Q3 2025 BioCryst Pharmaceuticals Inc Earnings Call
Speaker #1: Good day and welcome to BioCryst third quarter 2025 earnings conference call. All participants will be in the listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key, followed by zero.
Speaker #1: After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one, on a touch-tone phone.
Speaker #1: Not to withdraw your question, please press star, then two. Please note this event is being recorded. I would now like to turn the conference over to Nick Wilder.
Speaker #1: Please go ahead.
Speaker #2: Good Good morning and welcome to BioCryst's third quarter 2025 corporate update and financial results conference call. Participating with me today are CEO John Stonehouse, President and Chief Commercial Officer Charlie Gayer, Chief Development Officer Dr. Bill Sheridan, and Chief Financial Officer Bob Ghias.
Speaker #2: A press release and slide presentation about today's news are available on our Investor Relations website. Today's call may contain forward-looking statements, including statements regarding future financial results, unaudited and forward-looking financial information, as well as the company's future performance and/or achievements.
Speaker #2: 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.
Speaker #2: For additional information, including a detailed discussion of these risks, please refer to slide two of the presentation. In addition, today's conference call includes non-GAAP financial measures.
Speaker #2: For a reconciliation of these non-GAAP measures against the most directly comparable GAAP financial measure, please refer to the earnings press release. I'd now like to turn the call over to John Stonehouse.
Speaker #3: Thank you, Nick. We are very pleased to report yet another strong quarter for the year. Starting with Orladayo, we continue to see strong revenue growth year over year on a growing revenue base, well on our way to $1 million at peak.
Speaker #3: Charlie will share the details as this was the first quarter with new competition, and we continue to see strong underlying growth and a growing prescriber base as we predicted.
Speaker #3: Next, we close the sale of our European business and paid off our Pharmacon debt. And this not only cleaned up our balance sheet, but put us in a very strong financial position, generating operating profit and positive cash flow.
Speaker #3: Bob will share more details regarding our financial position. We are also making progress with our pipeline and expect early data that should give an initial view on activity and dose from our DME program, and we plan to share this early next year.
Speaker #3: If these data are encouraging, we have also made a decision that, given the program is outside our rare disease area of focus, we will look to spin out or partner this program to put it in the hands of someone better suited to advance it further.
Speaker #3: Regarding BCX 17725, Bill will share encouraging data from our Healthy Volunteer study, showing evidence that the drug does get to the skin following IV administration.
Speaker #3: This is important as this is where the target for Netherton syndrome is, and with a very potent inhibitor in BCX 17725, we are excited to see in Netherton syndrome patients what effect it has on the disease.
Speaker #3: Enrollment is taking a little bit longer than planned, and we now expect early data in a small number of Netherton syndrome patients, later in Q1 next year.
Speaker #3: Lastly, having announced the proposed acquisition of Astria last month and the expected close in Q1 next year, we are extremely excited to add a late-stage asset, Nevenabard, to our pipeline to leverage our expertise in HAE and bring patients a new treatment option with a low burden of administration.
Speaker #3: So clearly, we have been busy since last reporting quarterly earnings, and this is shaping up to be another outstanding year of performance for our company.
Speaker #3: With that, I will turn it over to Charlie.
Speaker #4: Thanks, John. We entered the final quarter of 2025 with continued momentum. We are raising our Orladayo revenue guidance to between $590 and $600 million for the year, even after closing the sale of our European operations on October 1st.
Speaker #4: And the exciting possibilities of the Orladayo granules launch for kids with HAE and the acquisition of Astria are just ahead. Orladayo continues to be the most differentiated prophylaxis therapy for patients with HAE.
Speaker #4: Most HAE patients would rather prevent their attacks with an oral therapy. Physicians know this, and they trust Orladayo. Even as two new prophylaxis products launched recently, offering patients the potential of once-monthly injectable dosing, new prescriptions for Orladayo continue at the same strong pace we have seen over the past two years.
Speaker #4: In fact, we slightly exceeded the new patient prescription total from the third quarter a year ago. We also continue to expand the number of Orladayo prescribers with 64 new prescribers in the US, exceeding the average of the past eight quarters.
Speaker #4: The well-established trends in patient retention remained unchanged, and we ended the quarter with a paid patient rate of 82%, right in line with the typical second-half pattern compared with the first half of the year.
Speaker #4: As always, we're very pleased with the great results, but not surprised. Our deep insight and market simulation work consistently predicted that the growth of Orladayo would not be affected by new competition.
Speaker #4: We updated that work over the summer, and the 2025 results were nearly identical to the 2024 results, as you can see on slide eight in today's presentation.
Speaker #4: With the expected addition of Orladayo granules on top of the existing strong growth trends for Orladayo capsules, our market simulation continues to predict $1 billion in peak revenue for BioCryst in 2029, even after the sale of our European business.
Speaker #4: The analysis demonstrates that new injectable therapies primarily compete with existing injectable therapies. This is why we are so enthusiastic about the prospect of adding Nevenabard to our portfolio.
Speaker #4: With Nevenabard, we could have the lowest burden, most differentiated injectable prophylactic therapy, along with a long-time leading oral therapy. Significantly expanding our ability to help patients in the HAE community.
Speaker #4: We expect Nevanabard to drive double-digit HAE revenue growth well into the 2030s, after Orladayo revenue reaches a steady plateau. We also expect to manage costs by using the same rare disease commercialization engine that has made Orladayo so successful.
Speaker #4: Today, I'm also very pleased to announce that Ron Dellinger will succeed me as Chief Commercial Officer when I move to the CEO role on January 1st.
Speaker #4: Ron led the sales team at Vaira Pharma during the early days of Synrise commercialization. While that drug changed the HAE treatment paradigm at the time, Ron always knew that an oral therapy was what many patients really wanted.
Speaker #4: And he wanted to be part of making that possible. Ron joined us in 2019 to build and lead the U.S. sales team for the launch of Orladayo.
Speaker #4: And since 2022, he has served as General Manager of our US and America's business. Fostering a team culture that is deeply caring and authentically focused on serving patients, while also being relentlessly driven to improve.
Speaker #4: That's a rare combination, and it has produced amazing results. I look forward to what our commercial team will achieve under Ron's leadership. As we look forward to helping a growing number of HAE patients, our excitement about the potential to help patients with Netherton syndrome is also growing.
Speaker #4: I'll turn it over to Bill to describe our progress with BCX 17725. Thanks, Charlie. I'm very pleased to be able to share some findings from our ongoing phase one study that BCX 17725, our novel investigational KLK5 inhibitor, designed to replace functions of the natural inhibitor that are deficient in individuals living with Netherton syndrome.
Speaker #4: This trial is designed with multiple goals in mind. Number one: understanding the preliminary safety profile of BCX17725. Number two: quantitating its systemic exposure with serum drug levels.
Speaker #4: Number three, evaluating the distribution of the drug into the epidermis. This is very important because the target enzyme, KLK5, is expressed in that location.
Speaker #4: Number four, assessing its potential early treatment effects on signs and symptoms of Netherton syndrome. We are planning to first do this in a few individuals living with NS in part three of the trial.
Speaker #4: The trial has so far progressed through multiple cohorts in healthy volunteers. With different cohorts administered single or multiple doses of study drug. This gives us a handle on the first three goals.
Speaker #4: The dose level of BCX17725 has been progressively increased, with up to 12 milligrams per kilogram administered by IV infusion. In the multiple ascending dose portion, three doses were given on a Q2 week schedule.
Speaker #4: In this trial, administration of BCX 17725 has been safe and well tolerated, with no safety signals seen. And preliminary assessment of systemic exposure profiles supports continued testing of up to every two weeks dosing regimens.
Speaker #4: As I'm representative images from skin biopsies taken before and after dosing in healthy subjects are shown on the accompanying slide. These small punch biopsies are taken under local anesthetic and processed for imaging.
Speaker #4: The images show user technique called immunofluorescence microscopy. Antibodies are applied that specifically bind to the protein you want to detect, in this case, the drug, BCX 17725.
Speaker #4: These complexes are then detected with secondary antibodies covalently tagged with a fluorochrome, which is a chemical that fluoresces typically under ultraviolet or near ultraviolet light.
Speaker #4: That means we can see a specific color based on the fluorochrome used, wherever the drug is located in the tissue specimen, and the more drug there is, the brighter the signal.
Speaker #4: We can also use other differently colored fluorochromes to pick out structures such as cell nuclei. Although minimally invasive, we are limited in the number of biopsies we can take.
Speaker #4: So we decided to obtain a baseline biopsy prior to the first dose as a control sample, and to post-dose biopsy five hours after the last dose of drug.
Speaker #4: The displayed biopsy sample images from a representative healthy volunteer in the 12 milligram per kilogram multiple dose cohort show the DNA located in cell nuclei in blue, and the drug located in the extracellular matrix in green.
Speaker #4: The pre-dose sample shows the loose dermis with wide leaf-based bright brune blue nuclei, and the dense epidermis with tightly packed nuclei, with a very faint green signal due to non-specific binding of the SA reagents.
Speaker #4: In the post-dose sample, there is an obvious difference, with much brighter green fluorescence. You can use the blue nuclei as a benchmark. In the post-dose image, the drug has flooded the loose connective tissue in the dermis and distributed throughout the epidermis.
Speaker #4: These are important findings. The drug was able to diffuse across the epidermal basement membrane into the extracellular matrix of all the layers of the epidermis.
Speaker #4: Drug getting to the epidermis will allow its access to the target enzyme, KLK5, in patients with Netherton syndrome. Our investigators are quite excited by these results, as are we.
Speaker #4: And we look forward to enrolling patients with NS into the trial in coming months. I'd now like to turn the call to Babar to walk you through the financial progress.
Speaker #1: Thanks, Bill. My first full quarter as CFO of BioCryst was extremely eventful and was marked by several significant achievements, which I believe position us well for future growth and profitability.
Speaker #1: On October 1st, we successfully closed the sale of our European business, providing an immediate boost to our financial position, enabling us to fully repay our pharmacon debt.
Speaker #1: During Q3, we worked diligently on a highly strategic and transformative acquisition of Astra Therapeutics, which we announced last month. This acquisition is expected to strengthen our presence in HAE and solidify our double-digit growth trajectory for our portfolio over the next decade.
Speaker #1: As part of this proposed transaction, we also worked on securing a strategic financing partnership with Blackstone, at a highly attractive cost of capital. Upon closing of the Astra acquisition, which is expected in Q1 2026, we will access up to $400 million of cash from this facility.
Speaker #1: But all of this was only made possible due to the continued strength of OLADEO and our improving operating performance. Please refer to our third quarter financials in today's press release.
Speaker #1: However, I would like to take a moment to elaborate on some of these accomplishments and their impact on our trajectory. Total OLADEO revenue was $159.1 million, representing 37% year-over-year growth.
Speaker #1: Of that, OLADEO revenue, $141.6 million or 89% came from the US. As you heard in Charlie's remarks, we continue to see strong momentum in our business despite the recently announced approvals.
Speaker #1: Non-GAAP operating expenses excluding stock-based comp and transaction-related costs were approximately $108 million for the third quarter of 2025. Up from approximately $92 million in the third quarter of 2024.
Speaker #1: Some of this increase was driven by continued investment in R&D, which continues to be a priority for us. As you heard from Bill, we are very excited about the promise of these programs.
Speaker #1: We have also made a strategic decision to seek partners for a DME program after we evaluate initial patient data. In light of sharpening our focus on rare diseases and focusing our capital allocation on programs where we can create most value.
Speaker #1: Non-GAAP operating profit, excluding stock-based compensation expense and transaction-related costs, was $51.7 million for the third quarter of 2025, an increase of 107% year-over-year as we continue to benefit from significant operating leverage.
Speaker #1: Our non-GAAP net income for the quarter was $35.6 million, resulting in non-GAAP EPS of $0.17 per share. We finished the quarter strong with $269 million in cash, which included cash from health or sale by European entities.
Speaker #1: Our strong cash flow profile enabled us to make a $50 million prepayment on our pharmacon term loan during Q3, and with the closing of the sale of European business, we also paid off the outstanding amount under the term loan of approximately $200 million.
Speaker #1: Our proforma cash balance, giving effect to these adjustments, is approximately $294 million, and zero term debt. Due to the strong expected cash flow generation, we anticipate reaching $1 billion in cash during 2029.
Speaker #1: However, we will continue to evaluate various capital allocation opportunities to generate value for our stockholders, much like our recently announced proposed acquisition of Astra Therapeutics.
Speaker #1: We will also explore, upon closing of the transaction, a European license of Novenibar and strategic opportunities for the STAR 310 program, which may yield further upsides.
Speaker #1: Moving on to guidance. Charlie already alluded to the revenue guidance, and at the same time, we are lowering our non-GAAP OPEX guidance to $430 to $440 million from our original guidance of $440 to $450 million.
Speaker #1: The European divestiture allows us the opportunity to continue to streamline our base business cost structure. We remain on track to deliver non-GAAP net income and positive cash flows for full year 2025.
Speaker #1: As previously stated in our acquisition press release, we are expecting to stay profitable on a non-GAAP basis as well as cash flow positive even during the development period of Novenibar.
Speaker #1: In closing, I'm proud of our team's continued focus and execution as we work to drive sustainable growth and deliver meaningful improvements in patients' lives.
Speaker #1: Our strong results and disciplined operational and financial strategies position us to capitalize on future growth opportunities, strengthen our leadership in rare diseases, and continue delivering value for our stockholders.
Speaker #1: Operator, we are now ready for your questions.
Speaker #2: Thank you. We will now begin the question and answer session. To ask a question, you may press star and then one on your touchstone phone.
Speaker #2: 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 two.
Speaker #2: At this time, we will pause momentarily to assemble our roster. First question comes from Jessica Fay, with JP Morgan. Please go ahead.
Speaker #3: This is Jose for Jessica. Thanks for taking our question. Of the 37 year-over-year OLADEO net revenue growth, how much of that was volume and how much of that was better paid rate or net price?
Speaker #3: And on that front, how should we think about gross to net this quarter and going into 2026? And very quickly, how confident are you that you can maintain steady patient retention rates given the increasingly competitive landscape?
Speaker #3: Thank you.
Speaker #1: I can start with that. That question. So of the 37% year-over-year, we had really steady volume growth over time, but there was a big portion of it that was price based on the improvement in paid rate that we described earlier this year, particularly in the Medicare segment.
Speaker #1: So the volume is growing at the pace that we expect and at the pace that we need to get to the $1 billion in peak revenue in 2029.
Speaker #1: As far as the patient retention with new competition coming in, as I mentioned in the remarks, our patient retention has been identical to our ongoing trend, not affected at all by the new products coming in the market.
Speaker #1: And we expect that to continue.
Speaker #3: Yeah. And just to add, the logic behind that is these patients are really well controlled. They're getting similar control to injectable drugs. And they're on a once-a-day pill.
Speaker #3: And so what on earth would they switch to that could be better than that?
Speaker #1: And then gross to net is still about 15% as we've announced earlier this year.
Speaker #3: And next year, in that 15 to 20?
Speaker #1: Yeah. Next year, it'll still be in the $15 to $20, probably a little closer to the $15.
Speaker #3: All right. Thank you. Great.
Speaker #1: You're welcome.
Speaker #2: The next question comes from Laura Chico with Redbush Securities. Please go ahead.
Speaker #4: Good morning. Thanks very much for taking the question. One question with respect to the new prescriber numbers. I think this is the second quarter in a row.
Speaker #4: You've been over 60. Just curious if you have any feedback, market research, that can help us understand why they're deciding to prescribe now. What has been kind of the motivating factor more recently to accelerate the ads here?
Speaker #4: And then I guess if you could share a little bit more color on what was the expected blended royalty rate look like in '26?
Speaker #4: I know you're projecting a step down over time here, but just kind of curious how we should be thinking about it directionally from '25 to '26.
Speaker #4: Thank you.
Speaker #1: I'll start with thanks, Laura. it over to Barbara on the royalties. So the motivating factors, and we've described this before, is just physicians getting more and more comfortable with the long-term evidence, the real-world evidence for how well OLADEO works.
Speaker #1: What they understand now is that OLADEO works very well, equally well to injectable products in most patients. It either works or it doesn't. And if the patients don't have the benefit that they need, they move on.
Speaker #1: So, physicians are really understanding. I'll start with the prescriber data, and then hand and accurately target means that we are able to find physicians who have a smaller number of patients.
Speaker #1: So if you have one HAE patient, we will find you. And OLADEO is becoming the treatment of choice for those doctors. Overall, as we grow the number of physicians, we consistently see a pretty equal balance between those smaller prescribers as well as the top 600 or so doctors that treat 50% of the market.
Speaker #1: So we keep chipping away at those top prescribers and launch to date over 80% of those doctors have prescribed. So we're really thrilled to show this consistent progress expanding the number of prescribers.
Speaker #3: And just one other thing I'd like to add, Charlie, is that there's still physicians out there, even in the top prescribers, that haven't written for OLADEO.
Speaker #3: And one of the things we're extremely excited about next year is the pediatric approval because these docs have pediatric patients, many of them. And there is no reason that they should use anything but OLADEO for prophylaxis for these patients.
Speaker #3: So, we think that's going to open up even more new prescribers next year.
Speaker #1: Yes. And on the royalty section, we are pleased to share that this quarter we are tripping over the lower threshold. And it'll continue to come down.
Speaker #1: As you can see in our slides prepared slides, the rate is in the early blended rate is in early teens. And while we have not given 2026 guidance, I can assure you that rate continues to come down because there's a cap on some of those royalties when you hit the 550.
Speaker #1: But as you can imagine, when we are out to provide you guidance, when you do the math, it'll continue to decline. And as we've said over time, it'll be in single digits as we pay off the OMRS liability altogether.
Speaker #3: Yeah. So as revenue goes up, profitability gets better and better and cash flow continues to flow. So it's very bright financial future.
Speaker #4: Thank you, guys.
Speaker #1: Yep.
Speaker #2: The The next question comes from Stacy Skou with TD Corvin. Please go ahead.
Speaker #4: Hey, good morning. Thanks so much for taking our questions and crap on the progress. So we have a couple of questions. First, on the new entrants, are KOLs to indicate there are a couple of patients switching from OLADEO to an injectables, but the same clinicians are also saying that they expect OLADEO share to stay stable.
Speaker #4: So beyond this anecdotal feedback and obviously you all have highlighted the one-year 60% retention, are you able to share any recent metrics to suggest OLADEO's unlikely to be impacted by these injectable entrants?
Speaker #4: So that's the first question. And then the second is on that pediatric HAE approval. As we approach the proof of date, maybe help us understand your views on the opportunity and what commercial strategy and preparation is ongoing to really make sure you all maximize that pediatric expansion.
Speaker #4: Are many of these patients already identified? Just help us understand, as we get to the new year, any type of expectations around maybe some latent patient demand.
Speaker #4: Thanks so much.
Speaker #1: Sure. Thanks, Stacy. As far as the new entrants, yeah, of course, some patients are switching from OLADEO because 40% of new patient starts on OLADEO drop off within the year.
Speaker #1: And in the past, they might have dropped off to Taxcyro and Hagarda. Now maybe they're more likely to switch to some of the new entrants.
Speaker #1: So that's exactly what we expected. What we're not seeing, though, is a change in our new patient prescribing patterns. Or a change in our overall retention rate.
Speaker #1: And as far as the data that give us confidence in this, as I mentioned, slide 8, we redid our market research. We redid our big conjoint analysis and market simulation.
Speaker #1: With all the new information about new and future competitors and what you see is no change to our prior versions of this market research.
Speaker #1: It shows that OLADEO patients remain very sticky, and we expect that to continue. As far as the pediatric approval, we've seen that there are about 500 patients today diagnosed with HAE under the age of 12.
Speaker #1: And only about 40% of those patients today are on or kind of in the prophylaxis space and have tried prophylaxis. So, we think that there's an opportunity both to grow the use of prophylaxis within pediatrics as well as for switching because an oral therapy is important to a lot of patients, but it's particularly important to kids with HAE.
Speaker #1: So, as far as our strategy, and John mentioned earlier, the doctors that treat kids with HAE tend to be the same physicians that are treating patients over age 12.
Speaker #1: So, we're already calling on these physicians. We know who is treating kids, and the team will be ready to go with the launch shortly after approval.
Speaker #4: Thank you.
Speaker #2: The next question comes from Steve Seedhouse with Canto. Please go ahead.
Speaker #5: Hey, good morning. Thanks so much. I was hoping you could expand on the decision to de-emphasize, I guess, an oral stat for DME? Have you had an early look at the Phase 1 data there?
Speaker #5: And then looking at the updated pipeline, slide, the undisclosed programs listed for rare diseases at least that are preclinical, can you give us some insight into what you're working on there?
Speaker #5: Preclinically and how close it might be to the clinic?
Speaker #3: Yeah, I'll take that one. So regarding a viral stat, now we haven't seen any of the data. We just enrolled the first cohort. And so this is a decision based on focus.
Speaker #3: And expense. By bringing a late-stage product like Noventa Bar into our pipeline, we need to create space to be able to fund and bring that to the finish line.
Speaker #3: And these DME programs get really expensive the further on you go in clinical development. And quite honestly, we don't have the expertise there. We do in rare disease.
Speaker #3: And so we just think it's better in the hands of somebody who has that expertise. And then on the undisclosed, we're not going to disclose what it is.
Speaker #3: It's early. It's exciting. But when it's ready to be shared, we'll have more information to share with you.
Speaker #5: Okay. And just quickly on Netherton, have you had any dialogue with regulators there and formed an understanding of what a pivotal program requirement might be?
Speaker #3: Yeah, we have. Not enough to share with you the design of the pivotal program at this point. I think the biggest thing and Bill, you can correct me if I get this wrong, is the bigger the treatment effect, the better options we have to move fast.
Speaker #3: With this program. And we'll figure that out once we start getting data. But too early to predict kind of the design of the pivotal program.
Speaker #3: Is that fair, Bill?
Speaker #1: That's very fair. I think once we have evidence of the effects of the drug in patients with NS and the safety of the drug in NS, then we'll have complete conversations with regulators about how to get it approved.
Speaker #5: All right. Thanks so much.
Speaker #1: You're welcome.
Speaker #2: The next question comes from Mauri Rickhop with Jefferies. Please go ahead.
Speaker #6: Hi, good morning. Congrats on the progress. And thanks for taking my questions. I'll just ask a couple of quick ones on Netherton. Wondering if you could just talk more about the slower enrollment there and how many patients you'll have in the first quarter data update next year.
Speaker #6: And do you anticipate dosing higher than the 12 meg per K? And I'm wondering if you're still exploring the subQ dose or is it going to be an IV dosing going forward?
Speaker #3: Yeah, I'll take the first part of it. You want to take the second? I mean, we're only off by a quarter, so it's a very slight delay.
Speaker #3: And the program and the enthusiasm as Bill said by investigators is really high, especially when they see the healthy volunteer data. We didn't expect to see the drug get to the target in healthy volunteers.
Speaker #3: And so that has been really encouraging data. And then, Bill, do you want to take the second part of the question?
Speaker #1: Sure. Yes, we're exploring both subcutaneous and intravenous administration. We'll continue to do that. And we may explore higher doses. That option is open.
Speaker #5: Got it. Thanks for taking my questions.
Speaker #3: You're welcome.
Speaker #2: The next question comes from Brian Abraham with RBC. Please go ahead.
Speaker #4: Hey, good morning. Congrats on the continued progress in the quarter, and thanks for taking my questions. Maybe just continuing on Netherton's, can you elaborate a little bit more on, I guess, what you're seeing from a PK/PD standpoint in those first couple of parts of the ongoing study?
Speaker #4: And I'm also curious what the trigger was for starting that part four, which I know you started in recent weeks. And then just secondarily, separately on Orlodeo, just wondering what you're seeing in terms of demand from the normal C1 inhibitor population.
Speaker #4: I think that was a growth driver you cited in the past. Thanks.
Speaker #3: Bill, you want to take the Netherton and Charlie can take the Orlodeo.
Speaker #1: Sure. So Netherton is a fascinating disease. It's all about what's happening in the epidermis. There aren't any plasma or serum biomarkers to measure.
Speaker #1: Secondly, we have a very tight-binding, very potent inhibitor. And you have to think about what relationship the plasma concentration is going to have to the effects in the epidermis and there could, in fact, be a disconnect between how long the drug sits in the epidermis after binding to the target compared to how long it circulates in the plasma.
Speaker #1: That being said, of course, we're measuring the blood concentrations of the drug. Nothing unexpected there. Solely on that basis, we think that it's worth continuing to explore up to every two weeks dosing.
Speaker #1: But really, it's going to be looking at the effects on the disease. There aren't any pharmacodynamic markers to measure. It's the effects on the disease in patients with Netherton.
Speaker #1: And when we get into that, just a clarification, we have not disclosed whether we've started part three or part four. Part three is just a few subjects with short-term dosing.
Speaker #1: That's the design. Part four enables longer-term dosing. And we look forward to stepping through both of those.
Speaker #3: Yeah. And the expectation is that the data we'll have in the first quarter is part three. Charlie?
Speaker #1: Yeah. And Brian, on C1 normal patients, launch to date, that's been about a third of the patients on Orlodeo. And that's what we saw in Q3.
Speaker #1: Q2, you might recall, we had an exceptional best-ever quarter for new patient starts. There was an additional bolus of C1 normal patients in Q2 because we released some new data.
Speaker #1: Q3 looked like the steady high demand that we've seen over the last two years, with about a third of the patients being C1 normal.
Speaker #4: Thank you.
Speaker #2: The next question is from the line of John Willoughby with Citizens. Please go ahead.
Speaker #6: Hey, thanks for taking the question. Just looking at sales so far this year and your guidance, it's implying that we're going to see a drop in fourth quarter over quarter sales for the first time.
Speaker #6: We haven't seen that seasonality before, so hoping you could talk a little bit about your expectations, what's driving that, and if that's something we should expect moving forward, or if this is going to be a one-time seasonality effect.
Speaker #3: Yeah, John, it's going to be a one-time seasonality because we just sold our European business. So we're losing $10 to $15 million of revenue that otherwise would have occurred.
Speaker #3: So next year, you will not see a drop in Q4.
Speaker #2: Mr. John, does that answer your question?
Speaker #5: Yes, yeah. Thanks, Charlie.
The, uh, part 3 data. Uh, so maybe if you can lay out, uh, you know what, we should expect uh, from this 1q 26, uh, data update from part 3, and then quickly just housekeeping questions regarding all the data. I, I know you mentioned some of the, um, calm like comments, but I do want to double check with the, uh, actual numbers regarding the retention rate. Um, I always do similar around 60% and the pay rate. I think last quarter, we talked about could be by year and 82 to 83% if that's due the same. And the last is the patient segment, you know, 50% switcher from other Pro. Is that still the same?
All right. So uh, Bill why don't you take the safety and and the design of the part 3? And then Charlie, you can take the early Dayo?
so, um, there's
The thing to say about safety and healthy subjects is that it's very safe so far. It's been very safe and well tolerated. So, uh, there have been no safety signals emerging with multiple doses of the drug, um, you know, through the dose that, uh, you mentioned. So.
That's really good news. Uh, you know, I think that with regard to...
what you can expect from part 3, this is very short term administration of the drug in part 3,
Um, you know we're at the cutting edge of clinical science in investigations into the internet and syndrome with a parental drug.
Uh, so we'll be discovering how long it takes in order to get an effect. Uh, so I don't know that yet.
Um, you know, will that short-term administration be enough to see an effect? I don't know, uh, if we do that, it would be very encouraging. If we don't, we'll just give the drug for longer and maybe we'll increase the dose.
See from short-term dosing in a few subjects with netherton. Obviously, we'll be looking at safety so we'll learn a lot and uh look forward to extending the dosing in part 4 of the study uh the sorts of things that you would measure are pretty obvious. Um, itch pain, uh, skin redness and the like
And Bill, we're testing multiple dosing doses in Part 3. So all kind of start to zoom in on what we then want to look at in Part 4. Is that right? Right? Right? It's, uh, it's the first step for more extensive testing in Part 4. Great.
Charlie, um, and Gina, as far as the oilo numbers. So yeah, the patient retention rate is in line with exactly what we've seen over the last several years. So 60% of patients who start Orlando, make it to a year and everything that we saw in queue Q3 tells us we're right on on track with that. That same number, the paid rate, we ended Q3 at 82%, um which is right about where we thought we would be in Q4. I wouldn't be surprised if we end closer to 81% even 80%, typically in the second half of the year, the, uh, the paid rate starts to decline because we have all these new patients coming in and less of an opportunity to switch people from long-term free product to paid product, that opportunity comes in q1 into early Q2 of, of, of the new year. And so we're we're right on track.
For where we need to be, and we expect to have a lot of those patients, then switching to paid therapy earlier in, uh, 2026 and then, as far as the source of business for patients, yeah, the same basic Trends, where we get close to, 50% of the people switching from other protein, history with other proy products and then other patients switching from uh acute only coming over to proy and then a good number of patients best. We can tell are starting orlano as their first ha treatment ever. Um, because more of those are are newly diagnosed patients.
Great. Thank you.
Thank you. This concludes the question and answer session, I would like to turn the conference back over to John Stonehouse for any closing remarks.
Yeah, we thought about ending the call with the Rolling Stones. This will be the last time, but the thought about different of it, but let me say this, um, it's been an honor to lead the employees, uh, bio Chris for nearly the last 2 decades, proud of what we built. Uh, what we've accomplished together and extremely excited and confident to see this team. Take the company into the future by delivering more and more Innovative treatments for patients living with rare disease because in this industry, that's how you create real value. So thank you for your interest in our company, and have a great day.
Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.