Pharming Group N.V. (PHARM) Earnings Call Transcript & Summary

Ladies and gentlemen, good afternoon or good morning. And welcome to this analyst conference call about the pivotal data that was released yesterday in our press release. And today, with me here is our colleague, our Chief Medical Officer, Dr. Anurag Relan, who can take you through the data in a little bit more detail and talk a little bit more about the APDS disease. But before we do that, I would like to draw your attention to this slide with the forward-looking statements. As you know, we're a listed company, obviously, and I have to make this -- warn you against forward-looking statements that circumstances and plans may change, as we all know. And having said that, I would like to then briefly introduce this. So the history here of leniolisib is that in August 2019, we in-licensed leniolisib from Novartis, and leniolisib is -- was under -- is under development for the treatment of APDS, activated phosphoinositide 3-kinase delta syndrome, which is a rare primary immune deficiency caused by genetic mutations, affecting about 1 to 2 people per million of the population. Typically, these patients are treated by immunologists, which is mostly pretty similar to hereditary angioedema patients, which enables us to leverage our existing infrastructure to a great extent. And hence, why we were very interested back in the days when Novartis was offering this compound for out-licensing. As it is a new disease and it is an ultra-rare disease, it is obviously very important that there's a good strategy to find these patients. The good news is these patients are mostly already treated. But the bad news is, of course, they need to have a formal diagnosis. And therefore, we, in the U.S., partnered with Invitae, a big diagnostic company, to launch a genetic testing program, navigateAPDS. That is therefore available for potential APDS patients in Canada and the U.S. We also received orphan drug designation from the European Commission whilst we had the rights from leniolisib over the last couple of years. And before that, Novartis already received a similar designation from the FDA for the U.S. Recently, we also received a positive outcome for our pediatric investigation plan from the European authorities, very important, obviously, because as you -- as it is a genetic disease, it is very relevant to find those patients as young as possible. And why we are here today, of course, in collaboration with Novartis, who was driving this trial, and it was during this trial, we have successfully completed this Phase II/III pivotal clinical study of leniolisib for the treatment of APDS. And we were very pleased to report yesterday that both primary endpoints were reached and leniolisib demonstrated clinical efficacy over placebo. And having said all of that, I would like to now hand over to my colleague, Dr. Anurag Relan, our Chief Medical Officer, to dive a little bit deeper into the disease and the top line data as presented in the press release yesterday. Anurag, over to you, please.

Thanks, Sijmen. So what I wanted to do before we talk about the results is just talk a little bit about APDS. You've heard us speak about it before, but really this is an ultra-rare disease. And as Sijmen mentioned, it has a prevalence of about 1 to 2 per million. But with that type of prevalence, we estimate that there's about at least 1,300 patients across these 3 major markets of the U.S., European Union and Japan. And to that end, through our own efforts and efforts of researchers in the field, we have identified more than 350 patients already with APDS. As there's a greater understanding of primary immune deficiencies in general, we are also finding more of these patients. As typical for rare diseases, especially newly-defined rare diseases, these patients spend years undiagnosed, misdiagnosed. They see lots of different specialists. The symptoms do usually begin early in childhood. And obviously, they can impact everything from school, social development. And then as these patients grow older, there's a significant impact on their quality of life. Surgical interventions that are often unnecessary are common. As we said earlier, there's many doctors involved in their care. And because of the severe nature of the disease, there's a significant impact on their mental health as well. The disease itself is manifest as this immune deficiency as well as this immune dysregulation. What that means is that these patients have recurrent infections, most commonly in the lungs, so they get frequent pneumonias. Because of the pneumonias and because of the disease itself, they can develop permanent lung damage called bronchiectasis. They can also develop autoimmune issues and inflammatory problems that lead to gastrointestinal disease. They can also develop hemolytic anemias. So their blood cell types -- blood cell counts go down. And -- but really, the hallmark of the disease is this lymphoproliferation. So because of this activation in this PI3K pathway, these patients have significantly swollen lymph nodes. They often have a large spleen, and sometimes you'll also see enlarged livers. And because there is this lymphoproliferation -- this unchecked lymphoproliferation which is part of the immune dysregulation of the disease, these patients can often go on to develop lymphoma, too. I mean that's, I think, a real serious consequence that many of these patients that we follow, we can see this happening. How are these patients treated? You see on the top right, it's really limited. It's supportive nonspecific therapies. So antibiotics are used if they get an infection. Corticosteroids are used to control the autoimmune aspects. Because there is immune deficiency, these patients are often given immunoglobulin replacement therapy. In some patients, to control this abnormal lymphoproliferation, they're given drugs that are in this mTOR inhibitor category. These are, of course, used off-label, and these drugs have significant side effects and they're difficult to manage and control these patients with, but sometimes they are necessary given the lack of treatment options. And then for some patients, really when there are no other treatment options, they're given a stem cell transplant. And these stem cell transplants, while they've improved over time, in general, these are still serious procedures, and they are associated with a lot of significant consequences due to the transplantation itself. The bottom line is there is no approved therapy for these patients. And that's really where we step in when we think about developing leniolisib. On the next slide, you can see some of the efforts that we have undertaken to find patients. So these are really threefold efforts in terms of first trying to building a network of key opinion leaders and a referral pathway of prescribers who were out there looking for doctors who have an interest in primary immune deficiency, of treating these patients and also help uncover these patients. On top of that, we're using a patient identification strategy to find patients who maybe have APDS but are not diagnosed yet. So they have a symptom profile; for example, they have enlarged spleens, enlarged livers. They're on immunoglobulin replacement therapy. They may have autoimmune phenomenon. And trying to piece that together to say, okay, this patient has the profile of an APDS patient, let's get this patient genetically tested . And that's really the third part of this. Here's the program we initiated last year, the navigateAPDS program that Sijmen mentioned, where we are out there offering a sponsored genetic test that allows physicians who have potential APDS patients to access a primary immune deficiency panel of more than 400 different genes through Invitae. And this allows the patient to eventually get properly diagnosed with APDS or sometimes many other primary immune deficiencies. We've been doing this now for several -- a better part of the last year, now several months. And hundreds of tests have now been ordered, and we are uncovering potential APDS patients through this program. So we're quite keen to continue this partnership with Invitae to offer this genetic testing to people -- patients to receive a diagnosis of APDS or any other monogenic primary immune deficiency. On the next slide, you can see what we're doing with leniolisib. And leniolisib is an effective orally selective PI3K delta inhibitor. It has a precision biomarker response to impact the root cause of the disease, and we'll walk through some of that data that we have on that. And they have the potential really to mitigate the progression of the disease, reduce treatment burden by eliminating the need potentially for other therapies. We've already talked about having a genetically -- a genetic test that's commercially available to help with the diagnosis of APDS. And as Sijmen has mentioned, the progress -- the regulatory progress that we've made in terms of orphan drug designation, the pediatric investigation plan and then the bottom line is that many of these APDS patients are treated by immunologists. So these are physicians that we're used to seeing due to our work in HAE, and this really allows us to continue to develop that presence in that immunology market. And on the next slide, I want to walk you through now the pivotal trial design. And the pivotal trial really consists of 2 studies as well as there's a separate study that I'll talk about, the open-label extension study. Now part 1 was a dose-finding exercise where we took 6 patients that were given 3 different doses of leniolisib, and they were given each of these doses for periods of 4 weeks at a time. These were adults with confirmed genetic diagnosis of APDS. They had typical symptoms, including the lymphoproliferation, the enlarged spleen and all of the other biomarkers that are typically seen with APDS. The outcomes in this part were safety and tolerability, of course, looking at the pharmacokinetics. And based on this, and I'll show you the data in the next slide, the dose of 70 milligrams twice daily was selected for Part 2. Part 2 is really what we announced yesterday in terms of the randomized placebo-controlled part of the study. In this study, there were 31 patients enrolled and treated who received leniolisib or placebo in a 2:1 ratio, so twice as many patients on leniolisib as placebo. And again, this was a blinded study. So patients, their caregivers, the investigator and, of course, the sponsor was blinded. We talked about the fact that this was a placebo-controlled study, so 1/3 of the patients received placebo. And there were 2 co-primary efficacy endpoints. And these co-primary efficacy endpoints are really the hallmark of the disease. They define the condition from a biochemical point of view, a biomarker point of view as well as clinically what we saw in terms of what I mentioned earlier in terms of the lymphoproliferation. So again, trying to quantify and measure the enlarged lymph nodes in these patients. And the 2 endpoints, we're looking at how these lesions, these large lymph nodes change over time as compared to the patient's baseline and looking at this on an imaging test in a very formal way. And then on top of that, trying to look at the patients' naive B cells. And so naive B cells, again, are B cells that are able to respond to antigens and infections. And looking at patients who had low levels of naive B cells and watching those evolve and change over time to look at the -- what's called the immunophenotype normalization. So can the B cells that these patients have now function properly? Do they have a normal amount of functioning B cells? And I'll walk you through some of the data that we have in Part 1 as well as what we saw and what we announced yesterday in Part 2. And then, of course, there's safety assessments. On top of that, all of these patients that are in the dose-finding part in Part 1 and Part 2 are able to roll over into a separate study, an open-label extension study. And really, that completes the picture in terms of the total data package that we will have on APDS for these patients. And that's actually quite a significant part of the data package because we have the dose-finding part, we have, of course, the placebo-controlled part, but these are short duration studies. And we see they're 12 weeks each in duration. The open-label extension study now is something that these patients can continue on for much, much longer. And in fact -- and we'll see some of the data. We have patients who started in that first group, that first initial cohort of 6 patients who've been now on the open-label extension study for several years, some of the patients for more than 5 years, and we have that data to be able to look back. And all of these patients, including in the placebo-controlled part, are able to roll over into this open-label extension study. And this, I think, will be a significant part of the data package to be able to offer to patients and eventually to discuss with regulators is to explain why there is a benefit in when we see this drug taken for long periods of time, and then also show eventually what that tolerability and safety profile looks like. On the next slide, you can see the -- some of the demographics of the 6 patients that were enrolled in Part 1. And these patients were -- you can see their ages. You can see the presence of enlarged spleen in the liver. You see some of the other autoimmune phenomena that these patients had in terms of cytopenias. So they had low -- oftentimes, low levels of different blood counts. You see that almost all of them also had recurrent infections that led to pulmonary problems. And you see that 3 out of the 6 had a history of developing lymphoma. And again, that's because of this unchecked lymphoproliferation and sort of this immune dysregulation that occurs in these patients. So again, these are seriously affected patients, and you see that the ages of these patients were fairly young. But you see that if we go back and actually look at what days these patients started having symptoms, it's even younger. So this is really a disease that these patients are born with and it begins to manifest very early, and then these patients suffer progressive complications due to the disease over time. And what we saw -- in the next slide you see in Part 1 was that the drug was well tolerated at all 3 doses. But as I said earlier, the 70-milligram dose was selected for use in Part 2. And we'll talk about that next. In Part 1, we did not see any significant side effects or study drug discontinuations. In general, we saw there was less disease activity and greater patient well-being from being on the drug for even just 12 weeks, including just 4 weeks at that 70-milligram dose. And what did we see? Specifically, we saw suppression of this hyperactivity that's present commonly in all of these patients is PI3K activity that was suppressed. We saw that their naive B cell levels normalized. So we saw what's called the transitional B cell levels go down. The naive B cells, these are the ones that, again, that can recognize antigens, we saw their levels go into the normal range. We saw a reduction of IgM levels. So oftentimes, these patients have elevated IgM, and we'll actually look at some of this data in a moment, too. We saw reduction in these dysfunctional and senescent T cells. So again, all of the biomarkers of the disease they see, okay, these patients' immune function is returning to normal. And as a consequence of that, you see in the last arrow there on the right, we saw regression of the lymph nodes and the large spleen that these patients have. And you see the numbers there in the table on the left, you saw the lymph node and spleen volumes and sizes decreased by about 40%. And this -- I think this is a significant finding that we saw even again in this short duration study. On the right, you see an example of a patient who has an enlarged spleen is actually given a drug off-label that I mentioned earlier, one of these so-called mTOR inhibitors, [indiscernible] really no significant change. And then was given leniolisib, which is coded there as CDZ173, and we see a rapid decrease in the volume of [ display in ] size of the spleen. And that's what we saw in the study as well. And if we go to the next slide we can see something that I think is actually probably one of the most relevant findings is, and this is what I mentioned earlier, is the long-term results. And what I mentioned earlier, that patients with APDS often have elevated levels of IgM. And you can see each of the patients here as represented by one of these solid lines on the far left, and you see there are levels that are increasing in many of the patients. You can see that as they take the drug -- so over the course of the 12 weeks of the dose-finding part of the study, we saw those levels decrease. And then interestingly enough, a couple of these patients, there was a short discontinuation. So they couldn't enroll immediately in the extension study. So you see those dash lines and you see their levels start to go up. So actually, it's almost like a withdrawal type of design, and that was done unintentionally, of course. But because these patients were off-drug, you can see the IgM levels increasing. And then when they're placed back on drug, you see their levels coming back down again in these patients. And there was one patient in particular, they had a long disruption in therapy, patient number three. She was on the West Coast of the U.S. and was unable to travel to the study site at the NIH. And so she was off-drug for a significant period of time, and you see her IgM levels between the time when she was on the drug versus when she stopped. And then when she resumed the drug almost 1.5 years later, you see her levels again were high and then dropped down significantly, again, as they did when she was first on the drug. So I think this is quite an elegant picture that shows a few things: one, that these patients have elevated IgM levels that respond to leniolisib; two, that stopping leniolisib worsens these IgM levels; and three, that these patients can be on leniolisib for significant periods of time. And again, this data was published actually back -- or presented at a conference back in 2018. So these patients now have even 3 more years of data beyond what is shown in this slide. And these patients have continued on therapy. And we continue to see the safety and tolerability profile of leniolisib in these patients, and we see that these patients respond well, including over long periods of time that these IgM levels have fallen. So I think this is quite an interesting finding and really relevant to use a new drug could potentially be used lifelong for these patients. But now on to the Part 2 of the study. And these are, again, the randomized controlled results. And these randomized controlled results, I will mention that we've just received the final results in the last couple of days. And of course, we wanted to share those with everyone on these positive results, but we're still in the process of analyzing all of these data, and we will be presenting these data next month at an upcoming medical conference. We'll have much more detail to provide then. But I do want to go ahead and share again that we -- the study met the primary endpoints, and these endpoints were the reduction in the lymphadenopathy lesion. So showing that it could decrease the size of these lymph nodes in these patients over that 12-week period as compared to placebo and receiving highly statistically significant p-value there. And on top of that, that we could also see a normalization of the immune dysfunction. So we could look at that proportion of naive B cells as a proportion of the total number of B cells and see that those levels also normalize and increase over time. We again will be looking at all of the data. And again, we'll be sharing that data at this upcoming medical conference toward the end of next month as well as looking forward to publishing these data in a peer-reviewed journal. And over the course of the year, we will be talking more about this and as well as other data that we've generated from [indiscernible]. In terms of safety, on the next slide, we see that in general, leniolisib was well tolerated, with the majority of adverse events in the leniolisib and placebo groups were mild. There were no adverse events in this randomized control part of the study that led to discontinuation or no deaths in the study. The incidence of serious adverse events were lower in the leniolisib group than the placebo group, and none of the serious adverse events were suspected to be related to study treatment. We plan to share full detail around all of these safety results again at this upcoming medical conference next month. On the next slide, you can see sort of the layout for the next couple of years in terms of these milestones for leniolisib. We've just announced the top line data around the pivotal study. We anticipate initiating the regulatory filings for this for APDS beginning with FDA in the first half of this year, followed by filings with EMA as well as MHRA in the second half of this year. You heard Sijmen mention and me mention before also that this is really a pediatric disease. These patients are born with these mutations, and that leads to the hyperactivity of this pathway. And we intend to begin work in a younger population because the patients that have been studied up until now, including this Part 2, were age 12 and above. But we also know that there are many APDS patients who are younger. We plan to initiate clinical studies in the younger population in the second half of this year. And then also important, we've identified patients in Japan, and we have -- we plan to initiate a small clinical trial in Japan to also evaluate the safety, tolerability and efficacy of leniolisib in Japanese APDS patients. If all goes well, we anticipate that we may achieve regulatory approval in the U.S. as well as commercial launch in the first half of next year, followed by similar milestones in Europe with regulatory approval in the first half and commercial launch potentially in the second half of next year. So quite a number of milestones with the availability now of these data. On top of that, we expect to have more data to share not only around this Part II study, but eventually around the open label extension study, which I think, again, will really complete the picture in terms of what happens to these patients when they take the drug for long periods of time. And I think this is a significant part of the entire leniolisib risk-benefit package when we offer this to the regulators also. But I will turn it back over to you, Sijmen, to close this out here.

Thanks very much, Anurag. Sorry, I had my phone on mute. Thanks very much, Anurag. Yes, it's going to be very busy as you heard from Anurag, coming 2 years with leniolisib. And you heard also that we are going to be heavily involved in finding those patients, amp up the efforts to find those -- as many APDS patients as soon as possible. And we're going to, therefore, invest heavily in the launch preparations for leniolisib. And we can do that because we're a well-funded business that are -- is supported by our commercial sales and our growing pipeline. And mainly, of course, thanks to our RUCONEST, which is our lead product in hereditary angioedema, approved for the treatment of acute attacks, which delivered sales of $146 million in the first 9 months of 2021. That is are we able to invest in all these things without having to go to the markets for additional funding. That's very, very important to note here. And of course, with these results from leniolisib, as discussed today, we now have this near-term inflection point coming where you heard Anurag say that we anticipate to launch leniolisib in the first quarter of '23 with a very significant market opportunity, which we believe has very significant and transformational commercial potential for our company. You heard already how efficacious leniolisib is in terms of treating those patients. So it's going to be transformational for those patients as well, but also for our company. Not only will we no longer will be a single product company in the market, but also it adds -- it will add a significant commercial [ lack ]. In addition to that, we have the possibility, of course, to investigate additional potential indications just as we're doing for C1 inhibitor for leniolisib to investigate. And we are also working very hard on our other R&D work, including the potentially curative hematopoietic autologous ex vivo hematopoietic stem cell therapy that we recently in-licensed from Orchard Therapeutics for hereditary angioedema. So we have lots of activities ahead of us whilst we are working towards this important inflection point. And therefore, we think we are well positioned at this point in time to drive the growth of the company in the short to medium term towards very new levels. So thank you very much for attending this. And this completes the presentation now. And I would like to now open the floor for questions. So operator, we're ready to take any questions from the audience. Thank you very much.

[Operator Instructions] We will take our first question today from Hartaj Singh of Oppenheimer.

Great, and really nice results, Sijmen and Anurag. I just got a couple of quick questions and then a follow-up. One is, Anurag, Sijmen, if you file the -- with regulators, FDA, especially in the second quarter of this year, you're hoping for an approval by the end of this year, early next year, 6 to 9 months. What is the line of sight you have and the rate-limiting steps into that, what I would call a kind of a priority review or faster approval kind of approach. And this data is really good. I would imagine, suggest that. And then my second question is, we've seen some diseases like PNH or aHUS that Alexion had with SOLIRIS where the difference between the initial patient population set and then later on, 5 or 10 years later, was 5 to 10x. And it's been as little as 1 to 10x increase for some other rare diseases that we've covered. Where do you think APDS could lie within that from your initial diligence? And I just got a quick follow-up after these 2 questions.

Anurag, would you like to take those questions?

Sure. Thanks, Hartaj. So in terms of regulatory process, we will, of course, need to discuss all of this with -- and share the data with FDA, have them look at this. We are, of course, hopeful that we can get a review that allows us to launch in that -- in the time period that we're planning. But of course, this has to be confirmed by the regulators. And I think we meet many of the criteria that we -- so we were, again, hopeful of this, and I think we qualify. But of course, the ultimate decision is made by FDA as well as EMA. So I think that was your first point. In terms of the actual prevalence of the disease, I mean I think it's a good point. We have been looking for these patients, and we found patients. And I think we're continuing to find patients, and it's really -- it's quite interesting, the more we talk to physicians here in the U.S. as well as in Europe and really across the world, we've been speaking to physicians in Canada, Japan, Australia, really across the world, we find more patients. So I do anticipate that these numbers that we've mentioned are certainly possible given the number that we've found already. And I think in general, we know that this process of diagnosing rare disease patients is not easy, especially when there is no therapy available, right? So in the absence of the specific therapy, not having a genetic diagnosis is problematic. But with a specific therapy, I think that we certainly have the potential to find more patients. What that number finally looks like, is it going to be 5x more or 20x more, I don't know. But I am encouraged by all of the work that our teams are doing in finding these patients already and seeing that result and including that from that navigateAPDS program, the partnership with Invitae, in finding those patients. I think that's already showing us that there are more patients out there, both in this diagnosed population as well as in the undiagnosed population. So I think our view is really in line with that potential. Hopefully, that answered your question.

Yes. Anurag, that really helps a lot. And then just my last question here is, in this environment, the biotech has been tough, Sijmen. Companies that are profitable that can fund their pipelines, we believe probably should be at a premium. Do you expect that you're launching leniolisib still to stay profitable, use your organic kind of cash flows to fund this development while you're also developing, looking at other indications?

Thanks, Hartaj. Yes, it's a good question. Like I said, we will not need any additional funding to actually execute on the launch and the launch preparations for leniolisib because of the combination of our strong sales, continuing strong sales of RUCONEST and the strong balance sheet that we have. So we have not given any formal guidance for this. So watch this space, I suppose, as and when we come to the full year results and will take a look into 2021, what it looked like. But it is going to be a serious year -- a year of serious investing, obviously, because of the fact that we have this unique opportunity for our company now to -- for the first time in our history, to launch a product ourselves. We have agreed amongst ourselves to do it right, and that means that we're going to really be very serious about that and do serious investments during '22 to make it a success for launch in '23. I hope that answers your question, Hartaj.

We'll now move over to our next question, which comes from Simon Scholes of First Berlin.

I was just wondering if there are any plans to extend the Invitae collaboration to Europe? And also, you've talked about discovering new patients. I mean can you just give us some feeling for how quickly you've -- or how many new patients you've discovered over the last year or so?

Can you comment on that, Anurag?

Sure. So Simon, we've had -- we certainly want to remove any barriers to diagnosis for patients with primary immune deficiencies. And I think that's really the essence of the program that we have with Invitae in the U.S. and Canada. We're also looking at what options there are for patients across the world, really, including in Europe. So that may be through Invitae, it maybe through other partners who have a footprint there and can operate easily in these markets. So we're in the process of doing that. Now that said, genetic testing seems to be a little bit easier to attain because there seem to be less payor restrictions around it in Europe. So it seems to be less of a barrier, but it definitely is something that we plan to work on and we're working on now. So we're still in the process of evaluating that. And I'm sorry, your second question again, sorry?

I was just wondering if you could give us some indication of how many new patients you've discovered over the last year?

Well, in earnest, really, most of the patients that we've discovered have been in the last year. For example, the patients that we found in the U.S., almost all of those were in the last year because we've really just begun going out there looking for these patients. Of course, we did this license back in 2019 and then there was the lost COVID years in between. So in terms of actually beginning a lot of work with feet on the ground out seeing physicians, much of that only took place in 2021. There is a patient registry of these patients with a genetically confirmed diagnosis of APDS that's run by the European Society of Immune Deficiencies, called ESID. And that registry has had patients in it for several years, and we've seen also significant growth in that patient registry even in the last year. So we're seeing growth in looking -- in finding these patients, whether it's in Europe, whether it's through our own efforts in the U.S. So it's -- I think it's pretty significant in terms of the patients that we're finding, and then on top of that, the potential patients we're finding through the Invitae program. So I think we're seeing this happen really from all different fronts.

[Operator Instructions] We're now going to move over to Christian Glennie of Stifel.

Congratulations on what looks like very nice data here. Three questions, please. The first one would be just on -- just to tease out a bit more in terms of relevant importance of the endpoints that you've hit here. I mean from a sort of -- from a medical perspective, what are the clinicians most focused on and therefore, might a regulator be most focused on in terms of the endpoint. Is it the lymph node reduction? Or is it a normalization of the B cells or maybe the spleen? And you've seen in the previous study, I think you saw sort of about a 40% reduction in terms of lymph node volume. Is that sort of seen as a clinically meaningful level? Just anything you can comment around the sort of endpoints and the relevance of them.

Sure. So I think really, when we look at the overall -- when we look at the risk-benefit profile for leniolisib, we need to really think -- look at the overall picture. And what we see is that there are -- these patients have this hyperactive pathway that leads to this problem of immune deficiency and immune dysregulation. Really, that's the hallmark of the disease that they -- their lymph nodes -- and as a consequence, their lymph nodes enlarge and their B and T cells don't work properly. So they have a functional loss of these B and T cells. And what we see is that when we get these patients leniolisib, we see this lymphoproliferation begin to reverse. So we see the lymph nodes decrease in size. We see that their B cells and T cells begin to work properly. So we see actually a reversal of the exact findings that define the disease. So I think just on that basis alone, we can begin to think about, okay, these are clinically relevant endpoints. And these are really the hallmarks of the disease that you've now stopped and begun to reverse. And I think if we go back and think about some of the data, I didn't even highlight this in that slide of those 6 patients who've been on the drug now for several years, we also see that patients now are stopping their immunoglobulin replacement therapy. So now you can say, okay, they were needing to take this exogenous supplementation of this donor immunoglobulin. And now because of the normalization of their immune phenotype, they're able to stop that. So I think that is further evidence of that these endpoints are clinically relevant and relevant for these patients in terms of the clinical manifestations of the disease. But also, you can see some of the other benefits that, okay, these patients no longer need to use other therapies to control the disease. And I think that's when we start to look at the entire picture of what this -- what leniolisib potentially offers in terms of that risk-benefit profile is that we think that, that will be favorable for these patients.

Okay. And a quick follow-up on that, sorry. Is it possible then maybe in the data that we'll see a difference in terms of things like infection rates maybe between placebo and treated group?

I think those are definitely things that we will look at, and I think those will really be manifest when you start thinking about using the drug for longer periods of time. So I think that's really when you'll start to see evidence of that. I think we focused on trying to reduce the need for these other therapies, but definitely, we'll be looking at things such as infection rates.

The medical conference next month, was it?

Yes. And we'll have more details in the coming -- probably in the next week or 2 on the exact details around that conference, and we'll be sure to update you.

And then just to confirm then this, the transition of patients into the open label, that all patients have transitioned and remain on treatment, is that correct? And the placebo then switched to the treatment on open label?

Yes. I'll be able to give you a lot more detail around that when we report the results on that. But I would say, certainly, the vast majority, if not almost all patients transitioned from both either the dose-finding or from that placebo-controlled part into the open-label extension study.

Okay. Great. And then finally, in terms of the synergies on the sales force, maybe for Sijmen. But obviously, that you can leverage some structure and immunologists, but assuming this will still require a bit of additional recruitment in terms -- and additional people, sales force. Can you give us a sense of size and scale for that maybe in the U.S. and Europe and sort of rough cost of how much you need to deploy that increased sales force?

Yes, sure. Happy to do that. So yes, indeed, the commercial -- existing commercial infrastructure can handle this. Now you have to realize that if you're in this rare and ultra-rare disease space, that actually the minority of the commercial organization is on the street because there's a lot of work to be done to take care of your patients that have these kind of -- use these kind of medicines. So having said that, of course, we will employ a specialized group of people who are going to increase the efforts with regards to finding those patients in the coming -- over the coming year before launch. And subsequently, of course, these people are going to be the commercial force. And you should think about kind of numbers for the U.S. Typically, these kind of sales force is, for lack of a better word, but they're not a sales force, obviously, these patient finders is sort of the low 20s, low to mid-20s type of number of people. And I would say, in Europe, you're going to do the same as probably half the number of people as you deploy in the U.S. because in Europe, it's very concentrated, the treatment of those -- more concentrated treatment of those diseases. And Europe is going to be a more gradual rollout as well, of course, because of the fact that there will be reimbursement discussions, which in some countries will be quite extensive and other countries are a bit quicker. So that's more gradual. But in the U.S., it is going to be more of a sort of on-off situation where we deploy these people, these kind of people very quickly. And then with regards to costs, well, you're looking into the single to mid-single-digit million dollars or something like that to actually fund such an amount of people, the low to mid-single digits, that sort of deployment. And then, of course, ancillary costs that are associated with it. Does that help you, Christian?

Yes. That's very helpful.

That was our final question for today. So I'll hand back to the management team.

All right. Thank you very much, again. Also on behalf of Anurag, thank you very much for your attendance. And as Anurag was stating, we will be communicating shortly about the medical conference and other occasions where we will discuss and present the more detailed clinical data of this study and the open-label extension study. Thank you very much again for attending. I wish you a very nice day. Goodbye.