Earnings call transcript: BioCryst’s Q1 2025 revenue and stock surge

BioCryst Pharmaceuticals Inc. (BCRX) reported its Q1 2025 earnings, revealing a significant revenue increase and a surprising stock surge. The company, currently valued at $2.07 billion, posted revenue of $145.5 million, surpassing the forecasted $127.9 million, driven largely by its flagship product, Orlodeyo. Earnings per share (EPS) came in at $0.00, outperforming the anticipated loss of $0.07. Following the earnings release, BioCryst shares rose by 13.77%, reflecting investor optimism about the company’s financial health and future prospects. According to InvestingPro data, the stock has delivered an impressive 100% return over the past year.

Key Takeaways

• BioCryst exceeded revenue expectations with $145.5 million, driven by strong Orlodeyo sales.
• EPS outperformed forecasts, coming in at $0.00 against a predicted loss of $0.07.
• Stock price surged by 13.77% following the earnings announcement.
• The company expects profitability for the full year 2025, a year ahead of schedule.
• BioCryst raised its annual revenue guidance for Orlodeyo to $580-600 million.

Company Performance

BioCryst Pharmaceuticals demonstrated robust performance in Q1 2025, with total revenue increasing significantly from the previous year. InvestingPro analysis shows the company’s revenue has grown 36% over the last twelve months, with a remarkable five-year CAGR of 56%. The company continues to lead the market in oral hereditary angioedema (HAE) prophylaxis, supported by strong real-world evidence of Orlodeyo’s efficacy. With an overall Financial Health Score of 3.08 (rated as "GREAT" by InvestingPro), the company has also focused on expanding its market potential through new product developments and strategic initiatives.

Financial Highlights

• Revenue: $145.5 million, surpassing the forecast of $127.9 million.
• Orlodeyo revenue: $134.2 million, with 89.5% from the U.S. market.
• Operating profit: $21.2 million.
• Operating expenses: $102.9 million, up from $93.6 million in Q1 2024.
• Cash at quarter-end: $317 million.

Earnings vs. Forecast

BioCryst’s earnings per share of $0.00 exceeded the forecasted loss of $0.07, marking a significant positive surprise. The revenue of $145.5 million also surpassed expectations by approximately 13.92%. This performance indicates a strong start to the year and suggests positive momentum for the company’s financial trajectory.

Market Reaction

Following the earnings announcement, BioCryst’s stock experienced a notable increase of 13.77%. The stock’s current price of $10.30 represents a significant gain, trading near its 52-week high. With a beta of 1.75, the stock shows higher volatility than the broader market. This positive market reaction reflects investor confidence in the company’s ability to achieve its revised revenue and profitability goals. Analysts maintain optimistic price targets, with InvestingPro showing targets ranging from $8 to $30 per share. For deeper insights into BioCryst’s valuation and growth potential, investors can access the comprehensive Pro Research Report, available exclusively to InvestingPro subscribers.

Outlook & Guidance

BioCryst has raised its annual revenue guidance for Orlodeyo to between $580 million and $600 million, representing a growth of 33-37%. The company expects non-GAAP operating expenses to range from $440 million to $450 million. BioCryst is optimistic about its pipeline development, particularly in Netherton syndrome and diabetic macular edema (DME), which could further enhance its market position.

Executive Commentary

CEO John Stonehouse stated, "We have never been in a stronger financial position," highlighting the company’s improved financial health. Charlie Guyer, Chief Commercial Officer, emphasized the potential impact of the pediatric formulation, stating, "An oral formulation is going to be the natural choice for starting prophylaxis with a kid." These comments underline the company’s strategic focus on expanding its product offerings and market reach.

Risks and Challenges

• Market competition: As a leader in oral HAE prophylaxis, BioCryst faces competition from other pharmaceutical companies.
• Regulatory approvals: The success of new product launches depends on obtaining timely regulatory approvals.
• Economic conditions: Macroeconomic pressures could affect healthcare spending and patient access.
• Pipeline development: Delays in clinical trials or product development could impact future growth.

BioCryst Pharmaceuticals’ Q1 2025 earnings report showcases the company’s strong market position and strategic initiatives, setting a positive tone for the remainder of the year. With a current ratio of 2.63, the company maintains strong liquidity to support its growth initiatives. InvestingPro subscribers can access 11 additional key insights about BioCryst, along with detailed financial metrics and expert analysis through the exclusive Pro Research Report, helping investors make more informed decisions about this rapidly growing biotech company.

Full transcript - BioCryst Pharmaceuticals Inc (BCRX) Q1 2025:

Conference Operator: Good day, and welcome to the BioCryst First Quarter twenty twenty five Earnings Call. All participants will be in listen only mode. After today’s presentation, there will be an opportunity to ask questions. To ask a question, you may press star then 1 on your telephone keypad. To withdraw your question, please press star then 2.

Please note that this event is being recorded. I would now like to turn the conference over to John Liu with Investor Relations with BioCryst. Please go ahead.

John Liu, Investor Relations, BioCryst: Thank you. Good morning, and welcome to BioCryst’s first quarter twenty twenty five corporate update and financial results conference call. Today’s press release and accompanying slides are available on our website. Participating with me today are CEO, John Stonehouse Chief Commercial Officer, Charlie Guyer and Chief R and D Officer, Doctor. Helen Thackray.

Following our remarks, we will answer your questions. Today’s conference call will contain forward looking statements, including those statements regarding future results, unaudited and forward looking financial information as well as the company’s future performance and or achievements. These statements are subject to known and unknown risks and uncertainties, which may cause our actual results, performance or achievements to be materially different from any future results or performance expressed or implied in this presentation. You should not place undue reliance on these forward looking statements. For additional information, including a detailed discussion of our risk factors, please refer to the company’s documents filed with the Securities and Exchange Commission, which can be accessed on our website.

In addition, today’s conference call includes non GAAP financial measures. For a reconciliation of these non GAAP measures against the most directly comparable GAAP financial measure, please refer to

John Stonehouse, CEO, BioCryst: the earnings press release posted in the press release section of our Investor Relations website at www.biocryst.com. I’d now like to turn the call over to John Stonehouse. Thank you, John. We’ve started 2025 with another quarter of outstanding performance. As you will hear from Charlie in more detail, the U.

S. Commercial team made tremendous progress in moving patients on ORLIDEAU from free drug to paid at a much faster rate than we expected. The result is quarterly revenue of $134,000,000 This improvement in the paid rate impacts revenue performance in Q1, but also through the rest of the year, leading us to raise annual revenue guidance for Orlodayo to between $580,000,000 and $600,000,000 which is 33% to 37% growth over last year. Our improved revenue growth significantly increases our margins and has also accelerated our cash flow and profitability goal by a year. We now expect to be profitable on a full year basis this year.

This increased financial strength and the positive cash flow it generates enabled us to pay down $75,000,000 of our debt in April, while continuing to invest in and advance our pipeline. In addition, we are now moving into Orlodeaux revenue levels where we no longer pay a royalty on sales above $550,000,000 and we’re getting closer to our peak sales for Orlodea of $1,000,000 In the current environment of uncertainty, having a company with growing sustainable revenue and advancing pipeline and financial strength to be profitable, pay down debt and be independent of the markets is hard to find in our industry, but that’s exactly what we have at BioCrest. With that, I’ll turn it over to Charlie to discuss our fantastic first quarter results. Charlie?

Charlie Guyer, Chief Commercial Officer, BioCryst: Thanks, John. The launch trajectory for Orlodayo has been consistently strong for the past four years, but the first quarter of twenty twenty five was our best yet because of the combination of great demand generation and amazing progress helping patients gain access to therapy. As we described previously, U. S. Patient demand in 2024 matched the first year of the launch.

Our team continued this momentum as first quarter new prescriptions slightly exceeded our best quarter from last year. In addition, our latest patient survey showed that regardless of their current treatment status, the percentage of USHA patients who strongly prefer oral prophylaxis grew to seventy percent, up from fifty one percent in 2023, as you can see on slide seven in today’s presentation. And HAE treaters are increasingly convinced that Orlodayo is very effective and convenient for patients based on their individual experience and the rapidly expanding body of real world evidence that they have seen. Orlodeyo is becoming their treatment of choice. What really drove Q1 performance though was a 10 percentage point jump in the rate of paid patients in The U.

S. Over where we ended 2024. We expected that level of improvement to take three years. We did it in four months. The Inflation Reduction Act drove about two thirds of the improvement because the IRA is achieving its intent of helping Medicare patients afford their prescription co payments.

Medicare patients were not only able to afford their Orlodeyo prescriptions, but they were able to do so earlier in the quarter than expected. And we also continued to make great progress among the roughly sixty percent of Orlodeyo patients who have commercial insurance. The paid rate in that segment increased to eighty four percent as we further improved our ability to convert patients from long term free product to paid product. By the April, we were nearly through the reauthorization season and approximately eighty four percent of all established patients on Orlodeyo were receiving paid therapy. That’s close to our long term goal of eighty five percent on the past $800,000,000 in U.

S. Revenue, a rate we forecasted would take at least three years to hit. This acceleration in paid rate improvement means a lot more revenue this year, allowing us to increase guidance significantly, as John noted. But it also positions us to capture more Orlodea revenue over the next several years as our patient base continues to grow. In other words, we’re still on a path to $1,000,000,000 in global revenue in 2029, and the path is now even more profitable.

As we look to the second quarter, our very strong first quarter means that the typical revenue jump in Q2 will still be the largest quarterly increase for the year, but less pronounced than in prior years, in the range of $10,000,000 to $12,000,000 Slide five shows visually how we expect this year to look different. We anticipate this pattern shift because we captured more revenue opportunity per patient in Q1, so the Q2 increase will move closer to the underlying patient growth trend. I’ll provide a bit more color to explain. As I mentioned earlier, patients moved to paid status more quickly than expected in Q1, which means we gave away less free product. Our team also continued to improve gross to net, which in Q1 allowed us to keep it closer to the lower end of our typical range of 15% to 20%, when in prior years it was closer to 20% in the first quarter.

We expect gross to net to improve throughout the rest of the year, but more gradually, so that the full year average will be right around 15%. Our great execution to start the year and accelerated Orlodayo outlook for the rest of 2025 come at an exciting time because our clinical pipeline is nearing important early milestones. The path to another differentiated rare disease product like Orlodayo could soon be increasingly clear. I’ll turn it over to Helen to describe our progress.

Helen Thackray, Chief R&D Officer, BioCryst: Thank you, Charlie. Good morning. Today, I’m pleased to share an update on recent significant milestones for our pipeline programs. First, we submitted our pediatric NDA for Orlodeyo to FDA, introducing an oral granule formulation for patients aged two to 11, with additional filings in Europe, Japan, and Canada also this year. This would be a significant advance in the treatment of children with HAE, as it would be the first targeted oral prophylactic therapy for this age group.

Next, I’m pleased to report that we received authorization to initiate patient enrollment for both the pipeline programs following ORLIDEAUBCX1775 in Nederton syndrome and of oralstat in diabetic macular edema, which is an important step on our path to having initial clinical data in patients for both programs by the end of the year. Today, I’ll focus on the Netherton Syndrome Program in detail and provide more information about the trial design, what we’re looking for, and what to expect by the end of the year. First, I’ll describe why we’re so excited about the potential for seventeen seventy five as a transformative treatment for people living with Nederjen syndrome. This is a devastating illness. Its consequences are very serious and lead to lifelong impacts on health and well-being.

We’ve heard from patients that the lack of treatment leads them to withdraw from medical care. We recently heard exactly the same feedback from our clinical site investigators. Just as it’s been for other rare diseases like HAE, we expect introducing a new potential treatment that could revolutionize care will attract patients back into the care system and into clinical trials. We designed seventeen seventy five to address the fundamental pathology that causes Nethersen syndrome, every aspect of which is ultimately caused by a genetically determined lack of an essential skin protein called sphincter five, also known as Lecti. Normally, this protein stops cells in the outer layer of the skin from prematurely separating from the cells below.

It achieves this by controlling the activity of key calacrine, KLK5, which digests bridging proteins that glue the outer layer skin cells together. In Nethersen syndrome, there is no breaking mechanism for this because KLK5 is continuously on, and so skin cells quickly separate and are lost. What that causes is a massive disruption of the essential barrier functions of the skin, which normally keeps warmth and moisture inside and microorganisms outside, but not in Nethersen syndrome. And in addition, KLK5 directly activates the rest of the Kalkine cascade in the skin via KLK7 and KLK14. Through cascading pathologic inflammatory and allergic pathways, the effect is magnified down into the deeper skin and tissue layers, ultimately also resulting in systemic inflammatory and atopic effects like asthma and food allergies.

All this stems from one faulty gene, leading to the lack of one protein, SYNC five, the regulator for KLK5. This means KLK5 is the key pharmacologic target in this disease because it’s the pinnacle protein, the one at the very top of the cascade that drives the whole process as we see in slide 13 in today’s presentation. Our scientists engineered seventeen thousand seven twenty five to replace the function of that missing protein in its control of KLK5. So, we have tremendous confidence in the target and the pharmacologic approach we are taking based on the significant experience of our scientists and many others who have published their clinical and preclinical work. A big challenge with a protein therapeutic in this disease is to get enough drug into the epidermis and have it stay put.

The epidermis, or the outer layer of the skin, is where it needs to act. So, to give us the best chance of success, our scientists designed this molecule with far greater potency compared to the natural inhibitor and very high affinity or stickiness for KLK5. These features give us the best chance to minimize the dose necessary and make every molecule that finds the target count by binding tightly and blocking KLK5. Today, we’re reporting that the IND has cleared in The U. S.

For enrolling patients with Nederton syndrome into our phase one trial. This clinical trial is set up to tell us quickly whether we’ve met our objectives and design of the drug. The trial plan is outlined on slide 14. We’re currently dosing healthy volunteers to evaluate basic information on exposure and safety, and we’re now identifying sites in both The U. S.

And Australia for the patient arm of the study. Patients will be given four weeks of treatment and about two months of continuing evaluation beyond that. Building on this, we also plan to expand the trial later in the year to evaluate a longer twelve week course of treatment as we learn more about the drug. Cohort size will be small as we expect to gain a significant amount of information from just a handful of patients and perhaps from every patient. To best inform the design of future trials and to provide early insights into the therapeutic potential of seventeen thousand seven hundred twenty five, we need to understand how the drug behaves in patients living with Nederton syndrome.

To do this, we’ll be looking at drug levels in the epidermis, both by using adhesive tape to collect skin epidermal cell samples and with small skin biopsies. We would be thrilled to see the presence of seventeen seventy five in those samples and normal levels of skin calacrine enzymatic activity achieved in patients who have Nederton syndrome, which would provide a strong signal of the potential for clinical efficacy. In addition, we’ll be looking at clinical impact. If we don’t see clinical benefit at a study dose level and dosing is safe, we intend to progress to higher doses. If we do see clinical benefit, as indicated by improvement in measures such as itch Score and Physician Global Assessment of Severity, we’ll have excellent information to inform dose selection for a future pivotal program and even higher confidence in the opportunity for 1775 to be a truly disease modifying therapy for people living with Netherton Syndrome.

Although it’s always a challenge to conduct clinical trials in rare diseases, we have plenty of experience with this. And we’re very encouraged by the clear enthusiasm for our trial that we heard during our recent clinical site visits. We look forward to sharing our initial phase one trial data in patients with Hethershin syndrome by year end. And now I’ll hand the call back to John for a financial review.

John Stonehouse, CEO, BioCryst: Thanks, Ellen. We are exiting the first quarter in a great financial position with stronger than expected revenue growth, increasing full year revenue guidance, accelerating full year profitability to this year, and last month we’ve reduced our outstanding debt. While you can find our detailed first quarter financials in today’s press release, I’d like to draw your attention to a few items. Total revenue for the quarter came in at $145,500,000 a hundred and $34,200,000 of which came from Orlodayo. Of that Orlodayo total revenue, dollars 120,200,000.0 or 89.5% is coming from The U.

S. Operating expenses, excluding stock based compensation, were $102,900,000 for the quarter, up from $93,600,000 in the same quarter last year. This was primarily driven by an increase in commercial expense to support our growing Orlodea revenue, our newly launched regions like Spain and Italy, and expanded international operations including global commercial support activities across finance, HR, IT and supply chain. Operating profit for the first quarter of twenty twenty five was $21,200,000 and net income was slightly positive. Cash at the end of the quarter was $317,000,000 As a result of the significant and durable improvements to revenue that Charlie discussed, we are revising our revenue guidance by 45 to $50,000,000 above our prior guidance, and which represents, as I mentioned before, a 33% to 37 growth over last year.

We now expect non GAAP operating expense for the year to be $440,000,000 to $450,000,000 a $15,000,000 increase over our prior guidance driven by expenses supporting our commercial growth and an increase in COGS as sales of RAPIVAB increased. The result of this strong revenue performance combined with our continued focus on disciplined capital allocation is that we now expect to be profitable for the full year on a net income and positive cash flow basis this year. This is one year earlier than we previously planned. Further, based on this improved financial strength in April, we made a pay down of $75,000,000 on our debt with Pharmacon and reduced our outstanding debt to $249,000,000 As a result, we expect to save approximately $23,000,000 in interest payments over the life of the debt net of the early prepayment penalty. I am immensely proud of the continued focus of our employees who are delivering meaningful improvements in patients’ lives, both today and in the future.

Our commercial and support teams are driving access and usage of Orlodayo, and our R and D team is advancing our pipeline to address challenges in new disease areas where patients are underserved. Financially, we are driving revenue growth and well on our way to $1,000,000,000 at peak, efficiently allocating capital in R and D to create sustainable and long term revenue growth, accelerating our profitability and reducing our outstanding debt. We have never been in a stronger financial position, and I am excited for how this sets us up for a very bright future. Operator, we are now ready for your questions.

Conference Operator: Thank you. We will now begin the question and answer session. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble our roster.

Our first question comes from Steven Seedhouse from Cantor. Please go ahead.

Steven Seedhouse, Analyst, Cantor: Good morning. Thanks so much for taking the question. Just looking ahead to another potential tailwind for ORLIDEA, which is the pediatric launch. Do you have a sense of how many pediatric HAE patients are on TAKHZYRO today in The U. S?

And do you think you’ll mainly be switching children from TAKHZYRO? Or can you sort of quantify how many patients maybe just don’t want a needle, but would be new starts opportunities for Orlodo prophylaxis altogether?

John Stonehouse, CEO, BioCryst: Charlie, you want to take that one?

Charlie Guyer, Chief Commercial Officer, BioCryst: Sure. We certainly do expect pediatrics to be a tailwind for us. Just as a reminder, any future revenues for pediatrics are not included in our 800,000,000 in The US or a billion dollar global peak sales. To answer your question, I don’t know exactly how many patients are on TAKHZYRO. We do think that there are about 500 pediatric patients in The US and at least 200 of whom could be appropriate for prophylactic therapy.

But once an oral is available, we actually think that that could grow. So I think where we’ll get patients is a mix of those switching from injectable therapies like TACSYRO. But we also think that the whole landscape for treating kids under age 12 could change and that more kids could start prophylaxis at a younger age to prevent attacks and really change the course of their life with the condition. An oral therapy really makes that happen because I would say there’s literally no preference for an injectable for children. So we think we’ll be very well positioned.

We’re excited about it.

John Stonehouse, CEO, BioCryst: Yeah, I would add, that when you consider that you can just sprinkle our medicine, the granules onto some soft food or into a glass of water versus the trauma of sticking a needle into a toddler, we should be the market leader. There’s no doubt in our minds that that’s going to be the case. And I think the other thing that Charlie’s referenced in the past is this halo effect. We still have some top HAE physicians that haven’t started switching patients, and we know they have pediatric patients, and there’s no reason for them to not start using our drug for pediatric patients. And when they see how well it works, our expectation is that that’s gonna expand their usage.

So we’re really excited about this. We haven’t put any hard numbers on it yet publicly, but we’re really excited about it.

Steven Seedhouse, Analyst, Cantor: Great. Just also on DME programs, it looks like you’re guiding for data this year. I’d be just curious if you could frame what you would view as a successful outcome for that first readout, given the precedent data, given obviously the novel delivery method, just what are you hoping to see there in the first group of patients?

Helen Thackray, Chief R&D Officer, BioCryst: Yeah, so we’ll have our first patients on drug. As I said, we have authorization to proceed with enrolling patients in that trial. And what we’re looking for is the obvious safety and tolerability, but more importantly to your question, we’re looking for the effect on the, thickness of the retina, the edema in the retina. So we’ll be able to, in those first patients, watch over several months of exposure, to assess that retinal thickness and whether that is changing. We do expect it will take a little bit of time to change but not very long.

I’d point to some of our preclinical data that shows that in a VEGF dependent model, the use of oral status of plasma calacrine inhibitor has a result of leakage of the vessels very quickly within six days. So just to say that a readout that we’ll be watching this year will be that retinal edema, retinal thickness, and we’ll be observing in the first few patients by the end of the year.

John Stonehouse, CEO, BioCryst: Yeah, normally we don’t get super excited about SAD studies, but this is in patients. And what we’ve seen in rabbits is that when you give a single dose, you still have a really high concentration out to six months. So a single dose of this drug in DME patients could tell us a lot. And so we’re excited to see what we see at the end of the year.

Steven Seedhouse, Analyst, Cantor: Thanks so much. You’re welcome.

Conference Operator: Thank you. Our next question comes from the line of Maury Raycroft from Jefferies. Please go ahead.

Maury Raycroft, Analyst, Jefferies: Hi, good morning. Congrats on the update today and thanks for taking my questions. Wondering if you could just talk more about getting patients onto paid drug and what you did there that worked better than expected. And should we expect the rate to be maintained or improved upon going forward? Or what are some of the drivers you’re focused on that could cause the rate to decrease again over time?

Charlie Guyer, Chief Commercial Officer, BioCryst: Sure, Maury. The number one thing that we did, and we’ve talked about this before, is we’ve, over the last couple of years, made investments in our team to make sure that we’re really prepared and really expert in this reauthorization process. We’ve gotten better every year and we knew that there was this potential tailwind with Medicare this year. We also knew there was more space that we could improve in the very important commercial segment. I would just say that the team has just reached a level of excellence that allowed them to execute this year, and we’re looking forward to further improvements going forward.

What we would expect the rest of this year is that the rate will stay about the same, maybe decrease a little bit because the rest of the year, our paid rate is driven more by new prescriptions as opposed to reauthorizations. But where we ended Q1, where we ended April becomes the floor for what I would expect in the future. I’m very confident we’ll reach our 85% goal. We’ll reach it ahead of when we expected to originally, and we’ll be looking to exceed it if we can.

John Stonehouse, CEO, BioCryst: The other thing I’d say is you should take a look at that slide that Charlie referred to around the pattern of revenue this year. It’s different, right? So we pulled forward revenue that would usually be a big bump from first quarter to second quarter into the first quarter. So you’re going to see less of a bump. I think the other thing, though, that’s exciting is that the underlying growth continues to be really strong.

And so that’s where we’re going to see incremental improvement over the course of the year. And we’re really excited to share that with you.

Maury Raycroft, Analyst, Jefferies: Got it, that’s helpful. And maybe just as a follow-up, if you could just provide more specifics on what you did to improve gross to net in first quarter and what you’re doing to better improve that over the course of the year as well.

Charlie Guyer, Chief Commercial Officer, BioCryst: Yeah, so couple things, Maury. One big, big impact was just fact that we got so many more Medicare patients paid, and that changed the overall gross to net mix. The other thing is the team’s just been really focused at every little detail that can make a difference, such as how much co payment assistance do we give to, commercial patients. And we’ve made some adjustments there that have improved gross to net. So the team is being very disciplined, not just about getting patients to paid, helping new patients come on board, but the team is very focused on maximizing the opportunity in all segments.

And so I’m really pleased that we made that kind of a progress in the first quarter, and I think that will be durable through the rest of the year.

Maury Raycroft, Analyst, Jefferies: Got it. Okay. Thanks for taking my questions.

Conference Operator: Welcome. Thank you. Your next question comes from Jessica Fye from JPMorgan. Please go ahead.

Jessica Fye, Analyst, JPMorgan: Hey, guys. Good morning. Thanks for taking the question. I was curious, more specific to the, guidance bump for Orlodayo, can you quantify how much of that increase is related to Part D redesign and a higher proportion of paid patients through that kind of mechanism versus higher than expected demand versus just execution dealing with the coverage re offs at the start of the year? And second question, just with profitability pulled forward here, how does that impact how you think about investing in the business?

And I guess, specifically, could that allow you to accelerate any development plans for your earlier stage pipeline? Thank you.

Charlie Guyer, Chief Commercial Officer, BioCryst: I can take the first part of that. As I mentioned in my remarks, of the 10% improvement in paid rate, about two thirds of that was related to the IRA helping patients afford their co pay. That’s great. But what I’m really excited about is how much progress we made in the sixty percent of patients who are on commercial insurance, where we improved by close to 5% over where we ended last year, ending up at 84%. That was the other third of that improvement.

Clearly, in terms of raising our guidance for the year, that increase in paid rate overall was the number one factor. But we have an underlying patient growth year over year close to 20%. And as I mentioned, we had one of our best years ever last year. And in the first quarter, we were a little bit better than that. And so that underlying demand is what’s going to drive this brand going forward.

And then John, do you want to talk Yeah, I’ll

John Stonehouse, CEO, BioCryst: take the profitability. So yeah, it’s territory we haven’t been in before and are really excited to be in it. The programs are fully funded already to go as fast as we possibly can. And I think the teams have done a great job of figuring out how to get the programs to move as quickly as possible. And then in terms of what are we investing, I think we gave you a pretty good clue by paying making a pay down of $75,000,000 of the Pharmakon debt.

Cleaning up the balance sheet, not having to pay significant amounts of interest over time is something that we’ll continue to look at as cash flow comes into the company. Operator, think we can go to the next question.

Conference Operator: Yes. Thank you. The next question comes from the line of Brian Abrahams from RBC Capital Markets. Please go ahead.

Nevan, Analyst, RBC Capital Markets: Hi, everyone. This is Nevan on for Brian. Congrats on the quarter and thanks for taking our questions. So just following up from some of the prior questions. So given that you’re on at around 84% paid drug and also that you’re on the lower end of your gross to net range for the year, does this potentially indicate that there was a dip in the total patients that were on Orlodayo, and how

John Liu, Investor Relations, BioCryst: do

Nevan, Analyst, RBC Capital Markets: you see that kind of evolving into the rest of the year?

Charlie Guyer, Chief Commercial Officer, BioCryst: Well, I can tell you, there wasn’t a dip in patients on early days. Maybe I’m not quite understanding your question, Nevan. We’ve had extremely consistent demand. So again, last year, we had as many new patient starts as we did in the first year of the launch. And then we did a little bit better than that in the first quarter.

The retention rate of patients has also been extremely consistent the last couple of years, where anybody who starts on Orlodayo, we get about sixty percent of those patients to stay on therapy through the first year, and then very few drop off after that. What we’re seeing in patient demand, is as strong, if not stronger than we’ve ever seen. Then you add on top the paid rate and the improved gross to net, it just means that we’re more profitable. And so we still see reaching $1,000,000,000 in 2029, but the path to get there every year with that underlying demand is just going to be more profitable than we previously expected. So it’s a great position to be in.

John Stonehouse, CEO, BioCryst: Yeah, I think, Nevan, I don’t know if you’re referring to that slide of the pattern of sales, which because of the fast change in free drug to paid, the pattern is different than previous years, and it’ll probably go back to the same pattern as previous years next year, but there is nothing that is slowing down. And we’re really excited about the underlying demand and continue and there’s more patients to get, quite frankly. I mean, I think the last update Charlie said is around 3,000 patients

Charlie Guyer, Chief Commercial Officer, BioCryst: the of last there’s

John Stonehouse, CEO, BioCryst: 10,000 available. So there’s plenty more to get. So no signs of slowing down. Just a

Nevan, Analyst, RBC Capital Markets: it. And then I guess on the uptick in patients that you’re seeing for preference of for oral prophylactic, what do you think is kind of driving that underlying dynamic there? Have rates of maybe needle phobia changed, or is this just a convenience factor that’s being appreciated more as they kind of see the more maturing launch of ORLIDEAL and the convenience that that offers?

Charlie Guyer, Chief Commercial Officer, BioCryst: Thanks for that question. I think what we’ve known since before launch that fundamentally, the great majority of patients prefer oral therapy to injectable. But what’s really important to patients is that they get control of their HAE attack, so they’ll never sacrifice, efficacy for convenience. But now four plus years into the launch, what they’re seeing is with all of our efforts is with Orlodayo, you can have both. You can have great efficacy, you can have convenience.

The patients have seen it themselves, they’ve heard from their peers, it’s a very connected community within HAE. Then their healthcare providers are just that much more confident, which always is a critical factor that the physicians have confidence in a drug. So you put all this together with the efforts that we’ve made from a sales and marketing perspective, it’s natural that patients’ underlying preferences is coming out. I think that’s why we’ve seen it grow by about 20% over the last couple of years. And I wouldn’t be surprised if it continues to grow.

John Stonehouse, CEO, BioCryst: I think it was around a year ago we told you, Charlie told you that there was a momentum change and that there was a confidence buildup. And that was because more and more physicians were having positive experiences with their patients. Patients talk and doctors talk about other patients to their patients saying, I have a patient that does really well on Orlodeya, you might want to consider trying it. And so it’s that confidence in the product that I think is reflected in the market research.

Nevan, Analyst, RBC Capital Markets: Great. Thank you all so much, and congrats again on the quarter.

John Stonehouse, CEO, BioCryst: Thank you.

Steven Seedhouse, Analyst, Cantor: Thank you.

Conference Operator: Your next question comes from Stacy Ku from TD Cowen. Please go ahead.

Stacy Ku, Analyst, TD Cowen: Thanks so much for taking our questions, and congratulations on the really impressive quarter. So first, as we think about these additional patient additions and strong patient demand, you’ve previously added around 60 prescribers per quarter. What are your expectations for this year? And

Helen Thackray, Chief R&D Officer, BioCryst: then

Stacy Ku, Analyst, TD Cowen: some follow ups on other trends. Are you able to make any disclosures on the Phase I early SADMAD results? Are you able to disclose anything at this point in time? Or can you narrow the timelines for any updates in other gen? And then I have a follow-up on other gen.

Charlie Guyer, Chief Commercial Officer, BioCryst: Okay, I’ll start with the healthcare providers. Good memory, Stacy. Last year, we actually averaged 61 new healthcare prescribers for Orlodayo per quarter. It was 62 in 2023, and in Q1 we had 59. It’s incredible consistency, at this stage in the launch that we’re still convincing new prescribers.

Our team will always go out and find new prescribers. The other thing though is, and John touched on this earlier, we’ve made progress in the Tier one physicians. 80 one percent of those doctors have now prescribed and we’re seeing more and more physicians become repeat prescribers and even some returning who prescribed some years ago now returning now that they better understand the product. The physician dynamics are excellent along with the overall patient dynamics. Then Helen, you might want

John Stonehouse, CEO, BioCryst: to talk about how we’re thinking about packaging all the data towards the end of the year.

Helen Thackray, Chief R&D Officer, BioCryst: Yes. So in terms of the results on the SEDMAD, Stacy, we’ve been following that trial. We have its intent with initial safety and PK data. We have the confidence now from that to open the dosing in patients, so you should see that as a sign of generally what we’re seeing. And then what’s most important, and we’ve been clear about looking for the skin outcomes in patients, what’s most important is what happens in patients.

So, we’ll bundle it all together. It’ll be by the end of the year. It will have the updates from the healthy volunteer data, then more importantly, that outcome in patients and are we at the dose that gets to skin healing.

John Stonehouse, CEO, BioCryst: So in healthy volunteers, no news is good news.

Stacy Ku, Analyst, TD Cowen: Okay, wonderful. Well, guess that leads to my then follow-up with that, Nethertin. I know you’ve talked about kind of the early interactions with investigators in the activations of states, but maybe Nuance Part four of the Phase one study. Sounds like you’re getting at least some sense of safety. Could you broaden the POC into younger patients or are you mainly seeing into adults?

Thank you.

Helen Thackray, Chief R&D Officer, BioCryst: Part IV is the extension of treatment. It is designed so that it’s additional patients. So what we’re hearing at the sites, we’re hearing clear enthusiasm, we’re hearing that a potent KLK5 inhibitor that could target at the top of the cascade is something that physicians want to try in their patients with Netherton Syndrome. It’ll be the first few patients who are on that Part three, and then we’re sort of continuing. We’ll open Part four and continue and broaden enrollment to get a longer term exposure.

I would think of them as sort of going together rather than being separate. And the result is by the end of the year, we’ll have patients on both sections with a longer term follow-up on those who’ve been dosed in Part three and then more recent follow-up in those dosed in Part four.

John Stonehouse, CEO, BioCryst: I think one other thing, Stacy, that I’m certainly learning as we learn more about this community and both the physicians and the patients is there are some significant differences from HAE. There’s no therapies in place. The organization for advocacy isn’t nearly as advanced as HAE was. So those are challenges in finding patients. But the flip side is the hope we’re offering these patients is off the charts, right?

They were hopeless, or they have been hopeless and coping because they have nothing to treat the underlying cause of their disease. When we start talking to patients and tell them what we’re trying to work on, I mean, it brings them to tears. So that’s powerful. And so if we can find these patients, and I’m confident we will, and this drug gets to the skin, we’ve got something really powerful to help them and give them hope.

Stacy Ku, Analyst, TD Cowen: Wonderful, thanks so much.

Steven Seedhouse, Analyst, Cantor: You’re welcome. Thank you.

Conference Operator: Next question comes from Gena Wang from Barclays. Please go ahead. Gena Wang, your line is unmuted. Please proceed with your question.

John Liu, Investor Relations, BioCryst0: Oh, thank you. Thank you for taking my questions. I have two questions. I think I joined a little bit late. So if already discussed, and I heard some of the answers, if already discussed, I apologize.

So for your paid rate, truly very impressive, like 10%, over 10% increase from the last quarter’s 73.5, now improved to 84%. You did a comment when you answered numerous questions, answered, you know, various parts. But, you know, can you help us understand, like, what make it, like, in such a short time that have such a big improvement? Can you walk us through the actual process what you did make it possible in short time see such a high increase regarding the pay rate? And then the, second, question is regarding the DME.

So you will have a patient data later this year. Could you give us some benchmark you are looking for that you will consider that will be encouraging to move forward?

John Stonehouse, CEO, BioCryst: Yeah. Hey, Charlie, maybe I’ll start first on this first one and then you can answer the rest. I want to remind everybody that when the Medicare negative thing happened, it snapped the other direction very quickly, like within a quarter. So this is a snapback, but I’ll let Charlie explain it in more detail.

Charlie Guyer, Chief Commercial Officer, BioCryst: Yeah, so again, Jean, one thing I explained is about two thirds of the improvement was Medicare. And as John said, that was a quick snapback, but it was because our team prepared. And so the snapback is, and I’ve always said this, that Medicare plans approve Orlodayo at the highest rate amongst all insurers that we see. It was just an affordability thing, for patients. It’s great that IRA is helping patients afford, and our paid rate amongst the twenty percent of our patients who are in Medicare is now eighty nine percent.

So that kind of underlines what I just said about it being the top segment for approvals. The other piece though, is the team really prepared on the commercial side. And one of the preparations is we have all this long term real world evidence. So what we know about the drug and the efficacy today is very different from what we knew four years ago. And so the team is able to use that more proactively with payers, and it’s convincing more and more payers that this is a very effective drug and therefore they’re choosing to pay for it for the patients.

That’s where I think we can still make progress, but it’s about the data, the preparation, and then also intended impact of the IRA coming true.

John Stonehouse, CEO, BioCryst: The other thing before I turn it over to Helen on the DME is back when patients were struggling to make their copay, we made a very conscious decision to give them free drug. And we kept the patients, and we actually gained patients as a result of that strategy. So then when the affordability got back to normal, those patients snapped back quickly. And I think strategically, that was, in hindsight, a good move to make. Helen, you want to talk about DME?

Helen Thackray, Chief R&D Officer, BioCryst: Yeah, so because we have authorization now to dose inpatients, this is a big milestone for this program. We are looking this year to have exposure and experience with a few patients with that single dose. As John mentioned earlier, this is a drug with long durability of exposure and we’re looking for the outcome, the retinal edema lessening, reduction in the size of the retinal thickness. We’re looking for that and we’ll be looking for that for the end of the year. In terms of what then is the benchmark to move forward, we’re looking for a really big effect.

We’re looking for a clear and uncontroversial reduction in edema that would then tell us that we have a dose level that’s got the exposure necessary to have that effect. If we don’t see that, we will increase the dose. We’ll either see a very significant reduction in edema and know that we have a dose we can take forward, or will not have achieved that yet and will expect to increase the dose until we do?

John Stonehouse, CEO, BioCryst: Yeah, I think we’ve always said we’re looking for signals of activity and starting to get a sense around dose, and that’s exactly what Helen said. When you have three patients per cohort, there’s a limited amount of information that you can get. But I think if we can see some sort of effect and duration of effect that gives us encouragement, nobody else with a kallikrein inhibitor has done that yet. And so that would be very exciting for the program.

John Liu, Investor Relations, BioCryst0: Sorry, if I can follow-up. So how many micron reduction you will consider clear and uncontroversial?

Helen Thackray, Chief R&D Officer, BioCryst: So I would use within the literature for what is generally accepted as something that’s gonna be predictive of likely response to visual acuity. I can’t give you a number today, but I can tell you we’re looking

John Liu, Investor Relations, BioCryst0: for an

Helen Thackray, Chief R&D Officer, BioCryst: uncontroversial difference, so not something that’s small.

John Liu, Investor Relations, BioCryst0: Okay, thank you.

Conference Operator: Thank you. Your next question comes from Laura Chico from Wedbush Securities. Please go ahead.

John Liu, Investor Relations, BioCryst1: Good morning, thanks very much for taking the questions. First one is just going back to the pediatric formulation for ORLIDEAU. Can you just remind us on maybe some of the timelines after a pediatric launch arrives? Would there be a lag in deployment to the channel upon approval, just getting material out for supply? And then as we’re thinking about the cadence of uptake in the pediatric population versus the adult, just kind of curious what dynamics we should be thinking about that might impact that uptake a little bit differently than what we’ve seen in the adults.

I have just one quick follow-up.

John Liu, Investor Relations, BioCryst2: Sure.

Charlie Guyer, Chief Commercial Officer, BioCryst: We will try to make the lag as small as possible. When we launched capsules back in 2020, it was only two weeks from approval to being in the channel. That was amazing. I don’t know if we’ll go quite that fast, but we’re looking to get it out as quickly as possible. The other thing we’ll do is prepare our team to begin promoting right away.

And I think that’s even more important because it’ll take a little time for kids to come in and visit physicians. The uptake dynamics, I alluded to some of this a little bit earlier. I think the biggest difference is that prophylaxis really hasn’t been the standard of care for kids 12. The historical conventional wisdom is that kids become symptomatic mainly around puberty. I think what we saw in our clinical trial is for many of these kids, that is very not true.

Many of these kids were, in fact, I think the average age of symptoms was age two. And so changing the way that the whole treatment paradigm for children, if you could prevent attacks so that patients could avoid that fear, so parents could avoid that fear, it could really change the course of a kid’s life living with HAE. I think that’ll be the biggest change. As John and I both said earlier, I think an oral formulation is going to be the natural choice, for that starting prophylaxis with a kid. So we’ll see how quickly it goes, but we’re hearing a lot of enthusiasm from both healthcare providers, and the patient community for the change that I’m describing.

Yes. I’d add

John Stonehouse, CEO, BioCryst: one of the things we learned with adults is it takes longer than you think. And so that’s why we’re not getting out over our skis here on giving you guidance on the uptake, cause we just don’t know yet. We’re confident that we will be the market leader because we believe we have a formulation that is way more acceptable to little kids than injectable. But the pattern to get there is, it’s just too early to predict.

John Liu, Investor Relations, BioCryst1: Understood. Okay, thank you for that one. And then one quick follow-up on. You remind us the dosing range you’re gonna be starting with for $17.75? And then I just wanted to clarify, I know you mentioned advancing later to twelve week dosing, but what is the actual trigger for that?

Is that dependent on accruing sufficient four week data in the initial cohorts? Any clarity there would be helpful. Thank you.

Helen Thackray, Chief R&D Officer, BioCryst: Yeah, sure. So, in terms of the dosing range, we have experience with a fairly broad dosing range now in healthy volunteers, and we’ll be dosing patients somewhere in the middle of that range. Six milligrams is the dose for patients in that initial part of Part three. There isn’t a trigger so much for the Part four, twelve weeks. It’s more that we’ll learn about the dose level, we’ll learn about whether we see initial effects quickly in Part three, and from that we’ll understand if we need to start with the same dose or dose escalate quickly in Part four.

It’s more that they’ll be dosing initially in Part three, learning from that as we initiate Part four, both going in parallel with ongoing observations over time. So as I said earlier, it’s more like a continuous sort of set of two arms that go together.

John Stonehouse, CEO, BioCryst: Yeah, the drug works, we’ll have an ability to keep patients on drugs.

John Liu, Investor Relations, BioCryst1: I see. Okay, thank you guys. Congrats on the quarter.

John Stonehouse, CEO, BioCryst: Thank you.

Conference Operator: Thank you. The next question comes from Lisa Bayko from Evercore ISI. Please go ahead.

Helen Thackray, Chief R&D Officer, BioCryst: Hi, there. Thanks for taking the question and congratulations on a strong quarter. Two parts to my question. First is, I just want to make sure I understand that the paid rate improvement that you saw, you’ve talked about it kind of being like a switch that flips on. Is there any chance this flips back?

Can you talk about the sustainability of this paid rate improvement as we head into next year and future years? And then part two is really, can you talk about the patients on treatment today? And then walk us through the kind of remaining pool of patients out there, at least in The US, who have not yet tried Orlodo and your plans to kind of increase utilization there? Thanks.

Charlie Guyer, Chief Commercial Officer, BioCryst: Sure. Thanks, Lisa. The paid rate, I believe, will be very sustainable. Based on the evidence that we’ve shown for Orlodeyo, it’s really changing our conversations with payers. I think that 84% is our new floor as we look forward over time.

Patients on therapy, so as I mentioned earlier, at the end of last year, three thousand patients in The US had tried out of a pool of about 10,000. Launch to date, fifty two percent of our patients have switched from other prophylaxis. Just over thirty percent have switched from acute only, and the remaining sixteen percent, eighteen percent, whatever it is, our patients best we can tell were naive to therapy. That last piece I’m excited about because what it shows is that this is a market that is still growing. We’ve known that the market for prophylaxis has been growing over time, but we’re finding new patients out there and they’re coming to prophylaxis.

We have at least another 7,000 or so patients who have not yet experienced Orlodayo and many of them will be appropriate for prophylaxis. You combine that with the 70% preference for oral prophylaxis that we discussed in the call today, and the growing healthcare provider enthusiasm, and the fact that we’re getting paid at such a high increases confidence overall. I think we’ll continue to drive Orlodeyo going forward. Yeah, and if

John Stonehouse, CEO, BioCryst: you think about it, if at the end of the fifth year since we got approval, we’re at about a third of the patients that have tried it and we’re at five eighty to 600,000,000, we are definitely on our path to $1,000,000,000

Helen Thackray, Chief R&D Officer, BioCryst: Okay, great. Thank you so much.

John Liu, Investor Relations, BioCryst3: You’re welcome.

Conference Operator: Thank you. Your next question comes from Serge Belanger from Needham and Company. Please go ahead.

John Liu, Investor Relations, BioCryst2: Hi. Good morning, and congrats on the the nice quarter. A couple of questions for Charlie. Now that you’ve reached your target for paid rate of 85%, should we expect continued improvements on that number? Is there more to do on the commercial or Medicare side?

And then just a follow-up on the patient add questions. It sounds like 1Q was one of your best quarters ever in terms of new patient adds. Just curious if you’re noticing a trend on where these patients are coming from, if it’s still 50% prophy and 30% acute or is that mix changing with this new batch of new patient adds? Thanks.

Charlie Guyer, Chief Commercial Officer, BioCryst: Sure, thanks Serge. Yeah, I think we’re almost to our long term goal of eighty five percent, a little more room there. But what we’ll do is we’ll probably up that number, we’ll keep striving to get better. I mentioned just a minute ago that in the Medicare segment, that’s twenty percent of our patients, the paid rate is now eighty nine percent. So that shows that we can improve past the eighty five percent and we’ll do everything we can to keep getting better.

I don’t expect another big tailwind like we had this year, but it’s just now going to be incremental improvements. In the first quarter, yes, fundamentally the patient base was very similar to what we’ve seen since the beginning of launch. The other thing I’d add is the mix of prescribers that I haven’t completely discussed today, but in the first quarter, ’50 ’5 percent of the prescriptions were from our top tier of doctors. Those physicians that we know treat about fifty percent of all HAE patients. And then the other 45% came from everyone else.

So really balanced across the board. I mentioned earlier, we had 59 new prescribers in the quarter, and so we just keep capturing more opportunity and we keep capturing it from all the different segments, which gives us that extra confidence in the sustainability of this growth over the next several years.

John Stonehouse, CEO, BioCryst: Operator, we can go to the next question.

Conference Operator: Perfect. Thank you. Your final question comes from John Wallabin from Citizens. Please go ahead.

John Liu, Investor Relations, BioCryst3: Hey. Thanks for taking the questions. A couple on Netherton for me. Can you remind us of your preclinical tox work that you’ve completed so far? And then, Helen, when you talk about seeing a clinical impact determining dosing higher, what metrics will you be looking at and what’s your bar entirely to determine whether or not you’re in a sufficient spot in terms of efficacy?

Helen Thackray, Chief R&D Officer, BioCryst: Yeah, sure. Preclinical talks, so this is the biologic, it’s protein therapeutic. There’s a fairly standard safety profile for protein therapeutics and we’re seeing a very consistent profile with that. I think the other thing to look at with preclinical tox is we have the authorization now to proceed not only in healthy volunteers but also in patients, and that includes authorization in The US and Australia. So just indicative of the range of confidence coming from the preclinical tox data.

John Stonehouse, CEO, BioCryst: Yeah, and Helen, I would add, we have an open IND, and we have the ability to dose in Part three up to four weeks, and Part four up to twelve weeks. So that gives you some sense of the duration of tox and the like.

Helen Thackray, Chief R&D Officer, BioCryst: Right, so standard toxicology to support that. In terms of the clinical impact, so what we’re looking for is really normalization of the skin. That means we’re assessing by how the patient feels about their skin, is there itch still, and we want to see the itch really go away. We’re looking also at a physician assessment of the skin and the severity index for thickening and scaling of the skin. And so we’re looking for that redness to go down and for the scaling to stop.

I expect that we’ll see some of that initially. I expect that it will probably improve over time and if we need to dose up to get to healing, meaning normal looking skin and patient not reporting itch, then we’ll dose up to that.

John Liu, Investor Relations, BioCryst3: How many patients per cohort can patients in Part three be included in Part four? Then how do you think about the time dependent nature of these improvements?

Helen Thackray, Chief R&D Officer, BioCryst: Part three is smaller than Part four. We could see what we need in single digit patients, so it’s going to be fewer than 10 in Part III. Part IV will be slightly larger, this is still an ultra rare disease and every patient will inform whether we’re at the dose and seeing what we need. So, it’ll be larger, but not much larger in Part IV, maybe more than 10. In terms of the time dependency, we just don’t know.

We do know that we expect the skin turnover in Ethershon syndrome to be about two weeks. We do know that we would expect healing to occur as the skin is turning over, so we may be seeing clinical signs as quickly as four or eight weeks in this. We also may be seeing continuing improvement in healing of the skin because the inflammatory components take a little bit longer to heal. But our goal is to see whether we are getting that initial quick result in the short term for eight week timeframe after end of dosing and then observe over time as we continue to expand Part IV and be able to dose patients for a longer period of time.

John Liu, Investor Relations, BioCryst3: Super helpful. Thanks, Helen.

Conference Operator: Thank you. This concludes our question and answer session. I would now like to turn the conference back over to Mr. Stonehouse for closing remarks.

John Stonehouse, CEO, BioCryst: Thank you. So, I mean, it was a great quarter. I don’t know what else to say. And I am I’ll repeat what I said earlier. I am immensely proud of the employees of BioCryst for delivering the results of this quarter.

But count on us to continue to be executing. We’re not going to rest on our laurels. There’s a lot more to do, a lot more to deliver over the course of the year, and you can count on us for continuing to work as hard as we can to do that. So thank you for your interest, and we’ll keep you updated along the way. Have a great day.

Conference Operator: The conference has now concluded. Thank you for attending today’s presentation. You may now disconnect.

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