Pharming Group NV

AEX:PHARM

Earnings Call Transcript 2023-Q2

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Thank you very much, Adam. Good morning or good afternoon, ladies and gentlemen. Welcome to our Second Quarter and First Half 2023 Financial Results Call.

Next slide, please. I’m here with my three colleagues, Dr. Anurag Relan, our Chief Medical Officer; Stephen Toor, our Chief Commercial Officer; and Jeroen Wakkerman, our Chief Financial Officer, to take you through the highlights of these results and, of course, to answer all your questions that you may have afterwards.

But before I do that, of course, I would like to point you to the next slide that says something about forward-looking statements because we will be making some forward-looking statements, of course, today, that are based upon our current plans, belief, market circumstances, et cetera, that may, of course, change towards the future.

And then without further ado, I would like to move on to 2 slides ahead and basically share with you some of the excitement over the last six months that we had, of course, and we had a very busy six months and indeed made a lot of progress.

And – but first and foremost, we’re, of course, very, very pleased to see that RUCONEST did it again, so to say, 20% growth over the second quarter results versus the first quarter is, of course, a very spectacular recovery from what was a one-off weakness in the first quarter.

And that means that if you look at it, we’re very confident that we can actually continue to be on track for the low single-digit growth for the entire year. And we say that based upon the leading indicators that all point in the right direction. Of course, Stephen, will talk a little bit more about that later in his part of the presentation.

Now that significant cash flows, of course, that RUCONEST has been generating over the years not only helped us to, back in the days of 2019, in license Joenja from Novartis but also helped us, of course, to finance the development of Novartis and of course – of Joenja, and of course, to actually prepare for the successful U.S. launch, and that’s exactly what happened.

The FDA approved the product a couple of days before the PDUFA date, and we were very quickly off to a strong start in the market and you’ve seen that. And I dare to say that in a ultra-rare business, having already 43 patients on paid therapy in the first quarter that you report results out of 60 that are already in the pipeline as of 30 June is no mean feat and it’s a testament to the preparation of our U.S. colleagues. And of course, it beats analyst expectations in so far that I have seen analyst reports predicting first quarter sales for Joenja.

We’ve also made a lot of progress, of course, in the regulatory reviews. We’ve submitted the file to a number of other territories, Canada, Australia and Israel. And of course, we made strides forward with a pediatric clinical program, of course. And that’s important because the current – although the current license for Joenja already incorporates the 12 years and upwards, so already partly the pediatrics, there is a big unmet medical needs to be fulfilled in those children younger than 12 years. And we’re working very hard to actually get that pediatric program done so that we can actually submit the file for the extension with – towards the younger children.

And then, of course, the third pillar there on that slide is, of course, as important, if not more, for the – let’s say, for the future significant inflection point that we believe that we can achieve with leniolisib, that is the second indication. And we, as you may have read already, have been already submitting our plans and have initiated discussions with the FDA on how – on our proposed development program for the second indication and Anurag will come back to that a little bit later.

Of course, last but not least, we continue to look intensively for in-licensing – additional in-licensing opportunities for rare disease assets that can actually further leverage our commercialization structure that we have in place.

And next slide, please. There you see a visual of the pipeline that has now changed. Of course, we’re still, of course, under review with the – in the European Union and the UK. The pediatric trial is, of course, has started.

Leniolisib Japan, we’re on the brink of starting that trial that we agreed with the Japanese authorities to do. Anurag will come a little bit later on Japan. And of course, you see here that we made progress, as I just alluded to, by submitting the files towards the Canadian, Australian and Israeli authorities, such as to increase the footprint for leniolisib or Joenja, called later in geographical footprint.

And then, of course, we also made great strides forward – next slide, please, with our leadership, strengthening of our leadership. We are very pleased to have found Dr. Richard Peters, as new Chairman elect to succeed Paul Sekhri, who came to his maximum term as allowed under Dutch law as Chairman of our company.

As you can see from the outline on Dr. Peters, he’s got an impressive track record, lot of experience in the health care industry, but also in academia, but especially in the rare diseases business with very successful companies such as Genzyme or Sanofi Genzyme, as is called nowadays. He’s been CEO of two NASDAQ-listed biotech companies. As you can see, he held positions in earlier successful companies such as Amgen and Sanofi. And of course, he is a medical doctor by education and has actually also served as an editor for a very prestigious journal.

So we’re very pleased that Richard was happy to join us as our Chairman elect and of course, we will organize an extraordinary general meeting of shareholders in the not-too-distant future to actually get him elected.

And then we’re very pleased as well to – and especially in the context of our growth strategy and our ambition to actually in-license or acquire additional late-stage assets for rare diseases, that Alexander Breidenbach has agreed to join us as our Chief Business Officer, who will be tasked with the growth strategy, the development and execution of our growth strategy and our future plans.

And he’s a very experienced individual as well at several senior positions, most recently as Chief Business Officer and Chief Development Officer at ACM Biosciences, a Swiss Basel-based company, but also a very distinguished and long career in Roche in Basel in the business development group. So we’re very pleased to have strengthened our team with these two extremely experienced and talented individuals.

Next slide, please. Let’s just look at – and then the next one, please, at what it actually means and what it brings, and what we need and what is our bread and butter, that’s our very strong rare disease commercial infrastructure. We have what it takes to actually be successful at this. We’ve already proven that, and we’re about to prove that again with Joenja going forward.

So we have these dedicated sales forces in the U.S., European Union and also we have people in the Middle East and North Africa, calling on these immunologists and academic hospitals. We have medical affairs team and that’s – medical affairs teams, that’s, of course, very important, especially in rare diseases as we have a very strong medical affairs team that include medical directors, medical science liaisons, molecular geneticists and publication specialists; very big medical teams that are absolutely essential for your success in commercialization of rare diseases.

And then, of course, as market access becomes more and more important, we have built up our market access teams over the last few years on both sides of the ocean. They include national directors in the U.S., health economic research specialists and directors, both sides of the ocean to actually work with the authorities to get the product to reimbursement. And you’ve seen how quickly we got the product reimbursed in the U.S. So I think we have an excellent team in place there.

And then there’s patient support teams, hub services in the U.S., reimbursement managers, patient care managers. We have a third-party nurse force to take care of our patients and clinical educators.

And then last but not least, we’re extremely active with everybody, including our sales force teams to be at conferences. And there’s a lot of education – disease education ongoing also directly to patients that we actually facilitate. We support the patient organizations and all.

So basically, it’s an extremely well-oiled team and that has shown that, for instance, with the launch of leniolisib, they know what they have to do, given the fact that we got it immediately reimbursed and found and identified those patients in a new disease, right? The disease was not even discovered 10 years ago.

And as you can see on the next slide, we’re really ready to leverage all of this for Joenja as and when Joenja gets approved, of course. And as you heard earlier, we’ve also now decided to expand to Australia, Japan, of course, and Canada that are not yet on this map because it’s just the established business.

Okay. And then one more slide from my end here about the durable commercial asset that RUCONEST represents. It’s quite rare, I would say, that a product that’s already nine years in the U.S. market is still growing and is still getting more and more meaningful. Why is it getting more meaningful and why is it growing? Because it has a very special place. It’s the only recombinant protein replacement therapy that is available in the hereditary angioedema market.

And that’s very important because although there is a big trend has been going towards prophylactic treatments for hereditary angioedema and those prophylactic treatments have become better, there’s also the notion and the fact that almost half of these patients suffer from so-called breakthrough attacks under their prophylactic therapy. That’s when it becomes important to have your breakthrough medication at hand at all times. And this is actually where RUCONEST is now beginning to make inroads and being used for breakthrough medication.

And that is a very important aspect because it means that more and more patients are discovering that it is the right drug to have for your breakthrough – as breakthrough medication and that more and more physicians are actually discovering that RUCONEST is the right choice for the patients at breakthrough medication.

And yes, RUCONEST is an IV drug that is self-administered, but we also know that the absolute vast majority, almost all patients are very, very confident and very well trained to actually do these self-injections, and they’re perfectly happy with that because they can rely on the product.

And you can see it on the slide here, that has an incredible good track record with regards to efficacy and they can basically count on to stop that breakthrough attack as it becomes clear that they’re getting a breakthrough attack. That’s why we think that RUCONEST has this very special – we know that RUCONEST has this very special place in the market and we’ll continue to have this very special place in the market going forward.

And then I would like to switch over to APDS, and I’ll switch over to now ask for Anurag to present the Joenja story. Anurag, over to you.

[Anurag Relan, Chief Medical Officer]

Thanks, Sijmen. And on the next slide, we can see a little bit of information about APDS, which is a rare, serious and progressive primary immune deficiency, and, as you heard from Sijmen, just first described about 10 years ago.

We think that APDS affects about 1.5 million – 1.5 patients per million based on literature estimates and our own patient finding efforts. And I’ll talk a little bit about those patient-finding efforts in a moment. But with those efforts, we’ve identified now more than 640 patients in key global markets already. We think that, that represents a portion of the total of 1,500 patients or so that are out there with APDS.

The signs and symptoms of APDS vary widely, and as with many rare diseases, there’s also a significant delay to diagnosis because of these varying symptoms and the rarity of the disease. These delays result in significant morbidity and mortality for these patients. And it’s something that we’re really trying to address with our own patient-finding efforts and making Joenja available, of course.

The treatments for APDS up till now have been focuse on symptom management. So really, when we think about the problems that these patients face, so with infections, so giving them antibiotics or giving them immunoglobulin replacement therapy, really not addressing the root cause, however. A genetic test, however, is a very simple way to make the diagnosis of APDS, and we’ll talk a little bit about some of the things that we’re doing on this front, too, in a moment.

On the next slide, we can see that Joenja was now approved by FDA earlier this year. Joenja modulates this hyperactive pathway and as a result, allows the immune system now to develop properly. This development of the immune system when it occurs improperly in these APDS patients leads to all of the problems that we see in these patients with autoimmune phenomenon as well as all of the infection-related problems that these patients face. With Joenja, we can try to balance this pathway and to support this immune function in a proper manner.

Next slide. And here’s a highlight of some of the data on Joenja. You can see in the top left, the indication statement that Joenja is approved in the U.S. to treat patients who are 12 years and older with APDS. And this was on the basis of a randomized placebo-controlled study, which showed that Joenja met both co-primary endpoints as well as meeting the several secondary endpoints and exploratory parameters as well.

From a safety standpoint, there were no drug-related serious adverse events or withdrawals due to Joenja in the study. But more importantly, what we saw was that when patients took Joenja on a long-term basis in the open-label study, we saw many other downstream clinical benefits, including reductions and discontinuation in the use of IVIg or immunoglobulin replacement therapy as well as reduction in infection rates.

And these results were consistent with what we saw in the randomized double-blind, placebo-controlled part of the study. And we continue to collect further data and we’ll report this data on lymphadenopathy as well as some of the biomarkers that were collected in the study, including markers of abnormal B-cell development as well as the production of some of the antibodies that we see are elevated in untreated APDS patients.

And as you’ve seen from our data so far, we’re off to a good start with the patients being able to start Joenja very quickly in the U.S., and Steve will report on this progress further shortly.

Next slide, please. And what are we doing now to look for APDS patients? So when we think about APDS, it’s really part of a larger pool of patients with what’s called inborn errors of immunity or sometimes also called primary immune deficiency. And through those efforts, we’ve, as I said, identified more than 640 patients worldwide with APDS, among which, there are 200 identified in the U.S.

Those efforts, you can see in the box on the left, are really focused around education, testing patients, family testing, multiple medical affairs activities, including raising awareness about the disease, raising awareness about the condition itself and really working with patients and clinicians to help identify patients.

But we also know, as with most rare diseases, there’s a large pool of undiagnosed APDS patients. So we’re out there with our medical and commercial teams trying to identify these patients. We know that many of these patients are seen by immunologists, but we also know that they’re also being seen by other providers where they don’t even have a diagnosis yet of a primary immune deficiency or an inborn error of immunity. And we’re making available in the U.S., a comprehensive genetic testing program to help get those undiagnosed patients the proper diagnosis.

And as a result of this genetic testing and the wider spread use of genetic testing, we’re also encountering many patients in the third box here on the right, and these are patients who have a result that is inconclusive, and this is called a VUS or a variant of uncertain significance. And what that means is that they have a variant in one of the two genes that leads to APDS, but that variant has not been described previously. There’s not much information in the literature about it or there is no information in the literature about it.

So we’re doing a number of efforts now to help those patients, which there are a significant portion of, that have this inconclusive results, that have a primary immune deficiency, that have already pathogenetic tests, but have a result that doesn’t give them a final diagnosis.

And we’re doing a number of things that you see there, including looking through the literature, going to other clinical laboratories and seeing what testing may have been done. We’re also embarking on functional testing, both in the U.S. as well as worldwide and then importantly, family testing to try to see if we can figure out if this variant is present in other family members and if those family members also have the condition or not.

And as we move forward, I expect that we’re going to find a significant number of patients in this population of patients who currently are sort of in limbo with this variant of uncertain significant diagnosis currently.

Next slide. And then thinking ahead beyond the FDA, as you heard from Sijmen, we are continuing to work with the European regulators, and we expect an opinion from the CHMP later this year with a potential approval subject to a positive opinion two months later.

We – and then if we think about the UK, if the CHMP issues its positive opinion, we can file in the UK very soon thereafter with a potential approval also two months later. The Japanese clinical study is open for enrollment and I expect the first patient to be enrolled and treated there in this quarter. And as you heard from Sijmen, we’ve also made progress with filings in Canada, Australia and Israel.

We’ve launched our named patient program to make Joenja available in certain markets. And we announced earlier this year that the pediatric patients are able to enroll in the first pediatric study, which is in the age group of 4 to 11 years old.

And as Sijmen mentioned, we’re also making significant progress in looking at other indications for leniolisib. And I expect to be able to talk about this in greater detail later this year toward the end of the third quarter, beginning of the fourth quarter, as we go through some of the regulatory discussions about our clinical development plans.

Also later this year, we’re going to be starting our second pediatric study. And so this is in the youngest age group. These are, again, patients who are aged one to six years old, and I expect to be able to start that study in the third quarter of this year.

Next slide. And just a quick update on where we are with EMA and the progress that we’ve made so far. So as you know, we submitted our responses to the CHMP Day 120 list of questions. And just a couple of weeks ago, we received further questions or what’s called list of outstanding issues as part of the Day 180 procedure.

We also understand now from CHMP, and we’re quite pleased with this, is that the CHMP will consult an ad hoc expert group. And they’ve acknowledged that the condition is rare and there’s an unmet need here and they’d like to see further guidance from an ad hoc expert group of clinicians to talk a little bit about APDS and the leniolisib trial results to put them in context.

This will be a closed meeting that will involve Pharming representatives where we’ll have some leniolisib investigators as well as APDS patients. And as I said earlier, we’re expecting the CHMP opinion in the fourth quarter of this year and, subject to a positive opinion, an approval two months later.

Next slide. And it’s over to Steve.

[Stephen Toor, Chief Commercial Officer]

Thanks, Anurag. Good morning, and good afternoon, everybody. I’m going to provide you with a short update on RUCONEST progress in Q2 in the first half and also the Joenja launch in Q2 of this year.

Next slide, please. So as Sijmen touched upon already, the disruptions we saw in the first quarter were HAE market-wide, and they also affected our competitors. And as I indicated in the Q1 call, they were transitory. In the second quarter, RUCONEST performed well.

The leading revenue indicators, including growth in unique prescribers, new patient enrollments and vials shipped to patients were all strong. In fact, new enrollments have hit 70-plus for both Q1 and Q2 despite the Q1 market issues. And this really clearly reflects the underlying demand in the HAE market and for RUCONEST specifically.

In the second quarter, RUCONEST revenues globally increased by 20% compared to the first quarter. And furthermore, we saw a 2% increase in revenues when comparing the second quarters of 2023 and 2022. So given the strong bounce back in the second quarter, which we did signal in the Q1 call, we’re maintaining our outlook of low single-digit revenue growth for the rest of 2023.

Next slide, please. This slide shows the number of unique prescribers continues to grow in the U.S., 687 represents 62% of the HAE prescribing community and is still growing nine years post-launch, as Sijmen mentioned earlier. And that’s despite the significant changes to the market throughout those years.

This clearly shows that despite the prophylactic launches and the genericization of FIRAZYR, there remains both a place and need in the treatment armamentarium for a C1-esterase-inhibitor and an enduring need for RUCONEST. We expect to continue growing the unique prescriber base in the coming months and years and with, of course, the base of patients that benefits from RUCONEST.

Next slide, please. So let’s turn now to the Joenja launch. As you would expect, Pharming has brought its A game and all its rare disease commercialization experience to bear in the U.S., which, as with all companies, is a must-win market. We have 54 salespeople and leaders comprised of the existing RUCONEST team, where approximately 30% of APDS patients reside, and then the Joenja institutional team, which joined us in August of last year. They focus on the centers of excellence to which the other 70% of APDS patients either already are being treated or will be referred to.

These two teams, along with other colleagues that Sijmen already outlined in an earlier slide, are tasked with both identifying patients and ensuring HCPs have all the information and education they need to confidently prescribe Joenja. We also have, amongst others, clinical educators to drive family mapping and testing. I think Anurag outlined how important that is.

And just to reiterate, APDS is not the same dominant condition. So there’s a 50-50 chance that siblings and other family members are also going to have APDS. And so family testing is critical for both them and their welfare and the long-term growth of Joenja, which, as we know, is a progressive disease.

Okay. Next slide, please. Just briefly before I pass over to Jeroen, a couple of things around the value proposition. As Anurag already shared, and we should just remind ourselves, this is the only indicated option for APDS patients, it’s a precision medication. That’s important.

When a physician – when a patient tests positive and a physician prescribes, both the physician and the payer know they’re prescribing a treatment that will actually work on modifying the root cause of the disease. Hence, at Pharming, we knew, therefore, that we were launching a product that physicians and the underserved patients would need access to and access to quickly. So let’s briefly look at the impact on a patient.

Next slide, please. So this is John. He’s a 20-something-year-old man who’s been dealing with APDS since he was 11 years old. Like most patients, he’s been in out of hospital, was having difficulty developing social skills, keeping friends, and was basically willing to try anything to remove the stress and the burden of taking 11 pills in the morning and nine pills at night to try and manage his symptoms. Joenja, of course, has removed that heavy pill burden and is treating the underlying cause of John’s APDS.

Since being prescribed Joenja, John’s life has already changed significantly for the better. His lymph node have decreased in size. And I think you can see the thought bubbles, his quote around that, his perception that they’re actually gone as opposed to just being reduced in size. And importantly, he’s starting to think about his future and what he wants to do in life.

And as you see here, that includes actually going to college, something he couldn’t have envisaged previously. That’s basically the promise that Joenja can and will continue to deliver for our patients, and it’s what will continue to fuel out this launch phase and also our future growth.

Next slide, please. So as we discussed in the last call, the preparation for this launch was very, very rigorous and thorough. And as expected, we’re off to a very good start. Our first fully reimbursed commercial shipments of Joenja occurred within two weeks of FDA approval, which is very quick and certainly unusual. And to date, we’ve enrolled 60 APDS patients and shipped to 43 of them on payer-approved product with the remaining 17 to the end of the first half in process.

With respect to market access, the teams are doing outstanding work, and we continue to make good progress partnering with the national and regional payers, including state Medicaid programs to prepare for clinical review and coverage policy development, many of which are now rolling out. And to date, no patient has been denied access to Joenja.

So as you can imagine, we’re very pleased with the first quarter of post-launch progress and expect to build on our early success in the coming months to both get eligible patients on therapy and grow the patient funnel for future patients. And that will continue the brand growth and of course, lay the foundations for Pharming’s continued success into 2024.

So now I’d like to hand over to Jeroen, who will cover the financials.

[Jeroen Wakkerman, Chief Financial Officer]

Yes. Thank you very much, Steve. Good morning, good afternoon, everybody. Moving to the next slide on the financial highlights for the second quarter of ‘22. Our revenues grew to $54.9 million, which is a growth of 9% versus last year. And the $54.9 million consists of $3.8 million of Joenja sales in the first quarter that we obviously report that Joenja sales, $51.1 million from RUCONEST. And that is a growth of 2% from last year’s second quarter, but 20% even from Q1. So a very strong recovery, as Sijmen and Steve mentioned before as well from Q1.

Gross profit grew to $49.2 million, which is plus 7%, which is roughly in line with the growth in revenues. Operating costs increased by $23.4 million, and that’s on a number of items, mostly marketing and sales, but I’ll give you some more detail later.

Also important to understand for the second quarter is that we had in what we call other income, so that’s between gross profit and operating costs in the P&L, we had an income of $21.1 million for the sale of the priority review voucher to Novartis, which was as per the agreed contract in 2019.

And also good maybe to tell you that in the last year’s second quarter, we also had some big other income that was connected to the BioConnection transaction, as you may remember, which brought us in $12.8 million. To cut a long story short, the increase in other income from this year to last year was $8 million.

Then on the operating profit, $5.3 million. That’s a decline and that’s roughly in line with the increase in the operating costs and the net profit went from $15.7 million to $1.3 million, so a decline of $14.4 million. And that is, by the way, an improvement from Q1 where we had a loss in – net loss in the quarter.

And if we look at the first half results on the next slide, total revenue grew by 1% to $97.4 million, the gross profit $87.6 million with a gross margin of 90% was a good gross profit income. Operating costs, $118.5 million from $82.2 million last year. So that’s an increase of $36.2 million, more detail about that later. The operating profit was $8.4 million negative, so an operating loss, so to say, and the net loss was – has been $10.9 million so far in the year.

If we then look at the revenue breakdown for the last few quarters on the next slide, you see indeed the enormous growth from Q1 and – well, the drop obviously was from the reimbursement issues that were apparent in the whole HAE market. But we showed that strong recovery of 20% in the second quarter to $51.1 million. And you see the $3.8 million sales from Joenja for the first time in our history.

Moving to the next slide on the costs, because they went up significantly, just a bit of color on where we spent the money. So in the second quarter, we had $10 million of milestone payment to be paid to Novartis related to Joenja. And we had a – basically, over time, you see a substantial increase in marketing and sales to support the launch of Joenja. So Steve just mentioned that the launch preparation was rigorous and thorough and that’s also what you see in the money that we spent on Joenja.

You see there a fairly stable development of G&A costs and an increase in R&D in the second quarter of this year of $5.3 million, which is largely related to the work we’re doing on approvals in several international markets like Europe, Canada, Australia and Israel and a buildup of our medical departments, both in U.S. and in Europe.

So apart from the cost categories, another way of looking at the increase in costs in the first half of this year, that was plus $36 million is that – so we spent $10.5 million in total on the milestones. We spent $7 million of the $36 million increase on leniolisib out-of-pocket expenses, think about R&D cost, but also marketing, market access and amortization cost of the license.

And we added $16 million of payroll and general expenses. Most of it is in payroll because we increased the number of people since last year from 319 at the end of the second half last – at the end of the first half last year to 383 now, so an increase of 64 FTEs. And that is across the board, most of them in marketing and sales, but across the board with growing the company as an investment in future growth.

But a short overview on the next slide of the cash flow over the last quarter. It increased by – the cash and cash equivalents increased by $8 million to $192.4 million, and that was mostly related to the sale of the priority review voucher, which is considered a cash flow from investing activities.

So that was the overview of the financial highlights. Then going to the outlook for this year on the next slide. We – driven by the strong recovery, we continue to guide on low single-digit growth for RUCONEST revenues for the full year. Joenja was approved at the end of March by the FDA, and we’ve been commercializing the product since April this year.

We expect a CHMP opinion for the EU in the fourth quarter of this year and the marketing authorization, subject to that positive outcome, two months later for Europe. In the UK, we will be filing leniolisib with the MHRA following the European Commission Decision Reliance Procedure. And again, that is subject to the positive outcome of the EMA review.

We continue to invest in operating costs to accelerate the growth of Joenja and RUCONEST and further details on the plans to develop additional indications for leniolisib will be provided later this year. And last but not least, we continue to look at investments on acquisitions and in-licensing of mid to late-stage opportunities in rare diseases to build the company further.

With that, I want to move to the next slide and give back to the operator to operate the Q&A, and please feel free to ask any question. Thank you.

[Operator]

Thank you. [Operator Instructions] And our first question comes from Christian Glennie from Stifel. Christian, your line is open. Please go ahead.

[Christian Glennie, Stifel]

Yes. Good afternoon, guys. Thanks for taking the question. I guess we’ll start with Joenja. And just initially on – just to explain or sort of clarify the 60 patients on enrollment versus the 43 on paid therapy, is it the case that some of those are – they’re on therapy, the other 17 are on therapy already, but still working through in terms of reimbursement? Or how should we think about those – the balance of those 17?

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Christian, when patients actually are enrolled, they get a free starter pack, which is a one-month supply of Joenja. So yes, once they are enrolled, they have access to the medication, so they have it and then, of course, the administrative procedures to get them reimbursed starts. And if that happens within the months, the second month will be a commercial pack. And if that procedure is not yet finished then there will be another month’s supply in the form of a bridging pack provided. So to answer your question, yes, they’re all having access to therapy once they enroll. I hope that’s clear to you.

[Christian Glennie, Stifel]

Yes. That’s good. Thanks. And then in terms of the patient – identified patient numbers, you’ve added 140 in terms of 640 versus the 500 you previously reported. I noticed that the U.S. has stayed the same. Just where is those extra 140 patients come from? Is that mostly these new international markets, Canada, Australia, Japan or where are they from?

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Could you comment on that, Anurag? Is that possible?

[Anurag Relan, Chief Medical Officer]

Sure. Hi, Christian. So we are finding patients – we’re continuing to find patients in the U.S., but we’re also finding patients in other markets. So that does include Japan, Australia and other markets where we intend to commercialize first.

[Christian Glennie, Stifel]

Okay. Thank you. And then in terms of the – you’ve got 200 patients in the U.S. identified, if you do your 1.5 per million in the U.S. there’s potentially about 500 or so out there. That’s already a 40% diagnosis rate. Where do you think that could – that diagnosis rate could go over the next few years in terms of identifying patients?

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Would you like to answer that as well, Anurag?

[Anurag Relan, Chief Medical Officer]

Sure. So we definitely see this trending up. I think when we think about markets in Europe and some other countries across the world where there are more centralized health care systems, we can see that the prevalence there already exceeds 1 per million. In the U.S., of course, we have a more distributed and less centralized system.

So the diagnosis of these patients is – and the care for these patients is a little bit more fragmented. And so we expect that, over time, that diagnosis rate will go up as there’s increasing awareness of the disease, but that there’s also an available therapy available for these patients.

So I think that we expect that to increase at the minimum approach what we see in some other countries, but likely increase beyond that. And that’s why we think we’re being reasonable about an estimate of 1.5 per million.

As I mentioned earlier, there is a significant population of patients that we found beyond the 200 in the U.S., for example, that have these variants of uncertain significance or what are termed to be VUS. And I think that, that will – that’s another pool of patients who have symptoms of a primary immune deficiency, have had a genetic test, oftentimes, that’s well before we’ve been involved in the picture even, but they still don’t have a clear diagnosis. And I think this will likely lead to an increase in the number of diagnosed patients over time.

[Christian Glennie, Stifel]

Sorry, as a quick follow-up to that then, is it your understanding that those patients would also be appropriate for Joenja even if they haven’t got sort of formally defined genetic mutations that are driving APDS currently, or understood to drive it?

[Anurag Relan, Chief Medical Officer]

Yes. That’s correct. They would be appropriate for Joenja because they would have APDS if that’s confirmed. Right now, they have a – oftentimes, they have symptoms and clinical manifestations of APDS, and they have variants or mutations in one of the two genes that leads to APDS.

The question is, are those mutations, are those variants disease causing? And that’s part of the effort that we’re helping clinicians gather information, get access to further testing, and help them resolve that question for those patients because they’re also, like I said earlier, sitting in limbo and don’t have a clear diagnosis yet. If they get a clear diagnosis of APDS, then those patients would be potentially eligible for treatment with Joenja.

[Christian Glennie, Stifel]

Thank you. One final one, if I can, and I’ll get back in the queue. Is there any possibility to give any rough sort of guidance for Joenja for the year, whether that’s in terms of patient numbers or revenues? Obviously, you’ve got 60 patients in the program already, $3.8 million revenue in the second quarter. That 60 patients is already a 40% penetration of the 150 patients in the U.S. that are over 12. So any sense for penetration rates or patient numbers by the end of the year would be great.

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Yeah, I understand that, Christian, but it’s early days, right? And yes, we’re off to a good start. And we would like to see a bit more development of numbers. Obviously, the numbers are ticking up all the time, right? And we’ll keep you updated on a quarterly basis for now until such time that we get a little bit more feel for the market and the development going forward. And then we will start giving some different guidance.

So for now, no, not yet. You have to be a little bit more patient for that. But we will eventually, of course, do that. But we’ll keep you, on a quarterly basis, updated on the number of patients that are on therapy and are enrolled, okay?

[Christian Glennie, Stifel]

Yes. Appreciate it. Thank you.

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Thank you.

[Operator]

The next question comes from Joe Pantginis from H.C. Wainwright. Sir, your line is open. Please go ahead.

[Joseph Pantginis, H.C. Wainwright]

Hey, guys. Thanks for all the details. I appreciate it. So a couple of questions on the initial dynamics of the Joenja launch. So I guess – and of course, prefacing it by, this is all early still, what is the general time it takes or approximate time it takes to get drugs to patients once they’re identified?

And then second, when you look at these numbers, the 60 and the 43, how many patients have gotten the drug or are on the drug, of the revenue number that you posted today, which, like you said, beat overall expectations, how much of that, if any, is based on just getting drugs into the inventory channel? Thanks.

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Okay, that’s an excellent question, probably for Steve to go into a little bit more detail. Steve, could you pick that one?

[Stephen Toor, Chief Commercial Officer]

Yes. Sure. Thank you so much. Good morning, Joe. Sure. So the first thing is, as Sijmen alluded to, once the patient’s enrolled, we give the starter pack out, and so they’re on therapy pretty quickly. And then in terms of the time it takes to get drug – sorry, to get approval for patients, it’s typically, we’ve seen so far between four and six weeks, which is pretty quick. We’ve seen one or two is a little quicker or one or two is a little more, but think of it in a four to six-week period.

So we’re not having to bridge too many patients beyond the starter pack. And then in terms of stocking, it’s almost zero. We put some in right at the very start. We were able to process patients very quickly after launch, which means we burned through that very quickly. And the way in which our partner works, PANTHERx, means we’re basically practicing just-in-time delivery. So for the most part, that revenue is generated by demand – by patient demand.

[Joseph Pantginis, H.C. Wainwright]

That’s great to hear. Thanks. And then, oh, yes, absolutely. So I feel I have to ask my next obligatory question that I usually go to. When you look at OTL-105, so obviously, you’re holding it close to your chest, but I’m curious, with the ongoing preclinical models that you’re doing, will we be able to see or when we’ll be able to see any of the data coming out of these models?

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Would you like to comment on that, Anurag?

[Anurag Relan, Chief Medical Officer]

Sure. Good morning, Joe. So we’re making progress together with Orchard in those models. I don’t have a firm timeline that I can say that it’s going to – this is going to progress in the next couple of weeks or not. But I can say that I expect probably toward – later this year, we should be able to provide some further updates on where we are with that program, the data that those preclinical models are generating, and how we plan to move the program forward.

[Joseph Pantginis, H.C. Wainwright]

Great. I appreciate the details, and nice to see the strong launch on Joenja.

[Anurag Relan, Chief Medical Officer]

Thank you.

[Operator]

The next question is from Sushila Hernandez from VLK. Sushila, your line is open. Please go ahead.

[Sushila Hernandez]

Yes, Thank you for taking my questions. Also on Joenja, so you mentioned it takes four to six weeks to get approval, but could you also elaborate a bit more on the time from identification to enrollment? Could you share a bit more on that? Thank you.

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Steve, would you like to comment on that?

[Stephen Toor, Chief Commercial Officer]

Yes. Thanks. So it’s obviously variable, but relatively quick once a physician and the patient have that discussion, it’s literally governed by the time it takes to complete the form, send it into the hub, and then generate the starter pack. So I mean it’s a day to a week, but really dependent on the speed at which that process happens. But it can be very, very quick, easily a day or two.

[Sushila Hernandez]

Okay, that’s clear. And just on RUCONEST, you mentioned that over 70 quarterly new patients. Where are these patients coming from? Are these treatment-naive patients or did they switch?

[Stephen Toor, Chief Commercial Officer]

For the most part, these will be switch patients. At this point in the evolution of the market, there are very few treatment-naive patients. So these are patients who are either not satisfied on their current acute therapy, or require, as per the guidelines, a second acute therapy to make sure that they have what they need to do with any breakthrough attacks.

[Sushila Hernandez]

That’s clear. Thank you. And then a final question, could you share progress on your BD activities? How is it progressing?

[Sijmen de Vries, Executive Director and Chief Executive Officer]

That’s a good one, Sushila. We have a very active team. I think if I sort of remember some numbers, they turned over 150 opportunities over the last 12 months. There were – the vast majority, of course, was quickly disposed off. But then we have an internal community, including Anurag and Stephen, who look and take a next look. And then, out of that, a much smaller number, of course, comes to the fore, and we do some more analysis on that. And we’ve done a few due diligences over this last year – just last year as well.

So we’re making – I think, I can say the efficiency of the BD process has significantly improved over the last year. And we came, a couple of times, very close, but we’re very careful, of course, with the first one. And as you know, in business development, it’s all or nothing, right? There’s no deal or there’s a deal.

So – but yes, we remain optimistic about being able to acquire or in-license, preferably in-license, of course, that’s the preferred mode of action, and another asset that is in mid to late-stage development so that we can actually plan for another asset to be launched in the not-too-distant future. And that’s all I can say at the moment, I’m afraid.

[Sushila Hernandez]

Okay. Looking forward to updates on that front as well.

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Thank you.

[Operator]

[Operator Instructions] And the next question comes from Natalia Webster from RBC. Natalia, your line is open. Please go ahead.

[Natalia Webster, RBC Capital Markets]

Hi there. Thank you for taking my questions. And I just have two, one on RUCONEST and one on the leniolisib. So on RUCONEST, we saw an improvement in Q2 and you reiterated your guidance for the full year. But I was wondering if there’s any risk of the reimbursement issues that we saw in Q1 reoccurring at all. And then also you mentioned sort of strong market demand and continued growth in unique prescribers. But I was wondering if you’re able to provide some color specifically around what you’re expecting for H2 and sort of in the near-term into 2024.

And then secondly, on leniolisib – or do you want to go to that first? I can ask the next one after?

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Yes, probably a good idea to let Stephen answer that question first, you’re okay?

[Stephen Toor, Chief Commercial Officer]

So firstly, the event that happened in Q1, we’re not expecting a repeat of that. It was a very specific market-wide event that was unrelated to Pharming. It affected everybody and it was rectified towards the end of Q1. My suspicion is that’s very much a one-time event and I don’t expect that to occur again in the future.

And then in terms of growth in prescribers, it’s actually been very consistent for the last seven or eight years, certainly I’ve been with Pharming, and we retook control of RUCONEST. There’s still, as I mentioned, another 38% of HAE-specific prescribers in the U.S. who’ve not yet tried RUCONEST and we continue to call on them as well as our core customers. So at this point, I see no reason, given the last seven or eight years, to not expect that same steady growth as we move forward.

[Natalia Webster, RBC Capital Markets]

Great. Thank you. And then just secondly on leniolisib, regarding the timing for the CHMP decision, you say that you expect the same queue for this year, but I think you said H2 previously, so just wondering if there’s been any delay there or you’re just being a bit more specific.

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Do you want to be answering that, Anurag?

[Anurag Relan, Chief Medical Officer]

Yes, I think we’re just continuing to work collaboratively with the CHMP and EMA in answering their questions. And I think we’re just giving some more detail as we have more detail around the timeline there, and that’s why we are saying the fourth quarter now.

[Natalia Webster, RBC Capital Markets]

Thank you.

[Operator]

Next question comes from Hartaj Singh from Oppenheimer. Hartaj, your line is open. Please go ahead.

[Unidentified Analyst]

Hey, this is a [indiscernible] on for Hartaj. Congratulations on the good quarter for RUCONEST and the nice start for Joenja. I have questions on the APDS patients. How can we think about the growth rate of APDS patient number quarter by quarter and would seasonality be a factor to consider? Thanks.

[Sijmen de Vries, Executive Director and Chief Executive Officer]

So you ask if there’s any seasonality in APDS, is that right?

[Unidentified Analyst]

Yes. I mean, the growth, like, how can we think of the growth rate of APDS patient number quarter by quarter and would seasonality be a factor to consider down the road?

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Steve, you’d like to comment on that?

[Stephen Toor, Chief Commercial Officer]

Thank you, Sijmen. I mean, obviously it’s an ultra rare disease. We’ve had a bonus of patients to start with, but we’re still through the – we’re still in the – very much in the launch phase. So I’d expect steady growth as we move forward and really no seasonality, but obviously in the outer years, you’ll start to see the rate of growth slow as you would do with any launch, but nothing specific in terms of seasonality that we – where we would expect significant drops or spikes. Does that answer the question?

[Unidentified Analyst]

Yes. Very helpful. Thank you.

[Operator]

We have a follow-up from Christian Glennie from Stifel. Christian, your line is open. Please go ahead.

[Christian Glennie, Stifel]

Hi. Thanks. Just I thought it’s worth pulling up on, obviously, you filed applications in Canada, Australia, Israel, potential approvals next year. What’s the commercial strategy there? Is it better to find partners? Is it worth doing it yourself in some of these markets? What should we expect there? And obviously in Japan, you need to run a trial, that’s a bit further down the track. What would be the strategy?

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Yes, yes. First of all, Christian, before I hand over to Stephen, there’s no trial requirements, right, in Australia and in Canada. We have submitted the files. We have received a priority review as well from those authorities. So it’s a matter of waiting for, first of all, the validation of the files – regulatory files. And then of course, we’ll go through that and then we’ll await the opinion of those regulatory authorities somewhere, as alluded to in someone, probably mid first half of next year.

Then I’ll hand over to Stephen to explain how we are approaching the commercialization in those markets.

[Stephen Toor, Chief Commercial Officer]

Thank you, Sijmen. Hi, Christian. So certainly, I think to answer the heart of the question, we have no plans to out-license in any of those markets and give away, frankly, the value of the product to other companies. The structure, though, in the go-to-market with just Joenja would be different from say the U.S. or Europe where we have pretty large footprint.

So it would be a light cost-efficient footprint. And in somewhere, for example, like Australia, you would service that market directly with probably a hybrid model, a combination of directly employed Pharming employees, and then local distributors and partners who can help us service certain elements of the Australian infrastructure. But to keep things really efficient from that market, you would also serve Hong Kong, South Korea, which is the third biggest market in Asia Pac, and other smaller markets.

So the plan is very much for us to keep control of the product, keep control of bringing patients on therapy and obviously, reaping the benefits of that for ourselves and our stakeholders. Does that answer the question, Christian?

[Christian Glennie, Stifel]

Yes, that’s very clear. Thank you.

[Stephen Toor, Chief Commercial Officer]

Thank you.

[Operator]

[Operator Instructions] As we have no further questions, I’ll hand back to the management team for any concluding remarks.

[Sijmen de Vries, Executive Director and Chief Executive Officer]

Thank you very much. Thank you, ladies and gentlemen, for attending our conference. And I would like to remind you of some of the elements of the outlook for the remainder of the year.

You’ve heard all the positive developments on the leading indicators, the forward-looking indicators, underpinning the sales of RUCONEST, that we remain confident to continue to guide on the low single-digit growth for RUCONEST revenues for this year. You’ve heard about the steady flow of new patients coming in for Joenja and, of course, the immediately available patients that could be brought to Joenja therapy over the coming quarters.

You’ve heard about the regulatory interactions that we have with the Europeans, the plans to follow-up in the United Kingdom and the submissions, of course, to broaden our footprint with the submissions in Canada and Australia. And, of course, that we are continuing to invest in the launch preparations in those markets and, of course, the clinical trial plans that we have for the second indications of leniolisib, which, of course, we will update you as and when we have received the feedback from the regulator on our plans that have been submitted to the regulators with regards to both the – what the new indication is and that indication, by the way, as you already have learned from us, it has a bigger patient potential than APDS. And we will refill that later on during the year.

And last but not least, we hope to be able to come back to you during the remainder of the year, of course, with in-licensing or acquisition news, because we are very keen and have the capabilities, of course, to further leverage our commercialization infrastructure that we have and that we are basically expanding towards the coming years, including markets like Australia, Canada, as you heard from Stephen, but also Japan, and to bring more products to that market to further significantly accelerate the growth of our company going forward.

So thank you again for being at our conference. And we look forward to updating you on the next quarter results somewhere in the last week of October. Thank you very much. Goodbye.