Pharming Group N.V. Q2 FY2024 Earnings Call

Good morning or good afternoon, everyone. Welcome to our results conference for the first half and second quarter of the year. I'm here with my colleagues, Stephen Toor, our Chief Commercial Officer; Anurag Relan, our Chief Medical Officer; and Jeroen Wakkerman, our Chief Financial Officer. Together, we will guide you through our presentation. Before we begin, I want to direct your attention to the forward-looking statement slide. We will be making statements during this presentation based on our current expectations and assumptions, which may involve risks and uncertainties. The actual results could differ materially from what we express or imply. Now, let's move to slide number 5. We have been working on building a leading global biopharma company focused on rare diseases, supported by two strong pillars. First, RUCONEST, which has been on the market in the U.S. for nearly a decade and continues to show significant sales growth. In the second quarter, we saw a 23% increase compared to last year, and a 16% increase when comparing the first half of this year to the same period last year. This is a strong performance that we are pleased with, and Stephen will provide more details on positive indicators for the second half of the year. We also launched Joenja last year, which was approved at the end of March and introduced to the market at the beginning of the second quarter. We are happy to report that Joenja has shown growth, achieving a 16% increase in the second quarter compared to the first quarter, and 44% growth when comparing the first half of this year to the last half of last year. Joenja is targeted towards a new and ultra-rare indication, and Stephen and Anurag will discuss the enormous commercial potential for Joenja in treating APDS and other indications. Now, turning to our pipeline, we are about to begin a Phase 2 study for the next indication of leniolisib and exploring another indication, which Anurag will detail later on. We are also focused on acquiring clinical-stage opportunities in rare diseases to enhance our portfolio. Next, I'd like to discuss the overview of hereditary angioedema. RUCONEST is unique in a competitive market, as it addresses all three pathways involved in the disease. Over the years, it has proven to be a reliable treatment for hereditary angioedema attacks. While there is competition, other products do not target all pathways, which allows RUCONEST to fill a crucial role for patients who do not find relief with other treatments. We believe that despite competition, RUCONEST will remain the preferred choice for those severely affected by the disease. Moving to the next slide, we also believe Joenja has significant potential. Currently, a substantial number of U.S. patients are receiving treatment, but we see great opportunities in validating variants of uncertain significance, which Anurag will elaborate on. Internationally, we are starting to see sales from early access programs and are working with regulatory agencies to expand availability for leniolisib to more regions. Additionally, we anticipate that about 25% of patients are under 12 years old and can be served once pediatric studies are completed. In summary, we see leniolisib and Joenja not only meeting current needs but also having substantial potential for growth beyond RUCONEST. Furthermore, we have already identified a second indication, and we plan to start a Phase 2 trial for that, alongside seeking regulatory feedback on a third indication. Joenja could evolve into a significant commercial asset for us in APDS, with the potential for even broader applications. With that, I will hand over to Stephen Toor to provide more details about the revenues from RUCONEST and Joenja.

Thank you, Sijmen. Good morning and good afternoon, everyone. Let's move to the next slide. As Sijmen mentioned, I will discuss the performance of RUCONEST and Joenja so far, and then on my last slide, before passing it to Anurag, I will provide an update on our medium-term expectations that support our confidence in the business. Looking at this slide, particularly for RUCONEST, the strong performance is tied to the unique characteristics of RUCONEST within the patient population we serve, specifically the more severely affected individuals. RUCONEST is the only recombinant C1 esterase inhibitor, with key benefits including that 97% of patients experience a resolution of their attack with a single dose. This sustained effect over several days is the key reason these patients prefer RUCONEST over other less effective options, driving our strong performance. Over the past decade, RUCONEST has become the second most prescribed acute therapy in the US, continuing to show solid results. In the first half of 2024, new patient enrollments have increased significantly compared to last year, with 170 new patients enrolled, representing an 18% increase from the first half of 2023. This growth is fueled by both new prescribers and retention of existing ones, with our sales teams adding 36 new prescribers in the first half of 2024, reaching a total of over 760, which is a record high. This growth translates into a quarterly increase of 23%, and a 16% increase compared to the first half of last year, as Sijmen mentioned. The unique attributes of RUCONEST, the patient demographic we serve, and the clinical perspective provided by Sijmen regarding RUCONEST's operation in all three pathways gives us confidence in our position even as the market evolves in the latter half of next year. Moving on to Joenja, which we launched on March 31 of last year for treating the ultra-rare disease APDS. This is a serious and progressive disease with a high mortality rate, and prior to Joenja's launch, there were no approved disease-modifying treatments. We have experienced strong momentum since the US launch, with patients fully reimbursed within less than a week. By the end of Q2 2024, 91 patients were on Joenja, with an additional two in process at the end of the quarter, likely to begin therapy early in Q3. We welcomed 10 newly diagnosed patients during the quarter, bringing the total to over 230, which is nearly half of the estimated patient population just 15 months post-launch. We think it's likely that there are more patients than the literature suggests as we actively search for more patients. Additionally, we are working with doctors to enroll another 40 diagnosed patients and have over 60 pediatric patients ready to start Joenja once we receive label expansion. To summarize Joenja's performance, we ended Q2 with $11.1 million in sales, reflecting a 16% increase from Q1. Our teams continue to focus on identifying new patients and conducting family mapping and testing, as this is not a dominant disease. This strategy has yielded an additional 28 patient leads in Q2 that we are working to confirm as APDS patients. We remain excited about the value we can provide to the APDS community both in the US and globally. Our financial results align with our expectations for the year. Looking ahead, we are confident in both RUCONEST and Joenja based on several key factors. Firstly, the continued strength of RUCONEST, supported by growth in prescribers, new enrollments, and year-on-year sales. Secondly, the execution of the Joenja launch and our progress in finding patients, family testing, and building our pipeline for the future. Additionally, we anticipate some significant developments that will positively impact our future. One key factor is the VUS resolution efforts, which should lead to a boost of patients in 2025. Another important aspect is geographic expansion; currently, we are launching in the US, but we plan to extend our efforts to key markets such as Japan, the UK, the EU, Canada, and the Middle East. We have identified almost 900 patients across these areas, which is close to half of the 2,000 patients that prevalence data indicates exist in these markets. We are also evaluating opportunities in Latin America. We are building a pipeline of pediatric patients globally, and once we obtain the necessary indications, we will see additional patient growth in the future. Finally, Sijmen mentioned our life cycle management for leniolisib, which will generate a pipeline of new indications, supporting several years of growth ahead for Joenja in APDS and potentially beyond. Following this, I would like to hand over to our Chief Medical Officer, Anurag Relan, to delve further into these related topics.

Thanks, Steve. Now, we can move to the next slide to discuss Joenja. Joenja has received FDA approval for treating activated PI3K delta syndrome, or APDS, in adults and children aged 12 and older. APDS is a rare and serious genetic condition caused by overactivity in the PI3K pathway, which can lead to early mortality, often due to lymphoma. Additionally, APDS is progressive, highlighting the importance of early intervention. Joenja acts as a PI3K delta inhibitor, which helps regulate the hyperactive signaling pathway in APDS patients. The FDA approval last year followed a randomized pivotal study and a long-term open-label extension study. Joenja addresses the root cause of APDS by correcting the fundamental immune defect, thus tackling both immune deficiency and dysregulation encountered in these patients. The safety of Joenja was assessed in a placebo-controlled study, along with a long-term study that is nearing completion, showing no severe drug-related adverse events or study withdrawals. On the next slide, we can look at our patient finding efforts. We are actively engaged in various activities to raise awareness of APDS, as well as to share information about leniolisib and Joenja. On the left, you can see the medical education initiatives we are involved in, collaborating with organizations to enhance awareness. Importantly, we also focus on ensuring patients receive accurate diagnoses, beginning with our no-cost genetic testing program, supported by genetic counselors. Additionally, we are working on facilitating family testing for those already diagnosed with APDS, as it is an inherited condition. We anticipate discovering more patients within families, even though many diagnosed APDS patients do not have diagnosed family members. One major area we are concentrating on involves individuals who receive genetic test results classified as variants of uncertain significance (VUS). This ambiguity indicates a novel gene abnormality, but it is unclear whether this leads to APDS. To assist doctors and patients, we have several projects aimed at definitively classifying VUS results. One strategy is Variant Curation, which gathers known data about the variant. We also provide programs for functional testing in patients, measuring the activity of the pathway in those with a VUS diagnosis. Lastly, we're supporting a large-scale project on multiplex assays to evaluate variant effects, allowing in vitro testing of nearly every possible variant. This study is set to yield results later this year and is crucial for our efforts to resolve VUS classifications. Moving to the next slide, we need to address the scale of the VUS issue, which causes frustration for patients and doctors and impedes the diagnosis of genetic diseases like APDS. We know of about 1,200 patients in the U.S. who have received VUS results for either the PIK3CD or PIK3R1 gene. This number will likely continue to rise, as VUS results are identified at a roughly four times higher rate than patients diagnosed with likely pathogenic or pathogenic variants. This issue is not confined to the U.S., as genetic testing revealing such results can happen globally. Literature shows that approximately 20% of VUSs are upgraded to likely pathogenic or pathogenic following reclassification efforts. In our pilot study of 25 patients with VUS results, we found consistent evidence of APDS in five of them, or 20%, with one patient already preparing for enrollment. Thus, we see a significant opportunity to identify additional APDS patients through VUS resolution strategies and will keep you updated on progress as we move through the year. Next, we'll discuss our efforts extending beyond the current FDA approval. The CHMP review has been extended to January 2026, and while we address one outstanding CMC request, the CHMP has recognized both the clinical benefits and safety, confirming these evaluations are complete. We expect a decision from the UK MHRA later this year, with no major objections noted in our Day 70 questions. Additionally, we've completed our clinical study in Japan and are engaging with PMDA regarding our filing strategy following the requisite studies. Our press release has highlighted significant clinician interest in our Expanded Access and Named Patient Programs, underlining the numerous diagnosed patients as well as the unmet needs in this population. Earlier this year, we also received marketing authorization in Israel, and submissions remain under review in Canada and Australia. We're also focusing on two pediatric studies of considerable importance since this is a progressive disease. We've identified many patients under 12, completed enrollment in our first study starting from age four, and are continuing enrollment in a second study. Now, I will spend the next couple of slides discussing our plans for leniolisib beyond APDS. We see numerous development opportunities for leniolisib. Primary immune deficiencies encompass a broad range of disorders, often genetically based, leading to heightened infection risk, with some experiencing immune dysregulation. This dysregulation can result in lymphoproliferation, autoimmunity, and other autoinflammatory conditions, contributing to high morbidity and mortality rates. APDS exemplifies such an immune deficiency with dysregulation, and we are examining leniolisib for additional primary immune deficiencies that exhibit similar characteristics. Our focus will begin on primary immune deficiencies associated with immune dysregulation linked to the relevant signaling pathway, which affects patients with clinical manifestations and disease progressions akin to APDS, for which there are currently no approved therapies. We will initiate a Phase 2 study soon. As Sijmen mentioned, we are also exploring another disease within the same domain and are currently obtaining regulatory feedback on our clinical development plan. This also represents a primary immune deficiency that shares the clinical phenotype of immune dysregulation, showcasing common traits across the three indications we are pursuing. On the next slide, you will see specific details about the impending Phase 2 study. This proof-of-concept study will soon commence at the NIH with 12 patients diagnosed with a hyperactive signaling condition linked to genetics. This includes several genes like ALPS-FAS, CTLA4, and PTEN. This demographic presents a treatable population estimated at about five per million, which is roughly three times more than APDS cases. This Phase 2 study will assess dosing, safety, and tolerability, with some exploratory efficacy measures, and aim to determine the optimal dose regimen for the Phase 3 study. We anticipate final IRB approvals, enabling us to start the study this month. Now, I will turn the floor over to my colleague Jeroen to discuss our financials.

Thank you, Anurag. Good morning and good afternoon, everyone. I will begin by discussing the financial highlights for the second quarter of 2024 compared to last year. Our revenues increased by 35%, mainly due to the sales volume of RUCONEST and Joenja. RUCONEST sales grew by 23%. Our gross profit remained stable at 89%, which aligns with our revenue growth. In terms of operating expenses, they rose from $65.8 million last year to $70.1 million this year, reflecting ongoing investments in Joenja across the US, EU, and other regions, as well as in compliance, IT, and HR initiatives to support our company's growth. When adjusted for certain one-offs last year, our operating profit gap narrowed from $5.3 million to $3.1 million this year, factoring in a milestone payment of $10.5 million and a gain from the Priority Review Voucher. The net profit was approximately $1.3 million last year, resulting in a loss of $1.2 million this year. Additionally, we incurred a financial gain of $3.4 million this year, as opposed to a loss of $1.8 million last year, primarily from convertible bonds and a reclassification of derivatives. Our overall cash and marketable securities decreased by nearly $42 million, mainly due to bond issuance and repurchase activities. The old bonds had a nominal value of EUR 125 million while the new bonds issued this year were valued at EUR 100 million, leading to a cash outflow of EUR 30 million. The remaining decline is chiefly attributed to increased receivables from higher sales. Looking at the first half of the year, revenues rose by 33%, primarily driven by product volume, with RUCONEST increasing by 16% as previously mentioned. Gross profit for the first half was 87%, with an increase to $113.3 million. Operating expenses also rose, amounting to $134 million, an increase of $15.5 million. The adjusted operating loss remained similar to last year, while net profit was a loss of $13.7 million, slightly worse than the previous year. Cash reserves decreased by $53 million to $161.8 million in the first half. Regarding Joenja sales, revenues nearly tripled to $11.1 million in Q2 2024, with significant contributions from the US along with early access and Named Patient Programs in other markets. For the first half, Joenja sales grew by 44% year-over-year. By the end of Q2, we had 91 patients on therapy in the US, an increase of eight in Q2, following an increase of two in Q1. It is important to note that our gross to net discount percentage has remained stable at 15%, indicating that discounts have not impacted our sales growth. For our 2024 financial guidance, we reaffirm our revenue projections of 14% to 20% growth, estimating total revenues between $280 million and $295 million for the full year. Joenja will be a key contributor to this growth, along with continued sales from our existing products. Our revenue expectations for Joenja are based on the continuing increase in patients on paid therapy, a strong adherence rate of 85%, an annual cost of $566,000 in the US, and a consistent discount of around 15%. In the second half of 2024, we plan to make adjustments and savings to operating expenses due to the EMA delay. Now, I will turn it over to Sijmen de Vries for insights on our 2024 outlook.

Thank you, Jeroen, and thank you very much. We are maintaining our total revenue guidance for this year within the range of $280 million to $295 million. There have been quarterly fluctuations, which are typical. You also heard about our patient recruitment efforts for Joenja and the increasing number of patients we have identified. We are optimistic about the initial results from a small trial regarding VUS validation efforts, which represent about 20% of the 1,200 patients expected to be available this coming year, significantly driving Joenja's growth in the US starting in '25. Regarding leniolisib sales, there's substantial interest, although Named Patient Programs have many administrative procedures that can slow things down. However, we are aware that several patients are in the pipeline waiting for entry into these programs worldwide. You heard Anurag discuss our clinical trials for regulatory filings in Japan, the second-largest market globally. There is also the pediatric label expansion, which will provide at least 25% more patients eligible for Joenja therapy. We are making progress with regulatory approvals, particularly in the UK, where we anticipate feedback from regulators by the end of Q4 this year. We are confident that we will re-engage with EMA following the submission in January '26 in response to their last remaining question, along with their confirmation of the clinical benefits and safety of leniolisib, making us optimistic about entering the European markets in 2026. You also learned about the initiation of a Phase 2 clinical trial for a second indication related to PIDs with immune dysregulation, and our plans for a third indication have been submitted to regulators, with feedback and the potential start of a trial expected soon. In summary, we are beginning to develop two new indications for Joenja. Lastly, our ongoing focus remains on potential acquisitions and in-licensing of clinical-stage opportunities in rare diseases to enhance our portfolio and diversify the company. We have much activity in this area and are very selective regarding the opportunities we pursue. That concludes the call, and I would now like to return to the operator to open the floor for questions. Thank you.

The first question comes from Sushila Hernandez from Van Lanschot Kempen.

I have a few questions, if I may. Regarding leniolisib, it's the first treatment for APDS, and you are about to commence Phase 2 studies in patients with immune dysregulation while also exploring a third indication. Could you provide more details on your decision to pursue this third indication? Do you anticipate a significant expansion of the patient population as a result? Additionally, on the VUS validation studies, can you explain how you identified the 12,000 patients in the US? How did you locate these patients, and how many do you expect to be diagnosed with APDS and referred for treatment? Lastly, with the MHRA decision approaching, how many patients have you identified in the UK? Similar to the US, can we expect a large percentage of these patients to start paid therapy within the first half of the launch?

Sushila, I'm happily handing over to Anurag to start answering your question. Sushila, so with respect to your first question about the Phase 2 study that we're starting. So that one is in patients who have one of the several genes. So the examples I gave were PTEN, CTLA4 or ALPS-FAS. These are genes that are known to be linked through hyperactive signaling and these patients have an immune deficiency as well as an immune dysregulation or the dysregulation of often times a predominant feature in these patients. So that's the first indication that we're pursuing outside of APDS. In addition to that, we are looking at another indication, which is, in fact, even larger. So yes, to your question that this will expand the potential population. But we're looking at this second indication, which also has immune dysregulation and is a subset of primary immune deficiency, and it has features again similar to APDS. So I think that's something you can see across these three potential indications is that they all have these features of immune dysregulation or autoimmunity and auto inflammation. So on the second question was about the US resolution efforts and how we expect that to evolve? So what we've identified already is 1,200 patients. So what does that mean? That means that these are patients who have had a genetic test usually as a part of a primary immune deficiency panel. And again, these are patients that have genetic testing most of which that we were not involved with. So they had this genetic testing performed. The result came back with a result that showed either in one of those two genes, this VUS result. And we are aware of this through these databases that we have access to at large genetic testing companies in the US. And we expect that over time, we'll be able to eventually resolve these in the US. Now we know again, historically, looking at other genes, that's about 20% of the VUSs get resolved and converted into disease causing or what's called likely pathogenic or pathogenic. The other data point that we have is that we recently tested 25 of these US patients, and we had what's called functional testing performed in these patients, and we found a similar number, so about 20%, five out of the 25 were then upgraded or reclassified into APDS. So when you start doing some simple math, you see that this could significantly increase the population of APDS patients in the US.

Thanks, Anurag. And with regards to your question about the UK, Sushila, we have currently 11 patients on early access therapy in the UK. There's 61 patients identified, of which 37 are over 12 years of age. So there's already a quite an interesting population in the UK available. And of course, we expect that once we have the reimbursement, which will take some time and will be somewhere, I suppose, normally in the first half next year, those first patients will go on paid therapy pretty quickly. And of course, by that time, we will have also clarified the VUSs. And of course, there will be in the UK also patients with the VUSs. So they will be additionally coming potentially on to therapy as well. So that's the sort of numbers for the UK that we currently see. And of course, we continue to seek for patients in the UK, but there's already one per million identified, as you can see from 61 out of a population of roughly 60 million in the UK. I hope that answers your question, Sushila.

Yes. And if I may ask one other question. Could you provide an update on your BD efforts? Have you brought in your search?

Yes, we will broaden. We have basically a lot more incoming and also we reached out a lot more because we have now a Chief Business Officer on board since the last quarter of last year. That has led to quite a few interactions, which actually even resulted in some non-binding offers that we issued. But of course, when you then look into the diligence following your non-binding offer, you sometimes find stuff that you were not expecting. And of course, it is also sometimes possible that the other party does not necessarily in the end, want to conclude the deal because it takes time 2 to 10 as you know. But yes, there's been a lot of activity, and we're virtually all the time assessing an asset under due diligence as we speak. So there's quite a lot of intensity here going on.

We will now take our next question. And the next question comes from the line of Jeff Jones from Oppenheimer.

Congratulations on the quarter. I have two questions. You touched on this earlier, but regarding RUCONEST and the expected launch of a competing product or products in 2025 and beyond, what impact do you anticipate? How are you preparing for your response? Additionally, concerning leniolisib in Europe, could you provide more details on what is needed to finalize your definition of regulatory starting materials? When do you expect to respond to the CHMP? I believe you mentioned January 2026, so how does that affect your potential approval timeline?

Jeff, thank you. To address your second question about Europe, we have started our preparations and established a timeline, which is why we agreed with the European authorities to extend our deadline to January 2026 for submitting our response. We are following their requirements precisely. We anticipate a probable opinion towards the end of the first quarter, and we feel confident about it due to the confirmation of the clinical benefits and safety of our product. Once that is settled, it typically takes two months for the European Commission to finalize their decision. Therefore, we expect to enter the European market, likely starting with Germany, around the end of the second quarter or the beginning of the third quarter of 2026. Regarding your first question about competition for RUCONEST, the slide I presented shows the hereditary angioedema market and highlights that RUCONEST is a protein replacement therapy. Stephen mentioned the consistent response rates with RUCONEST. Sebetralstat, which operates on the bradykinin/kallikrein pathway, has yielded positive results and offers new treatment options for patients. However, it's important to note that Sebetralstat was tested in a patient group that generally responds well to Icatibant or Firazyr, whereas our patients are those who have not had success with Icatibant and therefore require RUCONEST. We are confident that Sebetralstat will not significantly affect RUCONEST because it is aimed at a distinct patient population. We acknowledge that initially, some of our patients may try the new oral medication, as has been the case with prior competitors. However, it's crucial to understand that if a patient who opts for a pill needs a second dose to relieve their symptoms—which is often the case in clinical trials—they will continue to endure considerable discomfort. In contrast, RUCONEST users experience almost immediate relief once they administer the shot themselves, which, despite being less convenient, is something our patients manage confidently at home. The results for RUCONEST show very few breakthrough attacks or the need for additional doses, which emphasizes the effectiveness of our treatment. While the introduction of a new competitor is beneficial for patients seeking alternative options, our long-term outlook for RUCONEST remains strong. We believe that RUCONEST will continue to provide the advantages and positive experiences that our patients have come to expect. We recognize that there will be initial interest in the new drug, but ultimately, we are confident that RUCONEST will endure. This is why we emphasize the importance of replacing the C1 esterase inhibitor, which RUCONEST does effectively and promptly. I apologize for my lengthy response, Jeff, but I felt it was important to clarify these points.

I just really wanted to talk a little bit about Joenja. You've obviously got quite a significant pool of diagnosed patients in the US. Can you talk about the pathway from getting diagnosed patients to be basically enrolled? What are the key hurdles you have to overcome and then how onerous is that process?

Yes. I will now hand over to Steve.

It is, as you would expect, can be quite convoluted, but we try to make that as smooth as possible through our own patient services. So essentially, the first part of the process is obviously the patient coming in. That can take some years sometimes, although we're calling all those key centers of excellence. Then once the symptom is reviewed and the patient is worked up, it's the genetic test and if they get that positive test, then they immediately can go into our enrollment program where we'll start to work with their payer on getting them approved. And we've seen a mixed picture there with the payers. But what I will say is that our approval rate is at 98%. And that 2% is they are in NDC blocks. So they will eventually come on stream. They just take a little longer to actually pull through the entire market access or managed care system. So that's the kind of simplified version, which is patient comes in, patient gets diagnosed. They work with outpatient services and then land on therapy. What can sometimes slow things down, and that's why you see a bolus in the first part of the launch and then slower. But nevertheless, still growth as we move forward before those bigger inflection points that Anurag referred to with the US population and the pediatrics, is we're now into those groups where there may be other complications. So perhaps they're on chemotherapy or for whatever reason there are other comorbidities that are being managed. So they remain within our diagnosed pool, and we monitor and we worked already with the doctor and when we can, the patient tells them the right time they can move on to therapy. So I think that's the high-level overview of what happens with managed care. That's where we are today with the existing pool of patients before we get those next big boluses in '25, '26 and beyond. Is that okay Alister? Was there any other questions on that?

Can I follow up on that? Regarding the pool of 50 diagnosed patients over 12, there are some hurdles to get them on therapy. Do you have a sense of the pace at which they will start therapy before the significant increases you mentioned? I'm trying to understand the expected rate of patient additions before those major increases occur.

I would love to give you a specific answer on that, but unlike the mass markets I've worked on in the past, these are very low absolute numbers. For example, we added eight this quarter and two last quarter, and we have others we’re currently working through. The good news is we expect this to continue, but it won't be linear. In contrast, with cholesterol lowering, predictions are much easier. For instance, one patient is scheduled to come in July because they needed to finish their school year first. What I can tell you is that we are currently working through close to 50 patients over 40. We know every detail about their status and what the tipping point will be, even down to patients whose 12th birthday is this year. We are prepared to discuss this with physicians and inquire if the patients are in the appropriate place regarding weight and other factors. However, I cannot provide a good prediction on the pace at which these patients will come in or the timeframe for that. I can only say that we are working diligently on each one of them regularly and in a detailed manner.

And the next question comes from Simon Scholes from First Berlin.

I've got two. The first is on the second indication for leniolisib. I mean I gather that you're expecting the Phase 2 data early next year. Once you get the Phase 2 data, I was just wondering what the further timetable might look like as regards to Phase 3? And then the second question is on approval in Canada and Australia. I mean you're now talking about 2025 for both markets. Can you give us a slightly more precise timing for those markets? I mean, is it likely to be H1 or H2?

Yes. First of all, Simon, I think you're being quite optimistic about the timing of when this Phase 2 study will report. This is an open-label study, but I believe that we should consider the end of next year as a more realistic timeframe for gaining insights that will help us plan for the following Phase 3 trial. Additionally, we typically don't provide detailed information on regulatory interactions because they can be somewhat unpredictable. However, you are correct that we are anticipating regulatory actions in 2025 for those markets, rather than in 2024. So essentially, that is correct. I hope I have addressed your questions.

As there are no further questions, I would now like to hand back to Sijmen de Vries for any closing remarks.

Thank you for joining us today. We are pleased to report impressive results for both the second quarter and the first half of the year. We believe that RUCONEST will significantly impact our financial performance in the years ahead, especially as we cater to this distinct patient population, despite anticipated competition. While the growth for Joenja is ongoing this year, it will not follow a straightforward trajectory, but we expect a considerable influx of patients in the United States starting early next year due to anticipated outcomes related to the VUS, which will act as a catalyst for Joenja's growth in 2025 and 2026. We also look forward to positive discussions with European regulators in the first quarter of 2026 and are diligently working to finalize our pediatric and Japanese trials, aiming to submit to the Japanese authorities and tap into the second largest market globally, adding at least a 25% increase in patients under 12 for commercialization in the US and other regions, including the European Union. Additionally, we will initiate a Phase 2 study targeting primary immunodeficiencies with immune dysregulation as a new indication for Joenja and are awaiting regulatory feedback for a third indication to commence another Phase 2 trial in the near future. Lastly, we remain focused on potential acquisitions and in-licensing opportunities in rare diseases to enhance and diversify our portfolio, with numerous activities underway to identify suitable opportunities. That wraps up my remarks, and I would like to turn it back to the operator for questions. Thank you.

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