by limited revenue and elevated operating losses: FY 2024 net loss of $166.5M, primarily due to non-cash IPR&D and warrant expense; quarterly revenue is de minimis, reflecting no commercial products.
• Q3 2024 showed step-up in R&D and G&A expenses versus prior year (R&D $5.1M vs. $2.5M; G&A $3.5M vs. $2.7M), highlighting cost intensity amid pipeline advancement and strategic activities.
• Consensus coverage appears thin or unavailable for Q4 2024 (EPS, revenue), limiting market “beat/miss” framing; results must be judged on program momentum and regulatory progress rather than financial outperformance (*Values retrieved from S&P Global).

Transcript

Lain Dukes (Executive Chairman)

Good morning and welcome to the Traws Pharma Investor Call on bird flu and COVID, and Traws' innovative small molecule product candidates. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the discussion. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player. 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. With that, I'd like to turn the call over to Dr. Werner Cautreels, Chief Executive Officer of Traws Pharma. Please go ahead, Werner.

Werner Cautreels (CEO)

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 two antiviral product candidates.

Our two 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 needs and public health.

Robert Redfield (CMO)

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, 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. The pandemic risk, when this virus learns how to go human-to-human, can be catastrophic. The human cases that have occurred, particularly in South-east Asia, have had greater than a 40% mortality.

This does pose an enormous potential pandemic risk. 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. 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, it will learn how to go human-to-human. When that occurs, it will cause a catastrophic bird flu pandemic.

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 a strain of the individual that eventually died of bird flu in the United States. It's a very good pharmacokinetic profile in that one dose will provide protection for probably up to three weeks.

It's also been shown to reduce disease and mortality in three accepted preclinical animal models. It is able to cause a massive reduction in virus replication in vivo in all three of these animal models. One dose is able to maintain a plasma level above the EC90 for, as I mentioned, at least three weeks in our phase one studies. Overall, it has an excellent tolerability profile, which will enable even higher concentrations to potentially be used to treat or prevent bird flu.

Dave Pauza (CSO)

Good morning, everyone. I'm Dave 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. 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 had 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. On the right side, you see the EC50, or effective concentration 50%, in nanomolar for tivoxavir. You see it's all sub-nanomolar concentrations against these H5N1s.

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. Dr. Redfield also mentioned the transmission of this virus from a cow to a dairy worker in Texas. We think that we were very fortunate in that instance that that person did not subsequently transmit that virus to other humans.

The reason is because the virus in the dairy worker evolved nine unique mutations that were not present in the cow who infected him in the first place. Those mutations are all associated with increased efficiency of virus replication and increased transmissibility. I showed you the map there to show you the distribution of these. Those are the unique ones that separated the virus in man from cow.

As soon as that virus got into the Texas dairy worker, it started to adapt quickly. That's the problem that will fuel any future pandemic outbreak. When we look at commonly used antiviral agents that are used against seasonal flu, these were tested against the same Texas isolate, the A30/Texas/37 isolate. If we look at oseltamivir on the right, which is Tamiflu, against 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. 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. If he were to transmit that, you'd be transmitting a completely Tamiflu-resistant virus. Baloxavir is another compound that is available for seasonal flu. You can see it has a little bit about one and a half 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. 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.

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. 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 three.

We infected mice through the intranasal route and treated them one time with our compound, tivoxavir marboxil, by oral route. We are 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 six. That is 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. There is no adaptation here. The treatment with tivoxavir marboxil called TRX-100 on this slide provided 100% protection 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 in black for the untreated animals, and in red, no body weight loss for our treated animal group. In that initial animal study, tivoxavir marboxil was an outstanding antiviral.

To go a little bit more into this, the two main things we would be 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 ninth. If you did this with a typical seasonal influenza virus, maybe the highest you would have in this experiment is about 10 to the six virus titer. 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 can see that all animals had virus levels below the lower limit of quantitation. That's a stunning effect on the viremia. That means that we're close to six 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. We took ferrets. We inoculated them with a lethal dose of this A Texas virus. In this case, it was 1,000 infectious doses. We treated them with two different dose levels.

One dose level was equivalent by scaling to 120 milligrams dose given in humans, and the second dose was equivalent to 240 milligrams in humans. The previous mouse experiment was done with 240 milligrams in humans equivalent. I 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 kilograms, you can treat with 80.

You can see that those two approved dose levels are not very close to what we're looking at here. We had two groups of animals. We treated them. We looked at our three indications: survival, our body weight, and virus burden. We saw a pretty dramatic effect of the antiviral on these three endpoints.

In survival terms, all ferrets, untreated ferrets were dead by day four. Again, a highly, highly lethal infection. The animals treated with the equivalent to 240 doses had 50% survival by day 14. We saw what appears to be a dose effect, dose response effect by a little bit lower survival in the 120 milligram equivalent group. In terms of body weight, you see the same thing. When we looked at these data carefully and said we got the first two 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? The viremia data from this ferret model are essentially stunning.

You can see extremely high virus loads now clearly in the 10 to the nine range in some animals with a very large suppression of virus in animals treated with either of the doses of tivoxavir marboxil. The lower descriptors there, craniocaudal, describe portions of the lung that were sampled individually in this study. These animals were euthanized and tissues were removed to perform these analyses.

By three days after infection with a single treatment of tivoxavir marboxil, we got this result again showing the extraordinary antiviral efficacy. I wanted to just show that in a different way. 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, which are the lower viral loads.

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, but that lower right lung still has some appreciable viremia in it. That's telling us that this is the real site of attack of this virus. A virus that grows like this in the lower lung is very dangerous. 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.

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 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 non-human primates. These were in Rhesus macaques.

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. We have five animals per group. This experiment turned out to be a non-lethal infection. As I said, this was very early time with little experience of this virus in non-human primates. The virus dose was probably a little low.

We got a non-lethal infection, but it allowed us to explore the parameters again that were important to us. We do not 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. In terms of body weight, you can see it is a highly significant difference between animals that were treated and animals that were untreated with a very extraordinarily good p-value, especially for an animal study of this type. There was a clear differentiation in terms of body weight. There was a clear, even more clear differentiation in terms of lung viremia. We have color coded again the same way.

Because of the virus dose, we did not get up into the orange and reds 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. We have demonstrated the substantial impact on viremia and a highly significant impact on body weight loss, again, confirming the activity.

Now we have three species with very similar, very significant data telling us this antiviral is working. Maybe, Bob, you want to tell us the-well, I will continue. We asked ourselves, what would we do then to go through and begin to characterize this in humans? We have completed a phase one study in humans, which was healthy volunteers looking at safety and tolerability. 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. I think we see a nice dose response in the pharmacokinetics of a single dose. I want to keep emphasizing this, that this antiviral is given one time as soon as symptoms are apparent. Here in healthy volunteers, again, we gave only one time.

Differently than the other products, I want to really emphasize the range of doses that were evaluated in this study. 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. Here I've shown you in dotted lines what it would take to control a seasonal influenza withT this compound.

You can see that a single dose is going to give you good viral control out to about three weeks. We haven't really done any more development to try to extend that. There may be ways to even make that go farther. Three weeks would control against a seasonal influenza. It may also control dairy workers and poultry workers from that initial transmission event of the bird flu into them.

However, we know that we will require the high doses that will be necessary once this adapts to humans. I think this is also very encouraging data. The primary path for us to go forward is we want to apply this to bird flu. We believe that bird flu represents an exceptional situation for two 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 US It would be impossible to do a clinical trial of human-adapted bird flu at the present time. We believe that the risk is there, the threat is coming. I would remind everybody that we're in the beginning of the south to north bird migration. There's a wave of bird flu coming with these wild birds as they travel north. We have not seen the end of this. This is not like a seasonal flu, which will just be here for a few months.

Veterinary epidemiologists have predicted that this influenza will circulate in domestic animals for at least five to seven more years. This is an exceptional situation. 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.

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 of pharmacokinetics in human beings, and we are prepared to respond to the FDA guidance concerning going forward. Now I'm going to stop there. Now we're going to transition to COVID. I'd like to turn it back to Dr. Redfield

Robert Redfield (CMO)

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. 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. Again, they don't really have an impact on whether someone gets infected or not. Therefore, there's an enormous need to develop effective antiviral. The virus does continue to mutate. 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. The virus continues to evolve. There is a poor match between the vaccine and the circulating strains. It is an enormous clinical burden, as I mentioned, caused significant cause of premature death.

The economic burden is also substantial, particularly when you look at one of the consequences of COVID, which is that a significant percentage of people, and it has 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, etc.

There's really limitations of the current antiviral that we have, Paxlovid. It works. It's an excellent drug. The challenge with Paxlovid is it requires a PK enhancer, ritonavir, in order for it to get the levels it's needed to be efficacious. 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 to 13 million infections, 2 to 3 million people seeking outpatient visits for it, 200,000 to 400,000 basically being hospitalized. 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 emergency 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 13 times 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 one 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 and Paxlovid is used as a short course, five days. 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. 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.

Dave Pauza (CSO)

Okay. Thank you, Bob. I'm going to take you now through the data package on the COVID-19 drug, Ratutrelvir, its main protease inhibitor, as Dr. Redfield said, for a ritonavir-independent 10-day regimen. We'll explain the reasoning for these things as we go through. Ratutrelvir was compared using laboratory testing against a couple of other compounds. Nirmatrelvir is the protease inhibitor component of Paxlovid.

When you test nirmatrelvir in the lab against a large number of SARS-CoV-2 variants, you can see the EC50 values there on the left panel. In every case, ratutrelvir is more potent against the same virus tested at the same time. 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 coronavirus Mpro inhibitor that Pfizer is developing and has in late-stage clinical trials. It's important to note the potency differences here, more than 50 times difference against the original COVID strain and really not a very potent drug against the viruses that we see there. On the right-hand panel, I have taken again those three compounds, plus I have added ensitrelvir, which is the compound that is licensed in Japan and currently in clinical studies in the United States.

I have shown you the average EC50 across a number of strains. Nirmatrelvir, we looked at nine strains that were tested, 23 EC50, ensitrelvir, 69. For the three strains that I could find published, 123 for the ibuzatrelvir, and for our compound, 8.4, and that is tested against 18 different COVID strains.

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, we usually multiply that value by three, get a predicted EC90 value. That's really what's important for dosing considerations and safety considerations. You can see the EC90s there are quite substantial.

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. There's a substantial differentiation in terms of potency and efficacy. A very important issue in antiviral treatment is always the evolution of drug resistance.

Here I'm showing a little bit of information taken from the published literature, which now is beginning to reveal the frequency of nirmatrelvir resistance mutations in populations treated with Paxlovid. You can see that we got up to 10% of participants in this one study had a Paxlovid resistance mutation already. 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. You can see the one country in the world which is licensed ensitrelvir has a massive number of these mutations appearing. In the US, where it's been used mostly in clinical trials, we're also seeing mutations appearing as well against ensitrelvir.

In the right side, I give you a table which lists one by one all these amino acid changes in the protease gene which are associated with resistance. I have checked off which ones are found in nirmatrelvir clinical study and which ones are found in ensitrelvir clinical study. I have added the ones that we found in a laboratory study where we intentionally evolved the virus to be resistant to the drug.

You can see that there is very minimal overlap between our resistance pattern and the others. There is a little overlap between our compound and nirmatrelvir, zero overlap with the resistance pattern to ensitrelvir. Our unique pattern of drug resistance indicates that we may be effective against some of the variants that are appearing already. 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. 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.

As you can see, if you plot the pharmacokinetics over a short number of hours, if you plot it for the dose on day one and the dose on day 10, the first and last dose, you can see that there's 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've had to introduce ritonavir, and we're not really accumulating the drug either. In terms of antiviral, this is an extraordinarily well-behaved drug.

On the right side, I showed you the drug levels at 24 hours after each daily dose. It is also important that these drug levels are very stable and very reproducible across the whole profile of 10 days of treatment. We can summarize it all here. 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.

We internally have long believed that you have to very effectively suppress this virus and suppress it for long enough to prevent viral rebound. 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. Now we're starting to see the first amounts of real data being released from other groups proving this point.

This group presented a poster at the CROI meeting in 2025 demonstrating directly that 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. It is true for everyone, but it is exacerbated in women. It is the direct common sense view of this, right? If you do not get rid of the virus early and you let it linger, then bad things are going to happen.

We are seeing the real data of the bad things. Dr. Redfield has a lot of experience treating people with Long COVID and tells us stories which are sometimes quite horrifying. Here is 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.

They are, again, what you might imagine, this brain fog, shortness of breath, GI symptom. These are all the things that tell you you had a more intense infection and it lasted longer than it should have. 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. Finally, just to conclude, I wanted to return back to the PK curve.

This needs just a little explanation because you see the peak on day zero to one and another peak on nine to 10. That's because those are the only two days where we take these samples over a short period of time. You can see that, again, they look similar. The first and last dose look similar.

The trough levels are very consistent, and we get a kind of free two days after the treatment of days 11, 12 still being in the zone of therapeutics. 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 13 times the EC50, which means we have plenty of room in there for viruses with unanticipated behavior.

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're comfortably above that by a very wide margin without any metabolism inhibitor. We have extraordinary multiples up to our safety limit, our limit of exposure. This is a safe, well-behaved drug doing everything we wanted it to do in terms of profile and volunteers. Okay. Just to conclude, we've shown for the coronavirus drug that we can have very high safety and tolerability in human clinical trials.

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. We are pursuing the application and importance of this compound in the Long COVID space. Now I'd like to turn this back to Werner. Go ahead. Sorry, to Lain for some final remarks.

Lain Dukes (Executive Chairman)

Thank you, David. And thank you both, Dave and Bob. To conclude, we presented what I believe to be a compelling story for two best-in-class antiviral drugs that address critical threats to human health. First, for bird flu with tivoxavir marboxil. I think we've shown convincingly that we have a potent and broad resistance profile that includes strains resistant to other agents. We've shown very good data in three 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 three 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. 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, where again, with good safety, allowing a 10-day dosing regimen. That 10-day will allow for the prevention of both COVID rebound and Long COVID.

Next slide. 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 31 December were $21.3 million. 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. 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 ultimately need to be stockpiled to prevent pandemic threats.

For COVID, we have a potential best-in-class agent to replace existing therapies and prevent clinical rebound. Guidance along 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. Essentially, the first major update will be discussions with the FDA regarding the Animal Rule. We expect to get feedback from the FDA in Q2 2025.

We will also, in parallel, be finalizing formulations and CMC scale-up and finalizing also the 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 the milestones and endpoints for Long COVID in this quarter. At this point, I think I'll hand it over to Tara for Q&A. Tara?

Yes, thank you, Lain. At this time, we will be conducting a question-and-answer session with our speakers. As a reminder, if you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player. I'll now turn the call over to Bruce Mackle at LifeSci Advisors to moderate the session.

Operator (participant)

Thank you, Tara. 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?

Werner Cautreels (CEO)

That's a question for David.

Dave Pauza (CSO)

Yes, thank you, Bruce. 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. 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. We fit into both of those criteria, and we believe the Animal Rule is an appropriate path for us to address the FDA.

Werner Cautreels (CEO)

Thank you, David.

Operator (participant)

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?

Dave Pauza (CSO)

This is Dave Pauza again. We have submitted the pre-IND meeting request. 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. We will have that pre-IND meeting, and the important outcome will be their view about the applicability of Animal Rule for this program. 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. We should have feedback during that time from FDA about our status and their concept of where we should go next.

Werner Cautreels (CEO)

Thank you, David.

Operator (participant)

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?

Robert Redfield (CMO)

Yeah, 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. Again, the estimates are as low as 5% and as high as 20%. In my own view, it poses one of the largest economic burdens on the United States of the COVID pandemic. This Long COVID can be quite significant and severe.

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.

They can only really maintain themselves if they're in the lying down position. It's a quite significant disease. Hopefully, the NIH and others will invest heavily in trying to develop therapies that will improve this condition. I do agree with what they 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 five days.

We're hopeful that the approach that we're taking with a longer therapy for 10 days and even potential doing studies with our product that may even go out longer where we may treat for four, six, eight, twelve weeks to see if we can impact the occurrence of Long COVID.

Werner Cautreels (CEO)

Thank you very much, Bob.

Operator (participant)

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

Werner Cautreels (CEO)

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

Robert Redfield (CMO)

Yeah, I think the most I ran CDC and, of course, really important to the national defense is our stockpile, which Secretary Kennedy has just reprogrammed to go back to CDC to manage it. My own view is there'll be a high interest in trying to stockpile an effective antiviral for bird flu. 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.

Operator (participant)

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

Robert Redfield (CMO)

Yeah, I think it's critically important. If you look at the people that will benefit from Paxlovid currently to prevent serious illness, hospitalization, and deaths, 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.

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. 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. 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, the 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 five days. I think it's quite significant, the limitations that Paxlovid has. I probably think that's one of the reasons Pfizer is developing an alternative candidate themselves.

Werner Cautreels (CEO)

David, you have some additional comments?

Dave Pauza (CSO)

Yeah, I just wanted to comment on information released by Pfizer showed strong growth in request for treatment prescriptions both in 2023 and in 2024 and a market for Paxlovid well north of $5 billion. If we're 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.

Werner Cautreels (CEO)

Thank you, Dave.

Operator (participant)

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

Robert Redfield (CMO)

I think, yeah, I think as Dave alluded to in one of the slides, is really looking at the slope and decrease in viral replication in vivo. It really has probably been underappreciated the degree in which this virus replicates post-infection. I think the new thinking that many of us have 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.

That may be initially we were going to do 10 days. As I said, I could 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, the risk for rebound is relatively low. If you do treat people with Paxlovid, the risk for rebound is much higher. 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.

Werner Cautreels (CEO)

Thank you, Bob.

Operator (participant)

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

Werner Cautreels (CEO)

Dave?

Dave Pauza (CSO)

Throughout the presentation, we included data showing efficacy against seasonal flu. We have a lot more of that information, which we did not include today for time. For example, we have tested our compound against viruses that are resistant to baloxavir. 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. We are able to address that. We also have high potency against viruses that are resistant to Tamiflu, also oseltamivir, and very high potency against all seasonal flu strains that we have tested. Bob is going to add something here.

Robert Redfield (CMO)

I think it's important to look at just from the clinical perspective when patients present with influenza. It's complicated because the clinical availability of timely, real-time antiviral testing isn't really there. 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 circulating flus, I think will 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, three weeks in 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. 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. 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.

Werner Cautreels (CEO)

Thank you, Bob.

Operator (participant)

Next question. Can you talk about potential prophylactic settings for ?

Werner Cautreels (CEO)

Bob?

Robert Redfield (CMO)

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. 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.

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. As I mentioned, unfortunately, this virus now has spread into pigs and it's spread into sheep.

Werner Cautreels (CEO)

Thank you, Bob.

Operator (participant)

Next question. Can you comment on how the data from mice, ferret, and non-human primate studies are predictive of human studies?

Werner Cautreels (CEO)

Dave?

Dave Pauza (CSO)

Thank you. Yes, we're always careful about the translational relevance of data that we produce. We look in mice quickly. That gives us a very quick and relatively inexpensive way to do a preliminary study. It gives us a little information about dose. It gives us a little information about how the antiviral is working.

We really look to species like ferrets and non-human primates for really the final data that's going to stand up and really be proof of principle for this drug. We have been through one round of those animal studies already. We'll probably come back to them and refine the parameters and repeat that again. As I said, I think that the mouse was the introduction. The ferrets and the non-human primates really carry the weight of evidence. We are very glad that the activity of the drug has held up well in all of those tests.

Werner Cautreels (CEO)

Thank you, Dave.

Operator (participant)

Great. We are pushing up against an hour. So we are going to wrap here. I am going to turn the call back over to Werner for closing comments.

Werner Cautreels (CEO)

Thanks, Bruce. 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. I'll get back to Tara.

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