Pharming Group NV (PHAR) 2024 Q3 法說會逐字稿

Good morning. Good afternoon. Ladies and gentlemen, welcome to our reserve call. I'm happy, I'm here with the introduce my colleagues here, Stephen Toor Chief Commercial Officer and Anurag Relan our Chief Medical Officer and you can welcome on our Chief Financial Officer and we will take you through the results and obviously answer all your questions.

So, but before I do that, I would like to have the next slide and point you to the forward-looking statements. Because during this presentation, we will be making in the usual forward-looking statements which of course, you know, are expressions of our expectations, which can differ significantly, of course from future and future results. So having said that I would like to start with the next slide, you see a slide of my face there and you'll see no doubt the announcement that after '16 years here at the helm, which is actually precisely next week.

I have informed the board of directors that I will not be available for re-election. You know, the company is in great shape today. So, we have and I'm reaching a beautiful age of 65 next week. So it would be a good moment to basically hand over the helm to a successor who can continue to build the company as we have been over the last few years into this rare disease company that, you know, we are building as we speak, with a great pipeline and with a global geographical and geographical presence.

And having said that I would like them to know to the next slide because they see how we are going to build that. Ruconest obviously on the slide number five, please, on the on the next Ruconest is, of course, that the pillar of the of the company has been the pillar for a long time. And you see the results of Ruconest, you know, continues to grow more prescribers, more patients are using Ruconest in this increasingly competitive market resulting in, you know, a plus in the three-quarters, results of more than 60 almost $64 million and you know, almost $173 million for nine months in 2023.

So in other words, you can deliver significant cash flows from which we can actually, you know, build that company and build that portfolio and build out our commercial presence with, of course, Joenja, leniolisib, the first and only FDA approved treatment for APDS, a new ultra rare immune disorder where Anurag will speak later on about and you see, the revenues are marching quite nicely for an ultra-rare launch to actually make $32 million in the first nine months of this year, which is of course an incredible growth which is last year is no mean feat.

And of course, it's a new disease, it's rare. So, we'll talk a little bit later about the ways how we find these patients and about what's going on with regards to the further exploitation of additional markets beyond the currently approved UK US and Israel. And of course, the extension of the label by with our pediatric patients. And then on the right-hand side, of course, we're very excited that we have been able to start a Phase 2 in a way bigger indication for another primary human efficiency for any other set.

And, and we'll speak to that later on as well. And last, but not least as you well know, we continue to be focusing on extending the portfolio further with an emphasis in licensing or acquiring clinical stage with clinical proof of concept opportunities and other rare diseases to basically further leverage our commercialization presence in the US, UK, Europe, and also the future markets, like Japan and Australia.

And when you do the next slide, you see the pipeline depicted in in a visual is beginning to, to look like something you know, we are in these markets with the Ruconest and Joenja. And obviously you see there the graphic depiction of the further rollout of learn the ownership for APDS. And on the bottom, you see the Phase 2 stage where Leniolisib for the subsequent indication, the PRDs with immune dysregulation.

So we're beginning to build that pipeline and we're of course working very hard to extend it with additional assets that actually build that portfolio further and leverage our commercialization infrastructure and ability to do clinical trials and get regulatory approvals further.

And before I hand over to Steven to talk about commercial results, I would like to show you one thing and that's the next slide. That is where you see, you know, enormous, incredible a number of products that are available here for hereditary angioedema patients. So, it's really good news for hereditary angioedema patients in the US, mainly we're talking about here and that there are so many products available.

There's a lot of prophylactic therapies available here and there's a lot of there is of course acute products available as well. There's of course one outstanding product and that is ruin. That's the explanation why Ruconest continues to be so strong and will in the future continue to be so strong. Ruconest a high dose protein replacement therapy and all the products that you see there that are being on the market.

And, the main ones that are being used for the treatment of acute attacks for hereditary angioedema and breakthrough attacks are the ones that act on the Kallikrein independent pathway Bradykinin pathway. And a good example of that is (inaudible), which is by far the biggest volume of products used for the treatment of acute attacks. There are drawbacks associated with this approach.

These products are not IV which (inaudible)f And of course, all our patients are very confident to do IV cell injections. But these products are for instance(inaudible). There's potential news on the horizon or opportunities that are being actually reviewed by the FDA and our clinical stage to actually address the acute attacks.

However, these oral opportunities are tested in patients that are actually responsive to fears here. And that is a big difference here in terms of in terms of patients that were serving every patient that Ruconest that uses Ruconest (inaudible).

Hence why you can see there is a clear segmentation in the market where Ruconest its own segment on the severe end of the market. And that is of course, in relative terms, patients wise a relatively modest segment, but it is a segment where patients are very severely the disease.

A lot of the so-called type three patients which are the most severely affected and that have recently been developed and that has recently been, you know, acknowledged and discovered and where more and more are coming. And that's exactly where looking at with this unique mode of action (inaudible). All the pathways serves the purpose and we continue to serve the purpose and serves that unique segment of patients.

That is why we are confident and you see the result that after all those years in the market, more than 10 years in the US market by recons continued and continues and will continue to be the mainstay under our company delivering those cash flows which enable us to confidently develop the further growth potential of the company towards the future. And we said that I would like to now hand over to Steven to take us through the commercial aspects of the of the business and the resources Stephen over to you, please.

Thank you, Simon morning everybody. If you can move to the next slide, please. Thank you. I think Simon did a really nice job of describing there our patient population and why Ruconest is used. And that is of course, as you can see on this slide, why Ruconest is the second most prescribed acute product in the US market? And really that talks very much to the features there. It's an IV, it gives a burden of C1. So, it's highly effective. It's very quick acting. And as Simon said that that's really critical for the patient population we serve that has a more severe course of hie that doesn't respond well to the alternative therapies.

It's also important to remember that in an environment where current and future options may not serve that severely affected population as well as to why Ruconest will continue to endure and why we continue to be confident in the in the Ruconest growth story in the US.

We also continue to grow our prescriber base. And that's important to mention we have 57 new prescribers this year and we're heading towards 800 in total.

And then perhaps also that success is also best demonstrated through our leading and lagging metrics, all of which experienced double digit growth this year including new enrolments which gain momentum. In fact, we had over a 100 in Q3 and that's up 25% versus prior year.

And all of this translates into around 12% revenue growth for the year so far, which is outperforming last year where we were at 10% revenue growth. So next slide please.

So moving to the Joenja launch, we achieved as you know, a strong initial start to our US launch and that growth steadied which was expected as we come towards our next pending big inflection points.

Over the '18 months since launch, we found approximately 50% of the known patients, which the prevalence suggests exists.

And of those 25% are paediatrics’. So they'll begin therapy when we get that indication of the eligible patients, the eligible adult patients, we have 93 unpaid therapy and we have five pending already in this quarter pending insurance authorization which has been going very, very smoothly.

And as we continue to find patients and, and process the adult patients not on therapy, it's important to note that our next significant growth opportunities or reflection points will be the launch in the UK where Joenja was recently approved, the potential influx of the US patients in 2025 and then those paediatric patients I mentioned in 2026. So while we had the initial strong growth which is steadied in that adult population that we can serve, we have those three big inflection points coming along with global launches beyond that.

So for patients outside of the US and you can see here that it's approaching 900 it's important to note many of those are in various of our access programs over 20%. In fact, and as we roll out approvals and launches globally, they'll become eligible for reimbursed treatment.

So all of that translates so far to $32 million in sales here today.

And then the final section of this this slide shows we also continue to drive development of growth opportunities for outside of APDS markets with our teams working hard on life cycle management opportunities for Leniolisib over the molecule outside of APDS. And they have significant potential value to our patients and our customers. So, with that, I'd like to hand over to our CMO Anurag. Well, and to talk more about those.

Thank you.

And if we see on this slide, let's start by reviewing some more details about our activities in APDS. And as you see here, we have a number of strategies to help find and diagnose new APDS patients. And first on the left side, on the education front, we continue to share and present new data on APDS including the seriousness of the condition and on the use of leniolisib in these patients. And you see a number of conferences where we have shared this data including just last week at the European Society for Immune Deficiency Meeting in France.

In the middle You can see here a number of programs that we have to help diagnose new patients and that includes our sponsored no cost testing program, our work and family testing to help identify additional patients from family members of affected patients. And then lastly on the right. And most importantly, we know there are a large number of patients with so called variants of uncertain significance. And these are patients that have a genetic test result that has not been classified as having APDS or not, but they do have a mutation or a variant in one of the two genes that leads to APDS.

We have a number of initiatives. Now, in this work to resolve these patients with the US, we're actually doing a functional testing study with these patients to help get their blood samples reanalysed and be able to tell if there is pathway activation or not. And then a large scale project that we have and that's called the main project which is actually scheduled to complete this quarter will help us determine systematically and to be able to analyse all possible variants in these two genes.

And we expect that based on these results and based on the initial results that we have so far, that are up to 20% of patients with a variant of on certain certificates could turn out to have APDS. So, you can imagine quickly by doing the math there that this could lead to almost a doubling of the currently diagnosed APDS population within a short period of time.

And on the next slide, we can see the sources of future growth for Joenja.

First of all, we continue to make progress in addressing the CH MP remaining CMC request. And as we mentioned previously, the CHMP had already concluded positive clinical benefit and safety with many of APDS patients.

And as Stephen mentioned, we also have the UK marketing authorization just last month.

We're also making progress in our filing in Japan and we expect that we will be able to file in mid-2025.

We continue to receive numerous requests from doctors to access on in other markets where there isn't regulatory approval and we're providing that through our expanded access programs as well as named patient programs. Stephen also mentioned the Israeli marketing authorization and then we also have reviews ongoing in Canada and Australia.

And very importantly, we have now our first paediatric study where enrolment has been completed and we expect results shortly on that. And on that basis, we will be able to file, we think by mid to the second half of 2025 to expand the indication to a younger population down to the age of poor. This is very important for APDS because as you know, it's really a paediatrics disease. It's a disease that starts in early childhood. Of course, being able to treat a progressive disease earlier on is logical and we're working hard to getting these patients potential access to Joenja at a younger age.

And then we'll talk a little bit more on the on the next study that we just started, which is the use of lens in primary immune deficiencies where there is immune dysregulation.

And on the next slide, we can see the work that we're doing here.

And this work is work that we think there are significant opportunities to develop glen and other primary immune deficiencies. And experts really have come to us and say that there's a significant unmet need here and there's a potential of leniolisib to address this need. And in fact, they've been coming to us with requests to obtain access already. And this has been, in fact before we had the study up and running and we actually have some use of leniolisib in so called compassionate use cases.

And these patients actually are doing well with signs of disease improvement. And this group of primary immune deficiencies are a broad group of disorders that often have a genetic basis. And the key aspect is the immune dysfunction as well as the immune dysregulation. The dysfunction leads to the increased risk of infection and the dysregulation leads to younger complications such as lymphoproliferation and autoimmunity. And again, these are features that we also see in APDS. And unfortunately, they also share with APDS the high morbidity and mortality.

We are now developing leniolisib for these patients with these primary immune deficiencies. And we've listed here a number of mutations, a number of diseases such as CTLA4 haploinsufficiency, NFKB1 haploinsufficiency and PTEN deficiency where these patients will be enrolled into a study.

It's important to remember that these patients have clinical manifestations that are very similar to APDS. There are no specifically approved therapies for these patients and the patient population is significantly larger when we think of this group together approximately five times larger than that of APDS. And we're starting this clinical trial, this proof of concept based whose dose finding study just in the last week or two.

In addition, we're working on a third indication and we'll, we're in the process of obtaining regulatory feedback on this clinical development plan and we'll have more to share about that. So, and on the next slide, we can see some details about the study that we just started. So, this is again a Phase 2 proof of concept dose finding study in '12 patients. And in fact, we started this, we announced the start of the study on 10th of October. And we expect the first patient to actually to be dosed in the next couple of days.

The study will include patients with a number of these different variants. It's being conducted at the NIH. And again, the NIH was a critical partner for us as we developed Leniolisib for APDS and they again have come to us and say, look, there's further opportunities to use Leniolisib in another group of patients where there's a significant unmet need. And we're starting the study, as I said, a couple of days with the first patient being dosed.

So more to come on that soon as well as the third indication that I mentioned briefly. And with that, I'll turn it over to my colleague, Jeroen Wakkerman and to talk about our financials.

Thank you very much. Anurag, I'll first take you to the, through the financial highlights of this quarter and then the year-to-date figures. So, revenues in Q3 increased by 12%. Ruconest grew by 6% and Joenja by 73%.

And the growth in both products was mainly driven by volume growth.

Gross profit increased by 9.7 million, which was basically in line with the revenues and gross margin increased slightly.

The increase in operating expenses compared to the same quarter last year was caused by a combination of continuing investments in Joenja in the US. Launch preparation of Leniolisib ownership outside of the US and increased payroll expenses due to business growth.

The operating profit amounted to $4.1 million compared to an operating profit of 1.9 million last year and the increase was primarily due to the increase in gross profits. As I mentioned before, offset by increases in operating expenses.

We had a net loss of 1 million in the quarter compared to a net profit of $3.4 million last year. And the change was mainly due to higher finance expenses resulting from unfavourable euro, dollar exchange rate. Development, cash and cash equivalents increased from 161.8 million at the end of the second quarter of this year to 173,300,000.0 million. And that was primarily driven that growth in cash by positive cash flows from operations of 9.7 million last year. That was 3.5 million.

So I'm moving on to the figures for the first nine months of the year.

The total revenues increased by 25% in the first three quarters of 2024 to 204.5 million revenues of Ruconest were 12% higher. At 117 point 72.6 million. And Joenja grew by 210% compared to the first nine months of last year.

I remember last year, the first sales commenced at the start of the second quarter in 2023.

And the year-to-date revenues of Joenja also includes 3.2 million from EU and the rest of the world. So, ex US as sales, the gross profit increased by 35.3 million or 24%. And mainly due to the increase in revenues and the increase in operating expenses in the first nine months was caused by a combination of continued investments in Joenja in the US. Launch preparation for Leniolisib outside of the US and increasing R&D investments to expand the Leniolisib franchise that Anurag just mentioned and increased payroll expenses due to business growth.

The operating loss amounted to 15.3 million compared to 6.5 million last year. And excluding the one-off effects in 2023 from the Joenja milestone payments and Joenja PRV sale. The 15.3 million operating loss compares to $17.1 million last year. And that is depicted on the picture.

The company had a net loss of $14.7 million compared to a net loss of $7.4 million in the first nine months last year. And again, this is affected by the other income from the PRV and the milestone payment for Joenja last year, the financial income of 1.4 million was realized versus financial expense of 2.5 million last year. So, an income of 1.54 million versus expense of 2.5 million last year.

And the cash and cash equivalents compared to the beginning of the year decreased from 215 million to 173 million. And that was primarily driven by the refinancing of the convertible bonds earlier this year for an amount that was lower than the redeemed bonds.

A bit more detail on the next slide on the operating expenses on this year. So, the operating expenses in the third quarter decreased by 8% from 70.1 million in the second quarter of this year. And that brings our year-to-date OpEx to 198,700,000.0 million. And we do not expect the Q4 operating expenses to be significantly different from earlier quarters this year.

Then going to the next slide on the financial guidance for this year, we stick to the overall range in terms of the revenue to 82 to 95 million. And the current expectation is to end up around the midpoint of the range.

Joenja is a significant driver of the revenue growth, and we also expect continued Ruconest growth. And the Joenja revenue assumptions have not changed. We expect continued growth in patients on therapy and we expect a continued high adherence or compliance rate at above 85%. And the US pricing again, has not changed Annual cost. The work is $566,000 and the gross to net discount is approximately 15%.

And on the OpEx as discussed, we've made some OpEx adjustments and the so the overall OpEx expectation for the fourth quarter is around the levels of the prior quarters this year.

And with that, I'd like to hand back over to Simon for the

Outlook for this year. Thanks, Jeroen. Yes. And the outlook as you heard from your room, we expect to land in the middle of the year, the range with regards to total revenues, you heard land rack our continued progress in finding this, you know, if the patients and I think also very important to look forward to for next year. This significant additional growth of patient numbers that will become available during a 2nd next year as a result of the of the clarification of the VUS situation, increased revenues ex-U.S as well. Albeit of course, that goes on an individual patient basis via named patient programs, but it does really help and will continue to grow over time.

Obviously, you heard about the expansion, how we are looking towards the expansion towards Japan and the paediatric label expansion, which again will be two significant growth engines for Juan that can be expected somewhere in 2026 as is the subsequent launches on the European markets And of course, we were looking towards Canada and Australia for further regulatory actions towards the future.

And then we're very, very excited that we have been able to start that stage two trial in that population that is significantly bigger than APDS the PID with immune dysfunction where Anurag explains what the rationale is for that for that Phase 2. And we look forward to, of course, executing on that study and sharing the results as and when they come available with you. And those results obviously will be able to formulate the Phase 3 proposals that we will go down to the regulatory agencies with to get the product further, further developed.

And then of course, the last but not least we're very active with our small but efficient business development group to actually look at clinical stage opportunities that are as close as markets to as close to the market as possible in, in areas like immunology, hematology, respiratory and gastroenterology for instance. And of course, you know, this, of course, business development is it aimed over until you have the deal in hand. But we hope to update you on clinching a deal in the not-too-distant future.

We're very active in that respect and there are quite a few assets that are available that having said that I would like to now end this part of the, of this, of the call and would like to open the floor for any questions that you may have for me or my colleague. Thank you very much.

(Operator Instructions) Sushila Hernandez, Kempen.

Yes. Thank you for taking my questions. I have a few in Leniolisib and Joenja. I'll start with Ruconest again over 100 new patient enrolments this quarter. Do you see refills happening from previous quarters? And also, how do you see the ODT market developing in the coming years in terms of size? Thank you.

Would you like to answer that one, Stephen?

Yes, thank you, Sijmen. Sorry, just on muting. Yeah, we do see Sushila refills and they tend to reflect the patient's course of disease. So, with some patients, we see them more frequently than we do others just depends how frequently they attack and what their individual need is. But yeah, many of our patients come back with refills. And I'm sorry, I didn't catch the second question.

And how do you see the ODT market developing in the coming years in terms of size, The ODP market? Sorry,The on the month market?

Oh well, I think we've seen a, we've seen continued demand even with prophylactic therapies. So well, over 50% of patients still have regular acute attacks. And so, we, I don't think we've seen a huge we've seen with the genericization of some decline in revenue in dollars for other companies. But in terms of the market itself, patients continue to have breakthrough attacks and continue to have a need for acute therapies and Sijmen illustrated. So eloquently earlier, for richness specifically, we tend to serve a patient population as a pretty severe course of disease and that is not really or potentially won't be well treated by, by some of the new agents as well as the ones that exist today.

So pretty stable. And as we've demonstrated with our leading metrics some broke in certain areas.

Okay. That's clear. And then on Joenja in the UK, how are your discussions with the knife progressing any colour that you can share on that? And then also in the US, how many of the over 30 patients identified in the US? Do you expect to convert to Joenja and within what timeline? Thank you.

So, yeah, sure with nice, I mean, the discussions with nicer productive and ongoing but given that they're confidential, I really wouldn't want to comment beyond that, but we're having a very good dialogue with them. And in terms of the patients that we're identifying and finding it's obviously the speed at which they come on therapy depends on the discussions with their insurance providers.

But all eligible patients, I expect to eventually end up on therapy that want to be on therapy because our, our discussions with those insurers have gone very, very well. We haven't had any refusals at this point in time. Just different types of processes depending on who we're discussing the patient with.

That’s clear. Thank you.

Joe Paninis, HC Wainwright.

Hey, everybody. Thanks for taking the questions. First off Sijmen, I, I want to congratulate you for everything that you've done for the company and where you've brought it to date. And I just want to wish you the best of luck on your future adventures. You bet. So first, maybe a question for you on, just wanted to see what maybe the plan is for your remaining convertible bonds.

The plan, for the current convertible one, because the old one is completely redeemed. Right. There's nothing in the market anymore. So, the current one, we, we just keep in, keep on the market. There's no plan to redeem that one.

And in terms of the timing of redeeming it, that that's too early to tell.

Right. Sure. No, that's helpful. And then with regard to Joenja, obviously, very nice growth trajectory and you've described nicely how you're looking to expand that market. So, I was just curious, can you describe any of the hurdles or headwinds that you're seeing right now? That might not be considered the usual say, you know, being able to get on, you know, get patients to pay a status, you know, with regard to insurance or identifying patients or what would you define as the potential headwinds

Would like to take that one?

Yes, certainly. Thanks Joe I think there's a couple of things. I mean, obviously we had a big bonus of patients at the start. Probably the short-term headwind is when you've identified almost half the patients in the US and you've got a good chunk of those adult patients who are currently eligible for therapy on therapy. Then you expect the rate of growth to slow because we're still tapping into that one segment of the market. But we do have that funnel building.

So we have more adult patients coming in, we have pediatric patients coming in and we continue to find patients globally as the slide showed earlier, almost 900 already many of whom are on various types of access programs. So I think the before I pivot to some of the other challenges, the you know, it's what I said earlier is that we have those big bolus events coming through with the BD US next year, the UK launch and then and the pediatric indication.

So I think short term, it's just that we're tapping into an ever decreasing population of adult patients in terms of insurance challenges. I actually think that's going very well in the US. The as I mentioned, we haven't had a single patient rejected. We do have different, different stages within the insurance. So we could go anything from a fairly quick approval to an DC block which takes longer to negotiate all the way through to perhaps having to go to a judge and actually get the patient on therapy.

But every patient that so far wants to go on therapy is on therapy So, what we're really seeing is what you would typically see, you know, you have to educate physicians. It's a new disease. You also have to educate patients and make sure they understand the disease and the implications of APDS and why it's important to be on therapy and stay on therapy. And all of those are things that I think any commercial and medical organization would accept as pre par for the course. Is that to ask the question?

Certainly does. Thank you, Steven. And then my last question, I guess it's a short question in case you wanted to add any colour, but with regard to pipeline expansion potential. And you know, with your BD, if I sort of heard you correct or heard you correctly with regard to your comment about not too distant in the future, it's safe to assume that these are essentially mature discussions.

It was the, there's a few, there's a forward-looking statement on the job. But yes, I mean, but I would say that over, over if I look back at, at the last nine months, we have been in, in several, you know, mature further developed the discussions obviously. But again, as, as I just rightfully said, you know, it isn’t over until (inaudible) right? And yes, we are indeed having interesting discussions, but you know, that's why I said hopefully in the not-too-distant future. But yeah, we continue to be really looking at and, and getting quite a few interesting opportunities to, to look at.

But we are very, very selective obviously, with regards to, you know, what kind of disease, what kind of, you know, what kind of benefits that therapy gives. And if you look at, you know what Ruconest does for patients who have nowhere else to go and, and Joenja as a unique product in, in a disease that is, you know, dead and that is progressive. Then you see what, what we mean with making really making the difference for, for patients because that is, that's first and foremost, we are what we always look at and we bring real, real therapies in the Market.

Great. Thank you for all the details.

Simon Scholes, First Berlin.

Yes, good afternoon. Thanks for taking my question. I was just wondering if you could give us an update on what percentage of the market for or your volume for Ruconest is derived from those who are taking it as a rescue product and they're using prophylactic drugs and what percentage you're using as a first line. And if you could give us an idea of how those two segments of the market are growing relative to each other.

And then my second question is also on Ruconest I was just wondering whether in individual how many patients attacks usually proceed over one pathway or do they proceed? I mean, the patients, do individual patients have a tax proceeding over several different pathways? And if that's the case, I mean, if you've got patients where tax proceed over several different pathways, I mean, how do the out of the products which are orientated, say the Kallikrein pathway or the Bradykinin pathway cope with the, with the tax coming over different pathways.

Sijmen. Do you want me to take the first question? And then let that --

Yeah, that was my idea. Thanks.

Okay. So, in terms of the evolution of the prophylactic market, Simon, or both markets, actually, I'd say they're fairly stable right now. You have those three pro prophylactics launches over the course of two or three years, early, earlier in the decade. And it's so I think most we and most of the other players in this market would say it's around 78% of the way you've got patients on Prophylactic and then you've got the rest that are purely acute.

And then of course, all those prophylactic patients are also many of them carrying acute therapies on hand for breakthrough attacks. I would say it's fairly stable and I would expect it to remain. So even when new players come in and they just fight it out to share in terms of how I mean,

How much of your volume is going towards rescue attacks? So, sort of rescue therapy.

Yeah, that that was going to be the second part of my Simon. To your question is I would imagine that almost all patients on Ruconest are using for rescue therapy. And the reason I say that is you have three, you have, you have very good prophylactic options that are indicated for that, and they work very well. So, there is really no reason for a patient to want to use Ruconest for prophylaxis when they have those options available. So, I think the majority of our patients are on rescue therapy.

It's if that answers that satisfactory, that's fine. If that's okay to answer the more complicated question that you asked.

Hi Simon. So, it is indeed a complicated question. But I think I'll turn you back to Sijmen slide about the pathways. And if you count on there, there's actually 11 different points where C1 inhibitor acts to block the different esterase.

And we think again, most people think there's the contact activation system in the middle that leads to the production of Bradykinin.

And then Bradykinin acts on these one of two receptors to lead to angioma. But we know that again, in patients that actually deficient of C1 inhibitor, they're actually missing that protein and that it acts on all of these pathways. So, it's not possible to know, you know, in a given patient when an attack occurs, what the relevance of a given pathway is. But what we do know is that if you block one pathway or one protein, so let's say use a monoclonal to block Kallikrein we know that patients still have attacks, right?

So, we can block it nearly completely as you do with a monoclonal and you can, a patient can still have an attack. So, what that tells us, you know, by definition is that there must be some other element that's leading to the production of bradykinin.

We also know this in the case of an icatibant, right? So icatibant blocks the B2 receptor, but we see patients on a Canavan still having recurrent attacks requiring redosing. And we think that that probably is a consequence of bradykinin still being produced and acting on the B1 receptor. So in this case, you know, a targeted approach can be quite elegant, but it is certainly not comprehensive.

And I think the failures that we see again, these are very good drugs that are on the market, the FDA approved therapies, very good therapies, but they're not necessarily comprehensive in their approach to blocking the entire all of these cascades and all of these different points we see in their act. And I think that is the reason why you still have patients having breakthrough attacks. It's also the reason why you have patients needing redosing. And it's also the reason why we think there will remain a place for Ruconest for the, for these types of patients who aren't adequately treated by other therapies.

I hope that answers your question. Yes, thanks

Very much. That's very helpful.

So, thank you. There are no further questions on the phone lines at the moment. So, I will hand over to management to address any written questions.

Thank you. And we received indeed a few written questions here from us from Alistair Campbell from RBC.

He was asking a question about any insights into the patient ramp in the US field trajectory now slow and steady. I think we more or less addressed that Stephen, or would you like to provide additional colour on mask?

Yeah, I think there's a tumult. So, I mean, we are very active as you would expect in patient finding both in the US and globally, we continue to find patients some of whom are eligible more immediately and some of whom were not because they're paediatric or they have some other form of clinical path that first requires addressing. And we've been very successful in getting those patients that are eligible right now on insurance.

And I said, I'll just repeat it quickly one more time as you would expect in any launch, that rate of growth will slow as you put more. And more of the eligible patients on therapy, which we've done very well. And we got those, we've got those big inflection points coming. So that's global launches in some of the biggest markets outside of the US, the US population which should come online next year. And then the paediatric launches in 2026. So, I would say a strong steady progress at the moment with, with a patient funnel building for the future.

Thanks, Stephen and I don't know any more color you could give on the update on approval for all our ex-US and timelines and things.

Yeah. So, I think we have talked a little bit about that obviously. For Europe, we continue to make progress on addressing the one remaining CMC issue. We are in discussions with the Japanese regulators and special file next year there.

We've talked about pediatrics' also being able to have data in hand soon on the first study down to four and being able to file on that basis also in the second half of next year and again, a number of other markets where there's regulatory submissions and reviews ongoing Australia, Canada and of course, the recent success in the UK.

Yes. And then there's another question here. You know, I think on the on the cost base and, and plans to move the firm to profitability. So, he says, you know, if you enter slower than anticipated, what does cost base look like in the context of, you know what we just reported on, on getting the operator the cost and control. Could you give some more colour on that?

Yeah, sure. So, what we have already done this year is to reduce the, the OpEx from earlier plans because of the email launch. And that's what we will continue to do. So, so if, if due your growth is not as, as we expected it to be, then we will we will again and on a continuous basis, review our, our OpEx and act accordingly.

Because that's the game plan right to move the firm to profitability in the future.

That is the game plan. And as you've just seen, we delivered a profitable quarter already. So, we look, we look forward to, you know, updating you on the subsequent-on-subsequent results. And then the last question he has, of course, on my departure.

And that's an interesting question as the key attributes you want in the new CEO is for instance, strong VD experience, you know, the board has we have made a profile for, for candidates that are, of course, being looked at in, in international markets that indeed, you know, have experience in, in first of all, leading a company like this and of course, having experience in commercialization and knowledge about, you know, what it takes to be successful in, in rare disease commercialization, especially because that's, you know, that is a very different thing than mass markets.

And, you know, of course, you know, the BD experience now, of course, we also have a Chief Business Officer on board that makes of course a big difference where I used to be myself very much involved in BD activities. That's no longer the case. You know, Alexander Breidenbach and his team are doing the work nowadays. So, in other words, yes, the these are the kind of attributes that are, are looked at.

I have seen of course, the profile and help develop the profile for the, for the new candidates and of course, here, the search is in in motion and of course, we will update you as and when we have, we have candidates available.

And in the meanwhile, I like to illustrate that it is business as usual, we continue full speed ahead with what we have been doing in executing on the on the growth of the of the further growth of the company. And you know, I look forward also to then, you know, be able to work alongside new colleague because you know my term is not over until the next AGM, I look forward to actually bringing a new colleague into the company in due time. I hope it answers all of those questions any more questions that we can answer

(Operator Instructions) Jeff Jones, Oppenheimer.

Hey, this is fine. For just, thanks so much for the or updates. We have a couple questions. So, for 93 patients unpaid, the therapy plus five pending in third quarter, '24 for those diagnosed patient pending to be enrolled. How many of them in us?

And I'm curious about the main process to be done and the time to be waited before the formal enrolment. And how many patients of this you mentioned a lot larger than 30 diagnosed patients that are in the US. Just curious how many are in the US and how can we think about the average cost for each patient? I mean, APDS patient finding so far? Thank you,

Stephen. You want to comment on that.

Yes. So, the so all the patients, the patients that I flag were us patients. So, the 93 on paid therapy in the US, the five pending are all within the US did flag those up to 900 separately, obviously that are global. Many of whom are on some form of access program in terms of time to be on paid therapy. It can vary honestly. The average is between probably four to six weeks. We have some that go longer if there's an NDC block and we have to negotiate with the plan there. But generally, it runs pretty smoothly.

I mean, the, I think health plans recognize this is a severe disease with significant implications and it's progressive and you need to treat early. So, I think it's, it varies to be honest, but it's relatively quick for a rare disease in terms of value. I mean, I think that's very easy to probably work out your room referred earlier on to the to the gross to nets and you're aware of the price. I mean, these generally speaking, I think we provide high clinical value to patients in their positions for what is a very significant and, and tough disease. And on the flip side, obviously, we also received the majority of that value based on the on what we charge the market.

Thank you so much.

Thank you. There are no further questions at this time. So, I would like to hand back to the speakers for any closing comments. Thank you.

Thank you very much. Yes. Well, ladies and gentlemen, thank you very much for attending this result conference here. You know, I would like to really emphasize again, that we are you know, going towards the mid-range of our revenue guidance that we gave earlier in the year. You heard about the important growth engines that are ahead for the next segment of the APDS markets that can be added. Most notably in the near future, the expected doubling of the patient pool that can be available for therapy in the United States as a result of the VUS clarification effort.

It is a new disease, and the new disease is not fully described yet. And that is exactly what this US validation efforts will bring. Then subsequently, of course, the fact that you know, there will be a pediatric, we expect that there will be a pediatric indication, and we can serve those patients earlier on with this terrible chronic and dead disease. We will see continued increasing revenues from the name patient programs outside of the United States becoming more significant during next year as well. And of course, we expect that we will get further regulatory actions in those territories where we are.

The EU is defined, Canada, Australia are not well defined. Of course, when they, when we do see, expect to see some more regulatory action. And of course, in Japan, we know when we are going to file them and can get probably an accelerated review in Japan as well. But that of course, remains to be, to be seen. And I think it's important to realize that we're, we just embarked on, you know, creating potential, very significant inflection points towards the future with the start of the phase two study.

And for the for PRD with immune deregulation, a patient population that is well described and which is readily available when the product, it could be approved in the future, which is different, of course, than APDS, which is a new disease. So that is of course very for the longer term, a very important growth engine for the company and for the Leniolisib in franchise.

And last but not least, we hope to be able to update you on progress on the, on the PD front in the in the not-too-distant future. So, thank you very much for attending and we look forward to updating you in the near future on our full year results call, which will be normally in the somewhere in the beginning of March. Thank you very much for being here and on behalf of my colleagues. Thank you very much. Goodbye.