BioCryst at Jefferies Conference: Promising Pipeline and Financial Growth

On Wednesday, 04 June 2025, BioCryst Pharmaceuticals Inc. (NASDAQ:BCRX) presented at the Jefferies Global Healthcare Conference 2025, highlighting its strategic growth and development in rare disease therapies. The company reported strong performance in the first quarter, driven by its flagship product, Orlodayo, and shared optimistic updates on its pipeline projects. However, the journey also includes challenges in maintaining growth and managing debt.

Key Takeaways

• BioCryst raised its revenue guidance for Orlodayo to $580-$600 million, up from $535-$550 million.
• A PDUFA date for Orlodayo’s pediatric indication is set for September 12, 2025.
• The company is advancing its pipeline with promising data expected for Netherton Syndrome and DME by year-end.
• BioCryst aims to be net income and cash flow positive in 2025, focusing on debt reduction and strategic investments.
• Cash reserves decreased to approximately $240 million, with current debt at $249 million.

Financial Results

• Orlodayo Revenue Guidance:

- Initial: $535 million to $550 million

- Revised: $580 million to $600 million

• Cash Position:

- Q1: $317 million

- Current: Approximately $240 million

• Debt: $249 million
• Financial Outlook: BioCryst expects to achieve net income and cash flow positivity this year.
• Debt Reduction: The company has paid down $75 million in Pharmakon debt in 2025.

Operational Updates

• Orlodayo:

- Strong demand and improved access to paid therapy have bolstered performance.

- FDA accepted the supplemental NDA for pediatric use, with a priority review PDUFA date of September 12.

• Netherton Syndrome (17725):

- A KLK5 inhibitor is in clinical evaluation, with data expected by the end of the year.

- The focus is on systemic therapy for this severe skin condition.

• DME (Vorostat):

- Phase 1 study underway, utilizing a suprachoroidal delivery approach for sustained drug exposure.

- Initial clinical data is anticipated by year-end.

Future Outlook

• Orlodayo: The company aims to maintain growth and paid therapy rates, which are crucial for achieving the upper end of revenue guidance.
• Netherton Syndrome: BioCryst expects to update on data by the end of the year and may initiate a pivotal study based on Phase 1 results.
• DME: Data updates are expected by year-end, with a focus on assessing changes in retinal thickness.
• Financial Strategy: The company plans to continue reducing debt and investing in pipeline opportunities.

Q&A Highlights

• Orlodayo Pediatric Approval: BioCryst anticipates payer support for the pediatric population.
• Netherton Syndrome: The focus is on targeted treatment with significant skin improvement.
• DME: Preclinical data indicates a rapid decrease in retinal vascular leakage, with Phase 1 focusing on safety and efficacy.

In conclusion, BioCryst’s strategic initiatives and financial discipline position the company for a promising future. For a detailed analysis, refer to the full transcript below.

Full transcript - Jefferies Global Healthcare Conference 2025:

Maury Raycrofton, Biotech Analyst, Jefferies: Hi, everyone. My name is Maury Raycrofton, one of the biotech analysts at Jefferies. With great pleasure, I’d like to welcome Helen Thackery, the Chief R and D Officer from BioChris. Thanks so much for joining us today, Helen.

Helen Thackery, Chief R and D Officer, BioCryst: Thanks very much, Maury.

Maury Raycrofton, Biotech Analyst, Jefferies: And we’re going to do a fireside chat discussion. So maybe to start off, for those who are unfamiliar with BioCryst, if you can set the stage and talk about Orlodeaux and your pipeline.

Helen Thackery, Chief R and D Officer, BioCryst: Yeah, sure. So BioCryst is focused on rare disease. And Orlodayo is in its fifth year of launch for treatment of HAE, prophylaxis of HAE, and growing really well. We’re very, very pleased with performance and what it’s doing for patients. We have a pipeline as well with two programs in the clinic with milestones regulatory milestones and trial milestones already this year, and data for both before the end of the year.

And we’re a company with financial strength. We expect to be profitable this year. We’ve paid down debt already this year. And we are capital markets independent.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And with your lead drug Orlodayo, it’s been commercial. It’s doing really well commercially. First quarter, you guys beat expectations again, and you raised the guidance for the year to $580,000,000 to $600,000,000 versus the prior $535,000,000 to $550,000,000 Can you talk about the drivers that led to the increased guidance? And what are some of the key variables that investors should consider when determining whether you’re going to hit the upper or lower end of guidance this year?

Helen Thackery, Chief R and D Officer, BioCryst: Yeah. So, drivers demand there’s strong demand for Orlodea amongst patients and with physicians wanting to give it to their patients. And for first quarter also, getting patients to paid therapy. So, in particular, the Medicare population, but also commercial population getting to paid therapy was a big driver. In terms of variables going forward for the rest of the year, if we have continued strong growth and keep maintaining that paid rate, then we would we are going to see similar performances here.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Okay. Makes sense. And also wanted to ask just about thinking about the expansion of the opportunity. And you guys have talked about the pediatric opportunity.

And FDA has accepted the supplemental NDA with priority review, and you’ve got a PDUFA scheduled for September twelfth of this year. Wondering what data you included in the data package, And do you expect FDA to ask for longer term data? Have you gotten any feedback from FDA? And also payers as well.

Helen Thackery, Chief R and D Officer, BioCryst: So we have had the NDA accepted, as you said. We have PDUFA date mid September and priority review. The data package is it’s the data that’s needed to extend what we know for adolescents and adults into the pediatric population. So, in PK, as well as we have data on attack rate that’s submitted. This is to meet the pediatric requirements.

And so it’s fairly straightforward to submit a data set like that and have it reviewed by the regulators.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Okay. So wouldn’t expect any surprises as it stands there, based on some of the conversations. Same thing with payers as well. They’ll be on board with this population of patients with pediatric.

Helen Thackery, Chief R and D Officer, BioCryst: We certainly hope so.

Maury Raycrofton, Biotech Analyst, Jefferies: Yeah. Okay. Wanted to dive into the pipeline where you do have two data updates later this year where there’s a lot of interest so that you’ve got Netherton Syndrome and DME. Maybe starting with Netherton Syndrome, just remind us what the mechanism of action is for seventeen thousand seven hundred twenty five, and what data that you’ve seen so far that supports your confidence in pursuing this indication.

Helen Thackery, Chief R and D Officer, BioCryst: So seventeen thousand seven hundred twenty five is a KLK5 inhibitor. We’re pursuing this first of Neithersen syndrome, as you said. In terms of the mechanism, the data is this is a genetic disorder, and it is actually pretty clear. Faulty gene leads to faulty protein function, which leads to no control of KLK5. And so, the missing piece is a KLK5 inhibition.

And that is now in the clinic. It’s in the clinic for evaluation. We’ve had healthy volunteer evaluation so far, and expecting it to go into patients.

Maury Raycrofton, Biotech Analyst, Jefferies: Got him. And we’ve seen a few prior attempts for targeting KLK5 for Netherton. Maybe talk about those approaches where we haven’t seen a lot of success. And how does your drug differentiate versus these prior attempts, as well as the current competitors as well?

Helen Thackery, Chief R and D Officer, BioCryst: So this is an opportunity to inhibit at the top of the cascade. I was talking about KLK5 as the target for this drug. There have been other programs that have looked at KLKs, KLK5 and others. There are also other programs that have looked at of the inflammatory cytokines, and the programs that look at topical therapy. For disease, we believe that systemic therapy is appropriate in order to be able to get exposure throughout the body.

It’s a disease of it’s a fear skin disease, and it affects the skin body wise. So, you really need to be able to get something that is going to treat the whole person. It also is a disease where KLK5 is the driver, as I’ve said, but it activates subsequent calacrines and it also activates other inflammatory molecules. If you stop that cascade at KLK5 with inhibition there, you would see then this is what we expect you don’t need to stop anything further down the cascade because it will have been stopped at that top of the cascade. So it’s really KLK5 inhibition.

There’s one more piece I’ll add, and that is for our program, this is a very potent drug. It also has very high affinity, which means that it sticks to the target, and it sticks for the life of the target being in the skin. And that means we can give a dose, we think every two weeks, in order to give that effect of KLK5 inhibition throughout the turnover of the skin. And so this would be a subcutaneous dose of potent medicine about every two weeks.

Maury Raycrofton, Biotech Analyst, Jefferies: Have you disclosed the half life for what it is yet?

Helen Thackery, Chief R and D Officer, BioCryst: I don’t believe we have. But here, what may be more relevant is the skin turnover. With the high affinity and the drug sticks to that KLH5 target, the skin is going to turn over about every two weeks. That means you shed, and you would want to dose skin about every two weeks.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Okay, makes sense. And in the initial clinical experience, wondering if there’s anything you can comment on what you’re seeing there. I think in the past we’ve talked about whether you’re seeing ADAs or any GI or respiratory tox. And is there anything else you’re focused on as it relates to safety?

Helen Thackery, Chief R and D Officer, BioCryst: So we haven’t seen anything that we’ve specifically disclosed. But what we have seen so far in healthy volunteers is sufficient information, supportive data to allow us to move forward into patients. So you could expect that we’ve been looking at PK, we’ve been looking at safety. I don’t have any data today on ADA, but we have what we need in order to be able to dose patients more than once.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And what can you say about the PK? Is it tracking so far with your expectations? And you disclosed you’re going to start dosing at six mgs sub q. How many more dose levels do you expect to explore in other TIM patients?

Helen Thackery, Chief R and D Officer, BioCryst: So what we have PK in healthy volunteers looking at plasma exposure. It’s in line with what we expected it to be, which allows us to move forward into patients, as I said. We’re dosing in patients at six mgs per kg as the preliminary dose, and we’ll have three doses over four weeks for those first patients. What we the difference in healthy volunteers and patients is that with what matters is going to be exposure in the skin, which is where the target KLK5 is. We can’t measure that in healthy volunteers because KLK5’s not active, the drug won’t bind to it.

But in patients we’ll be able to measure that. So we’ll be looking for PK as measured by the presence of the drug in the skin in patients.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Okay, makes sense. And how often are you measuring drug activity with KLK5 suppression, and how long do you need to follow the patients to understand the healing effect with biomarker IGA or IASA measures?

Helen Thackery, Chief R and D Officer, BioCryst: So in order to measure the drug in the skin, we have to have samples of the skin. So we’re doing a skin biopsy, and we’re also doing an assessment of skin as can as it sort of sheds. So there’s something called skin taping. That we’ll do at baseline, and then we’ll do a skin biopsy at least once, and then the skin taping multiple times after. So we’ll have several different time points to look at drug in the skin.

In terms of the, what else we’ll see this year, so we are looking at the outcomes in the clinical settings, clinical sense, meaning we’re looking for how the skin improves. We’re looking at scaling, and is it decreasing? We’re looking at redness, is that improving? We’re looking at itching, is that improving? And so it’ll be a physician score measuring the quality of the skin, the scaling and itching.

It’ll be a patient score also, on how much does it itch.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And for the skin biopsies, in your initial data update, is there more you can say on just how frequently you’re getting those biopsies? I’m guessing at baseline, and then how many times?

Helen Thackery, Chief R and D Officer, BioCryst: One additional skin biopsy. But we’ll be following patients for a number of weeks. We’ll be following in the part three part of our study. We’ll be dosing for four weeks, and then following for about another two months after that. And we’ll have periodic looks at the skin through the skin taping piece.

It’s like putting a piece of tape on the skin and taking off a few cells. The skin biopsy is more invasive, we’ll just do that once after dosing.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Makes sense. And anything else you’re looking for just based on blood biomarkers that are downstream from the KLK5 pathway?

Helen Thackery, Chief R and D Officer, BioCryst: We will look at, in the skin we’ll look at PD markers and that would be downstream activity from the enzyme activity from KLK5. What I’m most interested in here is looking at the skin outcomes, that what you can actually see in the skin and then matching it back to what we see on PK exposure in the skin and on that PD activity in the skin. Because it’s going to be, what do we see visually on our observation of the skin that really matters, and tells us if we’re at a dose that is having the effect we want to see.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And these patients, maybe talk about just the amount of surface area that’s covered that’s affected by the disease.

Helen Thackery, Chief R and D Officer, BioCryst: So this is a disease that affects head to toe. And one of the diagnostic findings of the disease is something called bamboo hair. So it affects the head as well. And the bamboo hair, it’s the term describing how it looks under the microscope. It’s sort of broken in pieces.

And so it’s head to toe. It’s the entire surface area. There can be some patches of skin that are worse than others, but patients generally exhibit this body wide, unlike some of the other skin diseases.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And so just based on like how quickly you think you’d be able to see, detect some improvement in skin based on some of the accepted measures, I guess how do you think about just the rate of improvement and benefit for patients?

Helen Thackery, Chief R and D Officer, BioCryst: So, number one, I don’t know. Number two, with the rapid turnover in skin in patients with this disease about every two weeks, it may be fairly quickly that we see a response. And so we’ll be looking at four weeks, eight weeks, twelve weeks. What we know in the field is that there’s been recent testing of a topical serine protease inhibitor in patients with Netherton Syndrome, and a response seen relatively quickly, think in under six weeks. And so we may see it that fast as well.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And maybe talk more about the study design and just the rationale behind the phase one design. Why did you pick the four week treatment in part three and twelve week treatment in part four? And do you expect to roll over part three patients into part four?

Helen Thackery, Chief R and D Officer, BioCryst: So the study is designed so that we can get an incremental look first in a few patients. Our target with the patients is to understand, one, is the drug getting to the skin in the quantity that we want it to do? Two, are we seeing healing in the skin as a result? And so, four weeks of treatment will give us an opportunity to look at both of those and a glimpse as it will get is this drug getting to the skin? And then, is it starting to heal?

What we need to know is are we at the right dose? If we see skin healing with four weeks, then we know we’re at the right dose or close to it. If we don’t, then we’ll go up in dose to take the data that we have from skin penetration, but also dose up to be able to get to effect what we see in the skin. We may need to dose up before we get to the twelve week portion in part four of the study. And if we do, then we’ll dose up.

Part four, our goal is to confirm that we’re seeing the findings in the skin, how long they last, and confirm the dose. And what would happen next is that we may then move to a pivotal program or confirmatory trial.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And for patients that roll over, I guess would patients roll over from Part three

Helen Thackery, Chief R and D Officer, BioCryst: to Part Yeah. Patients can complete part three and then be eligible for part four. It’s not quite a roll over, but they could still participate in part four, yes. This is an ultra rare disease, so every patient matters in your clinical trial program. And it’s relatively short term to see something in the skin, and then we would have patients available to go into the next study.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And for an approvable endpoint, for how long you think you would need to treat patients and see improvement, What are your thoughts on that, and what just that duration would have to be?

Helen Thackery, Chief R and D Officer, BioCryst: Yeah. So we’ll have to have that conversation with the FDA and regulatory agencies, of course. I’d expect that we’ll be seeing it within a month or two. It may improve over time as well. As we treat and inhibit KLK5 at the top of that cascade I was describing, we would expect to see the inflammatory markers further down the cascade start to respond.

And that may take a little more time. So, may see some skin change and less scaling of the skin, but the deeper inflammation could take longer. And so, how long you need to study for a pivotal program, I don’t know, but I would imagine it’s at least a few months. Typically, the agency wants to see six or twelve months data, and so it’ll be somewhere in that timeframe.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And for the phase one, just in deciding whether to move forward to a pivotal, what do you want to see for biomarker and clinical healing data by the end of this year? I guess what’s your expectation, and is there a good benchmark out there for reference?

Helen Thackery, Chief R and D Officer, BioCryst: Yeah, so we’re looking for a really big change. So this is a targeted treatment potent drug, a disease with no targeted therapies available, and a very severe disease. We’re looking for a dramatic difference. So what I would want to see is improvement in the skin and match it with what we’re seeing in the PKPD in the skin in order to then inform moving to a pivotal program. If we don’t see that this year, then we’ll dose up, as I said, until we do.

But the information that we’re looking for then is, are we at a dose? And with that dose, are we seeing that dramatic change in the skin with healing?

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And a lot of Netherton Syndrome patients are infants and young children. What safety and efficacy data must be seen in this population to de risk the program?

Helen Thackery, Chief R and D Officer, BioCryst: This gives us an opportunity to include pediatric patients earlier in the program. We don’t have to wait until registration. With a biologic therapy where the class is generally safer, it means that we may have an opportunity to dose down in age as part of our development program and to include in our registration data set. So we’ll need to have PK data so we can judge the exposure that we need, and if the dose has to decrease. We’ll also need to have some exposure and safety in adolescents and adults before we go lower in age.

But we may be able to dose down to age six or so in this program, in part of the development program before we eventually go for registration.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And so you have the data at the end of this year. Would you meet with FDA after decide on what a pivotal would look like and then potentially start that pivotal study next year?

Helen Thackery, Chief R and D Officer, BioCryst: Yeah, I would expect a next step with the FDA would be to bring the data that we obtain in this study and then have a conversation about the path to registration.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Okay. Have you guys said if you’re going to start the study next year? I don’t think you’ve disclosed

Helen Thackery, Chief R and D Officer, BioCryst: A pivotal study? Yeah, a pivotal We have not. No. And it’ll depend on the data. If need to dose up and dose range a bit, it’ll take a little bit longer.

If we’ve hit the dose, which is not usually the case, then we could go sooner.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Okay. And for an accelerated approval path here, there’s not clear precedent out there from our understanding. What do you KOLs want you to do for this type of study?

Helen Thackery, Chief R and D Officer, BioCryst: Yeah, so there’s no regulatory precedent. There’s no targeted drugs, nothing approved yet for Netherson syndrome. And that means that we have some negotiating to do around the endpoints. It’s clear when we talk to physicians that they want to see skin healing. That’s what matters to them, and what they’re in their discussions with patients, what matters to patients.

When we’ve spoken with patients, and when I’ve had that conversation with a patient, they are most concerned about the skin scaling and the itching. And so I would expect those to be part of our pivotal endpoint, and those are the kinds of scores that we’re building in early. But we’ll need to understand with the agency if they agree with that. In terms of accelerated program, this is a severe disease, an ultra rare. We expect a big difference.

That’s what we’re looking for. And that means it could be a relatively efficient streamlined program, Whether it’s accelerated or full approval, that will depend on discussions with the agency.

Maury Raycrofton, Biotech Analyst, Jefferies: Are you bookending the number of patients that you could need for a pivotal study at this point, or is it too early?

Helen Thackery, Chief R and D Officer, BioCryst: It’s too early. But I think we can safely say that it would be relatively fewer than you’d see in other diseases. This is a targeted therapy, big difference that I’m looking for, as I said. And so I would expect it’s going be smaller numbers.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And for enrolling a pivotal study, maybe just talk about some of the challenges there and how that could work within because it’s a smaller patient population. What are you doing to plan for enrolling a pivotal study?

Helen Thackery, Chief R and D Officer, BioCryst: Yeah, ultra rare populations are always something you have to think about carefully as you want to enroll in a clinical trial. Patients are few and far between. We’ve been working with a number of sites and experts, and the experts who treat patients and have more than one, several patients. And the sites that we’re opening are those that have patients already in their patient base, and may be relatively straightforward to find those who participate in the trial. It is absolutely necessary to be talking to the investigators, the KOLs, early, and be working with the ones who know the disease best.

They’ll also have the biggest patient base.

Maury Raycrofton, Biotech Analyst, Jefferies: Makes sense. Is there a good reference study out there for investors to get a sense of what enrollment timelines could look like?

Helen Thackery, Chief R and D Officer, BioCryst: So they’re always going to be different. I don’t think I can point to a reference study for No, I understand. But it is just one more point on that, Maury. This is what we do. We work in rare disease and have for years.

And we’re very familiar with what you need to do to be able to understand with investigators how best to enroll patients in the trial.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Makes sense. And for the market opportunity, you’ve estimated about sixteen hundred Netherton patients in The United States based on the bamboo hair phenotype. And there may be up to five thousand patients if we consider a subset with the ichthyosis patients. Based on your research, how big is the Netherland syndrome market in The United States, and what percent can seventeen seventy five address?

Helen Thackery, Chief R and D Officer, BioCryst: So with targeted therapy, we would expect it to be something that maybe many patients would be interested in. I can’t give you a percent, but this would be the opportunity for them to have something that actually treats the source of the disease. In terms of the market size, it’s hard to say. That sixteen hundred that you mentioned, that’s taken from claims data looking at a clinical symptom. And it’s hard to know how many patients didn’t present with that complaint, didn’t get tested by their physician, and yet still have the disease.

And so, do expect that the recognized patient population may grow as a targeted therapy becomes available, and physicians do the genetic test and identify that a patient who’s perhaps known as having ichthyosis, in fact has Netherton syndrome as a cause of the ichthyosis.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And can you talk just a little bit about the spectrum of severity for the disease, and what the drivers are there?

Helen Thackery, Chief R and D Officer, BioCryst: Yeah. There is a range of severity. We understand that the most likely patients to be diagnosed are those who are most severe and may spend time in sub subspecialists’ office. The reason behind it is the genetic variability. There’s mutation that can be in different places, in two genes, or a pair of genes that any patient has, and something called a compound heterozygote, which means mutations in different places and you may get different expression of the spinc-five protein.

And so that translates into patients who may have quite severe disease and patients who may have less severe disease but still look like they have bad eczema. So they’re seeing a dermatologist, but not necessarily tested and identified as having Nederjen syndrome.

Maury Raycrofton, Biotech Analyst, Jefferies: Are the initial patients that you’re going to enroll, are they the compound heterozygotes?

Helen Thackery, Chief R and D Officer, BioCryst: So we’re looking, maybe, and I’m sure it will include some who are. Not enrolling based on their genetics, we’re enrolling based on their skin disease and having had severe and recognizable skin disease.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Okay. That’s helpful. And for patients that have this, especially kids, they’d likely be on therapy for their whole life, right? It’s genetic based disease.

Helen Thackery, Chief R and D Officer, BioCryst: Yes, it would be continuous treatment.

Maury Raycrofton, Biotech Analyst, Jefferies: Right, makes sense. And so I want to shift gears and talk about well, actually, other question, too. For 17725, are there other indications you could pursue with the drug?

Helen Thackery, Chief R and D Officer, BioCryst: That’s an interesting question that I’m not prepared to answer at this point. KLK5 is expressed in other tissues. The reason we chose Nethersen syndrome is because it is solely KLK5 that is the source of the disease. But as if we are able to demonstrate that this drug is safe, we identify a dose that’s effective in Ehlerschen syndrome, then we may move to other diseases as well.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Okay. And so for DME with you’ve got a lot of experience with vorlestat, which this drug has lower solubility than Orlodayo and could be ideal for the suprachoroidal approach that you’re pursuing in DME. What evidence, either from literature or ideally from clinical kallikrein inhibition experience, gives you confidence in the mechanism for DME?

Helen Thackery, Chief R and D Officer, BioCryst: So there’s actually a fair amount of evidence. We’re looking for the clinical evidence with this program. There is literature that supports that plasma kallikrein is expressed in the fluid inside the eye in a number of patients with DME. In fact, a wide range of patients with DME. And VEGF is also expressed, but not in all of those.

And there’s some overlap between the two, but then also patients who have one or the other. That suggests that VEGF it actually supports why VEGF inhibitors don’t work for all patients, and suggests that plasma calacrine may be an alternative mechanism. There’s also there have been some programs that have assessed plasma calacrine inhibition in the clinic, and they’ve had some initial results that are really interesting. They’re just not sustained. And so it’s more durable exposure at the site of the retina that’s probably what’s needed, and they think we can bring that with a oral stat.

Maury Raycrofton, Biotech Analyst, Jefferies: Because that’s what you’re doing with your approach. You’re getting that durable exposure at the retina, versus the other approaches, which could have been systemic or

Helen Thackery, Chief R and D Officer, BioCryst: Yeah, I think there’s been oral delivery, and there’s been intravitreal delivery. The suprachoroidal space is right around the back of the retina. Putting a vorostat, which is poorly soluble, as you said, in a suspension into the suprachoroidal space and allowing it to slowly solubilize over time, That would give, we think, a sustained slow release of the drug, almost like a depot. And deliver exposure right to the retina so that you have sufficient exposure in the right place for the right amount of time for a long duration, so that one ejection could get to the level of improvement that we want to see in the edema.

Maury Raycrofton, Biotech Analyst, Jefferies: Got him. And talk about the preclinical data you have so far, and how does that derisk translatability to humans in terms of dose, efficacy, and then safety and durability.

Helen Thackery, Chief R and D Officer, BioCryst: So we’re really excited about the preclinical data, because it is so very clear. We have data that’s been in some of our presentations on our website, showing that suprachoroidal dosing with Vorostat in an animal model, in a VEGF dependent animal model, has a fairly rapid and significant decrease in leakage in the retinal vasculature. What that means is in a VEGF model, plasma calacrine inhibition alone with a vorlestat delivered to the suprachoroidal space, the same root that we’re talking about in humans, has a clear, definitive reduction in retinal vascular leakage, and that’s the source of diabetic macular edema is that leakage in the vasculature. So that gives us confidence going forward. We also have data that shows exposure can last past six months with one injection in a similar model.

And that puts us in a position to go into the clinic then and assess for the same thing. If we give a fluoro stat with an injection in the eye and the suprachoroidal space, does that one injection have exposure and durability of exposure out to maybe six months? And does it also have that effect that we want to see in retinal thickness, retinal edema, which is easy to measure in the clinic.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. All makes sense. And that’s a good segue to the clinical study that you’re running. So maybe talk a little bit more about the phase one study design. And what do you want to see in this study in the first few patients that you show at the end of the year?

What’s the bar for success? Or what do you want to beat there?

Helen Thackery, Chief R and D Officer, BioCryst: So we have this will be a relatively small study. It’s first look and it’s a small investment. But it is looking at nine patients at three different dose levels. So dose escalation, dose ranging. And we are looking for safety and tolerability first, but we are also within four, eight, twelve weeks looking for changes in retinal thickness.

That’s easy to measure, it’s non invasive, it’s just an assessment of the thickness on scan. And that thickness, if it starts to change in that four, eight, twelve week timeframe, that tells us we have a drug. And it becomes a drug then that we’ll want to think about investing more to do further evaluation. So this is a first look, a small look, but it’ll give us an idea of are we seeing a difference in the retinal thickness.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And how many time points will you be assessing that then?

Helen Thackery, Chief R and D Officer, BioCryst: So pretty regularly, about once a month. And we’ll actually, we have the opportunity to assess for a number of different months. So if we start to see something, we’ll continue watching and then think about our next trial.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And maybe just going back to kind of the financials and operations, you guys paid down $75,000,000 in Pharmakon debt this year and you expect to be EPS positive this year. Can you remind just on what the cash position is and talk about what else you guys could do having a strong balance sheet potentially on the BD front?

Helen Thackery, Chief R and D Officer, BioCryst: Yeah. So we expect to be net income and cash flow positive this year. Cash at the end of Q1 was $317,000,000 Now it’s about $240,000,000 And debt remaining, since we had the ability to pay some down, is $249,000,000 Our plan would be to continue to pay down debt and clean up the balance sheet, get us into a sound financial position, and then continue to invest in our pipeline, both internal and perhaps through BD external.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. And for the two pipeline data updates later this year, are they going to happen at different times, at the same time? Any more clarity on just or granularity on the timing of these events?

Helen Thackery, Chief R and D Officer, BioCryst: I can’t say that. I think by the end of the year, we’ll have both.

Maury Raycrofton, Biotech Analyst, Jefferies: Got it. Okay. Well, Helen, thanks so much for joining us today.

Helen Thackery, Chief R and D Officer, BioCryst: Helen Thank you, Maury.

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