Q1 2024 Pharming Group NV Earnings Call

[music].

Operator: Good day, and thank you for standing by. Welcome to the Pharming Group NVQ1 2024 results conference call and webcast.

Okay.

Speaker Change: Good day and thank you for standing by welcome to the farming group N V Q1, 'twenty 'twenty four results conference call and webcast. At this time all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session.

Operator: At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 1 on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star 1 and 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Simon De Vries. Please go ahead.

Speaker Change: Ask that question you had necessity you will need to press star one one on your telephone you will then hear an automated message of Boston to harness race.

Speaker Change: A waste of your question. Please press star one on one again, please be advised that today's conference is being recorded.

Speaker Change: Now I'd like to hand, the conference over to your speaker today I'm on the raise please go ahead.

Sijmen de Vries: Thank you very much, Sandra, and welcome, ladies and gentlemen, to this first quarterly results conference. I'm here with my, next slide please. I'm here with my three colleagues in order of speaking, Stephen Toor, our Chief Commercial Officer who's joining us from our New Jersey office, Dr. Anurag Relan, our Chief Medical Officer joining us from our US office as well, and Jeroen Wakkerman, our Chief Financial Officer, based with me here in Leiden.

Speaker Change: Thank you very much.

Boston: And welcome ladies and gentlemen.

Boston: These are our first quarter results conference I'm here with my next slide piece I'm here with my my three colleagues.

Boston: In order of speaking Steven Tour, our Chief Commercial officer, who is joining us from our New Jersey office.

Stephen Toor: And Rocco Allen Chief.

Chief Medical Officer.

Speaker Change: Joining us from the U S office, as well and you don't walk them up.

Speaker Change: Our Chief Financial Officer.

Sijmen de Vries: And before I do that, I would like to point out on the next slide, please, number three, that is the forward-looking statement slide. We will be making forward-looking statements today in our presentation, and those are based upon our current plans and, you know, and insights into the, and situations in the current market circumstances. And, of course, actual results may differ from these forward-looking statements, so you cannot necessarily rely on them. So having said that, I would like to go to slide number four and, maybe even further onwards to slide number five, because you've seen my picture already.

Speaker Change: Base would be here in may.

Speaker Change: And before I do that I would like to point out to the next slide. Please number three it is the forward looking statements slides that we will be making forward looking statements today in our presentation and those are based upon our current plans.

Speaker Change: No.

Speaker Change: And insights of the and situations Oh.

Speaker Change: The current market circumstances and of course actual results may differ from these from these forward looking statements or you cannot.

Speaker Change: Niall dose.

Speaker Change: Having said that I would like to go to slide number four and maybe even onwards to slide number five because you've seen my picture already.

Sijmen de Vries: Yes, and here we are. We're building this global rare disease, leading global rare disease biopharmaceutical company. And we have, we do that based on three pillars. And this is a very familiar slice for you who have been here before.

Speaker Change: Yes, and here we are rebuilding is global.

Speaker Change: Leading global rare disease, Biopharma company and we as we.

Speaker Change: We do that.

Speaker Change: Based on three pillars and this is a very familiar slide for you gave before.

Sijmen de Vries: On the left-hand side, the foundation of our company, the product Reconest, which comes from our own research and has already been on the U.S. market for almost 10 years. It was approved in July 2014. Recombinant protein replacement therapy for hereditary angioedema attacks

Speaker Change: Left hand side.

Speaker Change: Foundation of our company the protocol <unk> that comes from our own research.

Speaker Change: As has already been on the U S market for almost 10 years. It was approved in July.

Speaker Change: July 2014.

Speaker Change: Recombinant protein replacement therapy for Herritarrok angioedema attacks and as you can see we are still growing this product and you know we had 8% growth. The first last year this quarter good growth.

Sijmen de Vries: And as you can see, we are still growing this product, and you know, we had an 8% growth versus last year this quarter. We had good growth last year as well. And we see increasing numbers of prescribers and patients. And there are many options for these patients available, but Reconest continues to play an important role, and we expect it to continue for the foreseeable future. And Steven will talk a lot more about that in his part of the presentation.

Speaker Change: Last year, as well and we see increasing numbers of prescribers and patients.

Speaker Change: And there's many options for these patients accretable, but <unk> continues to play an important role and we expect it to be continuing for the foreseeable future and Stephen will talk a lot more about that in his part of the presentation.

Sijmen de Vries: Next, you see here, Joenja, the product we in-licensed from Novartis for the treatment of APS, an ultra-rare immune disorder, a new disease that was only discovered 10 years ago, and we already have the first disease-modifying drug on the market that we launched now a year ago. You see, we had a very successful introduction of the product in the US market. Stephen will allude to that as well.

Stephen Toor: Next you see there.

Stephen Toor: Joe and John the product we in licensed from Novartis for the treatment of Aps and ultra rare immune disorder, a new disease that it was only discovered 10 years ago and we already have the first disease modifying drug on the market, we launched now a year ago.

Stephen Toor: We had a very successful introduction of the product in the U S. Steve will allude to that as well.

Sijmen de Vries: You know, we're very proud that we can actually, you know, record 9.6 million sales in this quarter, good growth versus 4Q of last year. And you see here, if you add both numbers, we realized 28 million dollars of sales for this product in the first 12 months on the market. It's a new way to describe an ultra-rare disease, and there's a very strong focus there for patient finding. Both Stephen and Anurag will talk about that, how we go about doing that to find those patients. We're also very pleased to see that, very recently, we got the second approval in Israel at the end of April 24.

Stephen Toor: We're very proud that we can actually record.

Stephen Toor: <unk> $9 6 million sales in this quarter good growth versus set for Q of last year and you see here if you add both numbers weeks we realized.

Stephen Toor: $28 million of sales for this product in the first 12 months on the market. It's annuity described an ultra rare disease and there is a very strong focus therefore patient finding both Stephen and Iraq will talk about that and how we go about that to find dose those patients. We're also very.

Stephen Toor: Pleased to see that very recently, we got the second approval in Israel at the end of April 24.

Stephen Toor: We have a lot of regulatory reviews ongoing and law trials ongoing in Iraq will talk about that a lot more and on the right hand side.

Sijmen de Vries: We have a lot of regulatory reviews ongoing and a lot of trials ongoing, and Anurag will talk about that. And on the right-hand side, the possibility to leverage our commercialization infrastructure both in the U.S. and outside of the U.S. by not only finding new compounds, but we're hunting for clinical stage or later stage compounds to in-license or acquire, to actually leverage. But first and foremost, we have a very interesting opportunity with Lenny-Odyssey to develop it further for a second indication for primary immune deficiencies with immune dysregulation beyond APDS, which we are preparing in the final stages for a phase two study.

Stephen Toor: The possibility to leverage our commercialization infrastructure, both in the U S and outside of the U S by not only our you know.

Stephen Toor: Finding new compounds with hunting for our four clinical stage or later stage compounds are to in license or acquire to actually leverage bust first and foremost we have a very interesting opportunity and lineal is shipped to the south you fill up its further for a second indication for prime.

Stephen Toor: Mary immune deficiencies with immune Dysregulation beyond <unk>, where we are preparing in final stages of preparing a phase II.

Sijmen de Vries: And in addition, we're working on a third primary immune deficiency indication in the early stage at this point in time. And Anurag will talk about that a lot more. And on the bottom of the slide, you see that we have total revenue guidance out between $280 and $295 million for this year. You know, driven, of course, by Jywanja. But, you know, the foundation is, of course, Rufinest underneath

Stephen Toor: Study and in addition, we're working on a third.

On a third.

Stephen Toor: Primary immune deficiency indication and early stage at this point in time and interact will talk about that I want more and on the bottom of the slide you see that we have.

Stephen Toor: Total revenue guidance out between 200, and AGN $295 million for this year.

Stephen Toor: Given of course by Joanne job, but the foundation is of course refinanced underneath that and then you see the next slide a little bit more in detail because we're going to talk a lot about the potential for <unk> today.

Sijmen de Vries: And then you see the next slide a little bit more in detail because we're going to talk a lot about the potential for Jywanja today. Joentgen for APDS is the first stage where we are currently in the market with a 12-plus indication in the U.S., where we have already found a significant portion of the identified patients on paid therapy. We have a lot of ongoing search for patients and so-called variants of uncertain significant mutations. That's ongoing.

Stephen Toor: <unk> Energia for Apd as is the first stage, where we are currently now in a market, where the 12 plus indication in the U S.

Stephen Toor: While we already found a significant portion of the identified patients on therapy or we have a lot of ongoing search for patients and so called variants of uncertain significance mutations is ongoing.

Sijmen de Vries: The next step, of course, which is, and this is, of course, an interesting observation on mobile, almost $1.1 million of sales in this quarter already outside of the U.S. So, in other words, we're starting to work on the global expansion of the product, and the pediatric studies will further boost that to get a full label and full geographic coverage for Joentgen APDS. Then, as I said earlier, the bigger indication that we are starting a concept trial in the not-too-distant future for the bigger indication of PIDs with immune dysregulation with similar symptomatology to APDS. So having given you this introduction, I would like to now hand over to my next speaker, Stephen Toor, our Chief Commercial Officer. Steve, over to you. Thank you so much, everybody.

Stephen Toor: The next step of course, a very or a C and that's of course, an interesting observation of mobile almost one point, while malian dollars of sales in this quarter already outside of the U S. So in other words, we're starting to work on the global expansion of the product and on the and the pediatric studies will further boost ACH.

Stephen Toor: To get a full label.

Stephen Toor: And Ah full geographic coverage charge originated yes, Dan as I said already earlier, the bigger indication that we are starting a concept.

Stephen Toor: Concept truck in the not so distant future for the bigger indication of Pid's with immune dysregulation with similar symptomatology two to Aps, So having a giving you. This introduction I would like to now point out.

Stephen Toor: Thank you very much. Okay, thank you so much. So, is that the background you're on, Anurag?

Stephen Toor: I would like to now hand over to <unk> to my next to the next speaker to Steven <unk>, Our Chief commercial officer, Steve over to you. Thank.

Stephen Toor: Everybody.

Stephen Toor: Yes.

Stephen Toor: Okay.

Stephen Toor: Okay.

Stephen Toor: Okay.

Stephen Toor:

Stephen Toor: So what.

Stephen Toor: Is it in Europe.

Stephen Toor: Yeah.

Stephen Toor: Okay, let's go to the next slide. So, the key features of the international trade haven't continued to underpin routes over the last 10 years since launch.

Stephen Toor: Okay.

Stephen Toor: But.

Stephen Toor: So the key.

Stephen Toor: The key fee initiatives.

Stephen Toor: You too.

Stephen Toor: Over the last years.

Stephen Toor: Those unique work attributes, the exceptional customer service and execution by our customer-facing teams, are why we continue to remain a highly relevant conversation in the H.A.P. That removes the case, despite the free information of the treatment landscape with prophylactic immunities, of the generic suspicion of mechanicality, and it will continue to remain the case in the face of oral acute competition in the coming years. HA patients usually have a more severe cause of disease, and they need a virtually guaranteed and fast efficacy that stops an attack in its tracks. Rukiness' unique product features and the mode of administration deliver that in a way that future options can't.

Stephen Toor: Launch.

Stephen Toor: Those unique attributes.

Stephen Toor: Mr Evensen execution, but in the face of claims.

Stephen Toor: Is one continues to be played out.

Stephen Toor: Conversation.

Stephen Toor: That.

Stephen Toor: Right.

Stephen Toor: As the treatment landscape.

Stephen Toor: In aerospace, we should be kind of thing.

Stephen Toor: And it continues to remain in the face of competition.

Stephen Toor: Competition in coming years.

Stephen Toor: H H.

Stephen Toor: Generally it will be closer to date.

Stephen Toor: And they need a virtually guarantee and fast and first efficacy that stops in the attack in its tracks.

Stephen Toor: <unk> unique product features in the motive administration deliver that in a way that future auctions call.

Stephen Toor: So, as you know, 2023 was a strong year with solid growth in prescribers, new patients, and sales. That success was in spite of the market-wide event related to reimbursement for government patients in Q1. And in Q4, we've seen less of an impact as the patients' out-of-pocket responsibility almost halved. The strength of leading indicators has continued into this year, and we've had a strong Q1, up 8% on the prior year, and we exit Q1 2024 on track to achieve the revenue guidance, which, as previously discussed, is assumed to be low to mid-single-digit growth for ReConnect. Can you go to Joanne's slide, please?

Stephen Toor: So as you know 2023 was a strong year with solid growth in prescribers new patients in sales that was successful despite of the market would have been related to reimbursement for government patients in Q1, and Q4, we've seen less of an impact as the patients' out of pocket responsibility almost half the.

Stephen Toor: The strength of bleeding in the cases continued into this year and we've had a strong Q1 up 8% on prior year and we exit 2020 Q1, 'twenty full on track to achieve the revenue guidance, which as previously discussed as it seemed to be low to mid single digit growth.

Stephen Toor: For recognize.

Stephen Toor: If you go to the joined the slide please.

Stephen Toor: As you know, we were strung out the gate with the launch of Joentgen, with patients fully reimbursed within days. And that momentum built through year one, and it continues into 2024. So we now have 83 patients fully reimbursed with Joentgen, and five more are in the process. With 15 newly diagnosed patients in court, we have taken us past 220, close to half the number of patients the literature suggests are out there, although we believe there are more, and we have over 50 more diagnosed patients who we're working with, with their physicians to enrol into our program.

Stephen Toor: As you know, we've Australia the gate with the launch of <unk> with patients fully reimbursed within days and that momentum built through year, one and it continues into 2024. So we now have 83 patients fully reimbursed with.

Stephen Toor: Probably more in process being process with 15 newly diagnosed patients in the quarter taken has passed 220 close to half the number of patients. The literature suggests that are out there. Although we believe there are more.

Stephen Toor: And we have over 50 more diagnosed patients whose doctors who.

And we're working with their physicians to enroll into our program plus across 50, plus pediatric patients with re diagnose you could potentially go GA treatment when the pediatric label expansion is approved.

Stephen Toor: Plus, of course, 50 plus paediatric patients will be re-diagnosed so you can potentially go and join the treatment when the paediatric label expansion is approved. So all this means we exit Q1 just shy of 10 million in sales and 21% up on the prior quarter, as we discussed in March on our 2023 four-year call. As we convert the caseload identifier at launch, our focus moving forward remains finding new patients. And given APDS is not the seminal dominant condition, this means testing families to uncover additional patients with this progressive disease, so they too can benefit from management and treatment.

Stephen Toor: So all this means we exit Q1, just like $10 million in sales and 21% up from prior quarter.

Stephen Toor: As we discussed in March 2023 fully full year call.

Stephen Toor: As we convert the caseload identified at launch our focus moving forward remains finding new patients.

Stephen Toor: And given <unk> is not with some dominant condition. This means testing families to uncover additional patients with this progressive disease. So they too can benefit from management and treatment.

Stephen Toor: We're also working to resolve VUSs for the many patients who have these results, which Anurag will discuss further, and as with Rukminis, the results for the quarter are in line with our financial guidance for the year. Can you go to the next slide, please?

Stephen Toor: We're also working to resolve the U S is for the many patients who have these results, which I will discuss further.

Stephen Toor: Yeah.

Stephen Toor: SP with recommenced the results for the quarter in line with our financial guidance for the year.

Speaker Change: You go to the next slide please.

Stephen Toor: So our U.S. teams continue their patient-finding education and genetic testing efforts to build the APDS patient base. At the same time, we remain laser-focused on root canister execution. And while at different stages in the commercial cycle, both Rukiness and Joenge are critical to our growth. Now, I've already covered the U.S. here that you see on the first pillar.

Speaker Change: So our U S teams continue their patient for any education of genetic testing efforts to build the Pds patient base at the same time, we remain laser focused on ruthless execution, while at different stages in the commercial cycle both route.

And Joe Andrew are critical to our growth.

Speaker Change: I've already covered.

Speaker Change: The U S.

Speaker Change: You see on the first pillar.

Stephen Toor: For Ex-US, alongside the US launch, we continue to build our capabilities in preparation for launches in the EU, UK, Japan, and Australia, and other Asia-Pacific countries. Our U.S. teams are focused on both educating, finding potential patients, testing, and diagnosing, and continuing to build that patient funnel, all in readiness for the steady flow of launches that we have in the coming years. And so far, we've identified over 800 patients in those key launch markets.

Speaker Change: For ex U S alongside the U S launch, we continue to build our capabilities in preparation for launches in the EU UK, Japan and Australia.

Speaker Change: And other Asia Pacific countries.

Speaker Change: <unk> teams.

Speaker Change: Our focused on.

Stephen Toor: And we also see multiple years of growth ahead for Joentgen, with initiatives such as family testing and VUS validation that should contribute modest additions to patient numbers in 2024. We expect those initiatives to have a more significant impact in 2025, when we see the potential for a few hundred patients to be on Joentgen. And all together, the APDS opportunity is at least 1.5 million patients. 1.5 patients per million, or approximately 2,000 patients in these key markets, of which we've already found a large number.

Speaker Change: But it's educating finding potential patients testing in diagnosing.

Speaker Change: And continue to build that patient funnel all in readiness for the steady flow of launches that we have in the coming years and so far we've identified over 800 patients who most key launch markets.

Speaker Change: And we also see multiple years of growth ahead for Julian jet with initiatives such as family testing validation that should contribute modest additions to patient homes. In 2024, we expect those initiatives such as a more significant impact in 2025, when we see a potential.

Speaker Change: A few hundred patients to be on Gilenya.

Speaker Change: Altogether, the Pds opportunity as you know is at least $1 5 million patients.

Speaker Change: One five sorry patients per million or approximately 2000 patients in these key markets of which we've already found a large number.

Stephen Toor: And while the ex-U.S. prices are expected to be lower than those in the U.S., the overall APDS opportunity is still significant. So while much of our organization is focused on Joe NGF or APDS, we're also, as you see in the final column, focused on developing learning oversight for additional indications. So this is a good moment to hand over to our chief medical officer, Anurag.

Speaker Change: And while the ex U S prices are expected to be lower than those in the U S. The overall <unk> opportunity is still significant.

So much of our organization is focused on FPGA on Joe and Jeff Ray Pds were also as you've seen the final column focus on developing lineage <unk> for additional indications. So this is a good moment to hand over to our chief Medical Officer and Alright.

Speaker Change: Thanks, Steve.

Speaker Change: Next slide please.

Anurag Relan: And then, if we can go to the U.S. launch of Joe and just slide, next slide, thank you. And as you mentioned, Steve, we've had a strong launch of JOANJA in the U.S. This reflects both the unmet need and the clinical experience with JOANJA. And to review, JOANJA is approved for the treatment of APDS in adult and pediatric patients 12 years of age and older. This approval was based on data from a randomized placebo-controlled study that showed JOANJA met both primary endpoints with significant benefits also seen in the secondary and other exploratory endpoints. Importantly, what we've seen across the development program is that Chuanjia has been generally safe and well tolerated.

And then if we can go to the U S launch of Joanne just slide next slide thank you.

Speaker Change: And as you mentioned, Steve we've had a strong launch of Joanna in the U S. This reflects both the unmet need and the clinical experience with <unk>.

Speaker Change: And to review Joanna is approved for the treatment of Atvs in adult and pediatric patients 12 years of age and older and this approval was based on data from a randomized placebo controlled study that showed no angina met both primary endpoints with.

Speaker Change: Significant benefits are also seen in the secondary or exploratory endpoints.

Anurag Relan: And this data has been seen not only in the randomized study, but also in the ongoing long-term open-label extension study. In that study, we also saw benefits with patients being able to reduce or discontinue their use of immune globulin replacement therapy, and we also saw reductions in infection rates over time. We will continue to share data on the long-term use of JoAnja from these studies, as well as from post-marketing experience. Next slide.

Speaker Change: Importantly, what we've seen across the development program is the trend has been generally safe and well tolerated and this data has been seen not only in the randomized study, but also in the ongoing long term open label extension study.

Speaker Change: In that study, we also saw benefits with patients being able to reduce or discontinue their use of <unk>.

Speaker Change: Immune globulin replacement therapy.

Speaker Change: Also saw reductions in infection rates overtime.

Speaker Change: We continue to share this data on the long term use of Joanna <unk>.

Speaker Change: From these studies as well as from post marketing experiences.

Speaker Change: Next slide.

Anurag Relan: And as with many rare diseases, patients have a long journey to reach a diagnosis. We have several efforts now ongoing to help patients get a correct diagnosis quickly. The FIRST centers around medical education to raise awareness about APDF and share data on Lenny illnesses.

Speaker Change: And as with many rare diseases patients had a long journey to reach a diagnosis. We have several efforts now ongoing to help patients get a correct diagnosis quickly.

Speaker Change: The first centers around medical education to raise awareness about a PDF and shared data on linear offices.

Anurag Relan: For example, recently, we shared information about the seriousness of APDS by publishing data on early mortality and the frequency of lymphoma in these patients. We've also been discussing, for example, the frequency of bronchiectasis, a lung complication that is often seen in these patients at a young age, to help doctors be able to recognize the types of symptoms that APDS patients may have and to be able to perform a genetic test, which is actually the only way to make a diagnosis. Now, to make that diagnosis, we've made genetic testing available through a sponsored, no-cost testing program.

Speaker Change: For example, recently we've shared information about the seriousness a PDF by publishing data on early mortality and the frequency of La Palma and these patients. We've also been discussing for example, the frequency of bronchiectasis a lung complications that is often seen in these patients at a young age to help Dr.

Speaker Change: <unk> be able to recognize the types of symptoms that patients may have and to be able to perform a genetic test, which is actually the only way to make a diagnosis.

Speaker Change: Now to make that diagnosis.

Speaker Change: Made that genetic testing available through a sponsored no cost testing program. We also have assistance from genetic counselors to be able to help patients and physicians interpret the results and we're working closely with these patients and their doctors to also help perform family testing because half of inherited disease, we know that.

Anurag Relan: We also have assistance from genetic counselors to be able to help patients and physicians interpret the results. And we're working closely with these patients and their doctors to also help perform family testing, because as an inherited disease, we know that there are more patients than the ones that we've uncovered so far. We found, in fact, that most patients have not had proper family testing, such as testing of parents or siblings, to ensure that all of those members of their families can also receive a correct diagnosis. And we have several programs now in place to help assist with that type of effort.

Speaker Change: There are more patients than the patients that we've uncovered so far.

Speaker Change: We found in fact that most patients have not had proper family testing such as testing of parents or siblings.

Speaker Change: Ensure that all of those members of their family can also receive a correct diagnosis and we have several programs now in place.

Speaker Change: <unk> assists with that type of effort.

Anurag Relan: And as you've heard us talk about several times now, getting a genetic test is important for these patients, but also interpreting the result is critical. And unfortunately, many patients can get a result called a variant of uncertain significance after they get a genetic test. What this means is that these patients have a variant or a mutation that hasn't been previously described. And what we found is that there are a significant number of patients who have actually already received VUS test results. Just in the U.S., alone, there are 1,100 such patients. We're working closely now with a number of groups to help curate all of this data and put that into a single central database.

Speaker Change: And as you heard us talk about several times now getting a genetic test is important for these patients but also interpret as a result is critical and unfortunately, many patients can after they kind of genetic tests can get resolved called a variants of uncertain significance. What this means is that these patients have a variants or mutations that hasnt.

Speaker Change: <unk> previously described.

Speaker Change: And what we found is that there is a significant number of patients who have actually already received a V. U S. SaaS results just in the U S.

Speaker Change: 100, such patients we're working closely now with a number of groups to help curate all of this data and put that into a single central database.

Anurag Relan: And on top of that, what we need to do is perform further testing to determine whether that variant is disease-causing or not. Recently, we were able to start a functional testing program whereby patients can get access to a functional test, and that can help them determine if they have APDS. And we're already seeing the results of those in the first quarter where patients who had a BUS result got a functional test and then eventually got a diagnosis of APDS, some of whom are already on Joanja now.

Speaker Change: And on top of that what we need to do is perform further testing to determine whether that variant as disease, causing or not.

Speaker Change: Recently, we've been able to start a functional testing program whereby patients can get access to a functional test that can help them determine if they have atvs and we're seeing already the results of those in the first quarter were patients who had a U S result.

Speaker Change: Functional tests and then eventually caught a diagnosis of <unk> some of whom already on your lines are now.

Anurag Relan: And to address this problem more thoroughly and more completely, we also have a large study called a MAVE study, which will allow us to determine all possible variants, and we're hoping that this will read out by the end of the fourth quarter. I should say we're expecting that this is going to read out by the end of the fourth quarter to eventually answer the question of which patients who have a BUS actually have a PDS. Next slide.

Speaker Change: And to address this problem more thoroughly on more completely we also have a large study called <unk> study, which will allow us to determine.

Speaker Change: All possible variants and we're hoping that this reads out by the end of the fourth quarter I.

Speaker Change: I should say, we're expecting that this is going to read out by the end of the fourth quarter to be able to eventually answer the question of.

Speaker Change: Which patients.

Half of the U S actually have a Pds group.

Speaker Change: Next slide.

Anurag Relan: In addition to the work that we're doing with JoAnna in the U.S., we have several projects to bring JoAnna to patients in other countries and to younger patients. We have an application under review, for example, in Europe, and we're awaiting a CHMP opinion now. We anticipate being on the May agenda for a CHMP opinion, so that would be later this month. We also have completed enrollment in our Japanese clinical study.

Speaker Change: In addition to the work that we're doing with Joe and in the U S. We have several projects to bring two engines of patients in other countries and to younger patients.

Speaker Change: Have an applications under review for example that in Europe, and we are waiting now.

Speaker Change: <unk> opinion, we anticipate being on the May agenda for AC HMP opinion, so that would be later this month.

Speaker Change: We also have completed enrollment in our Japanese clinical study.

Anurag Relan: And we're working with the regulatory authority there to determine the filing strategy following the completion of the clinical trials that are ongoing. And then we have two pediatric studies. The first is on children ages four to 11, and enrollment has already completed there.

Speaker Change: And we're working with the regulatory authority there to determine the filing strategy. Following the completion of the clinical trials that are ongoing.

Speaker Change: And then we'd have to pediatric settings. The first is on children ages four to 11 and enrollment is completed there and then we have an ongoing study that you see on the right for children ages, one to six year old using granules and we've had the first patient dosed last year and enrollment is continuing there.

Anurag Relan: And then we have an ongoing study that you see on the right for children ages one to six-years-old using granules. And we had the first patient dosed last year, and enrollment is continuing there. Considering all of these clinical trials, as well as the expanded access and named patient programs, we have 138 patients receiving JoAnja through these various programs. And as you heard from Simon, we recently received marketing authorization in Israel.

Speaker Change: Considering all of these clinical trials as well as expanded access and named patient programs would have 138 patients receiving Joanna through these various programs and thats It hurts from Simon.

Speaker Change: We also received recently the marketing authorization in Israel would have a number of reviews ongoing including in the UK, Canada, and Australia, and we're expecting regulatory action on those reviews in the course of 2024 and 2025.

Anurag Relan: We have a number of reviews ongoing, including in the UK, Canada, and Australia, and we're expecting regulatory action on those reviews in the course of 2024 and 2025. And we're very excited about the possibility of using Leni-ELSIB outside of APDS, so I'll talk a little bit more about that now. On the next slide, you can begin to see that through our work in APDS, we have a better understanding of the broader PID landscape. Next slide, please.

Speaker Change: And then we're very excited also about the possibility of using money also outside of <unk> and I'll be talking a little bit more about that now.

Speaker Change: And the next slide you can begin to see through our work in <unk>, we have a better understanding of the broader PIV landscape.

Speaker Change: Next slide please.

Anurag Relan: And what we see is that there are a large number of PIDs. Obviously, these PIDs have an increased risk of infection. But we also see there's a subgroup of PIDs that have not only this phenotype of increased risk of infection but also have this immune dysregulation phenotype. And what I'm referring to here is this concept where there's abnormal lymphopoietin proliferation and, frequently, autoimmunity. APDS, of course, is an example of such a primary immune deficiency with immune dysregulation.

Speaker Change: And what we see is that there are a large number of <unk>.

Speaker Change: Obviously these <unk> have an increased risk of infection, but we also see theres a subgroup.

Speaker Change: That have not only this phenotype of increased risk of infection, but also have this immune dysregulation phenotype of what I'm, referring to here is this concept, where there's abnormal liver proliferation and frequently autoimmunity and Pds of course is an example of such a primary immune deficiency with immune <unk>.

Anurag Relan: In the next slides, I'll talk a little bit about this first program, but we're already moving forward on a second non-APDS-PID indication, again, with encouragement from experts across the world suggesting that we should study leniolisin in these populations. Next slide, please.

Speaker Change: <unk>.

Speaker Change: And the next slides I will talk a little bit about this first program.

Speaker Change: We're already moving forward on a second non <unk> indications again with encouragement from experts across the world.

Speaker Change: Suggesting that we should study and he also in these populations next.

Speaker Change: Next slide please.

Anurag Relan: And what these experts are telling us is that there are many patients with clinical features similar to APDS that have similar disordered PI3K signaling but don't necessarily have the PI3K genetic abnormalities that we see in APDS. And that signaling, not surprisingly, leads to the clinical metastatic sites that you see on the right. And you see that these are very similar to the types of things that we see with APDS. Namely, we see abnormal lipoproliferation, so large lymph nodes, and large spleens. We see this also in the gut.

Speaker Change: And what these experts are telling us is that there are many patients with clinical features similar to a PDF that have similar disorder Pi three kinase signaling, but don't necessarily have the pi three K genetic abnormalities that we see.

Speaker Change: And that signaling not surprisingly leads to the clinical manifestations that you see on the right and you see that these are very similar to the types of things that we see with Aps, mainly we see abnormal literal proliferation. So large once nellix large swings.

Anurag Relan: On top of that, there's the problem of autoimmunity, again signaling the abnormal dysregulation in these patients' immune system. We see GI disease, lung disease, frequent infections, of course. And unfortunately, these patients also have a predilection toward developing early lymphoma. So there's clearly a high unmet need here.

Speaker Change: We see this also in the gut on.

Speaker Change: On top of that there is a problem of autoimmunity again.

Speaker Change: Signaling the abnormal dysregulation in these patient's immune system, we see Gi disease lung disease. The frequent infections of course and unfortunately. These patients also have a predilection toward developing early lymphoma. So there's clearly a high unmet need here and not surprisingly given that there is.

Anurag Relan: And not surprisingly, given that there is abnormal signaling and that the symptoms you see here on the right are similar to APDS, the treatments that are being applied for these patients, such as rapamycin and mTOR inhibitors or other immunosuppressive agents, have also been applied in this population. So overall, we see that there's a strong basis to study laniolacid in this group of patients. And you see some of the genetic abnormalities that are mentioned there, including the condition called ALPS caused by an abnormality in the FAST gene, CTLA-4, and T10.

Speaker Change: Abnormal signaling and the symptoms you see there on the right are similar to Atvs. The treatments that are being applied for these patients such as Rapamycin and EMCORE inhibitor or other immunosuppressive agents have also applied in this population.

Speaker Change: So overall, we see that there's a strong basis to study any wholesale MBS group of patients and you see some of the genetic abnormalities that are mentioned there, including the condition called Alps caused by an abnormality in the SaaS Jean <unk>, four and PD 10.

Anurag Relan: And on the next slide, you can see a little bit about the work that we're doing to advance this program. And we're working closely with the team at the NIH, and this includes Dr. Rao, who led the APDS clinical trial program at the NIH, and Dr. Uzell, who actually was part of the team that led to the discovery of APDS 10 years ago. And we're starting this phase two proof-of-concept dose-finding study.

Speaker Change: And on the next slide you can see a little bit about the work that we're doing to advance this program.

Speaker Change: And we're working closely with the team at the NIH and this includes stock Corral, who led the <unk> clinical trial program at the NIH and Dr. <unk> Zhao who actually was part of the team that led to the discovery of Atvs 10 years ago, and we're starting this phase II proof of concept dose finding study we're starting at doses that we used.

Anurag Relan: We're starting at doses that were used in the Leniolis development program for APDS also, so starting at the 10 milligram dose. And as I mentioned, we're using patients that have a number of abnormalities, including those listed there. The primary goal, of course, is to look at safety and tolerability, and we're also going to be looking at pharmacokinetic measures and various efficacy measures. And patients will receive doses for a number of weeks and then increase as they progress through the program.

Speaker Change: In the linear oldest of development program for Aps also starting with a 10 milligram dose and as I mentioned, we are using.

Speaker Change: Patients that have a number of abnormalities, including those listed there.

Speaker Change: Primary goal of course is to look at safety and Tolerability and we're also going to be looking at pharmacokinetic measures and various efficacy measures and patients will receive doses for.

Speaker Change: For a number of weeks and then escalate as it progressed through the program.

Anurag Relan: And the goal is to be able to pick the best dose regimen for the phase three study. And if we go to the next slide, we can see some of the populations that have already been characterized with these various genetic abnormalities. And you can see here several large cohorts with each of these different genetic forms of primary immune deficiency. And these large cohorts together tell us that there is a treatable population of approximately five patients per million across the world.

Speaker Change: And the goal is to be able to pick the best dose regimen for the phase III study.

Speaker Change: And if we go to the next slide we can see some of the populations that have already been characterized with these various genetic abnormalities and you can see here several large cohorts with each of the use different genetic forms of primary immune deficiency and these large cohorts together tell us that there is a treatable.

Speaker Change: Population.

Speaker Change: Proximately five patients per million.

Speaker Change: Across the world here.

Anurag Relan: So when we put all of this together, you can see we're very enthusiastic about the potential of joentia in APDS as well as beyond APDS in these various abnormalities that have clinical features that are similar to APDS. And with that, I will turn it over to my colleague Jeroen to talk about our finances.

Speaker Change: So we're when we put all of this together you can see we're very enthusiastic about the potential of <unk> in a P. D S as well as beyond a PDF and these various abnormalities that have clinical features that are similar to Aps and with that I will turn it over to my colleague here one to talk about our financials.

Speaker Change: Thank you very much.

Jeroen Wakkerman: Thank you very much, Anurag. Next slide. So in the first quarter of 2024, revenue increased by 31% to 55.6 million US dollars. And that's a comparison to the first quarter of last year. And this is driven by both the U.S. commercial launch of Joentia and revenue growth of Rukonesk. Rupert Nash's revenues increased by 8% to 46 million compared to the first quarter last year, and Joanne Jabb or Lenny Elisip's revenues were 9.6 million, and that's a 21% increase compared to the fourth quarter of last year. So overall, we're well on track for 2024 to hit our total revenue guidance, which is between 280 and 295 million US dollars, or 14 to 20% revenue growth.

Speaker Change: Jack.

Speaker Change: Next slide please.

Jack: So in the first quarter of 2024, the revenues increased by 31% to $55 $6 million.

Jack: And that's a comparison to first quarter of last year and this is driven by both the U S commercial launch of <unk>.

Jack: Revenue growth of <unk>.

Jack: <unk> revenues increased by 8% to $46 million compared to first quarter last year and Joanne job.

Jack: <unk> revenues were $9 6 million and Thats, a 21% increase compared to the fourth quarter of last year.

Jack: So overall, we are well on track for 2024 to hit our total revenue guidance, which is between.

280, and $295 million or 14% to 20% revenue growth.

Jeroen Wakkerman: Looking at gross profit, it increased in line with the sales increase, and gross margin dropped slightly, and that was because of a non-recurring inventory impairment of just over $2 million. [inaudible] Looking at OPEX, it went up compared to last year's first quarter, but it went down if I compare it to Q4 last year, as we already indicated at the time. So this increase versus last year was planned, and we are increasing the OPEX to support the launch of Joentgen in the US but also preparation for the launch outside of the US.

Jack: Looking at gross profit.

Jack: <unk> increased in line with the sales increase and gross margin.

Jack: Dropped slightly and that was because of a nonrecurring.

Jack: Inventory impairment of just over $2 million.

Jack: Looking at Opex went up compared to last year's first quarter.

Jack: <unk> went down if I compare it to Q4 last year as we already indicated at the time.

So this increase.

Jack: Last year was planned.

Jack: We are increasing the opex to support the launch of.

Jack: <unk> in the U S. But also in preparation for the launch outside of the U S.

Jeroen Wakkerman: The operating loss because of the increase in OPEX increased from 13.7 million US dollars to 16.3 million in the quarter, and the net profit remained fairly stable, increased by 0.2 million, and that is due to better net finance results in the quarter. Our overall cash and marketable securities position went from $215M to $203.5M, so a reduction of $11.5M, and that is on the back of mainly negative net cash flow from operating activities of $7.6M.

Jack: Yes.

Jack: The operating loss because of the increase in Opex.

Increased from $13 $7 million to $16 3 million in the quarter.

Jack: And the net profit.

It remains fairly stable increased by <unk> 2 million and that is compared to the operating loss is due to better net finance results in the in the quarter.

Jack: Our overall cash and marketable securities position went from $215 million to 200 up three five.

Jack: A reduction of $11 5 million and that is on the back of mainly.

Jack: Negative net cash flow from operating activities of seven 6 million.

Jeroen Wakkerman: On the next slide, we see the revenue breakdown by product and geographic segment. And just focusing on Joentje for the first quarter, we saw 8.5 million revenue in the US from 7.9 million in Q4 last year. We see 1.1 million outside of the US, and that was 0.3 million in the fourth quarter last year.

Jack: On the next slide we see the revenue breakdown by product and geographic segments.

Jack: Just focusing on joined Jeff for the first quarter.

Jack: We saw a $8 five revenue in the U S.

Jack: From $7 9 million Q4 last year.

Jack: We see $1 1 million.

Jack: Outside of the U S.

Jack: And that was three.

Jack: $3 million.

Jeroen Wakkerman: And this is sales from the Named Patients program. And if you look at the overall part of Joentje in the total revenues at 9.6, that's now 17.17% of total sales, and obviously last year was nothing, and we expect that share to go up going forward. Now, on the next slide, some more perspective on the OPEX. As I said, the OPEX went down from last quarter by around $10 million. And the OPEX really reflects the continued investment in Juenja in the US and the launch preparation in the US.

Jack: In the fourth quarter last year and this is.

Jack: Sales from named patient programs.

And if you look at the overall part of the <unk> in the total revenues at nine six Thats now 17, one 7%.

Jack: Of total sales and obviously last year was nothing and we.

Jack: Expect that share to go up going forward.

Jack: So next slide some more perspective on the on the Opex.

Jack: As I said.

Jack: The Opex went down from last quarter by.

Jack: Around $10 million.

Jack: And the Opex really reflects the continued investments in <unk> in the U S and the launch.

Jack: <unk> ex U S.

Jeroen Wakkerman: We also increased investments to expand the Laniolacib franchise, so think about the pediatric trial and new indications that we are working on that Anurag mentioned, and we also increased payroll costs. With that, I would like to hand over to Sijmen for the outlook for the remainder of the year. Thanks.

Jack: We also increased investments to expand the linear ownership franchise. So think about the pediatric trial and new indications that we're working on them that <unk> mentioned and we also increased payroll cost and that is because of a general business growth.

Assignment: With that I would like to handover to assignment for the for the outlook for the remainder of the year.

Sijmen de Vries: Thanks, Jeroen. And yes, I'm happy to present you with the next slide, the Outlook for 24. As you heard in the beginning, we gave guidance and we continue to give guidance between 280 and 295 for revenues for this year, which means between 14 and 20% growth, with of course quarterly fluctuations as expected. Duenja, you heard about the continued progress in finding the additional APDS patients in the US market, the patients that are already identified, of course, but also the supported by the family testing, the systematic family testing that we have embarked upon, and the first results of the VUS validation efforts, and of course, subsequently converting those patients to paid therapy, albeit you also heard from, of course, from Anurag that the MAVE experiment, which will provide the definitive answer of the full definition of APDS, will report at the end of this year.

Assignment: Thanks, Sharon and yes, I'm happy to present, you with the next slide the outlook for 'twenty four as you heard in the beginning.

Sijmen de Vries: So in other words, we expect a significant inflow of patients in the US from that experiment that will overdose more than 1,100 patients with the VUS. Then you heard about the ex-EUS increasing revenues from commercial availability through the named patient program, which we expect to continue to increase during the remainder of this year. The clinical trials, the pediatric trial, and, of course, the Japan trial continue. We also expect regulatory action.

Assignment: We gave guidance and we continue to give guidance between $2 80, and $2 95 for revenues for this year, which means between 14 and 20% growth.

Assignment: Of course quarterly fluctuations as expected.

Uh huh.

Assignment: You and Joe you heard about the continued progress in finding the additional <unk> patients in the in the U S market. The patients that are already identified of course, but also supported by the family testing. The systematic firmly testing that we have embarked upon and.

Assignment: The first results of the <unk> validation efforts and of course subsequently converting those patients to two beta therapy, albeit you also heard from Matt of course from <unk>, That's a D maze experiment, which will provide the definitive answer.

Assignment: The full definition of Aps will report at the end of this year. So in other words, we expect a significant inflow of patients in the U S from that from that experiment.

Assignment: That will that overdose more than 1100 patients with <unk> with <unk>.

Assignment: Then.

Assignment: You heard about the ex U S increasing revenues from the commercial availability through the named patient program.

Assignment: Which we expect to continue to increase during the remainder of this year.

The clinical trials.

The pediatric trial.

Sijmen de Vries: You heard this year from the various jurisdictions where we have regulatory files that are under review. We're very excited, of course, and expect in the very near future to be able to announce that the phase two proof of concept clinical trial in PID with immune dysregulation will actually start to significantly expand our commercial potential for Millennials, but you heard Anurag, you know, outlining the details about. And last but not least, we have an active business development group that looks primarily at licensing opportunities, but we also look at acquiring opportunities that are in the clinical stage of development or later.

Assignment: And of course, Japan trial continue.

Assignment: We also expect regulatory action you hurt this year from the various jurisdictions, where we have a regulatory files that are under review.

Assignment: We're very excited of course and expect in the very near future to be able to announce that the phase II proof of concept clinical trial in PID with immune Dysregulation is actually will be started.

Assignment: <unk> significantly expands our commercial potential of millennials, who puts you heard anorak outlaw.

Assignment: Outlining the details.

Assignment: About <unk> and then last not least <unk>.

Assignment: Have an active business development group that looks for primarily in licensing opportunities, but also we look at acquiring opt.

Assignment: Opportunities that are in clinical stage of development or later on.

Assignment: In those areas that are mentioned here on the slide immunology, hematology respiratory and gastro neurology preferred so in other words, we have a very busy remainder of the year ahead of us and we look forward of course to do.

Speaker Change: Updating you on that Rob, but let's switch over now to the operator first.

Sijmen de Vries: And, you know, in those areas that are mentioned here on the slide, immunology, hematology, respiratory, and gastroenterology, preferably. So, in other words, we have a very busy remainder of the year ahead of us, and we look forward, of course, to updating you on that later on. But let's switch over now to the operator, because there may be some questions that we happily answer. Over to you, operator.

Speaker Change: Because there may be some questions that we are happy to answer over to you operator.

Operator: Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 and 1 again. We will now take the first question. On the line of Christian Glennie from Stifel, please go ahead.

Operator: Thank you Sarah.

Operator: As a reminder to ask a question. Please press star one one on your telephone and wait for your name to be announced.

Speaker Change: To withdraw your question. Please press star one on Flanagan.

Speaker Change: We will now take the first question.

Speaker Change: From the line of Christian Glennie from Stifel. Please go ahead.

Christian Glennie: Thank you. Thanks, guys, for taking the question. Three questions, please.

Speaker Change: Yes.

Christian Glennie: Thank you thanks, guys for taking the question three questions. Please first one won't be on.

Christian Glennie: The first one will be on Joanja in the U.S. Just to understand a bit better the sort of potential moving parts here in terms of patient numbers, you talked about 83 being on treatment as of the 31st of March, but that compares to 81 at the end of December. So just a net two additional patients, but maybe there are some additional patients that have come on board, but then some have dropped off, and then maybe some comment around the duration of treatment that you've seen so far given that you now have some patients potentially who've been on it since it was launched 12 months ago. So just a better understanding of the patient dynamics there and what to expect through the rest of the year.

Christian Glennie: So engine U S just to understand better the sort of potential moving parts here in terms of.

Christian Glennie: Patient numbers.

Christian Glennie: You talked about.

Christian Glennie: Three being on <unk> therapy as of 31st of March but that compares to 81 at the end of December.

Christian Glennie: So just a net two additional but it may be that there's some additional.

Christian Glennie: <unk> patients.

Christian Glennie: Come on but then suddenly dropped off and then maybe some comment around the duration of treatment that you've seen so far given that.

Christian Glennie: We'll now have some patients potentially you've been honest since since it was launched 12 months ago. So just a better understanding of the patient dynamics, there and what to expect through the rest of the year.

Sijmen de Vries: Steve, would you be so kind?

Stephen Toor: Would you be so kind? Sure. Thanks, Christian. Good morning.

Steve would you would you be so kind.

Steve: Thanks Christian good morning, so yes.

Stephen Toor: So, yeah. So, we actually added four more group patients with AD1. In the quarter, There were two, though, that dropped out. One was post-transplant. Unfortunately, that patient passed away, unrelated to Joe Inger. And then, secondarily, another patient with an unknown adverse event. So the net of that is 83. We also diagnosed or had diagnosed 15 more patients during that quarter, and those are currently being processed, obviously, and will be additive to the current patient load. So as things stand right now, our outlook is much the same as Simon said. You know, we're on track to get to where we need to by year-end.

Steve: So we actually with 81 and we added four.

Steve: Group patients in the quarter.

Steve: We're too though that dropped one was post transplant, a fortunate that patient passed away unrelated to Joe and Jay.

Steve: And then secondarily, a patient with an unknown adverse events. So the net of that is 83, we will start diagnosed or diagnosed 15 more patients during that quarter and those are currently being processed obviously and it will be additive to the current patient load so as things stand right now.

Steve: Our outlook is much the same as Simon said, we were on track to.

Steve: Get to where we need to by year end.

Sijmen de Vries: I think, you know, first of all, thanks, Steve, for that. I think, you know, with all these sort of ultra-rare therapies, you will see, of course, especially in the beginning, you'll see some lumpiness in the cells, right? That's why we say quarterly fluctuations.

Speaker Change: I think firstly, thanks, thanks, Steve or is it I think.

Speaker Change: As with all these sort of ultra rare therapies, you will see of course, especially in the beginning you'll see some lumpiness in the sales right.

Speaker Change: That's why we say quarterly fluctuations that Christian.

Sijmen de Vries: Yeah, okay, thank you. And then, I mean, is it a working assumption that the majority of patients continue to be on therapy, or have you got an average duration of treatment that you can quote at the moment? I think you're right. I mean, people stopping therapy are far and few between what we see, right? Anurag, do you want to say something about that?

Christian Glennie: Yeah. Okay. Thank you and then if you go to.

Speaker Change: I mean is it.

Speaker Change: Working assumption.

Speaker Change: The majority of patients continues to be on therapy, or if you go onto an average duration of treatment that you can quite at the mine I think youre right I mean are.

People stopping therapies are as far and few between.

Speaker Change: But we see rights and rescue you want to say something about that.

Anurag Relan: Yeah, thanks, Simon. Hi Christian. Yeah, we see continued very high compliance with the product. We've seen that throughout the clinical development program, and we see infrequent discontinuation.

Speaker Change: Thanks, Simon Hi, Christian Yes, we see continue very high compliance with the product and we've seen that throughout the clinical development program and we see infrequent discontinuation.

Christian Glennie: Okay, thank you. And then the second one would be on Lenio, Jojo, and Europe flagging ongoing review with the EMA and, obviously, expecting a CHMP. Just wanted to try and understand a little bit, as much as you can tell, about what some of these issues could be or relate to. Do you have any outstanding issues there? And when you say... you expect to be on the agenda for May, is that not necessarily the same thing as being up for an opinion in May? I just want to clarify what your expectations are for the May committee.

Speaker Change: Okay. Thank you and then the second one would be on.

Simon: Linear GA in Europe.

Simon: Flagging.

Speaker Change: Ongoing review with EMA, and obviously expecting a C H M P.

Speaker Change: Just wanted to try and understand a little bit as much you can tell.

Speaker Change: All of these issues could be over late two do you have any outstanding issues, there and when you say.

Speaker Change: Do you expect to be on the agenda SMA.

Speaker Change: That's not necessarily the same thing as being up for an opinion and May I just wanted to clarify.

Speaker Change: What your expectation is for the May River May Committee.

Anurag Relan: Anurag, would you be happy to answer that question? Sure. So we...

Speaker Change: <unk> would you be happy to answer that question.

Anurag Relan: Sure, so we do expect to be on the CHMP agenda for their meeting at the end of May on the MAA. So that's our expectation. Of course, we'll wait for the CHMP feedback to confirm that.

Speaker Change: Sure. So we do expect to be on the <unk> agenda.

Speaker Change: For their meeting at the end of May.

Speaker Change: On the MAA.

Speaker Change: So that's our expectation of course, we will wait for the <unk> feedback to confirm that.

Christian Glennie: Okay, so we should be expecting, Joanne, that's your expectation, Joanne, that you will be up for an opinion in May? That's correct.

Speaker Change: Okay.

Speaker Change: We should be expecting that's your expectation ginger will be upfront opinion.

Speaker Change: In may.

Christian Glennie: And then just finally, on the name patient, roll out obviously 1.1 million. You said that will continue to grow. Can you give us a sense of growth there through the rest of the year and also the number of patients and sort of the prices that you're getting for these patients? Thank you.

Speaker Change: That's correct.

Speaker Change: Yes.

Speaker Change: And then just finally on on the named patient.

Speaker Change: Rollout, obviously $1 1 million you said that will continue to grow can you give us a sense for.

Speaker Change:

Speaker Change: The gross out through the rest of the year.

Speaker Change: And I'll say kind of the.

Speaker Change: The number of patients in the sort of the prices that you're getting for these patients. Thank you.

Stephen Toor: Steve, would you like to comment on that? So the prices are generally in line with the U.S. price.

Stephen Toor: So the prices are generally in line with the U.S. price, sometimes with a slight discount to that. So, generally, in that ballpark way. In terms of numbers, we don't necessarily forecast MPP out just because that's driven obviously by the doctor and their discussions with both the patient and local authorities in the country. But we would expect to see as the product becomes better known and the effect that it has, a positive effect on patients, becomes more widely understood, and as we await approvals, more patients do benefit from that. But there isn't a specific target as such. It's very much doctor driven, Christian. Okay, thank you. Thank you. We will now take the next question.

Speaker Change: <unk> would you like to comment on that.

Speaker Change: So the prices are generally in line with the U S price.

Speaker Change: Sometimes with.

Speaker Change: Slight discount to that so generally in that ballpark.

Speaker Change: In terms of numbers, we don't necessarily forecast and PPL, just just because that's driven obviously by the doctor and their discussions with both the patient and local authorities in country.

Speaker Change: But we would expect to see.

Speaker Change: The productivity becomes better known and the effect that it has a positive effect on patients becomes more widely understood that as we await approvals more patients to benefit from that but there isn't a specific target as such that's very much Dr drove accretion.

Speaker Change: Okay. Thank you.

Speaker Change: So as you think.

Speaker Change: We will now take the next question.

Operator: from the line of Sushila Hernandez from the Burn Lands Code Campaign: Please go ahead.

Sushi: From the line of Sushi.

Sushi: From bank loans could kimpton. Please go ahead.

Sushi: Yes. Thank you for taking my question also one.

Sushi: Yeah.

Sushi: Jason findings.

Sushi: Theyre 15 diagnosed patients in Q1, so how many of these patients do you expect to be converted to base stations and also on operating expenses are these the levels that we can expect throughout the year or are you foreseeing any increases or decreases compared to this quarter. Thank you.

Sushila Hernandez: Okay, so may I suggest, Stephen, that you answer the first one? Is that alright? Yes, absolutely. So, thanks for the question. We expect the majority of those patients, if not all of them, to be converted to paid therapy. We have not as yet had a rejection, so I would expect, in the course of business, that all those patients will come online. Would you like to comment on the operating expenses, Jeroen? What do we expect for that? You're probably on mute, Jeroen.

Sushi: Okay. So may I suggest Stephens do you answer the first one is that alright, yes, absolutely so.

Stephens: Thanks for the question, we expect the majority of those patients if not all of them to be converted onto paid therapy.

Speaker Change: Not as yet.

Stephens: Out of rejection, so I would expect in the course of business all those patients tools come online.

Would you like to comment on the on the operating expenses.

Stephens: Expenses.

Stephens: We expect for that.

Stephens: Youtube.

Stephen Toor: As I said last year on OPEX, when it was in the Q4, it was 73 million that we expected it to go down. It has gone down now, and I would expect it to be slightly up in the next quarters because we keep investing in Juventus, both in the US and outside the US. And so I don't expect a sharp drop or anything in OPEX in the next year quarter. Does that answer your question?

Stephens: As.

Speaker Change: As I said last year on the Opex, what it was in the Q4 was $73 million.

Speaker Change: We expected it to go down it has gone down now and I would expect it to be slightly up in the next quarters.

Speaker Change: Because we keep investing in and join you both in the U S and ex U S.

Speaker Change: And so I don't expect a sharp drop or anything in Opex in the next next few quarters.

Jeroen Wakkerman: Does that answer your question, Sushila?

Speaker Change: This is answer your question answer Sheila.

Speaker Change: Thank you alright pressure.

Speaker Change: Thank you.

Operator: We will now take the next question. On the line from Joe Pantginis from H.E. Wainwright, please go ahead.

Speaker Change: We will now take the next question.

Speaker Change: From the line of Joe Glenn Chin is from H C. Wainwright. Please go ahead.

Joseph Pantginis: Good morning and good afternoon, gentlemen. Thanks for taking the questions. So, a couple, please.

Speaker Change: Good morning, and good afternoon, gentlemen, thanks for taking the questions. So couple. Please so I just want to start at the end of your written comments today because more on curiosity I mean, obviously it didn't it's not impactful of your investment case, but you did disclose that.

Joseph Pantginis: So, I just want to start at the end of your written comments today because, more out of curiosity. I mean, obviously, it's not impactful on your investment case, but you did disclose that OTL 105 with orchards was discontinued. So, just curious about two things. Is there anything technical or scientific that impacted the decision to discontinue the program? And are there any payments either way for the termination? And will you be potentially looking for an additional or alternative gene therapy approach in the future?

Speaker Change: 105, with Orchard is being discontinued.

Speaker Change: Just curious if two things is there anything technical or science that impacted the.

Speaker Change: The decision to discontinue for the program.

Speaker Change: And.

Speaker Change: Are there any payments either way for the termination and will you be potentially looking for in <unk>.

Speaker Change: Additional or an alternative gene therapy approach for the future.

Sijmen de Vries: All right, Joe. First, no significant pavements. Secondly, yes, there was always a high hurdle, of course, involved in this, a high technical hurdle. And when you look at it, it's associated with both the ability to generate sufficient C1 inhibitor protein by means of the blood organ, that's the one, and then, of course, the non-toxic conditioning regimen developments. So those were the high hurdles.

Joe: Hi, Joe first.

Joe: No no significant payments secondly, yes, there was always a high hurdle of course involved in this high technical hurdle.

Joe: And when you look at it is associated with the both the ability to generate sufficient C. One inhibitor protein <unk>.

Joe: By means of the blood, Oregon as soon and then of course, the the non toxic conditioning regimen developments. So those were at a high hurdles.

Sijmen de Vries: And then, of course, you know, last but not least, but very importantly, we, at the time, did not have the opportunity to develop Laniolacib, and that's the main reason we developed Laniolacib. We were not expecting to be able to develop Laniolacib for two subsequent indications. So we're now about to kick off that phase two study for Laniolacib for the next indication. You heard from Anurag that this is a very, very significant indication which is fairly close to the market compared to a product like OTR-105. Obviously, there is no competition around, with long exclusivity guaranteed for Lenny Olsen.

Joe: And then of course.

Joe: Last not least but very importantly.

Joe: At the time, we did not have the opportunity to develop.

Joe: And that's the main reason to develop Lenny ownership, we were not expecting that to be able to develop than it was for two subsequent indications. So we're now about to kick off that phase II study for linear ownership for the next indications you've heard from <unk> is a very very significant indication which is <unk>.

Joe: Fairly nearby markets compare to also a product like OTR 105.

Joe: We see no competition around.

Joe: With a long exclusivity guaranteed for linearity secondly, we are looking at an even more and bigger PID indication going forward. So in other words, we have a lot of opportunities now that are more nearby more derisked.

Sijmen de Vries: Secondly, we are looking at an even more and bigger PID indication going further forward. So in other words, we have a lot of opportunities now that are more nearby, more de-risked, without any competitive threats here. So we decided, you know, given all the things together, that it is the best way forward to focus ourselves now on this with regard to our internal portfolio, and, of course, to continue to look for leveraging the infrastructure, the commercial infrastructure further. We are active in the licensing slash acquisition quest, so I hope it's a bit long winded. I hope I have answered your question.

Joe: Any competitive threats here, so we decided given all the things together that it is the best way forward to focus ourselves now on this with regards to our internal portfolio and of course, we'll continue to look for leveraging the infrastructure of the commercial infrastructure further.

Joe: In licensing slash acquisition.

Speaker Change: Quest, so I hope, it's a bit long winded I hope I answer your question Joe.

Joseph Pantginis: No, absolutely not. Thank you. And then on Rukiness, sort of a two-pronged question, how would you describe sort of the first quarter impact with regard to insurance resets that are usually expected? How much did that impact, at least just for the first quarter, to be able to get back on trajectory? And secondly, how would you describe the balance? Because obviously, it's very nice to see, you know, the continued addition of new physicians to the program and refill rates. Thanks a lot.

Joe: Absolutely. Thank you and then on <unk> that sort of a two pronged question.

Speaker Change: How would you describe it.

Speaker Change: Sort of the first quarter impact with regard to insurance resets that are usually expected how much did that impact at least just for the first quarter to be able to get back on trajectory and secondly, how would you describe the balance because obviously, it's very nice to see the continued addition of new physicians to the program and.

Speaker Change: Refill rates, thanks, a lot.

Sijmen de Vries: Yeah, of course, it's always part of the lumpiness, or the first quarter is always part and parcel of that renewal of prior authorizations. But let's just go to Steve to give a bit more insight into these things, right, Steve?

Speaker Change: Yeah of course, it's always part of the Lumpiness.

Speaker Change: First quarter is always part and parcel of that the renewals of the year of the prior authorizations, but let's just go to Steve give a bit more insight and these things might Steve yes.

Stephen Toor: Hi Joe, actually, things went well. As you know, we've been doing this now for a number of years, so we were able to prepare in Q4 and the prior authorizations in Q1 actually went pretty smoothly, and we completed almost all of them by the end of February. Now what complicated last year was some issues, as you know, that were external issues that hit the market for government patients.

Steve: Hi, Jeff.

Steve: The six well Joe as you know we've been doing this now for a number of years. So we were able to prepare and Q4.

Steve: The prior authorization <unk> in Q1, as you went pretty smoothly.

Steve: We completed almost all of them by the end of February now complicated last year was some some issues as you know that were external issues that hit the market with government patients we saw that impact.

Stephen Toor: We saw that impact decline quite significantly this year as patient out-of-pockets also came down in the Medicare space, and certainly for us, it was a significant decline in impact. So overall, I would say Q1, while you expect lumpiness in Q1, was a pretty successful reauthorization period for us.

Steve: Quite significantly this year is patient out of pocket. So also came down for many in the Medicare space.

Steve: Certainly for US it was it was a significant decline in impact. So overall I would say Q1, while you expect lumpiness in Q1, it was pretty successful reauthorization period for us.

Operator: Excellent. Thanks for all the details, guys.

Speaker Change: Excellent. Thanks for all the details guys.

Speaker Change: Thank you Joe.

Hartaj Singh: We will now take the next question, from the line of Hartaj Singh from Oppenheimer. Please go ahead.

Speaker Change: You.

Speaker Change: Yes.

Speaker Change: We will now take the next question.

Speaker Change: From the line of Carter Shang from Oppenheimer. Please go ahead.

Hartaj Singh: Great. Thank you. And thanks for the questions. I just have a couple. Really nice launch going on with JoAnja.

Carter Shang: Great. Thank you.

Carter Shang: So the questions I just have a couple.

Carter Shang: Tom.

Carter Shang: Really nice launch going on.

Hartaj Singh: But I just want to kind of go back to a previous question on the first quarter fluctuations. You know, two years in a row now we've had them, and they seem to be pretty extreme. I mean, are they, you know, other companies talk about payment into government programs, there's patient assistance programs, et cetera, et cetera.

Carter Shang: We're joined here, but I just wanted to kind of go back to a previous question on the first quarter.

Carter Shang: Fluctuations.

Two years in a row now we've had them and they seem to be pretty extreme I mean is it.

Carter Shang: Other companies they talk about.

Carter Shang: Payment into government program, there's patient assistant program et cetera, et cetera, I mean, what exactly happened in the first quarter, where you have this pretty large drop off.

Hartaj Singh: What exactly happens in the first quarter where you have this, you know, pretty large drop-off from the fourth quarter to the first quarter? It seems mostly Rukinus sales. And then is that the expectation going forward? Is that the way we should model this going forward, in that in future first quarters, you know, on a quarter-on-quarter sequential basis, we should expect a pretty significant decrease in Rukinus sales, and then that will pick up going on later?

Carter Shang: From the fourth quarter and the first quarter. It seems mostly looking at sales and then is that the expectation going forward should is that the way we should model this going forward and that in future first quarters.

Carter Shang: On a quarter on quarter sequential we should expect a pretty significant decrease in sales and then that will pick up going on later I mean is that the way to think about it. That's my first question I just got a couple of others. Thank you.

Hartaj Singh: I mean, is this the way to think about it? So that's my first question. I just have a couple of others. Thank you. Yeah.

Sijmen de Vries: Yeah, hey, Hartaj, I think that's been the case, right, for all those years and was aggravated last year by this special situation there, but it seems to be the case, right? Do you want to comment any further on this, Stephen?

Hey, guys I think it's been the case right for all those years and was aggravated last year by this by the special situation there but.

Speaker Change: It seems to be the case, if you want to comment any further on this Steven.

Stephen Toor: Good morning Hartaj, so I think it's certainly the case that in most Q1s you've seen over the years, Rukinus sees a slight decline due to the reauthorization of most of our patients in that period of time, and that does affect most companies. Last year was exacerbated by an impact on government patients. It was external.

Stephen Toor: Good morning, George So I think it's certainly the case that in most key ones you've seen over the years, we can see the slight decline due to the reauthorization.

Stephen Toor: Realizations of most of our patients in that period of time and that does affect most companies last year was exacerbated by an impact to government patients that was externally. It was isn't affected the whole Hai space that came down significantly. This year is patient out of pockets decline. So we saw about half the impact that we saw last year and next year.

Stephen Toor: It was in effect in the whole HA space, but that came down significantly this year as patient out-of-pockets declined. So we saw about half the impact that we saw last year. And next year, that should stabilize completely, I think, with patient out-of-pockets coming down to around $2,000. So I think you can say by the time we get to next year, it'll be in a steady state. So yeah, perhaps we should expect a decline as we always have year on year, but I don't expect what happened last year and this year to continue. That's the result of a very specific event affecting government patients.

Stephen Toor: <unk> completely I think with patient out of pockets coming down to around $2000. So I think you can say, but it's when we get to next year at steady state. So yes, perhaps we should expect to decline as we always have year on year, but I don't expect what's happened last year and this year to continue.

Stephen Toor: Result of a very specific event affecting government patients.

Hartaj Singh: No, Stephen, that makes sense. And we've heard that from other companies also. I think the IRA Inflation Reduction Act has exacerbated this first quarter fluctuation. The other question I would just have is on OPEX. You know, I really like all the color there.

Speaker Change: Yes, now Stephen that makes sense and we've heard that from other companies also I think the IRI inflation reduction act that exacerbated this first quarter fluctuation. The other question I would just have is on opex.

Sijmen de Vries: But, you know, there's a question asked previously. Let me put it another way, which is that, you know, if you're expecting, you know, your guidance suggests a pretty significant increase in revenues this year, is OPEX expected to grow at the same rate? I mean, or can we hope for some operating leverage, which would mean OPEX growing at a slower rate than revenues? And I've got one last question.

Speaker Change: Really like all the color there, but let me put it.

Speaker Change: Question asked previously let me put it another way, which is that if you were expecting.

Speaker Change: Your guidance suggests a pretty significant increase in revenues this year.

Opex is expected to grow at the same rate or can we hope for some operating leverage which would mean opex growing at a slower rate than revenues and I got one last question after that.

Sijmen de Vries: Yeah, sure. Now, I think Yerun already commented on that, Art Arch, about, you know, the still to be expected slight increase in operating expenses for the coming quarters. Having said that, you know, it's not the spectacular increase before because, you know, we did the U.S. launch, which is, of course, scary capital intensive. On the other hand, you know, we continue to invest in all those things in the U.S. market.

Speaker Change: Yeah sure no I think Jeroen already commented in Latin at Orange about the still to be expected slight increase in the operating expenses for the coming quarters, having said that.

Speaker Change: It's not the spectacular increasingly more before because we did the U S launch of course it was.

Speaker Change: It's very capital intensive on the other hand, we continue to invest in all those things in the U S. In the U S market.

Speaker Change: And of course, we are preparing for is human misery eluding to.

Sijmen de Vries: And, of course, we're preparing for, as you were already alluding to, of course, we're preparing for, as you were already alluding to, of course, the preparations for the launch of the WANJ outside of the US and in addition to that you also see that you know gradually R&D costs will not spectacularly but will continue to go up as well because of the fact that we are starting you know clinical trial programs for for Lady Olenship in the subsequent indications so all and all we're not a we're not at this point in time of course aiming for for profitability per se in this year because it's a lot is still a launch here right and it takes time and you already heard that for instance you know the leverage I think the real leverage if you look at the the patient growth in in ATDS you heard Steven say there that you know that that that that that's conclusive VUS may have experimented that Anorike was talking about will or should be bringing a very significant bolus of patients to the US in the US market towards becoming available for paid therapy be next year. So, you know, this is typically, you know, when you have a new disease, it's not fully described.

Speaker Change: The preparations for the launch of <unk> outside of the U S. And in addition to that you also see that.

Speaker Change: Gradually R&D cost will not spectacularly, but will continue to go up as well.

Speaker Change: Because of the fact that we are starting out with clinical trial programs for for a lady ownership into subsequent indications so all in all.

Speaker Change: We're not a we're not at this point in time of course.

Speaker Change: Aiming for for profitability per se this year, because it's still a loss share right.

Speaker Change: It takes time and you already heard that.

Speaker Change: For instance, the leverage I think the real leverage if you look at the patient growth in <unk> as you heard Stephen say their debt.

Speaker Change: That said that's conclusive V. U S may have experimented anorak was talking about will.

Speaker Change: Should be bringing.

Speaker Change: Very significant bolus of patients to the U S. In the U S market to watch becoming available for paid therapy next year. So this is typically when you have a new disease is not fully describes.

Sijmen de Vries: It is typically, you know, when you are dealing in ultra-rare diseases, it takes time and it takes a lot of investment, but eventually, it will be a very, of course, profitable operation. I hope that answers your question a little bit, Hartaj.

Speaker Change: It is typically when you are dealing in ultra rare diseases that it takes time and it takes a lot of investment, but eventually it will be a very of course profitable operation I hope that answers your question a little bit hot dogs.

Hartaj Singh: Yeah, no, no, absolutely not. And in line with what you've said before also previously, Simon, I just want to get more color around it. My last question is just on the Phase 2 design. Anurag, you might have mentioned this already, but, you know, can you just kind of walk us through, you know, roughly how long it would take for you to sort of get all the sites open, recruiting, you know, when, when, when could, you know, we see essentially what I'm trying to get to is when could we get to Phase 2? I'm trying to get to is when we could see a sort of a readout, you know, would that be a 2025 event or 2026? And thank you for all the questions.

Speaker Change: Yes, no absolutely.

Speaker Change: In line with what you've said before also critically Simon just wanted to get more color around it and my last question is just on.

Speaker Change: On the phase III design.

Speaker Change: I'm rock you might have mentioned this already but.

Speaker Change: Can you just kind of.

Speaker Change: Walk us through.

Speaker Change: Roughly how long would it take for you to sort of get all the sites open and recruiting.

Speaker Change: When when when could we see essentially what I'm trying to get to is when could we see a sort of a readout, what's that going to 2025 event or 2026 and thank you for all the questions. Thank.

Anurag Relan: Hi Hartaj. Yeah, so this next phase two dose finding study is being conducted at a single center, and that's at the NIH. So with that and the fact that we're anticipating 12 patients in this study, this is a center that has actually already identified which patients they anticipate being able to enroll. We believe that they'll be able to enroll the study in a relatively rapid fashion once we get going, and we expect to be able to read out the results probably in the course of 2025.

Anurag Relan: Thank you, Hartaj. Anurag, please. Hi, Hartaj. Yeah, so we, this next phase...

Speaker Change: Thank you Johan.

Speaker Change: Please.

Speaker Change: Yeah. So we this this next phase II dose finding study is being conducted on a single center and Thats at the NIH.

Speaker Change: With that and the fact that <unk>.

Speaker Change: We're anticipating 12 patients in this study this is.

Speaker Change: <unk> center that has actually already identified which patients they dissipate being able to enroll we believe that they'll be able to enroll the study.

Speaker Change: And relatively rapid fashion once we get going and we expect to be able to read out the results probably in the course of 2025.

Speaker Change: Great. Thank you all.

Speaker Change: Thank you.

Speaker Change: Thank you.

Operator: We will now take the next question. On the line from Alistair Campbell from the Royal Bank of Canada, please go ahead.

Speaker Change: We will now take the next question.

Speaker Change: From the line of Alistair Campbell from your Royal Bank of Canada. Please go ahead.

Alistair David Campbell: Thanks so much for taking the questions. I've got three, if that's okay.

Thanks, so much for taking my questions I've got three if that's okay.

Alistair David Campbell: Just first of all, looking at Juenja, I mean, obviously, we've seen more diagnosis through Q1, but we haven't seen progression in terms of patients on therapy. So, I just want to ask, you know, get a sense of that. I mean, just check we're not seeing an unblind dynamic here, or perhaps what you've done in the first instance is kind of honed in on the most severe patients, and maybe now we're moving into patients who are diagnosed but don't have quite as severe disease, and they're potentially harder to pick up.

Alistair David Campbell: Just first of all looking at <unk> I mean.

Alistair David Campbell: Obviously, we've seen more diagnoses through Q1, but we haven't seen progression in terms of patients on therapy.

Alistair David Campbell: Wanted to ask you get a sense of that I mean, just check we're not seeing an underlying dynamic here, where perhaps what you've done in the first instance.

Alistair David Campbell: Wanted to move it up in the most severe patients and maybe now we're moving into patients who are diagnosed but then have quite severe disease and there potentially harder to pick up some maybe some commentary on that in terms of what's happening with severity of patients on drug.

Alistair David Campbell: So, maybe some commentary on that in terms of what's happening with severity in patients on drugs. And then I do some quick mathematics, and assume you had about 80 patients paid for therapy through the quarter. That would sort of point me to a U.S. number based on the WAC, a chunk higher than reported sales. It sort of indicates something like a 25% gap in the system. Is that a good proxy for how much kind of discounting there might be from the WAC price in the system?

Alistair David Campbell: And then if I do some quick mathematics machining you had about 80 patients on.

Alistair David Campbell: Page therapy through the quarter.

Alistair David Campbell: I would sort of point me to the U S number based on the WAC.

Alistair David Campbell: Chunk higher than reported sales are sort of indicate something like a 25%.

Alistair David Campbell: Yes.

Alistair David Campbell: System.

Alistair David Campbell: Is that a good proxy for how much kind of discounting that might be from that from the WAC price in the system and then finally.

Alistair David Campbell: And then finally, just on the PID trials, is there any reason to think that PIDs need a different dose from APDS? I mean, do you perhaps need stronger suppression of the pathway? Just any sort of feedback might be interesting. Thank you.

Alistair David Campbell: Just on the PRD trials is there any reason to think that <unk> need a different dose from atvs means you make perhaps need stronger suppression of the pathway just any sort of feedback on that would be interesting. Thank you.

Sijmen de Vries: Okay, let's maybe start with, thanks Alistair, let's maybe start with two questions for Anurag about severity and PID dosing. Anurag, would you like to comment on that?

Speaker Change: Okay. That's maybe start with thanks, Alastair, let's maybe start with two questions from <unk> about the severity and the and the Tid dosing <unk> would you like to comment on that.

Anurag Relan: Sure, so Alistair, the first comment is correct that you know the patients that we initially were able to convert over to paid therapy, these were patients, of course, that were in the clinical trial program, in the expanded access program, so there was, of course, a bolus of those patients, and many of those patients were quite severely ill. Now APDS, in general, is a serious disease, so there's you know there aren All of these patients are sick; most of these patients are on IG replacement therapy, for example, so this is, you know, this is a serious disease and a progressive disease, so I think it's just a matter of continuing to reach out to these doctors and educate them as well as patients about their condition and the potential effects of Joanne. Now, on to the question about the dosing in this study, as well as any future studies. And I think that it's really an open question.

Speaker Change: Sure. So I think I'll start the first comment is correct that the patients that we initially were able to convert over to pay per therapy. These patients.

Speaker Change: Of course that we are in the clinical trial program in the expanded access program. So there was of course, a bolus of those patients and many of those patients were quite severely ill now <unk> in general is a serious disease. So there is.

Speaker Change: There arent a lot.

Speaker Change: March number of let's say asymptomatic patients that were floating around out there with all of these patients are sick. Most of these patients are on it.

Speaker Change: Replacement therapy for example, so this is.

Speaker Change: This is a serious disease progressive disease. So I think it's just a matter of continuing to reach out to these doctors and educate them as well as patients about their condition.

Speaker Change: And the potential effects of Gilenya.

Speaker Change: Onto the question about the dosing in the in this study as well as any future setting and I think Thats really an open question, we're starting with a lower dose than we have approved for Gilenya. Currently so we're starting at the 10 milligram dose which is the same dose that we used initially with AP.

Anurag Relan: We're starting with a lower dose than we have approved for Joentgen currently. So we're starting at the 10 milligram dose, which is the same dose that we used initially with APDS, and we'll progress these patients through. Based on everything that we know so far about the activation of the pathway in these patients and measurements that have been done about that activation relative to APDS patients, we feel like we're in the right dosing range.

Speaker Change: And we will progress these patients through.

Speaker Change: Based on everything that we know so far about the activation of the pathway in these patients and measurements that have been done about that activation relative to Aps patients. We feel like we're in the right dosing range. So we don't believe that we're going to need a higher dose.

Anurag Relan: So we don't believe that we're going to need a higher dose to so-called suppress the pathway but really trying to normalize and sort of balance the pathway. I think that that's probably a better way to think about it.

Speaker Change: So called suppress the pathway, but really trying to normalize and sort of balance the pathway I think that's probably the better way to think about it.

Jeroen Wakkerman: Okay, thanks. And then maybe Jeroen, you want to comment on Alistair's question about discounting or the... absence of it in New Asia?

Speaker Change: Okay. Thanks.

Speaker Change: Then maybe you want to comment on that.

Speaker Change: Asked this question about the.

Speaker Change: The discounting mode.

Speaker Change: Absence of it in Georgia.

Jeroen Wakkerman: Yeah absolutely. So basically, it's not just discounting like in other drugs; it's mainly because of the mix with Medicaid, Medicare patients, and mainly Medicare. And so we did have, for that reason, a discount of around 12%.

Speaker Change: Yeah, absolutely so basically it's not just discounting like in other directions, mainly.

Speaker Change: The mix with Medicaid Medicare patients mainly Medicare.

Speaker Change: So we did have for that region discounts.

Speaker Change: 12%.

Alistair David Campbell: Does that answer your question, Alistair?

Jeroen Wakkerman: Yeah, and there are no other discounts on that, Elsa.

Speaker Change: Does that answer your question Alastair.

Speaker Change: Yes.

Speaker Change: No other discounts on that Alice.

Alistair David Campbell: Yeah, that's good. It's very clear.

Yes, that's good sorry, Ken is that broadly what we should be thinking about carrying on going forward or do you think the mix will change over time.

Jeroen Wakkerman: And is that broadly what you should be thinking about carrying on going forward, or do you think the mix will change over time?

Ken: Good growth it really depends on the patient mix. So it was very difficult to say, but.

Ken: Other than that.

Jeroen Wakkerman: It really depends on the patient mix, so it's very difficult to say, but other than that, it's been relatively stable so far.

Ken: It's been relatively stable so far.

Alistair David Campbell: You should also realize that it's a relatively young population that we're treating right here in this case.

Speaker Change: Thanks, So much you realized it also it's a relatively young population that we're treating right here.

Alistair David Campbell: Very good, very clear, thank you. Thank you.

Speaker Change: In this case.

Speaker Change: Okay. Thank you.

Operator: Thank you. As a reminder, if you wish to ask a question, please press star one and one on your telephone. That's star one and one to ask a question. There are no further questions at this time. I would like now to turn the conference back to Simon De Vries for his closing remarks.

Speaker Change: Okay.

Speaker Change: Thank you as a reminder, if you wish to ask a question. Please press star one on one on your telephone.

Speaker Change: Star one to ask a question.

Speaker Change: There are no further questions at this time I would like.

Speaker Change: Mike.

Speaker Change: I would like now to turn the conference back to Cynthia.

Speaker Change: Tim on the race for closing remarks.

Sijmen de Vries: Sandra. Yes, thank you very much. Yes, so you heard, our total revenue guidance continued to be between 280 and 295. You heard about the progress of finding additional APDS patients in the US and outside of the US, of course, and them bringing also a relevant part of the revenues for JoAnja. You heard about the expectations for the big effort that's ongoing during the remainder of the year to clarify the full description of the disease by means of the MAVE experiment, which will, we expect, deliver a significant new bonus of patients next year becoming available for therapy.

Tim: Thank you Sandra yes, thank you very much.

Speaker Change: Yes.

Speaker Change: So you heard.

Tim: Our total revenue guidance continues to be between two adding 295.

Tim: You heard about the progress we're finding the additional <unk> patients in the U S and outside of the U S of course.

Tim: Bringing also.

Tim: Irrelevant relevant part of the revenue score for Joanne.

Tim: You heard about the.

Tim: <unk> towards the big effort is ongoing.

Tim: During the remainder of the year or to clarify the full description of the disease by means of the mayor of experiments to so which will we expect deliver a significant new bolus of patients next year, becoming available for therapy, obviously, the clinical trials are ongoing and especially here the pediatric label expansion.

Sijmen de Vries: Obviously, the clinical trials are ongoing, and especially here, the pediatric label expansion trial progresses very well, and that trial with the four 11-year-olds has the majority or the vast majority of the pediatric patients in it, and, you know, that, of course, will be delivering a significant bonus of patients in addition to that. You heard about the regulatory actions that are ongoing in the various territories outside the US and where we expect to see some progress there.

Tim: Ah trial progressed, very well and that.

Tim: The trial was the poor 11 year old has the majority or the vast majority of the pediatric patients in it and that of course, we will be delivering a significant bolus of patients in addition to that.

Tim: You heard about the regulatory actions that are ongoing in the various territories outside the U S and where we expect to see some some progress there continuing.

Sijmen de Vries: And then, of course, last but not least, we're very excited about the start of our phase two clinical trial, a proof of concept trial in PID with immune dysregulation that will very significantly expand the long-term commercial opportunity of laniolatib. And, very lastly, you know, we continue to look for licensing opportunities for clinical stage rare disease opportunities to be either in license, preferably or acquired. So with that, I would like to thank you all for being present at our conference. And we look forward to updating you on our next call, which will be our half-year results at the beginning of August. Thank you very much, and goodbye.

Tim: And then of course last but not least we're very excited about the start of our phase II clinical trial proof of concept trial in PID with immune dysregulation.

Tim: Regulation.

Tim: That will vary significantly expand long term commercial opportunity of linearity and very lastly.

Tim: We continue to look for in licensing opportunities of clinical stage rare disease opportunities to.

Speaker Change: To be either in licensed preferably or quiet, so with that I would like to thank you for being present at our at our conference and we look forward to updating you on our next call, which will be our half year results in the beginning of August. Thank you very much and that goodbye.

Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.

Speaker Change: This concludes today's conference call. Thank you for participating you may now disconnect.

Speaker Change: Okay.

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