BioCryst at Needham Conference: Growth Amidst Competition

On Wednesday, 09 April 2025, BioCryst Pharmaceuticals Inc. (NASDAQ: BCRX) presented at the 24th Annual Needham Virtual Healthcare Conference, highlighting its strategic growth trajectory. The company showcased the success of its flagship product, Orlodayo, while addressing the challenges of increasing competition. BioCryst's financial outlook remains strong, with plans for cash flow positivity and significant revenue growth.

Key Takeaways

• Orlodayo sales reached $437 million in 2024, marking a 36% increase year-over-year.
• BioCryst raised its 2025 revenue guidance due to the Inflation Reduction Act's impact on Medicare.
• The company aims for $800 million in US sales by 2029 and $1 billion globally.
• Pipeline developments include BCX 177205 for Netherton syndrome and avorolstat for diabetic macular edema.
• BioCryst projects financial strength with a path to profitability and substantial cash reserves.

Financial Results

• 2024 Sales: $437 million, a 36% year-over-year increase.
• 2025 Revenue Guidance: Raised to $535 million to $550 million.
• Gross Margin: Cost of goods is less than 3% of revenue.
• Peak US Sales: Expected to reach $800 million by 2029.
• Global Peak Sales: Targeting $1 billion by 2029.
• Cash Position: Ended 2024 with $343 million in cash.

Operational Updates

• Orlodayo Growth: Driven by physician and patient experience.
• New Patient Sources: 52% switch from other prophylaxis, 32% from acute-only treatment.
• Prescriber Base: Targeting 600 tier one physicians, with 80% prescribing Orlodayo.
• Retention Rates: Over 60% of patients remain on Orlodayo for 12+ months.
• Ex-US Commercialization: Orlodayo is commercialized in over 30 countries.

Future Outlook

• BCX 177205: Phase 1 trial underway for Netherton syndrome, data expected this year.
• Avorolstat: Entering clinic for diabetic macular edema, initial patient data expected this year.
• Financial Projections: Anticipating a 20-25% compound annual growth rate on revenue.

Q&A Highlights

• Tariffs: Minimal impact on Orlodayo due to low cost of goods.
• Competition: Orlodayo expected to maintain a 25% market share long term.
• Oral On-Demand Treatment: Seen as complementary to Orlodayo.

Readers are encouraged to refer to the full transcript for a detailed account of BioCryst's presentation at the conference.

Full transcript - 24th Annual Needham Virtual Healthcare Conference:

Serge Belanger, Healthcare Analyst, Needham: Hi. Hi. Good morning. I'm Serge Belanger, one of the health care analysts at Needham. Wanna welcome everybody to day three of Needham's twenty fourth, annual health care conference.

And for next fireside chat, we're happy to have the BioCryst Pharmaceuticals team with us. We have the CEO, John Stonehouse, company's chief commercial officer, Charlie Gair, and, the chief r and d officer, Ellen Thackway, with us, this morning. Before we move on to questions, just wanna, you know, provide details on how participants can submit questions. For those listening in on the portal, that's where you can submit questions. We'll take those as they come in.

And, with that being said, I'll hand it over to the the management team who's will give us an overview of of the company for those who may not be familiar with BioChris, and then we'll jump to q and a.

John Stonehouse, CEO, BioCryst Pharmaceuticals: Yeah. Thanks, Serge. Thanks for having us. Charlie, myself, and Helen are gonna make forward looking statements. So statements have risks and risk factors can be found on our website.

I I think BioCryst is a pretty interesting company to for investors to take a look at, especially in this environment. And and the reasons for that are, one, we've got a growing product in Orlodayo, that, you know, is is just growing at a beautiful trajectory over a half a billion dollars this year and on its way to a billion dollars, at peak, with IP protection, on two composition of matter patents out to 2035 and 2039. So just a really nice steady revenue growth, over the years. The second is we've got a pipeline, and and what's exciting about our pipeline is we have two programs in the clinic that we expect will have patient data by the end of the year that start to give us a sense of activity and dose. And so we believe we've got something beyond Orlodayo that can, again, create sustainable revenue for the company and create value.

And third, we're on a really nice path to profitability. We had an operating profit of over $60,000,000 last year. The second half of this year, we're gonna be at or approaching cash flow positivity, and next year for the full year, we'll be cash flow positive. So, there aren't many companies like that in our space, that that have all three of those. And and I think in in these uncertain times, it's even more important.

Serge Belanger, Healthcare Analyst, Needham: Right. And, one of the topic du jour currently is, tariffs. And so so far, pharmaceutical products have been exempted, but I think most people think that's only temporary. So just curious, if we were gonna see tariffs, what would be the the impact to Orlodayo and and and the company?

John Stonehouse, CEO, BioCryst Pharmaceuticals: Charlie, you wanna

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Sure. Obviously, it's a it's a evolving situation that we're monitoring. What we understand now, though, is it will have very little impact on Orlodea. Our current cost of goods are less than 3% of revenue, and the the the parts of the tariffs that could be could impact us would be on the active ingredient, the API. That's a a small component of that 3%.

So even with the impact of tariffs, it's it's not a material difference.

Serge Belanger, Healthcare Analyst, Needham: Got it. Okay. So let's talk about Orilodea. I think 2024 was a pretty exciting year for the product, kind of the the fourth or fifth year of the launch depending on when you stop start counting. But, you saw growth acceleration, which is not that common for that stage of a loss.

So maybe just highlight, you know, what drove that acceleration and how that sets up 2025.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Yeah. It we had over, 437,000,000 in sales last year. It was over 36% year over year growth. And the number one thing that drove that is just physicians and patients have learned through experience. They've seen our long term data.

They've experienced how Orlodea works in the real world, and they realize it's not just a convenient pill. That's obvious. But it's also a really effective product for most patients. And patients should expect to have competitive efficacy on Orlodayo, and that's what the doctors and patients are seeing. That we had more start forms, more news prescriptions in 2024 than we did in each of the previous years, and that rarely happens.

So that's a sign of acceleration. The other piece, Serge, is we're just every year, we're doing a better job getting more patients to paid therapy. And we made some nice strides forward last year in getting just more paid shipments throughout the year, and and that also drove some of that revenue acceleration.

Serge Belanger, Healthcare Analyst, Needham: Okay. And you provided guidance for for 2025 in believe it was in early January. And I think you're one of the few companies that has increased their guidance, so far this year.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Yeah.

Serge Belanger, Healthcare Analyst, Needham: So maybe just talk about why, why the guidance was increased, what what drove it.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Yeah. We we we started the year guiding to 05/15 to May. And we said the the the possible tailwind, if it happens, is whether the inflation reduction act being implemented would allow more Medicare patients on Orlodayo to reach paid therapy because their co payments would become more affordable. At the start of the year when we guided, we didn't know whether that would happen or not. By the time we did our q four earnings in February, we had early signs that that was starting to happen.

Medicare patients were able to afford their co pays, thanks to the IRA. And so that's what caused us to raise guidance to 505 hundred and 35 to 550,000,000. And on top of that, in the early part of the year, we saw the same really strong demand that we saw last year. So all gave all that together gave us confidence to raise guidance.

Serge Belanger, Healthcare Analyst, Needham: Okay. Maybe it'd be useful to talk about where, paid rates currently are across the the various segments of of coverage, commercial, Medicare, and Medicaid? Sure.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: We ended last year with an overall paid rate of seventy three and a half percent of our patients on therapy. It's high in our commercial segment, which is about sixty percent of the patients. Commercial ended the year close to 80% paid. Medicare, which is 20% of our patients, ended last year at 55% paid. And based on what I said earlier, it's not that the plans were saying no for Medicare patients.

It's just that the patients couldn't afford their co pay. And so that's where the IRA kicks in. We're still in the process that the early reauthorization process really goes through April into early May. So it's too soon to give you an exact paid rate. But with the the tailwind of more Medicare patients getting paid, we expect to be approaching 80% paid overall as we come out of the reauthorization season.

So big steps forward, and that makes makes obviously a big difference in revenue this year and in coming years.

Serge Belanger, Healthcare Analyst, Needham: Okay. Know in prior years, there was a a significant step down from four q to one q and then and then a big bounce back as you you gotten into two q. So with this level of paid rates, should we expect that difference to be, you know, much less than what we've seen in prior years?

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Well, what we've guided to for this year is, know, in past years, like you said, it was definitely down. The reason it's down is as we're going through reauthorization, some of the patients have to temporarily go to free product while going through reauthorization. We also have a bigger hit on gross to net, particularly in the commercial space where we pick up all the co payments, and and so many patients' co payments are are maxed out during the first quarter. With the the tailwind that I described, this year, we could be closer to flat rather than down. So down a little bit closer to flat versus definitely down the last couple of years.

Serge Belanger, Healthcare Analyst, Needham: Got it. And I think in the last couple of years, in terms of new patient growth, you you were hitting about 300 patients a year, on average, a little higher than what you, I think, had guided us to. Should we expect that to to continue going forward?

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Yeah. What and and just to remind everyone, what we guided to is peak sales we expect for The US to be $800,000,000. Coming out of 2023, what we needed to average was at least 200 net patients per year in The US through 2028. And in 2023, to your point, we were well above that. We're above that again in in 2024.

It only needs to be an average over that five year period, and we're well on track. So well well above 200 each of these early years. In the later years, maybe it goes below 200, but we're very much on track for 800,000,000 in 2029 in The US and peak sales globally of a billion dollars in 2029.

Serge Belanger, Healthcare Analyst, Needham: Okay. And does the the ease of access and this higher paid rate, can that influence the the rate of new patients?

John Stonehouse, CEO, BioCryst Pharmaceuticals: I think it

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: it I I think it it could always help, you know, particularly on the Medicare side where physicians and patients, they they want to get to paid. We've been very generous with free product because we want patients to have the good clinical experience. But for patients, confidence is really important knowing that their insurer will pay for Orlodayo or any HAE therapy is very important to them. And so I think this is just another thing that's gonna increase the already strong high confidence in in in the product. But but I'd also say, remember that this is a space where people are controlled.

Right?

John Stonehouse, CEO, BioCryst Pharmaceuticals: So it's not like people are desperate for a new therapy. And and so that kind of steady add is gonna continue for some period of time until we start to hit, you know, a saturation point in getting, you know, of the ten thousand patients, some percentage that have tried Orlodayo.

Serge Belanger, Healthcare Analyst, Needham: Okay.

John Stonehouse, CEO, BioCryst Pharmaceuticals: So it's a it's a it's not a hockey stick. It's a steady climb like we've been seeing.

Serge Belanger, Healthcare Analyst, Needham: Got it. From our discussions with KOL, it seems like Orlodayo is now kind of the de facto prophy treatment for for any new diagnosed treatment. So I'm curious from the the new patient ads that you've seen, are they coming are they newly diagnosed? Are they still switch those switching from other treatments? Just curious where what what the source of new patients is.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Yeah. Well, I mean, we're we've been thrilled all throughout the launch and the the the the percentages have stayed very consistent. We're getting patients from all three segments where we'd wanna get them. So launch to date, fifty two percent of the patients that have started Orlodayo have switched from another prophy product. So that's great.

Prophy is patients on prophy is the biggest segment, and we continue to get patients to switch. Thirty two percent, switched to Orlodayo from acute only. So they they they're coming to prophylaxis, this being their first prophylaxis product, adding it on top of acute only. And then the the remaining sixteen, seventeen percent is patients, best we can tell, are either newly diagnosed or just newly treated with an HAE therapy starting with Orlodea. So we're getting new patients.

We're getting experienced patients, and it's all because of the the the profile of the drug, pill once a day with really good efficacy for most patients.

Serge Belanger, Healthcare Analyst, Needham: Okay. And as we mentioned before, you're now in the fifth year of launch. So just curious, you know, what has changed in terms of the targeting or messaging of for Orlodayo and, you know, if you've changed your tactics on which tiers of doctors to to target now as to continue expanding the prescriber base for the product?

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Well, from a targeting perspective, it's been really consistent. We've got two tiers of physicians. There's roughly 600 physicians now that treat about fifty percent of HAE patients. That's tier one. At this point, around eighty percent of those physicians have prescribed Orlodayo.

So we still have room to grow, and certainly they the average doctor in that tier one has a lot more HAE patients. So there's opportunity to go deeper into their patient base. And then the the the bigger tier two, is patients or doctors who have, you know, even one or two patients. We call on everybody. Launch to date, we've had over 1,200 physicians prescribed, and it's been really steady every quarter, roughly 60 new prescribers of Orlodayo, come on board.

So great from that perspective. We'll we'll continue that. And from a messaging perspective, the messaging has been very consistent the last few years about convenience of a pill, but the long term efficacy in our clinical data and now our real world evidence, we're building a a real volume huge volume of real world evidence that we build into our messaging to increase, health care provider and patient confidence. So as we develop new evidence, it's just reinforcing what they're already seeing that this is a really effective product for patients.

John Stonehouse, CEO, BioCryst Pharmaceuticals: Hey, Serge. I I'd say one other thing. The commercial team has done a fabulous job of interpreting data along those five years or going into the fifth year of Yep. What's working, what's not. And there's these adjustments that Charlie's team has made along the way that just have gotten us better and better and better.

Like, the, you know, the easiest example for me to describe is that free drug to pay drug. Right? There were adjustments around people responsibility, internal, external, and we just got smarter because we understood the data. We made the changes, and now we're seeing the results. And and, you know, it might look simple to the outside world.

I can tell you it's a lot of work, and and, you know, stability of team and improving the team are all things that go into making this execution what it is, which is, I think, one of the best launches in a crowded market in the history of rare disease.

Serge Belanger, Healthcare Analyst, Needham: Regarding awareness of ERLIDEAU, is it at a point now where patients are going into their doctors and requesting the product, or it's still kind of a physician driven decision to to put patients on ERLIDEAU?

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Some some patients do request it, that but that's more of the minority. Most of this is the the conversations tend to be more physician driven. Physicians have a very high aware awareness of Orlydeo now way well into the 90%. What we try to do, though, is it still is a joint decision between the physicians and the patients. What we know is most patients would prefer to be on prophylaxis.

They prefer to be on oral prophylaxis. But patients in HAE, as in any condition, patients tend to be a little more hesitant to demand things from their physician on average. But if the physician brings up options, brings up Orlodeaux, the patient is likely to respond favorably, and that's what that's what creates a good conversation and a and a decision to to switch to Orlodeaux.

Serge Belanger, Healthcare Analyst, Needham: Okay. And are retention rates stable now as, you know, we we get into the fifth year? I mean Yeah.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Retention has been really strong, the last several years. Patients who start on Orlodan, sixty plus percent of them get to twelve months. And once they get to twelve months, they're there because they're doing really well. And so most of them stay on then long term. And we've actually put out some data from claims evidence showing that Borlodayo is statistically equal in terms of retention to TaxiRO.

Although numerically, it's like Borladeo is actually slightly better. So very competitive retention, and it's because of the profile of the product.

Serge Belanger, Healthcare Analyst, Needham: Got it. Okay. And then how do you how do you view the the outlook for competition? You know, as John mentioned, this is a a very competitive, market, and it looks like it's gonna be gonna get more competitive. There's there's more entrants.

So how do you view the the competition?

John Stonehouse, CEO, BioCryst Pharmaceuticals: Yeah. Let me start. And and I I think one thing that I think is really important for people to understand is what we're seeing in a competitive market already is only gonna be worse for the people that follow us. It's not gonna be better. Right?

People are controlled. They're seeing their doctor once a year. That's not gonna get any easier. So I'll let Charlie describe the rest.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Yeah. And and that's, you know, what I've been describing with the the efficacy that we're seeing with Orlodayo. If you are doing really well with your attack control on one pill once a day, what else do you need? You're you're you're you're basically living your life where you can just about forget that you have HAE. That's what patients are looking for.

So some patients will move on to other therapies if Orlodea turns out not to be the drug for them. But the patients who stay on is because this is solving their problem with with HAE. So that's intuitively, we're gonna hold on to those patients. But we don't just take our intuition, and and rely on that. We do a really big study every year.

We've done it four years now. That's been very predictive of the growth of Orlodea where we show a hundred patients, a 75 treaters, over 50 payers. The profile of every product on the market today plus everything that's coming in the future, we give those future products their best case scenario. If they good data in phase two, we assume that that's what they look like on the market. And we get patient and physician preference share and then run it through a 6,000 simulation Monte Carlo analysis to predict as John said, patients typically come in one time a year now for their HAE.

So what happens in that one visit? What happens this year, next year, five years from now as more products come onto the market? And what this simulation predicts is that Orlodea will grow to about 25% share in the market, and then we'll maintain that share even as new products, even new oral product comes to the market. We will maintain that share. So that by 2029 into the twenty thirties, when Orlodea was at a peak of about a billion dollars, we may be growing more slowly, but we'll be maintaining that share long term.

So we'll keep doing this research every year, but it's given us confidence in that our our intuition is right. What we're hearing from our customers is right. And, you know, we have a very bright future.

Serge Belanger, Healthcare Analyst, Needham: Okay. And it looks like you're you're gonna get some some company in terms of, on the oral treatment side. We do are expecting on demand treatment to get approval, I think, late June.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Looks like June. Yep.

Serge Belanger, Healthcare Analyst, Needham: Yeah. So do you view that product as a potential competitor or one that could provide some tailwinds for more adoption of, all oral HAE treatment?

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Yeah. Really, the latter. We're looking forward to it. We think it'll be great for patients to have an all oral, option. As I said earlier, what we know from patients and doctors is prophylaxis is the backbone of therapy.

So patients wanna prevent their attacks, but nearly every patient, whether you're on Orlodayo, Taksyro, any other product, you have occasional breakthrough attacks, and so you need a rescue medicine. And to be able to do that with another oral could be a great benefit for patients. So we we look forward to that.

Serge Belanger, Healthcare Analyst, Needham: Okay. I think you you've been running a p d a a trial with a pediatric formulation of Verlodale. I think it's fully enrolled now. Just tell us when we could see data and, I guess, there's some IP implication with this trial, but also kind of a expansion a small expansion of the market opportunity.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Helen, do you wanna do you wanna talk about the trial? I'll I'll talk about the opportunity.

Ellen Thackway, Chief R&D Officer, BioCryst Pharmaceuticals: Yeah. So think about an oral option and the difference that an oral option can make. This is an oral option for pediatric patients instead of injectable prophylaxis. What we have is oral granules that are simple for parents to use to sprinkle on food or put in a drink. And that makes dosing easy for pediatric patients and prophylaxis, therefore easy for parents to give to their kids.

In terms of the trial, we have completed the, the initial portion of the trial. We've actually reported the interim analysis for the trial that is the dataset that's necessary to, take this for registration. That analysis reported at Quad AI recently, and this is a a look at safety, a look at PK exposure, and, those are the parameters needed for registration. It's also look at efficacy. What we saw was twenty nine patients enrolled, twenty five patients still on drug at the interim analysis, so so doing really well.

The safety profile that's not only consistent with adults, but looks really good in pediatrics, and pediatric patients doing well in terms of their attack rates, having having excellent control of attacks while using this oral formulation for prophylaxis. So we're really excited about this program filing this year to be able to bring this oral option for prophylaxis to kids.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: And, Serge, as far as the opportunity in The US, Helen talked about the the the need for patients, but we've we've identified about five hundred diagnosed HAE patients 12. And we think that at least, you know well, a growing portion of those could be appropriate for prophylaxis. So, you know, a couple hundred patients could be the opportunity here. And an oral therapy is going to be the market leader for for kids. And so it's a it's a great opportunity for those kids and also families because it's a genetic disease.

You know, it's another way that families can get exposed to Orlodea and another way that some physicians who maybe haven't adopted Orlodayo yet can get a first experience with the product. So we're really looking forward to we're on track to file with the FDA this year, and and we're we're looking forward to bringing that to market.

Serge Belanger, Healthcare Analyst, Needham: Okay. And maybe just to finish off our conversation on Orlodeaux, if we can talk about the ex US commercialization efforts. I forget how many countries you're in now, but, you know, we're we're really seeing some some growth there. Maybe you can just give us an update. And, I guess if you're seeing the same level if you're retaining the same level of market share, ex US than than in The US.

Charlie Gair, Chief Commercial Officer, BioCryst Pharmaceuticals: Yeah. Orlodeyva is now commercialized in over 30 countries. We're really excited in in Europe. Yeah. We've we've gotten market access in every country in Western Europe short of The Netherlands, which we expect this month or or in May, and then we'll have a complete set, which is phenomenal for a rare disease product like this.

What we're seeing is the same trajectory of growth. The big difference is that it takes about five ex US patients on average from a pricing perspective to equal one US patient. And, of course, price doesn't go up ex US. It tends to go down. So the growth ex US is is about volume, and we're seeing really great uptake.

So at peak, we expect similar to what we we do in The US. Peak shares in the mid 20% depending on on the given countries. But the same trend towards prophylaxis being the backbone of therapy we're seeing in Europe. We're seeing it in Japan. We're seeing it in Canada, and we expect to see it in other countries around the world.

Serge Belanger, Healthcare Analyst, Needham: Right. Okay. I'll ask, Alan to talk about the pipeline. I feel it's a underappreciated part of the BioChris story, but one that I think will increase in focus as, well, probably starting this year as we we get data from the the first pipeline asset. So, BCX 17 7 20 5, I believe, is the the first one for Netherton syndrome.

Not sure everybody's familiar with, with that indication. So, Ellen, if you can just give us an overview and what we should expect from, the the first trial later this year.

Ellen Thackway, Chief R&D Officer, BioCryst Pharmaceuticals: Yeah. Sure. So our pipeline has two products that will that are or will be in the clinic this year, and both of those will have data coming this year. So we're really excited that our pipeline is in the clinic and moving forward. The the Netherton Syndrome program is a is one that could be transformative for patients with Netherton Syndrome.

This is a disease that is a serious skin disorder. It's one that can has a mortality rate associated in infancy from the the results of dehydration through the skin, and it affects patients through life. So it's it's very serious. There's no disease targeted therapy available, and it's one in which patients live with, skin that is red, inflamed, itchy, and peeling in large pieces from head to toe. It also affects hair, and and they have very brittle hair.

And it affects the they have food allergies, affects the GI system, they have food allergies. They also have asthma. So it's a really serious disease. Patients with Nederton syndrome are generally treated with supportive care used for the larger category of ichthyosis, which is which is bad skin disorders. And so this is an opportunity to bring a targeted therapy forward in trials to patients and potentially really transform how they live with their disease and and move their skin towards being more normal so that they can live with normal skin and normal hair in a way that the rest of us take for granted, and these patients just do not have.

So this program is it we have a protein therapeutic. It's a fusion protein. It's a KLK five inhibitor. It is a very potent molecule, and it has very high affinity. What that means is that this molecule can be delivered in a small concentration.

We believe it could be subcutaneously delivered. And once it hits the target, it sticks there for a long time. We think that means it could be dosed about every two weeks or longer. So for this drug, we are we are anticipating and and our goal is several different things. One, bring a functional cure for the disease with a targeted treatment to replace the missing protein function.

Two, do it in a simple package, a subcutaneous treatment that could be dosed every two weeks. And three, do it in a way that patients really experience tremendous difference in their disease and near normalization of their skin. The program today is in the clinic. We are in phase one. That phase one trial includes both healthy volunteers and patients.

So at the moment, we're dosing healthy volunteers. We started this last year, a SAD, MAD, single ascending, multiple ascending dose study. That needed to initiate to get the initial data to show that we are translating exposure levels to from, preclinical to humans as we expected. And as that continues, we're also moving to enroll patients now in this phase one study. This year, we'll be enrolling patients while in parallel continuing this ADMAD program.

And we'll be looking in patients for all the signs of the drug working in the ways that I'm I'm I'm describing. So one, we're looking for basic outcomes like getting to the skin. Drug can penetrate the skin, which we expect to see. Drug that that has on target activity in the skin biomarkers. But more importantly, we are also looking for the drug to have the effect, and we believe we're dosing in a range where we can see that this year.

We're dosing in patients, and we will be giving patients a small number of doses over a period of about a month so that we can then observe for their skin to see if we are observing those changes, that healing of the skin as measured by the physician, as measured by the patient and their experience, using endpoints that could become our pivotal endpoints. And in the course of this year, having a small number of patients for whom we have data on all three of those, drug in the skin, drug activity on target, the biomarker, and then clinical observation of healing on outcomes that could be the same as the pivotal endpoints. With that data this year, we'll be in a good position then to move next year into continued exposure of more patients and trials settling on the dose and preparing for a pivotal program. And as a program in a rare disease with no targeted therapy, this is one that could have a streamlined path to registration.

Serge Belanger, Healthcare Analyst, Needham: Okay. And avorolstat is now going back into the clinic, or maybe it's already in the clinic at this point?

Ellen Thackway, Chief R&D Officer, BioCryst Pharmaceuticals: Avorolstat's going back into the clinic this year. This is now for treatment of patients with diabetic macular edema, where we understand from previous experience and our own data now that plasma kallikrein is an alternative mechanism of action for treatment of diabetic macular edema. The preclinical evidence suggests that we'll be moving into the clinic to test that. We'll be doing that with a vorostat, which we believe is, really ideally suited for use in this indication, and I'll explain how. Vorostat is a drug that, for which we know from a systemic perspective, we know that it has a good safety profile because it has been evaluated in randomized phase three for oral administration.

Here, we'll be using one of its physical properties, which is poor solubility to deliver it into the back of the eye using suprachoroidal injections to deliver a suspension of a Vorostat into the back of the eye, and that will slowly solubilize over time to deliver Vorostat in its soluble form to the retina. What we're looking for here, we're looking for improvement of retinal vascular leakage. That is the source of edema in the eye. That is the source of the retinal edema that leads to poor visual acuity and loss of visual acuity in patients with diabetic macular edema. What we want to do with this program is evaluate Vorostat's ability to both deliver exposure over a long period of time with few injections for patients and then an alternative mechanism of action to treat retinal vascular leakage and to improve diabetic macular edema and improve visual acuity.

This year, we're dose we'll be dosing in patients. We'll have our first few patients on drug this year. It's a trial that will go into next year, but we are gonna be looking at patients one by one to observe for safety and tolerability in the eye, of course, that's standard. But also then on scan of the retina, are we seeing a reduction in retinal thickness that indicates reduction in edema in our first few patients this year? And then continuing enrollment and dosing next year to increase the sample size before making decisions about later trials.

Serge Belanger, Healthcare Analyst, Needham: Great. So maybe to finish off, we can talk about financials, you know, where you are with in terms of cash and your profitability timelines. And also maybe address, I think it was about a month ago, it was announced that, your CFO was departing. So just a kind of an update on where the search is at this point.

John Stonehouse, CEO, BioCryst Pharmaceuticals: Yeah. Search is going great. Anthony gave us a a nice transition period and and actually is gonna be helping us sporadically even in the coming month or two, which is great. So he's been really wonderful about helping us in the transition, the the search is well underway. And so confident we'll find a very qualified, excited CFO to join the company.

And then financially, you know, we ended the quarter with 343,000,000, or end of the year, I should say, last year, with 343,000,000 on the balance sheet. The guidance we've talked about with revenue already of $5.35 to $5.50, and then expense 5 or $4.25 to $4.35. So what's most important is where are we gonna end up profitability wise? And if you put this compound annual growth rate that we gave at the beginning of the year on revenue of 205% on expense, you end up with generating cash, after, interest and royalty of, $200,000,000 in 2027, you know, positive cash flow. And so that ends up giving you a balance of over $600,000,000 on the balance sheet and, you know, puts us in a really solid financial position.

So especially in times where, know, you don't wanna be dependent on your shares for bringing in more capital.

Serge Belanger, Healthcare Analyst, Needham: No. Not not in this environment. No. And then maybe just to wrap things up, John, I'll ask you to you know, what what do you feel is the aspect of the story that remains the most misunderstood or underappreciated by by investors? And we only have a couple minutes.

So

John Stonehouse, CEO, BioCryst Pharmaceuticals: Yeah. I listen. I think it's Orlodeaux. Right? I mean, here's a drug that's gonna do over $500,000,000 in revenue this year in its fifth year launch.

It's growing at a steady rate. That's undeniable what we've done so far, and and all the indicators we've given you have been spot on in terms of where it's going. And so it's on its way to a billion dollars. And, you know, yeah, there's competition coming, but we've explained to you in the most robust way, I think anybody has explained it, of how we see the market unfolding with new competition. And and then IP, as we had talked about before, between, you know, 2035 with one patent and '39 with another.

And so the value of that alone is significant, and and we're happy if investors are, you know, spooked by, oh, there's a, you know, more competition. There's a there was competition ahead of us that made it challenging, and and look at what we've done. Sit down with us and let us walk you through how we see the future with the robust analysis that we do and see if you come to a different conclusion because you might be missing out.

Serge Belanger, Healthcare Analyst, Needham: Yeah. Alright. I think on that note, we'll, we'll end our session here. So I wanna thank you all for joining us this morning. Appreciate your presence at, Needham's Healthcare Conference and on the BioChris story, pretty appealing in this in these times right now.

John Stonehouse, CEO, BioCryst Pharmaceuticals: Thanks, Serge.

Serge Belanger, Healthcare Analyst, Needham: Thanks, Serge.

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