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Good day, and thank you for standing by. Welcome to the Pharming Group N.V. 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'll be a question-and-answer session. To ask a question during the session, you will need to press star one and one on your telephone. You will hear an automated message advising your hand is raised. To withdraw your question, please press star one and one 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 Chouraqui, CEO. Please go ahead.

Thank you, operator, good morning and good afternoon, everyone, and welcome to our Q1 2026 earning 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 plan. 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 patient 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 dynamic in a few moments. Coming 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. 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, 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 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-$425 million for 2026, representing growth between 8%-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 two late-stage pipeline programs offering billion-dollar sales potential. RUCONEST is the foundation of our portfolio and a reliable cash engine for the future, even in the ever more crowded HAE market, given its differentiated value proposition for the difficult to treat patient subpopulation and 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 two phase II readout later this year. Anurag will discuss an exciting presentation at CIS conference taking place today that summarizes clinician experience treating patients with CVID, with immune dysregulation enrolled in our access program.

Last but not the least, napazimone, 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 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 three 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%. 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've seen measured impact from competition, specifically limited patient interest in trialing or switching to other therapies, with many returning. 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, in 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 nine 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 had 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. 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. We accelerated the rate of new patient starts to seven during the quarter, an improvement over the additions seen in the previous two 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 four to 11 years old group, 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 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 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. 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 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 indications 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 label to pediatrics for children ages four 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 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. We have that now, with the first step being the resubmission of the sNDA for the highest doses, specifically 40 and 50 mg. This took place in April, in fact, on the same day that we received the FDA's meeting minutes. 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, Pharming 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 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, an imbalance in the pathway which underlies 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 two 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 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.

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 the 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 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 readouts, we can see some important early clinical evidence supporting leniolisib's 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 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. Quite a bit to look forward later this year. 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 EUR 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%-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 $1 million-$2 million higher.

Total operating expenses were down by 9% year-on-year. Adjusted for non-recurring Abliva-related acquisition costs in Q1 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 of the non-recurring Abliva acquisition-related costs are excluded from the adjusted Q1 2025 figure shown on the slide. In 2026, we have incremental R&D investments for napazimone of EUR 2.7 million included. We generated positive operating cash flow in Q1 of EUR 2 million, reflecting continued strong cash, cost management and financial discipline. Total cash and marketable securities decreased by EUR 9.3 million to EUR 171.8 million, primarily due to a EUR 12.3 million payment related to early term-termination of the DSP facility lease.

For the full year 2026, we are pleased to reaffirm our expectation for total revenues of $405 million-$425 million, representing full year growth of approximately 8%-13% versus 2025. This growth is expected to be driven by continued expansion of RUCONEST in the U.S., partially offset 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 % 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 six-month FDA review period following resubmission with a launch right thereafter. We continue to expect operating expenses between $330 million-$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 EUR 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 pre-launch activities. With that, I'll now hand over to Fabrice for his closing remarks.

Thank you, Kenneth. In summary, this first quarter demonstrated important progress across the business while reflecting viability 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 two phase II trials for leniolisib in higher prevalent PIDs. 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 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 one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. We will now go to the first question. One moment, please. 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 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? 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? 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? Then secondly, on Joenja, perhaps if you could just help paint the picture about how meaningful you think the 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. Anything to build out that picture a little bit more for me would be, would be super useful. Thanks so much.

Thank you, Ben. Leverne?

Indeed. Ben, thank you so much for the question. I think your first one on further pressure in Q2 that we may be anticipating. 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 three to four reorder cycles for us to see the full impact of trialing behavior and switching behavior. 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. 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. As you know, we had a positive CHMP opinion earlier this year. We're waiting for final approval. Our first launch in Europe will be in Germany this year. We're really excited about that launch coming in at the end of toward the second quarter of this year.

That will be meaningful for us because we are anticipating commercial patients, so paid funded commercial patients, into the second quarter. 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 Joenja, in addition to the pediatric approval that we are anticipating for the higher doses in the U.S. Kenneth, do you want to respond to the inventory question?

Yeah, absolutely. Thanks for the question, Ben. In 2026, we have seen the inventory drawdown, which follows the normal cycle of the year. Compared to last year, where in 2025, the inventory drawdown was lower as the previous year's build was lower as well. 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. 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 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? 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 endpoints moving ahead into more pivotal aligned studies? Thank you.

Thank you, Jeff. I'll take the first part of your questions on the enrollment. Then I'll let Anurag cover the leniolisib part. When it comes to the enrollments that Leverne mentioned, these are 50 new patients which have been enrolled, will receive a script. These are not yet 50 new patients on the drug. There is always actually a delay between enrollment and a patient on therapy. 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 RUCONEST.

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.

Thank you for that.

All these new patients are expected to offset the small number of patients that may adopt, actually. As Leverne said today, you know, we've seen only a very limited interest from RUCONEST patients to try actually, and we've seen a very small number of these patients adopting the drug. 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. 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. The unmet need is all centered around immune dysregulation. 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. 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 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 both of the phase II studies. 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. Those will then form the basis for the phase III study. It's exactly, you know, the endpoints are, I think, very well aligned with the disease manifestation. 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 Suzanne Van Voorthuizen from Van Lanschot Kempen. Please go ahead.

Yes. Thank you for taking my questions. 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? 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? Thank you.

Kenneth Lynard.

Yeah. Thank you. This is Kenneth. Thanks, Suzanne. 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. 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 would be the primary driver.

Okay, that's clear. 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 II study? Thank you.

Sure.

Hi, Susila. It's actually a great question and something I didn't cover. 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. 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. 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 Joseph Pantginis from H.C. Wainwright. Please go ahead.

Hi, this is Josh on for Joe. Thanks for taking our questions. For the first one, could you guys provide more color around the proportion of the identified four to 11-year-old APDS patients in the U.S.? Specifically, how many could be covered by the initial 40 and 50-mgm resubmission? 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 four 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?

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. 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. 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. 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.

I think 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 Ijem from Canaccord. Please go ahead.

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

Anurag?

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. 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, Whitney.

Either quantitatively or more qualitatively.

A lot of the things that we're looking for, first of all, they're aligned with what we observed already in APDS. 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. We've seen that already in APDS. That's why, again, I really think it is a very nice proof of concept for what we've already done. What we know is this is also the unmet need in these other primary immune deficiencies, so really looking for the same things. 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. I think this is also, again, lines up very nicely with the data.

We presented today that I shared in the slide is that we see already in these in this early experience with these six patients, we see those same types of improvements. 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. 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 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? Secondly, appreciate it can take sort of three to four reorder cycles to see the full impact. 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? Finally on Joenja, you added seven net U.S. patients on paid therapy in Q1 and 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 patients in the coming quarters? Thank you.

Thank you, Natalia, for your question. I'll take the first part on RUCONEST and let Libby elaborate on the second part on Joenja. Clearly, we've seen over the past quarter really our ability to see a sustainable stream of new enrollments. Despite the launch of new therapies, whether these are 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 a significant number of new patients. 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 switchers, and doctors are more prone to engage with their patients on whether they are well controlled. We see an opportunity for RUCONEST to capture 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 RUCONEST and leverage this market dynamic with more switchers.

I will let now, Libby comment on the Joenja, on your questions related to Joenja.

Thanks, Fabrice, and thank you, Natalia. On the Joenja acceleration, we still have significant room for growth in the 12 and above patient population, right? As we mentioned, we added seven new patients on therapy in Q1, and we're seeing some good sustainable momentum into Q2 already. 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. 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?

Ex-U.S., as we mentioned, will be the launch in Germany and launch in Japan later this year. 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.

Great. That is very helpful. Thank you.

Thank you. The final question comes from the line of Simon Scholes 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 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. 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 as and, to try to do it in a way that allowed us to leverage the data we already had. That's why we went with this two-submission approach that allows this 40 and 50 mg submission to already occur. We submitted it, as I said, on the same day that we received the FDA meeting minutes. 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 the high-weight and lower weight patients. 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. 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. Then 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 Chouraqui for closing remarks. Please go ahead.

Thank you so much, operator. I hope 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 viability. I personally believe as the rest of the leadership team that we are those progress are really positioning Pharming Group extremely well for long-term value creation. 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.

Good day, thank you for standing by. Welcome to the Pharming Group N.V. fourth quarter and full year 2025 financial 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. To ask a question during the session, please press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please note that today's conference is being recorded. I would now like to hand the conference over to your first speaker, Mr. Fabrice Chouraqui, CEO. Please go ahead, sir.

Thank you, operator. Good morning and good afternoon, everyone, and welcome to our Q4 and full year 2025 earnings call. I'll be joined on this call today by LaVerne Marsh, our new Chief Commercial Officer, Anurag Relan, our Chief Medical Officer, and Kenneth Lynard, our Chief Financial Officer. On this call, we will be making forward-looking statements that are based upon our current insights and plans. As you know, these may differ from future results. As you saw in our press release, Pharming ended 2025 on a strong note, operationally and financially. Total revenues grew by 15% in the fourth quarter of 2025, and by 27% for the full year. Thanks to disciplined cost management, we delivered $26 million of operating profit in 2025, compared to a loss in 2024. We also significantly increased our cash position.

Operating cash flow came in at $55 million in 2025, putting our cash position at year-end above that of the end of 2024 level before the acquisition of Abliva. 2025 was marked by significant growth of our two commercial assets, RUCONEST and Joenja. RUCONEST grew 26% year-over-year and by 9% in the fourth quarter. With its efficacy, with its reliability and its rapid onset of action, RUCONEST is poised to remain an established on-demand treatment option for difficult to treat patients in an evolving HAE treatment landscape. LaVerne will talk more about RUCONEST performance and its unique value proposition.

Joenja grew 29% year-over-year and by 53% in the fourth quarter, fueled by the acceleration of new patients on drug in the U.S., but also increased demand in international markets, including in the U.K., where the drug was launched last spring, and in other countries through purchases under government-supported access program. These results underscore Pharming's transformation from a single asset company into a highly profitable high-growth biotech with two commercial products and a late-stage pipeline with two programs offering billion-dollar sales potential. We highlighted these programs at our Investor Day last month, offering investors unique insights to our high-value pipeline. RUCONEST is the foundation of our portfolio and a reliable cash engine for the future, even in a more crowded HAE on-demand market, given its efficacy profile on the difficult to treat patient sub-subpopulation.

Joenja is just at the beginning of its life cycle with multiple growth catalysts in APDS, international geographic expansion, and potential expansion into much larger PIDs. Napazimone, which we used to call KL1333 for primary mitochondrial disease is another billion-dollar-plus opportunity with the registrational study now well underway. This combination of durable revenue, first in disease innovation, and an advancing late-stage pipeline positions Pharming well for substantial near-term and long-term value creation. Let me now turn to our outlook for the remainder of 2026. As announced at our Investor Day in February, we expect 2026 revenue between $405 million and $425 million this year, representing an 8%-13% growth, with operating expenses increasing at a slower overall pace, even with substantially higher R&D investment in our pipeline to fuel future growth.

We expect continued RUCONEST growth for the reason mentioned earlier and accelerating Joenja growth fueled by the uptake in APDS patients above 12 years in the U.S. and potential future regulatory approval internationally. Regarding the U.S. pediatric label expansion, we've been working to address the FDA request, and we expect to have greater clarity on the resubmission requirements and timeline following the FDA Type A meeting, which is now scheduled at the end of March. 2026 is an important year for our pipeline with the materialization of potential value inflection points. We have now completed the enrollment of two leniolisib phase II trials for lower prevalence PIDs, and we expect a top-line data readout in the second half of this year. We also expect to complete enrollment in the napazimone pivotal study this year to be in a position for a data readout at the end of 2027.

We are clearly determined to maintain strong financial discipline to optimize capital allocations on our growth drivers. This is critical as we strive to build an efficient and scalable organization and make Pharming a leading rare, ultra-rare disease company and deliver sustainable value for our shareholders. Let me now turn to LaVerne Marsh for deeper insights on the performance of our commercial portfolio.

Good day, everybody. Let me start with RUCONEST, where the U.S. business delivered another year of strong and resilient performance. In 2025, despite the first new wave of treatment options in the HAE market in almost five years, RUCONEST continued to grow as an essential therapy for patients living with severe high-frequency HAE attacks. Our strategy remains consistent. Focus on high-attack patients who require fast, reliable, on-demand treatment and ensure that we continue to execute against that differentiated value proposition even as new agents enter the market. For the full year, RUCONEST delivered 26% global revenue growth and a volume growth in the U.S. of 20%. A clear indicator of the strong and durable demand for RUCONEST in the acute segment.

In quarter four, we delivered 9% global revenue growth versus the prior year quarter and a 2% volume growth in the core U.S. market, continuing the upward trajectory of RUCONEST. As expected, through Q4, we began to observe impact of newly launched therapies for HAE in the U.S. market, with some patients trialing and some already returning to RUCONEST. Despite these competitive dynamics, we welcomed over 60 new enrollments in the U.S. in the fourth quarter, slightly above Q3. RUCONEST added both new patients and new prescribers in the quarter, underscoring the resilience of our position in the difficult-to-treat patient segments and the clinical trust placed in RUCONEST in real-world settings. That said, the high burden of HAE matters for patients who have high-frequency attacks. Attacks are often unpredictable and potentially life-threatening, and symptom severity often escalate within hours.

Importantly, for patients experiencing multiple attacks per month, or patients who experience suboptimal responses to other options, dependable rapid relief is not optional, it is essential. This high-frequency attack segment is precisely where we have seen consistent, durable use of RUCONEST over time and where we expect RUCONEST to remain highly relevant even as new treatments enter the market. To that end, a meaningful proportion of new patient enrollments in the U.S. are switches to RUCONEST from other on-demand therapies, further emphasizing the continued need that high-attack patients have for an effective, reliable one-and-done therapy like RUCONEST. When you put this together, the unpredictability of the disease, the high burden carried by certain patient segments, the limitations of some other acute therapies, and consistently strong clinical performance associated with RUCONEST, the unique value proposition for RUCONEST remains clear.

Looking ahead, we foresee some pressure on our growth early in the year, but with no change in the need for an effective, rapid-onset, reliable one-dose treatment like RUCONEST. With that in mind, let me turn to Joenja. For Joenja, we delivered a strong fourth quarter, building on the momentum we established throughout the year. Revenue grew 53% compared to the fourth quarter in 2024, reaching $19.8 million globally. For the full year, Joenja generated $58 million, representing 29% growth year-on-year and demonstrating both sustained utilization from patients and the expanding clinical recognition and treatment of APDS. In the United States, patient growth remained a central driver of performance. By the end of 2025, we had 120 patients on paid therapy, representing a 25% increase over year-end 2024.

This steady expansion of our treated population reflects strong physician confidence, consistent engagement with patient communities, and a team that executes with discipline and with urgency. Equally important, we made significant progress in broadening the pool of identified APDS patients, one of the most critical leading indicators in an ultra-rare disease. In 2025, the number of U.S. patients we identified diagnosed with APDS increased by 40, more than double the increase of 18 we saw in 2024. This growth in identified patients with APDS shows that our educational efforts, our diagnostic partnerships, and our medical engagement in the U.S. are working. Outside the U.S., we saw strengthening demand across international markets, including a solid first-year uptake in the United Kingdom following the launch in April 2025. We also benefited from government-supported access programs, which allowed us to reach more patients who currently have limited therapeutic options.

Taken together, these results give us a strong platform for Joenja in the years ahead. Finally, we expect geographic expansion and the anticipated four to 11-year approval in the United States to be meaningful contributors to growth. These two catalysts remain materially important to increase the number of patients who can benefit from Joenja and expand the global footprint of the APDS business. Internationally, we've already demonstrated our ability to execute. In the U.K., where Joenja launched in April 2025, we have seen solid early uptake and strong engagement for complexity. That success reinforces that our teams have the capability, the infrastructure, and the strategic focus needed to deliver in new markets. In the United States, our commercial teams are fully prepared to launch Joenja for children ages four to 11, pending FDA approval.

Importantly, we already have 52 eligible patients identified, one-third of them currently on therapy through our early access program, ready to transition at approval. This will give us a running start and positions us for early momentum once the label is approved. Beyond the U.S., our international organization is deeply engaged in progressing regulatory submissions and ensuring that reimbursement discussions can start when approvals are granted across Europe, Japan, and Canada. Across these three regions, we have over 80 patients already receiving Joenja through early access mechanisms, awaiting full regulatory approval and commercial availability. This represents a significant built-in foundation for launch acceleration once those approvals are secured. As we're stepping into 2026, we do so with confidence.

For Joenja, we have the right growth catalysts in front of us, and we have an organization that has demonstrated that it can execute launches with precision and continuity. This gives us confidence not just in the next quarter, but in the sustained global expansion of Joenja over the coming years. With that, I'll now hand over to Dr. Anurag Relan, our Chief Medical Officer, who will walk you through our progress across the pipeline and the upcoming development and regulatory milestones.

Thank you, LaVerne. As we discussed at our Investor Day in February, PI3K delta is a master regulator of the immune system, and imbalances here contribute to immune dysregulation in a number of primary immune deficiencies or PIDs. This understanding serves as the foundation and rationale for our Joenja development efforts. APDS, where Joenja is currently approved, is a primary immune deficiency caused by a genetic defect that leads to PI3K delta hyperactivation. This results in the dysfunction of the immune system and is characterized by frequent and severe infections and a wide array of immune dysregulation consequences, as you see here. APDS is a progressive disease and leads to early mortality due to these complications, with unfortunately about 25% of patients dying by the age of 30.

Based on this understanding of APDS, we have two ongoing phase II proof-of-concept clinical trials evaluating leniolisib in more prevalent PIDs, which share unmet medical needs, mechanisms, and disease pathology with APDS. These include the genetically identified primary immune deficiencies with immune dysregulation linked to altered PI3K delta signaling and common variable immune deficiency, or CVID, with immune dysregulation, which is identified independently of genetics. As Fabrice mentioned, both of these studies have now completed enrollment. As you see here, APDS falls under the broader CVID umbrella diagnosis, and Joenja, in fact, serves as a proof of concept for the work we are doing now in these much more prevalent PIDs. This slide highlights the opportunity now to broaden the use of Joenja.

The prevalence figures here are for the U.S., but they illustrate the larger opportunity to serve patients and underpin peak sales potential above $1 billion. We're very excited about the work that I just discussed to study Joenja in these additional PIDs with immune dysregulation beyond APDS. These address significantly larger patient populations, which are five to 26 times the prevalence of APDS. In APDS, LaVerne already discussed progress with patient identification and our commercial preparations for geographic and pediatric expansion. Let me update you now on the variants of uncertain significance project and the opportunity there. Following various discussions over many months involving Columbia and genetic testing labs, it became clear that the labs require additional evidence to reclassify VUSs. Understanding the consequences of VUSs remain a significant unmet need and actually a public health problem for clinicians and patients.

As you see, the number of patients with VUS continues to grow. To complement the significant first batch of data which were published in Cell, we are now planning new experiments to generate the data needed to allow genetic testing labs to evaluate VUSs. Following completion of these experiments, we plan to provide an estimate how many VUSs may be reclassified and how many patients may be ultimately diagnosed with APDS. In addition, the work published in Cell also suggests that the prevalence of APDS could be significantly higher than we currently estimate. We convened a global advisory board and are now initiating work to explore and better understand the prevalence of APDS, as well as the spectrum of disease. I will now cover the progress we are making in APDS, including some of our near-term regulatory milestones.

Overall, we made good progress in APDS during 2025 and early this year. While we are disappointed in the complete response letter we received from FDA in January regarding our regulatory submission for the pediatric label expansion for Joenja for the treatment of APDS in children ages four to 11, we believe we can address both the clinical pharmacology and analytical batch testing methodology issues outlined in the letter. A Type A meeting has now been scheduled with FDA for later this month, and we expect to discuss the agency's feedback and align on the path forward for resubmission. In Europe, we have filed a marketing authorization application for leniolisib for patients 12 years and older, and now responded to CHMP's questions on manufacturing activities and quality controls and believe we have addressed their concerns.

We now expect a CHMP opinion on the MAA to take place at their meeting later this month, with potential EC approval in the first half of this year. Regarding the Japan NDA for leniolisib for the treatment of APDS in patients four years of age and over, the Pharmaceutical Affairs and Food Sanitation Council meeting has recommended approval. This news was covered in the Pink Sheet, who importantly noted that this would represent the first approval for children with APDS ages four to eleven. We now await the formal decision by the PMDA by the end of March. I'll now turn to our next pipeline asset, napazimone, or formerly known as KL1333. Napazimone has also progressed significantly in the past year. This is being developed for primary mitochondrial diseases, which is a group of rare disorders where mutations in mitochondrial DNA lead to significant fatigue and muscle weakness.

Napazimone addresses this underlying disorder by normalizing the NAD+ to NADH ratio, which is abnormally low in these patients. There are a large number of these patients already diagnosed across the U.S. and large European countries, where they are treated at centers of excellence and part of strong advocacy groups. Here we have a registration-enabling study underway with endpoints agreed upon with FDA. Importantly, there was a blinded interim analysis in which both endpoints passed futility. Since completing the acquisition of Abliva last year, we are making good progress in the second wave of the study and are on track to complete enrollment later this year, with readout in 2027 and potential approval later in 2028. With that, I'll turn it over to Kenneth now to discuss our financial results.

Thank you very much, Anurag. I'm pleased to now provide some color on our strong 2025 financial performance and our outlook for 2026. The fourth quarter was a strong finish, with revenues of EUR 106.5 million, being 15% growth versus Q4 of 2024. This was driven by continued momentum across our portfolio, including a 9% growth for RUCONEST and a 53% growth for Joenja. Notably, Joenja annual revenues exceeded EUR 50 million for the first time, triggering our first EUR 5 million sales milestone payment in the quarter. As a reminder, this milestone is recorded in cost of goods sold and therefore affected gross margin for the fourth quarter. Adjusted operating profit was broadly stable year-over-year after several offsetting one-off items.

Fourth quarter 2025 expenses include EUR 9.3 million in expenses related to Abliva and napazimone following the completion of the Abliva acquisition this year, as well as the EUR 5 million Joenja sales milestone payment just mentioned. Excluding these items to compare operating profit on a like-for-like basis to the fourth quarter of 2024, operating profit in the fourth quarter of 2025 would have been EUR 14 million higher. Finally, cash and marketable securities increased by EUR 12.2 million from EUR 168.9 million at the end of Q3 to EUR 181 million at year-end, primarily driven by positive operating cash flow, reflecting the strength of our commercial performance. Turning to our full year 2025 results, our financials shows the continued strong execution of our strategy.

Total revenues increased 27% to EUR 376.1 million, driven by robust double-digit growth from both RUCONEST and Joenja. Gross margin remained stable at approximately 88% despite the EUR 5 million Joenja sales milestone recorded in the fourth quarter. Operating expenses rose to EUR 311.3 million. Excluding EUR 4.1 million of one-off restructuring costs related to our G&A reduction program announced in October, operating expenses were EUR 307.2 million and within our previously communicated guidance range of EUR 304-EUR 308 million. Importantly, when also excluding the full EUR 29.7 million of Abliva related expenses, operating expenses increased only 2% on a like for like basis. This reflects disciplined cost management.

In total, adjusted operating profit, which excludes non-recurring Abliva acquisition related costs and other offsetting items, was EUR 36.4 million, compared with a loss of EUR 8.6 million in 2024. Excluding recurring Abliva expenses and the EUR 5 million Joenja sales milestone, operating profit for 2025 would have been EUR 24.4 million higher. Cash flow from operating activities totals EUR 54.7 million versus being slightly negative in 2024, showing the improved profitability and cash generation of the business. Cash and marketable securities increased EUR 11.7 million to EUR 181.1 million, despite EUR 68 million used for the Abliva acquisition. Again, highlighting the strength of our underlying operational cash generation.

Turning to our 2026 outlook, we reaffirm our expectation for total revenues of EUR 405 million-EUR 425 million, representing full year growth of approximately 8%-13% versus 2025. The growth is expected to be driven by continued growth for RUCONEST in the US, partly offset by declining ex-US revenue as we exit those markets and accelerated growth for Joenja. For RUCONEST, quarterly revenue typically fluctuates with patient ordering patterns and channel inventory movements, with the first quarter usually being the lowest. In Q1 2026 inventory drawdowns are expected to impact US RUCONEST revenue growth by 7%-9% year-over-year as market dynamics settle. This is factored into our full year guidance, which assumes mid-single-digit RUCONEST growth at the midpoint of the range.

For Joenja, we expect growth to accelerate with annual growth approximately 10 percentage points higher than in 2025. The pediatric APDS indication remains an important future growth driver, and we look forward to clarity on the U.S. approval timeline for patients aged four to 11 following the upcoming FDA Type A meeting. In the meantime, U.S. pediatric revenues are excluded from our 2026 guidance. For operating expenses, we anticipate a range of EUR 330 million-EUR 335 million, including more than EUR 60 million of incremental R&D investments. This guidance reflects the EUR 9 million favorable impact from the 20% G&A headcount reduction program announced in October 2025, along with stable marketing and sales spending. Overall, we remain committed to financial discipline, prioritizing investment that drive near and long-term value creation for our shareholders.

Because Joenja revenue is not expected to exceed EUR 100 million in 2026, we do not assume the EUR 10 million commercial milestone payments which otherwise would be recorded in cost of goods sold. As communicated during our Investor Day in February and aligned with ex-US rollout plans, no additional milestone payments are expected. We estimate cost of goods sold at 10% of revenues, corresponding to a gross margin of 90%. Finally, available cash and future operating cash flows are expected to fully support pipeline investments, including all pre-launch activities. With that, I will now hand over to Fabrice for his closing remarks.

Thank you, Kenneth. In summary, we are pleased to report another strong quarter and a record year for Pharming in 2025 with $76 million of revenues and a shift to operating profitability and positive operating cash flow. Looking ahead, RUCONEST is poised to remain a cornerstone treatment for severe HAE patients, underpinning a strong revenue base. We see clear revenue catalyst ahead for Joenja, with the product well positioned to generate a significant proportion of our revenues in the future. Our upcoming clinical data readouts, including the leniolisib phase II later this year and the napazimone pivotal study readout next year, each have the potential to unlock significant value and take the company to a whole new level. Finally, the decisive steps we have taken to improve financial discipline will support driving the positive bottom line.

With strong commercial and development capabilities, a fit-for-purpose leadership team with strong new additions like LaVerne and Kenneth and a scalable organization, we are committed to making 2026 another stepping stone in achieving our vision of becoming a leading global rare disease company. Let me now open the line for questions.

Thank you. As a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Once again, please press star one one to ask a question and wait for your name to be announced. To withdraw your question, please press star one one again. Thank you. We are now going to proceed with our first question. The question comes from the line of Lucy Codrington from Jefferies. Please ask your question.

Hi. Thank you for taking my questions. To begin with, Joenja growth this year, how much of that are you expecting to come from the US market versus international markets? Secondly, looking at the US market, of those 61 eligible patients that are not on treatment in the US, how many of these do you think could be converted to paid therapy or how many have been considered versus how many have been ruled out? Finally, in terms of RUCONEST dynamics, you mentioned that you have heard of patients coming back to treatment having tried the orals. Do you have any, I guess, it would be anecdotal, commentary on how quickly the patients return having tried the orals? Thank you.

Very good. Thank you so much, Lucy, for those questions. I'll turn to LaVerne in a minute, actually. Let me start with the last one on RUCONEST, and then we can take your two questions on Joenja. It is true that we've seen some patients trying and coming back. As you know, and as LaVerne reinforced, HA is a very severe disease and patients got to be controlled. Especially patients who were used to a highly reliable treatment.

When those patients try another treatment and see that their crisis is not properly controlled, they tend to come back to their previous medication fairly quickly, because not controlling a crisis could be life-threatening. Now, when it comes to Joenja's growth, as we said, we see the growth in this year in 2026 being fueled both by the continued growth in the U.S. as well as growth increasing in international markets. It's obviously the growth in international markets will come from the U.K., where the drug has been launched, new launch countries.

This will happen in a staged fashion, since once we receive marketing approval, we'll have to negotiate a price and reimbursement. Ultimately, a bigger portion of the growth will come from international market, but that's going to be gradual. When it comes to more specifics on Joenja's patient funnel, I'll ask LaVerne to comment.

Thank you. Thank you, Lucy, for your question. How we would think about the patients considered for Joenja or eligible for Joenja in the US and the pull-through to patients on therapy, that there would be a lag there as patients are going through the patient journey, a fairly complicated patient journey, seeing multiple physicians, the enrollment and then the reimbursement process, before we get to patients on paid therapy. How I would think about the delta there and the opportunity, there's still a substantial proportion of patients both eligible and potentially reimbursable that would drive growth for us in the US in 2026.

Maybe, Lucy, this is Kenneth speaking. Maybe I can just add, out of the expected Joenja growth in 2026, it will probably be around about 70%-75% that will come from the US.

70-75% from the U.S.?

Of the growth in 2026 for Joenja. Yes.

Got it. Thank you very much.

We are now going to proceed with our next question. The question comes from the line of Joseph Pantginis from H.C. Wainwright & Co. Please ask your question.

Hey, everybody. Good morning. Thanks for taking the questions. I know might not be able to give color here ahead of the Type A, but I'm going to ask anyway. Obviously the reasons, you know, for your discussions, as Anurag said, were the clinical pharmacology and the analytical batches. Is there anything that you would consider sort of the lead, rate-limiting step here? That's question number one. Question number two regarding RUCONEST. You touched upon this a little bit, but I guess, you know, the RUCONEST case can be split into two components in my belief. First you have the medical component, which continues to make the case, and I'd like to touch upon the investor component and specifically your comments that, you know, patients are still seeing switches from the new therapies to RUCONEST.

I was hoping you can provide some additional color as to why those switches are taking place. Thanks a lot.

Thank you, Joe, for these questions. On the Type A meeting, it's very difficult to speculate. I think Anurag has been clear on the questions that were raised by FDA, and we are really looking forward to engage with the agency later this month to address their feedback and discuss a path forward. Too soon to tell. Clearly, given what they've raised, we feel actually that these questions are addressable. And once again, we look forward to engaging with them. When it comes to RUCONEST, I'll let LaVerne answer your question.

Joe, thanks for your question. An important one. As we've seen new agents entering the HAE market in the U.S. between June and August last year, as expected, we saw some trialing of both acute agents and new prophylactic agents in the U.S. market. What we're observing in our data currently, and it's still early, is within about three to six months, some of these patterns may start to shift. We've seen some return of RUCONEST patients that have originally adopted or trialed a different product coming back to RUCONEST. Again, early days, and we're monitoring this closely, and we continue to execute competitively, based on RUCONEST's very different value proposition for patients, specifically in the high attack segment, where they are increasingly concerned with reliability and a fast on-demand treatment like RUCONEST.

Appreciate the color. Thank you.

We are now going to proceed with our next question. The question's come from the line of Jeff Jones from Oppenheimer. Please ask your question.

Good morning, guys, and congrats on the great year 2025. A couple of questions from us. You spoke a little bit to the cadence of moving patients from early access onto paid therapy. Any notable variations between Europe, Japan, Canada as you look to that? And then as you look at the other primary immune deficiencies for Joenja and the phase II readouts that you're anticipating, can you speak a little bit about next steps, what types of additional trials might be needed and how to think about the path forward there? Thank you.

Thank you, Jeff, for these questions. When it comes to access to paid therapies for Joenja in international markets, most of these markets have centrally driven access. The dynamic is different compared to the U.S., where in a sense, each patient, you know, needs to deal with different payers. In a centralized access system, things are slower at the beginning because you need to negotiate, obviously, with the authorities for reimbursement. Once you get reimbursement, then afterwards, the reimbursement process is extremely efficient. We don't expect to see the same type of dynamic international. When it comes to higher prevalent PMDs, I'll ask Anurag to elaborate.

Hi, Jeff. On the question about the what happens next. As I mentioned, the studies have completed enrollment. We expect results later this year. The results that we're looking for, again, the endpoints that we're evaluating are clinically relevant endpoints similar to the ones that we looked at in APDS, as well as other clinically relevant endpoints. As we look at those endpoints, we'll plan to have a discussion with FDA and other regulators about the path forward. I think our base case here is that we would expect to do a phase III randomized type of study. However, I think you've also seen from FDA some openness and willingness to look at alternative mechanisms and pathways for patients with rare diseases, especially those where there's a plausible mechanism and there's a mechanism that's understood.

Those are the types of discussions that we would have with FDA, again, once we have the data to be able to plan the path forward.

Great. Appreciate the color, guys. Thanks.

Thank you. We are now going to proceed with our next question. The question's come from the line of Sheila Hernandez from VRK. Please ask your question.

Yes. Thank you for taking my questions. On Joenja, you mentioned different launch dynamics for international markets. What kind of timelines are you working with for getting these patients in Japan and Canada on paid therapy? And in the UK, will you start reporting the numbers of patients on paid therapy? Currently, how many patients in the UK are on paid therapy, and how many have you identified? Thank you.

When it comes to timeline, we've elaborated a bit on our expectations when it comes to regulatory timelines in the very near future, when it comes to CHMP opinion from Europe and PMDA approval in Japan. We will in Japan specifically, since you asked the questions, we would be submitting a price very shortly for reimbursement, and it takes about three months actually for the price to be granted. Today we have launch timelines planned for the summer. We will be reporting more information on international market on Joenja in a pooled fashion as soon as we have launches in more than one country.

This should happen very soon. It's absolutely essential, and you can count on transparency here. For the second part of your question, I'll let LaVerne elaborate.

Certainly. As Fabrice said prior, as we look at different approvals coming online at different times in this year, every country fundamentally will be a country-by-country process as the approval and reimbursement processes are quite unique for the countries that we discussed. How we thinking about conversion is conversion will depend on physician experience, diagnostic confirmation and testing, and access. We are building those enablers systematically with the international teams to make sure that we are able to execute upon approval.

Okay. That's clear. Thank you.

We are now going to proceed with our next question. The question comes from the line of Natalia Webster from RBC Capital Markets. Please ask your question.

Hi there. Thanks for taking my questions. My first one is a follow-up on Joenja and the patients on paid therapy in the U.S. You added 18 in H1 2025 and six in H2. Appreciate that this takes time, but are you expecting for this rate to pick up into 2026? The second question is just on costs. You're guiding 6%-8% growth in OpEx in 2026. You mentioned some phasing considerations on the revenue side. Are there any particular phasing considerations for the costs through the year, particularly around the higher R&D costs and G&A cost savings? Just finally on M&A. In the release, you mentioned continued focus on potential acquisitions and in-licensing opportunities. Any additional color on what your thoughts are there would be helpful. Thank you.

Very good. Thank you so much, Natalia, for your questions. I'll start with the last one when it comes to M&A. We have clearly a number of growth catalysts both in our commercial portfolio and in our pipeline in the years to come. Obviously there is no urgency to do any transaction hastily to compensate for any sort of a weakness. Yet we clearly aspire to leveraging proven capabilities and a great growth platform to take that to a whole new level and make Pharming a leading rare disease or ultra-rare disease player.

We are constantly looking out for opportunities to expand our pipeline. Now, it is absolutely essential that these opportunities, if they were to materialize, would be value accretive. That's really our commitment to our shareholders. It's not about actually leveraging any external growth opportunities, but making sure that anything that we would consider would be complementary would fulfill our mission, and will be quickly accretive from a value perspective. From a cost perspective, I'll let Kenneth elaborate.

Yeah, thanks for the question. I think, you know, the way to think about it is in the 2025 baseline, we obviously had also some one-off costs that were related to the transaction of the Abliva, so non-recurring transaction cost of about EUR 10 million. We also communicated earlier that we had about EUR 4 million in costs related to the G&A reduction program. When you're looking into the more than EUR 60 million incremental investments in 2026, we of course see the EUR 9 billion of savings in G&A come fully through. You know, then we have seen the impact in our planning of the strengthened capital allocation, which has allowed us to keep also marketing and sales costs flat.

There are different dynamics that are playing in, but, I think, you know, picture speaks for itself that we're fueling where we're seeing the opportunities to advance, in this case, 2026, the pipeline, and are very diligent around spend discipline across all other areas.

Lastly, coming to your question on Joenja, which is actually a very important question. Because as I said, I really see Joenja taking a larger part of our revenues as the drug continue to grow significantly and realize its full potential. You heard that last year we really accelerated the uptake of the drug. We had more new paid patient on therapy in the US that we had in 2024. Also, we've identified more APDS patients in the US in 2025 than we did in 2024. This is really fueling the growth.

This year we expect to continue to accelerate patient enrollment on Joenja and as a consequence accelerate our revenue growth.

Great. Thank you.

We are now going to proceed with our next question. The question come from the line of Simon Scholes from First Berlin. Please ask your question.

Yes. Hello. Thanks for taking my questions. I've just got two. So I was wondering if you could give us a timeline on the performance and collation of the results from these additional experiments you need to perform with regard to the variants of uncertain significance. And also, are you still confident that 20% of these VUSs will turn out to be APDS? And then just on RUCONEST, you were talking about a possible inventory-related decline in or inventory-related effect on sales in Q1. Is this an unusually large inventory drawdown that you're expecting to see in Q1? I mean, that was my impression. And if so, why do you think you saw such a large inventory build up towards the tail end of last year?

Thank you, Simon. Let's start with VUS. Clearly this is a sizable opportunity and we are really committed to helping those patients accessing the right diagnostic. Anurag?

Simon, we are now planning these new experiments. These experiments, again, we're working with Columbia. They're actually gonna be using new technology, new base editing technology to be able to generate different types of variants, generate more controls, as they go through this process. It's too soon to tell in terms of the timelines as well as the actual number of patients that will actually be reclassified. But as this work gets underway, over the coming months, we should be able to provide more details around it.

Okay, thanks.

Simon, on the inventory part, the way we're thinking about it is that there's always this quarterly fluctuation of the RUCONEST business given the patient ordering patterns and the you know general movement. We have also historically, if you go back in the previous years, seen that you know similar dynamics in the early part of the year. Now it's a little bit let's say higher in terms of inventory drawdown and dynamics this year, and we kind of attribute that simply to some of those market dynamics are kind of settling now, and that inventory levels are just kind of returning to a little bit more of the normalized level.

Impact wise it's a little bit higher, but the mechanics of how the quarters are fluctuating and the fact that their inventory impact in the first quarter are not new to us.

Okay. Thanks very much.

Very good. Listen, I think with this we are going to close our call. Thank you so much for these additional questions and we look forward to keeping you closely informed on our plan. There are a number of important milestone coming up and so we look forward to reconnecting with you very soon. Thank you so much. Thank you, operator.

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