Pharming Group N.V.

Good day and thank you for standing by. Welcome to the Farming Group NV first quarter 2026 results webcast and conference call. 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 and 1 on your telephone. You will then hear an automated message advising 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 first speaker today, Fabrice Chiraki, CEO. Please go ahead.

Thank you, operator, and good morning and good afternoon, everyone, and welcome to our Q1 2026 earning call. I'll be joined on this call today by Libran March, our Chief Commercial Officer, Anurag Relan, our Chief Medical Officer, and Kenneth Linus, our Chief Financial Officer. Next slide. In this call, we will be making forward-looking statements that are based upon our current insights and plans. As you know, this may differ from future results. Next slide. As you saw in our press release, we made important progress across the business in this first quarter, despite the drop in quarterly revenue driven by WKNF. The reconnaissance revenue decline was largely expected due to inventory drawdown at specialty pharmacies, which we discussed on our Q4 2025 call in March. The commercial exit from non-US markets also contributed to the year-on-year decline. We announced that decision last year as part of our renewed financial discipline, since the commercialization of reconnaissance in these markets was not financially sustainable. Now, if we look at the underlying fundamentals, we see limited interest from patients on RECONNESS to trial alternative therapies. Nine months after the launch of the new oral therapy, we have retained the overwhelming majority of RECONNESS patients, and we continue to see new patients starting RECONNESS. Leverne will elaborate on this market dynamic in a few moments. Coming now to Johanja, this product is an important growth driver still early in its lifecycle. JoinJar revenues grew by 34%, reflecting strong momentum both in the US, where the number of patients increased by 25% year on year, but also in international markets. We've also made meaningful regulatory progress this quarter, positioning us well to launch JoinJar in Japan, and in Europe later this year, and to extend join just label to the pediatric population in the U.S. After the disappointing CRL, we had a constructive dialogue with the FDA, and we've already resubmitted the SNDA for the two highest dose, covering a meaningful proportion of children from four to 11. We are also planning to submit an SNDA this summer for the lowest dose. Finally, our disciplined cost management helps us to maintain positive cash flow from operations in this quarter, despite the viability in revenues. We are maintaining our revenue guidance of $405 to $425 million for 2026, representing growth between 8% and 13% year-on-year. Next slide. As you can see, the durability of the Rukoneth franchise and the strong momentum and growth potential of Georgia underpin the transformation of farming into a profitable high-growth biotech with two late-stage pipeline programs offering billion-dollar sales potential. Rukoneth is the foundation of our portfolio and a reliable cash engine for the future. Even in an ever more crowded HAE market, given its differentiated value proposition for the difficult-to-treat patients subpopulation and its highly specific manufacturing process. Joinger is just at the beginning of its life cycle with multiple growth catalysts in APDS through pediatric and geographic expansion and the potential expansion into higher-prevalent PIDs with two Phase II readouts later this year. Anurag will discuss an exciting presentation at CIS conference taking place today that summarizes clinician experience treating patients with CBIT with immune dysregulation enrolled in our ACCESS program. And last but not the least, Napa Zimot, previously known as KL1333, for primary mitochondrial disease is another billion-dollar-plus opportunity, with the registrational study expected to complete enrollment this year and readout next year. These commercial assets and high-value pipelines, combined with durable source of cash flow, provide a solid foundation for farming to become a leading global rare and ultra-rare disease company with substantial near and long-term value creation potential. Let me now turn it over to Lever who will provide deeper insights into the performance of our commercial products.

Good morning, good afternoon, everybody.

Let me start with Ruconet's performance in the first quarter. Revenue was down 15% year-on-year, Importantly, as Fabrice mentioned, this was anticipated and largely driven by three distinct factors. First, inventory dynamics, which reduce quarterly revenue by 8%. This reflects what we previously stated on our March Q4 call and accounts for the majority of the impact. Second, our planned exit from ex-U.S. markets contributed approximately 3%, and this is consistent with our strategy to focus our resources where we can generate the highest return. Third, with new treatment options entering the USHAE market, we've seen measured impact from competition, specifically limited patient interest in trialing or switching to other therapies with many returning, and this has been in line with our expectations. Additionally, what's important is what's happening underneath these headline numbers. We added approximately 50 new patient enrollments in the first quarter this year. and we brought on 23 new prescribers onto Ruconest. This is a meaningful signal that clinicians continue to see the value of Ruconest, specifically in the high attack, high severity segment, and are initiating new patients even as the treatment landscape expands. Next slide, please. On this slide, this really gets to the heart of why Ruconest continues to play a critical role in HAE management. We know HAE is not a uniform disease. For patients on the more severe end of the spectrum, meaning those with frequent attacks, rapid onset symptoms, or high anxiety around unpredictability or the attack location, the need is very clear. They require a treatment that works quickly, consistently, and durably, and that's exactly where Rucanus fits, and it's reflected in what we're seeing in the market today. After nine months into the launch of a new oral competitor in HAE in the U.S., the overwhelming majority of Rukanest patients have remained on therapy. Among those who had explored alternatives, many high-burden patients are returning to Rukanest, in particular when response to new treatments have not been adequate. This reinforces the importance of having a dependable on-demand therapy like Rukanest and underpins our confidence in the long-term role of Rukanest in this evolving HAE market. Next slide, please. So turning to Joenja, we delivered another strong quarter, building on the momentum from last year. Revenue grew 34% compared to the first quarter of 2025, reaching $14.1 million globally. In the United States, patient growth is the central driver of performance. By the end of the quarter, we had 127 patients on paid therapy in the U.S. alone, which represents a 25% increase over the first quarter of 2025. And we accelerated the rate of new patient starts to seven during the quarter, an improvement over the addition seen in the previous two quarters. The U.S. full rate remained high at 85%, reflecting our highly effective reimbursement support at patient services process. Equally important, we continue to broaden the pool of APDS patients. We've identified 187 APDS patients older than 12 years old in the US and an additional 57 eligible patients in the 4 to 11 years old group. And this represents the next frontier for growth in the US. In international markets, we continue to see strong patient uptake in the UK. and significant growth in the number of patients on government-supported access programs in other countries. This momentum sets us well to drive growth in APDS and other indications to come. Next slide, please. Now, stepping beyond the quarter, I want to put JOENJA into its broader strategic context. We are building more than a single rare disease product. We are building indeed a scalable immunology franchise with multiple clearly defined growth levers. The first growth lever is continued expansion within APDS itself. We are still early in identifying APDS patients, and there is significant proportion of patients yet to be identified. The second growth lever is further U.S. APDS expansion, which includes the pediatric launch in the United States. and an upside VUS reclassification opportunity across all ages. Thirdly is international expansion. We are in the early stages outside the United States, and upcoming launches in Europe and Japan will open meaningful new markets for us. And finally, the fourth growth lever is lifecycle and label expansion beyond APDS, specifically exponentially larger patient pools in genetic PIDs and CVID with immune dysregulation. Taken together, these four levers create sequential growth engines over the coming years. APDS drives the initial growing foundation. Pediatric expansion deepens penetration. Geographic expansion broadens reach. And new patients continue to give us access to significantly larger patient segments, which extends our platform. Now to share more about our pediatric submission and lifecycle efforts on Joenja, I will now hand it over to Dr. Anurag Relin, our Chief Medical Officer.

Thank you, Laverne. In addition to the important regulatory milestones in Japan and Europe, we made significant progress in the U.S. in our efforts to expand the Joenja label to pediatrics for children ages 4 to 11 with APDS, following the receipt of a CRL from FDA in January. As we previously explained, we believe the clinical pharmacology and analytical batch testing methodology issues outlined in the FDA letter were addressable. We held a Type A meeting with FDA at the end of March, which included two APDS expert physicians, and we were pleased with the constructive dialogue and understanding of the issues raised by FDA and the CRL. The FDA also appreciated the unmet need, including the serious and progressive nature of APDS, as well as challenges with clinical trial recruitment in young children with an ultra-rare disease. We worked collaboratively with FDA to define the most expedient path forward, and we have that now, with the first step being the resubmission of the SNDA for the highest doses, specifically 40 and 50 milligrams. This took place in April, in fact, on the same day that we received the FDA's meeting minutes, and as is typical, we plan to issue a press release upon FDA acceptance of the resubmission. These doses, as Fabrice mentioned, cover a meaningful proportion of four to 11-year-old children. An FDA decision on this is expected in six months or sooner. The second step will be a new SNDA for the doses covering the lowest-weight patients, which is planned for this summer. For this SNDA, we also expect a six-month review. Next slide. At the Clinical Immunology Society annual meeting this week, Farming and our collaborators are presenting seven abstracts, five expanding the evidence base in APDS, and two that begin to provide data on the much larger opportunity in other PIDs with immune dysregulation. These include the clinical expanded access experience with leniolisib to treat immune dysregulation in patients with common variable immune deficiency, or CVID, and CVID-like disorders, which I will cover in more detail in a few slides. As you see, APDS is just the beginning for linoleic acid. Next slide. In addition to APDS, we continue to make progress in other PIDs with immune dysregulation, which is based on the observation of the key role of PI3K delta as an important regulator in immune cells and imbalance in the pathway, which underlies the immune dysfunction across several primary immune deficiencies. This mechanistic understanding forms the scientific rationale for our Joengia development program. Joengia, as you know, is currently approved for APDS where gain-of-function mutations drive a hyperactive pathway leading to immune deficiency alongside broad immune dysregulation. APDS, in fact, serves as proof of concept for the ongoing two Phase II studies, Evaluing Leniolisib and other PIDs. These have significantly greater prevalence in APDS but share unmet medical needs underlying mechanisms, and disease pathology. The programs target two similar populations. The first is genetically identified PIDs with immune dysregulation, which represent a prevalence that's five times greater than APDS, or more than 2,500 patients in the U.S. alone. And the second is common variable immune deficiency with immune dysregulation, which is identified independently of genetics, and this is even a larger group of patients, which is approximately 26 times size of APDS, or more than 13,000 patients in the U.S. alone. I'll now talk to you about the studies in the next slide. Both proof-of-concept studies share a common design architecture, single-arm, open-label dose range finding, allowing cross-study comparability. The CVID study is a multicenter study enrolling 20 patients, And the genetic PID study is a single center study conducted at the NIH with 12 patients. Both studies are now fully enrolled with trial readouts expected later this year. Both also employ a three-dose escalation design to characterize dose response and confirm the optimal dosing strategy. The studies address two core objectives. First, of course, to address assess safety, tolerability, and the pharmacokinetics and pharmacodynamics to confirm dosing. Second, and most clinically meaningful, to estimate the efficacy against immune dysregulation, specifically looking at the lymphoproliferation and autoimmune aspects. These efficacy endpoints are aligned with the key disease manifestations, which are focused on these aspects. In addition, we'll also be collecting patient-recorded outcome measures, which were developed through a custom process involving expert input and formal interview studies with CVID patients. Next slide, please. Ahead of these study results, we can see some important early clinical evidence supporting laniolus potential in CVID with immune dysregulation being presented today at the CIS meeting. Six CVID or CVID-like patients with immune dysregulation amongst the sickest patients refractory to other therapies received laniolisib through an expanded access program for a median of 1.4 years, with individual exposure ranging from half a year to two and a half years, providing meaningful duration of observation for a small cohort. The clinical signal is encouraging and consistent across disease manifestations. Clinicians reported improvement with no patient showing progression spanning cytopenias, splenomegaly, lymphadenopathy, liver disease, and lung disease. Immune profile showed reduced transitional and CD21 low B cells confirming the meaningful PI3K delta pathway modulation consistent with the APDS experience. This biomarker data is also being collected in the Phase II studies. Regarding safety, Adverse events were generally manageable and consistent with the disease severity. While this is clinician-reported data and not a prospective clinical study, the breadth and consistency of improvement across these various endpoints is a compelling early signal ahead of the formal study readouts in the second half of this year. So quite a bit to look forward later this year. And with that, I'll turn it over to Kenneth to walk through our financials.

Thank you, Anurag. I will now briefly cover our Q1 2026 results and our full-year outlook. Q1 revenues were 72.4 million, down 8% year-on-year. Ruconest revenue declined 15%, reflecting the expected U.S. inventory normalization contributing 8% decline, consistent with our expectation for 7% to 9% headwind that we communicated on the March Q4 call, as well as also our planned strategic exit from U.S. markets, which contributed 3% to the decline. Q1 is also typically the lowest seasonal quarter for Ruconest due to ordering patterns and inventory dynamics. Joentja revenues were strong and increased 34% year on year, driven by strong U.S. momentum, continued patient growth, and expanding international demand. Revenue was modestly affected by inventory timing, and excluding this, growth would have been 1 to 2 million US dollars higher. Total operating expenses were down by 9% year on year, adjusted for non-recurring Abliva-related acquisition costs in Q1 of 2025. Overall expenses were flat. This demonstrates our ability to increase pipeline investments without increasing costs overall. Adjusted operating profit declined slightly year over year, noting that 7.8 million US dollar of the non-recurring Ableva acquisition related costs are excluded from the adjusted Q125 figure shown on the slide. And in 2026, we have incremental R&D investments for Napasinone of 2.7 billion included. We generated positive operating cash flow in Q1 of 2 million, reflecting continued strong cost management and financial discipline. Total cash and marketable securities decreased by 9.3 million to 171.8 million, primarily due to a 12.3 million payment related to early termination of the DSP facility lease. For the full year 2026, we are pleased to reaffirm our expectation for total revenues of 405 to 425 million US dollars representing full year growth of approximately eight to 13% versus 2025. This growth is expected to be driven by continued expansion of Ruconest in the US, partially offset by the excess from by the exit from ex-US markets and significant and accelerating growth for Durenge. We delivered a strong exit to Q1, and the low percentage of HAE patients switching to competing oral therapies gives us confidence in our guidance range. Overall, we assume low single-digit annual Rucanest growth at the midpoint of our guidance range, with some pressure expected on Rucanest revenue in Q2, and growth in the second half of the year. For Joangia, we are well positioned for launches in Japan and Europe this year. We also now include expected US pediatric label revenues later this year, previously excluded from our guidance in our outlook. We expect Joangia growth to accelerate with annual growth over 10 percentage points higher than in 2025. The pediatric APDS indication remains an important long-term driver. And for planning purposes, we conservatively assume a six-month FDA review period following resubmission with a launch right thereafter. We continue to expect operating expenses between 330 to 335 million US dollars, including 60 million in incremental R&D investment to advance our pipeline This includes up to 30 million additional for the development of Napassimo. This also reflects the 9 million benefit from the 20% G&A structural headcount reduction announced in October 2025, alongside stable marketing and sales spending. We remain very committed to strong cost management and financial discipline, prioritizing investments that support both NIA and long-term value creation. There are no changes made to any other guidance assumptions, including milestone payments or gross margins. As a reminder, for Juangia, we do not assume the 10 million commercial milestone or additional milestone payments this year. Gross margin is expected to be approximately 90%. Finally, as previously stated, our available cash and future operating cash flows I expect it to fully support all pipeline investments, including all pre-launch activities. And with that, I'll now hand over to Fabrice for his closing remarks.

Thank you, Kenneth. So in summary, this first quarter demonstrated important progress across the business while reflecting viability and recognized revenues. We are encouraged by the opportunity we see for Joinja in the short and long term, and the potential for RecurNest to remain a significant cash engine as an important on-demand treatment for the difficult-to-treat patient subpopulations. We have significant pipeline catalysts later this year. First, the readout of the two Phase II trials for lanylysis in higher-prevalent CIDs, and second, the completion of the enrollment of the Napazimone registrational study in primary mitochondrial disease. As you've seen, the decisive steps that we've taken to improve financial discipline, including optimizing DNA accounts, are starting to deliver tangible results. With our strong commercial and development capabilities, a growth-oriented leadership team, and a scalable organization, We are committed to driving sustainable revenue growth and value creation to achieve our vision of being a leading global rare disease company. Let me now open the line for questions.

Thank you. To ask a question, you will need to press star 1 and 1 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 go to the first question. One moment, please. And your first question today comes from the line of Benjamin Jackson from Jefferies. Please go ahead.

Brilliant. Thank you for the question, guys. I've got two, if I may. The first, just on ReefNest, could you talk a little bit more about why you think you'll see further pressure in the second quarter on that sales line, and then why you think that you, or what gives you the confidence of returning to growth into the second half of the year beyond what you've already described? And then within that also, are you expecting any reversal of this inventory drawdown at all that may help as a bit of a tailwind in context of that? And then secondly, on Joe Enger, perhaps if you could just help paint the picture about how meaningful you think Europe will be this year and how quickly we should anticipate this ramping. Perhaps you could touch on which countries will likely come online in Europe when and how quickly you think you can secure reimbursement there. So anything to build out that picture a little bit more for me would be super useful. Thanks so much.

Thank you, Ben. Yves?

Indeed. So, Ben, thank you so much for the question. I think it's your first one on further pressure in Q2 that we may be anticipating. So we're in the early stages of competitive entry, right? Nine months into the Ceva Trial Stat launch followed quickly by prophylactic treatments. What we're seeing is it takes a few reorder cycles, so three to four reorder cycles for us to see the full impact of trialing behavior and switching behavior. And so as we get into essentially the fourth quarter of a launch post-Ceva Trial Stats, we'll start to see further impact normalized in the second quarter. The second piece that you asked around growth in the second half of the year, today we continue to add both new prescribers and new patient enrollments to RUCANES. What that tells us is there is a clearly defined subpopulation of HAE patients who are high burden patients, so high frequency of attack patients, high attack location patients, where RUCANES continues to have So despite competitive entries, we continue to see new patient generation and new prescriber dynamics in that segment. I'll let Kenneth speak to the inventory drawdown, and I'll talk about Joenja, the question that you had on European launches. So as you know, we had a positive CHMP opinion earlier this year. We're waiting for final approval. And our first launch in Europe will be in Germany this year. So we're really excited about that launch. coming in at the end of toward the second quarter of this year. And that will be meaningful for us because we are anticipating commercial patients, so paid funded commercial patients, into the second quarter. And then additionally, our Japan approval that we received also earlier this year, we're anticipating that launch in August of this year. some key growth drivers for us in the second year for Joenger, in addition to the pediatric approval that we are anticipating for the high doses in the US. Kenneth, do you want to respond to the inventory question?

Yeah, absolutely. And thanks for the question, Ben. So in 2026, we have seen the inventory drawdown, which follows the normal cycle of the year, and compared to last year, where in 2025, the inventory drawdown was lower as the previous year's build was lower as well. So we do anticipate that we are in a year that, again, is more reflective of the normal cycle where there will be inventory built during the second half of the year to basically reflect the demand. So that's how we are looking into the rest of the year.

Great. Thank you so much.

Thank you. Your next question today. comes from the line of Jeff Jones from Oppenheimer. Please go ahead.

Good morning or good afternoon, guys, and thanks for taking the question. Maybe one follow-up on Rucanest and then on Leniolisib. Can you help us maybe uh link the four percent drop in revenue uh not associated with the inventory drawdowns in the planned u.s or the xus exit um with the offset of the 50 new patients on therapy that you mentioned during one queue and then for lineal acid um You talked a little bit about the readouts from the Phase 1-2s that you're running currently for PIDF and CVID. Can you help us link those efficacy-related readouts to expectations around endpoints in Phase 3 and how we can think about expectations and the endpoints moving ahead into more pivotal online studies. Thank you.

Thank you, Jeff. I'll take the first part of your questions on the enrollment, and then I'll let Anne Reich cover the linearity part. When it comes to the enrollments that Livian mentioned, these are 50 new patients which have been enrolled will receive a script. These are not yet 50 new patients on the drug. And so there is always actually a delay between enrollment and patient on therapy. And obviously we'll be working actively on that. I think you should look at enrollment as patient in the pipes that ultimately will, for a large proportion, be treated by RECONNESS. And so, again, seeing a significant number of new enrollment, new scripts for RECONNESS and a significant number of new prescribers, I think, reinforce the recognition of RECONNESS as a distinctive treatment in the HEA on-demand category. I hope I was able to bring color. Thank you for that. These new patients are expected to offset the small number of patients that may adopt actually. As Yvon said today, we've seen only a very limited interest from reconnaissance to try actually. and we've seen a very small number of these patients adopting the drug. And this is obviously linked to the nature of these patients, which are, for the vast majority of them, have a high-burden disease, and often have already failed a number of treatments. Anne Wright, would you like to elaborate on the lennoxib data that are being presented today?

Sure. So, Jeff, I think we have to zoom out of here a bit and look at what the unmet need really here is in this group of patients. And the unmet need is all centered around immune dysregulation. And the immune dysregulation we're talking about is these aspects such as lymphoproliferation and autoimmune disease that isn't being managed adequately by immune globulin replacement therapy that these patients currently receive. So those are the disease manifestations that we're looking at. Those are, in fact, what we see in the expanded access program, these six patients that are being presented today at the CIS meeting. You can see these same disease manifestations, whether it's improvements in their cytopenias, improvements in lymph proliferation, or improvements in some of the other aspects of the autoimmune disease. Those are the things that we're also going to be measuring in both of the phase two studies. So we're looking at lymph node size, spleen size. We're looking at the blood counts. We're looking at some of these other markers of end organ disease activity. And those will then form the basis for the phase three study. But it's exactly, you know, the end points are, I think, very well aligned with the disease manifestation. And again, what we see early from these six patients is improvement or stabilization in all of these aspects.

Thank you very much.

Thank you. Your next question comes from the line of Susila Hernandez from Landshark Kempen. Please go ahead.

Yes, thank you for taking my questions. On your revenue guidance, what could be key drivers that would make the difference between hitting the top end and the bottom end of your range. What are your assumptions here? And could you share more color on the compassionate use experience in CVID? How much do these patients resemble the patients in your phase two study? Thank you.

Yeah, thank you. This is Kenneth here. Thanks, Susheela. So, I think the way to think about it is that we are anticipating six months for approval and launch right thereafter for the US pediatric population following the submission. And obviously, an accelerated timing of the approval and launch will will provide an upside compared to what we are kind of looking into now, and therefore would put us higher up in the guidance range. That would be the primary driver.

Okay, that's clear. And could you share more color on the data that was presented at CIS on the compassionate use experience in CVID? How much do these six patients resemble the patients in your phase two study? Thank you.

So it's actually a great question. It's something I didn't cover, but these CBID patients and CBID-like patients in the compassionate use experience very much resemble the types of patients that are being enrolled in the CBID study, so the 20-patient multicenter study. And the reason for that is that these patients, all of them have those aspects of immune dysregulation. Now, I would say the only difference here is that this is a much sicker group than the general CVID immune dysregulation population, which is already quite ill to begin with, but this is a group that has been even more refractory to other types of therapies. So the fact that we can see improvements here is, I think, quite meaningful and quite encouraging for us as we look ahead to the results later this year.

Okay, that's clear. Thank you.

Thank you. Your next question. comes from the line of Joe Pant-Guinness from H.C. Wainwright. Please go ahead.

Hi, this is Josh. I'm for Joe. Thanks for taking our questions. So for the first one, could you guys provide more color around the proportion of the identified 4 to 11-year-old APDS patients in the U.S.? So specifically, how many could be covered by the initial 40 and 50 milligram resubmission? And then for the type A meeting, did the FDA feedback change how you're thinking about pediatric dosing more broadly, or has your overall strategy remained largely unchanged?

On the first part of the question, Lieberman?

Sure. Thanks, Josh. On the first one, on the 4 to 11 age group, You can assume approximately half, so roughly 50% of that population would be eligible for the high-dose linoleus and half would be on the lower end.

And Ray? And so, Josh, on the Type A meeting and the feedback that we got and actually all of the discussions that we've had, I think it really has not changed our dosing strategy. And in fact, what I think, you know, based on this constructive dialogue that we had with FDA, they were, we shared with them the efficacy that we'd observed across the doses, and that has allowed us to maintain the same doses in our resubmission strategy. So the lower weight patients would be maintained on, or we're proposing to maintain them on the same doses that were used in the clinical trial. And that really is tied to the efficacy that was observed in the lower weight patients, which was very similar to the efficacy that was observed in the higher weight patients. So I think that on that basis, we have not changed the dosing strategy. And I think we've come to an agreement with FDA on what the contents of these two resubmissions would be.

Great. Thank you. Very helpful.

Thank you. Your next question comes from the line of Whitney Idem from Canaccord. Please go ahead.

Hey, good morning, guys. Thanks for taking the question. Just to follow up to clarify for the Phase 2 linealysis readouts in the second half, just wanted to confirm, will those be read out at the same time, so it's one readout for both, or is it two, could they come at different times?

On the right. So the study is completed enrollment around the same time. One of the studies is one month shorter in duration. So it is possible that that one, we have all of the data available slightly earlier than the other study. And once we have the data cleaned and available to evaluate, we'll have more specifics on the exact timing of that readout.

Okay, got it. And then headed into those, can you help set investor expectations, I guess, in terms of what would be good data or what you're looking for in both of those studies?

Sure.

Either quantitatively or more qualitatively.

So a lot of the things that we're looking for, first of all, they're aligned with what we observed already in APDS. So we saw... We saw lymph nodes shrink. We saw spleens get smaller. We saw improvements in immune profiles. We saw improvements in blood counts, so the cytopenias, autoimmune cytopenias that occur in these patients. So we've seen that already in APDS, and that's why, again, I really think it is a very nice proof of concept for what we've already done. And then what we know is this is also the unmet need in these other primary immune deficiencies. So really looking for the same things. So we're looking to see if lymph nodes get smaller. We're looking to see if the spleens get smaller. We're looking to see platelet counts or other blood cell counts increase. We're looking for other end organ disease manifestations to see how they also improve. And I think this is also, again, lines up very nicely with the data that will be presented today. that I shared in the slide is that we see already in this early experience with these six patients, we see those same types of improvements. And I think that is, again, a very encouraging early sign. It's not a clinical trial, but it's an early sign that both based on the APDS experience as well as this six-patient expanded access experience, the kinds of things that we can expect to see in the readouts of these two Phase II studies.

Got it.

Thank you. Thank you. As a reminder, if you would like to ask a question, please press star one and one on your telephone. That is star one and one to ask a question. We'll now go to the next question. And the next question today comes from the line of Natalia Webster from RBC. Please go ahead.

Hi there. Thanks for taking my questions. I have a couple of follow ups, please. Firstly, on Rukinest, just on the around 50 new enrollments that you've seen and 23 new prescribers in Q1, do you see this as a sustainable run rate going forward? And then secondly, appreciate it can take three to four reorder cycles to see the full impact, but are you able to provide any quantification on what sort of percentage of your patient base has tried XRV? and what sort of return rate you're seeing to date. And then finally, on Jovenger, you added seven NETS US patients on paid therapy in Q1, and I believe you previously guided to accelerating enrollment this year. Is this acceleration dependent on the pediatric approval, or are you also expecting an acceleration in adult additions in the coming quarters? Thank you.

So I'm going to take that. Thank you, Natalia, for your question. I'll take the first part on reconnaissance and let Lieber elaborate on the second part on joint job. Clearly, we've seen over the past quarter really our ability to see really a sustainable stream of new environments. So despite the launch of new therapies, whether these are prophy therapies, prophylactic therapies, or on-demand therapy, we've seen that because of the differentiated profile of ReConnect, we've been able to gain quarter after quarter, I think, a number of new patients. And we don't see that changing. Specifically at the launch of actually is making the on-demand market more dynamic. We see a significant increase of switches, and doctors are more prone to engage with their patients on whether they are well controlled. And we see an opportunity for RUCONEST to capture even a higher number of patients that would not be controlled correctly on their current treatment. To complement what Kenneth said earlier, this is also a significant element to reach the upper end of our guidance. Clearly, reaching the upper end of our guidance is about the timing for the U.S. approval of the pediatric extension, but also our ability to grow, reconnect, and leverage this market dynamic with more switches. I will now leave a comment on the join jar, on your questions ready to join jar.

Thanks, Fabrice, and thank you, Natalia. So on the Joangia acceleration, we still have significant room for growth in the 12 and above patient population, right? So as we mentioned, we added seven new patients on therapy in Q1, and we're seeing some good sustainable momentum into Q2 already. So as you think about that adult, 12 and above opportunity, we continue to identify new patients, we continue to convert those new patients, and that, A, is a sustainable source of growth for us in the future because there's a lot of room for us to grow. And then I think the point that you mentioned on the pediatric indication in the second half of the year will be an additional growth level for us in the U.S., right? And then ex-U.S., as we mentioned, will be the launch in Germany and launch in Japan later this year. So I would think about the year in these sort of phase steps of acceleration in the current population, the pediatric population, and the international expansion in the second half of the year.

Great. That's very helpful. Thank you.

Thank you. We will now take our final question for today. And the final question comes from the line of Simon Scholles from First Berlin. Please go ahead.

Yes, hello, thanks for taking my question. I've got a question on leniolisib and the type A meeting. My impression in March was that you would be able to deliver the additional information that the FDA required and that probably you'd be able to make immediate resubmissions in both the high dose and the low dose. Could you just outline what extra work you're going to need to do on the low-dose patients until you resubmit in the summer?

Sure, I can answer that. So I think what we really, you know, when we met with FDA, and I think what we tried to define was the fastest way to bring Joenja to this youngest group of patients was and to try to do it in a way that allowed us to leverage the data we already had. And that's why we went with this two submission approach that allows this 40 and 50 milligram submission to already occur. In fact, we submitted it, as I said, on the same day that we received the FDA meeting minutes. So I think that was a very important outcome. For the second group, really this was just making sure that we had all of the efficacy data And as I said earlier, the efficacy data that lined up very nicely in both the high dose and the low dose groups or the high weight and lower weight patients. So it's really just putting that data package together. I think the key piece or the key point to note is that we have an agreement with FDA on what the contents of that submission will be. And importantly, it doesn't require an additional clinical trial, this submission. I think that's where we are, and that's why we went with this two-submission approach, and we expect to make the second submission in this summer.

Okay. Thanks very much.

Thank you. I will now hand the call back to Fabrice Sharuraki for closing remarks. Please go ahead.

Thank you so much, operator. I hope we were able to provide clarity on our performance in the first quarter. As we said, we've seen meaningful improvements across the business, despite some revenue viability. I personally believe, as the rest of the leadership team, that those progress are really positioning farming extremely well. for long-term value creation. And so we look forward to updating you on our plan for the short and mid-term and long-term as well. Thank you so much.

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