Q4 2023 BioCryst Pharmaceuticals Inc Earnings Call

Operator: Good day, and welcome to the BioCryst Fourth Quarter 2023 Earnings Conference Call. All participants will be in a listen-only mode.

Good day and welcome to the Biocryst fourth quarter 2023 earnings Conference call.

All participants will be in a listen only mode.

Operator: Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star and 1 on a touch-tone phone.

Should you need assistance. Please signal a conference specialist by pressing the star key followed by zero.

After todays presentation, there will be an opportunity to ask questions.

To ask a question you May press Star then one on a touchtone phone.

Operator: To withdraw your question, please press star then 2. Please note, this event is being recorded. I would now like to turn the conference over to John Bluth at BioCryst. Please go ahead.

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 John Bluth at Biocryst. Please go ahead.

John Bluth: Thank you very much. Good morning, and welcome to BioCryst's fourth quarter and year-end 2023 Corporate Update and Financial Results Conference call. Today's press release and accompanying slides are available on our website. Participating with me today are CEO John Stonehouse, CFO Anthony Doyle, Chief Commercial Officer Charlie Geyer, and Chief Medical Officer Dr. Ryan Arnold. Following our remarks, we'll answer your questions. Before we begin, please note that today's conference call will contain forward-looking statements, including those statements regarding future results and unaudited and forward-looking financial information, as well as the company's future performance and or achievements. These statements are subject to known and unknown risks and uncertainties, which may cause our actual results, performance, or achievements to be materially different from any future results or performance expressed or implied in this presentation.

John Bluth: Thank you very much good morning, and welcome to Biocryst fourth quarter and year end 2023, corporate update and financial results Conference call.

Today's press release and accompanying slides are available on our website.

John Bluth: Participating with me today are CEO, Jon Stonehouse, CFO, Anthony Doyle, Chief Commercial Officer, Charlie Gayer, Chief Medical Officer, Dr. Ryan Arnold following our remarks, we will answer your questions before we begin. Please note that today's conference call will contain forward looking statements, including those statements regarding future results are unaudited and forward looking financial.

John Bluth: <unk> as well as the Companys future performance <unk> achievements. These statements are subject to known and unknown risks and uncertainties, which may cause our actual results performance or achievements to be materially different from any future results or performance expressed or implied in this presentation you should not place undue reliance on these forward looking statements for additional information, including a detailed discussion of our risk factors.

John Bluth: You should not place undue reliance on these forward-looking statements. For additional information, including a detailed discussion of our risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website. In addition, today's conference call includes non-GAAP pro forma financial measures. For reconciliation of these non-GAAP measures against the most directly comparable GAAP financial measure, please refer to the earnings press release posted in the press releases section of our investor relations website at BioCryst.com. Now, I'd like to turn the call over to Jon Stonehouse.

John Bluth: Please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website.

John Bluth: In addition, today's conference call includes non-GAAP pro forma financial measures for a reconciliation of these non-GAAP measures against the most directly comparable GAAP financial measure. Please refer to the earnings press release posted in the press releases section of our Investor Relations website at Biocryst Dot com.

John Bluth: Now I'd like to turn the call over to Jon Stonehouse.

Jon P. Stonehouse: Thanks, John. 2023 was another impressive year for Orladeo, starting with generating $326 million in revenue in just the third year of launch. We continue to make great progress toward our goal of global peak revenue of $1 billion. Let me explain why.

Jon P. Stonehouse: Thanks, John.

Jon P. Stonehouse: 2023 was another impressive year for Orla, Dale starting with generating $326 million in revenue and just the third year of launch.

Jon P. Stonehouse: We continue to make great progress toward our goal of global peak revenue of $1 billion.

Jon P. Stonehouse: Let me explain why late last year, we laid out a set of assumptions that would lead us to $800 million in peak sales in the U S. The first assumption was to exit last year with a base of approximately 1050 patients on therapy.

Jon P. Stonehouse: Late last year, we laid out a set of assumptions that would lead us to $800 million in peak sales in the U.S. The first assumption was to exit last year with a base of approximately 1,050 patients on therapy. We actually ended the year with a base of over 1,100 patients. Second, we added over 300 net new patients, well above the average of 200 per year we need. Third, we improved the percentage of paid therapy in the commercially insured part of the business from 7% to 79%. And fourth, we made a modest net annual price increase in the U.S. In all four of these assumptions, Charlie executed such that we met or exceeded each of these goals.

Jon P. Stonehouse: We actually exited the year with a base of over 1100 patients on therapy.

Jon P. Stonehouse: We added over 300, net new patients well above the average of 200 per year, we need there.

Jon P. Stonehouse: Third we improved the percentage of paid therapy in the commercially insured part of the business from 7% to 79%.

Jon P. Stonehouse: And fourth we made a modest net annual price increase in the U S.

In all four of these assumptions Charlie.

Jon P. Stonehouse: Executed such that we met or exceeded each of these goals, that's great execution and real progress towards our goal.

Jon P. Stonehouse: That's great execution and real progress towards our goal. Today we'll focus our prepared remarks on Orladeo and the finances. We'll start with Ryan, who will cover the data presented at Quad AI this past weekend and how many patients on Orlade are seeing excellent control of their HAEs, along with the convenience of one's daily dosing. With that, I'll pass it over to Ryan.

Jon P. Stonehouse: Today, we will focus our prepared remarks on Orla Dale and the financials, we'll start with Ryan who will cover the data presented at quite a high this past weekend and how many patients on Orla day are seeing excellent control of their H, a along with the convenience of once daily dosing with that I'll pass it over to Ryan.

Dr. Ryan Arnold: Thanks, John. I've had the privilege during my career to work on several therapies that help change the lives of patients who live with chronic, life-altering diseases. An important lesson I've learned is that long-term data, and particularly evidence from real-world experience, especially in rare diseases, are critical to understanding how a treatment can address unmet needs and change the lives of differing patient populations. This is an exciting time for Orladeo because after three, four years on the market, we are seeing a very consistent picture emerge from the building evidence. Realtor experience and the long-term clinical data are telling a very consistent story of how Orladeo can provide meaningful benefits to a variety of HAE patients. This is the final analysis of data from the open-label long-term extension portion of the APEX II study of barotraulstat. The patients who started on blinded baritrol set, 150 milligrams, and completed the full two years of the study had an average reduction of 90.8% in HAE tax compared to their baseline rate. But most of these studies don't measure their tax and percentage.

Ryan Arnold: Thanks, John.

Ryan Arnold: I had the privilege during my career to work on several therapies that helped changed the lives of patients who live with chronic life altering diseases.

Ryan Arnold: An important lesson I've learned is that long term data and particularly evidenced from real world experience, especially in rare disease are critical to understanding how a treatment can address unmet needs and change the lives of different patient populations.

Ryan Arnold: This is an exciting time for early data because after three four years on the market. We are seeing a very consistent picture emerged from the building evidence.

Ryan Arnold: Reorder experience and the long term clinical data are telling a very consistent story on how early they all can provide meaningful benefits to a variety of HAE patients.

Ryan Arnold: There's the final analysis data from the open label long term extension portion of the apex two study of <unk>.

Ryan Arnold: The patients who started on blinded Barrett Charles said 150 milligrams and completed a full two years of the study had an average reduction of 98% NHI attacks compared to their baseline rates.

Ryan Arnold: But most of US don't measure their tax percentages, what's most meaningful to people living with H a is that they get the chance to live a normal life by minimizing their tax burden and experienced meaningful improvements in their everyday quality of life.

Dr. Ryan Arnold: What's most meaningful to people living with HAE is that they get the chance to live a normal life by minimizing their attack burden and experiencing meaningful improvements in their everyday quality of life, all while avoiding the unnecessary potential burdens of treatment. Orladeo-treated patients in this long-term study reported rapid and sustained improvements from a baseline of 3.3 attacks per month to 0.3 attacks per month after two years, with the median attack rate of zero at month 24. These patients also reported meaningful long-term improvements in quality of life, treatment satisfaction, and an overall safety profile that is very reassuring for people living with this lifelong disease. That kind of change and the sustained low rate of attacks with just one pill once a day is transformative for many patients.

Ryan Arnold: All while avoiding the unnecessary potential burdens of treatment.

Ryan Arnold: Or are they all treated patients in this long term study reported rapid and sustained improvements from baseline of 3.3 attacks per month to <unk>.

Ryan Arnold: 0.3 attacks per month after two years with the median attack rate of zero at month 24.

Ryan Arnold: These patients also reported meaningful long term improvements in quality of life treatment satisfaction and an overall safety profile that is very reassuring for people living with this life long disease.

Ryan Arnold: That kind of change and the sustained low rate of attacks with just one pill. Once a day is transformative for many patients.

Dr. Ryan Arnold: These long-term data from our clinical program tell an important part of the story, which is being consistently reinforced by our expanding base of real-world evidence. This past weekend at the Quad AI meeting in Washington, DC, we presented five posters showing strong real-world evidence with Orladeo in a variety of patients with HAE. What patients are experiencing in the real world is consistent with the two-year clinical data. Patients with type 1 or 2 HAE are reporting long-term median attack rates of around half an attack per month after switching from other prophylactic therapies. By their own account, these patients are having fewer attacks on Orlandale than on their prior therapy.

Ryan Arnold: These long term data from our clinical program to one important part of the story, which is being consistently reinforced by our expanding base of real world evidence.

Ryan Arnold: This past weekend at the quality I mean meeting in Washington D. C. We presented five posters showing strong real world evidence with Orla, Dale and a variety of patients with AA.

Ryan Arnold: What patients are experiencing in the real world is consistent with the two year clinical data.

Ryan Arnold: Patients with type one or two H E. A reporting long term median attack rates of around half an attack per month.

Ryan Arnold: Switching from other prophylactic therapies.

Ryan Arnold: By their own account these patients are having fewer attacks on sale than on their prior therapies.

Dr. Ryan Arnold: Patients report a rapid and sustained reduction in attacks or maintaining attack-free status, regardless of whether their baseline monthly attack rate was very high or very low prior to starting on Orladele. These data on effect, regardless of baseline attack rate, are consistent with evidence we have presented from our clinical trials. Patients diagnosed by their physicians as having HAE with normal C1 inhibitor levels also are reporting rapid and sustained reductions in attacks on Liddell.

Ryan Arnold: Patients report rapid and sustained reduction in attacks or maintaining a tax free status, regardless of whether their baseline monthly attack rate was very high or very low prior to starting on or the orla Dale.

Ryan Arnold: These data on effect, regardless of baseline attack rate are consistent with evidence we presented from our clinical trials.

Ryan Arnold: Patients diagnosed by their physicians as having a J with normal C. One inhibitor levels also are reporting rapid and sustained reductions in attacks on early Dale.

Dr. Ryan Arnold: And we are seeing similar outside of the United States, particularly in countries like France, where patients can be followed in comprehensive programs with the active involvement of health care providers. This body of evidence demonstrating the long-term safety and effectiveness of Rolodeo is exciting. Our team has been hearing the stories of Orlodeo for the past three years, and these data further illustrate why it is such a favorable treatment option for people living with HAE. What is even more exciting is that the data we presented at Quad AI are just the start.

And we are seeing similar outside of the United States, particularly in countries like France, where patients can be followed and comprehensive programs with the active involvement of health care providers.

Ryan Arnold: This real world evidence demonstrating the long term safety and effectiveness of roller Dale is exciting.

Ryan Arnold: Our team has been hearing the stories of oil a day over the past three years and these data further illustrate why it is such a favorable treatment option for people living with H E.

Ryan Arnold: What is even more exciting is that the data we presented at quality are just the start.

Dr. Ryan Arnold: We will continue to generate more real-world evidence with Orladeo over the coming years, and we look forward to showing again and again how this treatment can help change the lives of patients and families impacted by HAE. I'll now turn it over to Charlie to describe how this emerging evidence is translating to our commercial efforts. Thanks, Brian.

Ryan Arnold: We will continue to generate more real as evidenced with the other day all over the coming years, and we look forward to showing again and again, how this treatment can help change the lives of patients and families impacted by H E.

Ryan Arnold: I'll now turn it over to Charlie described how this emerging evidence is translating to our commercial efforts.

Charlie Gayer: Thanks, Brian as John noted earlier, we recently described how consistent net patient growth of 200 per year for the next several years puts us on track for $800 million in sales in the United States.

Charlie Geyer: As Jon noted earlier, we recently described how consistent net patient growth of 200 per year for the next several years puts us on track for $800 million in sales in the United States. Entering our fourth year on the market, we are very much on track because we added 321 Orladeo patients in the U.S. in 2023. The real-world evidence that Ryan described helps explain this growth. Patients would like convenience. There's no doubt about that.

Charlie Gayer: Entering our fourth year on the market. We are very much on track because we added 321 orla data of patients in the U S. In 2023.

Charlie Gayer: The real World evidence that Brian described helps explain this growth.

Charlie Gayer: Patients would like convenience theres, no doubt about that but what they demand is efficacy.

Charlie Geyer: But what they demand is efficacy, control of their attacks. The real-world data with Orladeo clearly demonstrate that patients can have both efficacy and convenience. There are no trade-offs.

Charlie Gayer: Troll if their attacks.

Charlie Gayer: The real world data with early data clearly demonstrate that patients can have both efficacy and convenience no tradeoffs.

Charlie Geyer: Our teams have done a very good job of launching Orladeo, but in the end, patient experience will dictate how far we go. Brian shared that after switching to Orladeo from other prophylaxis therapies, patients experienced a median rate of about half an attack per month. What that means for patients is that many or most months are attack-free, and attacks that need to be treated are often less severe.

Charlie Gayer: Our teams have done our teams have done.

Charlie Gayer: A very good job of launching orla down but in the end patient experience will dictate how far how far we go.

Charlie Gayer: Brian sure that after switching to Orlando from other prophylaxis therapies patients experienced a median rate of about half an attack per month.

Charlie Gayer: What that means for patients is that many or most months are attack free and attacks that need to be treated are often less severe.

Charlie Geyer: Half an attack per month is also an important benchmark. We do market research with large samples of HAE patients, and we've reported previously at a medical congress that half an attack per month matches the level of attack control reported by patients taking injectable prophylaxis therapies in the real world. This low and consistent rate of attacks in Orladeo meets patients' expectations because they know from experience that perfect control is unlikely with any product. For many patients, to be able to get that level of control with an oral once-daily therapy is transforming how they live with HAE. We recently conducted an anonymous market research project with a sizable cohort of patients who have experience with Orladeo and asked them, as part of an exercise, to write a letter to Orladeo describing that experience, with themes such as, "You Gave Me Confidence. You Changed My Life." And I feel like a normal person again. We're ordinary.

Charlie Gayer: Half an attack per month is auto unimportant benchmark.

Charlie Gayer: We do market research with large samples of HIV patients and we've reported previously at a medical Congress Congress that half an attack per month matches the level of attack control reported by patients taking injectable prophylaxis therapies in the real world.

Charlie Gayer: This low and consistent rate of attacks in Orlando meets patients' expectations, because they know from experience that perfect control is unlikely with any product.

Charlie Gayer: For many patients to be able to get that level of control with an oral once daily therapy is transforming how they live with H E.

Charlie Gayer: We recently conducted an anonymous market research project with a sizeable cohort of patients who have experienced with oil down.

Charlie Gayer: And asked them as part of an exercise to write a letter to orla DAU describing that experience.

Charlie Gayer: Themes, such as you gave me confidence you changed my life.

Charlie Gayer: And I feel like a normal person again were common.

Charlie Geyer: The strong evidence from patients also continues to shape prescriber expectations and give them confidence. For example, our large quarterly surveys of allergists in 2023 showed they consistently expected to grow the proportion of their HAE patients treated with Orladeo by about 30% over the next 12 months. As we noted in our press release today, the number of patients on paid therapy, or our long-term free product program, also grew by 30% in 2023, tracking with physician predictions. Currently, about 50% of patients on Orlodeo have switched from other prophylaxes. But the allergists in our 2023 surveys expected about two-thirds of Orlodeo growth over the next year to come from switching from injectable prophylaxis. By the end of 2023, Orladeo was prescribed over 2,500 times in the United States.

Charlie Gayer: The strong evidence from patients also continues to shape prescriber expectations and give them confidence.

Charlie Gayer: Our large quarterly surveys of allergists in 2023 show they consistently expected to grow the proportion of their HIV patients treated with <unk> by about 30% over the next 12 months.

Charlie Gayer: As we noted in our press release today, the number of patients on paid therapy or our long term free product program also grew by 30% in 2023 tracking with physician predictions.

Charlie Gayer: Currently about 50% of patients on oral <unk> has switched from other prophylaxis.

Charlie Gayer: But but the allergists and our 2023 surveys expect about two thirds of Orlando growth over the next year to come from switches from injectable prophylaxis.

Charlie Gayer: By the end of 2023, Orla Deyoe had been prescribed over 2500 times in the United States.

Charlie Geyer: That means that at least 5,000 diagnosed and treated patients have not yet tried Orliban. Over 1,000 U.S. health care providers have now prescribed Orladeo, including over 200 new prescribers in 2023, but clearly, there is an opportunity for HAH readers to treat many, many more of their patients, just as our market research predicts. We have way more opportunity in front of us than behind us, and the growing body of evidence about how Orladeo is changing patients' lives is going to help us get there. I'll pass it to Anthony to describe our financial performance. Thanks, Charlie.

Charlie Gayer: That means that at least 5000 diagnosed and treated patients have not yet tried orlando.

Charlie Gayer: Over 1000 U S health care providers have now prescribed oral adele, including over 200, new prescribers in 2023, but clearly there is an opportunity for HAE treaters to prison.

Charlie Gayer: For many many more of their patients just as our market research predicts.

Charlie Gayer: We have way more opportunity in front of us than behind us and the growing body of evidence about how all the day. It was changing patients' lives is going to help us get there.

Charlie Gayer: Pass it to Anthony to describe our financial performance.

Anthony Doyle: Thanks, Charlie.

Anthony Doyle: It was great to see such a strong Q4 and full year 2023 for Orladeo. Not just the revenue performance, but the continued underlying strength in net new patient ads, giving us confidence of achieving between $380 million in global Orladeo revenue this year on our path to peak sales of $1 billion. You can find our detailed fourth quarter financials and today's earnings press release and I call your attention to a few items. Total revenue for the quarter came in at $93.4 million, $90.9 of which came from Orladeo, and Orladeo net sales for full year 2023 at $326 million, an increase of $74 million, or 30% year-over-year. Of the $90.9 million of global Orladeo revenue, $79.4 million came from U.S. sales with the remaining 11.5 or 12.7 percent coming from ex-U.S. On a full-year basis, U.S. Orladeo sales contributed $288.4 million of the $326 million global total, with the remaining 37.6 or 11.5 percent coming from ex-U.S. Operating expenses, not including noncash.com for the quarter, were approximately $119.6 million, included in this are significant one-time expenses.

Anthony Doyle: It was great to see such a strong Q4 and full year 2023 for Orlando not just the revenue performance, but the continued underlying strength in net new patient adds giving us confidence of achieving between $380 million in global.

Anthony Doyle: All of the day, our revenue this year on our path to peak sales of $1 billion.

Anthony Doyle: You can find our detailed fourth quarter financials in today's earnings press release, and I call your attention to a few items.

Anthony Doyle: Total revenue for the quarter came in at $93 $4 million $90 nine of which came from Orlando and <unk> net sales for full year 2023 of $326 million, an increase of 74 million or 30% year over year.

Anthony Doyle: Of the $99 million of global early day of revenue $79 4 million came from U S sales with the remaining 11, five or 12, 7% coming from ex U S.

Anthony Doyle: On a full year basis U S oil a day on sales contributed $288 4 million of the 326 million global total with the remaining 37, six or 11, 5% coming from ex U S.

Anthony Doyle: Operating expenses, not including noncash stock comp for the quarter were approximately $119 $6 million.

Anthony Doyle: Included in this are some significant one time expenses. These include about $5 4 million attributable to the R&D reorganization, including costs related to the reduction in force and the postponement of the expansion of the Discovery Center in Birmingham, Alabama.

Anthony Doyle: These include about $5.4 million attributable to the R&D reorganization, including costs related to the reduction in force and the postponement of the expansion of the Discovery Center in Birmingham, Alabama; the $5 million upfront payment we made to ClearSide related to our partnership, as well as around $7 million in CMC and other trial costs related to our partnership decision for BCX10013, all of which explain the increase in OpEx from Q3 of 2020. Operating expenses, not including non-cash.com for the full year, came in at $379.5 million, which, when excluding the $5.4 million of restructuring one-time adjustments I mentioned, landed it within our guidance range. We expect that quarterly expenses in 2024 will normalize in the low to mid $90 million range, taking us in line with our full year 2024 guidance of between $365 and $375 million and essentially flat to 2023. Cash at the end of the year was at $390.8 million, and net cash utilization for the quarter was $8.4 million.

Anthony Doyle: The $5 million upfront payment, we made to clear side related to our partnership as well as around $7 million in CMC and other trials costs related to our partnership decision for BC X tens or 13.

Anthony Doyle: All of which explain the increase in Opex from Q3 of 2023.

Anthony Doyle: Operating expenses, not including noncash stock comp for the full year came in at $379 5 million, which when excluding the $5 4 million of restructuring one time adjustments I mentioned blended it within our guidance range.

Anthony Doyle: We expect our quarterly expenses in 2024 will normalize in the low to mid $90 million range, taking us in line with our full year 2024 guidance of between 365 and $375 million and essentially flat to 2023.

Anthony Doyle: Cash at the end of the year was that $398 million and net cash utilization for the quarter was $8 4 million.

Anthony Doyle: In January we provided guidance on our near term timeline to achieve profitability for 2024, we expect that revenue will exceed opex, not including noncash stock comp and this will result in us generating an operating profit this year.

Anthony Doyle: Additionally, with revenue exceeding $350 million it puts us into a tier whereby the incremental revenue will be more profitable as the blended royalty rate is reduced.

Operator: In January, we provided guidance on our near-term timeline to achieve profit. For 2024, we expect that revenue will exceed OPEX, not including non-cash.com, and this will result in us generating an operating profit. Additionally, with revenue exceeding $350 million, it puts us into a tier whereby the incremental revenue will be more profitable as the blended royalty rate is reduced. In the second half of 2025, we expect to be approaching net income and cash flow positivity on a quarterly basis. And then in 2026, we expect to achieve net income and cash flow positivity on a full year basis. Achieving independence from the capital markets, while we also continue to invest in further expanding our global reach for Orladeo and expanding our label with the pediatric indication, while also further advancing our exciting early stage pipeline, puts the company in a very strong position moving forward. The operator will now open it up for Q&A. We will now begin the question and answer session. To ask a question, you may press star then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys.

Anthony Doyle: In the second half of 2025, we expect to be approaching net income and cash flow positivity on a quarterly basis and then in 2026, we expect to achieve net income and cash flow positivity on a full year basis.

Anthony Doyle: Achieving independence from the capital markets. While we also continue to invest in further expanding our global reach for Orlando and expanding our label with the pediatric indication. While also further advancing our exciting early early stage pipeline puts the company in a very strong position moving forward operator, well now open it up for Q&A.

Speaker Change: We will now begin the question and answer session.

Speaker Change: To ask a question you May Press Star then one on your Touchtone phone.

Speaker Change: If you are using a speakerphone please pick up your handset before pressing the keys.

Is it any time your question has been addressed and we would like to withdraw your question. Please press Star then two.

Speaker Change: At this time, we will pause momentarily to assemble our roster.

Speaker Change: Okay.

Speaker Change: The first question comes from <unk> Ahmed with Bank of America. Please go ahead.

Ahmed: Hey, guys. Good morning, Thanks for taking my question.

Ahmed: Can you give us a little bit of color regarding the patients that you were able to add last year. They came at <unk> <unk> higher than what you anticipated was there a particular profile of patients that was added.

Tazeen Ahmad: If at any time your question has been addressed and you would like to withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. The first question comes from Tazeen Ahmad with Bank of America. Please go ahead. Hi guys, good morning.

Ahmed: We're expecting and in general.

Ahmed: Have a sense of what level of baseline attack.

Ahmed: Patients have when they are switching in particular to your drug from another got it and then I have a follow up thanks.

Tazeen Ahmad: Thanks for taking my question. Can you give us a little bit of color regarding the patients that you were able to add last year? They came, as you said, higher than what you anticipated.

Ahmed: Yeah.

Ahmed: Sure.

Ahmed: <unk>.

Speaker Change: There wasn't really a profile that we werent expecting we were since the beginning of launch we've been getting patients from all different profiles as Brian laid out with some of the data excuse me.

Unidentified: Was there a particular profile of patients that was added that you weren't expecting? And in general, do you have a sense of what level of baseline attacks patients have when they are switching, in particular, to your drug from another drug? And then I have a follow-up. Thanks. Thanks. I'm Chris Chappell.

Speaker Change: Alright.

Speaker Change: Some of the data.

Speaker Change: We presented this weekend at Quad AI.

Speaker Change: Regardless of baseline attack rate, regardless of background therapy patients do really well on <unk>.

Unidentified: Thank you. Thank you. Sure. Tazeen, there wasn't really a profile that we weren't expecting.

Speaker Change: And if I can.

Speaker Change: Do you want to take the rest of that Ryan Yes. There is there any there any phenotype I think what she is asking is is there a baseline attack rate is there any phenotype that we're seeing any particular group that's going into.

Unidentified: Since the beginning of launch, we've been getting patients from all different profiles, as Ryan laid out with some of the data. Thank you very much. Sorry, some of the data that we presented this weekend at Quad AI, regardless of baseline attack rate, regardless of background therapy, patients do really well on Orlodeo, and... Do you want to take the rest of that, Brian? Yeah. Is there any phenotype?

Speaker Change: <unk>.

Ryan Arnold: Switching to Orla day yeah.

Orla Deyoe: I'll call your attention to.

Orla Deyoe: Slide six and slide eight in our deck both of these speak to the background.

Orla Deyoe: Baseline attack rates and what Youll see here is despite varying attack rate speeds higher low patients do very well in orla Dale.

Unidentified: I think what she's asking is, is there a baseline attack rate? Is there any phenotype that we're seeing, any particular group that's going into switching to Orladeo? Yeah, and I'll call your attention to slides 6 and 8 in our deck.

Orla Deyoe: Slide eight specifically calls out our baseline attack rate of $1 three three at baseline for those with <unk> type one or type two and again those patients did very well achieving an attach rate of <unk> five a day 540. So he had a rapid and sustained reduction in their tax rates. So basically a variety of patients can benefit from.

Unidentified: Both of these speak to the background or baseline attack rates. And what you'll see here is, despite varying attack rates being high or low, patients do very well in Orladeo. Slide 8 specifically calls out a baseline attack rate of 1.33 at baseline for those with HAE type 1 or type 2. And again, those patients did very well, achieving an attack rate of 0.5 at day 540. So basically, a variety of patients can benefit from Orladeo regardless of what their baseline attack rate is. Yeah, so Tazeen, you really can't predict it. So the goal is to get everybody to try it and see if it works. I was more asking about whether in real life you were seeing something different relative to what you would see in real life. Trials seem like the answer to that.

Orla Dale regardless of what their baseline attack rate is.

Speaker Change: Yeah. So dizzying, you really cant predict it so the goal is to get everybody to try it and see if it works for them.

Speaker Change: Yes.

Speaker Change: 21 patients whether in real life, you're seeing something different relative to what you've been seeing in clinical trials.

Speaker Change: The answer to that is now.

Speaker Change: And then maybe this does a follow up how are you thinking about discontinuation rates on a go forward basis.

Speaker Change: How have they been trending any changes from the time you launch thanks.

Speaker Change: Thanks.

So Charlie is alive.

Speaker Change: Again, my asthma attacks.

Charlie Gayer: The discontinuation, it's been really steady in 2023 in the last few years so.

Charlie Gayer: Still.

Unidentified: And then maybe just as a follow-up, how are you thinking about discontinuation rates on a go-forward basis? How have they been trending? Any changes from the time that you launched? Thanks. I think I can talk again. It's my asthma attack.

Charlie Gayer: When a patient starts early data, we get 60% of those patients to 12 months and then very few discontinued continuations after that and I think relating to your earlier questions too. We see the same retention rate regardless of of patients' background, so regardless of their attack rate regardless on whether they are switching.

Unidentified: The discontinuation rate has been really steady in 2023 and the last few years. So, still, when a patient starts Orladea, we get 60% of those patients to 12 months, and then very few discontinuations after that. And I think relating to your earlier questions too, we see the same retention rate regardless of the patient's background. So regardless of their attack rate, regardless of whether they're switching from prophylaxis or coming in from acute only, they're all staying on it at about that same rate, 60% a year. Okay, thank you.

Charlie Gayer: From prophylaxis or coming in from acute only they're all staying on it at about that same rate 60% in the year.

Speaker Change: Okay. Thank you.

Speaker Change: Okay.

The next question comes from Brian Abrahams with RBC capital markets. Please go ahead.

Brian Corey Abrahams: Oh, Hey, good morning, guys. Thanks for taking my question Congrats on the continued progress.

Brian Corey Abrahams: Thank you. The next question comes from Brian Abrahams with RBC Capital Markets. Please go ahead. Hey, good morning, guys.

Brian Corey Abrahams: I'm curious if you could talk a little bit about the.

<unk>.

Brian Corey Abrahams: I guess your sales and marketing strategy this year relative to last year.

Brian Corey Abrahams: Thanks for taking my question. Congratulations on the continued progress. I'm curious if you could talk a little bit about your sales and marketing strategy this year relative to last year. Do you expect, I guess, continued pull-through from some of the team territory changes that were implemented in 2023?

Brian Corey Abrahams: Hum.

Brian Corey Abrahams: Do you expect I guess continued pull through from some of the team territory changes that were implemented in 2023 in 2024.

Brian Corey Abrahams: What do you expect to be the focus of the additional SG&A investment for this year and are there any changes to your commercial approach or strategy with an expected greater proportion of the opportunity now coming from from the switchers versus those patients who are on demand only.

Charlie Geyer: In 2024, what do you expect to be the focus of the additional SG&A investment for this year? And are there any changes to your commercial approach or strategy with an expected greater proportion of the opportunity now coming from the switchers versus those patients who are on demand only? Charlie, do you want to take that? Yeah. Hey, Brian.

Brian Corey Abrahams: Charlie you want to take that Yeah, Hey, Brian So.

Charlie Gayer: One of the reasons I do think we did so well last year as we did make those adjustments to the team in the beginning of 2023 by the end of last year. The additional sales folks the additional patient services market access that we added everyone was was active in really comfortable in their roles and working well together.

Charlie Geyer: One of the reasons I think we did so well last year is that we did make those adjustments to the team at the beginning of 2023. By the end of last year, the additional sales folks, the additional patient services, and market access that we added, everyone was active and really comfortable in their roles and working well together. And I think that that is a big part of our performance. And then going forward to your question about any changes in the kind of data that, again, Ryan presented, I think is really critical. And we're very focused on getting patients and physicians comfortable with the idea that switching from an injectable prophylaxis to Orladeo is an opportunity for patients to really benefit. And I think we're seeing that our customers are starting to understand that. So we'll keep the focus on that message. And Brian got it.

Charlie Gayer: And I think that that that is a big part of our performance.

Charlie Gayer: And then going forward to your question about any any changes in the kind of data that again that Ryan presented I think is really critical and we're very focused on.

Charlie Gayer: Getting patient patients and physicians comfortable with either switching from.

Charlie Gayer: Injectable prophylaxis to oral it al is opportunity for patients to really benefit and I think we're seeing that our customers are starting to understand that so well with the focus on that messaging and Brian got it. Thank you.

Jon P. Stonehouse: Thank you. One thing I'd add, Brian, is that Charlie mentioned this increasing confidence. And, you know, one of the things that we're seeing at Quad AI and other places, we had a standing room only session at Quad AI, and the confidence in the docs is really high. You compare that to a year ago, where people were still kind of on the fence, and it's really because they've had experience and they're seeing it work extremely well in patients. So that'll have an effect on them that'll be really positive for Orladea and for patients. Thanks, Jon.

Speaker Change: One thing I'd add Brian is that Charlie mentioned was this increasing costs.

Speaker Change: And one of the things that we're seeing that quad AI. Another place we had a standing room only session that quad AI and <unk>.

Confidence in the Docs is really high and you compare that to a year ago, where people were still kind of on the fence and and it's usually because they've had experience and theyre seeing it work extremely well in patients. So that'll have an effect time that it'll be really positive for all the data and for patients got it got it.

Brian Corey Abrahams: And maybe just a quick follow-up, it sounds like you've got some visibility to getting to the goal of a paid rate of 85% by the end of the decade. Where do you think you can get the paid rate this year relative to 2023? What's embedded in your guidance and how much potential upside there could be versus your guidance if things go better than expected on that front? And I'll hop back in the queue.

Speaker Change: Thanks, John and maybe just a quick follow up it sounds like you've got some visibility to getting to our goal of a paid rate of 85% by the end of the decade, where do you think you can get the paid rate this year relative to 2023, what's embedded in your guidance and how much potential upside could there be versus your guidance if things go better than expected on that front.

Speaker Change: And I'll hop back in the queue. Thanks.

John Bluth: Brian what we said before is that that 85% number yeah. We're very confident we'll get there, but it's going to take us a few years and so we announced this morning in the press release that we were we ended last year at a rate of 71, 5%. So we'll make some incremental improvements to that but don't expect any any major.

Charlie Geyer: Brian, what we've said before is that that 85% number, yeah, we're very confident we'll get there, but it's going to take us a few years. And so we announced this morning in the press release that we ended last year at a rate of 71.5%. So we'll make some incremental improvements to that, but don't expect any major changes. We're not going to jump straight to 85%. We'll probably get there faster in the 2026-2027 timeframe. Got it. Thanks, Charlie. Thanks again.

John Bluth: <unk>, we're not going to jump straight to 85%.

We'll get there probably more in the 2026 2027 timeframe.

Got it thanks, Charlie Thanks again.

John Bluth: The next question comes from Jessica Fye with Jpmorgan. Please go ahead.

Jessica Fye: Hey, guys. Good morning, Thanks for taking my question.

Jessica Fye: Talk about the extent to which your near and long term top line expectations for Orlando reflects the introduction of less frequently dose injectables.

Jessica Fye: The next question comes from Jessica Fye with J.P. Morgan. Please go ahead. Hey guys, good morning.

Unidentified: Thanks for taking my question. Can you just talk about the extent to which your near and long-term top-line expectations for Orladeo reflect the introduction of less frequently dosed injectables and other orals? Hi Jeff.

Jessica Fye: And other oral <unk>.

Jessica Fye: <unk>.

Jessica Fye: Yes, Hi, Jeff.

Jessica Fye: We take into account all the introductions of new products, including new Injectables and possibly in the future.

Speaker Change: New oral <unk> and what we what Jinky Rosselli and I described at the last earnings call is that.

Unidentified: We take into account all the introductions of new products, including new injectables and, possibly, in the future, new orals. And what Jinky Roselli and I described at the last earnings call is that patients, once they're on a therapy and doing well, tend to be really sticky on that therapy. And when patients are doing as well as they are on Oral-A-Deo, we don't see them moving to other therapies. The other key part of it is that we have a very differentiated product in a once-daily oral, and that's something that patients and healthcare providers really want. And so a new injectable therapy offers some incremental benefits, but it is not highly differentiated the way Oral-A-Deo is. Yeah, I think Jeff, flip the question around and ask. Why would they go on to another product? What's the incremental benefit? And I think what Charlie presented today and what Ryan presented is that patients aren't sacrificing efficacy for convenience. This drug works spectacularly well in certain patients, and it's a once daily drug.

Speaker Change: The patients once they're honest a therapy and doing well are tend to be really sticky on that therapy and when patients are doing as well as they are on oral <unk>.

Speaker Change: We don't see them moving to other therapies. The other the other key part of it is that we have a very differentiated product in a once daily oral and and Thats something that patients and health care providers really want and so our new injectable therapy offer some incremental benefits.

Speaker Change: But it is not highly differentiated the way early to ours.

Speaker Change: Just flip the question around and ask.

Speaker Change: Why would they go onto another product, but what what what's the incremental benefit and and I think what Charlie presented today and what Ryan presented is patients aren't sacrificing efficacy for convenience. This drug works spectacularly well in in certain patients and it's a once a day.

Speaker Change: <unk>, so what incremental benefit is going to cause them to switch.

Jon P. Stonehouse: So what incremental benefit is gonna cause them to switch? And we've seen that we get switches; you have to have some incremental benefit. So the question is, it can't be efficacy, right? Because if you're controlled on our drugs, then you can't do any better.

Speaker Change: And we've seen.

Speaker Change: We're getting switches you have to have some incremental benefit. So the question is it can't be efficacy right because if youre controls on our drugs. Then then you can't do any better.

Unidentified: Thank you. You're welcome. The next question comes from Liisa Bayko with Evercore ISI. Please go ahead.

Speaker Change: Thank you.

Speaker Change: Youre welcome.

Speaker Change: The next question comes from Lisa <unk> with Evercore ISI. Please go ahead.

Liisa A. Bayko: Hi, just to follow up on that. I mean, you do have a half an attack rate per month, right, which is one every two months, which is six per year after switching from other prophylaxis. So would that not be?

Lisa: Hi, just a follow up on that.

Lisa: You do have a half an attack rate per month, right, which is one every two months to six per year. After switching from other prophylaxis, so would that not be.

Unidentified: Like those types of patients, would they not be interested in maybe trying something else? That would just be my one question, but I actually have other questions beyond that. Do you want to tackle that one? I mean, the bottom line is that nobody does it better than that.

Lisa: Like those types of patients would they not be interested in maybe trying something else that would just be my one question, but as you have further questions beyond that.

Speaker Change: Thank you.

Speaker Change: Tackle that one I mean, the bottom line is nobody does better than that that's kind of the standard every drug has breakthrough attacks and in that number is a mixture of people that arent, having attacks and some that are and so but Brian I don't know if theres anything else to add yes, as John alluded to I mean, this is you've seen similar attack control with.

Unidentified: That's kind of the standard. Every drug has breakthrough attacks. And, you know, in that number is a mixture of people that aren't having attacks and some that are. And so, Ryan, I don't know if there's anything else to add. Yeah.

Dr. Ryan Arnold: As Jon alluded to, I mean, this is, you're seeing similar attack control with other injectable therapies. And, you know, we view this not as a trade-off, but a trade-off because, again, patients don't want just attack control. They want the added conveniences as quality of life improvements.

Brian: The other injectable therapies, and we view this not as a tradeoff, but a trade up because again patients don't want just attack control. They want the added convenience as well as the quality of life improvements and again, we've reported all of that Olson, our clinical studies as well as in the real world evidence.

Brian: I have an attack per month is doing very well and again that doesn't include the tax severity, which for some.

Dr. Ryan Arnold: And, again, we've reported all of that both in our clinical studies as well as in real-world evidence. So half an attack per month is doing very well. And again, that doesn't include attack severity, which for some, they've shared these are very manageable. So again, this is a very notable improvement and looks very similar to injectables in terms of attack rate control. Yeah, so Liisa, don't get confused by the numbers of attack rate reduction in a pivotal study because the confidence intervals from those studies overlap. They all work, the bottom line, and they're not perfect.

Brian: Sure. These are very manageable. So again. This is this is a very notable improvement in looks very similar to injectables in terms of the Tac rate control, yes, So Lisa don't get confused by the the the numbers of attack rate reduction in our pivotal study because the confidence intervals from those studies overlap there. They all work is the boss.

Brian: Online and Theyre not perfect. They all have some breakthrough attacks.

Speaker Change: Okay and have you done any convenience analysis like market research on this sort of like very long acting agents because it seems like.

Jon P. Stonehouse: They all have some breakthrough attack. Okay. And have you done any convenience analysis like market research on these sort of, you know, very long-acting agents? Because it seems like, you know, at some point, you might tip the balance between taking an oral pill and infrequent injections. I realize that some people don't like injections too, but is there any...

Speaker Change: So at some point you might get the balance between <unk> and <unk>.

Speaker Change: So I realize there's some people don't like injection to but is there any.

Speaker Change: I guess like.

Speaker Change: Elasticity there in a way.

Speaker Change: Yeah, No. That's a really good question, because we're super paranoid and one of the things I ask Janky is what's the tipping point on frequency of injectable dosing that would make it as attractive as it once daily oral found it yet I mean, we run that research we haven't found it yet and so okay.

Unidentified: I guess, like, elasticity there, in a way. Yeah, no, that's a really good question, because we're super paranoid, and one of the things I ask Jenki is, what's the tipping point on the frequency of injectable dosing that would make it as attractive as once daily oral? We haven't found it yet. I mean, we've run that research. We haven't found it yet, and so, but we'll keep looking. Sorry to interrupt, but I would just add that people underestimate the fear of injections that patients experience, and while it can be convenient for some, I think that fear and fatigue of injections can be underestimated, so we hear that continuously from our physicians and from patients as well. So, they are seeking convenience as well as that aspect of normality, having a normal life and carrying around a once a day oral feels very normal for a lot of patients.

Janky: Yeah, well, we'll keep looking.

Speaker Change: Sorry to interrupt I would just add I think people underestimate the fear of injections that patients experiencing while it can be convenient for some.

Speaker Change: I think that fear and fatigue of injections can be underestimated, so and we hear that continuously from our physicians and from patients as well. So they are seeking convenience as well as that aspect of normal having a normal life and carrying around a once a day oral feels very normal for a lot of patients.

Speaker Change: Okay, Great and then just.

Speaker Change: Quick question for me.

Speaker Change: I have to go through the math of like how many patients you've treated so far.

Speaker Change: How many patients.

Like HIV patients are out there and how many more need to try orla Dale given that kind of like stickiness of the product like it you know maybe whatever half the patients are still lined up like sticking to it long term.

Speaker Change: That kind of.

Speaker Change: Go through from here to get to that sort of $800 million number.

Unidentified: Okay, great. And then I have just a quick question for you. Can you kind of go through the math of how many patients you've treated so far? How many patients? Like HAU patients are out there, and how many more need to try Orladeo given the kind of like stickiness of the product, like it? Maybe half the patients or so end up like sticking to it long term. It's a kind of like go through from here to get to that sort of $800 million U.S. number. So let's start with the 7,500 and work backwards.

Speaker Change: So start with the 7500 and work backwards fit yes, Lisa.

Speaker Change: Near the end of my remarks.

Speaker Change: Today I pointed out that there are at least 5000 patients who have not yet tried oral it out based on our previous estimates that there are about 7500 diagnosed and treated patients. We've had 2500 prescriptions to date. So there's at least another 2000 patients and.

Speaker Change: With what we're hearing from physicians and patients we expect a lot more trials in that in that 5000, so plenty and plenty of room to grow.

Charlie Geyer: Yeah, Liisa, near the end of my remarks today, I pointed out that there are at least 5,000 patients who have not yet tried Orladeo. That's based on our previous estimates that there are about 7,500 diagnosed and treated patients. We've had 2,500 prescriptions to date.

Speaker Change: Okay, and what like as you think about what you need to get to that 800 number you know how is it like half of those that need the triad or what is the amount.

Charlie Geyer: So there are at least another 1,000 patients, and with what we're hearing from physicians and patients, we expect a lot more trials in that 5,000. So there is plenty of room to grow.

Speaker Change: That's probably a pretty good a pretty good estimate what we need to get us to about 2000 patients who are sticky it at peak.

Speaker Change: We are more than halfway there at this point.

Charlie Geyer: Okay, and what, like, as you think about what you need to get to that 800 number, you know, how much is it like half of those that need to try it, or what is the amount? That's probably a pretty good estimate. What we need to get is about 2,000 patients who are sticky at peak. We are more than halfway there at this point. Great. Thank you so much, guys. The next question comes from Stacey Kuh with TD Cowan. Please go ahead.

Speaker Change: Great. Thank you so much guys.

Speaker Change: You're welcome.

Speaker Change: Yeah.

Speaker Change: The next question comes from Stacy <unk> with TD Cowen. Please go ahead.

Stacy: Thanks for taking our questions. So first question is around kind of potential implications with the change in the Medicare part D. Redesign did I hear right. So could there be any potential impact to patient volumes with a decrease in the Max out of pocket spend.

Stacy: And what would be the timing of something like this so that's one and then just a follow up too.

Stacey Kuh: Thanks for taking our questions. So, my first question is around the potential implications of the change in the Medicare Part D redesign due to IRA. So, could there be any potential impact to patient volumes with a decrease in the max out-of-pocket spend? And what would be the timing of something like this?

Stacy: Some of the questions have been asked can you just further characterized your commentary around the clinicians that are prescribing and more academic community.

Stacy: So does that 50% split now thanks, so much.

Stacy:

Speaker Change: Thanks, Stacy so on the <unk>.

Charlie Geyer: So, that's one. And then just a follow-up to some of the questions that have been asked. Can you just further characterize your commentary around the clinicians that are prescribing and more academic, more community? Is it really still just that 50% split now? Thanks so much.

Speaker Change: Particularly next year when the Max out of pocket shift to $2000. We think that will be an advantage for patients in terms of afore affordability and then very important is that next year that $2000 can be.

Charlie Geyer: Thanks, Stacy. So, on the IRA, particularly next year when the max out-of-pocket shifts to $2,000, we think that will be an advantage for patients in terms of affordability. And very important is that next year $2,000 can be paid over the course of the year in 12-month increments.

Speaker Change: Paid over the course of the year.

Speaker Change: Uh huh.

Speaker Change: The 12 month increments and so we think that that'll that'll increase affordability and likely increase that rate.

Speaker Change: For the day I don't think it will really change the volume of patients treated it's just going to affect the rate.

Speaker Change: And then as far as clinicians.

Charlie Geyer: And so we think that that will increase affordability and likely increase the rate for Orladeo. Don't think it will really change the volume of patients treated; it's just going to affect the rate. And then, as far as clinicians are concerned, we see a great mix. Again, we see academic physicians, as well as a lot of community physicians.

Speaker Change: We see a great mix again, we see the academic physicians.

Speaker Change: As well as a lot of community physicians as I said over a 1000 health care providers have prescribed so far and that is really distributed very evenly across the desk styles of our.

Speaker Change:

Speaker Change: Our our health care provider potential index, and it's been very consistent that way every quarter. So we're getting both academic and community.

Charlie Geyer: As I said, over 1,000 healthcare providers have prescribed so far, and that is really distributed very evenly across the deciles of our healthcare provider potential index. And it's been very consistent that way every quarter.

Speaker Change: Understood and just a follow up does that mean that you think as the rate has improved for kind of the.

Charlie Geyer: So we're getting both academic and community support. Understandable. And just to follow up, does that mean that as the rate is improved for kind of the IRA changes, you do think that you'll be able to kind of switch more patients over to paid drugs? Is that a fair way of thinking about it? Yes, we do. Next year, 2025 and beyond.

Speaker Change: And <unk> changes do you think that you'll be able to kind of just put some more patients over to paint.

Speaker Change: Is that is that a fair.

Speaker Change: Yes, we do next year in 2025 and beyond.

Speaker Change: Okay wonderful thank you.

Speaker Change: Okay.

Speaker Change: The next question comes from Sergey <unk> LNG with Needham <unk> co. Please go ahead.

Charlie Geyer: Okay, wonderful. Thank you. The next question comes from Serge Belanger with Needham & Co. Please go ahead. Hi, good morning.

Speaker Change: Yes.

Sergey: Hi, Good morning, Thanks for taking my questions I guess, the first one for Charlie.

Sergey: Give a little color on the <unk> seasonality. This year is it similar to prior years.

Serge Belanger: Thanks for taking my question. I guess the first one for Charlie, can you just give a little color on the 1Q seasonality this year? Is it similar to prior years? And then the second question, I guess, for Jon and maybe the rest of the team.

Sergey: And then second question I guess for John and maybe the rest of the team.

Sergey: I think we've all been consistent that you do expect.

Charlie Geyer: I think you've all been consistent that you do expect competition from an oral prophylactic by the end of the decade. Just curious about your thoughts on an oral on-demand treatment and what impact that could have on the market. Thanks. Hey, Serge.

Sergey: Competition from an oral prophylactic, but by the end of the decade.

Sergey: Just curious your thoughts on an oral on demand treatment and what impact that could have.

Sergey: For the market. Thanks.

Sure Hey, Serge I'll start with that for <unk>, Yes, we would expect similar seasonality with the first quarter revenue being down versus Q4.

Charlie Geyer: I'll start with that. For 1Q, yes, we expect similar seasonality with the first quarter revenue being down versus Q4. We had a really strong Q4, so we actually think the percentage reduction could be a little bit more this year, so I think 7% or 8% drop from Q4 and probably the mid-80s in revenue for Q1.

Sergey: We had a really strong Q4, so we actually think the percentage reduction could be a little bit.

Sergey: More of this year, so think 7% or 8% drop from Q4, and probably mid Eighty's in revenue for Q1.

Jon P. Stonehouse: And with regard to oral competition, specifically on-demand therapy, I mean... We certainly can't argue that orals are important, and if you have an oral alternative for a breakthrough attack, we think that's great. And so having that as a choice for patients, we think, is just another benefit. And an all-oral option would be fantastic, right?

Sergey: And with regard to oral competition spa.

Sergey: Specifically on demand therapy.

Sergey: We certainly can't argue that oral are important and if you have an oral alternative for a breakthrough attack. We think that's great and so having that as a choice for patients that we think is just another benefit.

Sergey: And an all oral option would be fantastic right appropriate and when you have a breakthrough attack taken oral on demand.

Charlie Geyer: A pro-phe, and when you have a breakthrough attack, take an oral on demand. Great, thanks. You're welcome. As a reminder, if you would like to ask a question, please press star then 1 to be added to the question queue. The next question comes from Gena Wang with Barclays. Please go ahead.

Speaker Change: Great. Thanks.

Speaker Change: Youre welcome.

Speaker Change: As a reminder, if you would like to ask a question. Please press Star then one to be joined into the question queue.

Speaker Change: The next question comes from Gena Wang with Barclays. Please go ahead.

Gena Wang: Thank you for taking my questions. I just have one regarding the data report. I think if we look at slide 678, when we look at the number of patients, more than two-thirds of patients, I mean, the beginning of a patient number and the end of a patient number, it was about one-third of patients continued until the end of the data report. So, any color you could give regarding the other two-thirds of the patients? Yeah, and these, well, maybe I'll let you start, Ryan.

Gena Wang: Thank you for taking my questions I just have one regarding the data report I think if we look at the slides six seven days a.

Gena Wang: When we look at number of patients more than two third of patients.

Gena Wang: At the beginning of a patient number and if a patient numbers.

Gena Wang: It was about one third of patients continue to the end of data report. So any color you could give me the other two third of the patient.

Speaker Change: Yeah, well, maybe I'll, let you start Ryan yes.

Dr. Ryan Arnold: Yeah, I mean, thanks for the question. These are patients that are, you know, they're reporting, self-reporting their attack rates. So, and because this is real-world data, there's always limitations in terms of how that is recorded. For example, in some months, patients may not share what their attack rates are, but that doesn't necessarily mean they've necessarily come off of therapy.

Ryan Arnold: Thanks for the question.

Ryan Arnold: These are patients that are they're reporting self reporting their attack rates. So.

Ryan Arnold: And because this is real world data, there's always limitations in terms of how that is recorded in some months patients may not share what the attack rates are and so but that doesn't mean, they necessarily come off therapy and all of these patients have that you've seen in these slides have completed 540 days of therapy, we're still waiting for some time to complete.

Dr. Ryan Arnold: And all of these patients that you've seen in these slides have completed 540 days of therapy. We're still waiting for some to complete that same timeframe to include them in the analysis. Keeping somebody in a study for two years is challenging, certainly.

Ryan Arnold: That same timeframe to include them in the analysis.

Ryan Arnold: Somebody in a study for two years is challenging.

Jon P. Stonehouse: And remember, some patients don't do well on our drug. We've got about 60% retention. And so it's not uncommon to see people not succeed.

Speaker Change: Certainly and remember some patients don't do well and our drug we've got about a 60% risk retention and so it's not uncommon to see people not succeed in them and you'll see that in some of these results just to just underline what Bryan said just to make sure it's really clear in.

Dr. Ryan Arnold: And you see that in some of these results. Just to underline what Ryan said, just to make sure it's really clear, in this real-world evidence, we measure patients based on the length of time that they've been in therapy, and some of them just haven't had the opportunity to reach 540 days because they started at a later time point.

Speaker Change: In those in this real world evidence, we measure patients based on the length of time that they have in therapy and some of them just haven't had the opportunity to reach 540 days because they started at a later time point. So it's a dynamic sample of course, some patients do drop out, but this represents how well patients when they're doing well.

Charlie Geyer: So it's a dynamic sample. Of course, some patients do drop out. But this represents how well patients, when they're doing well in Orladeo, they're doing really well and sticking with therapy. That's the point, Gena, is that the patients that do well do really well on drugs. Okay, great. Thank you. The next question comes from Francois Brizbois with Oppenheimer.

And Orlando, they're doing really well and sticking on therapy. That's the point Gina is that the patients that do well do really well in drug.

Speaker Change: Okay, great. Thank you.

Speaker Change: Yeah.

Speaker Change: The next question comes from Francois Brisbois with Oppenheimer. Please go ahead.

Francois Brizbois: Please go ahead. Hi, thanks for taking the question. I was just wondering, in terms of the discontinuation rate, what leads to this discontinuation rate? Is it that, you know, for those patients that just aren't doing well, or is there any other reason out there? And if they do discontinue, what do they usually end up doing?

Speaker Change: Yeah.

Francois Brisbois: Alright, Thanks for taking the question I was just wondering in terms of the discontinuation rate.

What leads to this discontinuation rate is it that you know for those patients that just arent doing well or is there are there any other reason out there and if they do discontinue what do they usually end up doing.

Francois Brisbois: Yeah.

Speaker Change: Thanks, Francois the discontinuation rate there are two main reasons for discontinuation and these won't be surprising. The number one reason is perceived lack of efficacy. So as we've said no drug is perfect that node no one <unk> therapies for everybody and so that's that.

Charlie Geyer: Thanks, Francois. The discontinuation rate, there are two main reasons for discontinuation, and these won't be surprising. The number one reason is perceived lack of efficacy.

Charlie Geyer: So, as we've said, no drug is perfect, and no one HA therapy is for everybody. And so that's the number one reason reported. The number two reason is adverse events, specifically gastrointestinal, which is not surprising given the product label in our clinical trial experience.

Speaker Change: It's the number one reason reported the number two reason is adverse events, specifically gastrointestinal which is not surprising given.

Speaker Change: Given the product label in our clinical trial experience. What we do know is that some patients give up too early and so part of our messaging is for physicians and others to set expectations that you can have a breakthrough attack you might have Gi events the Gi.

Charlie Geyer: What we do know is that some patients give up too early, and so part of our messaging is for physicians and others to set expectations that you can have a breakthrough attack, you might have GI events, but the GI events tend to go away after a few weeks of therapy for most patients.

Speaker Change: I tend to go away.

Speaker Change: After a few weeks of therapy for most patients.

Charlie Geyer: And so it's important that patients don't give up too early. We actually see that in 2023, about 10% of the patients starting Orladeo were actually restarts. They're people who gave up in the past and came back because they knew that they'd given up too early.

Speaker Change: So it's important that patients don't give up too early we actually see in 2023.

Speaker Change: 10% of the patients starting oral it out we're actually restarts there are people who gave up in the past and came back because they knew that they had given up to two early and Francois John concerned yet the slide but one of the slides we've had in previous decks shows the pattern of discontinuation over two years and it's <unk>.

Charlie Geyer: And Francois, Jon can send you the slide, but one of the slides we've had in previous decks shows the pattern of discontinuations over two years, and it's flat. I think now we have a pretty good idea of what that pattern is, and if we've got you for out to a year, we've got you. Okay. And then, can you just help me understand a little bit about the U.S. versus ex-U.S. dynamics in terms of growth and your assumptions and expectations? Are there challenges, maybe ex-U.S. that aren't happening in the U.S.? Just any color that would, Sure.

Speaker Change: <unk>.

Speaker Change: So I think now we have a pretty good idea of what that pattern is and if we got you for out to a year. We've got you.

Speaker Change: Understood and then can you just help me understand a little bit the U S versus ex U S dynamics in terms of the growth and your assumptions and expectations and their challenges maybe ex U S that aren't happening in the U S. Just any color there would be helpful. Thank you.

Charlie Geyer: XUS, first of all, the biggest challenge or the biggest time factor is getting market access in an XUS market. And so that always takes longer, and we have countries rolling on all the time. So a number of countries in Europe, for example, like Germany, the UK, and France, we got market access a few years ago, but we're just now getting market access in others like Spain and Italy.

Speaker Change: Sure.

Ex U S first of all once we the biggest challenge or the biggest time.

Speaker Change: Time factor is getting market access in an ex U S market and so that always takes longer than we have countries that rolling on all the time so.

Speaker Change: A number of countries in Europe for example, like Germany, UK and France, We got market access a few years ago, but we're just now getting market access and others like Spain, and Italy, and so that's that's one factor.

Charlie Geyer: And so that's one factor. Pricing is a lot lower for XUS, so it takes four to five XUS patients to add up to one US patient. So our strategy is very much a volume strategy outside the US. And then finally, what we're seeing in the real world, in these countries where we have market access and we've launched, is the same consistent pattern of patient ads, depending on the market, the HA market dynamics, sometimes that's patients switching from other professions, sometimes there's a growing prophylaxis market with a drug like Orladeo. At peak, we expect Ex-U.S. to equal about $200 million of the billion dollars in sales, and what we see so far gives us confidence that we'll get there. And if TxIRO is an analog here, right at the time that the U.S. starts to flatten out, Ex-U.S. continues to grow, so you have overall growth of the brand still.

Speaker Change: <unk> is a lot lower.

Speaker Change: Ex U S. So it takes four to five X U S patients to add up to one U S. Patient. So our strategy is very much a volume strategy.

Speaker Change: Outside the U S.

Speaker Change: And then finally, what we're seeing in the real world in these countries, where we have market access that we've launched is the same consistent pattern of patient adds depending on the market.

Speaker Change: The HSA market dynamics, sometimes that's patients switching from other pro fees, sometimes there's growing the prophylaxis market with a with a drug like like Orla Dale at peak, we expect ex U S to equal about $200 million of the $1 billion in sales and what we see so far.

Speaker Change: <unk> gives us confidence that we'll get there and if tech sorrows, an analog here right.

Speaker Change: At a time that the U S starts to flatten out.

Speaker Change: Ex U S continues to grow so you have overall growth of the brand still so that's what we're expecting right now.

Jon P. Stonehouse: So that's what we're expecting right now. Understandable. Thank you very much, to all. The next question comes from Maury Raycroft with Jeffries. Please go ahead.

Speaker Change: Understood. Thank you very much.

Speaker Change: Youre welcome.

Speaker Change: The next question comes from Maury Raycroft with Jefferies. Please go ahead.

Maury Raycroft: Hi, good morning, and thanks for taking my questions. I just wanted to ask a clarifying question on the seasonality this quarter. Is that for the same reason as in first quarter 23, where there were budget issues with external charities, which increased the number of patients on the free drug program? Or what are you seeing this year so far? Sure, Maury.

Maury Raycroft: Hi, good morning, and thanks for taking my questions.

Maury Raycroft: Just wanted to ask a clarifying question on the seasonality. This quarter is that for the same reason as in first quarter 'twenty, three where there were budget issues with external charities, which increase the number of patients on free drug program or what are you seeing this year so far.

Speaker Change: Sure Marty.

Charlie Geyer: That's one of the situations, the Medicare issue. We've got a little bit of insight into that. What I'd say is it's not solved yet. It doesn't seem to be worse than that, but it's not solved.

Marty: That's that's one of the situations to Medicare issue.

Marty: We've got a little bit of insight into that and what I'd say is it's not solved yet it doesn't seem to be worse than <unk>, but it's not solved.

Charlie Geyer: We think next year, as I said earlier, with the IRA rolling in fully, we have expectations that that budget issue will be more solved in 2025. The main reason for the dip in Q1 is the broader... patients getting reauthorizations. And when that happens, we have to drop many patients back temporarily to free product. And then also, in the first quarters, it's the highest hit to gross to net because in the commercial market, we're helping pick up patient co-pays, and the majority of that happens in the first quarter. And you'll see a corresponding nice pop in the second quarter when we get those people back.

Marty: We think next year as I said earlier with the IRA Rolling in fully we have expectations that that that budget issue will be more solved in 2025. The main the main reason for the dip in Q1 is the broader.

Marty: <unk> is getting reauthorization.

Marty: And when that happens we have to drop many patients back temporarily to free product.

Marty: And then also in the first quarters, it's the highest hit to gross to net because of the commercial market we're helping.

Marty: Helping pick up patient co pays and the majority of that happens in the first quarter and you'll see.

Marty: A corresponding nice pop in the second quarter, when we get those people back to paid.

Charlie Geyer: Got it, makes sense. And one other quick question: what proportion of the 321 new patients are on short-term quick start and how long, on average, does it take to convert these patients to long-term pay patients? The 321 was the net growth across the whole year, so what we did say is that we ended the year with 1,104 patients on either paid therapy or long-term free product. There was also a sizable chunk of patients on short-term quick start, new patients coming in, and it usually takes us; we get the product out very quickly. For most patients, we get them to either a paid or free product within about a month.

Got it makes sense and one other quick question.

What proportion of the 321, new patients are on short term quick start and how long on average does it take to convert these patients long term pay patients.

Marty: The $3 21 was the net growth across the whole year. So what we did say is that we ended the year with a thousand.

Marty: Sorry.

Marty: 1104 patients on either paid therapy or long term.

Marty: Free product there was also.

Marty: Sizable chunk of patients on short term quick start new patients coming in.

Marty: And it usually takes us we get the product out very quickly.

Marty: For most patients we get them to either paid or <unk>.

Charlie Geyer: Got it. Okay, thanks for doing my question. Welcome. Your final question today comes from John Wallenby with Citizens. Please go ahead. Hi, this is Catherine, on behalf of John.

Marty: Free products within about a month.

Speaker Change: Got it okay. Thanks for taking my questions.

Speaker Change: Welcome.

Speaker Change: Your final question today comes from John Walsh with citizens. Please go ahead.

Speaker Change: Hi, Katherine on for John.

Catherine: I just have a question about how you're thinking about profitability versus your earlier pipeline, kind of prioritizing those. And then just a question about the data coming. Is it still coming in mid-year for the PNH trial?

John Bluth: <unk> about how you're thinking about profitability versus your earlier pipeline kind of prioritizing those and then just a question about the data coming is it still coming in midyear for.

Jon P. Stonehouse: Thanks. Yeah, I think we've been very clear about our path to profitability, and very excited to get to the point where, you know, we're independent of capital markets. We've been seeing over the past years the convergence of the lines between revenue and OPEX. We will continue to see it this year and beyond.

Speaker Change: The <unk> trial.

Speaker Change: Thanks.

Speaker Change: Yeah, I think we've been very clear about our path to profitability very excited to get to the point, where we're independent of capital markets. We've been seeing over the past year is that convergence of the lines between revenue and Opex. We continue to see it this year and beyond so being able to generate an operating profit this year.

Jon P. Stonehouse: So being able to generate an operating profit this year, getting towards both cash positivity and EPS at the end of next year and then achieving it in 2026, I think, puts us in a great spot. And we do that at the same time as continuing to invest in that early phase pipeline. So the two things coexist, and actually, the opportunity to be able to invest in, you know, whatever we can do to move as fast as we can in those periods because that early phase pipeline that we generated in or that we announced in November is, in fact, early phase, puts us in a spot where the expenditure within the next kind of three years is not as meaningful as it would be when you get them to pivotal trials. So, you know, I think And if there's anything we can do to accelerate, we absolutely will, and there's nothing to update on 10-0-13, nothing to change.

Speaker Change: Getting towards.

Speaker Change: Both cash positivity and EPS at the end of next year and then achieving it in 2026 I think is puts us in a great spot we do that at the same time as continuing to invest in that early phase pipeline.

Speaker Change: So.

Speaker Change: Two things the two things co exist.

Actually the opportunity to be able to invest in whatever we can do to move as fast as we can and in those periods because that early phase pipeline that we generated in our that we announced in November is in fact early phase.

Speaker Change: It puts us in a spot where the expenditure within the next three years as you know not as.

Speaker Change: Meaningful as it would be when you get them to a pivotal trials so.

I think the company is in a great spot and if theres anything we can do to accelerate we absolutely will.

And there's nothing to update on 10 zero 13, nothing's changed on the timeline.

Jon P. Stonehouse: Thank you. 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: Welcome.

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.

Jon P. Stonehouse: Thank you. So one of the things that we're hearing from investors is that they have so many things coming at them. And it's hard to keep up with the opportunities to invest in. And if you're in that camp, a question you may want to stop and ask yourself is, how many companies do I have in my portfolio that have a growing product? have a discovery engine that created the growing product, and have a pipeline that came from the discovery engine that's gonna create another growing product or more, and has an accelerated path to profitability where we're probably gonna be cashflow positive or near that in the second half of next year. And if the answer to that is none or too few, and you wanna diversify your portfolio, reach out to us.

Jon P. Stonehouse: Thank you so one of the things that we're hearing from investors is is they have so many things coming at them and.

Jon P. Stonehouse: And it's hard to keep up with the opportunities to invest in.

Jon P. Stonehouse: And if you're in that camp, but question you may want to stop and ask yourself is how many companies do I have in my portfolio that have a growing product have a discovery engine that created the growing product have a pipeline that came from the discovery engine, that's going to create another growing product or more.

Jon P. Stonehouse: And it has an accelerated path to profitability, where we're probably going to be cash flow positive or near that in the second half of next year.

Jon P. Stonehouse: And if the answer to that is none or too few.

And you want to diversify your pipe your portfolio reach out to US we're happy to get you up to speed on our company and and answer any questions you may have.

Operator: We're happy to get you up to speed on our company and answer any questions you may have. So, have a great day and thanks for your interest in BioCryst. Thank you. Thank you. Thank you. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect. BF-WATCH TV 2021

Speaker Change: So have a great day and thanks for your interest in Biocryst.

Speaker Change: Yeah.

Okay.

Speaker Change: The conference has now concluded. Thank you for attending today's presentation you may now disconnect.

Speaker Change: Yes.

Speaker Change: Hi.

Speaker Change: Yeah.

Speaker Change: [music].

Speaker Change: Okay.