Q2 2024 Pharming Group NV Earnings Call
Good day and thank you for standing by. Welcome to the Pharming Group NV second quarter and first half 2024 results conference call and webcast.
Speaker Change: At this time, all participants are in a listen-only mode.
Speaker Change: After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1, 1 on your telephone. You will then hear an automated message advising your hand is raised.
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Speaker Change: 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 Vries, please go ahead
Unknown Executive: Thank you very much. Good morning or good afternoon, ladies and gentlemen.
Simon Scholes: I'm here at... Next slide, please. Welcome to our results conference for the first half. And that brings me to the pipeline on the right-hand side. We are very soon embarking on a phase two study for the next indication for late onset. And we are also exploring a third indication, and Anurag Relan will talk to you about that in more detail. And, of course, last but not least, we continue to focus on licensing or acquiring clinical stage opportunities in rare diseases to broaden our portfolio, which we can, of course, given our strong financial performance.
Simon Vries: Thank you very much. Good morning, or good afternoon, ladies and gentlemen. I'm here at, next slide, please. Welcome to our results conference for the first half and second quarter of this year.
Simon Vries: this year.
Simon Vries: and I'm here with my colleagues.
Simon Vries: Stephen Toor, our Chief Commercial Officer, Anurag Relan, our Chief Medical Officer, and Jeroen Wakkerman, our Chief Financial Officer.
Simon Vries: We will collectively guide you through the story. But before I do that, I would like to have the next slide and point you to this forward-looking statement slide.
Simon Vries: So we will be making forward-looking statements in this presentation.
Simon Vries: And as you well know, these are based upon future expectations that are based on our current expectations and assumptions and may involve unknown risks and uncertainties.
Simon Vries: As you will know that the results eventually could differ materially from what we have
Simon Vries: expressed or implied in our statements.
Simon Vries: Next slide please and then you can immediately move on to slide number five please.
Speaker Change: So what we're doing is, you know, this is the strategy that we've been embarked on for quite some time now. We're building this leading global rare disease biopharma company. And we do that on the basis of two strong pillars. The first one on the left, of course, is Rucanest, which has now been on the market.
Speaker Change: for close to 10 years in the U.S.
Speaker Change: And, of course, deliver sales mainly from the U.S. market. And we were very pleased to see that Rukiness continues to grow very significantly, both in context of the comparison to the previous quarters. In the second quarter, 23 percent.
Speaker Change: versus last year, and both when you compare the first half to last year's first half, 16%.
Speaker Change: which is, you know, I would say a very strong performance, which we're very pleased with. And Steven will a little bit later give you more details on the underlying, you know, positive indicators also going forward into the second half of the year.
Speaker Change: And then, of course, we have Joentje, which we launched last year in...
Speaker Change: [inaudible]
Speaker Change: The first half of this year to the last half of last year.
Speaker Change: So, we are continuing to grow Joentgen into the market.
Speaker Change: And, of course, this, as we all know, is a very new disease.
Speaker Change: And a ultra-rare indication, and our colleagues, Steven and Anurag, will respectively, you know, address you and tell you why we are continuing to be very optimistic of the enormous commercial potential for Joentgen, not only in APDS but also in subsequent therapies.
Stephen: and subsequent indications.
Stephen: And that brings me to the pipeline on the right-hand side. We are very soon embarking on a phase two study for the next indication for lenial onset.
Speaker Change: And we are also exploring a third indication and Anurag Relan will talk to you about that in more detail. And of course, last but not least, we continue to focus on in licensing or acquiring clinical stage opportunities in rare diseases to broaden our portfolio, which we can, of course, given our strong financial performance.
Anurag Relan: And then, I would like to have the slides, the next slide on the cascade, the disease overview, not this one. Yeah, thank you very much. And this slide is an important one, because, you know, Rucanest is in a very competitive market.
Anurag Relan: Rucanest, however, is a unique product, as you can see here, because these are the three pathways that represent an attack of hereditary angioedema.
Anurag Relan: And C1 inhibitor is the missing protein, and Rucanest is protein replacement therapy, is the only actively promoted C1 inhibitor on the U.S. market, and addresses all the pathways as you can see.
Simon Scholes: LUCIDEST has proven throughout the years to be a reliable product to actually treat those attacks of hereditary angiotema. And there is, of course, a lot of competition, but all of these competing products that are in development do not address all three paths.
Speaker Change: RUCADESC has proven throughout the years to be a reliable product to actually treat those attacks of hereditary angiotema.
Speaker Change: And there's of course a lot of competition, but all of these competing products that are in development do not address all the three pathways.
Unknown Executive: And Rucanest, a typical patient profile for Rucanest, therefore, over the years has evolved and has become that type of patient that does not respond to products that are actually only serving that, for instance, colloquium independent pathway in the middle or the HMWK releasing the BK pathway on the bottom. So Rucanest basically built its own unique position there, and all those patients that are using the other products suffer from breakthrough attacks. And also in this case, Rucanest comes into view.
Speaker Change: and Rukinest, a typical patient profile for Rukinest, therefore over the years has evolved.
Speaker Change: and has become that type of patient that does not respond.
Speaker Change: to products that are actually only serving that, for instance, colloquium-independent pathway in the middle, or the HMWK releasing the BK pathway on the bottom.
Speaker Change: So Rucanest basically builds its own unique position there, and all those patients that are using these other products suffer from breakthrough attacks. And also in this case, Rucanest comes into view. So in other words...
Unknown Executive: So in other words, we strongly believe that despite current competition and previous competition, which we have seen, and uncommon competition, which all serve that single pathway, Rucanest will be the go-to product for those severely affected patients, also known, for instance, as type 3 hereditary angioedema, of which more and more patients are getting diagnosed. That explains to you why more and more patients come to Rucanest, and Rucanest becomes the mainstay of their therapy for hereditary angioedema because they cannot get by on any of these other drugs. Hence, we are very optimistic and very confident about the future delivery of Rucanest to basically underpin the growth of our company.
Speaker Change: We strongly believe that despite current competition and previous competition, which we have seen, and uncommon competition, which all are serving that single pathway, Rucanest will be the go-to product for those severely affected patients.
Speaker Change: Also known, for instance, as type 3 hereditary angioedema, of which more and more get diagnosed. That explains to you why more and more patients come to Rukanes, and Rukanes becomes the mainstay for their therapy for hereditary angioedema, because they cannot get by on any of these other products.
Speaker Change: Hence, we are very optimistic and very confident about the future delivery of Rucanest to basically underpin the growth of our company.
Speaker Change: And let's move then to the next slide.
Speaker Change: And again, Jowinja, we believe, has a significant potential as well.
Speaker Change: Stephen and Anurag will go into more detail.
Speaker Change: where we are at the moment with Joanne Zhao.
Speaker Change: A significant portion of the U.S. patients already on pay therapy are the ones that have been identified so far. We, however, have a great potential going forward with regards to finding, validating the variance of uncertain significance.
Anurag Relan: and Anurag will talk about that, when that and how that will happen and what kind of potential big impact that will have on the number of patients that become available in the US market.
Anurag Relan: Outside of the U.S. we started to see sales and will continue to see sales, growing sales from patients on early access and inpatient programs.
Anurag Relan: We're working with more regulatory agencies and looking forward to bringing Lenny-Odyssey for APDS in more territories in the world. And last but not least,
Anurag Relan: An estimated 25% of patients are below 12.
Anurag Relan: and can be served as and when the pediatric studies.
Anurag Relan: Will the report end as and when we get the paediatric label expansion?
Anurag Relan: as well. So in other words,
Speaker Change: Leni Osep, Joanne Jha in APDS has a significant, a very significant potential. We believe even way beyond Rukinast.
Anurag Relan: at this point in time.
Anurag Relan: And that's only for APDS.
Anurag Relan: So the other thing on the right hand side there is that we are now, of course, identifying, we have identified the second indication.
Anurag Relan: And we'll start a phase two trial in that second indication, which is, as you can see on this slide, about more than three times the estimated incidence of APDS, the PID, Primary Immune Deficiency.
Simon Scholes: In addition to that, we are now seeking regulatory feedback on a third primary immune deficiency indication. In other words, we believe that not only does Joentgen have the enormous potential over the coming years to develop itself into a very significant commercial asset for our company in APDS. So with this said, I happily hand over to our Chief Commercial Officer, Stephen Toor, to take you through a little bit more details on the revenues of Ruknest and Joen. Thank you, Simon. Morning and good afternoon, everybody.
Anurag Relan: In addition to that, we are now seeking regulatory feedback on the third primary immune deficiency.
Speaker Change: so in other words we believe that not only does Joentjes have an enormous potential over the coming years to develop itself into a very significant commercial asset for our company in APDS
Speaker Change: But on top of that, it has an even bigger potential to actually become a pipeline in a product, given that we have now identified at least two indications from which we could start developing programs very soon.
Speaker Change: So with this said, I happily hand over to our Chief Commercial Officer, Stephen Toor, to take you through a little bit more details on the revenues of Ruknest and Joentgen.
Stephen Toor: We go to the next slide. So I will, as Simon said, take you through the Rukiness and the Joentgen performance so far, and then on the last slide, for me, before handing over to Anurag, just give you a little update on our kind of medium-term expectations and why we're so confident in the business. So looking at this slide, specifically root canal. Rucanest is, as you know, the only recombinant C1 SRAs inhibitor.
Stephen Toor: Thank you Simon, good morning and good afternoon everybody, we go to the next slide.
Stephen Toor: So I will, as Simon said, take you through the Rukines and the Joentgen performance so far. And then on the last slide, for me, before handing over to Anurag, just give you a little update on our kind of medium-term expectations of why we're so confident in the business.
Stephen Toor: So, looking at this line specifically, Rukanest.
Stephen Toor: You can see, I think, in those first four boxes at the top that the consistent strength in performance really relates to the unique attributes of Rucanest and the patient population we serve, that Simon alluded to, that more severely affected group.
Stephen Toor: And those key core benefits of 97% of patients, whose attack is resolved in a single dose and that sustained effect over a period of days, are really why those patients that, Why those patients for whom a catapult and other products don't work as well find a home with Rucanest, and it's what drives our continued strong performance. And that performance over a decade now has made Ruconest the second most prescribed acute therapy in the US, and, of course, it is still posting solid results.
Stephen Toor: Rucanest is, as you know, the only recombinant C1 SRAs inhibitor and those key core benefits of 97% of patients
Stephen Toor: whose attack is resolved in a single dose, and that sustained effect over a period of days, is really why those patients that...
Stephen Toor: Why those patients for whom a catapult and other products don't work as well find a home with root canister. It's what drives our continued strong performance.
Stephen Toor: And that performance over a decade now has made Ruconest the second most prescribed acute therapy in the U.S. and of course still posting solid results.
Stephen Toor: In the first half of 2024, new patient enrollments have continued to strengthen over and above last year. And in that first half, we actually enrolled 170 new patients. And that represents an increase of 18% over the first half of 2023.
Stephen Toor: And that represents an increase of 18% over the first half of 2023. And just as a reminder, that's a serious and progressive disease with high mortality. And until Joentgen was launched, there was no indicated disease-modifying treatment.
Stephen Toor: That, as you would expect, is driven by an increase in new prescribers as well as maintaining our existing ones.
Stephen Toor: And our sales team has added another 36 new prescribers in the first half of 2024, taking the total to over 760, which is an all-time high.
Stephen Toor: So as you would expect, this translates into that quarterly growth of 23% and that plus 16% versus the first half of last year that Simon alluded to.
Speaker Change: And I think for the attributes I mentioned, the patient population we serve, and also the clinical overview Sijmen gave of where Rukin is operating, all three pathways, is why we're very confident that we're well positioned, even as the market evolves in the second half of next year.
Stephen Toor: Next slide, please.
Stephen Toor: So, switching gears now to Joenja, that is, as Simon said, a product that we launched on the 31st of March last year to treat the ultra-rare disease, APDS.
Stephen Toor: and just as a reminder that's a serious and progressive disease with high mortality and until Joentgen was launched there was no indicated disease modifying treatment.
Speaker Change: As you also know, we were strung out the gate with the US launch and patients were on Joe Njet and fully reimbursed within days, within less than a week in fact.
Speaker Change: So, we continue to make good progress in 2024. At the end of Q2, 91 patients were on JoeEnger.
Speaker Change: Another two were in process at the end of the quarter and we should come on to therapy early in Q3. We added 10 newly diagnosed patients in the quarter, taking us past 230, which is close to half the total number the literature suggests are out there already, just 15 months post-launch.
Speaker Change: And we believe it's highly likely, as with any ultra-rare disease, now that we're out there more actively patient-finding, that actually there'll be more patients than the literature suggests.
Stephen Toor: We also have in our pipeline 40 more diagnosed patients whose doctors we're working with to enroll in our program, plus 60 and counting pediatric patients who've been diagnosed. Next slide, please. Our teams remain, as you would expect, firmly focused on finding new patients and then, when found, mapping and testing the whole family, given this is an autosomal dominant disease. And this approach, as you're aware, netted an additional 28 patient leads in Q2 that we're now working through to confirm whether they're actually APDs, and it's through these efforts that we remain excited and confident in the value we can bring to the APDS community, both in the US and ultimately globally.
Speaker Change: We also have in our pipeline 40 more diagnosed patients whose doctors we're working with to enroll in our program, plus 60 and counting pediatric patients who've been diagnosed within our pipeline who'll be ready to go on Juvenger when we get the label expansion in the fullness of time.
Speaker Change: So, just to summarize Joe Engine performance, we exited Q2 with $11.1 million in sales, which as Simon said is an increase of 16% over Q1.
Speaker Change: Next slide, please.
Speaker Change: Our teams remain, as you would expect, firmly focused on finding new patients and then, when found, mapping and testing the whole family, given this is an autosomal dominant disease.
Speaker Change: And this approach, as you're aware, netted an additional 28 patient leads in Q2 that we're now working through to confirm whether they're actually APDS patients.
Anurag Relan: and Anurag Relan.
Stephen Toor: And as a result. The first is the continued strength of Rukanist and the reasons that we've already mentioned for why it holds the position it does in the market, which is, of course, underpinned by growth in prescribers, new enrollments, and sales year on year. But also, for Joanne, I just want to expand briefly on some of the bullets on this slide.
Speaker Change: Now, if we look a little bit further forward, you know, I think we've expressed confidence in both RootKinesis and, of course, the future of GeoENGIA, and that's based on a few key factors.
Speaker Change: So the first is the continued strength of Rukanist and the reasons that we've already mentioned for why that holds the position it does in the market, which is of course underpinned by growth in prescribers, new enrollments and sales year on year.
Speaker Change: The second is the execution around the Joanja launch.
Speaker Change: and the progress being made in patient found finding, family testing and building a pipeline for future months and years.
Speaker Change: But also for Joenjo, I just want to expand briefly on some of the bullets on this slide.
Stephen Toor: Good confidence in the future. One is the VUS resolution efforts that Simon alluded to and that Anurag will discuss. That'll be a significant inflection point for us and should deliver a bonus of patience in 2025. Another important factor is geographic expansion.
Speaker Change: There are another few factors, another four factors that give us...
Simon Vries: Good confidence in the future. So one is the VUS resolution efforts that Simon alluded to and that Anurag will discuss That'll be a significant inflection point for us and should deliver a bonus of patience in 2025
Stephen Toor: Right now, we're launching in the U.S., but we will launch in other key markets, which include Japan, the world's second biggest market in the broader APAC region, the United Kingdom, the European Union, Canada, the Middle East, and across these countries and regions, we've so far found almost 900 patients, which represents almost half of the 2,000 that the prevalence data would suggest that in these And additionally, we're currently assessing, while we work through those other key markets, the key countries in LATAM and our options there.
Simon Vries: Another important factor is geographic expansion. Right now we're launching in the U.S.
Simon Vries: But we will launch in other key markets which include Japan, the world's second biggest market and the broader APAC region.
Speaker Change: The United Kingdom, the European Union, Canada, the Middle East, and across these countries and regions we've so far found almost 900 patients, which represents almost half of the 2,000 that the prevalence data would suggest are in these markets.
Speaker Change: and additionally we're currently assessing while we work through those other key markets the key countries in LATAM and our options there.
Stephen Toor: We have, as I alluded to, pediatric patients, and we're building that pipeline globally. And over time, when we get that indication, that'll be another bolus of patients that comes through in the future. And then finally, and Simon talked about this, the lifecycle management of LeniolaCip to create a pipeline of new indications for the molecule. So to expand on these and other related themes, I'd like now to hand over to our Chief Medical Officer, Anurag Relan. APDS, as Steve mentioned, is a rare, serious genetic disease caused by hyperactivity in this PI3K pathway, and it's associated with early mortality, often due to lung cancer. The Pivotal Study, as well as an open-label long-term extension.
Speaker Change: We have, as I alluded to, the pediatric patients, and we're building that pipeline up globally, and over time, when we get that indication, that'll be another bolus of patients that comes through in the future.
Sijmen Vries: And finally, and Sijmen talked about this, the life cycle management of Laniolacib to create a pipeline of new indications for the molecule.
Sijmen Vries: And as these launches and events occur, we see multiple years of growth ahead from JoAnger for APDS and potentially those other indications.
Sijmen Vries: So to expand on these and other related themes, I'd like now to hand over to our Chief Medical Officer, Anurag Relan.
Anurag Relan: Thanks Steve. I don't know if we can jump to the next slide and we can review some first some detail about Joentgen. So Joentgen is FDA approved to treat activated PI3K delta syndrome or APDS in adult and pediatric patients who are 12 years of age and older.
Speaker Change: APDS, as Steve mentioned, is a rare, serious genetic disease caused by hyperactivity in this PI3K pathway, and it's associated with early mortality, often due to lymphoma.
Speaker Change: And it's also important to note that ABDS is progressive, so experts state that early treatment is important. Joentgen has a PI3K delta inhibitor, which regulates this hyperactive signaling pathway that's found in APDS patients.
Speaker Change: The FDA approval last year was based on a randomized
Speaker Change: Pivotal Study, as well as an open-lapel long-term extension study, and Jalindja treats the root cause of APDS by correcting the underlying immune defect, thereby addressing both the immune deficiency and immune dysregulation that's found in APDS patients.
Anurag Relan: The safety of Joanna was evaluated in this placebo-controlled study as well as the long-term study, which is just wrapping up, in fact. Specifically, we are supporting numerous activities to raise the awareness of APDS and share data about Leni-Elisabeth and Joe. But also importantly, we have several efforts to help patients get an accurate diagnosis. Because APDS is an inherited disease, we expect to find patients within the family.
Speaker Change: The safety of Joanna was evaluated in this placebo-controlled study as well as the long-term study that is just wrapping up, in fact. And no drug-related serious adverse events or study withdrawals were seen in these trials.
Speaker Change: And on the next slide, we can see some of our patient-finding efforts.
Speaker Change: Specifically, we are supporting numerous activities to raise the awareness of APDS and share data about Laniolus of Angiolingia.
Speaker Change: So on the left you can see the medical education types of things that we engage with and the organizations that we're working with to raise this type of awareness.
Speaker Change: But also importantly, we have several efforts to help patients get an accurate diagnosis.
Speaker Change: The first of which is genetic testing, and we have a sponsored, no-cost genetic testing program. We have support from genetic counselors, and as Steve mentioned, we're also working to help perform family testing among patients who've already been diagnosed with APDS.
Steve: Because APDS is an inherited disease, we expect to find patients within families.
Steve: But most APDF patients that have been diagnosed and that are in our databases actually don't have family members diagnosed. So we're supporting clinicians.
Steve: to be able to educate and encourage family testing and also offering.
Steve: patient-initiated testing so that patients with family members can get those family members tested easily.
Anurag Relan: And then on the right side, one large area where we're focused on is when a patient actually goes through all of this process and receives their genetic test results, but unfortunately, they get what's called a variant of uncertain significance, or a VUS. And in essence, this is an inconclusive result that indicates that a patient has a novel gene abnormality, but it is not known whether this abnormality causes APDS or not So some ways that we do this are first, what's called variant curation, which is collecting known data about the variant.
Steve: And then on the right side, one large area where we're focused on is when a patient actually goes through all of this process and receives their genetic test results, but unfortunately it's what's called a Variant of Uncertain Significance or a VUS.
Steve: And in essence, this is an inconclusive result that indicates that a patient has a novel gene abnormality, but it is not known whether this abnormality causes APDS or not.
Steve: To help doctors and patients, we have several projects which will enable these BUS results to be definitively classified. So some ways that we do this is first just what's called variant curation, which is collecting known data about the variant.
Anurag Relan: In addition, we also make available and support programs to allow functional testing to occur in patients. For example, measuring the activity of the pathway in a patient who has a VUS diagnosis or a VUS result. And then lastly, we're supporting a large-scale experiment, what's called a multiplex assay of the variant effect, which is a high-throughput method whereby we can do in vitro testing of every or almost every possible variant that could exist.
Steve: In addition, we also make available and support programs to allow functional testing to occur in patients. So actually measuring the activity of the pathway in a patient who has a VUS diagnosis or a VUS result.
Steve: And then lastly, we're supporting a large scale experiment, what's called a multiplex assay of a variant effect.
Steve: which is a high-throughput method whereby we can do in-vitro testing of every or almost every possible variant.
Anurag Relan: And this is a study that's going to be published later this year, which we think will be very important in helping the U.S. resolution efforts. And on the next slide, we can talk a little bit more about the scale of the problem, because this VUS problem is something that frustrates patients and doctors and limits the diagnosis of genetic diseases such as APDS. And we are aware of more than 1,200 or approximately 1,200 patients in the US that have received a BUS result for either the PIK3CD gene or the PIK3R1 gene.
Steve: that could exist and this is a study that's going to read out later this year which we think will be very important in helping these BUS resolution efforts.
Steve: And on the next slide, we can talk a little bit more about the scale of the problem. Because this VUS problem is something that frustrates patients and doctors and limits the diagnosis of genetic diseases such as APDS.
Steve: And we are aware of more than 1,200 or approximately 1,200 patients in the U.S. that have received a BUS result in either of the PIK3CD gene or the PIK3R1 gene.
Anurag Relan: This figure will continue to grow over time because anytime that a patient gets a genetic test done, this remains a possibility. And in fact, BUS results or BUS patients are identified at approximately four times the rate of an APDS or what's called a likely pathogenic or a pathogenic. Of course, this is a worldwide problem since these patients who get genetic testing can get this type of result anywhere.
Steve: This figure will continue to grow over time because any time that a patient gets a genetic test done, this remains a possibility.
Steve: And, in fact, BUS results or BUS patients are identified at approximately four times the rate of an APDS or what's called a likely pathogenic or a pathogenic variant.
Steve: Of course, this is a worldwide problem since these patients who get genetic testing can get this type of result anywhere.
Steve: And when we look in the literature, what we see is, across all genes, what we see is that once...
Unknown Executive: When there are reclassification efforts put in place, approximately 20% of all of the BUSs that are out there get upgraded to likely pathogenic or pathogenic, or what's called disease-causing, and this, again, has crossed many. In the case of APDS, we've done a pilot study with 25 patients who have a BUS result, and we found consistent findings of APDS in five of these 25 patients, or 20%, and one of these pitchers is already preparing for enrollment. So the key takeaway for us is that there is a significant opportunity to identify additional patients with APDS through these VUS resolution efforts. There is a single outstanding CMC request.
Steve: When there are reclassification efforts put in place, then approximately 20% of all of the VUSs that are out there get upgraded to a likely pathogenic or pathogenic, or what's called disease-causing. And this, again, has crossed many genes.
Steve: In the case of APDS, we've done a pilot study with 25 patients who have a BUS result, and we found consistent findings of APDS in 5 of these 25 patients, or 20%.
Steve: And one of these pages is already preparing for enrollment now.
Steve: So, the key takeaway for us is that there's a significant opportunity to identify incremental patients with APDS through these VUS resolution efforts, and we'll look for more news for this as the year goes on, especially toward the end of the year.
Steve: On the next slide, I'd like to talk to you a little bit about some of the other efforts beyond the current FDA approval. As we've previously discussed,
Speaker Change: The CHMP review has been extended to January 2026. There is a single outstanding CMC request and the CHMP have determined positive clinical benefit as well as safety which has now concluded.
Unknown Executive: And the CHMP has determined positive clinical benefit, as well as safety, which has now concluded. In addition, we are expecting a decision from the UK MHRA later this year, and importantly, no major objections were noted in our Day 70 questions from the MHRA. And you've seen in our press release, too, there is significant clinician interest in our expanded access and named patient programs, again, reflecting the number of patients that are diagnosed out there but also the unmet need in this patient population. And as previously mentioned, we received marketing authorization in Israel earlier this year, and we have submissions under review in Canada as well as Australia.
Speaker Change: In addition, we are expecting a decision from the UK MHRA later this year, and importantly, no major objections were noted in our Day 70 questions from the MHRA.
Speaker Change: We've also completed our Japanese clinical study and we're engaged with PMDA to discuss the filing strategy there following the completion of the necessary studies.
Speaker Change: And you've seen in our press release too, there is significant clinician interest in our expanded access and named patient programs. Again, reflecting the number of patients that are diagnosed out there, but also the unmet need in this patient population.
Speaker Change: And as previously mentioned, we've received marketing authorization in Israel earlier this year. We have submissions under review in Canada as well as Australia.
Unknown Executive: And we have two pediatric studies which are also very important because, as we mentioned, this is a progressive disease. We've already identified a significant number, so when we think about that, we see. Just as a review, primary immune deficiencies are a broad group of disorders with several key features. Often, they have a genetic basis. Of course, as an immune deficiency, they have an increased risk of infection, but there's also a subset of these immune deficiencies that also have a feature of immune dysregulation.
Speaker Change: And we have two pediatric studies which are also very important because, as we mentioned, this is a progressive disease. We've already identified a significant number of patients who are below the age of 12, and we have now completed enrollment in our first study that goes down to age 4, and then there's a second study where enrollment is continuing.
Speaker Change: And then I'll spend the next couple of slides talking to you a little bit about our plans beyond APDS with Lenny Yolison.
Lenny Yolison: So, when we think about that, we see...
Lenny Yolison: Several development opportunities for Lenny Olson.
Speaker Change: Just as a review, primary immune deficiencies are a broad group of disorders with several key features.
Speaker Change: Often they have a genetic basis.
Speaker Change: Of course, as an immune deficiency, they have an increased risk of infection, but there's also a subset of these immune deficiencies that also have a feature of immune dysregulation.
Jeroen Wakkerman: Specifically, that immune dysregulation causes lymphoproliferation, autoimmunity, and other autoinflammatory conditions, the first of which will be we're looking at PIDs with immune dysregulation linked to this specific signaling pathway. Overall, this represents a treatable population estimated at approximately five per million, or which is about three times as large as APD. So with that, I will turn over to my colleague, Jeroen, to review our. Thank you very much, Anurag, and good morning, good afternoon, everybody.
Speaker Change: Specifically, that immune dysregulation causes lymphoproliferation, autoimmunity, and other autoinflammatory conditions. And because of that, these PIDs are associated with high morbidity and mortality.
Speaker Change: APDS, of course, is an example of one of these immune deficiencies with dysregulation. And now we are looking at leniolisib for other PIDs with these same features.
Speaker Change: The first of which will be, we're looking at PIDs with immune dysregulation linked to this specific signaling pathway.
Speaker Change: And we'll talk a little bit about this in the next slide, but these are, again, the patients who have clinical manifestations, disease onset, and severity very similar to APDS. There are no specifically approved therapies for this, and we're beginning with a phase two study imminently.
Speaker Change: In addition, as Sijmen mentioned, we are working on another disease in the same area, and we're in the midst of obtaining regulatory feedback on the proposed clinical development plan.
Sijmen Vries: But in essence, this is another primary immune deficiency with the same clinical phenotype of immune dysregulation. So something obviously very common across these three indications that we're pursuing.
Sijmen Vries: And then on the next slide, you can see some details about the Phase 2 study that's about to start.
Sijmen Vries: And this is a phase two proof of concept study that's going to be starting soon at the NIH with 12 patients.
Sijmen Vries: These are going to be patients that are known to have hyperactive signaling based on a genetic diagnosis of one of the, and you see there are several of the genes that are involved, including what's called the ALPSFAST gene, CTLA-4, P10, as well as a couple others.
Sijmen Vries: Overall, this represents a treatable population estimated at approximately 5 per million, or which is about three times as large as APDS.
Sijmen Vries: This Phase 2 study will look at dosing, but also safety and tolerability, and we'll also have some exploratory efficacy measures here. And the goal is to pick the best dose regimen for the Phase 3 study. And as I mentioned, we're expecting the final IRB approval imminently, which will enable us to start the study this month.
Sijmen Vries: So with that, I will turn it over to my colleague Jeroen to review our plan.
Jeroen Wakkerman: Starting off with the financial highlights of the second quarter of 2024 versus last year, you see that we grew our revenues by 35%, and that was driven by volume of both Reconest and Angewandia. Reconest volume went up by 23%.
Jeroen Wakkerman: Thank you very much, Anurag, and good morning, good afternoon, everybody.
Jeroen Wakkerman: Starting off with the financial highlights of the second quarter of 2024 versus last year. You see that we grew our revenues by 35% and that was driven by volume of both Rukonest and Joentje. Rukonest went up by 23%.
Jeroen Wakkerman: Gross profit was fairly stable at 89%, so the margin was at 89%, so the gross profit basically grew in line with our revenues.
Jeroen Wakkerman: OPEX development. The OPEX went from 65.8 last year in the period to 70.1. And that is reflecting a continued investment in Joentgen, both in the US and EU, and in the rest of the world, and also investment in compliance, IT, and HR-related areas, and that is to support the growth of the company. You see an operating profit that we adjusted. So this is not the reported operating profit, but adjusted for a few one-offs that we had last year, we had a milestone payment of 10.5 million.
Jeroen Wakkerman: OPEX development, the OPEX went from 65.8 last year in the period to 70.1 and that is reflecting a continued investment in Joentgen.
Jeroen Wakkerman: both in the US and EU, rest of the world, and also investment in compliance, IT, HR-related areas.
Jeroen Wakkerman: and that is to support the growth of the company.
Jeroen Wakkerman: You see an operating profit that we adjusted, so this is not the reported operating profit, but adjusted for a few one-offs that we had last year. We had a milestone payment of 10.5 million, so that was a cost, but we also had a gain on the priority review voucher that you may remember.
Jeroen Wakkerman: So that was a cost, but we also had a gain on the priority review voucher that you may remember. But basically, on a like for like basis, we see that the operating profit gap narrowed from $5.3 million last year to $3.1 million this year. And the net profit was around 0 compared with 1.3 last year minus 1.2, so a loss this year.
Jeroen Wakkerman: But basically on a like-for-like basis, we see that the operating profit gap narrowed from $5.3 million last year to $3.1 million this year.
Unknown Executive: And please be aware for the analysts that in the finance result, we had a gain of 3.4 million this year versus a loss of 1.8 million, and that gain is related to the convertible bonds and a reclassification of the derivative to equity. So it's a technical adjustment that's good to be aware of. And the overall cash and marketable securities went down by almost 42 million. The biggest driver of that was the issue and the repurchase of the bonds, and there's a bit of a focus on the Joentia revenues on the next slide. So that's the breakdown of the geographies in the different periods.
Jeroen Wakkerman: And the net profit was around 0, 1.3 last year, minus 1.2, so a loss this year. And please be aware for the analysts that in the finance result we had a...
Speaker Change: Gain of 3.4 million this year versus a loss of 1.8 million. And that gain is related to the convertible bonds and a reclassification of the derivative to equity. So it's a technical adjustment that's good to be aware of.
Speaker Change: And the overall cash and marketable securities, they went down by almost 42 million. The biggest driver of that was the issue and the repurchase of the bonds.
Speaker Change: All the bonds had a nominal value of 125.
Speaker Change: million euros, the new one that we issued this year.
Speaker Change: had a value of 100 million and overall the cash out because of the payback was 30 million.
Speaker Change: and the remainder is mainly driven by an increase in receivables from higher sales than quarter before.
Speaker Change: So moving on to the same KPIs but for the first half of the year, revenues increased by 33 percent, again mainly volume from both products, Rukiness went up 16 percent as was mentioned before.
Speaker Change: Gross profit for the first half was 87%, gross margin was 87%, and the gross profit increased to $113.3 million.
Speaker Change: OPEX reflected the same, basically, development as I've just mentioned, so went up by 15.5 million to 134 million.
Speaker Change: million
Speaker Change: The adjusted operating loss was roughly the same as it was last year, and the net profit was minus 13.7, so a loss of 13.7, a slight increase versus last year.
Speaker Change: And in the first half year, for the reasons that I've just mentioned, went down by 53 million to 161.8 million.
Speaker Change: Sijmen Vries, Anurag Relan, Stephen Toor, Sijmen Vries, Anurag Relan, Stephen Toor,
Speaker Change: And a bit of a focus on the Joentia revenues on the next slide, so that's the breakdown of the geographies in the different periods.
Unknown Executive: So quarterly, revenue almost tripled to 11.1 million, and the Q2 2024 revenue mainly came obviously from the US but also already from early access and named patient programs outside of the US. And looking at the financial guidance on the next slide for 2024, we reconfirm our revenue guidance of 14 to 20% sales growth, being between 280 and 295 million dollars for the full year. And obviously, JoAnjo will be a significant driver, but we also expect to continue Rukunos' growth and the US pricing with an annual cost of 566,000 US dollars and a continuing discount of around GTM of around 15%.
Speaker Change: So quarterly the revenue almost tripled to $11.1 million.
Speaker Change: and the Q2 2024 revenue mainly came obviously from the US but also already from the early access and named patient programs outside of the US.
Speaker Change: And for the half year we increased the Joentia sales by 44% against last year and you see the
Speaker Change: All the different numbers per region.
Speaker Change: And by the end of Q2, we had 91 patients on therapy in the US.
Speaker Change: which meant an increase of eight patients in Q2.
Speaker Change: and in Q1 we had an increase of 2 patients. Also important to note is that we've had a very stable gross to net discount percentage of 15% versus previous year.
Speaker Change: i.e. the discounts don't play a role in increased sales.
Speaker Change: And looking at the financial guidance on the next slide for 2024, so we reconfirm our revenue guidance of 14-20% sales growth, being between 280 and 295 million dollars for the full year.
Speaker Change: And obviously, JoAnjo will be a significant driver, but we also continue, expect to continue, rigorous growth.
Joenjo: And for Joentje, the revenue assumptions are continued growth in patients on PEC therapy, as we have shown so far this year. Continued high adherence or compliance rate of 85%.
Joenjo: And the US pricing with an annual cost of 566,000 US dollars and continuing discount of around, GTN discount of around 15%.
Unknown Executive: For the second half of 2024, in terms of OPEX, we are making some adjustments and savings therefore because of the EMA delay. The AXUS Lanyard Zip sales, you have heard that there is a great interest in that.
Joenjo: For the second half of 2024, in terms of OPEX, we are making some adjustments and savings therefore because of the EMA delay.
Anurag Relan: and Anurag Relan.
Anurag Relan: And with that, I would like to hand over back to Sijmen Vries for the 2024 Outlook.
Sijmen Vries: Thank you, Jeroen. Thank you very much. So, yes, you have just heard from Jeroen that we are sticking to our total revenue guidance for this year between 280 and 295. Obviously, there were these quarterly fluctuations which are typical.
Speaker Change: Then you heard about our patient-finding efforts on all fronts for Joentgen.
Speaker Change: and the number of increasing patients that we have identified, and especially
Speaker Change: The expectations that we currently have on the basis of current initial results from that small trial with regards to the VUS validation efforts, which
Speaker Change: amount to about 20% of those 1,200 patients that we expect to become available over the coming year, and of course will drive significantly the growth of Joentgen in the U.S. in 2025 and onwards.
Speaker Change: The AXUS Lanyard Ship Sales, you have heard that there is a great interest in that, obviously.
Unknown Executive: Obviously, these named patient programs have a lot of administrative procedures and are, of course, not always very fast. But we know that there's quite a few patients in the pipeline waiting for clearance to enter into the program all over the world. You heard about the regulatory approval progress, especially in the United Kingdom, where we expect the fourth quarter of this year to hear back from the regulators, and of course that we are confident that we will be able to speak to EMA again following the submission in January 26th of the last remaining question by EMA, and the confirmation of course that EMA confirmed the clinical benefits and safety of Lenio's, it makes us very confident that we're looking forward to also getting into the European markets in 2026.
Speaker Change: These named patient programs have a lot of administrative procedures and are, of course, not always very fast, but we know that there's quite a few patients in the pipeline waiting for clearance to enter into the program all over the world.
Speaker Change: The clinical trials you heard Anurag talk about for the regulatory findings for Japan, the second biggest market in the world, and of course the pediatric label expansion which will make, again, a bolus of at least 25% of additional patients available for therapy for Joanna.
Speaker Change: You heard about the regulatory approval progress, especially in the United Kingdom, where we expect the fourth quarter of this year to hear back from the regulators.
Speaker Change: And of course that we are confident that we will be able to speak to IMA again following the submission in January 26th of the last remaining question by IMA. And the confirmation of course that IMA confirmed the clinical benefits.
Speaker Change: and Safety of Reneo's, it makes us very confident that we're looking forward to also getting into the European markets in 2026.
Speaker Change: Then you heard about the initiation of that phase 2 clinical trial for that second indication which Anurag described for PIDs with immune dysregulation and our plans for the third that have been submitted to the regulators.
Speaker Change: and where we're expecting feedback and hopefully starting a trial in the not-too-distant future as well. So in other words, we will then start developing two subsequent indications for for Joentgen.
Speaker Change: And last but not least, the continued focus on potential acquisitions and the enlisting of clinical stage.
Speaker Change: Opportunities in Rare Diseases to further build our portfolio and diversify the company further. And I can tell you we have a lot of activity going on there, but we are of course, you know, very precise in terms of what kind of opportunities we actually will bolt on to our company.
Speaker Change: So that concludes the call and I would like to now go back to the operator and open the floor for questions. Thank you.
Speaker Change: Thank you. As a reminder to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster.
Unknown Executive: To withdraw your question, please press star 1 1 again. Please stand by while we compile the Q&A roster. And the first question comes from the line of Sushila Hernandez from Van Lanschot Kempen. Please go ahead; your line is now open. Thank you, Sushila.
Speaker Change: We will now take our first question.
Speaker Change: And the first question comes from the line of Sushila Hernandez from Van Lanschot Kempen. Please go ahead, your line is now open.
Susheela Hernandez: Yes, thank you for taking my questions. I have a few, if I may.
Susheela Hernandez: Unknown Speaker, So it's approved in APDS, and you're about to start the Phase II studies in PIDs with immune death regulation, and now looking into a third indication. Could you share a bit more on what prompts you going after this third indication? And are you expecting that this would expand addressable patient population significantly?
Speaker Change: and also on the VUS Salidation Studies. Could you elaborate on the 12,000 patients identified in the US? How did you find these patients? And how many of these patients would you expect to be diagnosed with APDS and conferred to Juenja treatment? And then lastly, with the MHRA decision near, how many patients have you already identified in the UK? And similar to the US, can we expect a large portion of these patients to get on day therapy in the first half year of the launch? Thank you.
Anurag Relan: I'm happy handing it over to Anurag to start answering your questions. In addition to that, we are looking at another indication, which is, in fact, even larger. So, yes, to your question that this will expand the potential population, but we're looking at this second indication, which also has immune dysregulation and is a subset of primary immune deficiency. And we expect that over time, we'll be able to eventually resolve these VUSs. Now, again, historically, looking at other genes, that about 20% of VUSs get resolved and converted into disease-causing or what's called likely pathogenic or pathogenic. The other data point that we have is that we recently tested 25 of these VUS patients. Thanks, Anurag.
Susheela Hernandez: Thank you, Sushila. I am happy handing over to Anurag to start answering your questions. Anurag?
Anurag Relan: Hi, Susheela. So, with respect to your first question about the Phase 2 study that we're starting, so that one is in patients who have one of one of these several genes, so the examples I gave were p10,
Anurag Relan: CTLA-4 or ALPS-FAS. These are genes that are known to be linked to hyperactive signaling and these patients have an immune deficiency as well as an immune dysregulation or the dysregulation of oftentimes the predominant feature in these patients.
Anurag Relan: So that's the first indication that we're pursuing outside of APDS.
Anurag Relan: In addition to that, we are looking at another indication, which is, in fact, even larger. So yes to your question that this will expand the potential population, but we're looking at this second indication, which also has immune dysregulation.
Anurag Relan: And it's a subset of...
Anurag Relan: Primary Immune Deficiency.
Anurag Relan: and it has features, again, similar to APDS. So I think that's something you can see across these three potential indications is that they all have these features of immune dysregulation or autoimmunity and autoinflammation.
Speaker Change: So the second question was about the VUS resolution efforts
Anurag Relan: So, you know, what we've identified already is 1200 patients. So what does that mean? That means that these are patients who are have had a genetic test, usually as a part of a primary immune deficiency panel.
Anurag Relan: And again, these are patients that, you know, had genetic testing, most of which that we were not involved with. So they had this genetic testing performed, the result came back with a result that showed either in one of those two genes, this VUS result.
Anurag Relan: And we are aware of this through these databases that we have access to at large genetic testing companies in the U.S.
Anurag Relan: And we expect that over time, we'll be able to...
Anurag Relan: Eventually resolve these BUSs. Now we know again historically looking at other genes that's about 20% of BUSs get resolved and converted into disease causing or what's called likely pathogenic or pathogenic.
Anurag Relan: The other data point that we have is that we've recently tested 25 of these VUS patients.
Anurag Relan: and we had what's called functional testing performed in these patients and we found a similar number so about 20% 5 out of the 25 were then upgraded or reclassified into APDS.
Anurag Relan: So, you know, when you start doing some simple math, you see that this could significantly increase the population of APDS patients in the U.S.
Unknown Executive: So with regard to your question about the UK, Sushila, we currently have 11 patients on early access therapy in the UK. There are 61 patients identified, of which 37 are over 12 years of age, so there's already quite an interesting population in the UK available. And of course, we expect that once we have the reimbursement, which will take some time and will be somewhere, I suppose, normally in the first half of next year, those first patients will go on paid therapy pretty quickly.
Anurag Relan: Thanks Anurag. So with regards to your question about the UK, Sushila, we have currently 11 patients on early access therapy in the UK, 61 patients identified, of which 37 are over 12 years of age, so there is already a
Anurag Relan: Quite an interesting population in the UK available and of course we expect that once we have the reimbursement which
Speaker Change: We'll take some time and we'll be somewhere, I suppose.
Anurag Relan: Normally in the first half of next year, those first patients will go on pain therapy pretty quickly. And of course, by that time we will have also clarified the VUSs, and of course there will be in the UK also patients with VUSs.
Unknown Executive: And of course, by that time, we will have also clarified the VUSs. And, of course, there will also be patients with VUSs in the UK. So there will be additionally coming onto therapy as well. I hope that answers your questions, Sushila. Yes, we have broadened, we have basically a lot more incoming, and also, you know, we reached out to a lot more because we have now a Chief Business Officer on board since the last quarter of last year. That has led to quite a few interactions, which actually even resulted in some, you know, non-binding offers that we issued.
Anurag Relan: So there will be, additionally, coming potentially on to therapy as well. So that's the sort of numbers for the UK that we currently see. And of course, we continue to seek for patients in the UK. But there's already one per million identified, as you can see, from 61 out of a population of roughly 60.
Shreya: millions in the UK. I hope that answers your questions, Sushila.
Sushila: Yes, thank you. And if I may ask one other question. Could you provide an update on your BD efforts? Have you broadened your search? Thank you.
Speaker Change: Yes, we have broadened, we have basically a lot more incoming and also we reached out to a lot more because we have now a Chief Business Officer on board since the last quarter of last year. It has led to quite a few interactions.
Unknown Executive: But of course, you know, when you then look into due diligence, following your non-binding offer, you sometimes find stuff that you were not expecting. And of course, it is also sometimes possible that the other party does not necessarily, in the end, want to conclude the deal, because it takes two to tango, as you know.
Sushila: which actually even resulted in some non-binding offers that we issued. But of course, when you then look into the diligence...
Anurag Relan: Following your non-binding offer, you sometimes find stuff that you were not expecting, and of course, it is also sometimes possible.
Anurag Relan: The other party does not necessarily in the end want to conclude the deal, because it takes two to tango, as you know. But yes, there's been a lot of activity and we're virtually all the time assessing an asset.
Unknown Executive: But yes, there's been a lot of activity. And we're, you know, virtually all the time, assessing an asset under due diligence as we speak. So there's quite a lot of intensity here going on.
Anurag Relan: Under due diligence as we speak, so there's quite a lot of intensity here going on.
Anurag Relan: Thank you, that's clear.
Unknown Executive: Please stand by. And the next question comes from the line of Jeff Jones from Oppenheimer. Please go ahead. Your line is now open. And when would you anticipate being able to respond to the CHMP? Simon, I think you almost said January 26. And in that case, how does that impact your... Having said that,
Speaker Change: Thank you. We will now take our next question.
Speaker Change: Please stand by.
Speaker Change: And the next question comes from the line of Geoff Jones from Oppenheimer. Please go ahead, your line is now open.
Geoff Jones: All right, congratulations on the quarter, gentlemen. Good morning and thanks for taking the call.
Geoff Jones: Just two from us. You spoke to a degree early on.
Speaker Change: But for Rootkinest, with the anticipated launch as a competing product or competing products in 2025 and beyond,
Speaker Change: What do you see the impact to be and how are you planning your response?
Speaker Change: And then for Linneasland in Europe or in the EU specifically.
Speaker Change: Can you provide any additional detail on the work that needs to be done in completing your definition of regulatory starting materials?
Speaker Change: And when would you anticipate being able to respond to the CHMP? Simon, I think you almost said January of 26. And in that case, how does that impact your...
Speaker Change: your potential approval timeline.
Speaker Change: Thank you. All right, Jeff. Thanks. So let me just first answer your second question about Europe .
Speaker Change: Yes, we are, we have already initiated that work and we have a precise timeline. That's why we agreed with the European authorities to actually grant us the extension until 26.
Speaker Change: January 26. That is when we plan to hand in the response.
Speaker Change: We precisely do what they want, so that is also very clear.
Speaker Change: And then, in that case, we expect that probably towards the end of the first quarter, there could be an opinion, which we are quite confident because we have received confirmation of clinical benefit and safety of the product.
Speaker Change: And when we have resolved that, we are quite confident about the opinion being positive. So all that said, then it takes two months for the European Commission to confirm that. So in other words...
Speaker Change: You could expect that we enter the European, the first European market that's probably Germany in, let's say, the end of the second quarter, beginning of the third quarter of 26.
Speaker Change: That's basically the timeline at this point in time for entering the European markets.
Speaker Change: Oh yeah, the competition for Rukiness, thank you.
Speaker Change: Yes, well, the slide I showed about the heritage and geodema markets is there showing that basically Arucanest is protein replacement therapy.
Speaker Change: and Stephen alluded to the consistent response rates on Rupinest.
Speaker Change: Sibaltrolstat is a product that works on that bradykinin colloquium pathway and has of course good results. So it's good news for patients that there's new therapeutic options available. However,
Speaker Change: We're also aware that Cervaltrostat was tested in a patient population that is generally responsive to Icatiband or Ferrazier. And that's exactly the difference between the patient population that they tested.
Speaker Change: and the patient population that we are testing, i.e., that we are serving, i.e., we serve patients that have failed on e-catubant and, therefore, must use Zircones because they can't get by on a product that only serves the bradykinin color-created pathway.
Speaker Change: So, in other words, we're pretty confident that this, in the end, will not have a significant impact on arucanests going forward because we serve that unique patient population.
Speaker Change: Having said that, we are of course very aware that in the very beginning of the project being launched, a number of our patients, as we have seen with previous competitive entries,
Speaker Change: We'll try, of course, whether they can be successful in treating their hereditary angioedema attacks with the oral alternative.
Speaker Change: Having said that...
Speaker Change: You also have to realize that if you take a pill, which is of course a much more convenient way,
Speaker Change: And you actually then see that you have to take a second dose, which is not rarely the case with a product like Subaltros. If I read the clinical trials correctly.
Speaker Change: then that patient will continue to suffer enormously from that very, very painful hereditary angioedema attack. You really just have to realize that, right? And then if you take, after six hours of suffering, another pill—
Speaker Change: because the symptoms don't necessarily go away or come back. And that is a very different experience than when you are used to Rukinus, where you actually place a shot, which is admittedly less convenient because you have to basically place a shot, but you are well-trained and confident.
Simon Scholes: Unknown Attendee, Sijmen Vries, Sijmen Vries, Sushila Hernandez, Fanyi Zhong, Jabine Meijs, So I think you should really carefully consider those elements when you look at an incoming new competitor. That is, of course, good news for patients who now have to give stinging and painful subcutaneous shots, for instance, Ekatiband. And then the pill, of course, is a very nice alternative.
Speaker Change: Almost all of our patients do that in the in the privacy of their own home.
Speaker Change: Then you basically have a normal experience where almost immediately the symptoms start fading away and the attack doesn't come through.
Speaker Change: is, you know, basically, if you look at the Rukinus response rate, you see nothing about breakthrough attacks or hardly anything about, nothing about second shots being necessary.
Speaker Change: So I think you should really carefully consider those elements when you look at an oncoming new competitor. That is of course good news for patients who now have to give stinging and painful subcutaneous shots.
Simon Scholes: But unfortunately, for our patients, you know, they probably will not have the best of experiences in most cases. And we are therefore confident that Ruconest will continue to bring them the benefits and the good experience that they have had with Ruconest over a longer period of time. Again, having said that, we are aware, of course, that people will start trying this drug. But in the long term, we believe that Ruconest is here to stay.
Speaker Change: For instance, Ecatiband. And then the pill, of course, is a very nice alternative.
Speaker Change: But unfortunately for our patients, they probably will have not the best of experiences in most of the cases.
Speaker Change: And we are therefore confident that Ruknes will continue to bring them the benefits and the good experience that they have with Ruknes.
Speaker Change: over the longer time. Again, having said that, we are aware of course that people will start trying this this drug, but in the long term we believe that Rucanest is there to stay, hence why we showed this this slide where it is absolutely clear that the missing protein C1S trace inhibitor is the protein that we replace in a very good dose.
Simon Scholes: Hence why we showed this slide, where it is absolutely clear that the missing protein C1S3 inhibitor is the protein that we replace in a very good dose, in a very strong, in a very high doses and in a bolus injection with Ruconest that the protein is immediately there to actually make the attack go away. Sorry for the long winded answer, Jeff, but I thought it was necessary to actually explain this.
Speaker Change: in a very strong, in a very high doses and in the bolus injection with Rucanestat, the protein is immediately there to actually make the attack go away. Sorry for the long-winded answer, Jeff, but I thought it was necessary to actually explain these elements.
Unknown Executive: Yeah, greatly appreciated, Simon. And thank you very much for taking the questions. We will now take our next question. Please stand by. And the next question comes from the line of Alistair Campbell from the Royal Bank of Canada. Please go ahead; your line is now open.
Jeff: Greatly appreciated, Simon, and thank you very much for taking the questions.
Speaker Change: Pleasure.
Speaker Change: Thank you. We will now take our next question.
Speaker Change: And the next question comes from the line of Alistair Campbell from Royal Bank of Canada. Please go ahead, your line is now open.
Unknown Executive: Thanks, everyone. Thanks for taking the time. It can be quite convoluted, but we try to make that as smooth as possible throughout through our own patient services. So essentially, the first part of the process is obviously the patient coming in. That can take some years sometimes, although we're calling all those key centers of excellence. Then, once the symptoms are reviewed and the patient's worked up, it's the genetic test. And if they get that positive test, then they can immediately go into our enrollment program where we start to work with their payer on getting them approved.
Alistair Campbell: Thanks everyone, thanks for taking the question. I just really wanted to talk a little bit about Juenja. You've obviously got quite a significant pool of diagnosed patients.
Speaker Change: in the U.S., can you talk about the pathway from getting a diagnosed patient's...
Speaker Change: to be basically...
Anurag Relan: Unrolled What are the key hurdles you would have to overcome?
Anurag Relan: versus that process.
Anurag Relan: Yes, sir. I'll hand over to Steven here in this case.
Stephen Toor: Alistair, thanks for the question, and the is, as you'd expect...
Speaker Change: Can be quite convoluted, but we try to make that as smooth as possible through our own patient services. So, essentially, the first part of the process is obviously the patient coming in. That can take some years sometimes, although we're calling all those key centres of excellence.
Anurag Relan: Then, once the symptoms are reviewed and the patient's worked up, it's the genetic test and if they get that positive test
Anurag Relan: Then they immediately can go into our enrollment program where we'll start to work with their payer on getting them approved.
Unknown Executive: We've seen a mixed picture there with the payers, but what I will say is that our approval rate is at 98%, and that 2% is their NDC blocks. So they will eventually come on stream; they just take a little longer to actually pull through. The entire market access will manage care system.
Speaker Change: We've seen a mixed picture there with the payers for what I will say is that our approval rate is at 98% and that 2% is their NDC blocks so that they will eventually come on stream they just take a little longer to actually pull through.
Unknown Executive: So that's the kind of simplified version, which is, you know, patient comes in, patient gets diagnosed, they work with our patient services, and then land on therapy. What can sometimes slow things down, and that's why you see a bolus in the first part of the launch, then slower, but nevertheless still growth as we move forward, before those bigger inflection points that Anurag referred to with the VUS population of pediatrics, is that we're now into those groups where there may be other complications.
Anurag Relan: The entire market access will manage care system.
Unknown Executive: So perhaps they're on chemotherapy or, for whatever reason, there are other comorbidities that are being managed, so they remain within our diagnosed pool, and we monitor them, and we work directly with the doctor and, when we can, with the patient, so at the right time, they can move on to therapy. So I think that's a high-level overview of what happens with managed care. That's where we are today with the existing pool of patients before we get those next big boluses in 2025, 2026, and beyond. Is that okay, Alistair? Are there any other questions on that? Yeah, can I just follow up on that? So in terms of those, like, if you've got, let's say, a pool of 50 diagrams...
Anurag Relan: So that's the kind of simplified version, which is, you know, patient comes in, patient gets diagnosed, they work with our patient services and then land on therapy.
Anurag Relan: We can sometimes slow things down and that's why you see a bolus in the first part of the launch then slower but nevertheless still growth as we move forward in before those bigger inflection points that Anurag referred to with the VUS population and the pediatrics.
Speaker Change: is we're now into those groups where there may be other complications, so perhaps they're on chemotherapy or
Anurag Relan: For whatever reason, there are other comorbidities that are being managed, so they remain within our diagnosed pool and we monitor and we work directly with the doctor and when we can the patient so at the right time they can move on to therapy.
Anurag Relan: So, I think that's the high-level overview of what happens with managed care. That's where we are today with the existing pool of patients before we get those next big boluses in 2025, 2026 and beyond.
Anurag Relan: Is that okay Alistair? Are there any other questions on that?
Alistair Campbell: Yeah, maybe just, can I just follow up on that? So in terms of those like the, if you've got, let's say a pool of 50 diagnosed patients over 12.
Alistair Campbell: So you have some of these hurdles to maybe sort of get them on therapy, do you have any kind of sense of the pace at which you see them sort of come on to therapy ahead of the boluses to come? Just kind of get a sense of the tempo we should be thinking about in terms of patient ads before some of those big boluses you've pointed come through.
Alistair Campbell: That's right.
Alistair Campbell: It's...
Speaker Change: I would love to give you a specific answer on that, but unlike the mass markets I've worked in in the past, these are very low absolute numbers.
Speaker Change: So, for example, we added eight this quarter.
Alistair Campbell: I think it was two last quarter, and we have these ones that we're working through today. The good news is we would expect that to keep going, but it just won't be linear. Whereas if we say cholesterol lowering, you can very easily predict that. With this, I'll give you some examples. There was literally one patient who's going to come in in July because they needed to finish their school year first.
Speaker Change: So, but what I can say is that those over 40 patients or close to 50 right now that we're working through
Speaker Change: We know every detail there is to pretty much know about where they're at and what the tipping point will be.
Speaker Change: Even down to patients whose 12th birthday will be this year, you know, we're ready and primed to go and to speak to those physicians and say, okay, the 12th birthday is coming up.
Speaker Change: Are they in the right place now? Are they the right weight? Etc, etc.
Speaker Change: But the simple answer is, I couldn't give you...
Speaker Change: A good prediction on the pace at which all those patients will come in and over what time period.
Speaker Change: Only that we're working very hard on every single one of them on a very regular basis and in a very detailed way.
Unknown Speaker: Unknown Speaker, That's great. I appreciate it, Carlo. Thank you. Thank you. We will now take our next question. Please stand by. Yes, hello. Once you get the phase two data, I was just wondering what the further timetable might look like as regards phase three. Yeah, maybe.
Speaker Change: That's great. I appreciate it, Carlo. Thank you.
Carlo: Thank you.
Speaker Change: Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again.
Speaker Change: You will now take our next question.
Speaker Change: Please stand by.
Speaker Change: And the next question comes from the line of Simon Scholes from First Berlin. Please go ahead, your line is now open.
Simon Scholes: Yes, hello, thanks very much for taking my questions. I've got two. The first is on the second indication for Leni Olasib.
Simon Scholes: I gather that you're expecting the Phase 2 data early next year. Once you get the Phase 2 data, I was just wondering what the further timetable might look like as regards Phase 3.
Simon Scholes: And then the second question is on approval in Canada and Australia. I mean, you're now talking about 2025 for both markets.
Speaker Change: Can you give us a slightly more precise timing for those markets and is it likely to be H1 or H2?
Unknown Executive: First of all, Simon, I think you're a tad optimistic here with regard to when this Phase 2 study will be completed. Obviously, it's an open-label study, but I think you should think more about it, and Anurag, correct me if I'm wrong here, but by the end of next year, it's probably a more likely thing that we will have insights and can actually formulate how we are going about with regard to the following Phase 3 trial.
Speaker Change: Yeah, maybe. First of all, Simon, I think you're a tad optimistic here with regards to when this Phase 2 study reports.
Speaker Change: This is an open label study, but I think you should more think about, and Anurag correct me if I'm wrong here, but by the end of next year it's probably a more likely thing that we will have insights.
Anurag Relan: and can actually formulate how we are going about with regards to the following phase 3 trial.
Unknown Executive: And secondly, we don't necessarily always give detailed information on regulatory interactions because they can be a little bit unpredictable. But you're right, you have seen that these smart... We are anticipating that we will get regulatory action in 2025 from these and not necessarily in 2024.
Speaker Change: And secondly, we don't necessarily always give detailed information on regulatory interactions because they can be a little bit unpredictable. But you're right, you have seen that these markets...
Speaker Change: We are anticipating that we get regulatory action in 2025 from those and not necessarily in 2024.
Unknown Executive: Okay, yes, that's fine. Thanks very much. And then you heard, of course, how we are going to build a pipeline and a product by starting with a Phase II study for PIDs with immune dysregulation as a second indication for Djoengia imminently, and we are waiting for regulatory feedback for the start of a third indication, also a Phase II trial that we expect to start in the not-too-distant future. And last but not least... This concludes today's conference call. Thank you for participating. You may now disconnect.
Speaker Change: So basically, yeah, that is correct. I hope I answered those questions.
Speaker Change: Okay, yes, that's fine. Thanks very much.
Speaker Change: Thank you.
Speaker Change: As a reminder, to ask a question please press star 11 on your telephone and wait for your name to be announced.
Speaker Change: As there are no further questions, I would now like to hand back to Sijmen Vries for any closing remarks.
Sijmen Vries: Thank you very much, and thanks ladies and gentlemen for attending our conference. As you've seen, we've posted some stellar results.
Sijmen Vries: for both the second quarter and the first half of this year.
Speaker Change: We illustrate to you that we are very confident that Ruknes will be an important driver for our financials for the coming years to come, given the fact that we serve this very unique patient population despite expected competitive entries.
Anurag Relan: and Anurag Relan.
Speaker Change: We also showed you that, although indeed, as you heard, the growth for Joentgen is continuing this year, it is not going to be linear from Steven.
Speaker Change: but that we have a big bolus of patients expecting to come online in the United States.
Speaker Change: From beginning of next year onwards, because of the expected outcomes of the VUS, which will of course be an important growth stimulus.
Speaker Change: for Juenja in 2025 and 2026.
Speaker Change: You also heard that we expect that we get a positive discussion with the Europeans in the first quarter of 2026.
Speaker Change: and that we are working very hard on getting our pediatrics and our Japanese trials worked out so that we can actually submit to the Japanese authorities and enter the second biggest market.
Speaker Change: in the world, and have another at least 25% bonus of additional patients under the age of 12 available for commercialization, both at that point in time, of course, in the U.S. and the rest of the world and the European Union, where we expect to be on the market by then.
Speaker Change: And then you heard, of course, how we are going to build a pipeline and a product by starting with a phase two study for PIDs with immune dysregulation.
Speaker Change: as a second indication for Djoengia imminently and we are waiting for regulatory feedback for the start of a third indication, also a phase two trial that we expect to start in the not too distant future.
Speaker Change: And last but not least, about the intensifying efforts to enlicense or acquire new opportunities so that we can broaden our portfolio in rare diseases and build this global rare disease company.
Speaker Change: So, thank you very much for being here and we look forward to updating you on our next occasion at the end of October when we have our third quarter results. Thank you very much.
Speaker Change: This concludes today's conference call. Thank you for participating. You may now disconnect.