Good day and thank you for standing by. Welcome to the Pharming Group N.V. Third Quarter 2023 Results Conference Call and Webcast. At this time, all participants are in a listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. [Operator Instructions]. Please be advised that today’s conference is being recorded. I would now like to hand the conference over to your first speaker today, Sijmen de Vries, CEO of Pharming Group. Please go ahead, sir.

Thank you very much and good morning or good afternoon, ladies and gentlemen. I’m here with my three colleagues, Stephen Toor, our Chief Commercial Officer; Anurag Relan, our Chief Medical Officer; and Jeroen Wakkerman, our Chief Financial Officer and we are delighted to take you through the third quarter results of this year. Before I do that, however, I would like to point you to the forward-looking statement slides, because this presentation may contain or will probably contain forward-looking statements that, as you know, are statements of future expectations that are based on our current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in these statements. And the rest I leave to you to read. So let’s just move on to the next slide and then, of course, to the next slide. About building a sustainable business in rare diseases. And that’s what we are about. And this is, of course, a very interesting moment in time, quarter results of 2023. And you see that on the left-hand side, how we are going to start to build that rare disease, the sustainable rare disease business. We have significant positive cash flows for more than $200 million of moving annual total sales of RUCONEST that can fund Joenja launches and pipeline development to start with. And we are very pleased, of course, with the results and a strong revenue growth of RUCONEST 18% up on the second quarter and 11% up on last year’s third quarter. And also, if you look back nine months, so year-to-date, 2% up on last year. That means that, we are on track to deliver our low single-digit revenue growth for RUCONEST for 2023. And then, of…

Thank you, Sijmen. Good morning, everybody. As Sijmen said, I’ll give you a brief overview of RUCONEST performance and also some insights around the Joenja launch and update you on that progress today. Next slide, please. So as communicated at the end of Q1 and as you’re all aware, the HAE market underwent a significant event, which affected all products. The event was short-lived, and as we said, we would, we bounced back strongly in Q2 and Q3. As you can see in the first bullet, we posted strong growth in Q3. And even with the softening for Q1, as Sijmen showed, we have grown versus prior year. So we’re really pleased with our performance. And this has been driven by strong performances across all of our leading metrics, but I especially want to flag new patient enrollments, which have exceeded 70 over each of the past three quarters, which is stronger than we’ve seen in the past. And so hence, as Sijmen said, we continue to go up to low single-digit growth for RUCONEST this year. Next slide, please. So as many of you know, RUCONEST was launched in 2015. We’ve actually though been active in the HAE community since around 2000. And over those 23 years, we collaborated with all key stakeholders, including the clinical ones and patient advocacy groups such as the HAEA. And that has been the remainder driver for the consistent success of RUCONEST over the nine years post-launch, and it’s why the prescriber base continues to grow with 700 in the US to-date, and also why we’ve treated over 2,000 patients, and that metric continues to grow as well. So I think what that clearly underlines is the importance and the ongoing need for a recombinant IV C1 esterase inhibitor, and that’s despite the…

Thanks, Steve. I’ll begin on the next slide with a little background information about APDS. So APDS was first described in 2013. And based on our estimates and literature review, we believe that there are more than 1,500 patients worldwide diagnosed with APDS or almost 1,500 patients with APDS. We have already found more than 640 of those patients. These patients who have APDS have really had limited treatment options until recently to only treat the symptoms of the disease. The disease manifests itself in childhood and worsens over time without anything specifically indicated for treatment; physicians and patients who are quite limited in their treatment options. And as with most rare diseases, the signs and symptoms vary across patients. This makes the challenge of diagnosis even more difficult beyond just a rare disease. Fortunately, there is a genetic test that can provide a definitive diagnosis for APDS and I’ll be spending more time in the coming slides talking about our plans and efforts to help find more patients with APDS. On the next slide, we can see what Joenja now brings to patients in the US as a potential treatment option for them for their condition. It is approved by FDA for the treatment of APDS in adults and pediatric patients from ages 12 years of old and older. We have randomized clinical trial data showing that Joenja met both primary endpoints as well as meeting several significant other clinically relevant endpoints. In addition, we’ve seen a well-tolerated and generally safe adverse event profile. There were no drug-related or serious adverse events and the study of withdrawals due to the drug in the study. And more importantly, we have long-term data, and I’ll be sharing some of that with you that we’ve been publishing and presenting at conferences recently…

Thank you very much, Anurag. Focusing first on the financial highlights of the third quarter 2023. Total revenues increased to $66.7 million, so an increase of $12.5 million or 23%. Gross profit increased to $58.4 million, an increase of $6.5 million. Operating costs increased from $44.7 million to $56.8 million. And the increase of $12.1 million is mainly because of R&D, additional investments of $8 million, and marketing and sales of $5 million. And that is all directed towards the launch or most of it is directed to launch of Joenja and the first development of the market. The operating loss was a profit in this case is $1.9 million, and the net profit was $3.5 million in the quarter, and that was on the back of a positive financing income and a tax credit, which is a timing effect. Sijmen mentioned it already, but the cash and cash equivalents increased to $199 million at the end of the quarter. Looking at the figures year-to-date, nine-month year-to-date, the revenue increased by 9% to $164.1 million. Gross profit increased to $146 million. And as was guided earlier this year, we further increased our OpEx as I said, into mainly marketing and sales and R&D and the operating costs were $175.3 million, i.e., an increase of $48.4 million versus the same period last year. Consequentially, the operating loss was $6.5 million for the three-quarter period. And the net loss was $7.4 million, which is an improvement from Q2 this year. If we go to the next slide, we see the growth in revenue over the quarters. The third quarter revenue was $66.7 million, and that’s a 23% increase from last year driven by both RUCONEST and obviously, Joenja, as you can see on the picture. And also accelerated growth is seen in…

Thank you. [Operator Instructions]. We will now go to your first question and your first question comes from the line of Christian Glennie from Stifel. Please go ahead.

Yeah. Good morning, good afternoon, guys and thanks for taking the questions. Three, please. I’ll take them in order. Let’s start with RUCONEST and a strong quarterly sales print. Just to be clear around whether there’s anything to be aware of in the Q3 numbers, maybe they’re stocking or some impact, that means it should be a clean quarter. And then any implications for as we think about the fourth quarter as well, typically your strongest quarter, particularly in the US for RUCONEST, any reasons why Q4 wouldn’t still be your strongest quarter for the year?

Thanks, Christian. That’s an interesting question. Would you like to comment on that, Steve?

Yeah, sure. Thanks, Christian. So you’re right. Q3 is strong, and we occasionally see stocking, but it’s sporadic. There’s no real pattern to it. So I would still expect at this stage, Q4 to be our strongest quarter and for us to see how the year strong.

Thanks. And then maybe a quick follow-up there. I mean, you’ve called out the new patient starts. I mean I was just curious why you’re still getting this very sort of strong patient starts and physician uptake and anything else to comment on that around –

Yes, it’s interesting. We actually restructured our team a month before COVID hit, and then we had to mothball them. So I think you’re seeing a combination of different things happening. But certainly, the restructuring of that team is now paying off, and that’s why you’re seeing actually an increase in enrollment and expect consistent increase in enrollment across three quarters. So I think that makes a big difference. And the other thing I would say is, we have a very well tenured team, so deep relationships within our physicians’ offices and with their staff. And I think that’s really helped in identifying new patients. I mean, as you would have heard us allude to, we have a much broader mix of patients now than we have historically, whereas if it launches you would expect, it was refractory patients who were predominantly using RUCONEST. Now it’s across mild, moderate, and severe, it’s pretty evenly spread. So I think it’s a combination of time and market, trust, execution. And as I mentioned earlier, the continued need for IV C1 esterase inhibitors despite that quite disruptive changes to the market.

Okay, thank you. And then turning to Joenja then, if you can. Just firstly, on the European approval process, the Advisory Group Meeting, as I understand, still to be held. Is there a timing on that or any outcome that comes from that Advisory Group Meeting?

Hi, Christian, it’s Anurag. So this meeting has been scheduled. It is a closed meeting, and we’re not going to provide any further guidance on the ongoing regulatory interaction other than to say that we continue to expect the CHMP opinion in this quarter.

Okay. And then as we think about, obviously, the Q3 numbers around patients on paid therapy and things, I mean, anything to flag in terms of expectations for Q4 versus the sort of current run rate of enrolled patients and patients on therapy. And then particularly maybe there’s any commentary insight you can give on the numbers of patients, obviously, presuming a large proportion on starters by how many bridge packs are people having to give you seem to imply and you’re getting patients on to paid therapy pretty quickly. But that bridge is still something that’s a reasonable factor in the mix.

Maybe, Steve, do you want to comment on that?

Certainly. So again, as Anurag said, Christian, we continue to aggressively pursue our patient finding efforts, and actually, we’re ramping that up now. We’re through that early launch and conversion state. In terms of starter and bridge, yeah, I mean, we’ve actually, of course, most of those patients have been on starter, but we’re having to bridge very few or when we do we bridge for a pretty short period of time relative to what we may have seen with RUCONEST back in the past, and that’s because of this pretty fast approval rate and our ability to get commercial product in patients’ hands quickly. So yes, it’s going very well in that regard, and we’re not having to give away too much free stock.

Okay, great. Thanks. I’ll jump back in the queue.

Thank you. I will now get to our next question. And the next question comes from the line of Alistair Campbell from Royal Bank of Canada. Please go ahead.

Thanks very much. Hopefully, you can hear me. A couple of questions, please. Another follow-on on RUCONEST, which is following on from Christian’s question to an extent. But you’re obviously pointing towards adding prescribing physicians, and that’s growing at around give or take 10% per annum, but also the product is growing at low-single-digits. So how should I think about that disconnect? Is that a price effect? Or is that lower utilization per patient? Or is it just the incremental prescribers you’re adding are sort of less active? So that’s question one. And then question two, if I could just sort of fish my look a bit on additional indications. Looking at some of those publications you flagged in the presentation, I think one of the suggestions is you could look at areas where mTOR inhibitors are currently used, given us the same pathway. And that sort of brings to mind areas like autoimmune with things like transplant rejection. There are also oncology areas like neuroendocrine tumors. Can I press you to see whether any of those areas or things you’re thinking about right now? Thanks.

So, maybe the first question you want to answer, Stephen?

Certainly. So you’re right to flag, I think, the apparent or the perceived disconnect. For the most part, what I would say that is, is we went from 30% of patients on prophylactic therapy three, four years ago to over 70% now in the mid-70s. So what you’re seeing is better controlled patients having less attacks and therefore, utilizing less acute therapy. But we haven’t actually lost that many patients. What we’ve seen is, and we think of it as cohorts of mild, moderate and severe. So not the disease itself but the number of attacks. So with some patients in that severe end or frequent attack to move then the moderate into the mild area. So it’s more patients, more prescribing physicians, but often a less severe course of disease, leading to a slightly less acute utilization.

Can I quickly follow-up on that? If that sort of mix change in the patient population let’s say, it’s more or less played out, does that mean that perhaps as more physicians are added, that disconnect could actually lessen over time?

Logically, yes, it could.

Okay, thank you.

And then I think your question about our next indication, I think you’re thinking along the same lines that we are. For example, we know that in APDS in the past, especially, but even now in some areas where Joenja is not available, mTOR inhibitors are used. They have tolerability issues and they’re not quite the perfect target for the condition itself. So we are looking at other areas where mTOR inhibitors are used and where leniolisib could prove to be a better suited for that disease. We’re not specific. I can already comment that we’re not specifically looking within oncology. I think it’s something that we may do in the future. But at the present time, we’re really focused on other rare diseases where we think that this pathway is overactive that some of the things that we see is basically trying to take the learnings from APDS. Some of the features of APDS that we see, where else do we see that type of problem in the immune system. And I think that’s what we’re in active discussions with the FDA on trying to finalize the clinical trial plan, and I expect to be able to give an update on that later this quarter.

Great. Thanks so much.

Thank you. We will now go to the next question. And your next question comes from the line of Sushila Hernandez, Van Lanschot Kempen. Please go ahead.

Yes. Thank you for taking my question. Could you walk us through the development of your operating expenses? As you mentioned, we’ve seen an increase in marketing and sales costs due to the launch but will this increase further or is this level what we can expect for the coming quarters? And also on R&D costs with the second indication for leniolisib is it feasible to target profitability next year? Thank you.

Yeah. Thank you very much for the question, Sushila. On OpEx for Joenja, we will support the European launch going forward. So we will shift probably some of the funds from the US to Europe. On a net basis, it’s too early to say what the outcome of that shift will be. And yeah for next year also on the new indication, yes, we will invest in R&D and in a trial. Again, there, it’s too early to say what the exact cost is, but I don’t expect necessarily a reduction in OpEx next year.

Okay, thank you.

Thank you. We will now go to the next question. And your next question comes from the line of Joe Pantginis from H.C. Wainwright. Please go ahead.

Hey, guys. Thanks for taking the question. A couple if you don’t mind. So first, I wanted to focus on Stephen’s comment on the HAE market. Obviously, there’s a lot of disruptive changes to the market that are either ongoing or coming. And I’ll phrase my question this way. Obviously, we know where we stand and where Pharming stands with regard to the role of RUCONEST. But I guess, maybe more feedback from your new prescribers, for example, and even existing prescribers about the potential threats that are coming, even though they are focused on the prophylactic standpoint. So basically, the external views of needing a rescue therapy such as RUCONEST.

Do you want to comment on that, Stephen?

Sure. I mean, as you know, Joe, good morning, by the way. We hold our boards pretty regularly. We’re all of us active in the year, myself and Anurag regularly in front of our customers in the US. And I think certainly some physicians are quite excited by what may be coming in the future. I think what’s interesting for me is patients still need, despite all of these disruptions, that occasional bolus of therapy that you get from an IV product such as RUCONEST. So although we see disruption and as I mentioned earlier, we see sometimes a decrease or in some places, even a normalcy increase in utilization. We still see the need there. So I certainly wouldn’t want to be complacent, and we look at the future as closely as any company would. But through all of the disruptions, certainly since I joined Pharming seven years ago, we see that initial period of disruption and fluctuation in volume. And then we see things settle down and we see a continued clinical need for an IV C1 esterase inhibitor. So does that answer your question, Joe?

No, it certainly does. I appreciate that. And I guess, looking more towards just switching a little bit to Joenja. Assuming a positive CHMP opinion later this quarter, maybe if you could provide a little more color with regard to your country-by-country strategy. I know previously you discussed targeting Germany first, but how should we view beyond that, how things should go?

Do you want me to take that, Sijmen?

No, no, Stephen go ahead.

Yes. Thanks, Joe. You’re right. I mean Germany would be the typical market to go to right out of the gate, and we’ll certainly do that. We also will then target the other Big 4 in Europe. Anurag mentioned the UK and a submission there. Specifically, there that it’s not part of the EU. And then we’ll get through Spain, Italy, France, as major nations but we won’t ignore the rest of Europe either. So we have a pretty lean operation in Europe, and we cluster the other 22 member states around those major markets. And you’ll see us through ‘24 and ‘25 in a steady sequence start to go to all those markets. And by the way, we’ve identified patients, I think, in every single one of those markets. And in addition to that, we have submissions in Australia, which will enable us to set up a base of operations in APAC in the key markets outside of Japan. The ongoing trial in Japan and a submission with Health Canada right now as well is that, I believe, a frank market globally. So I think we have a pretty careful, well-considered sequenced approach that gets us into markets at the right time. And you’ll see that putting up through ‘24 and ‘25.

Got it. And then just lastly, I guess it’s a quick logistical question. With regard to the VUSs and unclassified variance, if you will, is there anything that needs to be done as you generate data about these variants on the regulatory front or in the label to identify these?

Hey, Joe. Good morning. So the answer there is no. Because these patients actually have APDS, the label is -- that is for APDS. Right now, the question is this variant, which hasn’t been previously described or previously published, when the genetic testing company gets that result, they don’t know what to do with it, so they throw it into this bucket of the USs, and many, many results come back into this VUS classification. But once that is reclassified based usually on functional testing data or even as I mentioned, that using that multiplex approach. Once that’s reclassified, then that patient has APDS and would qualify for treatment for the label.

Great. Thanks for the clarification. And thanks for all the answers guys.

Welcome –

Thank you. We will now get to your next question. And your next question comes from the line of Hartaj Singh from Oppenheimer. Please go ahead.

Great, thank you. Thanks, Nadia. I got a couple of questions and really nice update everyone. The two questions I have just following-up to a previous question on the cadence of the launches ex-US. I know Australia, Canada, Israel in ‘24 and ‘25, Europe later this year and then discussions there. Can you just give us an idea of the relative TAM of that market? And then could there be boluses in Europe, the UK, Australia, Canada, because you have been working very hard to identify patients. I imagine there are patients in these various territories, ready to get on drug and then how would pricing potentially look relative to the US market? So that’s the first question. The second question is just on your family testing. Previous research we had done before leniolisib was approved indicated there could be as little as one more family member and as much as three more extended family members that might have some indication of APDS and could potentially qualify for treatment. I know these are early days, but if you could just give us some color around there. What do you expect to see as you ramp up this family testing? Thanks for the questions.

Yeah. Thanks, Hartaj. Hey, Steve, do you want to comment on those patient numbers ex-US?

Certainly. I didn’t quite catch the front end of the question, Hartaj, so if I miss anything, then please just pick me up as we go through. So I think you’re right to flag that the medical affairs group across the world have been actively identifying patients with key opinion leaders in those key centers in each country. So there will be a bolus of patients for waiting therapy, and many of them will already be in the Early Access program, for example. There will be a slight delay because from approval in many of those countries, you then need to negotiate reimbursement, which means we set the price slightly later than the clinical approval. But in terms of your pricing question, the price outside of the US will, as you know, for the most part, always be lower. It’s highly unlikely to match that price, and there’ll be a variation in what that price – it looks like country-by-country. What I would say though is without preempting what that price might look like is, as with all ultra-rare diseases and rare diseases, we can still make a market and build a very healthy business in each of those countries, and that’s fully what we expect to do.

That’s great, Stephen. And then just on the question of the family testing and then how big could that patient population be just roughly speaking? Thanks.

Yeah. So, Hartaj, it’s a great question. And it’s certainly something that we’re trying to address right now, which is, we know it’s an autosomal dominant transmitted disease. So we expect that there should be other family members with the condition. And as we said many times, it may not be immediate family members, even extended family members. What we’ve been a little surprised by those, and I guess it relates to the fragmented nature of our healthcare system is that, oftentimes these family members haven’t been tested. Some of that is just due to lack of awareness even amongst patients about the genetics of the disease, and some of that is just due to the healthcare system, idiosyncrasies and how it’s difficult to get genetic testing done. So we’re changing the way we approach this and really putting the patient right at the center of this. So allowing patients and families to actually initiate testing. So if a patient is diagnosed with APDS and a family member wants to get tested, we started a program that will allow that to happen by having the family member themselves initiate the process, and it doesn’t need to go through, for example, the patient specialists who may not be immediately available to see the family member, for example, or may not even be a patient on the family number in most cases. So I think we’re moving these barriers to genetic testing to allow appropriate testing in family is, I think, will likely be a significant source of newly diagnosed patients. And we’re starting that program. We’ve started a little bit of that already, but really putting that in full force now.

Great and that helps. Thank you everyone for the question.

Thank you. We will now go to the next question. And your next question comes from the line of Simon Scholes from First Berlin. Please go ahead.

Yes. Hello. Thanks for taking my question. So you’ve already identified 150 APDS patients over the age of 12 in the US. I was just wondering how many of those patients do you ultimately expect to be able to enroll?

I would say the vast majority of those, Simon there. Well almost all of it.

Okay. So almost all.

And I mean that’s just the beginning, right? Because you heard –

Yes, I know there are other patients, but I was just interested in patients you already identified, so we should assume over 90% or 95%?

Well, I think there will be a very high percentage of patients that indeed will be interested to get into major treatment, correct. That’s our experience so far at least.

Okay. And particularly in the US, you don’t expect to encounter a problem with the last 10% or 20% because of lack of insurance coverage. How does that work? I mean, presumably, there will be some patients without insurance coverage? I mean, can you get those as paid therapy as well?

Although those questions are difficult to answer, but generally speaking, if we look at our experience in RUCONEST, we don’t see any issues with related to that coming up. And, of course, RUCONEST also has patients that have limited or no insurance coverage, but there’s always a ways and means. Maybe you want to comment on that, Stephen?

Yeah, I think I mean there’s all kinds of different types of support available for patients and also public programs that try and make sure that patients have access to something. So [inaudible] I haven’t looked at this for a while, but I believe we have very, very few RUCONEST patients, for example, in our patient assistance program, which will be essentially free supply on an ongoing basis. And even every year, we’re working with them and with their physicians to find an insurance plan for them. We’ll find an option that will be to paid therapy. So I apologize, I can’t give you a specific answer. But if I look at the RUCONEST experience and my experience in rare diseases outside of Pharming, I think the vast majority of patients in the end will be on paid therapy. It can sometimes just be a heavy lift in those last few percent together.

Okay. Thanks very much. That’s very helpful.

Thank you. [Operator Instructions]. We will now go to the next question. And your next question comes from the line of Christian Glennie from Stifel. Please go ahead.

Hi, guys. So just a quick follow-up, if I can, on Joenja and the pediatric study in the 4 to 11-year olds, looking at enrollment almost complete there. So just a reminder in terms of the endpoint for that trial, the timing of the standpoint and therefore, when we might see data? And then the expected sort of rough mix of the under 12s as it relates to this 4 to 11-year-olds. So I mean, if you think about, say, the 50 remaining patients identified in the US that we know, how many of those would be 4 to 11?

So let me answer the second question first, Christian. So again, based on our current experience in APDS, about 1/4 of patients overall are below the age of 12. Amongst that quarter, at least 3/4 are in the age range of the first study or 4 to 11-year old study. So, we know these patients actually have the disease at birth and that many patients do begin to manifest symptoms early on. But oftentimes, they’re not diagnosed at that very early age. And that results in many patients in the older age groups, especially in that above 4 age group. So that’s a little bit on the breakdown of the age distributions across APDS. In terms of the pediatric study and the endpoints that we’ve had in the adolescent and adult study. So I think what we’ll be able to do is once the study is fully enrolled, and we have these last four patients enrolled, we’ll give you some more guidance on the timing of the data releases as well as some of the regulatory work that we anticipate being able to do if the results are positive.

Okay, thanks. That’s helpful.

Thank you. There are currently no further questions. I will hand the call back.

All right. Thank you very much. Maybe a few closing remarks. Thanks for attending. You can see now that and as stated last quarter, the company is now starting a long growth trajectory, supported by the foundation that RUCONEST provides, and of course, driven by the future expansion of Joenja outside of the United States, but also inside the United States, supported by lots of efforts that we are undertaking and initiating to actually broaden the patient base. And of course, as always, with new genetic diseases, the definition of the disease will broaden. So therefore, we look forward to the future with optimism and with a company that will significantly grow and change over the coming years, putting us again as a combination of our commercialization capabilities, clinical development and regulatory skills putting us again as hopefully, the ideal partner or go to partner in the future for the other rare disease assets that we can take on board and actually complete the clinical development/approvals and do the successful commercialization as we do with RUCONEST and with Joenja. So that said, thank you very much for attending, and we look forward to updating you again on our full year results call, which will be in March of next year. Thank you very much. Goodbye.

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