Pharming Group N.V.

Good morning or good afternoon, ladies and gentlemen. I'm here with my three colleagues, Stephen Thor, our Chief Commercial Officer, Anne Radwellen, our Chief Medical Officer, and Jeroen Wakkamon, our Chief Financial Officer. And we are delighted to take you through the third quarter results of this year. Before I do that, however, I would like to point you to the forward-looking statement slide, because we may contain, this presentation may contain or will probably contain forward-looking statements that, as you know, statements of future expectations that are based on our current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in these statements. And the rest I leave to you to read. So let's just move on to the next slide, and then, of course, to the next slide, about building a sustainable business in rare diseases. And that's what we are about, and this is, of course, you know, a very interesting moment in time for the results of 2023. And you see that on the left-hand side, how we are going to build, start to build that rare disease, sustainable rare disease business. We have significant positive cash flows for more than 200 million of, you know, moving annual total sales of Rukinest that confront the Joenja launches and pipeline development to start with. And we are very pleased, of course, with the results and the strong revenue growth of Rukines, 18% up on the second quarter and 11% up on last year's third quarter. And also, if you look back nine months, so year to date, 2% up on last year. That means that we are on track to deliver our low single-digit revenue growth for Rukines for 2023. And then, of course, you move to the middle pillar, and you see there, of course, the global approvals and commercialization of Joe and Ja that can be funded from those cash flows from Ruconest. And, of course, we were pleased, very pleased, to get that very fast approval from the FDA back in March, brought the product to the market, and got reimbursable, reimbursed patients almost immediately when we were on the market, such that we could already record revenues in the second quarter of this year, which was the first quarter Joenja was on the market. And now, of course, we're very proud of the continued growth of Joenja, where in this quarter we've booked 6.5 million of revenues, and year-to-date, 10.3 million. In addition to that, of course, regulatory reviews are ongoing for Joenja in Europe, Canada, Australia, Israel, and we have a pediatric clinical trial program ongoing as our label is currently 12 years and upwards. And, of course, on the right-hand side, you see further growth accelerators beyond Joangia in APDS. First and foremost, and that is where we will come back to you before year-end to update you on that, we are in dialogue with the FDA about the second Lelionis indication, and we'll provide you with more details towards the end of the year, and colleague Anurag will talk about a lot more. And last but not least, as we have a very... strong commercialization infrastructure in both the U.S. and Europe. We're hunting, as we speak, for new in-licensing opportunities or acquisitions for additional products in rare diseases that we can actually continue to develop, critical development, and bring to the market and then successfully commercialize. So we're looking for products that have clinical proof of concept. And if you see at the next slide, you see that there is actually space. to have such products in our pipeline. You see here the extensive work we do by enlarging our footprint by means of bringing Laniolisip to markets, a field like, as far a field as Japan, but also Canada, Australia, and Israel, and of course the other indications. So you see there's space in this pipeline to further accelerate the growth of the company going forward. And with that said, I would like to now hand over to my colleague, Steven Tor, who will give you some more insights in the commercialization operations on Ruconest and GeoEngine. Steven, over to you.

Thank you, Simon. Good morning, everybody. As Simon said, I'll give you a brief overview of Ruconest performance and also some insights around the GeoEngine launch and update you on that progress to date. Next slide, please. So as communicated at the end of Q1, and as you're all aware, the HA market underwent a significant event which affected all products. The event was short-lived, and as we said we would, we bounced back strongly in Q2 and Q3. As you can see in the first bullet, we posted strong growth in Q3, and even with the soft nipper Q1, as Simon showed, we have grown versus prior year. So we're really pleased with that performance. And this has been driven by strong performances across all of our leading metrics, but I especially want to flag new patient enrollments, which have exceeded 70 over each of the past three quarters, which is stronger than we've seen in the past. And so hence, as Simon said, we continue to guide the low single-digit growth for Rukaness this year. Next slide, please. So as many of you know, Rucanest was launched in 2015. We've actually, though, been active in the HA community since around 2000. And over those 23 years, we collaborated with all key stakeholders, including the clinical ones and patient advocacy groups such as the HAEA. And that has been the major driver for the consistent success of Rucanest over the nine years post-launch. And it's why the prescriber base continues to grow with 700 in the U.S. to date. and also why we've treated over 2,000 patients. And that metric continues to grow as well. So I think what that clearly underlines is the importance and the ongoing need for a recombinant IV C1 esterase inhibitor. And that's despite the fact over 70% of patients are now on prophylactic treatment today. So next slide, please. So moving to Joe Enger, as Simon showed earlier in the presentation, we're off to a very strong start in the US with our launch. And as indicated in previous calls, and I think as everybody on this call knows in relation to the environment more broadly, access, once a patient is diagnosed, is one of our key pillars for success and the ongoing success of this launch. And we partnered with an organization called Panther of RX that specializes in ultra-rare or rare diseases to build a program that we thought would enable us to quickly provide patients with access to Joengia once they're covered for chronic use. And I'm pleased to report that in only six months post-launch, Farmers Access and Medical Teams, in partnership with key opinion leaders across the country, have secured APDS coverage policies in over 90% of our target plans across commercial and government payers. And the result is a 93% approval rate with zero denials. And so I just want to repeat those two. 93% approval rate with zero denials, despite the rarity of this condition and the heavy lift on education. So that's really a very strong performance. Also, as you know, from enrollment to shipping to patients, the gold standard in rare disease is 30 days. And I'm pleased to report to you that we're averaging 26 days typically, and sometimes we're getting from enrollment to putting product in patient's hand in less than 20 days. And really, this is based on exceptional customer focus and execution, which further instills, I believe, in our confidence in our stakeholders, but most importantly, you know, the patients and treating physicians. So next slide, please. So I've mentioned, you know, farming strong customer and patient focus, and I think combined with the exceptional execution I've already mentioned, our U.S. team have delivered strong results in that first six months since launch. We have, as the slide shows, 76 eligible patients, 63 shipping, and that represents well over half of the eligible patients we have on therapy. This has led to the revenues of $10.3 million that Simon also showed. And as already mentioned, payer discussions have and continue to go very well, which creates, importantly, an excellent environment for us to pull those patients through once they're diagnosed and enrolled. So finally, I just want to flag now that we're through the immediate launch phase, and with many of the previously identified patients on therapy, we'll be placing additional time and resources now on family testing. Most of the patients we have are patient zero, so to speak, so we believe there's a lot of opportunity there to help those families by better educating them and testing all of them to see whether there are others in need of therapy. And with that, I'd like to hand over now to our CMO, Dr. Anurag Raman.

Thanks, Steve. I'll begin on the next slide with a little background information about APDS. So APDS was first described in 2013, and based on our estimates and literature review, we believe that there are more than 1,500 patients worldwide diagnosed with APDS, or 1,500 patients with APDS. We have already found more than 640 of those patients. These patients who have APDS have really had limited treatment options until recently to only treat the symptoms of the disease. The disease manifests itself in childhood and worsens over time, but without anything specifically indicated for treatment, physicians and patients were quite limited in their treatment options. And as with most rare diseases, the signs and symptoms vary across patients. This makes the challenge of diagnosis even more difficult beyond just a rare disease. Fortunately, there is a genetic test that can provide a definitive diagnosis for APDS, and I'll be spending more time in the coming slides talking about our plans and efforts to help find more patients with APDS. On the next slide, we can see what Joenja now brings to patients in the U.S. as a potential treatment option for them for their condition. It is approved by FDA for the treatment of APDS in adults and pediatric patients from ages 12 years of old and older. We have randomized clinical trial data showing that Joangia met both primary endpoints, as well as meeting several significant other clinically relevant endpoints. In addition, we've seen a well-tolerated and generally safe adverse event profile. There were no drug-related serious adverse events in the study or withdrawals due to the drug in the study. And more importantly, we have long-term data, and I'll be sharing some of that with you that we've been publishing and presenting at conferences recently, about the long-term benefits of using Joenja over several years in many cases. And this includes for patients in some cases to discontinue the use of immune globulin replacement therapy, reduction in infection rates, and persistence of the benefits that we see from the randomized clinical trial. And we can see that both in key measures of what's called lymph proliferation, so their lymph nodes continue to stay not enlarged, and we see benefits also in their immune cell function. And as Steve mentioned, this has led to a strong start for Joenja. I think this speaks both to the unmet need that exists in this APDS population, but also speaks to the seriousness of the condition. On the next slide, you can see some of our things that we're doing beyond the work that we've done in the U.S. As we discussed in August, we received the day 180 list of outstanding issues from the European Medicines Agency, and we can confirm now that in October we have submitted our responses. We remain on track to expect an opinion in this quarter, and with potential approval two months later. If we receive a positive opinion from the CHMP in this quarter, we can then go ahead and file with the UK MHRA agency with potential approval also two months later. And as we previously announced, we've started a program in Japan to enable registration there eventually, and we've also now filed in Australia, Canada, and Israel, and those applications are proceeding along their review We've also started a named patient program to eventually be able to help patients obtain access in territories across the world. And our pediatric study is enrolling quite well with the majority of enrollment already complete in the four to 11 study. And the one to six year old study has now started recruiting. So we expect that first patient also to be treated very soon. And as Simon mentioned, We have been engaged with FDA about the second indication, and we expect to be able to provide further details on the second indication later this quarter. On the next slide, I want to review with you some of the patient-finding efforts that we've initiated and are ongoing at this time. The first, of course, is APDS is a rare disease, and it's critical to raise awareness about APDS. And now we have a plethora of data also on laniolis that we can share. These data highlight the seriousness of APDS, and I think it also highlights, I think, the experience that we have with Leniolis have been treating many of these patients. On top of that, we have our ongoing Navigate APDS program that offers no-cost testing available to patients in the U.S. and Canada. And these patients, once they have this testing available, often have questions. So we have genetic counselors available to help them consider the testing and then also review the results with them. And then a big effort that we're really pushing on right now is that when we look at the diagnosed patients that we have in the US, especially, we find that most of those patients actually don't have family members that have even been tested. And we know that APDS is an inherited disease, but there's this gap in terms of testing. So we've initiated several efforts here, both with physicians and with family members themselves, be able to reduce the barriers to allow further testing amongst family members, which we think will be important to help uncover and find more patients. On the next slide, I want to review with you a little bit of information on something called variants of uncertain significance. And what these are are genetic test results that are basically unclear or, I would better say, unclassified at this point. And with the growth in genetic testing, We get more of these inconclusive results. These are basically variants that have not been previously seen. And this is really frustrating for patients and doctors because they have patients who have clinical symptoms of APDS often, but the genetic test result is inconclusive. And so we have several efforts ongoing. And I'm not going to review all of them with you in detail here, but these efforts involve trying to review the existing data and try to collate all of that information and publish that. We've just started a partnership, for example, with Genominon to develop these genomic landscapes, which will be available to all clinicians to be able to easily access variant information. We have a number of efforts ongoing to increase the availability of functional testing. And then lastly, I think I'm really excited about this possibility of this new effort that we started looking at a way to, in a single experiment, test all possible variants and quickly determine whether a result is pathogenic or disease-causing or not. And I think the nice thing here, in a sense, is that this is a problem, it's a new problem for APDS, but we're really using a playbook that exists already for many other genetic diseases. And we're following that playbook to be able to help these APDS patients who may still have this unclear diagnosis. On the next slide, you can see some of the conferences we've been presenting at and some of these abstracts we presented. These abstracts vary both in terms of what we're talking about in terms of the seriousness of the condition, so the mortality, for example, associated with APDS, but also the healthcare costs associated with APDS and especially untreated APDS. And these data, I think, highlight very nicely the serious burden that these APDS patients face. On top of that, we continue to get more data out of our clinical trial program. So we have a second interim analysis that will be published at the IPIC conference next month. And we also have a number of case series as well as abstracts on single patients. These are from many times from our expanded access program or compassionate use program where, for example, the second bullet under the IPIC heading is a patient who was previously transplanted, unsuccessfully, unfortunately, but then was treated with laniolisib under this compassionate use program, and the data at the abstract will show the benefits that this patient was able to experience. On top of that, on the next slide, you can see some of the publications. So the first publication is the first interim analysis, and that's available now in a full paper. And then the next publication is also a key publication describing the mechanism of action of laniolisib in APDS. And I think it describes clearly how APDS leads to this primary immune deficiency with this immune dysregulatory phenotype and how laniolisib benefits in these patients. And with that, I'll turn it over to my colleague, Jeroen Walkerman, our Chief Financial Officer.

Thank you very much Anurag. Focusing first on the financial highlights of the third quarter 2023, total revenues increased to 66.7 million, so an increase of 12.5 million or 23%. Gross profit increased to 58.4 million, an increase of 6.5 million. Operating costs increased from 44.7 to 56.8, and the increase of 12.1 million is mainly because of R&D, additional investments of 8 million, and marketing and sales of 5 million. And that is all directed towards the launch, or most of it is directed towards the launch of Joenja and the further developments of the market. The operating loss was profit in this case is 1.9 million and the net profit was 3.5 million in the quarter and that was on the back of positive financing income and a tax credit which is a timing effect. Simon mentioned it already, but the cash and cash equivalents increased to 199 million at the end of that quarter. Looking at the figures year-to-date, nine-month year-to-date, the revenue increased by 9% to 164.1 million. Gross profit increased to 146 And as was guided earlier this year, we further increased our OPEX, as I said, into mainly marketing and sales and R&D. And the operating costs were 175.3 million, i.e. an increase of 48.4 million versus the same period last year. Consequently, the operating loss was 6.5 million for the three-quarter period, and the net loss was 7.4 million, which is an improvement from Q2 this year.

If we go to the next slide, We see the growth in revenue over the quarters.

The third quarter revenue was 66.7 million, and that's a 23% increase from last year, driven by both Ruconest and obviously Joengia, as you can see on the picture. And also accelerated growth is seen in Ruconest. So you will remember that in Q1, There was a temporary reimbursement issue. It was a market circumstance, so we had a dip in sales in RUKUNAS, but we have very well recovered from that, and we are now on a positive note, and that is in line with the guidance that we gave earlier this year. Cost development, as I said, investment in the Geoengineer launch and further development of learning fellowship continues. And we have a quarterly OPEX of almost 57 million. And you see also that the increase is mainly, as you would expect, both in research and development and marketing and sales. and the general and admin costs are relatively stable. The increase in R&D, or the stable for now, was mainly guided towards clinical, operational, and medical affairs. And if you look at the development over the quarters, as we guided earlier in the year, it's fairly stable, especially if you exclude the one-off milestone payment in the second quarter. Then going to the outlook for this year, we remain on track for single digit growth in Ruconest revenues, and that's only been confirmed by the numbers that we've shown in Q3. Joangio was improved in the first quarter, and we've been commercializing in the US since early April, as my colleague Steve alluded to. The CHMP opinion is expected in the fourth quarter of this year and the marketing authorizations subject to the positive outcome of the review is expected in Europe two months later. We will file Leniolosib with UK's MHRA following the ECTRP route and we will continue to invest in accelerated growth for the future in operating costs. In the remainder of the year, we will detail further our plans to develop Laniolosib in additional indications, and as Simon mentioned, we keep looking for investments in licensing and also acquisitions of assets to Indria Disease for future growth. With that, I want to start off, kick off the Q&A. So any questions are welcome. Thank you.

Thank you. To ask a question, you will need to press star 1 and 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 and 1 again. We will now go to your first question. And your first question comes from the line of Christian Glennie from Seville. Please go ahead.

Yeah, good morning, good afternoon, guys. Thanks for taking the questions. Three, please. I'll take them in order. Let's start with Rukanest and a strong quarterly sale print. Just to be clear around whether there's anything to be aware of in the Q3 numbers, maybe there's stocking or some impact that means it should be a clean quarter. And then in implications for, as we think about the fourth quarter as well, typically your strongest quarter, particularly in the U.S. for Reconest, any reasons why Q4 wouldn't still be your strongest quarter for the year?

Thanks, Christian. That's an interesting question. Would you like to comment on that, Steve?

Yeah, sure. Thanks, Christian. So you're right. Q3 is strong, and we occasionally see stock in, but it's sporadic. There's no real pattern to it. So I would still expect at this stage Q4 to be our strongest quarter and for us to see out the year strong.

Thanks. And then maybe a quick follow-up to that. I mean, anything, I mean, you've called up the new patient starts. I mean, it's just curious why you're still getting this very sort of

strong uh patient starts and physician uptake and things anything else to comment on that yes i think it's interesting we actually restructured our team a month before covid hit and then we had to mothball them so i think you're seeing a combination of different things happening but certainly the restructure of that team is now paying off and that's why you're seeing actually an increase in enrollments and that consistent increase in enrollments across three quarters so i think that makes a big difference and the other thing i would say is we have a very well tenured team um So deep relationships within our physicians' offices and with their staff. And I think that's really helped in identifying new patients. I mean, as you would have heard us allude to, we have a much broader mix of patients now than we have historically, whereas if at launch, as you would expect, it was refractory patients who were predominantly using rutin-S, now it's across mild, moderate, and severe, and it's pretty evenly spread. So I think it's a combination of time in market, trust, execution, And as I mentioned earlier, a continued need for IV C1 esterase inhibitors despite the quite disruptive changes to the market.

Okay, thank you. And then turning to Juenja then, if we can, just firstly on the European approval process, the advisory group meeting, as I understand, is still to be held. Is there a timing on that or any outcome that comes from that advisory group meeting?

Hi, Christian. It's Anurag. So this meeting has been scheduled. It is a closed meeting, and we're not going to provide any further guidance on the ongoing regulatory interaction other than to say that we continue to expect the CHMP opinion in this quarter.

OK, thank you. And then as we think about obviously the Q3 numbers around patient patients on pay therapy and things. I mean, anything to flag in terms of expectations for Q4 versus the sort of current run rate of enrolled patients and patients on therapy. And then particularly, maybe there's any commentary, insight you can give on the numbers of patients. Obviously, presumably a large proportion on starters, but how many bridge packs are people having to give? You seem to imply you're getting patients on to

paid therapy pretty quickly but I don't know if bridge is still something that's a reasonable factor in the mix maybe Steve you want to comment on that certainly so again as I said Christian we continue to aggressively pursue our patient finding efforts and actually we're ramping that up now we're through that early launch and conversion stage in terms of starter and bridge yeah I mean we've actually of course most of those patients have been on starter but we're We're having to bridge very few, or when we do, we bridge for a pretty short period of time relative to what we may have seen with Rukinus back in the past, and that's because of this pretty fast approval rate and our ability to get commercial product in patients' hands quickly. So, yeah, it's going very well in that regard, and we're not having to give away too much free stock.

Okay, great. Thanks. I'll jump back in the queue.

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

Thanks so much. Hopefully you can hear me. A couple of questions, please. There's another follow-on on Ruconest, which is following on from Christian's question to an extent. But you're obviously pointing towards adding prescribing physicians, and that's growing at about, give or take, 10% per annum. But also the product's growing at low single digits. How should I think about that disconnect? Is that a price effect, or is that lower utilization per patient, or is it just the incremental prescribers you're adding are sort of less active? So that's question one. And then question two, if I could just sort of push my luck a bit on additional indications, looking at some of those publications you've flagged in the presentation, I think one of the suggestions is you could look at areas where mTOR inhibitors are currently used, given it's the same pathway. And that sort of brings to mind areas like autoimmune with things like transplant rejection, but it's also oncology areas like neuroendocrine tumors. Can I press you to see whether any of those areas are things you're thinking about right now? Thanks.

So maybe the first question you want to answer, Stephen?

Certainly. So you're right to flag, I think, the apparent or the perceived disconnect. For the most part, what I would say that is, is we went from 30% of patients on prophylactic therapy three, four years ago to over 70% now in the mid-70s. So what you're seeing is better controlled patients having less attacks and therefore utilizing less acute therapy. But we haven't actually lost that many patients. What we've seen is, and we think of it as cohorts of mild, moderate, and severe. So not the disease itself, but the number of attacks. So we've seen patients in that severe end or frequent attacks move into the moderate and from the moderate into the mild area. So it's more patients, more prescribing positions, but often a less severe course of disease leading to a slightly less acute utilization.

Can I quickly follow up on that? If that sort of mixed change in the patient population is, let's say it's more or less played out, does that mean that perhaps as more physicians are added, that that disconnect could actually lessen over time?

Logically, yes, it could.

OK, thank you.

And then I think your question about our next indication I think you're thinking along the same lines that we are. For example, we know that in APDS, in the past especially, but even now in some areas where Joann is not available, mTOR inhibitors are used. They have tolerability issues and they're not quite the perfect target for the condition itself. So we are looking at other areas where mTOR inhibitors are used and where laniolisib could prove to be a better suited for that disease. We're not specifically, I can already comment that we're not specifically looking within oncology. I think it's something that we may do in the future, but at the present time, we're really focused on other rare diseases where we think that this pathway is overactive, that some of the things that we see, basically trying to take the learnings from APDS some of the features of APDS that we see. Where else do we see that type of problem in the immune system? And I think that's what we're in active discussions with FDA on trying to finalize the clinical trial plan, and I expect to be able to give an update on that later this quarter.

Great, thanks very much.

Thank you. We will now go to the next question. And your next question comes from the line of Cecilia Hernandez from Lanshot Kempen. Please go ahead.

Thank you for taking my question. Could you walk us through the development of your operating expenses? As you mentioned, we've seen an increase in marketing and sales costs due to the launch. But will this increase further? Or is this level what we can expect for the coming quarters? And also on R&D costs with the second indication for Leonid, is it feasible to target profitability next year? Thank you.

Yeah, thank you very much for the question, Sushila. On OPEX for GeoIndia, we will support the European launch going forward. So we will shift probably some of the funds from the US to Europe. On a net basis, it's too early to say what the outcome of that shift will be. And for next year, also on the new indication, yes, we will invest in R&D and in a trial. Again, there it's too early to say what the exact cost is. I don't expect necessarily a reduction in OPEX next year.

Okay, thank you.

Thank you. We will now go to the next question. And your next question comes from the line of Jay from HC Wainwright. Please go ahead.

Hey, guys. Thanks for taking the question. A couple, if you don't mind. So first, I wanted to focus on Stephen's comment on the HAE market. Obviously, there's a lot of disruptive changes to the market that are either ongoing or coming. And I'll phrase my question this way. Obviously, we know where, you know, we stand and where farming stands with regard to the role of Rukanest. But I guess, you know, maybe more feedback from, you know, your new prescribers, for example, and even existing prescribers about the potential threats that are coming, even though they are focused on the prophylactic standpoint. So basically, the external views of, you know, needing a rescue therapy such as Rukanest.

You wanna comment on that, Steven?

Sure, I mean, as you know, Joe, morning, by the way, we hold ad boards pretty regularly. We're all of us active in the year, myself and Anurag are regularly in front of customers in the US. And I think certainly some physicians are quite excited by what may be coming in the future. I think what's interesting for me is patients still need, despite all of these disruptions, that occasional bolus of therapy that you get from an IV product such as Rucanus. So although we see disruption, and as I mentioned earlier, we see sometimes a decrease or in some patients even a normalcy, an increase in utilization, we still see the need there. So I certainly wouldn't want to be complacent and we'll look at the future as closely as any company would. But through all of the disruptions, certainly since I joined farming seven years ago, we see that initial period of disruption and fluctuation in volume, and then we see things settle down, and we see a continued clinical need for an IVC1S-raised inhibitor. So does that answer your question, Joe?

No, it certainly does. I appreciate that. And I guess, you know, looking more towards just switching a little bit to Joenja, Assuming a positive CHMP opinion later this quarter, maybe if you could provide a little more color with regard to your country-by-country strategy. I know previously you discussed targeting Germany first, but how should we view beyond that, how things should go?

Do you want me to take that on? No, go ahead, Stephen.

Go ahead.

Yes, thanks, Joe. You're right. I mean, Germany would be the typical market to go to right out of the gate, and we'll certainly do that. We also will then target the other big four in Europe. Anurag mentioned the UK and a submission there. Now it's specifically there, now it's not part of the EU. And then we'll go through Spain, Italy, France as major nations. But we won't ignore the rest of Europe either. So we have a pretty lean operation in Europe and we cluster the other 22 member states around those major markets. And you'll see us through 24 and 25 in a steady sequence start to go through all those markets And by the way, we've identified patients, I think, in every single one of those markets. And in addition to that, we have submissions in Australia, which will enable us to set up a base of operations in APAC in the key markets outside of Japan, the ongoing trial in Japan, and a submission with Health Canada right now as well as that, I believe, eight-rank market globally. So I think we have a pretty careful, well-considered, sequenced approach that gets us into markets at the right time. And you'll see that pointing out through 24 and 25.

Got it. And then just lastly, I guess it's a quick logistical question. With regard to the VUSs and unclassified variants, if you will, is there anything that needs to be done as you generate data about these variants on the regulatory front or in the label to identify these?

Hey, Joe. Good morning. So the answer there is no, because these patients actually have APDS and the label is that is for APDS. Right now, the question is this variant, which hasn't been previously described or previously published, when the genetic testing company gets that result, they don't know what to do with it, so they throw it into this bucket of VUSs. And many, many results come back into this VUS classification. But once that is reclassified based usually on functional testing data or even as I mentioned that using that multiplex approach, once that's reclassified, then that patient has APDS and would qualify for treatment for the label.

Great. Thanks for the clarification and thanks for all the answers, guys.

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

Great. Thank you. Thanks, Olivia. I got a couple of questions and really nice update, everyone. The two questions I have, just following up to a previous question on the cadence of the launches, XUS, I know Australia, Canada, Israel in 24 and 25, you know, Europe later this year, and then discussions there. Can you just give us an idea of, you know, the relative TAM of that market? And then, you know, could there be boluses in Europe, the UK, Australia, Canada, because you have been working very hard to identify patients. I imagine there are patients in these various territories. you know, ready to get on drug? And then, you know, how would pricing, you know, potentially look relative to the U.S. market? So that's the first question. The second question is just on your family testing. You know, previous research we had done before lenulocin was approved indicated there could be as little as one more family member and as much as three more extended family members that might have some, you know, indication of APDS and could potentially qualify for treatment. I know these are early days. But if you could just give us some some color around there, you know, what would you expect to see as you as you wrap up this test? Thanks for the question.

Thanks. Hey, Steve, you want to comment on those patient numbers?

So certainly I didn't quite catch the front end of the question. So if I if I miss anything, then please just pick me up as we go through. So I think you're right to flag that. You know, the medical affairs group across the world have been actively identifying patients with key opinion leaders in those key centers in each country. So there will be a bolus of patients waiting therapy, and many of them will already be in the early access program, for example. There will be a slight delay because from approval in many of those countries, you then need to negotiate reimbursement, which means we set the price slightly later than the clinical approval. But in terms of your pricing question, The price outside of the US will, as you know, for the most part, always be lower. It's highly unlikely to match that price. And there'll be a variation in what that price looks like country by country. What I would say, though, is without preempting what that price might look like is, as with all ultra rare diseases and rare diseases, we can still make a market and build a very healthy business in each of those countries. And that's fully what we expect to do.

Thanks, Steve. That's great, Stephen. And then just on the question of the family testing and then how big could that patient population be, just roughly speaking? Thank you.

Yeah, so, Artaj, it's a great question, and it's certainly something that we're trying to address right now, which is, you know, we know it's an autosomally dominant transmitted disease. So, We expect that there should be other family members with the condition. And as you said, many times it may not be immediate family members, even extended family members. What we've been trying, what we've been a little surprised by, though, and I guess it relates to the fragmented nature of our health care system, is that oftentimes these family members haven't been tested. Some of that is just due to lack of awareness, even amongst patients. about the genetics of the disease. And some of that is just due to the healthcare system idiosyncrasies and how it's difficult to get genetic testing done. So we're changing the way we approach this and really moving, putting the patient right at the center of this. So allowing patients and families to actually initiate testing. So if a patient is diagnosed with APDS and a family member wants to get tested, we've started a program that will allow that to happen by having the family member themselves initiate the process, and it doesn't need to go through the, for example, the patient specialist who may not be immediately available to see the family member, for example, or may not even be a patient of the family member in most cases. So I think, you know, removing these barriers to genetic testing to allow appropriate testing in families is, I think, will likely be a significant source of newly diagnosed patients And we're starting that program. We've started a little bit of that already, but really putting that in full force now.

Great, Anurag. That helps. Thank you, everyone, for the question.

Thank you. We will now go to the next question. And your next question comes from the line of Simon Scholz from First Berlin. Please go ahead.

Yes, hello. Thanks for taking my question. So you've already identified 150 APDS patients over the age of 12 in the US. I was just wondering how many of those patients do you ultimately expect to be able to enroll?

I'd say the vast majority of those, Simon, almost all of them.

OK, so almost all.

And that's just the beginning, right? Because you heard.

Yes, I know there are other patients, but I was just interested in patients you've already identified. So we should assume over 90% or 95%.

I think there will be a very high percentage of patients that indeed will be interested to get into major treatment, correct. That's our experience so far, at least.

Okay, and particularly in the U.S., you don't expect to encounter a problem with the last 10% or 20% because of lack of insurance coverage. I mean, how does that work? I mean, presumably there will be some patients without insurance coverage. I mean, can you get those on paid therapy as well?

Although those questions are difficult to answer, but generally speaking, if we look at our experience with Ruconest, we don't see any issues related to that coming up. And, of course, Ruconest also has patients that have limited or no insurance coverage, but there's always a way. Maybe you want to comment on that, Stephen?

Yeah, I think there's all kinds of different types of support available for patients, and also public programs that try and make sure that patients have access to something. So to be honest, Simon, I haven't looked at this for a while, but I believe we have very, very few ruchinous patients, for example, in our patient assistance program, which would be essentially free supply on an ongoing basis. And even when they are in there, every year we're working with them and with their physicians to find an insurance plan for them or find an option that will lead to paid therapy. So I apologize, I can't give you a specific answer, but if I look at the Rukanest experience and my experience in rare diseases outside of farming, I think the vast majority of patients in the end will be on paid therapy. It can sometimes just be a heavy lift in those last few percent to get there. Okay, thanks very much. That's very helpful.

Thank you. As a reminder, if you would like to ask a question, please press star 1 and 1 on your telephone and wait for your name to be announced. We will now go to the next question. And your next question comes from the line of Christian Glennie from Stiefel. Please go ahead.

Hi, guys. I thought just a quick follow up, if I can, on Juangia and the pediatric study in the 4 to 11-year-olds. Looking at enrollment almost complete there. So just a reminder in terms of the endpoint for that trial, the timing of that endpoint, and therefore when we might see data. And then the expected sort of rough mix of the under 12s as it relates to this 4 to 11-year-olds. I mean, if you think about, say, the 50 remaining patients identified in the US that we know, how many of those would be 4 to 11?

So let me answer that question, the second question first, Christian. So again, based on our current experience in APDS, about a quarter of patients overall are below the age of 12. Amongst that quarter, three quarters are in the age range, at least three quarters are in the age range of the first study, or four to 11-year-old study. You know, we know these patients actually have the disease at birth, and many patients do begin to manifest symptoms early on, but oftentimes they're not diagnosed at that very early age, and that results in many patients in the older age groups, especially in that above four age group. So that's a little bit on the breakdown of the age distributions across APDS. In terms of the pediatric study endpoint, the endpoints that we had in the adolescent and adult study. So, you know, I think what we'll be able to do is once the study is fully enrolled and we have these last four patients enrolled, we'll give you some more guidance on the timing of the data releases as well as some of the regulatory work that we anticipate being able to do if the results are possible.

Okay. Thanks. That's helpful.

Thank you. There are currently no further questions. I will hand the call back.

All right, thank you very much. A few closing remarks. Thanks for attending. You can see now that, as stated last quarter, that the company is now starting a long growth trajectory supported by the foundation that Rukines provides and, of course, driven by the future expansion of Joangia outside of the United States, but also inside of the United States, supported by lots of efforts that we are undertaking and initiating to actually broaden the patient base. And of course, as always, with new genetic diseases, the definition of the disease will broaden. So therefore, we look forward to the future with optimism and with a company that will significantly grow and change over the coming years, putting us again as a combination of our commercialization capabilities, clinical development and regulatory skills, putting us again as hopefully the ideal partner or the go-to partner in the future for other rare disease assets. that we can take on board and actually complete the clinical development slash approvals and do the successful commercialization as we do with Ruconest and with Joangia. So that said, thank you very much for attending, and we look forward to updating you again on our full year results call, which will be in March of next year. Thank you very much. Goodbye.