Q4 2023 Pharming Group N.V. Earnings Call

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Operator: or by p ur p u r p u p r p u p u p u p u p u p u p u p u p u p u p u p u p u p u p u p u p u p u p u p u At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. As a reminder, the company will only take questions from dial-in participants. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 and 1 again.

Okay.

Good day and thank you for standing by welcome to the farming group N V full year 'twenty 'twenty result conference call and webcast. At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session. As a reminder, the company will only take questions from dial in participants.

To ask a question during the session you will need to press star one one on your telephone you'll have that would have an automated message advising you of hundreds raised towards the oil question. Please press star one on one again. Please be advised that today's conference is being recorded I would now like to turn the conference over to your first speaker today Simon.

Operator: Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Simon de Vries, CEO of Farming Group. Please go ahead, sir.

As CEO of farming group. Please go ahead, Sir thank you very much and.

Sijmen de Vries: Thank you very much. Welcome, ladies and gentlemen. Good morning, good afternoon, wherever you are at our conference. Please, next slide. And we're very happy to take you to the full year results. And you can give me the next slide, because before I do that, I would like to point out that forward-looking statements slide that you now see, where we will be making, you know, forward-looking statements that are based upon our current beliefs and expectations, which may, of course, differ from what we expect. So having said that, I would like to now go to the next slide, where you can see my face, and then move on immediately to the next slide. Thank you very much. That's the one I want.

Welcome Ladies and gentlemen, good morning. Good afternoon graph you are to our conference a piece next slide.

And we're very happy to take you to the full year results.

And you can give me the next slides goes before I do that I would like to point out.

Two dots are forward looking statements.

I ask that you now see where we will be making forward.

Forward looking statements that are based upon our current beliefs and expectations, which may of course differ from what we are what we expect so having said that I would like to now go to the next slide where you can see my face them move on immediately to the next slide. Thank you very much that's the one yes, we are indeed.

Sijmen de Vries: Yes, we are indeed looking back to 2023 as a very successful year where, by delivering strong growth, we built the foundation for that global rare disease company that we are setting out to build. And that's why we can build that. We can all finance that by, of course, the cash flows that come from the marketing of Ruknest, which delivers considerable positive cash flows that can help us to build that foundation further. So we delivered them. We're very pleased that we delivered more than two hundred and twenty seven million dollars of revenue, which is a 10 percent growth versus last year, and which significantly exceeded the expected single-digit growth for Ruknest. And we saw that because we had some very good parameters, forward-looking parameters that were really working. The number of patients increased, and the number of prescribers increased. And, you know, basically, it means that.

Looking back to 2023 is a very successful year aware by delivering strong growth.

<unk> built the foundation for that global rare disease company that we are sitting out to.

<unk> built a and that's we can build that we can all you know finance that by of course, the cash flows that come from the marketing Ultra reconnects, which delivers a considerable positive cash flows that can help us to build that foundation further so we deliver it.

We're very pleased that we delivered to more than $227 million of revenue, which is 10% growth versus last year, which exceeded significantly the expected single digit growths, Florida for weakness.

We sold out because we had some very good.

Parameters are forward looking parameters that we're really working that number of patients increased number of prescribers increased.

So basically it means that.

Sijmen de Vries: Patients continue to be reliant on Ruconest despite increased therapy options that are available in the market, which of course are good for patients. But you can see that Ruconest continues to be that reliable cornerstone, and my colleague Stephen Toor will elaborate a little bit further on that, obviously. Now, the next exciting bit, of course, that we could therefore start to execute on was the launch in the United States for Joentja Laniolacib, which is a product we in-licensed from Novartis in 2019, and we were very proud to actually, you know, almost immediately after FDA approval in April, bring that product to the market and immediately get commercial coverage for that product and, you know, bring in more than 18 millions of sales during those first nine months in the market.

Patients continue to be reliant or weakness despite increased therapy options that are available in the market, which of course are good for patients, but you can see that <unk> continues to be that reliable cornerstone and my colleague Stephen will torvill will elaborate little bit further on that obviously now the next exciting bit of course.

We could therefore I start to execute on was the the launch in the United States for Georgia, Millennial to ship, which product we in licensed from the Hawks in 2019.

We were very proud to actually you know.

Almost immediately after FDA approval in April, bringing that brought to the markets and immediately get commercial coverage for that product and bringing in more than 18 millions of sales June dose first nine months in the markets.

Sijmen de Vries: In addition to that, Joentgen has been filed with a number of regulatory authorities in Europe, Canada, Australia, Israel, and, as of two days ago, in the United Kingdom, and we are awaiting, of course, and we're working with all these regulatory authorities, and we are awaiting, you know, the next steps and necessary approvals in the not-too-distant future. Then, of course, very important, the label of Juvenja is for 12 years and older.

In addition to that Joann J has been filed with a number of regulatory authorities in Europe got Australia, Israel and as of two days ago in United Kingdom, and we are awaiting of course, and we're working with all these leg regulator authorities and we are awaiting.

The next steps are.

Necessary approvals in the not too distant future.

Then of course very important the label of Joanne jaw is for 12 years and older and we have a number of pediatric trials that are ongoing which are of course important and last but not least we also have a completed the Japanese small Japanese clinical trial. So we are preparing for submission to Japanese authorities.

Sijmen de Vries: We have a number of pediatric trials that are ongoing, which are, of course, important. And last but not least, we also have a completed small Japanese clinical trial. So we are preparing for submission to Japanese authorities by the end of this year.

By the end of this year and my colleague and rack Allen, our Chief Medical Officer will talk more about that and as it is an ultra rare disease and a very new disease that were already described 10 years ago.

Anurag Relan: And my colleague Anurag Relan, our chief medical officer, will talk more about that. And as it is an ultra rare disease and a very new disease that was only described 10 years ago, we have a very strong focus on patient finding. And again, Dr. Relan will talk about that later.

Have a very strong focus on patient finding and again, Dr. Andrew Allen will talk about that later.

Sijmen de Vries: And then I move to the right-hand side, which is, of course, even more exciting going forward towards the future, because we strongly believe that leniolecib has vast additional potential for further development. Hence, we have basically set out to start a phase two B study in the second quarter of this year for the subsequent indication, which is significantly larger than APDS in patient numbers, PID with immune dyscirculation. And again, Anurag Relan will talk about that in more detail a little bit later in this presentation. And last but not least, we are very, very active.

And then I'll move to the right hand side, which of course is even more exciting going forward towards the future because we strongly believe that linear always hip highest abbas additional potential for further development and hence we have basically set out too.

Start a phase II B study in the second quarter of this year for the subsequent indication, which is significantly larger than a P. D S in patient numbers.

B I D with immune to circulation and again under a ground, we'll talk about that in more detail a bit later in this presentation and last but not least we are very very active and we continue to be very active.

Sijmen de Vries: We continue to be very active to in-license or acquire clinical stage programs in rare diseases, preferably in immunology, hematology, respiratory, and gastroenterology, to further leverage our commercialization structure that we have been building up and are building up as we speak. And then, at the bottom of the slide, you see that for the first time in our history, we gave total revenue guidance, and that will be between 280 and $295 million, which is driven, of course, by Jywanja, but strongly supported by Rukanesta in 2024. And then I would like to go to the next slide, please, where you see a depiction of the pipeline that we have, Ruknest obviously in the market, Joenja in the US market, and you see that subsequently under regulatory review by many of the regulatory authorities and the pediatric program that's ongoing and the Japan program that's ongoing.

To in license or acquire a clinical stage programs in rare diseases.

Preferably immunology, hematology respiratory and gastro neurology two further.

To further leverage our commercialization structure that we have been building up and are building up S. As we speak and then on the bottom of the slide you see that for the first time in our history. We gave total revenue guidance.

It will be between 280 and $295 million, which is driven of course by Joanne job, but strongly supported by Baidu canasta during that 2024.

And then I would like to go to the next slide please.

Where you see that in a depiction of the pipeline that we have <unk>, obviously in the markets Joanne <unk> in the U S market and you see down subsequently.

Under regulatory review by many of the regulatory authorities.

And the Patriotic program, that's ongoing and the Japanese the Japan program. That's ongoing and then of course, the very exciting fact that we are going to do this the phase Iia study for linear owes who put a subsequent indication and now.

Sijmen de Vries: And then, of course, the very exciting fact that we are going to do this, the Phase IIa study for lenial issue for the subsequent indication. And last but not least, our very early stage program, the HAE gene therapy that is in the early preclinical stage. With that said, I would like to turn over to my colleague, Stephen Toor, our chief commercial officer, to take you through the commercial updates. Thank you. Thank you, Simon. Good morning, good afternoon, everybody.

Some of them at least are very early stage program that H a gene therapy.

That is in early clinical and preclinical stage without that I would like to turn over to my colleague Stephen Tour, our Chief commercial officer to take you through the commercial update thank you.

Thank you Simon and good morning, good afternoon everybody.

Stephen Toor: So this is a slide I think you'll be largely familiar with. And I think the key thing to take away from this is that the key features of root cannabis, so namely the only recombinant C1 treating the root cause of the disease and 97% efficacy in one dose, are what continues to fuel the growth of root cannabis and our success over the last nine years. These product features, allied to the excellent work our commercial, medical, and patient services teams deliver for customers and patients and their carers, is also why RootKinesis remains a highly relevant part of the conversation in the USHA community and globally. That's remained the case despite three prophylactic launches over the last few years, leading to generally better controlled patients and the genericization of Academy, and I fully expect that to remain the case even in the face of And that's because HA patients using root cannabis tend to have a more severe course of disease. In that instance, the need for virtually guaranteed and fast efficacy that stops the attack in its tracks is critical, and it's typically the patient's only real object. In most cases, that overriding need for efficacy won't be replaced by a convenience plan.

So this is a slide I think youll be largely familiar with.

And I think the key thing to take a takeaway from this is that the key features of weakness so, namely the only recombinant C. One treating the root cause of the disease and 97% efficacy in one dose is will continues to fuel <unk> growth and our success over the last nine years. These.

These product features our allied to the excellent work out commercial medical a patient services teams delivered for customers of patients in the cameras.

Also while <unk> remains highly relevant part of the conversation in the U S H H immunity and globally.

That's remained the case, despite three prophylactic launches over the last few years, leading to generally better control patients.

And the generalization of the Capex.

And I fully expect it to remain the case, even in the face of acute competition in the future.

And that's because HLA patients using <unk> tend to have generally a more severe course of disease and in that instance, the need for virtually guaranteed them first efficacy that stops the attack and extracts is critical and it typically the patients only real objective.

In most cases.

That overriding need for efficacy won't be replaced by a convenience play.

Stephen Toor: So looking at 2023, Rukinus' performance was characterized by continued growth in both prescribers and new patient enrollment, and it was also successful despite that market-wide event we saw in Q1 last year related to government-reimbursed patients. Now, we have seen some disruption from that this year, but it's been muted by the almost halving of those patients' out-of-pocket costs. And moving into 2024, we've also seen that the strength of our leading indicators has continued into this year, namely new prescribers and continued support from existing prescribers and new patient enrollments. So despite some continued disruption in that government segment, we're still on track for where we expect to be in Q1. Next slide, please. So this is, again, something you're very familiar with.

So looking at 2023 recognize performance was characterized by the continued growth in both prescribers and new patient enrollments.

And he was also successful despite that market wide event, we saw in Q1 last year related to government reimbursed patients.

We have seen some disruption from that this year, but its been muted by numerous harald and if those patients out of pocket costs in the U S.

And moving into 'twenty four we've also seen that the strength of our leading indicators has continued into this year, namely.

New prescribers and continued support from existing prescribers and new patient enrollments. So despite some continued disruption in that government segment.

We're still on track.

For where we expect to be in Q1.

The next slide please.

So this is again some of you are very familiar with your firm has been in this space and committed to this community for over 20 years now.

It is really that commitment.

With the product itself refinanced our people and the excellent say deliberate.

Stephen Toor: Pharming has been in this space and committed to this community for over 20 years. And it's really that commitment, combined with the product itself, Rootkiness, our people, and the excellence they deliver, which is why, on the right-hand side there, our prescriber base continues to grow, and as a result, our patient base continues to grow. And it's why, as I said, we remain enthused and confident in the continued growth of Rukinus, both this year and in the years ahead. Next slide, please. So switching gears now to Joenja.

Which is why you see on the right hand side there a prescriber base continues to grow as a result, our patient base continues to grow.

It was I said, we remain it used and confident in the continued growth of Brokenness. Both this year and in the years ahead.

Next slide please.

So switching gears now to Joe and Jeff.

So switching gears to join Jeff We had as you know a strong strong first year and as we closeout that first year at the end of this month.

Like to reinforce what a great launch the team here at farming deliberate for us.

So the launch preparation as you've heard me say in the past was first class and I think I wouldn't underplay, the what Simon said earlier, which is that within one week of approval.

Stephen Toor: So, switching gears to Joentgen, we had, as you know, a strong first year, and as we close out that first year at the end of this month, I'd just like to reinforce what a great launch the team here at Pharming delivered for us. So, the launch preparation, as you've heard me say in the past, was first class, and I think I wouldn't underplay what Simon said earlier, which is that within one week of approval, we had commercially covered patients with product in hand, which is outstanding. The patient base steadily grew throughout the year, and we exited, as you know, at the end of the year with 81 patients on paid Joe Injure therapy. In that time, importantly, we've seen very few discontinuations, and we have adherence rates close to 90%.

We had commercially covered patients with product in hand, which is outstanding.

The patient base steadily grew throughout the year and we exited as you know at the end of the year with 81 patients on page Joanne <unk> therapy.

In that toilet poorly we've seen very few discontinuation and we have adherence rates close to 90%.

So as we convert that caseload that we'd already identified at launch our focus on surprisingly moving forward remains finding those new patients for this rare disease.

And then given it some <unk> noticed some autosomal dominant condition.

Testing their families to uncover additional patients so that they too can benefit from the management of treatment with joined <unk>, which as you know is the only indicated product with which you can treat IP Pds and.

And then the other important factor to talk about here. In addition to the U S is of course alongside that launch we continue to build out Eric's U S capabilities in preparation for launches in the European Union, United Kingdom, Japan, Australia, but other countries in the Asia Pacific region.

Stephen Toor: So as we convert that caseload that we'd already identified at launch, our focus on surprisingly moving forward remains finding those new patients for this rare disease and then, given that APDS is an autosomal dominant condition, testing their families to uncover additional patients so that they, too, can benefit from the management of treatment with Joentgen, which, as you know, is the only indicated product with which you can treat APDS. And then the other important factor to talk about here, in addition to the U.S., is, of course, alongside that launch, we continue to build out our H-U.S. capabilities in preparation for launches in the European Union, the United Kingdom, Japan, Australia, and other countries in the Asia-Pacific region, and also in the Middle East and here in North America and Canada. So with that, I'd like to pass over now to Dr. Relan, who's our Chief Medical Officer, for a medical update. Thanks, Steve.

And also in the Middle East and in here in North America and Canada.

So with that I'd like to pass I've announced that Dr. <unk>, Who's our chief Medical officer for a medical update.

Thanks, Steve.

So what I'm going to do today is talk a little bit about Atvs and then provide an update on Joanne jet as well as where we see some additional possibilities for applying lineal SIB and the second indication. So on this slide you can see.

A little bit of information about <unk>, which is a rare primary immune deficiency that as Simon said was only characterized in 2013.

We estimate the prevalence of a P. D. S. At approximately 1.5 patients per million and to that end, we have already identified more than 840 patients across the world in key global markets.

But as with many rare diseases, the signs and symptoms of <unk> Pds can vary across patients even within family members, who have the same variant.

This unfortunate leads to many potential delays in diagnosis and care and a lot of frustration amongst clinicians and patients as they try to treat these patients.

Anurag Relan: So what I'm going to do today is talk a little bit about APDS and then provide an update on Joanja, as well as where we see some additional possibilities for applying Leni-Olsen in this second indication. We estimate the prevalence of APDS at approximately 1.5 patients per million, and to that end, we have already identified more than 840 patients across the world in key global markets. As with many rare diseases, the signs and symptoms of APDF can vary across patients, even within family members who have the same variant.

Either a simple genetic tests can provide a definitive diagnosis pds and until the availability of Geo engineer in the United States recently treatments for <unk> really only been limited to addressing the symptoms of the disease again be symptoms manifest early in childhood because these patients have this genetic.

Condition that are born with.

These treatments do not address the root cause of Pds and without a specific indicated treatment. This was quite complicated for these patients to.

To manage their condition and physicians to be able to treat them effectively.

Next slide.

And you can see now with the launch of Joanne Joe <unk> patients have a choice now specifically patients who are adult and pediatric patients ages 12 years of age and older and we've been able to demonstrate this.

By a randomized placebo controlled study, where Joe and Joe met both primary and secondary endpoints with significant efficacy results and we also saw positive benefits in other.

Anurag Relan: This unfortunately leads to many potential delays in diagnosis and care and a lot of frustration amongst clinicians and patients as they try to treat these patients. Fortunately, a simple genetic test can provide a definitive diagnosis of APDS, and until the availability of Jalendra in the United States recently, treatments for APDS have really only been limited to addressing the symptoms of the disease. Again, these symptoms manifest early in childhood because these patients have this genetic condition that they're born with, but these treatments do not address the root cause of APDS.

Key secondary parameters as well exploratory measures.

On the safety side, we saw no drug related serious adverse events were studying withdrawals in the <unk> studies and we've also collected quite a bit of data now on long term use of Gilenya from the open label extension studies and we provided some of this data including reductions.

Discontinuation in immune globulin replacement therapy or <unk>.

We've also shown reductions in infection rates overtime.

Anurag Relan: And without a specific indicated treatment, it was quite complicated for these patients to manage their condition, and physicians to be able to treat them effectively. Next slide. And you can see now, with the launch of JoAnjo, APDS patients have a choice now, specifically patients who are adult and pediatric patients ages 12 years of age and older. And we've been able to demonstrate this in a randomized placebo-controlled study where JoAnjo met both primary and secondary endpoints with significant efficacy results. We also saw positive benefits in other key secondary parameters as well as exploratory measures. On the safety side, we saw no drug-related serious adverse events or study withdrawals in the Joanja studies, and we've also collected quite a bit of data now on long-term use of Joanja from the open-label extension studies, and we provided some of this data, including reductions and discontinuations in immune globulin replacement therapy, or IVIG. We've also shown reductions in infection rates over time, and we've also seen that safety is consistent with what we see in the short term.

And we've also seen that the safety is consistent with what we've seen in the short term. So when we these patients are on therapy in the open label extension study for several years in many cases, we are we see the same types of safety profile that we saw in the short term and the randomized control study we continue to collect this data including showing.

Sustained benefits and the size of their lymph nodes the size of their spleen some of their immune parameters, including their levels of AGM and we presented some of this data at some medical conferences throughout 2023, and we expect to continue to present more data from these long term studies in the coming year.

On the next slide we can see what we're looking at beyond the FTA approval. So as we mentioned in the press release, we are working closely with C. H M. P to address remaining outstanding issues and that we are now awaiting the <unk> opinion on millennials have M&A. We in fact expect that lineal so we'll be on.

The CH MP meeting agenda next week, but we are waiting see HMP confirmation for this.

As Simon mentioned also the Japan clinical study the enrollment is completed there now.

And we are finishing the remaining studies to be able to file in Japan, hopefully towards the end of this year beginning of next year.

Oh just earlier this week, we filed our application for the <unk>.

And the U K with me.

NHRA.

Anurag Relan: So when these patients are on therapy in the open-label extension study for several years, in many cases, we see the same safety profile that we saw in the short-term in the randomized control study. We continue to collect this data, including showing sustained benefits in the size of their lymph nodes, the size of their spleen, and some of their immune parameters, including their levels of IgM, and we presented some of this data at some medical conferences throughout 2023, and we expect to continue to present more data from these long-term studies in the coming year. On the next slide, we can see what we're looking at beyond FDA approval. As we mentioned in the press release, we are working closely with CHMP to address remaining outstanding issues. And now we are awaiting the CHMP's opinion on the Lenny Olseb MAA. We, in fact, expect that Lenny Olseb will be on the CHMP meeting agenda next week, but we are awaiting CHMP confirmation on this.

And we also have several applications already under review in Canada, Australia, and Israel, and we expect regulatory action on these throughout the course of 2024 on.

On the pediatric side, we have two studies that are ongoing the first is in children ages four to 11 and this study is.

Spector to complete enrollment very soon.

And then the other study, which we just started with the first patient dosed in November 2023 is continuing as planned.

On top of that we mentioned that we have a number of patients in expanded access programs across the world.

And as well as some new patients that are getting.

Getting access to therapy through named patient programs, and then I'll talk a little bit more in the next couple of slides about some work that we're doing for the second indication where and that progress is on target with the initiation of the development for the second indication.

Next slide so let's talk a little bit about the patient finding because I think this is critical for any rare disease, but also for a one of these newer rare diseases such as <unk>.

One key pillar of that is medical education, and we're doing.

A number of activities to support this education, obviously, we attend.

Anurag Relan: As Simon mentioned, the Japan clinical study, enrollment is completed there now, and we are finishing the remaining studies to be able to file in Japan, hopefully toward the end of this year or beginning of next year. Just earlier this week, we filed our application for the MAA in the UK with the MHRA, and we also have several applications already under review in Canada, Australia, and Israel, and we expect regulatory action on these throughout the course of 2024. On the pediatric side, we have two studies that are ongoing. The first is in children ages 4 to 11, and this study is expected to complete enrollment very soon. And then the other study, which we just started with the first patient dosed in November 2023, is continuing as planned.

Conferences and Congresses, we make present abstracts, both on <unk> and the seriousness of a PDF as well as some of the emerging data that we have.

And ongoing data that we have on the use of linear also in these patients and what course publish.

A number of these results and we've done that throughout the course of this year you see a list of some of the conferences that we presented at during 2023 and there'll be a similarly long list for 2024.

Because a simple genetic tests can make the diagnosis of <unk> quite easy and we have a sponsored no cost testing program in place with genetic counselors available to help review test results with patients and physicians as well as well as to provide pretest posttest guidance.

We've also partnered with a number of genetic testing companies to identify patients that have already been tested and diagnosed with <unk>, so really reaching out in numerous ways. Other genetic testing front and then as Steve mentioned <unk> is an autosomal dominant condition, but we're finding through our work is that most family members.

Anurag Relan: On top of that, we mentioned that we have a number of patients in expanded access programs across the world, as well as some new patients that are getting access to therapy through named patient programs. And I'll talk a little bit more in the next couple of slides about some work that we're doing for the second indication, and that progress is on target with the initiation of the development for the second indication. So let's talk a little bit about patient finding, because I think this is critical for any rare disease, but also for one of these newer rare diseases, such as APD. One key pillar of that is medical education, and we're doing a number of activities to support this education.

As happened actually been tested for a PDF and this is due to a number of factors, but we're trying to address one by making genetic testing.

More widely available, but also education. So we're doing a number of things to work with clinicians and patients to encourage family testing and we have a program in place now that allows patients to directly request. This through genome medical if they suspect Aps or if they have a family member that has a P. T S.

The goal here is to remove barriers to testing for patients that may be having a pts.

On the next slide you can see a little bit more about the activities that we're doing on the on what's called variants of uncertain significance. We privilege previously mentioned that there are more than 1100 patients that we're aware of in the United States alone that have.

Anurag Relan: Obviously, we attend numerous conferences and congresses. We present abstracts, both on APDS and the seriousness of APDS, as well as some of the emerging data that we have and ongoing data that we have on the use of leniolazib in these patients. And we, of course, publish a number of these results, and we've done that throughout the course of this year. You see a list of some of the conferences that we presented at in 2023, and there'll be a similarly long list for 2024. Because a simple genetic test can make the diagnosis of APDS quite easy, we have a sponsored no-cost testing program in place with genetic counselors available to help review test results with patients and physicians as well as to provide pre-test and post-test guidance.

This category of diagnosis, which is called the U S and what that means is that they have some symptoms that led them to get a genetic test done but the genetic test result is inclusive inconclusive and it's inconclusive, primarily because that genetic variant hasnt been previously seen in it hasn't been evaluated whether.

It's a disease, causing or not so we're doing a number of things here to help resolve this frustration for patients and clinicians. The first is we're working with experts, including those at Clinton Gen to develop specific criteria for classifying variants are also partnering with a number of companies, including genome went on to make clearly.

<unk>, what variance are causing disease, we're trying to gather data in and these efforts that I mentioned in here about already led to a number of patients getting correctly diagnosed with Aps.

Anurag Relan: We've also partnered with a number of genetic testing companies to identify patients that have already been tested and diagnosed with APDS, so we are really reaching out in numerous ways on the genetic testing front. And then, as Steve mentioned, APDS is an autosomal dominant condition, but we're finding through our work that most family members haven't actually been tested for APDS, and this is due to a number of factors that we're trying to address, one by making genetic testing more widely available, but also education. So we're doing a number of things to work with clinicians and patients to encourage family testing, and we have a program in place now that allows patients to directly request this through Genome Medical if they suspect APDS or if they have a family member that has APDS.

On top of that we're really trying to make functional testing more widely available and we're doing a number of things here to support this type of activity working with a number of research.

First of all I labs to try to make this test more widely available because ultimately this is the way to resolve any.

<unk> of uncertain significance and then it's not only one thing to test patients. But then also to share. These results and we're doing that through a number of databases, including.

The one sponsored by the NIH called Clinton var.

And then lastly.

Involved in a project with high throughput methods that will allow testing nearly all possible variants and creating a variant effect map, including variants that haven't been tested yet or haven't been observed yet and this will allow us to eventually make it possible so that in the future there.

Won't be any patient that has this type of diagnosis or it has this inconclusive result, and those efforts are continuing on plan and we expect later this year to be able to talk more about the results from that project.

Anurag Relan: Really, the goal here is to remove barriers to testing for patients that may be having APDS. On the next slide, you can see a little bit more about the activities that we're doing on what's called Variants of Uncertain Significance. We previously mentioned that there are more than 1,100 patients that we're aware of in the United States alone that have this category of diagnosis, which is called a VUS. And what that means is that they have some symptoms that led them to get a genetic test done, but the genetic test result is inconclusive.

And then on the next slide you can see some of the medical conferences that we presented at over the past year.

These data.

Talk about the seriousness of a P D S and you'll see the data on mortality that we presented data on lymphoma, but they also present data from the ongoing use of any also in the AP.

Yes long term results, we've seen data as well presented on the different manifestations, including.

Anurag Relan: And it's inconclusive primarily because that genetic variant hasn't been previously seen and hasn't been evaluated to see whether it's disease-causing or not. So we're doing a number of things here to help resolve this frustration for patients and clinicians. The first is that we're working with experts, including those at ClinGen, to develop specific criteria for classifying variants. We're also partnering with a number of companies, including Genominon, to make clearly available what variants are causing disease. We're trying to gather data, and these efforts that I'm mentioning here have already led to a number of patients getting correctly diagnosed with APD. On top of that, we're really trying to make functional testing more widely available, and we're doing a number of things here to support this type of activity, working with a number of research laboratories to try to make this test more widely available, because ultimately, this is the way to resolve a variant of uncertain significance.

Manifestations in these patients got in their lungs, and then lastly, we presented just last month.

New data on the use of our navigate Apd sponsored genetic testing program and how that is uncovering patients and helping patients get the correct diagnosis. So as I said earlier, we're going to.

Continue to present, a number of at a number of conferences. This year have a number of abstracts that number of publications that are coming out where we can really add.

Take the broader physician community patient community about a P. D asked about the seriousness of the condition as well as the.

Ongoing data that we're collecting.

Next slide.

Now turning a bit to the next indication that we're pursuing so obviously a P. D. S is a primary immune deficiency with immune dysregulation, but there are other immune deficiencies with immune dysregulation and they often have similar clinical phenotype for clinical presentations as you see.

Anurag Relan: And then it's not only one thing to test patients, but also to share these results, and we're doing that through a number of databases, including one sponsored by the NIH called ClinVar. And then lastly, we are involved in a project with high-throughput methods that will allow testing nearly all possible variants and creating a variant effect map, including variants that haven't been tested yet or haven't been observed yet And this will eventually allow us to make it possible so that in the future, there won't be any patient that has this type of diagnosis or gets this inconclusive result. And those efforts are continuing on schedule, and we expect later this year to be able to talk more about the results from that project.

With <unk>, specifically, what we see is that these patients often get a similar problems related to limp proliferation or enlarged spleens and livers excuse me enlarged spleens and lymph nodes, but also they also have this problem of autoimmunity, where not only is their immune system not functioning.

It's also attacking the body and what we're seeing is that.

There is a number of these pid's or primary immune deficiencies with immune dysregulation that have a clinical phenotype that is similar to a P. T S and oftentimes are even managed.

Before the available of Joanne, Jeff our Aps in the same way so that there's a strong rationale to see what's going on here and I think if you see on the next slide the clinical presentation of these diseases looks very similar to what we've seen with a P. D. S. In fact, when you look at the right you see all of the same types of things are many of the same types.

Anurag Relan: And on the next slide, you can see some of the medical conferences that we presented at over the past year, these data talk about the seriousness of APDF, and then you see the data on mortality that we presented, the data on lymphoma, but they also present data from the ongoing use of Laniolacib in APDF, long-term results. We've seen data as well on the different manifestations, including manifestations in these patients' guts and in their lungs.

The thing that we see with <unk>.

We also know that these patients have a high unmet need and.

Again, the standard of care immunosuppressive therapies such as.

Sirolimus Rapamycin that had been used have a lot of the limited concerns due to limited efficacy and tolerability. So there is an unmet need here and we know that these patients based on work that's already been done.

Anurag Relan: And lastly, we presented new data last month on the use of our Navigate APDS-sponsored genetic testing program and how that is uncovering patients and helping patients get the correct diet. So, as I said earlier, we're going to continue to present a number of, at a number of conferences this year, have a number of abstracts, a number of publications that are coming out where we can really educate the broader physician community and patient community about APDS, about the seriousness of the condition, as well as the ongoing data that we're collecting. Next slide.

In these various genetic disorders have altered pi three kinase signaling and we known at that altered signaling leads to the clinical symptoms that you see on the right and as such we think lineal SIB is well suited to to restore that signaling to normal there.

By helping these patients clinical presentation also.

To that end on the next slide what we're doing is advancing this with a clinical trial to.

About the.

Using linear also in this patient population again, the principle is that by reducing this <unk> K Delta activity, we're trying to rebalance the immune dysregulation and improve their clinical symptoms.

Anurag Relan: Now, turning a bit to the next indication that we're pursuing. So obviously, APDS is a primary immune deficiency with immune dysregulation. But there are other immune deficiencies with immune dysregulation, and they often have similar clinical phenotypes or clinical presentations, as you see with APDS. Specifically, what we see is that these patients often get similar problems related to lymphoproliferation or enlarged spleens. And livers, excuse me, enlarged spleens, and lymph nodes.

Been partnered with the NIH on this and where we're expecting to start a clinical trial soon.

The data suggest that when we look at the patients with specific mutations.

That have this type of immune dysregulation of the prevalence of approximately five per million, which is a little bit more than what we've seen with Aps and in fact, three times more than we've seen with Atvs and we have been engaged with FDA on this and we've gotten feedback on the clinical trial plans.

Anurag Relan: But they also have this problem of autoimmunity, where not only is their immune system not functioning properly, but it's also attacking the body. And what we're seeing is that there are a number of these PIDs, or primary immune deficiencies with immune dysregulation, that have a clinical phenotype that is similar to APDS. And oftentimes, they are even managed before the availability of Joentgen for APDS in the same way. So there's a strong rationale to see what's going on here. And I think, if you see on the next slide, the clinical presentation of these diseases looks very similar to what we've seen with APDS. In fact, when you look on the right, you see all of the same types of things or many of the same types of things that we see with APDS.

And we are underway now to begin the clinical trial, shortly which you can see on the next slide describing the study design for that its a phase two proof of concept study single arm was 12 patients will where we will ramp patients up starting at 10 milligrams, then progressing to 30 milligrams and 70 milligrams.

Anurag Relan: We also know that these patients have a high unmet need, and again, the standard of care immunosuppressive therapies such as sirolimus rapamycin that have been used have a lot of limited concerns due to limited efficacy and tolerability. So there's an unmet need here, and we know that these patients, based on work that's already been done in these various genetic disorders, have altered PI3K signaling. And we know that that altered signaling leads to the clinical symptoms that you see on the right. And as such, we think that leniolisib is well suited to restore that signaling to normal, thereby helping these patients' clinical presentation also.

This study will include patients, where we know that the genetic defect and you see that some of the genetic defects listed there Alps, CTO before affluence insufficiency, and <unk> deficiency, among the others, where we will where these patients have this altered <unk> K delta.

Signaling. So we think that linear also is appropriately suited to be able to.

Alter and restore that signal and back to normal.

The primary objective of the study of course, the safety and Tolerability, but we will be looking at PK and PD measures efficacy measures similar to the types of measures that we studied in the a P. D. S population and the goal really is to confirm the safety and Tolerability and then pick the best dose regimen for a phase III study and as I mentioned earlier, we're partnered with.

Anurag Relan: And to that end, on the next slide, what we're doing is advancing this with a clinical trial to use Leniolis in this patient population. Again, the principle is that by reducing this PI3K delta activity, we're trying to rebalance the immune dysregulation and improve their clinical symptoms. We're partnered with the NIH on this, and we're expecting to start a clinical trial soon. The data suggest that when we look at the patients with specific mutations that have this type of immune dysregulation, the prevalence is approximately five per million, which is a little bit more than what we've seen with APDS, in fact, three times more than we've seen with APDS.

The NIH on this so look for more updates to come soon about the initiation of this study and with that I'll turn it over to my colleague you rune to discuss the financials.

Yes. Thank you very much on Iraq, and I'm very happy to take you through the financial highlights to start off with the Q4 2023.

Versus last year, we had a revenue growth in the quarter of 49%.

<unk> grew by 34% in Q4 and are recorded at.

Anurag Relan: We have been engaged with FDA on this, and we've gotten feedback on the clinical trial plan, and we are now underway to begin that clinical trial shortly, which you can see on the next slide describing the study design for that. It's a phase two proof-of-concept study, single-arm with 12 patients where we will ramp patients up, starting at 10 milligrams, then progress into 30 milligrams and 70 milligrams This study will include patients where we know that the genetic defect, and you see some of the genetic defects listed there, ALPS, CTLA-4, haplodens insufficiency, and P10 deficiency, among others, where these patients have this altered PI3K delta signaling, so we think that leniolisib is appropriately suited to be able to alter and restore that signaling back to normal.

It had a record revenue of $73.3 million.

And you May remember that we were at.

Growth of 2% a year to date at the end of Q3. So we're very happy with these Q4 sales results.

And we saw strong performance in leading key revenue indicators in the U S, including new physicians prescribing <unk>, new patient enrollments, including high frequency attack patients.

The total number of patients.

<unk> revenue grew by 21% versus the previous previous quarter. So Q3, 2023, and the revenue was $7 $9 million and by year end, we had a S.

Steve also said 92 Apd S patients enrolled in the U S and 81 patients on therapy on Joe and Joe.

The gross profit in the fourth quarter of 2023 increased by $25 8 million compared to the fourth quarter of last year and this growth was driven by higher revenues, partially offset by increased <unk> production cost arrow royalty payments on <unk> sales.

Anurag Relan: The primary objective of the study, of course, is safety and tolerability, but we will be looking at PK and PD measures, and efficacy measures, similar to the types of measures that we studied in the APDS population. And the goal really is to confirm safety and tolerability and then pick the best dose regimen for a phase three study. And as I mentioned earlier, we're partnered with the NIH on this. So look for more updates to come about the initiation of this study. And with that, I'll turn it over to my colleague Jeroen to discuss the finances. Yeah, thank you very much, Anurag.

The operating cost increased by $16 million into the in the fourth quarter compared to last year and about half of this $8 3 million was directly related to R&D and marketing and sales expenses for linear ownership, respectively, Joe and Joe.

And our expansion efforts driven by preparation for the launch and further commercialization of Joanne job less to a $7 1 million increase in <unk>.

Payroll expenses.

The operating profit of $1 1 million was realized in contrast to an operating loss of $10 2 million in the fourth quarter of 2022.

This improvement was primarily driven by a rise in gross profit partially offset by the increase in operating expenses.

Jeroen Wakkerman: And I'm very happy to take you through the financial highlights. To start off, in Q4 2023 versus last year, we had revenue growth of 49% in the quarter, and Rukiness grew by 34% in Q4 and had a record revenue of 73.3 million. You may remember that we were at 2% year-to-date growth at the end of Q3, so we're very happy with these Q4 sales results. We saw strong performance in leading key revenue indicators in the US, including new physicians prescribing Ruconest, new patient enrollments, including high-frequency attack patients, and the total number of faiths. Thank you. Goenjia revenue grew by 21% versus the previous quarter, so Q3 2023, and the revenue was $7.9 million. And by year-end, we had, as Steve also said, 92 APDS patients enrolled in the U.S. and 81 patients on therapy at Joe and Joe's.

The net loss was $2 7 million and our cash position improved and grew from $209 million at the beginning of the year to $215 million at year end.

If I then go to the next slide with the full year results our revenues grew by 19%.

Which was a result of the higher <unk> sales volumes and supported by a price increase which was below CPI in the U S market.

The initial sales of Gilenya was $18 2 million in 2023 following the launch in April of the same year.

And our revenues in Europe, and the rest of the world increased by 12% to $6 2 million in 2023.

The gross profit increased by $32 million or 17% one 7%.

This development was broadly in line with revenue growth.

Our other income reflects.

For this year are well 2023 to sale of the priority review voucher to Novartis, which was for a pre agreed.

Price of $121 3 million and as a.

Okay.

Okay.

Chairman buttery reduction of our minority stake in by a connection and at the time, we recognized a gain of $12 2 million so that was in.

Jeroen Wakkerman: The gross profit in the fourth quarter of 2023 increased by 25.8 million compared to the fourth quarter of last year, and this growth was driven by higher revenues and partially offset by increased Ruknash production costs and royalty payments on Joenja. The operating cost increased by 16 million in the fourth quarter compared to last year, and about half of this 8.3 million was directly related to R&D and marketing and sales expenses for Lenny Olusep and Joenja. And our expansion efforts, driven by preparation for the launch and further commercialization of Joenja, led to a 7.1 million increase in payroll expenses. The operating profit of 1.1 million was realized in contrast to an operating loss of 10.2 million in the fourth quarter of 2022. This improvement was primarily driven by a rise in gross profit and partially offset by an increase in operating costs.

<unk> 2022.

The operating costs increased by $64 5 million of which tempered forest attributed to milestone payments for Joe and Jeff Following the first commercial sale in the second quarter of last year.

An additional $25 7 million of expenses is directly.

Related to R&D expenses in marketing and sales expenses for linear ownership stroke, Joe and Joe.

And $24 2 million increase was from payroll expenses.

Given by our expansion efforts.

In preparation for the launch and the further commercialization of Joe and Joe.

And finally, we incurred impairment expenses related to our DSP facility and that was for an amount of $4 7 million in 2023.

So the operating profit decreased from $18 2 million to minus $5.4 million and that was as a result of the increase in operating cost to build our <unk> business.

The total net loss in 2023 amounted to $10 $1 million compared to a net profit.

Jeroen Wakkerman: The net loss was $2.7 million, and our cash position improved and grew from $209 million at the beginning of the year to $215 million at year-end. If I then go to the next slide with the full-year results, our revenues grew by 19%, which was a result of higher recognized sales volumes and supported by a price increase which was below CPI in the US market. The initial sales of Joe Angel were 18.2 million in 2023, following the launch in April of the same year, and revenues in Europe and the rest of the world increased by 12% to 6.2 million in 2023. The gross profit increased by $32 million, or 17%, one-seventh, and this development was broadly in line with the revenue growth.

Of $13 seven in the year before and the decrease was primarily caused by higher operating costs.

And in addition fluctuations in foreign exchange rates adversely impacted the foreign currency results in the statement of income.

On the next slide we give a overview of the revenue in <unk>.

<unk>.

Over the last years.

And obviously for last year, you see also joined yet but.

Richard asked has grown by 10% in 2022, and we saw a record <unk> revenue.

Since the launch of the product in the U S over nine years ago.

Now let me out of SAP is driving enhanced growth we achieved.

Overall, 19% revenue growth in 2023.

And we're very pleased with these results and with the continued growth of <unk> from 2021.

On the next slide you see the <unk>.

Opex.

And cost category breakdown by by quarter and the message is that we continue to invest in farming future growth.

Jeroen Wakkerman: Our other income reflects for this year and well 2023 the sale of the Priority Review Voucher to Novartis, which was for a pre-agreed price of 21.3 million and is a... Last year's GDP growth forecast was determined by the reduction of our minority stake in bioconnection, and at the time, we recognized a gain of 12.2 million, so that was in 2022. The operating costs increased by 64.5 million, of which 10.4 million is attributed to milestone payments for Joenja following the first commercial sale in the second quarter of last year.

I've provided more detail on the growth of the operational costs earlier specific to Q4.

Operating expenses increased by $16 million in the fourth quarter compared to last year and 8 million. So almost half of it was related to a linear ownership and Joe and Jeff.

In terms of marketing sales and R&D and 7 million was related to two payroll expenses to support the growth of the organization.

And for 2024, we expect quarterly opex to be less than the Opex in Q4 2023.

Jeroen Wakkerman: An additional $25.7 million of expenses were directly related to R&D expenses and marketing sales expenses for Laniola CYP, Stroke, and Joannia, and $24.2 million of the increase was from payroll expenses, driven by our expansion efforts in preparation for the launch and the further commercialization of Joentgen. And finally, we incurred impairment expenses related to our DSP facility, and that was for an amount of $4.7 million in 2023. So the operating profit decreased from $18.2 million to minus $5.4 million, and that was as a result of the increase in operating costs to build our Jo-En-Ja. The total net loss in 2023 amounted to $10.1 million compared to a net profit of $13.7 million in the year before, and the decrease was primarily caused by higher operating costs. And, in addition, fluctuations in foreign exchange rates adversely impact foreign currency results in the Statement of Income.

Now moving on the next slide to the cash flow.

I said before it increased from 209 million to $215 million.

And the graph graph shows the key changes in our cash position.

Cash flow from operating activities was negative and offset by the cash from the sale of the earlier mentioned priority review voucher.

And then in addition, there were favorable currency exchange rate fluctuations.

With a positive impact on the cash.

And that was amongst all of us on the cash that we hold in euros and the Euro dollar exchange rates increased throughout the year.

Yes.

And going to the revenue guidance for 2024 on the next slide.

We give a revenue guidance of between $280 million and $295 million for 2024.

And that means a growth between 14 and 20%.

We as in earlier years expect quarterly fluctuations.

Gilenya is a significant driver of this revenue growth.

But also we expect continued growth from our request.

And.

The <unk> growth rate is higher than the guidance that we gave and then in 'twenty two 'twenty three because we expect.

Some of the momentum from the second half of 2023 to continue.

Jeroen Wakkerman: On the next slide, we give an overview of the revenue in Ruconest over the last years. And obviously, for last year, you see also Joenja, but Ruconest has grown by 10% in 2022. And we saw a record revenue since the launch of the product in the US over nine years. Helene Jollestrup is driving enhanced growth.

Last year's guidance was low single digits and we.

We are confident to move that now to low to mid single digit growth for <unk>.

The Georgia assumptions that.

We expect continued growth in patients on therapy.

And the pricing in the U S is at an annual weighted average cost of 566000.

Jeroen Wakkerman: We achieved overall 19% revenue growth in 2023, and we're very pleased with these results and with the continued growth of Reconest in 2021. On the next slide, you see the OPEX in cost category breakdown by quarter.

U S dollar.

<unk> to patients.

Now moving onto the outlook for 2024.

As I said total revenue between expected to be.

Between 200 and 295.

<unk>.

Joanne.

We expect continued progress finding additional <unk> patients and that is supported by family testing and the U S validation efforts as mentioned by Iraq.

Jeroen Wakkerman: And the message is that we should continue to invest in farming's future growth. I've provided more detail on the growth of the operational costs earlier, and specific to Q4, the operating expenses increased by 16 million in the fourth quarter compared to last year, and 8 million, so almost half of it, was related to Lenny Olusip and Joenja, in terms of marketing, sales, and R&D, and 7 million was related to payroll expenses to support the growth of the organization. And for 2024, we expect quarterly O Moving on to the next slide to the cash flow, as I said before, it increased from $209 million to $215 million. And the graph shows the key changes in our cash position. The cash flow from operating activities was negative and was offset by the cash from the sale of the earlier mentioned priority review voucher.

Subsequently converting patients to therapy.

Plenty ownership outside of the U S. We expect increasing revenues from commercial availability or through our named patient program and other funded early access program programs in key global markets.

We expect to complete Lenny ownership clinical trials to support the regulatory filings for approval in Japan and for the pediatric label expansion in key global markets.

And we expect progress towards regulatory approvals for <unk> in Europe, The U K, Canada, Australia and Israel.

We will initiate in advance a phase II clinical trial for <unk> <unk> with immune dysregulation linked to <unk> K Delta signaling too.

It significantly expands the long term commercial potential of <unk>.

Jeroen Wakkerman: And in addition, there were favorable currency exchange rate fluctuations with a positive impact on cash. This was, amongst others, on the cash that we hold in euros, and the euro-dollar exchange rate increased throughout the year. I'm going to revenue guidance for 2024 on the next slide. We give a revenue guidance of between 280 million and 295 million for 2024. And that means growth between 14 and 20 percent. We, as in earlier years, expect quarterly fluctuations, and Joenja is a significant driver of this revenue growth, but we also expect continued growth from Rukonan, and The recognized growth rate is higher than the guidance that we gave in 2023 because we expect some of the momentum from the second half of 2023 to continue. Last year's guidance was low single-digits, and we are confident to move that now to low to mid-single-digit growth for Rukonan. The Joentia assumptions are that we expect continued growth in patients on pain therapy, and the pricing in the U.S. is at an annual weighted average cost of $566,000 per year.

And we continue to focus on potential acquisitions and in licensing of clinical stage opportunities in rare diseases.

In.

Therapeutic areas like immunology, and hematology in respiratory and gastro and urology and that is to further leverage our commercial infrastructure globally.

Yes.

Now with that I would.

Like to move on to the next slide and open up for <unk> for Q&A.

And over to the to the operator, thank you.

Thank you Todd.

Can I ask a question you will need to press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one on one again.

We will now go to your first question.

One moment please.

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

Hi, good afternoon.

Guys.

Start off with them with recast I guess.

Just to get a bit more of a sense for.

These underlying drivers, obviously, a very strong fourth quarter.

You seem to be guiding for mid single digit growth in 2024 now.

Is there a scenario where it could.

It could get north of that and then another sort of 10%.

I'm trying to get a bit more sense for some of the drivers on reconnects this year.

Yes, thanks, Christine on the very nice.

Sure.

Jeroen Wakkerman: And moving on to the outlook for 2024, as I said, total revenue is expected to be between $280 and $295 million. Joenja, in the US, we expect continued progress finding additional APDS patients, and that will be supported by family testing and VUS, validation efforts, as mentioned by Anurag, and subsequently converting patients to bait therapy. For Lenny Olisip, outside of the US, we expect increasing revenues from commercial availability or through our named patient program and other funded early access programs in key global markets. We expect to complete linealisip clinical trials to support regulatory filings for approval in Japan and for the pediatric label expansion in key global markets, and we expect progress towards regulatory approvals for lenialisib in Europe, the UK, Canada, Australia, and Israel.

Yes.

You can ask indeed has had some very strong and Steve was already alluding to it as some very strong underlying.

Indicators in the market, which he says continue into the first quarter.

We are of course.

The fact that we are in a market which is.

Base rent.

Lower competition around.

We continue to be optimistic, let's say, it's year 10 rider request in the market. So we can be optimistic by saying that we have the mid to low to mid single digit growth.

And as and when we see indicating indicators before us.

The North obviously, we will update guidance during the year and now we would like to stick to that.

In and respected recognized.

And natural follow up to that I mean, you touched on this as Steven touched on this in the.

Remarks around.

Potential new entrants here on the oil and convenience.

Next year.

Jeroen Wakkerman: We will initiate and advance a Phase 2 clinical trial for Laniolacib in PIDs with immune dysregulation linked to PR3K delta signaling to significantly expand the long-term commercial potential of Lenny Ellison, and we continue to focus on potential acquisitions and licensing of clinical stage opportunities in rare diseases, in therapeutic areas like immunology and hematology, respiratory, and gastroenterology, to further leverage our commercial infrastructure globally.

Just just tick.

Can you just kind.

And a bit more insight I guess in terms of.

The patient profile here at <unk>.

Sort of your market intelligence tells us that.

Yes, you are going to lose patients effectively to that convenience option.

Yes, I think Iraq and Stephen both are absorbed as Steven alluded to it.

Of course, we'd see a very different patient profile that are using <unk>.

And basically speaking when you look at the clinical results of those new acute options you see that there is a necessity to.

Jeroen Wakkerman: And with that, I would like to move on to the next slide and open up for Q&A and hand over to the operator. 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.

<unk>.

Multiple doses and B you know.

Still needs rescue therapy, if you look at the <unk> results. The words rescue therapy doesn't figure there because <unk> protein replacement therapy for that missing <unk>.

Operator: To withdraw your question, please press star 1 and 1 again. We will now go to your first question. One moment, please. And your first question comes from the line of Christian Glennie from Stiefel. Please go ahead. Hi. Good afternoon, guys. Let's start off with Ruccas, I guess.

Are not functioning C. One inhibitor.

<unk> in patients with territory angioedema, hence why we believe that these products in fact serve a different segment of the population that surface from heritage Re-injure demos.

Christian Glennie: Just to get a bit more of a sense for these underlying drivers, obviously, a very strong fourth quarter. You seem to be gliding for mid-single-digit growth in 2024 now. Is there a scenario in which it could get north of that and do another sort of 10%? Just trying to get a bit more sense for some of the drivers on Ruccas this year.

We will see we expect therefore that these oral.

Acute product.

Products if approved of course, we will serve that patient segments that is now currently of course, using a lot of convenience products as well such as subcutaneous injections.

And by the way, a stinging and painful and which you have to give repeatedly often to treat one attack and that the hurdle for those patients to actually.

Sijmen de Vries: Yeah, thanks Christian, a very nice introduction. Yeah, Rukiness indeed has some very strong, and Steve was already alluding to it, has some very strong underlying, you know, indicators in the market, which he says will continue into the first quarter. We are, of course, you know, aware of the fact that we are in a market with a lot of competition around. But we continue to be optimistic, let's say it's year 10, right, that Rukiness is in the market, so we continue to be optimistic by saying that we have mid, low to mid single-digit growth. And as and when we see indicators moving towards, you know, the north, obviously, we will update guidance during the year. But for now, we would like to stick to that in respect of the year.

Step over into an oral.

Would be a fairly low, whereas I think that patients that rely on <unk> that are not used so any convenience in therapy, but are relying on the.

Reliability of efficacy of recognized that hurdle will be a little higher what can never totally exclude of course patients will try it and may be successful.

But in the other hand, we.

Microsoft we serve a very different patient profile with very with higher attack frequencies than we see in all those clinical trials that are being that are being done by those new oncoming competitors I hope that answers your question sorry to be long winded here Christian.

Hi, Matt.

That's very helpful. Thank you and then one final one on <unk>.

And John I'll get back in the queue I guess.

Sijmen de Vries: A natural follow-up to that, I mean, you touched on this, Stephen touched on this in the remarks around potential new entrants here in oral and convenience next year, just to get a bit more insight, I guess, in terms of the patient profile here and what your market intelligence tells you that you aren't going to lose patients effectively to that convenience option. Yeah, I think Anurag and Stephen both, sorry Stephen alluded to it already, we see a very different patient profile that is using Rukinest, and basically, when you look at the clinical results of those new acute options, you see that there is a necessity to a, have multiple doses and b, you know, still need rescue therapy. If you look at the Rukinest results, the word rescue therapy doesn't figure there because Rukinest is protein replacement therapy for that missing C1 or not functioning C1 inhibitor protein in patients with hereditary angioedema.

Your guidance implying five.

5% gets to about 240, <unk> balance is somewhere between 40 and 55.

Many and for this year, if I'm understanding correctly and therefore, what are your assumptions around.

The sales in markets that will contribute to that to that.

Great.

The low and high end of that say is it mostly still U S.

Would that be reasonable contributions from other markets.

I think what room.

First and foremost if you will.

As you heard from interact a lot of that.

Steve.

Two of these are going to find those patients in the U S. However.

First a numbers of patients that we have of course, our own drug we will see inflow steady inflow in the United States. During this year from for instance family testing efforts that will be systematically applied as we as you heard.

Sijmen de Vries: Hence why we believe that, you know, these products, in fact, serve a different segment of the population that suffers from hereditary angioedema where we will see, we expect therefore that these oral acute products, if approved, will serve that patient segment that is now currently, of course, using a lot of convenience products as well, such as, you know, subcutaneous injections that are, by the way, very stinging and painful Whereas I think that patients that rely on Rukinest that are not used to any convenience in therapy but are relying on the, you know, reliability and efficacy of Rukinest, that hurdle will be a lot higher.

The other thing is of course, there will be small batches of initially small batches of <unk> test it and that will actually deliver.

Albeit at the beginning a limited number of additional patients as well, whereas by the end of the year, but that's more for 25 of course, we expect that may have experiment, where anorak talks about a combinatorial.

Experiment to deliver the bulk of the U S and as soon as a bit more indication of what kind of percentage. We we actually have on the U S. We will of course update the market as well, but some of that early days for that at this point in time no.

That's where the U S market with respect to.

Ex U S.

We don't expect any significant sales from the European markets, because obviously as you know reimbursement takes a lot of time, so the European markets sales will only cut in in 'twenty five and further on even further on because some of those markets will take multiple years before you got to an approval. So the ex U S sales will.

Sijmen de Vries: One can never totally exclude, of course, that patients will try it and may be successful. But on the other hand, we, like we said, serve a very different patient profile with very, with higher attack frequencies than we see in all those clinical trials that are being done by those new oncoming drugs. I hope that answers your question. Sorry to be a little long-winded here, Chris. That's very helpful, thank you. And then one final one on Juenja, and I'll get back in the queue.

Mainly come from those early access programs fade early access programs with some of those markets and from the named patients that are actually already being served.

You can also expect of course.

For instance in the fruit into <unk> results you will see that there is some sales reported X U S. Because that's ongoing as we speak so in other words.

The fluctuation in the Geo angio numbers I think depend on.

Sijmen de Vries: I guess, you know, your guidance implying, you know, Rukness 5% gets to about $240 million, so Juenja, the balance is somewhere between $40 million and $55 million for this year, if I understand correctly. And therefore, what are your assumptions around sales and markets that will contribute to that growth, and what gets you to the low and high ends of that? So, you know, is it mostly still the U.S., or will there be reasonable contributions from other markets? I think what we will see first and foremost in the U.S. this week, as you heard from Anurag, a lot of activities are ongoing to find those patients in the U.S. However, the first number of patients that we had, of course, are on drugs.

Mainly I think on the numbers of patients that will come of course from there from the U S market I hope I answer that question.

Christian.

Yes. Thank you thanks Aman.

Okay.

Thank you.

We will now go to our next question.

And your next question comes from the line of Alistair Campbell from Royal Bank of Canada. Please go ahead.

Thanks, Alright, thanks for taking my questions. This morning.

I have a couple on <unk>, if that's all right first of all obviously.

Launching very well in the U S and you talked about.

Over 90% adherence rate, which is which is good but just in the context of that just serves to confirm that what youre actually seeing in real world use.

In line with what you saw in clinical trials in terms of side effect profile and stuff like that that would be useful to get a sense of that and then secondly, just thinking about the second indication the PID.

You mean, just regulation, obviously, that's going to cover.

Sijmen de Vries: We will see steady inflows into the United States during this year from, for instance, family testing efforts that will be systematically applied, as you heard. The other thing is, of course, there will be small batches of, initially small batches of VUSs tested, and that will actually deliver, you know, albeit in the beginning, a limited number of additional patients as well, whereas by the end of the year, but that's more for 25, we expect that MAVE experiment where Anurag talked about a combinatorial experiment to deliver the bulk of the VUSs. And as soon as we have a bit more indication of what kind of percentage we actually have on VUSs, we will, of course, update the market there as well. But it's a little early days for that at this point in time.

Brian do you have different genetic causation I guess, what I'm trying to get for myself with a feeling of the risk around the profile of this program basically is your expectation that all of those genetic.

Dysfunction areas.

Really biologically should respond or do you think some of them will or do you think they are all high rise I'm, just trying to get a sense of what the risk profile. It looks like if I might.

Trading is that at least some of those should probably come through but just to get a sense of how do you view that would be great. Thank you.

Happy to hand, it over to Iraq of course here to mitigate that Eric would you mind asking a question sure.

Sure. So maybe we'll start with the.

The second question first.

The additional indication in primary immune deficiencies with immune Dysregulation and you're right. We're looking at a number of specific genetic variants genetic mutations.

Sijmen de Vries: Now that's for the U.S. market. With respect to ex-U.S., you know, we don't expect any significant sales from the European markets because, obviously, as you know, reimbursement takes a lot of time. So the European market sales will, you know, only cut in after 25 and further on, even further on, because some of those markets will take multiple years before you get approval. So the ex-U.S. sales will mainly come from those early access programs, paid early access programs in some of those markets, and from the named patients that are actually already being served. And that's what you can also expect, of course. For instance, in the one queue results, you will see that there are some sales reported ex-U.S. because that's ongoing as we speak.

That are causing these.

This altered signaling and that already has been described right. So it's known that patients with Alps that patients with <unk> for patients with <unk> deficiency have this abnormal signaling through that pathway and its also known that they have immune dysregulation as a result of that and then lastly.

They are being treated with immunosuppressive therapies, such as rabbit rapamycin to modulate that pathway. So we think it's quite logical to try to modulate the pathway with Lenny older SIB in the same way that we did with.

Aps patients. So I think I think from our perspective and really this program came to us through our interactions with the immunology community.

Sijmen de Vries: So in other words, the fluctuation in the Joentia numbers will depend, I think, mainly on the numbers of patients that will come, of course, from the U.S. market. I hope I answered that question. Yes. Thank you. Thanks, Simon.

Through numerous work through all the work that we're doing on <unk>. They kept on saying look there are other patients that they believe could benefit and they listed all of these reasons that I just mentioned to you and it was really on that basis that we partnered again with the NIH who.

Operator: Thank you. We will now go to our next question. And your next question comes from the line of Alistair Campbell from the Royal Bank of Canada. Please go ahead. Thank you, everyone, thanks for taking the time, and I have a couple.

Who are leaders in these in the specifically in this areas of Alps, and <unk> for <unk>.

<unk> to come up with this clinical trial program because they were so enthusiastic about being able to one address the unmet need but to to be able to use something that they were very comfortable user.

Alistair David Campbell: You know, first of all, obviously, well in the U.S., good, but just in the context of that. And then secondly, just thinking about the... Obviously, that's what we're going to cover right here. I guess what I'm trying to get for myself is a feeling... Program, www.globalonenessproject.org. All right, I'm happy to hand that over to Anurag, of course, in this case. Anurag, would you mind asking me a question? Sure. So maybe we'll start with the second question first, about the additional indication in primary immune deficiencies with immune dysregulation. And you're right, we're looking at a number of specific genetic variants, genetic mutations that are causing this altered signaling.

Using for Pds and made it work have that confidence because they had been treating patients with <unk> with <unk>.

Lenny also for several years and I think that comes to your second or your first question, which was on the on really the the real world use of lineal assumed and how does that compare compared to what we've seen in our clinical trials and I think what we're seeing is number one we are seeing that it is continues to be.

Generally safe and well tolerated so we're seeing nothing new form.

Anurag Relan: And that already has been described, right? So it's known that patients with ALPS, that patients with CTLA-4, that patients with P10 deficiency have this abnormal signaling through that pathway. And it's also known that they have immune dysregulation as a result of that.

Our pharmacovigilance efforts.

On the real world use, suggesting a different safety or efficacy profile.

But two I think what we're also hearing is a lot of the other benefits that we didn't even capture in the clinical trial program, So and we're going to and we're trying to get all of that data. We in fact, we have a registry underway in the U S, where we're going to be following a PBS patients longitudinally.

Anurag Relan: And then lastly, they're being treated with immunosuppressive therapies such as rapamycin to modulate that pathway. So we think it's quite logical to try to modulate the pathway with Laniolacib in the same way that we did with APDS patients. So I think from our perspective, and really this program came to us.., through our interactions with the immunology community. They, through numerous work, through all the work that we're doing on APDS, they kept on saying, look, there are other patients that they believe could benefit, and they lifted all of these reasons that I just mentioned to you. And it was really on that basis that we partnered, again, with the NIH, who are leaders in these, specifically in these areas of ALPS and CTLA-4, haploinsufficiency, to come up with this clinical trial program, because they were so enthusiastic about being able to, one, address unmet need, but two, to be able to use something that they were very comfortable using for APDS, and they were, you know, had that confidence, because they had been treating patients with APDS with Laniolacib for several years.

The hope actually to try to capture a lot of the data that we didn't address in the original clinical trial, because we werent aware of all of the possible benefits that these patients experience. So I think that's something else to look forward to us.

As the year continues.

Just a quick follow up on that as well.

When do you think it is.

Central time, and you might have something from the registry that would be worth sharing with us.

With physicians.

So the registry is just underway, but we are continuing to collect and publish data on the use.

The use of expanded access. So these are neither again this is essentially compassionate use patients in the U S. We don't qualify for commercial drug or outside the U S who are on therapy.

We are collecting that data and we've shared some of that last year, you'll see a lot more of that.

Data from the expanded access program or <unk>.

Case reports or case series of patients in the expanded access program Youll see that at conferences. This year I think the registry because it just started and I think thats more likely to be a.

Anurag Relan: And that brings me to your second, or your first question, which was about the real-world use of Laniolacib, and how does that compare to what we've seen in the clinical trials? And I think what we're seeing is, number one, that it continues to be generally safe and well-tolerated, so we're seeing nothing new from our pharmacovigilance efforts in real-world use suggesting a different safety or efficacy profile. But two, I think what we're also hearing is a lot of other benefits that we didn't even capture in the clinical trial program. So, and we're going to, and we're trying to get all of that data. In fact, we have a registry underway in the U.S. where we're gonna be following APDS patients longitudinally, and with the hope, actually, to try to capture a lot of the data that we didn't address in the original clinical trial because we weren't aware of all of the possible benefits that these patients experience. So I think that's something else to look forward to as the year continues. Just a quick follow-up. Wengie.

25 type of data, but I think that youre going to see through the expanded access program data coming out this year that reinforces what we saw in the clinical trial program and really.

Extends even beyond that.

Great. Thank you.

Thank you.

We will now go to the next question.

And your next question comes from the line of David Panter.

From H C. Wainwright. Please go ahead.

Hello, gentlemen, thank you for taking the question.

I have a couple of questions on <unk> I'm going to start very specific and then just talk more to the broader disease. If you don't mind. So first Steven earlier was talking about and of course, you guys have great adherence rates. So I was curious on the other and what are some of the reasons you see for a lack of adherence on the drug.

Thanks, Joe.

Do you have any insights nuts that you can share with you.

Yes, I think it's really just one off cases, Joe where in fact, some of the cases, where we've where we've seen it because patients are underweight.

Anurag Relan: So the registry is just underway, but we are continuing to collect and publish data on the use of expanded access. So these are, again, patients in the U.S. who don't qualify for commercial drugs or outside the U.S. who are on therapy. We are collecting that data, and we shared some of that last year. You'll see a lot more of that data from the expanded access program, or from case reports or case series of patients in the expanded access program. You'll see that at conferences this year.

And.

They need to be put on a lower dose.

That's not possible in the commercial programs. So that's one example.

It comes to the top of my mind, but.

It's not anything we're seeing from a safety point of view that suggests any concern or something that we saw it didnt see in the clinical trial program.

I don't think Theres anything.

A substantive here.

Anurag Relan: I think the registry, because it's just started, I think that's more likely to be a 25 type of data. But I think that you're gonna see through the expanded access program data coming out this year that reinforces what we saw in the clinical trial program and really extends even beyond that. Thank you. We will now go to the next question. And your next question comes from the line of Do Pantginis from HC Wainwright. Please go ahead. Hello gentlemen, thank you for taking the question. So, I have a couple of questions about Juwenga.

That's very helpful. Thanks, and then I guess.

Simon if I heard you correctly earlier it sounded like you might be disclosing in the future the role or the amount or proportion of the U S. As part of your.

Joe and your revenue profile first was that correct and then second when do you anticipate I know this is really forward looking that the U S could start to have a real impact on the revenue growth for Joe Andrea.

Joseph Pantginis: So first, Stephen earlier was talking about, and of course, you guys have great adherence rates, so I was curious on the other end, you know, what are some of the... Thanks, Joe. Anurag, do you have any insights on that that you can share with Joe? Yeah, I think it's really just one-off cases, Joe, where, you know, in fact, some of the cases where we've seen that patients are underweight, and they need to be put on a lower dose. So that's not possible in the commercial program.

Yes, Joe that is indeed forward looking yes.

Indeed, something later.

We are seeing.

You see that slide from interact you saw it in the middle there that those individuals are now being evaluated and that's actually all.

Starting and happening as we speak so the first small batches of those are expected to come through in the very near future, which may give us some early insights not.

Like I said earlier, it's not going to deliver bulks operations, but it will deliver patients.

And the bulk I think will.

Anurag Relan: So that's one example that comes to the top of my mind, but it's not anything we're seeing from a safety point of view that suggests any concern or anything that we saw and didn't see in the clinical trial program. So I don't think there's anything substantive here. That's very helpful.

We'll be seen following the closure of the mayor of experiment and we should expect or as <unk> was alluding to by the end of this year. So I think 25 will be the year, where the bulk of the <unk> patients will become will become available Florida for treatment I think that's a reasonable.

Anurag Relan: Thanks. And then, I guess, Simon, if I heard you correctly earlier, it sounded like you might... losing in the future the role or the amount or proportion of VUSs as part of your Joe Nja Revenue Profile. First, was that correct? And then second, when do you anticipate, I know this is really forward-looking, that VUSs could start to have a real impact? Yes, Joe, that is indeed forward-looking.

Forward looking statements for now or Joe.

Got it no that's fair and my broader question about the disease sort of ties in with.

Your recent data at Quad AI, obviously, very intriguing data with regard to the molecular diagnostics and I guess I would ask analog.

The role that Joe and you could play with regard to multiple statements made in describing the disease, where some patients do not have clinical action ability. So I'm. Just curious first can you for all of US helped define why patients not might not be actionable from it.

Sijmen de Vries: Yeah, I said actually something like that. We're seeing, you know, you see that slide from Anurag, you saw in the middle there that those individual VUSs are now being evaluated. And that's actually, you know, starting and happening as we speak.

Clinical standpoint, or medical standpoint, and if Joe and you could have an impact on that.

Sijmen de Vries: So the first small batches of those are expected to come through in the very near future, which may give us some early insights into that. It's not, like I said earlier, it's not going to deliver bulks of patients, but it will deliver patients. And the bulk, I think, will be seen following their closure of the MAVE experiment, which is expected, as Anurag was alluding to, by the end of this year.

Yes, I think.

It's a good question and that's something we're doing a lot of work on us.

Really educating patients and clinicians about Aps I think.

It's a foregone conclusion that amongst our team of course that this is a serious disease and that this there is a significant mortality associated with it that many of these patients. Unfortunately go onto developed lymphoma and lymphoma.

Sijmen de Vries: So I think 25 will be the year when the bulk of the VUS patients will become available for treatment. I think that's a reasonable forward-looking statement for now. Got it. No, that's fair.

As a key reason for the high mortality in these patients and lymphoma that these patients develop is often not easier to treat.

Joseph Pantginis: And my broader question about...sort of ties in with your recent data at Quad AI, obviously very intriguing data with regard to molecular diagnostics, and I guess I would ask Anurag about the role that Joentgen could play with regard to, you know, multiple statements where some patients do not have clinical actionability. So I'm just curious, you know, first, can you, you know, for all of us, help define why patients might not be actionable from a clinical standpoint or medical standpoint and whether Joentgen could have an impact. Yes, I think it's a good question.

And the mortality rates are much higher than you'd see in other lymphomas for example, or in other patients. So I think theres a lot of education to talk talk about that I think it's also important to recognize that these patients do have different clinical manifestation. So.

Some patients that may be very obvious with a high infection rate some patients.

Infections may not be the most predominant feature but it could be the lymphadenopathy or the large spleen.

So I think it's really educating clinicians also on what to look for in these patients and to be able to monitor these patients, but really all of these patients I think have a serious condition and they all are potentially eligible for Joe and Jim So I hope that answers your question.

Anurag Relan: It's something we're doing a lot of work on educating patients and clinicians about APDS. I think it's, you know, it's a foregone conclusion amongst our team, of course, that this is a serious disease and that there's a significant mortality associated with it, that many of these patients unfortunately go on to develop lymphoma, and lymphoma is a key reason for the high The lymphoma that these patients develop is often not easy to treat, and the mortality rates are much higher than you'd see in other lymphomas, for example, or in other patients.

It certainly does and my last question and thank you for bearing with me it's more towards you.

Your continued strengthening balance sheet and with that said do you feel that your increased cash helps leverage additional business development discussions and can you talk to the potential or can you can you talk to the relative maturity of some of your ongoing discussions to in license Patel.

<unk> assets. Thanks.

Yes, Joe Yes, things, yes of course, it always helps to have a bit more cash at hand in case, one wants to do an in licensing.

Anurag Relan: So I think there's a lot of education to talk about that. I think it's also important to recognize that these patients do have different clinical manifestations. So, you know, some patients, it may be very obvious with a high infection rate. In some patients, you know, infections may not be the most predominant feature, but it could be lymphadenopathy or an enlarged spleen.

Pursuant in licensing opportunity, which of course as we said before is our preferred modus operandi.

That's a much easier.

Two to deal with.

That merger and acquisitions, having said that I think with the with your rival of Alexander Breidenbach are.

Our chief business Officer.

He's been he's been really proactively working and we've got a very nice pipeline.

Anurag Relan: So I think it's really educating clinicians also on what to look for in these patients and to be able to monitor these patients. But really, all of these patients, I think, have a serious condition, and they are all potentially eligible for joanjan. So I hope that answers your question. It certainly does.

Or are in advanced stage of discussions with a couple of a couple of possibility. So we have a nice.

Your line of sight as we call it for opportunities that we are evaluating however.

However, as you know in business development such as before.

It doesn't count until you have a deal so yes.

Yes, but we are we remain very active and I think what also is what we see is.

Sijmen de Vries: And my last question, and thank you for bearing with me, is more towards, you know, your... Continued Strengthening Balance. With that said... feel that your increased cash helps leverage additional business development. Gosh, talk, or can you talk, about the relative maturity of some of your ongoing discussions.

With our commercial success and with the.

Ongoing ability.

We are very successful in being able to market against competition in the <unk> market and as we are basically and know how to develop.

New markets.

Even in a new disease, we got a lot more visibility now that we are that we are a company that is potentially an interesting partner of choice for those companies that you know.

Sijmen de Vries: Yeah, Joe, yeah, thanks. Yeah, of course, it always helps to have a bit more cash at hand in case one wants to pursue an in-licensing opportunity, which, of course, as we said before, is our preferred modus operandi, because that's much easier to deal with than mergers and acquisitions. Having said that, you know, I think with the arrival of Alexander Breidenbach, our Chief Business Officer, he's been, you know, he's been really proactively working, and we've got a very nice pipeline. And we are in the advanced stage of discussions with a couple of possibilities. So we have a nice line of sight, as we call it, for opportunities that we are evaluating. However, as you know, in business development, and I said this before, it doesn't count, you know, until you have a deal.

Should not go into commercialization because they will become single product companies.

And commercialization is very expensive and very risky.

And we basically therefore.

Like I said, because we have now got this under our belt and become more and more we see that on.

On the radar screen and we're getting a lot more inbounds and we use it got so we are.

Continue to be optimistic that we get so we get some opportunity. This year to you know to update you on the on a deal that we have crunched here with cliffs and that.

We have actually expanded our pipeline.

Very helpful. Thank you for all the answers guys.

Sure Joe.

Thank you.

We will now take our next question.

And your next question comes from the line of potash saving from Oppenheimer. Please go ahead.

Hey, everyone Mystify hartzell hectares.

Thanks for the question.

Sijmen de Vries: So, yes, but we remain very active. And I think what we also see is that with our commercial success and with the, you know, ongoing ability that we are very successful in being able to market against competition in the HEE market and that we basically know how to develop a new market, even in a new disease. We get a lot more visibility now that we are, you know, that we are a company that is potentially an interesting partner of choice for those companies that should not go into commercialization because And we basically, you know, therefore, like I said, because we have now got this under our belts and become more and more we see that, you know, on the radar screen, and we're getting a lot more inbounds than we used to get, continue to be optimistic that we will get some opportunity this year to, you know, to update you on a deal that we have crunched. And that we have actually expanded our services to be very helpful. Thank you for all. That's you, Joe.

Two questions from our end.

First one for we can ask Kelly do you.

Steve <unk> will conduct Inc. First quarter sales of previous years any color on that and the second one for Joe and John.

Can you provide any color on that.

<unk> of the patients.

So far.

Thanks, John John was launched around like three quarters nine months.

And your estimate on the ABF patient number of wells and conduct a fine. Thank you.

Yes, good idea.

And it over to you of Stephen those questions into one.

Could you repeat the questions because they weren't we weren't completely clear.

And.

Sure. The first one for Luca now can you can we can we still expect our season Lal D for connect Inc. First quarter sales.

Previously.

Yes. So thank you for clarifying so yes, I think you can broadly expect to see similar patterns to those which you saw last year because the same types of events are happening in the quarter. For example, Q1 is.

The prior authorization season, and as we indicated last year. There was some disruption to government patients. So as I said, we remain on track for what we expect to do this quarter that the leading indicators and the performance is where I expect it to be but.

Operator: Thank you. We'll now take your next question. And your next question comes from the line of Hartaj Singh from Oppenheimer. Please go ahead. Hey, everyone, this is Phan-Yi for Hartaj.

But you should expect to see the same overall patents through the year I imagine certainly in the first half.

Thank you and then the second question.

Sure Julien.

Can we now some color on the duration of the patients Joe and Jeff So far thanks.

Operator: Thanks for the questions. Two questions from our end. So, first one for Reconnect. Can we still expect seasonality for Reconnect in first quarter sales as we have seen in previous years? Any color on that?

And it was launched around three quarters.

The duration of the patients.

Patient Julien.

That's it.

I don't know like I said.

Sure.

Operator: And the second one for Joe and John, can you provide any color on the duration of the patients, Joe and John, so far? Thank you, since Joandaz was launched around three quarters nine months ago, and your estimates on the APDF patient number growth in 2024. Thank you. Yeah, could I just hand it over to you, Stephen, those questions, is that all right?

Prescript I'd like 30 days for each patient.

Patients in.

Okay I've got you now so as we mentioned earlier patients.

That hearing well unless there's.

You know either a weight issue or some such so that typically being prescribed on a monthly basis and <unk> on a monthly basis, and we see that cadence with patients.

Thanks.

So any.

Ask me.

A projection on that ABF patient numbers growth in 'twenty on far more specifically.

Stephen Toor: Could you repeat the questions because they weren't completely clear? Mine was: Sure, the first one for Ruconex: can we still expect seasonality for Ruconex in first quarter sales as we did previously? Yes, thank you for clarifying. So yeah, I think you can broadly expect to see similar patterns to those which you saw last year because the same types of events are happening in the quarters.

Yes, so like I said before we said we will continue to get new faces on products in the USA right. The adherence rate is very high it's of course chronic therapy.

And.

We don't give any.

We will update sorry, we'll update the numbers of patients to watch the future.

On a quarterly basis right when we get these yourselves.

Stephen Toor: So, for example, Q1 is the prior authorization season, and as we indicated last year, there is some disruption to government patients. So, as I said, we remain on track for what we expect to do this quarter. The leading indicators and the performance is where I expect it to be, but you should expect to see the same overall pattern through the year, I imagine, certainly in the first. Thank you. And the second question?

The answer to your question.

Yes. Thank you so much.

Yeah.

Thank you.

We will now take our final question for today.

And your final question comes from the line of Simon from Fast Berlin. Please go ahead.

Hello, Thanks for taking my question.

So the exclusivity on <unk>.

In the U S expires in two years' time, a bit more in two years' time.

Just wondering if you what kind of impact if any you expect that to have on refinish.

Stephen Toor: For Joe and Jeff, can we know some color on the duration of the patients on Joe and Jeff so far? Since it was launched around three quarters, like nine months. The duration of the patients? I've got you now.

Yes, we expect no impact whatsoever on that.

And recognized in that respect because we believe that.

There's nobody that's actually is working on or has any appetite to.

Stephen Toor: So as we mentioned earlier, patients are adhering well unless there's either a weight issue or some such. So they're typically being prescribed on a monthly basis and dispensed, and we see that cadence with patients. Thanks. So any athletes?

To develop a transgenic platform to make a biosimilar.

For this product.

Given also that this.

Stephen Toor: Projection on the APDF patient numbers growth in 2004 more specifically. Yeah, so, you know, like I said before, we said, you know, we will continue to get new patients on products in the USA, right? The adherence rate is very high.

Is of course, a great product, but it has in the greater context.

<unk>.

Commercial.

It's not a huge commercial opportunity. So therefore, no sales from no no no effect no. It's okay.

I mean, just a follow up from that.

What's your current thinking on the likely timing of the first gene therapy.

Sijmen de Vries: It's, of course, chronic therapy. And, you know, we don't give any, you know, we will, we will update, sorry, we will update the numbers of patients to watch the future in on a quarterly basis, right when we get these results. Did that answer your question? Yeah. Yeah.

Hey, I mean, besides your own product of course.

I think that will be.

Still a lot of years away.

Only the first patients are being tested now gene therapy is not the quickest development pathway forward I would say.

Sijmen de Vries: Thank you so much. Thank you. We will now take our final question for today. And your final question comes from the line of Simon Scholes from First Berlin. Please go ahead. Hello, thanks for taking my question. How are you?

Maybe you can say something on that.

No I think thats a timing.

There are some initial results.

In a small number of patients, but I think this will require.

The typical development path phase II phase III as well as long term follow up.

Simon Scholes: So the exclusivity on Rukinist in the US expires in two years' time, a bit more than two years. I'm just wondering what kind of impact, if any, you expect that to have on the roof. Yeah, we expect no impact whatsoever on Ruknest in that respect because we believe that, you know, there's nobody that actually is working on or has any appetite to develop a transgenic platform to make a biosimilar for this product, given also that it is, you know, it is, you know, a great product, but it has, So therefore, no, no, no, no, no effect, no impact. And just, I mean, just to follow up from that, I mean... What's your current thinking on the likely timing of the first gene therapy? in HAE, I mean besides your own product.

Which will take several years at the minimum.

Okay. Thanks very much.

Thanks Sam.

Thank you.

I'll now hand, the call back for closing remarks.

Thank you very much ladies and gentlemen, thank you for attending our full year conference.

I said at the beginning we laid in 2023 because of our very significant 19% growth in revenues related to foundation on the start of a long trajectory of growth, which this company is now going on embarking on and of course, that's why we guide this year for additional significant <unk>.

Both.

For for the revenues fueled by of course, the continued to growth expectations for <unk> and the continued growth of Joe and John.

Sijmen de Vries: I think that we'll still be, you know, a lot of years away. You know, only the first patients are being tested. Now, gene therapy is not the quickest development pathway forward, I would say. But maybe you can say something about that, Anurag.

And we feel very confident about the fact that we have started now all the systematic efforts to find those patients with the B U S patients in the U S. Validation efforts. We mentioned the family testing was was mentioned and of course the M. The increasing availability of.

Anurag Relan: No, I think that's it, Simon, that, you know, there are some initial results in a small number of patients. But I think this will require the typical development path, phase 2, phase 3, as well as long-term follow-up, which will take several years at the minimum. Okay, thanks very much.

Any ownership.

Ex U S.

We're through our named patient programs and other early access programs, we expect to expect revenues and.

And of course, the the completion of the clinical trials going forward that will support the approval in Japan in the future. This is of course not at 2024 story as we all understand because the file will only be ready to be submitted by the end of 2024.

Sijmen de Vries: Thanks, Sam. Thank you. I will now hand the call back to you for closing remarks. Thank you very much.

Sijmen de Vries: Yes, ladies and gentlemen, thank you for attending our full year conference. Like I said at the beginning, we will lay off in 2023 because of our very significant 19 percent growth in revenues. We laid the foundation and the start of a long trajectory of growth, which this company is now embarking on. And of course, that's why we guide this year for additional significant growth for revenues, fuelled by, of course, the continued growth expectations for Rucanest and the continued growth of Joentgen. And we feel very confident about the fact that we have now started all the systematic efforts to find those patients.

We look forward to.

Receiving.

The regulatory feedback from the various regulatory authorities and expect approvals during during 2004 and we are very very excited of course that we can significantly and launched a potential of linear ownership.

With that second indication PID with immune dysregulation.

<unk> to the Pi three kinase delta signaling to which <unk> alluded.

Which is a significantly larger opportunity going forward and when to areas, where we believe there is a very very strong scientific rationale underpinning.

And of course, not something that we will report in 2024, but we will be very happy to update you of course are once this trial is started and once this trial of course has the results and hopefully brings us to the next stage in development of any also for that second indication and that is my ladies and gentlemen, not even that.

Sijmen de Vries: The US patients, the US validation efforts we mentioned, the family testing was mentioned. And, of course, the increasing availability of Rucanest and leniolecip XUS, where through our named patient programs and other early access programs, we expect to generate revenues. And, of course, the completion of the clinical trials going forward that will support approval in Japan in the future. This is, of course, not a 2024 story, as we all understand because the file will only be ready to be submitted by the end of 2024. We look forward to, you know, receiving regulatory feedback from the various regulatory authorities and expect approvals during 24. And we are very, very excited, of course, that we can significantly enlarge the potential of Laniolacept with that second indication PID with immune dysregulation linked to the PI3 kinase delta signaling to which Anurag alluded, which is a significantly larger opportunity going forward. And whether we believe there is a very, very strong scientific rationale underpinning the approach.

Beginning because we are looking at additional opportunities to.

Luke apply millennial ship in this in adjacent areas and more of that nor news that will be coming in the future about our efforts in that respect announcement at least.

I was alluding to we have a very interesting line of sight of opportunities to in license or do M&A activities.

For our clinical stage opportunities in rare diseases, where we are feeling most comfortable to deal in immunology hematology expert, Georgia in gastroenterology. So thank you again for attending our conference our full year 2023 results conference and we look forward to updating you on the next quarter.

Else sometime in May Thank you very much goodbye.

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

Sijmen de Vries: And, of course, not something that we'll report in 2024, but, you know, we will be very happy to update you, of course, once this trial has started and once this trial, of course, has the results and hopefully brings us to the next stage in the development of Laniolacept for that second indication. And that is, ladies and gentlemen, not even the beginning, because we are looking at additional opportunities to, you know, apply Laniolacept in adjacent areas. And more of that, more news that will be coming in the future about our efforts in that respect. And last but not least, as I was alluding to, we have a very interesting line of sight on opportunities to in-license or, you know, do M&A activities for clinical stage opportunities in rare diseases, where we feel most comfortable dealing with immunology, hematology, respiratology, and gastroenterology.

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Yeah.

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So thank you again for attending our conference, our full year 2023 results conference, and we look forward to updating you on the next quarter results sometime in May. Thank you very much. Goodbye. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect. www.mooji.org Copyright 2019 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent.

Okay.

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