Pharming Group N.V. (PHAR) Q1 2026 Earnings Report, Transcript and Summary

Good day, and thank you for standing by. Welcome to the Pharming Group N.V. First Quarter 2026 Results Webcast and Conference Call. [Operator Instructions] 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 Chouraqui, CEO. Please go ahead.

Thank you, operator, and good morning and good afternoon, everyone, and welcome to our Q1 2026 earnings call. I'll be joined on this call today by Leverne Marsh, our Chief Commercial Officer; Anurag Relan, our Chief Medical Officer; and Kenneth Lynard, our Chief Financial Officer. Next slide. In this call, we will be making forward-looking statements that are based upon our current insight 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 a drop in quarterly revenue driven by RUCONEST. The RUCONEST revenue decline was largely expected due to inventory drawdown at specialty pharmacy, which we discussed on our Q4 2025 call in March. The commercial exit from non-U.S. 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 RUCONEST in this market was not financially sustainable. Now if we look at the underlying fundamentals, we see limited interest from patients on RUCONEST to try alternative therapies. Nine months after the launch of a new oral therapy, we have retained the overwhelming majority of RUCONEST patients, and we continue to see new patients starting RUCONEST. Leverne will elaborate on this market dynamics in a few moments. Turning now to Joenja. This product is an important growth driver still early in its life cycle. Joenja revenues grew by 34%, reflecting strong momentum, both in the U.S. 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 Joenja in Japan and in Europe later this year and to extend Joenja's 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 2 highest dose, covering a meaningful proportion of children from 4 to 11. We are also planning to submit an sNDA this summer for the lowest doses. Finally, our disciplined cost management helped us to maintain positive cash flow from operations in this quarter despite the variability in revenues. We are maintaining our revenue guidance of $405 million to $425 million for 2026, representing growth between 8% and 13% year-on-year. Next slide. As you can see, the durability of the RUCONEST franchise and the strong momentum and growth potential of Joenja underpin the transformation of Pharming into a profitable high-growth biotech with 2 late-stage pipeline programs offering $1 billion sales potential. RUCONEST 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 patient subpopulation and it's highly manufacturing -- its highly specific manufacturing process. Joenja 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 2 Phase II readouts later this year. Anurag will discuss an exciting presentation at the CIS conference taking place today that summarizes clinician experience treating patients with CVID with immune dysregulation enrolled in our access program. And last but not the least, napazimone, previously known as KL1333 for primary mitochondrial disease is another $1 billion-plus opportunity with the registrational study expected to complete enrollment this year and read out next year. These commercial assets and high-value pipeline, combined with durable source of cash flow, provide a solid foundation for Pharming 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 Leverne, who will provide deeper insights into the performance of our commercial products.

Good morning, good afternoon, everybody. Let me start with RUCONEST performance in the first quarter. Revenue was down 15% year-on-year. Importantly, as Fabrice mentioned, this was anticipated and largely driven by 3 distinct factors. First, inventory dynamics, which reduced 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 U.S. HAE market, we see 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 on to RUCONEST. This is a meaningful signal that clinicians continue to see the value of RUCONEST and 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 RUCONEST fits, and it's reflected in what we're seeing in the market today. After 9 months into the launch of a new oral competitor in HAE in the U.S., the overwhelming majority of RUCONEST patients have remained on therapy. Among those who have explored alternatives, many high-burden patients are returning to RUCONEST, in particular, when response to new treatments have not been adequate. This reinforces the importance of having a dependable on-demand therapy like RUCONEST and underpins our confidence in the long-term role of RUCONEST 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 7 during the quarter, an improvement over the additions seen in the previous 2 quarters. The U.S. fill rate remained high at 85%, reflecting our highly effective reimbursement support and 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 U.S. and an additional 57 eligible patients in the 4 to 11 years old group, and this represents the next frontier for growth in the U.S. In international markets, we continue to see strong patient uptake in the U.K. 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 a 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 the U.S. 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 life cycle and label expansion beyond APDS, specifically exponentially larger patient pools in genetic PIDs and CVID with immune dysregulation. Taken together, these 4 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 life cycle efforts on Joenja, I will now hand it over to Dr. Anurag Relan, our Chief Medical Officer.

Thank you, Leverne. 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 labeled 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 2 APDS expert physicians, and we were pleased with the constructive dialogue and understanding of the issues raised by FDA in 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 milligrams 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 4- to 11-year-old children. An FDA decision on this is expected in 6 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 6-month review. Next slide. At the Clinical Immunology Society Annual Meeting this week, Pharming and our collaborators are presenting 7 abstracts, 5 expanding the evidence base in APDS and 2 that begin to provide data on a 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 leniolisib. 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 of immune cells and the imbalance in the pathway, which underlines the immune dysfunction across several primary immune deficiencies. This mechanistic understanding forms the scientific rationale for our Joenja development program. Joenja, 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 2 Phase II studies evaluating leniolisib in other PIDs. These have significantly greater prevalence in APDS but share unmet medical needs, underlying mechanisms and disease pathology. The programs target 2 similar populations. The first is genetically identified PIDs with immune dysregulation, which represent a prevalence that's 5x 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 26x 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 3-dose escalation design to characterize dose response and confirm the optimal dosing strategy. The studies address 2 core objectives. First, of course, to address -- assess safety, tolerability and 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-reported 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 readouts, we can see some important early clinical evidence supporting leniolisib 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 leniolisib through an expanded access program for a median of 1.4 years with individual exposure ranging from 0.5 year to 2.5 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 patients 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. Joenja 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 USD 1 million to USD 2 million higher. Total operating expenses were down by 9% year-on-year. Adjusted for nonrecurring 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 USD 7.8 million of the nonrecurring Abliva acquisition-related costs are excluded from the adjusted Q1 '25 figure shown on the slide. And in 2026, we have incremental R&D investments for napazimone of $2.7 million 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 USD 405 million to USD 425 million, representing full year growth of approximately 8% to 13% versus 2025. This growth is expected to be driven by continued expansion of RUCONEST in the U.S. partially offset by the excess -- by the exit from ex U.S. markets and significant and accelerating growth for Joenja. 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 RUCONEST growth at the midpoint of our guidance range with some pressure expected on RUCONEST revenue in Q2 and growth in the second half of the year. For Joenja, we are well positioned for launches in Japan and Europe this year. We also now include expected U.S. pediatric label revenues later this year, previously excluded from our guidance in our outlook. We expect Joenja 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 6-month FDA review period following resubmission with a launch right thereafter. We continue to expect operating expenses between USD 330 million to USD 335 million, including $60 million in incremental R&D investment to advance our pipeline. This includes up to $30 million additional for the development of napazimone. 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 near- 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 Joenja, 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 are expected to fully support all pipeline investments, including all prelaunch 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 variability in RUCONEST revenues. We are encouraged by the opportunity we see for Joenja in the short and long term and the potential for RUCONEST to remain a significant cash engine as an important on-demand treatment for the difficult-to-treat patient subpopulation. We have significant pipeline catalysts later this year. First, the readout of the 2 Phase II trials for leniolisib in higher prevalent PID. 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 G&A headcounts 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.

[Operator Instructions] And your first question today comes from the line of Benjamin Jackson from Jefferies.

I've got 2, if I may. The first just on RUCONEST. 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 Joenja, 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.

Thank you, Ben. Leverne?

Indeed. So Ben, thank you so much for the question. I think to your first one on further pressure in Q2 that we may be anticipating. So we're in the early stages of competitive entry, right, 9 months into the sebetralstat launch followed quickly by prophylactic treatments. What we're seeing is it takes a few reorder cycles. So 3 to 4 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 sebetralstat, we'll start to see further impact normalize 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 RUCONEST. 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 RUCONEST continues to have a place. 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 -- towards 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. So some key growth drivers for us in the second year for Joenja in addition to the pediatric approval that we are anticipating for the high doses in the U.S. Kenneth, do you want to respond to the inventory question?

Yes, 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 build 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.

Your next question today comes from the line of Jeff Jones from Oppenheimer.

Maybe one follow-up on RUCONEST and then on leniolisib. Can you help us maybe link the 4% drop in revenue not associated with the inventory drawdowns in the planned U.S. or the ex U.S. exit with the offset of the 50 new patients on therapy that you mentioned during 1Q? And then for leniolisib, you talked a little bit about the readouts from the Phase I/IIs that you're running currently for PIDs and CVID. Can you help us link those efficacy-related readouts to expectations around endpoints in Phase III and how we can think about expectations and the endpoints moving ahead into more pivotal aligned studies?

Thank you, Jeff. I'll take the first part of your questions on the enrollment, and then I'll let Anurag cover the leniolisib part. When it comes to the enrollment that Leverne mentioned, these are 50 new patients which have been enrolled, who 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 patients in the pipes that ultimately will, for a large proportion, be treated by RUCONEST. And so again, seeing a significant number of new enrollment, new scripts for RUCONEST and a significant number of new prescribers I think, reinforce the recognition of RUCONEST as a distinctive treatment in the HAE on-demand category. I hope I was able to bring color. These new patients are expected to offset the small number of patients that may adopt Ekterly. As Leverne said today, we've seen only a very limited interest from RUCONEST patients to try Ekterly, 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 vast majority of them have a high burden disease and often have already failed a number of treatments. Anurag, would you like to elaborate on the leniolisib data that are being presented today?

Sure. So Jeff, I think you have to zoom out 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 immunoglobulin replacement therapy that these patients currently receive. So that's the -- those are the disease manifestations that we're looking at. Those are, in fact, what we see in the expanded access program, these 6 patients that are being presented today at the CIS meeting, you can see the disease -- the same disease manifestations, whether it's improvements in their cytopenias, improvements in lymphoproliferation 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 the -- in both of the Phase II 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 III study. But it's exactly -- the endpoints are, I think, very well aligned with the disease manifestation. And again, what we see early from these 6 patients is improvement or stabilization in all of these aspects.

Your next question comes from the line of Sushila Hernandez from Lanschot Kempen.

On your revenue guidance, what could be key drivers that could 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 II study?

Yes. Thank you. This is Kenneth here. Thanks, Sushila. So I think the way to think about it is that we are anticipating 6 months for approval and launch right thereafter for the U.S. pediatric population following the submission. And obviously, an accelerated timing of the approval and launch 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 will 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 6 patients resemble the patients in your Phase II study?

Sushila, so it's actually a great question. It's something I didn't cover, but these CVID patients and CVID-like patients in the compassionate use experience very much resemble the types of patients that are being enrolled in the CVID 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 is even more -- 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.

Your next question comes from the line of Joe Pantginis from H.C. Wainwright.

This is Josh on for Joe. 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-milligram 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, Leverne?

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 leniolisib and half would be on the lower end.

Anurag?

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 based on this constructive dialogue that we had with FDA, they were -- we shared with them the efficacy that we had 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 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 2 resubmissions would be.

Your next question comes from the line of Whitney Ijem from Canaccord.

Just a follow-up to clarify for the Phase II leniolisib readouts in the second half. I just wanted to confirm, will those be read out at the same time? So it's one readout for both? Or is it 2 -- could they come at different times?

Anurag?

So the study has completed enrollment around the same time. One of the studies is 1 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 heading 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, either quantitatively or more qualitatively?

Sure, Whitney. So a lot of the things that we're looking for, they are -- first of all, they're aligned with what we observed already in APDS. So 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 these are -- this is also the unmet need in these other primary immune deficiencies. So we're 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 manifest -- 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 and I shared in the slide, is that we see already in this early experience with these 6 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 the 6-patient expanded access experience, the kinds of things that we can expect to see in the readouts of these 2 Phase II studies.

[Operator Instructions] And the next question today comes from the line of Natalia Webster from RBC.

I have a couple of follow-ups, please. Firstly, on RUCONEST. 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, I appreciate that it can take sort of 3 to 4 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 Ekterly and what sort of return rate you're seeing to date? And then finally, on Joenja, you added 7 net U.S. patients on paid therapy in Q1, and I believe you previously guided to accelerating enrollment this year. Is this acceleration dependent on pediatric approval? Or are you also expecting an acceleration in adult additions in the coming quarters?

So I'm going to take. Thank you, Natalia, for your question. I'll take the first part on RUCONEST and let Leverne elaborate on the second part on Joenja. Clearly, we've seen over the past quarters really our ability to see really a sustainable stream of new enrollment. So despite the launch of new therapies, whether these are prophy therapy -- prophylactic therapies or on-demand therapy, we've seen that because of the differentiated profile of RUCONEST, we've been able to gain quarter after quarter, I think, a number of new patients. And we don't see that changing. Specifically as the launch of Ekterly 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 could not be controlled correctly on their current treatment. And 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 RUCONEST and leverage this market dynamic with more switches. I would let now Leverne comment on the Joenja -- on your questions related to Joenja.

Okay. Thanks, Fabrice, and thank you, Natalia. So on the Joenja acceleration, we still have significant room for growth in the 12 and above patient population, right? So as we mentioned, we added 7 new patients on therapy in Q1, and we're seeing some good sustainable momentum into Q2 already. So as you think about the adult 12 and above opportunity, we continue to identify new patients. We continue to convert those new patients, and that 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 lever for us in the U.S., right? And then ex U.S., as we mentioned, will be the launch in Germany and the launch in Japan later this year. So I would think about the year in these sort of phased steps of acceleration in the current population, the pediatric population and the international expansion in the second half of the year.

We will now take our final question for today. And the final question comes from the line of Simon Scholes from First Berlin.

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 resubmissions, 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, Simon. So I think what we really -- 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 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 2 submission approach that allows this 40-milligram 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 with the in both the high dose and the low dose groups, or sort of 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. So I think that's where we are, and that's why we went with this 2 submission approach. And then, we expect to make the second submission in this summer.

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

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

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