Earnings Call Transcript - PHAR Q4 2023

Operator, Operator

Good day and thank you for standing by. Welcome to the Pharming Group N.V. Full Year 2023 Results Conference Call and Webcast. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. As a reminder, the company will only take questions from dial-in participants. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Sijmen de Vries, CEO of Pharming Group. Please go ahead, sir.

Sijmen de Vries, CEO

Thank you very much, operator. Welcome everyone. Good morning or good afternoon, depending on your location. We are excited to share our full year results with you. Please move to the next slide. Before we proceed, I want to highlight the forward-looking statements slide. Our forthcoming statements are based on current beliefs and expectations, which may vary from actual outcomes. Now, let’s go to the next slide so you can see my face, and then we'll move forward. Thank you. As we reflect on 2023, it has been a successful year, during which we achieved strong growth and laid the groundwork for becoming a global rare disease company. This foundation can be financially supported by the significant cash flows generated from the marketing of RUCONEST. We are pleased to report over $227 million in revenue, marking a 10% increase compared to last year, significantly surpassing expectations for single-digit growth for RUCONEST. This increase is attributed to favorable trends, including more patients and more prescribers, indicating that patients continue to rely on RUCONEST despite the increasing treatment options available, which is beneficial for them. RUCONEST remains a reliable cornerstone, and my colleague Stephen Toor will expand on this further. Another exciting development is our launch of Joenja in the United States, a product we licensed from Novartis in 2019. We were proud to bring this product to market right after receiving FDA approval in April, achieving over $18 million in sales during its first nine months. Joenja has been submitted for review to various regulatory authorities in Europe, Canada, Australia, Israel, and, just two days ago, in the United Kingdom. We are actively working with these authorities and look forward to upcoming approvals. It is important to note that the label for Joenja is for patients aged 12 and older, and we are conducting several pediatric trials. Additionally, we've completed a small clinical trial in Japan and plan to submit our findings to Japanese authorities by the end of this year. My colleague Anurag Relan, our Chief Medical Officer, will provide more details on that. Since Joenja deals with an ultra-rare disease, we are focused on patient recruitment, and again, Dr. Relan will discuss this later. Looking ahead, we firmly believe that leniolisib has significant further development potential. We plan to initiate a Phase 2b study in the second quarter for a subsequent indication, which has a considerably larger patient population compared to APDS. Dr. Relan will discuss this in more detail shortly. We are also actively seeking to in-license or acquire clinical-stage programs in rare diseases, particularly in immunology, hematology, respiratory, and gastroenterology, to enhance our commercialization efforts. For the first time, we are providing total revenue guidance, forecasting between $280 million and $295 million, driven primarily by Joenja but also supported by RUCONEST in 2024. Now, please move to the next slide, which shows our pipeline including RUCONEST currently in the market and Joenja in the U.S. market, along with various regulatory reviews, ongoing pediatric programs, and our Japanese program. Excitingly, we are also preparing to conduct a Phase 2a study for leniolisib for the next indication, along with our early-stage HAE gene therapy program in preclinical stages. With that, I would like to hand it over to my colleague, Stephen Toor, our Chief Commercial Officer, for a commercial update. Thank you.

Stephen Toor, Chief Commercial Officer

Thank you, Sijmen. Good morning, good afternoon everybody. So this is a slide, I think you'll be largely familiar with. And I think the key thing to take away from this is that the key features of RUCONEST. So namely the only recombinant C1 treating the root cause of the disease and 97% efficacy in one dose is what continues to fuel the RUCONEST growth and our success over the last nine years. These product features are allied to the excellent work our commercial medical and patient services teams deliver for customers, patients and their carers is also why RUCONEST remains a highly relevant part of the conversation in the U.S. HAE community and globally. That's remained the case despite three prophylactic launches over the last few years leading to generally better controlled patients and the genericization of a canape, and I fully expect it to remain the case even in the face of acute competition in the future. And that's because HAE patients using RUCONEST tend to have generally a more severe course of the disease. And in that instance, the need for virtually guaranteed and fast efficacy that stops the attack in its tracks is critical, and it's typically the patient's only real objective. In most cases, that override in need for efficacy won't be replaced by a convenience play. So, looking at 2023 RUCONEST performance was characterized by the continued growth in both prescribers and new patient enrollments, and it was also successful despite that market-wide event we saw in Q1 last year related to government reimbursed patients. Now, we have seen some disruption from that this year, but it's been muted by you're almost having those patients out-of-pocket costs in the US. And moving into 2024, we've also seen that the strength of our leading indicators has continued into this year, namely new prescribers and continued support from existing prescribers and new patient enrollments. So despite some continued disruption in that government segment, we're still on track for where we expect to be in Q1. Next slide please. So this is again something you're very familiar with. Pharming's been in this space and committed to this community for over 20 years now. And it's really that commitment combined with the product itself RUCONEST, our people and the excellence they deliver, which is why you see on the right-hand side there our prescriber base continues to grow. And as a result, our patient base continues to grow. And it's why as I said, we remain enthused and confident in the continued growth of RUCONEST both this year and in the years ahead. Next slide please. So switching gears now to Joenja. We had, as you know, a strong first year. And as we close out that first year at the end of this month, I'd just like to reinforce what a great launch the team here at Pharming delivered for us. So the launch preparation as you've heard me say in the past was first class. And I think I wouldn't underplay what Sijmen said earlier, which is that within one week of approval, we had commercially covered patients with product in hand, which is outstanding. The patient base steadily grew throughout the year and we exited, as you know, at the end of the year with 81 patients on paid Joenja therapy. In that time importantly, we've seen very few discontinuations and we have adherence rates close to 90%. So as we convert that caseload that we'd already identified at launch, our focus on surprisingly moving forward remains finding those new patients for this rare disease. And then given it's an APDS, autosomal dominant condition, testing their families to uncover additional patients, so that they too can benefit from the management of treatment with Joenja, which as you know is the only indicated product with which you can treat APDS. And then the other important factor to talk about here in addition to the US is, of course, alongside that launch, we continue to build out our US capabilities in preparation for launches in the European Union, the United Kingdom, Japan, Australia and other countries in the Asia Pacific region and also in the Middle East and here in North America and Canada. So with that, I'd like to pass over now to Dr. Relan who's our Chief Medical Officer for a medical update.

Anurag Relan, Chief Medical Officer

Thank you, Steve. Today, I will discuss APDS and provide an update on Joenja, along with potential applications for leniolisib in a second indication. This slide presents information about APDS, a rare primary immune deficiency identified in 2013. We estimate about 1.5 patients per million have this condition, and we have already identified over 840 patients globally in key markets. As with many rare diseases, the signs and symptoms of APDS can differ among patients, even within the same family. This can lead to delays in diagnosis and treatment, causing frustration for both clinicians and patients. Fortunately, a simple genetic test can definitively diagnose APDS. Prior to Joenja's availability in the United States, treatments for APDS mainly focused on symptom management, which started early in childhood due to the genetic condition. Unfortunately, these treatments did not address the underlying cause of APDS, complicating effective management for both patients and physicians. With the launch of Joenja, APDS patients aged 12 and older now have a treatment option. We showed this through a randomized placebo-controlled study, where Joenja met primary and secondary endpoints with significant efficacy results. Furthermore, we observed positive effects in other secondary parameters and exploratory measures. On the safety front, there were no drug-related serious adverse events or withdrawals in Joenja studies. We have also gathered substantial long-term data on Joenja’s use and reported reductions in discontinuations of immunoglobulin replacement therapy as well as decreased infection rates over time. The long-term safety profile remains consistent with short-term results. Ongoing data collection includes maintaining benefits in lymph node and spleen size, as well as immune parameters like IgM levels. We presented some of this data at various medical conferences throughout 2023 and plan to continue sharing more findings in the coming year. Looking beyond FDA approval, we are collaborating with CHMP to address outstanding issues and are awaiting their opinion on the millennial MAA. We expect leniolisib to be on the agenda for the upcoming CHMP meeting. In Japan, we've completed enrollment for the clinical study and are on track to file for approval by the end of this year or early next year. We filed our application for MAA in the UK with MHRA this week and have several applications under review in Canada, Australia, and Israel, with expected regulatory actions throughout 2024. We also have two ongoing studies for pediatric patients aged 4 to 11, with one study nearing enrollment completion and another having recently begun in November 2023. Additionally, patients in expanded access programs worldwide are accessing therapy through named patient programs. Next, I want to highlight our efforts in patient identification, which is crucial for rare diseases like APDS. Medical education is a key pillar of our strategy, and we support this through various activities. We participate in conferences, present abstracts on APDS and emerging data on leniolisib, and publish results to raise awareness. Since genetic testing is a straightforward way to diagnose APDS, we have a no-cost testing program with genetic counselors available for pre-test and post-test guidance. We are also collaborating with genetic testing companies to identify patients already tested and diagnosed with APDS. Our work reveals that many family members have yet to be tested for APDS, so we’re making testing more accessible and promoting education for family testing. Patients can now request genetic testing if they suspect they or a family member may have APDS. Regarding variants of uncertain significance (VUS), we're aware of over 1,100 patients in the U.S. with inconclusive genetic test results. We're collaborating with experts to establish criteria for classifying variants and partnering with companies to make information on disease-causing variants available. We're working to gather data and increase the availability of functional testing, engaging with commercial labs for broader access. We share results through databases including the NIH's ClinVar and are involved in a project to test nearly all possible variants, which will help eliminate inconclusive results in the future. We have presented data at medical conferences about the seriousness of APDS, including mortality rates, lymphoma data, and long-term results from leniolisib use. Our goal is to continue educating the broader community about APDS and the essential data we are collecting. Turning to the second indication we are pursuing, APDS is associated with immune disregulation, as are other immune deficiencies presenting similar clinical symptoms. These patients often experience lymphoproliferation and autoimmunity, and existing treatments like immunosuppressive therapies have limited efficacy. There's a strong rationale to explore potential benefits of leniolisib in this context. We plan to advance a clinical trial for this patient population aimed at balancing immune function and improving clinical symptoms. We are collaborating with the NIH, with plans for a Phase 2 proof-of-concept study, which will involve up to 12 patients with specific mutations related to immune disregulation. The primary goal is to confirm safety and tolerability while determining the optimal dosing regimen for a Phase 3 study. We look forward to sharing updates on this upcoming trial. Now, I'll turn it over to Jeroen to discuss the financials.

Jeroen Wakkerman, CFO

Yes, thank you very much, Anurag. I'm pleased to go over the financial highlights. To begin with, in Q4 2023 compared to last year, we experienced a revenue growth of 49% during the quarter. RUCONEST saw a growth of 34% in Q4, achieving record revenue of $73.3 million. It's worth noting that we had only 2% growth year-to-date by the end of Q3, so we are very satisfied with these Q4 sales results. We also observed strong performance in key revenue indicators in the U.S., including new physicians prescribing RUCONEST, new patient enrollments, especially among high-frequency attack patients, and a total increase in patients. Joenja revenue increased by 21% compared to Q3 2023, bringing its revenue to $7.9 million. By year-end, we had 92 APDS patients enrolled in the U.S., with 81 patients receiving therapy on Joenja. The gross profit in Q4 2023 rose by $25.8 million compared to the same quarter last year, primarily driven by higher revenues, although this was partially offset by increased production costs for RUCONEST and royalty payments on Joenja sales. Operating costs increased by $16 million in the fourth quarter compared to last year, with approximately half of this increase, $8.3 million, linked directly to R&D and marketing and sales expenses for leniolisib and Joenja. Additionally, our expansion efforts in preparation for the launch and commercialization of Joenja contributed to a $7.1 million rise in payroll expenses. We recorded an operating profit of $1.1 million, a significant improvement from an operating loss of $10.2 million in Q4 2022, primarily due to the increase in gross profit, which was partially offset by rising operating expenses. The net loss was $2.7 million, while our cash position improved from $209 million at the start of the year to $215 million by year-end. Looking at the full-year results, our revenues increased by 19%, largely due to higher sales volumes of RUCONEST and supported by a price increase that remained below the CPI in the U.S. market. Initial sales of Joenja reached $18.2 million in 2023 following its launch in April that year, and revenues across Europe and the rest of the world rose by 12% to $6.2 million. Gross profit climbed by $32 million or 17%, generally in line with revenue growth. This year's other income includes the sale of the Priority Review Voucher to Novartis for a pre-agreed price of $21.3 million, along with a recognized gain from the reduction of our minority stake in BioConnection, amounting to $12.2 million in 2022. Operating costs rose by $64.5 million, with $10.4 million attributed to milestone payments for Joenja following its first commercial sale in the second quarter of last year. An additional $25.7 million of expenses was directly related to R&D and marketing for leniolisib/Joenja, while payroll expenses saw a $24.2 million increase due to our expansion efforts related to the launch and further commercialization of Joenja. We also faced impairment expenses of $4.7 million related to our DSP facility in 2023. Consequently, our operating profit decreased from $18.2 million to a loss of $5.4 million, mainly due to the increase in operating costs to support our Joenja business. The total net loss for 2023 was $10.1 million, compared to a net profit of $13.7 million the previous year, with the decline primarily resulting from higher operating costs and unfavorable fluctuations in foreign exchange rates affecting our income statement. We have provided an overview of the revenue growth for RUCONEST over the past years. In 2022, RUCONEST revenue grew by 10%, setting a record since the launch of the product in the U.S. nine years ago. Leniolisib continues to drive enhanced growth, with an overall revenue growth of 19% in 2023. We are pleased with these results and the continued growth of RUCONEST since 2021. In terms of operating expenses, we have continued to invest in our future growth. In Q4 2023, operating expenses rose by $16 million compared to the previous year, with almost half related to leniolisib and Joenja in terms of marketing, sales, and R&D, while payroll expenses increased by $7 million to support employee growth. For 2024, we anticipate that quarterly operating expenses will be lower than those of Q4 2023. Regarding cash flow, our cash position increased from $209 million to $215 million. The negative cash flow from operating activities was offset by cash from the sale of the previously mentioned Priority Review Voucher. We also benefited from favorable currency exchange rate fluctuations, particularly affecting our cash holdings in euros, as the euro-dollar exchange rate increased over the year. Looking ahead, we provide revenue guidance for 2024 in the range of $280 million to $295 million, representing growth of 14% to 20%. As in prior years, we expect quarterly fluctuations, with Joenja being a significant contributor to this revenue growth alongside continued growth from RUCONEST. The expected growth rate for RUCONEST is higher than what we provided in 2023, as we anticipate the momentum from the latter half of 2023 continuing. Last year's guidance was for low single-digit growth, which we now confidently revise to low to mid-single-digit growth for RUCONEST. For Joenja, we anticipate ongoing growth in patients on paid therapy, with the pricing in the U.S. being an annual weighted average cost of $566,000 per patient. For the overall outlook for 2024, we expect total revenues between $280 million and $295 million. For Joenja in the U.S., we foresee continued progress in identifying additional APDS patients through family testing and validation efforts, which will help convert them to paid therapy. Outside the U.S., we expect increasing revenues from leniolisib’s commercial availability via our named patient program and other funded early access programs in key global markets. We aim to finalize leniolisib clinical trials to support regulatory filings for approval in Japan and for pediatric label expansion in major global markets, while also progressing toward regulatory approvals for leniolisib in Europe, the UK, Canada, Australia, and Israel. We will initiate and advance a Phase 2 clinical trial for leniolisib concerning PIDs with immune disregulation related to PI3K delta signaling to significantly broaden its long-term commercial potential. Our focus remains on potential acquisitions and in-licensing opportunities within the rare diseases sector across therapeutic areas such as immunology, hematology, respiratory, and gastroenterology, to further leverage our global commercial infrastructure. Now, I would like to transition to the next slide and open the floor for Q&A. Thank you.

Operator, Operator

Thank you. And your first question comes from the line of Christian Glennie from Stifel. Please go ahead.

Christian Glennie, Analyst

Hi. Good afternoon, guys. Let's start off with RUCONEST, I guess, just to get a bit more of a sense for these underlying drivers, obviously, a very strong fourth quarter. You seem to be guiding for mid-single-digit growth in 2024 now. Is there a scenario in which you could get north of that and do another sort of 10%? Just trying to get a bit more sense for some of the drivers on RUCONEST this year?

Sijmen de Vries, CEO

Thank you for the question, Christian. RUCONEST does show some strong underlying market indicators, which Steve mentioned are continuing into the first quarter. We recognize that there is significant competition in the market. However, we remain optimistic, as it's now the tenth year for RUCONEST. We anticipate mid to low to mid-single-digit growth. As we observe any positive movement in indicators, we will update our guidance throughout the year, but for now, we want to maintain our current outlook for RUCONEST.

Christian Glennie, Analyst

A natural follow-up to that, I mean you touched on this Stephen touched on this in the remarks around potential new entrants here on oral and convenience next year. Just to get a bit more insight I guess in terms of the patient profile here and what the sort of your market intelligence tells you that you aren't going to lose patients effectively to that convenience option.

Sijmen de Vries, CEO

Yes, I think Anurag and Stephen have already mentioned this. We observe a distinct patient profile using RUCONEST. When examining the clinical results of the new acute options, it becomes clear that there is a need for multiple doses and still a requirement for rescue therapy. In the case of RUCONEST, rescue therapy is not applicable, as it provides protein replacement for the missing or non-functioning C1 inhibitor protein in patients with hereditary angioedema. Therefore, we believe that these new products target a different segment of the population suffering from hereditary angioedema. We anticipate that if approved, these oral acute products will cater to patients who currently rely on various convenience products, such as subcutaneous injections, which can be quite painful and must be administered multiple times to address a single attack. The transition for these patients to oral treatment may be relatively easy. On the other hand, patients who depend on RUCONEST are not accustomed to convenience in therapy and instead rely on the consistent efficacy of RUCONEST, making it more challenging for them to switch. However, it is possible that some may try these alternatives and find success. Nevertheless, we cater to a distinct patient profile with higher attack frequencies compared to what is observed in the clinical trials of the incoming competitors. I hope that clarifies your question; I apologize for the lengthy response.

Christian Glennie, Analyst

No, that's very helpful. Thank you. And then one final one on Joenja and I get back in the queue. I guess your guidance implying RUCONEST 5% gets to about 240, so Joenja the balance is somewhere between 40 million and 55 million for this year if I'm understanding it correctly. And therefore what are your assumptions around the sales and markets that will contribute to that growth and what gets you to the low and high end of that? So, is it mostly still U.S.? Or will there be reasonable contributions from other markets?

Sijmen de Vries, CEO

I think first and foremost, as you heard from Anurag, many efforts are underway to identify patients in the U.S. The initial numbers we have are for patients already on the drug. We expect a steady influx of patients in the United States this year, driven by systematic family testing efforts. Additionally, there will be small batches of U.S. tested patients that will provide a limited number of new patients at first, but by the end of the year, we anticipate that the combinatorial experiment Anurag mentioned will generate the majority of U.S. patients. Once we have more clarity on the percentage of patients we actually have on POS, we will update the market accordingly, though it is still early in that process. Regarding the international market, we do not foresee significant sales from Europe soon, as reimbursement processes are lengthy. Sales in Europe are expected to begin in 2025 and may take even longer in some markets due to approval timelines. Ex-U.S. sales will mainly arise from early access programs and from named patients who are already being treated. In the 1Q results, you will notice some reported sales internationally, reflecting ongoing activities. Therefore, the fluctuations in Joenja sales numbers will primarily relate to the patient numbers from the U.S. market. I hope that answers your question, Christian.

Operator, Operator

Thank you. We will now go to our next question. And your next question comes from the line of Alistair Campbell from Royal Bank of Canada. Please go ahead.

Alistair Campbell, Analyst

Thanks, everyone. Thanks for taking my question this morning. I have a couple on Joenja if that's all right. First of all, obviously, Joenja is launching very well in the US and you talked about I think at over a 90% adherence rate which is good. But just in the context of that just sort of to confirm that what you're actually seeing in real-world use is kind of a line of what you saw in clinical trials in terms of side effect profile and stuff that will sort of get a sense of that? And then secondly, just thinking about the second indication the PID with immune disregulation, obviously that's going to cover a variety of different genetic causes. And I guess what I'm trying to get for myself is a feeling of the risk around the profile of this program. I mean basically is your expectation that all of those genetic dysfunction areas really biologically should respond? Or you think some of them will? Or do you think they're all high rates? I'm just trying to get a sense of what the risk profile looks like. I mean my feeling is that at least some of those should probably come through but just to get a sense of how you view that would be great? Thank you.

Sijmen de Vries, CEO

Happy to hand it over to Anurag, of course, here in this case. Anurag would you mind answering that question?

Anurag Relan, Chief Medical Officer

Sure, let's start with the second question regarding the additional indication in primary immune deficiencies with immune dysregulation. We are examining specific genetic variants and mutations responsible for this altered signaling, which has already been established. It's recognized that patients with ALPS, CTLA-4 deficiency, and P10 deficiency exhibit this abnormal signaling and experience immune dysregulation as a consequence. They are currently treated with immunosuppressive therapies like rapamycin to modulate that pathway. Therefore, it seems logical for us to consider modulating the pathway with leniolisib similarly to our approach with APDS patients. This initiative arose from our discussions with the immunology community, where they expressed that there are other patients who could benefit and provided various reasons supporting this. Based on that feedback, we collaborated with the NIH, who are experts in the areas of ALPS and CTLA-4 haploinsufficiency, to develop a clinical trial program, as they were eager to address the unmet need and utilize a treatment they are already confident in from their experience with APDS patients receiving leniolisib for several years. Now, regarding your first question about the real-world use of leniolisib compared to clinical trials, we have observed that it remains generally safe and well tolerated, with nothing new from our pharmacovigilance efforts indicating any different safety or efficacy profile. Additionally, we are receiving feedback on various benefits that were not fully captured in the clinical trial program. We are working to gather all this data through a registry in the US where we will follow APDS patients over time, with the goal of capturing more information about the potential benefits these patients experience that we weren't aware of during the initial clinical trial. This is something we look forward to as the year progresses.

Alistair Campbell, Analyst

Just a quick follow-up on that. When do you think in the sense of timing you might have something from the registry that would be worth sharing with us and obviously with physicians?

Anurag Relan, Chief Medical Officer

So the registry is just underway, but we are continuing to collect and publish data from the use of expanded access. So these are again, this is essentially compassionate use patients in the US who don't qualify for commercial drug or outside the US who are on therapy. We are collecting that data and we've shared some of that last year. You'll see a lot more of that data from the expanded access program or case reports or case series of patients in the expanded access program. You'll see that at conferences this year. I think the registry because it's just started, I think that's more likely to be a 2025 type of data. But I think that you're going to see through the expanded access program data coming out this year that reinforces what we saw in the clinical trial program and really extends even beyond that.

Operator, Operator

Thank you. We will now go to the next question. And your next question comes from the line of Joe Pantginis from H.C. Wainwright. Please go ahead.

Joe Pantginis, Analyst

Hello, gentleman. Thanks for taking the question. So I have a couple of questions on Joenja. I'm going to start very specific and then just talk more to the broader disease if you don't mind. So first, Stephen earlier was talking about and of course you guys have great adherence rates. So I was curious on the other end what are some of the reasons you see for lack of adherence on the drug?

Sijmen de Vries, CEO

Thanks, Joe. Anurag, do you have any insights on that that you can share with Joe?

Anurag Relan, Chief Medical Officer

Yeah. I think it's really just one-off cases Joe, where in fact some of the cases where we've seen as these patients are underweight and they need to be put on a lower dose. So that's not possible in the commercial program. So that's one example that comes to the top of my mind, but it's not anything we're seeing from a safety point of view, that suggests any concern or something that we saw didn't see in the clinical trial program. So I don't think there's anything substantive here.

Joe Pantginis, Analyst

That's very helpful. Thanks. Sijmen, if I heard you correctly earlier, it sounded like you might be sharing in the future the role or the amount or proportion of VUSs as part of your Joenja revenue profile. Was that correct? When do you anticipate that the VUS could start to have a significant impact on the revenue growth for Joenja?

Sijmen de Vries, CEO

Yes, Joe, that statement is indeed forward-looking. I mentioned something similar earlier. We're currently evaluating the individual VUSs, as shown in Anurag's slide, and this process is already underway. We expect the first small batches to come through very soon, which may provide us with some early insights. While it won't deliver a large number of patients initially, there will still be some patients. The majority will likely be seen after we conclude the MAVE experiment, which we anticipate will happen by the end of this year. Therefore, I believe that 2025 will be the year when the majority of VUS patients will be available for treatment. That seems like a reasonable forward-looking statement for now, Joe.

Joe Pantginis, Analyst

Got it. That's fair. My broader question about the disease connects to your recent data at Quad AI, which is quite intriguing regarding the molecular diagnostics. I would like to ask Anurag about the role Joenja could play in relation to the multiple statements made about the disease, particularly concerning patients who lack clinical actionability. Can you help us understand why some patients might not be actionable from a clinical or medical perspective and if Joenja could influence that?

Anurag Relan, Chief Medical Officer

Yeah. So I think it's a good question. It's something we're doing a lot of work on is really educating patients and clinicians about APDS. I think it's a foregone conclusion amongst our team of course that this is a serious disease and that there's a significant mortality associated with it that many of these patients, unfortunately go on and develop lymphoma and lymphoma is key reason for the high mortality in these patients, the lymphoma that these patients develop is often not easy to treat. And the mortality rates are much higher than you'd see in other lymphomas for example, or in other patients. So I think there's a lot of education to talk about that. I think it's also important to recognize that these patients do have different clinical manifestations. So some patients that may be very obvious without a high infection rate, some patients infections may not be the most predominant feature, but it could be the lymphadenopathy or the enlarged spleen. So I think it's really educating clinicians also on what to look for in these patients and to be able to monitor these patients. But really all of these patients, I think, have a serious condition and they all are potentially eligible for Joenja. So I hope that answers your question.

Joe Pantginis, Analyst

Thank you for your patience. My final question is about your improving balance sheet. Do you think the increased cash will help with further business development discussions? Also, can you discuss the current status of your ongoing talks regarding potential asset licensing? Thank you.

Sijmen de Vries, CEO

Yes, Joe. Thanks for your question. Having extra cash available certainly aids in pursuing in-licensing opportunities, which, as we’ve mentioned before, is our preferred approach since it’s generally simpler than mergers and acquisitions. With the addition of Alexander Breidenbach as our Chief Business Officer, we’ve been proactive in our efforts and have developed a promising pipeline. We are currently in advanced discussions with a few potential opportunities, so we have a clear view of what we are evaluating. However, as I’ve stated previously in business development, nothing is certain until a deal is finalized. We are actively pursuing opportunities and, given our commercial success in the HAE market, we are gaining recognition as an attractive partner for companies that seek to avoid the risks and costs associated with commercialization, especially those focused on single products. As we solidify our position, we are receiving more interest than usual. Therefore, we remain optimistic that we’ll have news to share this year regarding a deal that we’ve initiated to expand our pipeline.

Operator, Operator

Thank you. We will now take your next question. And your next question comes from the line of Hartaj Singh from Oppenheimer. Please go ahead.

Unidentified Analyst, Analyst

Hey, everyone. This is Faee on for Hartaj. Thanks for the question. Two questions from our end. So, first one for RUCONEST. Can we still expect the seasonality for RUCONEST in first quarter sales as previous years? Any color on that? And the second one for Joenja, can you provide any color on the duration of the patients Joenja so far since Joenja was launched around like three quarters nine months and your estimates on the APDS patient number growth in 2024? Thank you.

Sijmen de Vries, CEO

Yes. Could I just hand it over to you Stephen, those questions, right?

Stephen Toor, Chief Commercial Officer

Could you repeat the questions, because they weren't completely clear for me?

Unidentified Analyst, Analyst

Sure. Can we still expect seasonality for RUCONEST in first quarter sales like we saw in the previous year?

Stephen Toor, Chief Commercial Officer

Yes. So, thank you for clarifying. So yes, I think you can broadly expect to see similar patterns to those which you saw last year, because the same types of events are happening in the quarter. So for example, Q1 is the prior authorization season. And as we indicated last year, there is some disruption to government patients. So, as I said, we remain on track for what we expect to do this quarter. The leading indicators and the performance is where I expect it to be. But you should expect to see the same overall pattern through the year I imagine certainly in the first half.

Unidentified Analyst, Analyst

Thank you. For Joenja. So can we know some color on the duration of the patients on Joenja so far since it was launched around three quarters like nine months?

Stephen Toor, Chief Commercial Officer

The duration of the patients? I've got you now. So as we mentioned earlier patients are adhering well unless there's either a weight issue or some such. So they're typically being prescribed on a monthly basis and dispensed on a monthly basis and we see that cadence with patients.

Unidentified Analyst, Analyst

Thanks. So any estimates or projection on the APDS patient numbers growth in 2024 more specifically?

Sijmen de Vries, CEO

Yes, as I mentioned earlier, we will keep bringing in new patients for the product in the USA. The adherence rate is quite high since it’s a chronic therapy. We will provide updates on the number of patients quarterly as we receive those results. Does that answer your question?

Unidentified Analyst, Analyst

Yes. Understood. Yes. Thank you so much.

Stephen Toor, Chief Commercial Officer

All right.

Operator, Operator

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

Simon Scholes, Analyst

Hello. Thanks for taking my question.

Sijmen de Vries, CEO

Hi, Simon.

Simon Scholes, Analyst

The exclusivity on RUCONEST in the US expired a bit more than two years ago. I was just wondering what kind of impact, if any, you expect that to have on RUCONEST?

Sijmen de Vries, CEO

Yes. We expect no impact whatsoever on RUCONEST in that respect because we believe that there is nobody that actually is working on or has any appetite to develop the transgenic platform to make a biosimilar for this product given also that it is of course a great product but it has in the greater context not a huge commercial is not a huge commercial opportunity. So therefore no is the answer no effect. No impact.

Simon Scholes, Analyst

Okay. I just wanted to follow up on that. What are your current thoughts on the likely timing of the first gene therapy for HAE, aside from your own product?

Sijmen de Vries, CEO

I think that will be a long time from now since only the first patients are being tested. Gene therapy is not the fastest development pathway. But maybe you can share your thoughts on that, Anurag?

Anurag Relan, Chief Medical Officer

No. I think that said Simon that there's some initial results in a small number of patients, but I think this will require the typical development path Phase II, Phase III as well as long-term follow-up which will take several years at the minimum.

Simon Scholes, Analyst

Okay. Thanks very much.

Anurag Relan, Chief Medical Officer

Thanks, Simon.

Operator, Operator

Thank you. I will now hand the call back for closing remarks.

Sijmen de Vries, CEO

Thank you very much for joining our full year conference. As I mentioned at the start, we achieved a significant 19% growth in revenues in 2023, marking the beginning of a promising growth trajectory for our company. This is why we anticipate further substantial revenue growth this year, driven by our continued growth expectations for RUCONEST and Joenja. We are confident in our systematic efforts to identify patients with VUS, the VUS validation efforts, and family testing. Additionally, we see growing opportunities for Leniolisib outside the U.S. through our Named Patient Programs and other Early Access Programs, where we expect to see revenue increases. We are also completing clinical trials that will support future approval in Japan, though this is not a 2024 story, as the submission will only be ready by the end of that year. We anticipate receiving regulatory feedback from various authorities and expect approvals throughout 2024. We are excited about expanding the potential of Leniolisib for a second indication related to immune regulation linked to PI3Kinase Delta signaling, which represents a significant growth opportunity. While we won't have updates in 2024, we will keep you informed once the trial starts and results are available, ideally leading to the next development stage for Leniolisib focused on that second indicated patient. This is just the beginning, as we are exploring additional opportunities to apply Leniolisib in related areas, with more updates to come in the future. Lastly, we’re actively seeking opportunities for in-licensing or M&A in clinical stage products targeting rare diseases, particularly in Immunology, Haematology, Respirology, and Gastroenterology. Thank you again for attending our conference, and we look forward to updating you on our next quarter results in May. Thank you very much, and goodbye.

Operator, Operator

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