Good morning or good afternoon, all, and welcome to Pharming's first half 2023 results call. My name is Adam, and I'll be your operator for today. If you'd like to ask a question at the Q&A portion of today's call, you may do so by pressing star followed by 1 on your telephone keypad. I will now hand the floor over to Sijmen de Vries to begin. Sijmen, please go ahead when you are ready.
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. Before I do that, of course, I would like to point you to the next slide, 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.
Without further ado, I would like to move on to two slides ahead and, basically, you know, share with you some of the excitement over the last six months that we had, of course. We had a very busy six months and, indeed, made a lot of progress. First and foremost, we're of course, very, very pleased to see that, you know, 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. 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.
We say that based upon, you know, the leading indicators that all point in the right direction. Of course, Stephen Toor will talk a little bit more about that later in his part of the presentation. 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, of Joenja, and of course, to actually prepare for the successful US launch. 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 to a strong start in the market.
You've seen that, and I dare to say that, you know, 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 30th of June, is no mean feat, and is a testament to the preparation of our US colleagues. Of course, it beats analysts' expectations insofar as I've seen analysts' 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 the pediatric program, of course. That's important because the current...
Although the current license for Joenja already incorporates the 12 years and upwards, so already partly the pediatrics, you know, there is a big unmet medical need to be fulfilled in those children younger than 12 years. We're working very hard to actually get that pediatric program done, so that we can actually submit the file for the extension with the towards the younger children. 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.
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, for in-licensing, additional in-licensing opportunities for rare disease assets that can actually further leverage our commercialization, commercialization structure that we have in place. 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 is, you know, 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 on Japan. Of course, you see here that we made progress, as I've just alluded to, by submitting the files towards the Canadian, Australian and Israeli authorities, so as to increase the footprints for leniolisib, or Joenja, called later, in geographical footprint. Of course, we also made great strides forward, next slide, please, with our with our leadership, strengthening of our leadership. We're very pleased to have found, Dr.
Richard Peters, as the 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, from the, the, outline on, on Dr. Peters, he's got an impressive track record, a lot of experience in the healthcare industry, but also in academia, but especially in the rare diseases business, with very successful companies such as, you know, Genzyme or Sanofi Genzyme, as it's called nowadays. He's been CEO of two Nasdaq-listed biotech companies, as you can see. He held positions in, in, in earlier successful companies such as Amgen and Sanofi.
Of course, he, he is a, a medical doctor by education and has, has actually also served as an editor for, you know, very prestigious, journals. We're very pleased that Richard was happy to join us as our, 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.
We're very pleased as well to, and that is especially in the context of our growth strategy and our ambition to actually, you know, 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, you know, the, the growth strategy, the development and execution of our growth strategy and, and our future plans. 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, in Roche, in, in Basel, in the business, the business development, the business development group.
We're very pleased to have strengthened our team with these, these two, extremely experienced and talented individuals. Next slide, please. Let's just look at... Then the next one, please, at what it actually means and what it brings and what it, what we need, and what is our bread and butter. That's our very strong rare disease commercial infrastructure. You know, it, 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. 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 is medical affairs teams.
That's, of course, very important, especially in rare diseases, that you have a very strong medical affairs team. That include medical directors, medical science liaisons, molecular geneticists, and publication specialists. Very big, very big, big medical teams that are absolutely essential for your success in commercialization of rare diseases. 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 oceans. They include national account directors in the US, health economic research as specialists and directors, both sides of the ocean, to actually work with the authorities to get the product to reimbursement.
You've seen, you know, how quickly we got the, the product reimbursed in the U.S., so I think we have an excellent team in place there. Then there's patient support teams that help 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. Then last but not least, we're extremely active with everybody, including our sales force teams, to be at conferences. There's a lot of education, disease education ongoing, also directly to patients, that we, that we actually facilitate. We support the patient organizations and all.
Basically, it's an extremely, you know, 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, and found, and identified those patients in a new disease, right? A disease not even discovered 10 years ago. As you can see on the next slide, you know, we're, we're really ready to leverage all of this for the, for Joenja, as and when Joenja gets approved, of course. You know, 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. One more slide from my end here about, you know, the durable commercial asset that RUCONEST represents.
It's, 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. That's very important because although there's a big trend has been going towards prophylactic treatments for hereditary angioedema, and those prophylactic treatments have become better, there's also a the notion and the fact that almost the 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.
This is actually where RUCONEST is now beginning, and beginning to make inroads and being used for breakthrough medication. 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 their patients as breakthrough medication. Yes, RUCONEST is an IV drug that, 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, do these self injections.
They're perfectly happy with that because they can rely on the product, and you can see it on the, on the slide here, that has, you know, an incredible good track record with regards to efficacy and that they can actually, 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 will continue to have this very special place in the markets going forward.
I would like to switch over to APDS, and I switch over to now ask for Anurag to present the Joenja story. Anurag, over to you.
Thanks, Sijmen. On the next slide, we can see a little bit of information about APDS, which is a rare, serious, and progressive primary immunodeficiency. As you heard from Sijmen, just first described about 10 years ago. We think that APDS affects about 1.5 patients per million, based on literature estimates and our own patient-finding efforts. I'll talk a little bit about those patient-finding efforts in a moment. 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, 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 focused on symptom management. Really, when we think about the problems that these patients face, so with infections, so giving them antibiotics or giving them immune globulin 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 phenomena, 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. Here's a highlight of some of the data on Joenja. You can see in the top left, the indication statement that it, Joenja is approved in the US to treat patients who are 12 years and older with APDS.
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. 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 in discontinuation, in the use of IVIG or immune globulin replacement therapy, as well as reduction in infection rates. These results were consistent with what we saw in the randomized, double-blind, placebo-controlled part of the study.
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. 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 US, and Steve will report on this progress further shortly. Next slide, please. What are we doing now to look for APDS patients? 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 immunodeficiency.
Through those efforts, we've, as I said, identified more than 640 patients worldwide in, in, with APDS, among which there are 200 identified in the US. 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, and really working with patients and clinicians to help identify patients. We also know, as with most rare diseases, there's a large pool of undiagnosed APDS patients. 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 immunodeficiency or an inborn errors of immunity. We're making available in the US a comprehensive genetic testing program to help get those undiagnosed patients the proper diagnosis. 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. These are patients who have a result that is inconclusive, and this is called a VUS or a variant of uncertain significance. 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. We're doing a number of efforts now to help those patients, which there are a significant portion of, that have this inconclusive result, that have a primary immunodeficiency, that have already had a genetic test, but have a result that doesn't give them a final diagnosis. 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've also embarking on functional testing, both in the US as well as worldwide.
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. 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 Significance diagnosis currently. Next slide. 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 2 months later. We...
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 2 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 4-11 years old.
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. Later this year, we're going to be starting our second pediatric study, this is in the youngest age group. These are, again, patients who are age one to six years old, and I expect to be able to start that study in the third quarter of this year. Next slide. Just a quick update on where we are with EMA and the progress that we've made so far.
As you know, we submitted our responses to the CHMP Day 120 List of Questions, and just a couple of weeks ago, we received the further questions, 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 seek 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.
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. It's over to Steve.
Thank you, 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. Sijmen touched upon already, the disruptions we saw in the first quarter were HAE market-wide, and they also affected our competitors. As 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 vial ship to patients, were all strong. In fact, new enrollments have hit 70+ for both Q1 and Q2, despite the Q1 market issues. 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. Furthermore, we saw a 2% increase in revenues when comparing the second quarters of 2023 and 2022. 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 it, of course, the base of patients that benefits from RUCONEST. Next slide, please. Let's turn now to the Joenja launch. As you would expect, Pharming bought 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, 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. Just to reiterate, APDS is not the same with dominant condition, so there's a 50/50 chance the siblings and other family members are also gonna have APDS. So family testing is critical for both them and their welfare and the, the long-term growth of Joenja, which, as we know, is a, is a progressive disease. Okay, next slide, please.
Just briefly, before I pass over to Jeroen, a couple of things around the value proposition. You know, as Anurag already shared, and we should just remind ourselves, this is the only indicated option for APDS patients, is a precision medication. That's important. 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 with physicians and their underserved patients would need access to, and access to quickly. Let's briefly look at the impact on a patient. Next slide, please. This is John. He's a twenty-something-year-old man who's been dealing with APDS since he was 11 years old.
Like most patients, he's been in and 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 9 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 nodes have decreased in size, and I think you, you, you can see in the thought bubbles, you know, his quote around that, you know, his percentages are actually gone as opposed to just being reduced in size. Importantly, he's starting to think about his future and what he wants to do in life.
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 our, you know, this launch, this launch phase, and also our future growth. Next slide, please. As we discussed in the last call, you know, 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 2 weeks of FDA approval, which is very quick and certainly unusual. 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. To date, no patient has been denied access to Joenja. 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. That will continue the brand growth and, of course, lay the foundations for Pharming's continued success into 2024. Now I'd like to hand over to Jeroen, who will cover the financials.
Yeah, thank you very much, Steve. Good morning. Good afternoon, everybody. Moving to the next slide, on the financial highlights for the second quarter of 2022. Our revenues grew to EUR 54.9 million, which is a growth of 9% versus last year. The EUR 54.9 million consists of EUR 3.8 million of Joenja sales. The first quarter that we obviously report that, Joenja sales. EUR 51.1 million from RUCONEST, and that is a growth of 2% from last year's second quarter, but 20% even from Q1. A very strong recovery as Sijmen and Steve mentioned before as well, from Q1.
Gross profit grew to $49.2 million, which is +7%, which is roughly in line with the growth in revenues. Operating costs increased by $23.4 million. 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.
Also good maybe to tell you that in the last 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 EUR 12.8 million. To cut a long story short, the increase in other income from this year to last year was EUR 8 million. On the operating profit, EUR 5.3 million, that's a decline, and that's roughly in line with the increase in the operating costs. The net profit went from EUR 15.7 million to EUR 1.3 million, so a decline of EUR 14.4 million.
That is, by the way, an improvement from Q1, where we had a loss in a net, net loss in the quarter. If we look at the first half results on the next slide, total revenue grew by 1% to EUR 97.4. The gross profit, EUR 87.6, with a gross margin of 90%, was a good gross profit income. Operating cost EUR 118.5 million from EUR 82.2 million last year, so that's an increase of EUR 36.2 million. More detail about that later. The operating profit was EUR 8.4 million negative, so an operating loss, so to say, and the net loss has been EUR 10.9 million so far in the year.
If we then look at the revenue breakdown for for the last few quarters on the next slide, you see indeed the enormous growth from from Q1. Well, the drop obviously was from the reimbursement issues that were apparent in the whole HAE market. We showed a strong recovery of 20% in the second quarter to $51.1 million, and you see the $3.8 million sales from from Joenja for the first time in our in our history. Moving to the next slide on the costs, because they went up significantly, just a bit of color on on where we spent the money.
In the second quarter, we had $10 million of milestone payment to be paid to Novartis related to Joenja. Basically, over time, you see a substantial increase, increase in marketing and sales to support the launch of Joenja. Steve just mentioned that the launch preparation was rigorous and thorough, and this was also what you see in the money that we spend on Joenja.
You see that a fairly stable development of G&A cost 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 the approvals in several international markets like Europe, Canada, Australia and Israel, and a build-up of our medical departments, both in the U.S. and in Europe. Apart from the cost categories, another way of looking at the increase in cost in the first half of this year, that was +$36 million, is that we spent $10.5 million in total on the milestones.
We spent $7 million of the $36 increase on leniolisib out-of-pocket expenses. Think about R&D costs, but also marketing, market access, and amortization costs of the license. 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 of 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, we're growing the company as an investment in future growth. A short overview on the next slide of the cash flow.
Over the last 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. That was the overview of the financial highlights. Going to the outlook for 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 since April of this year.
We expect a CHMP opinion for the EU in the fourth quarter of this year, 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, 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. Further details on the plans to develop additional indications for leniolisib will be provided later this year. 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. Please feel free to ask any question.
... Thank you.
Thank you. As a reminder, if you'd like to ask a question today, please press star followed by one on your telephone keypad now. When preparing to ask your question, please ensure your headset is fully plugged in and unmuted locally. Press star followed by one to ask a question today. Our first question comes from Christian Glennie from Stifel. Christian, your line is open. Please go ahead.
Yeah. Good afternoon, guys. Thanks for taking the question. I guess we'll start with Joenja, and just initially on just to explain or clarify the 60 patients on enrollment versus the 43 on paid therapy. Is, is it the case that some of those they're, they're on therapy already, but still working through in terms of reimbursement? Or how, how, how should we think about those, those, the balance of those 17?
Hey, Christian, when patients actually are enrolled, they get a free starter pack, which is a 1-month supply of Joenja. Yes, once they are enrolled, they have access to the medication, so they have it. Of course, you know, the administrative procedures to get them reimbursed, they start. If that happens within the month, the second month will be a commercial pack. If that procedure is not yet finished, then there will be another month's supply in the form of a bridging pack provided. Yes, they're all having access to therapy once they are enrolled. I hope that's clear to you.
Yeah. That, that, that's good. Thanks. Then in terms of the patient, identified patient numbers, you've added 140 in terms of, you know, 640 versus the 500 you previously reported. I noticed that, the U.S. has stayed the same. Just where, where those extra 140 patients come from? Is that, is that mostly the new international markets, Canada, Australia, Japan, or, or where are they from?
Could you comment on that, Anurag? Is that possible?
Sure. Hi, hi, Christian. We are finding patients... We're continuing to find patients in the U.S., but we're also finding patients in other markets. That does include Japan, Australia, and other markets where we intend to commercialize first.
Okay, thank you. Then, and then in terms of the- you've got 200 patients in the U.S. identified, you know, your 1.5 per million in the US, you know, there's 500 or so out there. That, that's already a 40% diagnosis rate. Where do you, where do you think that, that, that could, that, that diagnosis rate could go over the next few years in terms of identifying?
Would you like to answer that as well, Anurag?
Sure. We, we definitely see this trending up. I think, you know, when we think about, when we think about markets in Europe and some other countries across the world where there are more centralized healthcare 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, the, the diagnosis of these patients is, and the care for these patients is a little bit more fragmented. 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 avail- for these patients.
I think that we expect that to increase, and at the minimum approach, what we see in some other countries, but likely increase beyond that, and that's why we're, we think we're being, being reasonable about an estimate of 1.5 per million. As I mentioned earlier, there's a significant population of patients that we found beyond the 200 in the U.S., for example, that have this that have these variants of uncertain significance, or what are termed VUSs. I think that That's another pool of patients who have symptoms of a primary immunodeficiency, have had a genetic test, oftentimes that's, you know, well before we've been involved in the picture even, but they still don't have a clear diagnosis.
I think this will likely lead to an increase in the number of diagnosed patients over time.
Sorry, as a quick follow-up to that then, is, is it your understanding that those patients would also be appropriate for Joenja, even if they haven't gotten sort of formally find, APDS currently?
Yes.
APDS currently.
That's correct. They would be appropriate for Joenja because they would have APDS if that's confirmed. Right now, they have a, you know, oftentimes they have symptoms and, and, and clinical manifestations of APDS, and they have variants, so, or, or mutations in one of the two genes that leads to APDS. The question is: Are those mutations, are those variants, disease-causing? That's, 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, 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.
One, one final one, if I can, I'll get back in the queue. Is it possible to give any, any rough sort of guidance for Joenja for the year, whether that's in terms of patient numbers or, or revenues? Obviously, you've got 60 patients in the program already, $3.8 million revenue in the second quarter. You know, the 60 patients is already a 40% penetration of, you know, the 150 patients in the US that are over 12.
... Any, any sense for penetration rates or patient numbers, by the end of the year, would be great.
Yeah, I understand that, Christian, but, you know, it's early days, right? Yes, we're off to a good start, and we would like to see a bit more development of the numbers. Obviously, the numbers are ticking up all the time, right? We'll keep you updated on a quarterly basis for now, until such time that we get a little bit more, you know, feel for the market and the development going forward, then we will start, you know, giving some different guidance. For now, no, not yet. Have to be a little bit more patient for that, but we will eventually, of course, do that. We'll keep you, on a quarterly basis, updated on the number of patients that are on therapy and are enrolled. Okay?
Yeah. Appreciate it. Thank you.
Thank you.
The next question comes from Joe Pantginis from H.C. Wainwright. Joe, your line is open. Please go ahead.
Hey, guys. Thanks for all the details. I appreciate it. A couple questions on the initial dynamics of the Joenja launch. 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, once they're identified? Then second, when you look at these numbers, you know, the 60 and the 43, how many patients, you know, have gotten the drug or are on the drug? You know, of the revenue number that you posted today, which, you know, like you said, beat, overall expectations, you know, how much of that, if any, is based on just getting drug into the inventory channel? Thanks.
Yeah. It's an excellent question, probably for Steve to to go into much more, a little bit more detail. Steve, could you pick that one?
Yeah, sure. Thank you, Sijmen. Morning, Joe. The first thing is, as Sijmen alluded to, once the patient's enrolled, we get the starter packs out, so they're on therapy pretty quickly. 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 4 and 6 weeks, which is pretty quick. We've seen 1 or 2 is a little quicker, and 1 or 2 is a little more, but think of it in a 4 to 6-week period. We're not having to bridge too many patients beyond the starter pack. In terms of stocking, it's almost 0. I mean, we put some in right at the very start.
We were able to, we were able to process patients very quickly after launch, which means we burned through that very quickly. The way in which our partner works, PANTHERx, means we're, we're basically practicing just-in-time delivery. For the most part, that revenue is generated by demand, by patient demand.
That's great to hear. Thanks. Oh, yeah, absolutely. I, I feel I have to ask my next obligatory question that I usually go to. When you look at OTL-105, so obviously, you know, it's 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 will we be able to see any of the data coming out of these models?
Would you like to comment on that, Anurag?
Sure. Good morning, Joe. We're, we're making progress, together with Orchard in those models. I, I don't have a firm timeline that I can say that it's gonna, you know, this is going to progress, you know, in the next couple of weeks or not. 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.
Great. Appreciate the details, and nice to see the strong launch on Joenja.
Thanks, Joe.
The next question is from Sushila Hernandez from VLK. Sushila, your line is open. Please go ahead.
Yes, thank you for taking my question. Also on Joenja, you mentioned it takes four to six weeks to get approval. Could you elaborate a bit more on the time for identification to enrollment? Could you share a bit more on that? Thank you.
Steve, would you like to comment on that?
Yeah. Thanks, Sijmen. 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. I mean, it's a day to a week, but really dependent on the speed at which that process happens. It can be very, very quick. Easily a day or two.
Okay, that's clear. Thank you. Just on the leniolisib, you mentioned that over 70 quarterly new patients, where are these patients coming from? Are these treatment-naive patients, or did they switch?
Okay.
Yeah, very sorry. For the most part, these will be switched patients. At this point in the evolution of the market, there are very few treatment-naive patients. 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 deal with any breakthrough attacks.
That's clear. Thank you. Then a final question, could you share progress on your BD activities? How is it progressing?
Ah, that's a good one, Sushila. We have a very active team. I, I think if I sort of recognize remember some numbers, they turned over 150 opportunities over the last 12 months. There were, the, the vast majority, of course, was quickly disposed of. But then we have an internal committee, increasing, including Anurag and Stephen, who looked and take the next look. Then out of that a small, a much smaller number, of course, comes to the fore, and we do some more analysis on that. We've done a few due diligences over this, this last year, just last year as well.
We're making, you know, I think, I can say the efficiency of the BD process has significantly improved over the last year. You know, we came a couple of times very close, but we're very careful, of course, with the first one. As you know, in business development, it's all or nothing, right? There's no deal or there's a deal. But yeah, we remain optimistic about being able to acquire or in-license, preferably in-license, of course, that's the preferred mode of action. Another asset that is in mid to late stage development, so that we can actually, you know, plan for another asset to be launched in the not-too-distant future.
That's all I can say at the moment, I'm afraid.
Okay, thank you. Looking forward to updates on that front as well.
Thank you.
As a reminder, press Star followed by One on your telephone keypad to ask a question. The next question comes from Natalia Webster from RBC. Natalia, your line is open. Please go ahead.
Hi there. Thank you for taking my questions. I just have 2, one on RUCONEST and one on leniolisib. On RUCONEST, we saw an improvement in Q2, and you reiterated your guidance for the full year. I was wondering if there's any risk of sort of the reimbursement issues that we saw in Q1 reoccurring at all. Then also, you mentioned sort of strong market demand and continued growth in unique prescribers. 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.
Um, uh-
Then secondly, on leniolisib, do you want to go to that first, so I can ask the next one after?
Yeah, probably a good idea to let Stephen ask that, answer that question first. Is that okay?
Sure. Firstly, the, the event that happened in Q1, we're, we're not expecting a repeat of that. It was a very specific market-wide, market-wide event that was unrelated to Pharming. It affected everybody, and it was rectified towards the end of Q1. My, my suspicion is that's very much a one-time event, and I don't expect that to occur again in the future. In terms of growth in, in prescribers, it's actually been very consistent for the last 7 or 8 years. Certainly, I've been with Pharming, and we, we retook control of, of RUCONEST. There's still, as I mentioned, another 38% of HAE-specific prescribers in the US who've not yet tried RUCONEST, and we continue to call on them as well as our core customers.
At this point, I, I see no reason, given the last seven or eight years, to, to expect that same steady growth as we move forward.
Great. Thank you. Just secondly, on leniolisib, regarding the timing for the CHMP decision, you say that you expect this in Q4 this year, but I think you said H2 previously. Just wondering if there's been any delay there or just being a bit more specific?
Do you want to be answering that, Henri?
Yeah. I think we're, we're just continuing to work collaboratively, collaboratively with the CHMP and EMA and answering their questions. I think we're just giving some more detail on... as we have more detail around the timeline there. That's why we're saying, the fourth quarter now.
Thank you.
Next question comes from Hartaj Singh from Oppenheimer. Hartaj, your line is open. Please go ahead.
Hey, this is Asahi Jeong, for Hartaj. Congratulations on the good quarter for RUCONEST and the nice start for Joyn- Joenja. I have questions on the BDNF patient. How can we think about the growth rate of APDS patient number, quarter by quarter? Is seasonality a factor to consider? Thanks.
You asked if there's any seasonality in, in APDS? Is that right?
Yeah, I mean, the growth, like, how can we think of the growth rate...
Ah.
of APDS p atient numbers quarter by quarter, and would, seasonality be a factor to consider?
Right.
down the road?
Stephen, you'd like to comment on that?
Thank you, Sijmen. I mean, obviously it's an ultra-rare disease. We had a bonus of patients to start with, but we're still through the launch. We're still in the, very much in the launch phase. I'd expect steady growth as we move forward, and really no seasonality. Obviously, in the outer years, you start to see the rate of growth slow, as you would do with any launch. Nothing specific in terms of seasonality that, where, where we would expect significant drops or spikes. Does that answer the question?
Yes. Very helpful. Thank you.
We have a follow-up from Christian Glennie from Stifel. Christian, your line is open. Please go ahead.
Hi, thanks. Just I thought it was worth following up on, you know, obviously you filed applications, Canada, Australia, Israel, potential approvals next year. What, what's the, what's the s- commercial strategy there? Is, is, is that you're gonna find... You know, is it, is it better to find partners? Is it, is it worth doing it yourself in, in some of these markets? What should we expect there? And obviously, in Japan, you need to run a trial a bit further down the track. What would be the strategy?
Yeah, yeah. 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. It's a matter of waiting for, first of all, the validation of the file, of the files, regulatory files. Then, of course, we'll go through that, and then we'll await the opinion of those regulatory authorities, somewhere as, as alluded to in some of them. Probably mid the first half of next year. I'll hand over to Stephen to explain, you know, how we are approaching the commercialization in those, in those markets.
Great. Thank you, Anurag. Hi, Christian. Certainly to, I think, to answer the, what's at the heart of the question, we have no plans to out-license in any of those markets, and give away or, or frankly, the, the value of the product to other companies. The structure, though, in the go-to markets, with just Joenja would be different from, say, the US or Europe, where we have a pretty large footprint. It would be a large, sorry, a light, cost-efficient footprint. In somewhere, for example, like Australia, you would service that market directly with a, 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 , of the Australian infrastructure.
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. The, 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, for, for ourselves and our stakeholders. Does that answer the question, Christian?
Yeah. No, that's, that's very clear. Thank you.
Thank you.
As a final reminder, that's star followed by one on your telephone keypad. As we have no further questions, I'll hand back to the management team for any concluding remarks.
Thank you very much. Thank you, ladies and gentlemen, for, for attending our conference. I would like to, you know, remind you of some of the elements of the outlook for the remainder of the year. You've heard, you know, all the positive developments on the leading indicators, the, the forward-looking indicators underpinning the sales of RUCONEST, that we remain confident to continue to f- to guide on the low single-digit growth for RUCONEST revenues for this year. You've heard about the, 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 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 grow our footprint with the submissions in Canada and, and Australia. 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 on as and when we have received the feedback from the regulator on our plans that have been that have been submitted to the regulators with regards to both the, what the new indication is.
That indication, by the way, as you already have learned from us, it has a bigger patient potential than than APDS, and we will reveal that later on during the year. Last but not least, you know, we hope to be able to come back to you during the remainder of the year, of course, with, you know, 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, you know, including markets like Australia, Canada, as you heard from Steven, but also Japan, and to bring more products to that market to, to further significantly accelerate the growth of our company going forward.
Thank you again for being at our conference, and we look forward to updating you on the next quarterly results, somewhere in the last week of October. Thank you very much. Goodbye.