Q4 2024 BioCryst Pharmaceuticals Inc Earnings Call
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Thank you. Thank you.
Good morning and welcome to the BioChrist fourth quarter 2024 earnings call.
Whether its no longer having to inject your toddler with their medicine for H, a finally, having a treatment to change the underlying cause of netherton syndrome, or giving dnb patients hope of a new therapy that may work for more patients and be given with fewer injections.
The execution of our teams last year has put us in a great position to get data and answers on these programs later this year.
And finally, we executed so well last year that we not only generated a non-GAAP operating profit, but this profit was over $60 million, which is three times larger than what we had planned.
The magnitude of the free cash flow, we now expect over the next three years will likely further transform our company.
Charlie: The place we find ourselves in today it was intentional as the execution by the employees at Biocryst has never been better and the momentum we have is carrying over to this year and likely many years to come I'll now turn it over to Charlie.
Charlie: Thanks, John Orla Deyoe gained momentum in 2024 with over 34% growth in the fourth year on the market and that increasing momentum is carrying into 2025.
Charlie: Demand in early 2025 has continued at the same strong pace, we saw in 2024, but an even bigger source of early strength has been the impact of the inflation reduction act for Medicare patients.
Charlie: We are seeing that a much higher percentage of Medicare patients on oral or Dale can afford their co payments and this is happening at a rate ahead of our prior expectations.
Charlie: As a result, we are raising our Orlando revenue guidance for the year to $535 million to $550 million.
Charlie: The full reauthorization season will run for at least two more months and most re offs within our large commercially insured patient base are still in process.
Charlie: The outcome of those cases will dictate where the revenue ends up relative to the increased guidance range.
Charlie: We've described previously how Hai treaters are gaining enthusiasm for all of them and we have four new posters of real world evidence being presented this coming weekend at the Quad AI conference in San Diego that help explain why.
Charlie: Two of the posters stratify patient reported outcomes by baseline attack rate in type, one and two patients as well as HD patients with normal C. One inhibitor.
And then examine long term outcomes at 12 and 18 months.
Charlie: These analyses include hundreds of patients each which we believe are much larger volumes of evidence that had been reported for any other prophylactic medication.
Charlie: The poster showed that Orlando dramatically reduces attack rates for patients with very high baseline rates and helps patients were attack free maintain zero attacks, while benefiting from oral administration and.
Charlie: Other words this is a treatment that works well for all types of patients not just patients with so called mild disease.
Charlie: Our latest market tracking study completed in December underscored the momentum building among prescribers.
Charlie: Slide eight shows that 97% of the 60 <unk> treaters surveyed are considered considering prescribing oral or Dale.
Charlie: Among those who are prescribed 59% say they are extremely likely to prescribe Orlando to more patients are metrics that is up from just 26% just 18 18 months prior.
Charlie: That prescribing momentum showed up in 2024 is the number of new prescriptions was exactly the same as in 2021, the first year for launch.
Charlie: Slide nine shows that HCA treaters expect to continue the momentum by prescribing oral or Dale to 17% more of their current patients in 2025 with an emphasis on prescribing to current injectable profi patients.
Charlie: Over the first four years of the launch this forward view of the coming year from physicians has been very predictive of the oral data growth trajectory.
Charlie: And physician that intent is aligning with patient preference.
Charlie: Slide 10 shows that over half of injectable profi patients would prefer an oral route of administration well only one in five preferreds and injectable.
Charlie: Over 1200, USA treaters are prescribed oral it out over 3000 patients through the end of 2024.
And both patients and physicians are telling us to expect a lot more growth ahead.
Helen: I'll turn it over to Helen.
Helen: Describe other exciting sources of future growth.
Helen: Thanks, Charlie.
Helen: In our pipeline, we were making great progress already this year advancing the VCX 17, 75 in <unk> syndrome and of oral stat in diabetic macular edema towards meaningful clinical data readouts and submitting our NDA this year to expand the range for all the detail to kids ages two to 11.
Helen: I'll start with Netherton syndrome, or severe disease that has no approved treatment and for which we will have initial clinical data later this year as we evaluate these C 17, 75 for the potential to deliver a functional cure pay.
Helen: Patients with <unk> syndrome have a genetic mutation, causing abnormal skin turnover in inflammation with premature separation and peeling of the outer layers of skin.
Helen: They experienced intense chronic itching and redness, along with severe atopic symptoms like asthma, and food allergies, which means the patients live with the disease that involves much more than red peeling skin the effect on their health and well being is profound.
Helen: One patient I spoke with describe the constant battle she faces to fee per scan in good condition.
Hours, a day applying ointments elections, all over her body everyday life for her means having itchy fragile skin and being unable to prevent it from peeling off in big pieces, even with your best efforts. She has still been in a hospital multiple times for infections is a child and also as an adult.
Helen: There are no disease modifying options for patients like her even though she has confirmed diagnosis and these specialists for her care.
Speaker Change: Our goal is to change this.
Speaker Change: We've engineered <unk> 75 to replace the missing protein function and.
Speaker Change: To deliver this with very high potency for subcutaneous delivery potential and high affinity the ability to stick to the target for a long time and have a lasting effect.
Speaker Change: We are aiming for a long dosing interval every two weeks or longer which we believe could deliver a differentiated therapy for netherton syndrome.
Speaker Change: Hey, VCX 17, 75 is in a phase one trial with dose escalation underway in healthy volunteers next we will start dosing patients and we plan to have data this year to confirm that the drug gets to the skin in patients and that the drug has the intended biomarker activity on the target K, Okay five in the skin.
Speaker Change: These patients will receive multiple doses of the drug. So we can assess for healing of the skin using known endpoints for chronic skin disease.
Speaker Change: Because there is no cure for physicians to offer patients. We believe netherton syndrome is under diagnosed.
Speaker Change: We know today is that Netherton syndrome is an ultra rare disease and our studies estimate about 1600 patients in the U S based on the reporting of a known feature called bamboo here.
Speaker Change: We also know that patients with a diagnosis of severe ichthyosis were in flames scaly skin may not be tested for the genetic mutation and yet many may in fact habit.
Speaker Change: We've seen her diagnosis rates change once the disease targeting treatment becomes available for rare disease.
Speaker Change: Not too long ago H E E was thought to affect only about 2000 patients in the U S. But today changes in therapy led to a known market more than five times. The initial estimate about 11000 patients in the U S. It is possible Netherton syndrome will follow this pattern.
Speaker Change: And even more attractive opportunity for a drug like <unk> 75.
Speaker Change: Next in the pipeline of oral stat will be moving into the clinic in patients with diabetic macular edema. This year.
Speaker Change: We've had a lot of interest from physicians and pursuing an alternative mechanism to treat DNA because veg F inhibitors are effective only for a little over half of all patients.
Speaker Change: This gap in treatment leaves, many with continuing loss of visual acuity, making independent living more and more difficult.
Speaker Change: Earlier this year, we presented images from preclinical model that showed the cessation of vascular leakage. After a supercritical injection of the world that plasma Calcarine inhibitor images, which you can see on slide 19, our from an animal model of retinal vascular leakage and show the change in that basket.
Speaker Change: <unk> in the retina before and six days after treatment with oral stat.
Speaker Change: Its effect last is 321 days before leaking started to return by the next time point at day 36.
Speaker Change: This is a clear effects and we believe it demonstrates the involvement of the Calpine beta freed accounting pathway in retinal leakage and importantly provides strong evidence that plasma, California inhibition, maybe an alternative pathway for reducing retinal vascular leakage.
Speaker Change: Of course, the real assessment of potential for both efficacy and durability in treating DNA can only be made in patients. So we look forward to moving the program into the clinic.
Speaker Change: Later this year, we plan to enroll patients with newly diagnosed yummy and including patients who received a few injections of anti VEGF therapy.
Speaker Change: Our goal is that by the end of the year, we may be evaluating for activity such as measurable changes in edema and the first few patients on the trial.
And last following Charlie's description at the robust real world evidence, we are presenting this coming weekend at Quad AI I'm really excited to report that the first data from our apex P trial with the pediatric oral granule formulation of oil a day and children under 12 with H E E will be highlighted in a late breaking out.
Speaker Change: Strike on Sunday.
Speaker Change: This is the largest trial to date evaluating prophylactic therapy for H I E. In this age group and we are thrilled with the results.
Speaker Change: I want to thank all of the children and their families and our investigators who made this trial possible.
Speaker Change: There is an urgent medical need for an oral therapy to prevent H M E attacks in children.
Speaker Change: It's both a pediatrician and mom I am truly excited that we are getting closer to making <unk> available for children with H E E.
Speaker Change: And the apex P trial, we saw that the granules for safe and well tolerated in this pediatric population and children achieved early and sustained reduction in monthly H E attack rates. In fact 25 out of 29 children remain on the study.
Speaker Change: These results for safety and efficacy are consistent with the adolescent and adult experience and we are on track to file our NDA this year.
Speaker Change: We also learned that children with H a are experiencing severe swelling attacks at a very young age with a median age of onset at two years.
Speaker Change: These findings support an earlier age of symptom onset and need for H, a prophylaxis Dan has generally been understood.
Speaker Change: And we've learned that the oral granule formulation for Orla do also allows simple prophylaxis with great attack control to be provided for the youngest children. These.
Speaker Change: These outstanding data will be included in our NDA submission, which is on track for later this year.
Speaker Change: So we have a very exciting 2025 ahead with the pediatric NDA for the day and our initial clinical data coming from both our Netherton syndrome and DNA programs.
Anthony: And now I'll turn the call over to Anthony.
Anthony: Thanks Alan.
Anthony: The beginning of last year, we laid out our goals for strong commercial growth for early Dio advancing our early pipeline into the clinic and moving towards sustainable and meaningful profitability in the short term.
Anthony: We shared earlier, it's great to see that we've exceeded even our own expectations and achieving these goals.
Anthony: You can find our detailed fourth quarter financials in today's earnings press release, and I'd like to call your attention to a few items.
Anthony: Total revenue for the quarter came in at $131 $5 million $124 2 million of which came from Orlando for.
Anthony: For full year 2024, total revenue was $457 million with Orlando contributing 437.7 million off that.
Anthony: For quarter, $417 2 million or 13, 9% of the $124 2 million in total for early day O came from X U S. Well for full year, it was $51 $7 million or 11, 8% of the 437.7 billion total.
Anthony: Yeah.
Anthony: Operating expenses, not including noncash stock compensation for the quarter were approximately $115 million.
Anthony: Operating expenses, not including noncash non stock based comp for full year 2024 came in at $388 million, an increase of just 8 million versus 2023.
Anthony: With revenue, increasing $119 million year over year and this small increase in Opex. This resulted in an operating profit not including stock based comp of $62 $9 million, that's an increase of $111 million versus a non-GAAP operating loss of $48 1 million from 2023.
Anthony: A remarkable achievement that sets us up for 2025 and beyond.
Anthony: Cash at the end of the year was approximately $343 million and that kind of utilization for the quarter was $8 4 million.
Charley: Charley sure the increase in guidance for early day of revenue for this year of between 535 and $550 million based on the progress that we've seen thus far in Q1 around reauthorization on Medicare reimbursement.
For total revenue, we are adjusting guidance upwards in line with the Orlando to increase to between 560 and $575 million.
Charley: Theres some increased uncertainty around future government funding for wrap up Bob. We're also seeing strong commercial demand for the product given the prevalence of flu at the moment.
Charley: For Opex.
Charley: The improved Orlando commercial performance will result in increased expenses around Cogs distribution fees and incentive compensation, but should remain bound by the upper end of our $425 million to $435 million guidance that we provided previously.
Charley: That puts us in a great position to achieve our 2025 goals of positive and sustainable quarterly cash flow and EPS in the second half of the year.
Charley: Longer term.
Charley: Earlier in the year, we provided guidance for revenue with a three year CAGR of 20% so north of $750 million by 2027, and also reiterated our belief of getting to 1 billion global revenue by 2029.
Charley: We also provided a CAGR for opex, not including stock based comp of 5% so closer to $450 million by 2027.
Charley: With positive quarterly cash flow this year annual positive cash flow generation next year and the cash flow that we will generate in 2027 when revenue was greater than the opex by more than $300 million, we expect to have more than $600 million of cash on hand at that time, allowing us to reduce our debt and our cost of cap.
Charley: It'll on reinforcing our position.
Charley: Capital markets independent.
Charley: Operator, we can open it up for Q&A.
Charley: We will now begin the question and answer session to ask a question you May Press Star then one on your telephone keypad, if youre 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.
Charley: Please press Star then two.
Charley: At this time, we will pause momentarily to assemble our roster.
Charley: The first question.
Charley: Comes from.
Charley: <unk> Ahmed with Bank of America. Please go ahead.
Thanks, guys good morning.
Speaker Change: Thanks for all the color I wanted to start maybe with a question on another 10.
Speaker Change: Youre expecting data from patients later this year can you potentially narrow down when the theory.
Speaker Change: Got it okay.
Speaker Change: And then secondly can you talk about what would be positive data in your view do you think that the amount of patients that you've enrolled would allow for a a sense that I think you see in a clinical setting beyond the biomarker data that you've talked about releasing and if that'd be that is encouraging what do you think.
Speaker Change: The path forward could be for another thing just given that there is nothing approved in patients right now and it is an area of high demand.
Speaker Change: Do you want to take that.
Speaker Change: Thanks, <unk>. So first of all and we have we will have data this year and that's our that's the guidance, we're giving at the moment in terms of what we expect to see some how many patient. There's one thing about this disease is a a genetically driven disease is that we really only need to see data in a very small number of <unk>.
Speaker Change: It's to have confidence that we're hitting the mechanism and we're looking to make us a functional replacement of the missing protein and we may see that with with single digit patients.
Speaker Change: In terms of what we're looking for then we're looking at that first of all as I said the activity in the skin, but with that specifically we're looking for are the drugs effect on K. Okay. Five activity in the scanner suppression of K L. P. Five activity what that will lead to then is healing in the skin and so we're looking for.
Speaker Change: As with graded.
Speaker Change: Observed <unk> of the skin and is it actually demonstrating signs of healing them. So that we would it be able to see I later this year or possibly in early next year as well for healing of the skin.
Speaker Change: In terms of the development path forward.
Speaker Change: The data we will get this year is very important to us because that few patients worth of data showing activity in the skin that the drug is getting into the skin and having its activity. We would then expect to see some degree of healing following from there and we would move pretty quickly into assessing that in a.
Speaker Change: The next study this is an ultra rare population with a serious outcome and a pretty clear a response that we're looking for it so it could be a very.
Speaker Change: Sure path to pivotal studies as soon as we have a dose which I'd expect to have at some point next year, then we'll move into a pivotal program that would be the registration program and it probably is a single pivotal trial program supported.
Speaker Change: Supported by the data that we'll be collecting this year and next.
Speaker Change: And Helen the profile, we're shooting for is a functional cure so the magnitude of effect will drive what the pivotal program looks like in the number of patients necessary. So the bigger the effect the faster we probably can go in the fewer patients who need is that a fair. So yes, okay. Yes, that's great.
Speaker Change: Okay. Thank you.
Speaker Change: The next question comes from Jessica Fye with Jpmorgan. Please go ahead.
Jessica Fye: Hey, guys. Good morning, Thanks for taking my questions one on Orla Dale and one just following up on the prior question for another 10.
Jessica Fye: Personal scale, where are you tracking towards for the proportion of paid patients overall and within Medicare specifically and what is the current orla day of guidance and that there and then second.
Jessica Fye: How are how quickly could we expect to see this mechanism result in skin healing and another 10.
Jessica Fye: Just thinking about the mechanism and the underlying disease pathology.
Jessica Fye: Charlie.
Charlie: Take the Orla data question. Thanks Jess.
Charlie: As far as the proportion of paid patients. We ended last year at 73, 5% paid across our whole patient base.
Charlie: I can't give you an exact number yet because we're literally right in the middle of the reauthorization seasons of what that means is a lot of our patients who were previously on long term free products.
Charlie: Or even paid product have moved temporarily into quick start product. So any number that I would give you now would not be accurate I have said, though before that with a swing back in Medicare paid patients that could push us toward 80%.
Charlie: And so by the end of the quarter, we'll be able to we'll be able to see where we are so I would expect to report that in the next earnings.
Charlie: We do think because of all of the the reauthorization season revenue for the first quarter is still going to be flat to slightly down versus Q4, just because of all the free products that we have to give away as well as the impact to gross to net from the.
Charlie: The co payment assistance that we provide to commercial patients. There is also a little bit of it.
Charlie:
Charlie: A headwind as it relates to foreign exchange. So included in Charlie's increased guidance. There is you know a headwind probably around $5 million give or take in the EU. So it makes the number that we're achieving in terms of the increased guidance for here in the U S. You know all the more impressive hey, Charlie.
Charlie: Our assumption prior to getting into the new year was that it would that Medicare thing would happen over a couple year to three year period.
Charlie: That's not what you're seeing the pace of it is significantly faster and that's the reason for the guide.
Charlie: That's correct, we assume that we would get back to.
Charlie: Our high paid rate in Medicare by 2020, it's looking like we'll get much more of that back this year, but we won't know the final results until after the quarter.
Charlie: When you want to take the.
Speaker Change: So Jeff on your question about Netherton syndrome, and how quickly we would expect to see killing in the skin. The short answer is we don't know.
Speaker Change: But what we do know is that we will see the the activity on target activity first and it could be just a very few months after that that we're seeing healing of the skin and we'll be looking at four weeks eight weeks 12 weeks et cetera.
Speaker Change: And once we see that our target on target activity of the biomarker.
Speaker Change: We'll know that we're at the dose and then we'll just continue treating longer term and following for that his first few months to assess for healing of the skin.
Speaker Change: How long can you talk about skin turnover and it's not like it's years to see the fact that yes, just talk a little bit about that yeah. So it says can turnover is actually pretty fast and normal skin. You expect are the skin layers to turn over about every two weeks or so and so with his strategy when I talk about seeing activity on target at Caltech.
Speaker Change: Five activity then we would expect that activity to be there for the duration of that skin layer being at present, so it's gonna be two weeks and longer that we'd expect to see them.
Speaker Change: The effect of the drug for each for each dose and then we're looking to see what happens with asking overtime. So that that's why I look back to it could be very few months four weeks eight weeks 12 weeks follow up and given what we see in terms of potency and affinity of this molecule the treatment effect that we're expecting is pretty significant.
Speaker Change: It should come pretty quickly and.
Speaker Change: In general in terms of the results that we see from this early study, yes, we're looking for a pretty big effect here and this is this is a very potent drug. It is very sticky that's at high affinity and we're looking for a really obvious effects. So and that's that's why we think it's something that we might see pretty quickly and is it safe to say that the derisking.
Speaker Change: The drug getting to the skin in patients yes, okay.
Speaker Change: Thanks.
Speaker Change: Yeah.
Speaker Change: And was there a follow up Ms Fi.
Speaker Change: Thank you.
Steve <unk>: The next question comes from Steve <unk> with TD Cowen. Please go ahead.
Steve: Okay, well, thanks, so much for taking our questions and congratulations on the result.
Speaker Change:
Quick follow up on the other than we might have most of those have you talked about specifically when do you plan on dosing patients.
Speaker Change: Some specific timing on that and then again on this so now we're all about almost every result.
Speaker Change: Are you kind of finding that the attack rates are similar to other prophylaxis therapies kind of curious your take or with it as it relates to new patients that are welcome to call on oral for patients that are well controlled.
Speaker Change: That's helpful.
Speaker Change: And then my last question is just kind of another follow up on the guidance.
What exactly are you seeing kind of in the last month and a half that kind of goes with conviction in your updated guidance.
Speaker Change: Is it set up a charity is is it really just that Medicare.
Speaker Change: Let us update and remind us kind of every 1% that you're converting is that is that $5 million. Thank you. So much.
Speaker Change: Yeah.
Speaker Change: So another 10 syndrome.
Speaker Change: In terms of when we'd be dosing. So we are we havent said exactly however, what I can say is we are dosing in healthy volunteers now and we're moving towards dosing patients Netherton syndrome. Soon so it will be sometime around the middle of the year third quarter and that's that's what would give US then the opportunity to assess the active.
Speaker Change: If any of the skin and B looking at healing by the end of the year.
Speaker Change: And then.
Speaker Change: As far as the attack free or I'm, sorry, the attack rate reduction.
Speaker Change: Seeing in the real World, Yeah, I think we see that patients on Orla Dale are getting too really low rates of attacks. If they don't they move on and so what we said before is no drug is perfect for every patient.
Speaker Change: But this is related to our really strong retention rate for early day of patients of 60% at a year patients are staying on because they're doing really well that's what you'll see in the posters that we presented at quad AI. This coming weekend that patients whether they started at a baseline attack rate that was really high over 5%.
Speaker Change: Tax a month or whether they started.
Speaker Change: Zero attacks at baseline, they're doing really well over time, so we think they're getting a very competitive efficacy rate.
Speaker Change: And the things that give us confidence so far in the year. The number one thing is the Medicare patients moving to paid therapy. We think that this is really because the iras is making it more affordable.
Speaker Change: Probably makes it more affordable for the charities, but what we're just seeing is patients are getting approved by their plans, they're able to afford their co payments and so theyre staying on unpaid therapy. So that that gives us confidence and then the the continued demand that we're seeing in the first half of the first quarter is very.
Speaker Change: Distant to what we saw last year and so those two things together give us confidence to raise guidance at this point it Charlie just one more piece on the control with the real World data that we see do you really see it when you are controlled on Orla do is there a difference in the control versus the therapies on the market are the ones that are coming in the data that.
Speaker Change: We see in the future.
Speaker Change: Not not based on what we've seen in our market research. So the patients very few patients across the board regardless of what product, Iran are truly attack free the goal for patients is to have very infrequent attacks have those attacks be very manageable. So they tend to be more miles on on prophylaxis, that's what we're seeing on <unk>.
Speaker Change: Oh, that's what we're seeing on injectable products in and we think it's it's consistent to what we'll see with future products that reach the market as well and as physicians see that data or they have that experience with their own patients that's what's driving that.
Speaker Change: Excitement about prescribing more of it in the future, yes, that's what's exactly so not only are they saying physicians telling us as of December that they will prescribe to 17% more of their patients. They expect over 60% of those prescriptions to come from injectable prophylaxis switches, it's because they have confidence in what they are.
Speaker Change: With oil down so Stacy I think the bottom line is the there's control with Orla, Dale and any incremental anybody that's saying that theres incremental control with our future product or a current product really isn't true it either works or it doesn't work.
Speaker Change: Okay understood. Thank you so much.
Speaker Change: Youre welcome.
Speaker Change: The next question comes from Brian Abrahams with RBC capital markets. Please go ahead.
Brian Abrahams: Oh, Hey, good morning, Thanks for taking my questions and congrats on all the progress too.
Brian Abrahams: Two from me I guess first on the AR on the pediatric study.
Brian Abrahams: Can you talk about how tolerability compared to the adult experience and maybe just remind us your expectations for the regulatory bar in the U S. As you prepare the NDA filing there and then kind of what you're planning for for the.
Brian Abrahams: International approvals and filings and then secondly, I guess speaking of international.
Brian Abrahams: Or the day of commercially in fourth quarter. It looks like you saw an uptick in the contribution from Europe, I know that can be variable and sometimes higher in fourth quarter.
Brian Abrahams: And of course, we'll need to think about the FX headwind for next year, but where do you see that demand outside the U S tracking in 2025.
Brian Abrahams: Okay.
Brian Abrahams: Right so on pediatrics.
Brian Abrahams: And so this is this is the new formulation for pediatrics is oral granules and they are and what we know from the study is that those are delivering well patients are unable to use them easily we're seeing a.
Brian Abrahams: Good exposure levels, which means that they are compliant with receiving them and we're seeing very good tolerability with the oral granules as well, it's very similar to what we'd expect in terms of efficacy and safety for the adults for the adolescent. So so this is a formulation that we're very.
Brian Abrahams: Very pleased with how it's doing in pediatric patients.
Brian Abrahams: In terms of the regulatory bar for approval of this is actually at a pediatric extrapolation is what it's called it means where we're matching safety and exposure for the pediatric population to extend labeling for adults and adolescents down to the younger children that means that the primary outcomes are safety and pharmacokinetics and we have that data and we've already <unk>.
Brian Abrahams: Gus that with regulators in the U S. This is this is a fairly straightforward approach with something called a written request with F. D. A in Europe, it's under a pediatric investigative plan with EMA and both of those are pre define the path to approval in the U S and Europe and we're on track to submit the data that meets those requirements.
Brian Abrahams: So we think we're in a really great place with this dataset and looking forward to bring this spring this to children.
Speaker Change: And we've had comfort well go ahead sorry.
Speaker Change: We had conversations with the Japanese authorities, yes, and so we have agreement on what the path forward for that as well. So so we expect that filings will occur in multiple countries either all this year or into the early part of next year.
Speaker Change: And then maybe as far as ex U S demand I'll cover the demand and Anthony can talk about kind of the cadence of the revenue.
Anthony: What we're seeing in Europe in Canada, and Japan is the same type of growing confidence in Orlando that we're seeing in the U S different markets are at a different place depending on where the launch was so for example, we're seeing really transformative confidence with oral <unk> in the United.
Anthony: Which has been on the market for several years now we're seeing great early confidence in Italy that just launched last year is as as examples.
Anthony: But what they're seeing is oral data was a really effective drug and we're also very excited in in Europe that countries that historically have used more androgen steroids are going away from that and patients are being switched over new patients are not being prescribed androgen anymore and so I think we're still seeing it.
Anthony: <unk> formation of how prophylaxis is understood around the world and oral data was playing a big part of that.
Anthony: Specifically as it relates to Q.
Anthony: Q4.
Anthony: Yes, so the percentage for Q4 ex U S was higher than the total for the year, So 13.9 versus 111 point H.
Anthony: For full year <unk>.
Anthony: Some of the drivers are in Europe.
Anthony: It helps in that regard, but also some of the Q4 dynamics distributors that we have whether it's you know in Latin America, whether it's in eastern Europe, whether it's in the middle East some of there are.
Anthony: Annual.
Anthony: Distribution shipments go out and buy Q4 time period, so that that can be a small driver. The other one is we renegotiated and kind of refocused on the Japan side of the house in the year and we were able to renegotiate our revised term around flipping the economics for performance over a certain number we achieve that number in.
Anthony: In Q4.
Anthony: I'm, we're able to get a higher share therefore, the licensing revenue for the territory.
Anthony: In terms of how that plays out into 2025.
Anthony: For Q1.
Anthony: Probably get to the point where.
Anthony: You know flat to lower on.
Anthony: Total revenue for the rest of the year the same dynamic would play out including this Q4 dynamic that I just described in terms of the percentage of.
Anthony: Ex U S compared to the total for all the detail does.
Anthony: This year might be a little bit different we would normally say you'd get about a percentage increase or uptick on your way to about 20% with the significant increase that we're seeing here in the U S that might be slightly deflated, but that has nothing to do with the continued growth that we would expect to see ex U S.
Anthony: The counterpoint of significant strength that we'll see on the U S side.
Speaker Change: Super helpful. Thanks, so much.
Speaker Change: Hey, Brian just one more vessel the tolerability of the retention rate in the pediatric study I can't remember the exact numbers, but it was pretty high but it was 25 patients out of <unk> 29, who stayed on drug.
Speaker Change: We're also using that formulation and having the effect that they used a lot of times I can reflect some of the Tolerability Brian's got it thats really helpful. Thank you.
Speaker Change: Yes.
Gena Wang: The next question comes from Gena Wang with Barclays. Please go ahead.
Thank you for taking my questions.
Gena Wang: I have one also regarding all looked at you so maybe like.
Gena Wang: You did mentioned the Medicare patients to benefit from the low co pay.
Gena Wang: But can you share with us what percentage of patients who are Medicare patients.
Gena Wang: Soon those Medicare patient in 2024 of $40 20 for Pete.
Speaker Change: Pete percentages 73, 5%.
Gena Wang: <unk> will go up right.
Speaker Change: Second question regarding the leather.
Speaker Change: Syndrome, and you did mention that with Starwood healthy volunteer and then switch to patients. So maybe can you give us a little bit more color regarding what kind of how many dose escalation you were testing in healthy volunteers.
Speaker Change: Hello T five activity, you'll be looking for to switch to patients and then can you give us the benchmark and what are you looking for regarding the killer T five activity.
Speaker Change: I'll take the question about Medicare.
Speaker Change: Medicare is about 20% of the patients on oral or DAU are covered by Medicare. The the 73, 5% paid rate was across our entire book of business in Medicare. It was actually lower so we finished last year at about a $55, 56% paid right here.
Speaker Change: Storage really the Medicare plans tend to say, yes that they will cover all the Dow at 80% or more the problem has just been the affordability and so what we're seeing in Q1 as the plans are still saying, yes. The affordability seems to be there for the patients and so they're able to move to to pay it.
Speaker Change: Therapy, and this is a big part getting that that proportion of our Medicare patients over to paid therapy is a big part of our path to 85% paid over the long term, which is represented by 2029 that will represent about $100 million in it.
Speaker Change: Increased revenue towards our $800 million.
Speaker Change: Future view of revenue in the U S. So what we're seeing is this year that may be accelerating a bit and we'll know the final answer after the reauthorization season is complete.
Speaker Change: Helen maybe just describe the design of going from sad to Mad to then patients and the differences between what you can see in healthy versus what you can see in patients yeah. So another since syndrome do you know that.
Speaker Change: We are in a phase one study that phase one is in healthy volunteers and will include patients and healthy volunteers, who were doing single ascending dose. We will proceed also with multiple ascending dose and what we're looking for there is simple safety and pharmacokinetics exposure level. So that we can identify a dose that is likely to have activity.
Speaker Change: <unk> and goes to patients from there we would expect to include patients in the study while continuing with the dose escalation in healthy volunteers. So it's not it's not in series and dependent on that.
Speaker Change: And there's an interesting aspect of this disease, which is that K. Okay. Five activity is normal and healthy volunteers, which which means we can't really look for activity there and we want to get to patients as quickly as possible. That's why we felt the patient portion of straight into the phase. One study. That's why we're dose escalating so quickly in healthy volunteers to get to the likely affair.
A dose range and then we're moving to patients within that study. So that we can look at the activity of the drug in the skin, where okay. Okay five activity as abnormal and look at weather drag is inhibiting activity at the desk level is there.
Speaker Change: And so we'll be looking at a range of doses that we're expecting to be in an effective range inpatients and we'll be looking for that suppression. Okay. Okay, five activity to give us confidence that the drugs, having the effect and to extend dosing then in those patients just asked for the healing we were talking about earlier in the call.
Speaker Change: What percentage of the suppression you were thinking kill K five.
Speaker Change: That would lead to the clinical benefit.
Speaker Change: Yeah. So so short answer that's that's not known but what we're looking for with this drug is very potent them and so we're talking about has this stickiness as high affinity what we're looking for is suppression. So that's that's nearly complete suppression of can't pay five mm and as we learn more about what's you know whether that's actually required for healing Act.
Speaker Change: You will learn more later on in the program, but in the near term, we're looking for complete suppression of can't pay five.
Speaker Change: Okay. Thank you.
Speaker Change: Our next question comes from John Walden with citizens JMP. Please go ahead.
Hey, good morning, Thanks for taking the questions just a couple from me Charlie.
Speaker Change: Charlie I'm wondering if you could talk a little bit about the historical reauthorization rates and what you guys have seen in prior first quarters and how it's tracking so far this year.
Speaker Change: And then for the pediatric opportunity I Wonder if you guys have thrown that in your market model. What we should think about that opportunity. If that's included in kind of your projections that you have on slide 12 of your deck.
Speaker Change: Sure Thanks, Jon as.
Speaker Change: As far as the reauthorization, what we see is roughly half of our patients across all payers go through reauthorization in the first quarter.
Speaker Change: But it's really more than just the first quarter it tends to drift into the early part of the second quarter. That's what we saw last year.
Speaker Change: And so when I said earlier, we're right in the middle of it. It's because we are we're right in the middle of it now the last as I've talked about previously the last few years. Our team has done a tremendous amount of work to be ready for this reauthorization every year, we think we get better at it based on what we learned from the previous year.
Speaker Change: And so.
Speaker Change: I'm pleased with what we see so far but we won't know the final results until we get through everything as far as the pes opportunity is not baked into our <unk>.
Speaker Change: Our billion dollar peak.
Speaker Change: Peak global revenue forecast.
Speaker Change: At some point, particularly obviously when we get the approval will will probably build that in but what we have said is in the United States. There are about 500 patients that we believe are under age 12, and diagnosed with H E. E. Historically, we've thought maybe 40% of them 200, or so where appropriate for <unk>.
Speaker Change: Prophylaxis therapy based on what Helen was describing earlier and the young age that we saw at the patients in our trial the young age when they first had their attacks. We're rethinking. This we think that there may be more of an opportunity within that within that under age 12 population.
And again, we think Orlando as an oral drug is going to be transformative for these kids. So we expect a lot of changes in how kids with HPE are treated in the future and Charlie is it safe to say that even with the increase in guidance and the tailwind that we're getting with free drug to paid drug that the first quarter <unk>.
Speaker Change: <unk> still exist and.
Speaker Change: Theres still free drug that were given to people go into re off and Theres still as you said before gross to net issue. So at flat to slightly down as flat to slightly down for Q1, just because of all of that regardless of how well we do that is that as us.
Speaker Change: Dynamic that we cannot defeat.
Speaker Change: And Charlie maybe just one quick follow up how do you categorize the pediatric patients as appropriate for prophylactic therapy.
Speaker Change: Well, John I think that it's a great question and I think that's what we're gonna see changing over time I think historically.
Speaker Change: Physician HAE treaters have not.
Speaker Change: Not seen as many kids.
Speaker Change: With with attacks because they really didn't have options for treating now they have some injectable options, which is great.
Speaker Change: But what it led to as families coping you know physicians coping with this AD treating kids are.
Speaker Change: Acutely, but that puts a huge burden on the kids and their families and so with an available oral therapy. We think it's gonna have physicians parents, obviously, the kids rethink how to treat H E.
Speaker Change: It could create an opportunity where kids grow up rarely having attacks, which could really change the trajectory of their whole childhood there their whole life their whole relationship with with a J.
Speaker Change: So we're really excited about working with the community to make that happen for kids.
Two when we saw this data.
Speaker Change: I think.
Speaker Change: Many of US were surprised at how sick and how early kids got sick with this disease that changes our view of the market a bit that there are younger kids that really need this drug and so that could increase the opportunity zone.
Speaker Change: Thanks for the color guys.
Speaker Change: Yes.
Speaker Change: Again, if you have a question. Please press Star then one.
Speaker Change: The next question comes from Lisa pay cope with Evercore ISI. Please go ahead.
Speaker Change: Hi, This is <unk> on for Lisa I have a question on that.
Speaker Change: That Indiana.
Speaker Change: What's the target product profile for this drug and why should we be looking for in basin.
Speaker Change: Data to start to do this asset towards this topic.
Speaker Change: Thank you.
Charlie: Charlie you want to take that.
Charlie: Sure then maybe Helen can comment on this too.
Speaker Change: But the the TPP, we're looking at for oral step for patients with DMD.
Speaker Change: Physicians are looking for other options. They are looking for other other therapies because over over 50 or close to 50% of patients don't respond fully to VEGF inhibitors.
Speaker Change: So what we're looking for is.
Speaker Change: And infrequent injection that helps prevent leakage. So this could be every three months. It could be every every six months, which could greatly reduce the burden of injections and improve efficacy for many patients.
Speaker Change: Was there a follow up.
Speaker Change: I'm just going to do can you speak about the phase one what is that define what should we look for.
Speaker Change: And then moving into patients.
Speaker Change: So we're going directly into patient yeah, let Helen described that yeah. So this is this is a program that will actually go straight to patients for the phase one will be in patients.
Speaker Change: And it'll be using the injection supercritical injection of Royal stat in the suspension.
Speaker Change: In order to observe.
Safety and patients Tolerability locally in the eye, but also with that injection to absorb to observe in individual patients.
Speaker Change: Right from the first patient dose to see if there is a change in the edema in the eye.
Speaker Change: And then longer term change in visual acuity. So so the first study will be exploratory.
Speaker Change: Exploratory looking at using that injection and then and then assessing just one injection assessing over time again sort of over.
Speaker Change: Four weeks eight weeks 12 weeks 16 weeks with his choices to observe for the edema in the eye and I'm sorry for any changes in the edema. Once we have a confidence that we've got a dose we're saying that the changes that we want to see then we would move to a randomized program probably randomize phase two to assess this in the controls.
Speaker Change: <unk> for the.
Speaker Change: For the pivotal program planning how long is it fair to say that this is an unusual setting where a sad and Mad study could tell you a lot because youre in patients yes, right. So.
Speaker Change: With the oral stat, we know we already know a lot about the systemic safety of the trials because we tested it in a phase III oral program. Some time ago I'm now worried if at a point, where we're just looking at that from a safety perspective, the local tolerability and because the strike is potent and the suspension has a depot like a factory.
Speaker Change: One dose could be sufficient to see that effect in each patient that puts us in a position to have them.
Speaker Change: First second and third patient instead of the very first patient. So we put on the trials for the ones, who we observed with that one dose.
Speaker Change: Observe over a number of months to see how they do.
Speaker Change: That's very helpful. Thank you.
Speaker Change: The next question comes from Serge Belanger with Needham and company. Please go ahead.
Serge Belanger: Hi, good morning.
Speaker Change: A couple of questions for Charlie on Orlando.
Serge Belanger: First one can you tell us how many patients are on drug.
Speaker Change: At year end and how that number compares to year end 2023.
Speaker Change: And then secondly.
Speaker Change: Regarding the positive impacts you've seen from the from <unk> So far.
Speaker Change: You've highlighted the <unk>.
Speaker Change: Improvements in paid rates, but do you also expect it could.
Speaker Change: Helps.
Speaker Change: Improved volumes in the form of new patient adds.
Thanks Serge.
Speaker Change: I haven't I haven't commented specifically on the number of patients. What we have said before is that in that path to $1 billion in the past to $800 million in the U S. We need to average 200 patients through 2029, we were well above that in 2023, and we said it in the.
Speaker Change: Early years, we would expect to be above that we were well above that number again in 2024. So we are we are well on our path to what we laid out.
Speaker Change: And that $800 million two to the U S. And then the demand that I described today, there's no sign that that the opportunity is slowing down or running out in any way.
Speaker Change:
Speaker Change: As far as I think the other part of your question was on the Medicare paid rate and whether that could have a positive impact in prescribing.
Speaker Change: It's a possibility it's a good question.
Speaker Change: I don't think we've seen that yet, but but for patients and for physicians getting to paid therapy gives them confidence knowing that their payer will pay for this drug.
Speaker Change: It gives them more confidence about prescribing and we've known that since before the launch we've always done everything that we can to remove that that paid rate paid of therapy insurance approval remove that as a fear for patients and doctors, but it's always there and so.
Speaker Change: Seeing more patients get to paid therapy, I think generally gives confidence in it.
Speaker Change: Can't help but have a positive impact over time and I think something that's really important that maybe isn't obvious is the.
Speaker Change: The the machinery that Charlie has built and the team that Charlie has built to make that go smoothly is a real competitive advantage I think in terms of just it's taken stress away from doctors I mean, Charlie and I heard from a doctor recently about how our empower patient services is like a model for other.
Speaker Change: Other drugs, even outside of HLA and that took time to build that took investment in and.
Speaker Change: I think his team is really good at it.
Speaker Change: And a shout out to the team because again they are right in the middle of what we call the blizzard season.
Speaker Change: Because it's cold and because theres a lot of work to do so they are they are working super hard to help as many patients as possible.
Speaker Change: Okay.
Okay was there a follow up.
Speaker Change: Thanks.
Speaker Change: Your final question comes from Maury Raycroft with Jefferies. Please go ahead.
Maury Raycroft: Hi, good morning, Congrats on the progress and thanks for taking my questions.
Maury Raycroft: You talked about another 10, being underdiagnosed or does biocryst doing or planning to do to help find these patients and get them on the radar or your clinical study program and to help set up the commercial opportunity.
Maury Raycroft: Charlie you want to start of how we're thinking about how we identify patients and what we plan to put in place and.
Maury Raycroft: Helen alluded to some of this in her comments as bamboo hair is a distinctive feature.
Maury Raycroft: That patients with Netherton has there is no diagnosis code for Netherton syndrome, but most of these patients do have this bamboo hair, we did our claims study that.
Maury Raycroft: It helped us identify about 600 patients with this bamboo hair feature and so.
Maury Raycroft: Part of our plan is to to expand on that and as we're getting into the clinical trials here make sure. We're we're working to find more sites, where these patients are treated there are some a small handful of real expert centers at this point, but most of these patients has held was saying are probably law.
Maury Raycroft: Just a little bit in the broader dermatology practice potentially miss diagnosed with general <unk> and so as we move into this next phase of trials, we expect to start doing more pitches to to educate the market about the need for this and the differentiate the differential diagnosis for the for these patients.
Maury Raycroft: And there's some great playbooks on.
Maury Raycroft: Rare diseases, where there was no drug and no diagnostic code and how did you find the patients and I think one of the beauties here is the genetic test and what we do with that genetic tests and how do we implement that playbook to start and when you have a therapy that has you know we're hoping for a real.
Maury Raycroft: Significant treatment effect those two things in combination you start to really be able to find patients. So I don't think we have to recreate anything here. There. There are playbooks for this stuff that we can follow that will help us build that over time.
Maury Raycroft: Just one piece of one part of that playbook is to engage very closely with the patient community and we've started doing that with another tens community and the patient voice in all of this is in rare diseases becomes really important and so we will do what we can to.
Maury Raycroft: To work with them and and our early interactions with them has been very positive.
Speaker Change: Got it that's helpful and maybe one quick second question just for the Orlando pediatric formulation do you plan to price that differently than the adult version.
Speaker Change: We haven't made any final decisions on that but but in most markets probably not it would probably be comparable.
Speaker Change: But that'll be a decision that we make as we get closer to launch.
Speaker Change: Got it okay. Thanks for taking my questions.
Speaker Change: Thanks, Laura.
Speaker Change: This concludes our question and answer session I would like to turn the conference back over to Jon Stonehouse for any closing remarks.
Speaker Change: Thank you.
Speaker Change: So as I said at the beginning 2024 was one of the best years in the company's history in terms of performance and execution.
Speaker Change: And the evidence for that is the strong continued growth in Orla day, Oh on its path to $1 billion programs now advancing and getting to the point, where they're going into the clinic and then our path to profitability. So.
Speaker Change: There's no letting up going into this year. We you know we've got a lot of momentum we're off to a strong start as you can see by the raising of our guidance and we're really excited to continue to update you over the course of this year. Thank you.
Speaker Change: The conference has now concluded. Thank you for attending today's presentation you may now disconnect.
Speaker Change: Okay.
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