Good day, and thank you for standing by. Welcome to the Pharming Group N.V. Q1 2024 Results Conference Call and Webcast. At this time all participants are in a listen-only mode. After the speaker's 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 speaker today, Sijmen de Vries. Please go ahead.

Thank you very much Sandra, and welcome, ladies and gentlemen, to this -- our first quarter results conference. I'm here with my -- next slide, please. I'm here with my three colleagues, in order of speaking, Stephen Toor, our Chief Commercial Officer, who is joining us from our New Jersey office; Dr. Anurag Relan, our Chief Medical Officer, joining us from our U.S. office as well; and Jeroen Wakkerman, our Chief Financial Officer, who's based with me here in Leiden. Before I do that, I would like to point out to the next slide, please, number three, that is the forward-looking statement slide. We will be making forward-looking statements today in our presentation, and those are based upon our current plans, and insights of the -- and situations of the current market circumstances. And of course, actual results may differ from these forward-looking statements, so you cannot necessarily rely on those. So having said that, I would like to go to slide number four and maybe even onwards to slide number five, because you've seen my picture already. Yes. And here we are. We're building this global -- leading global rare disease biopharma company. And we have -- we do that based on three pillars. And this is a very familiar slide for you, you have seen this before. On the left-hand side, the foundation of our company, the product RUCONEST that comes from our own research and it has already been on the U.S. market for almost 10 years. It was approved in July 2014. Recombinant protein replacement therapy for hereditary angioedema attacks. And as you can see, we are still growing this product and we had an 8% growth versus last year this quarter. Good growth last year as well. And we see increasing numbers of prescribers and…

Thank you, Sijmen. Thank you, everybody. If you could go to -- okay. So the key things [technical difficulty]. Those unique product attributes and the exceptional customer service and execution by [technical difficulty]. That remains the case despite the transformation of the treatment landscape with [technical difficulty] and it will continue to remain in the face of more acute competition in the coming years. [Technical Difficulty] generally have a more severe cause of disease and they need a virtually guaranteed and fast efficacy that stops an attack [indiscernible]. RUCONEST's unique product features in the mode of administration deliver that in a way that future options can't. So, as you know, 2023 was a strong year with solid growth in prescribers, new patients and sales. That was -- that success was in spite of the market wide event related to reimbursement for government patients in Q1. And in Q4, we've seen less of an impact as the patients out-of-pocket responsibility almost half. The strength of leading indicators have continued into this year and we've had a strong Q1, up 8% on prior year and we exit Q1 '24 on track to achieve the revenue guidance, which, as previously discussed, is seemed to be low to mid single digit growth for RUCONEST. If you go to the Joenja slide, please. As you know, we were strong out the gate with the launch of Joenja, with patients fully reimbursed within days. And that momentum built through year one and it continues into 2024. So, we now have 83 patients fully reimbursed with five more in process being processed, with 15 newly diagnosed patients in the quarter taken us past 220, close to half the number of patients the literature suggests are out there, although we believe there are more. And we have over…

Thanks, Steve. Next slide, please. And then, if we can go to the U.S. launch of Joenja slide. Next slide. Thank you. And as you mentioned, Steve, we've had a strong launch of Joenja in the U.S. This reflects both the unmet need and the clinical experience with Joenja. And to review, Joenja is approved for the treatment of APDS in adult and pediatric patients 12 years of age and older. And this approval was based on data from a randomized placebo-controlled study that showed Joenja met both primary endpoints with significant benefits also seen in the secondary and other exploratory endpoints. Importantly, what we've seen across the development program is that Joenja has been generally safe and well-tolerated. And this data has been seen not only in the randomized study, but also in the ongoing long-term open-label extension study. In that study, we also saw benefits with patients being able to reduce or discontinue their use of immunoglobulin replacement therapy, and we also saw reductions in infection rates over time. We continue to share this data on the long-term use of Joenja from these studies as well as from post-marketing experiences. Next slide. And as with many of our diseases, patients have a long journey to reach a diagnosis. We have several efforts now ongoing to help patients get a correct diagnosis quickly. The first center is around medical education to raise awareness of APDS and share data on leniolisib. For example, recently, we've shared information about the seriousness of APDS by publishing data on early mortality and the frequency of lymphoma in these patients. We've also been discussing, for example, the frequency of bronchiectasis, a lung complication that is often seen in these patients at a young age to help doctors be able to recognize the types of…

Thank you very much, Anurag. Next slide, please. So, in the first quarter of 2024, the revenues increased by 31% to US$55.6 million and that's in comparison to first quarter of last year. And this is driven by both the U.S. commercial launch of Joenja and revenue growth of RUCONEST. RUCONEST revenues increased by 8% to $46 million compared to first quarter last year. And Joenja or leniolisib revenues were $9.6 million, and that's a 21% increase compared to the fourth quarter of last year. So, overall, we are well on track for 2024 to hit our total revenue guidance, which is between US$280 million and US$295 million or 14% to 20% revenue growth. Looking at gross profit. It increased in line with the sales increase. Gross margin dropped slightly, and that was because of a non-recurring inventory impairment of just over $2 million. Looking at OpEx, went up compared to last year's first quarter, but went down if I compare it to Q4 last year as we already indicated at the time. So, this increase versus last year was planned, and we are increasing the OpEx to support the launch of Joenja in the U.S., but also preparation for the outside of the U.S. The operating loss because of the increase in OpEx, increased from US$13.7 million to US$16.3 million in the quarter. And the net profit remains fairly stable, increased by $0.2 million and that is compared to the operating loss is due to better net finance results in the quarter. Our overall cash and marketable securities position went from $215 million to $203.5 million. So, a reduction of $11.5 million and that is on the back of mainly negative net cash flow from operating activities of $7.6 million. On the next slide, we see revenue breakdown by product and geographic segment. Just focusing on Joenja for the first quarter, we saw a $8.5 million revenue in the U.S. from $7.9 million Q4 last year. We see $1.1 million outside of the U.S., and that was $0.3 million in the fourth quarter last year, and this is sales from named patient progress. And if you look at the overall part of Joenja in the total revenues at $9.6 million, that's now 17% of total sales. And obviously, last year was nothing. And we expect that share to go up going forward. Next slide. Some more perspective on the OpEx. As I said, the OpEx went down from the quarter by around $10 million. And the OpEx really reflects the continued investment in Joenja in the U.S. and the loss preparation ex-U.S. We also increased investments to expand the leniolisib franchise. So, think about the pediatric trial and new indications that we are working on and that Anurag mentioned, and we also increased payroll costs that is because of a general business growth. With that, I would like to hand over to Sijmen for the outlook for the remainder of the year.

Thanks, Jeroen. And yes, I'm happy to present you with the next slide. The outlook for '24. As you heard in the beginning, we gave guidance and we continue to give guidance between $280 million and $295 million for revenues for this year, which means between 14% and 20% growth with, of course, quarterly fluctuations as expected. Joenja, you heard about the continued progress in finding the additional APDS patients in the U.S. market. The patients that are already identified, of course, but also is supported by the family testing, the systematic family testing that we have embarked upon and the first results of the VUS validation efforts and of course, subsequently converting those patients to paid therapy. Albeit you also heard from, of course, from Anurag that the MAVE experiment, which will provide the definitive answer of the full definition of APDS, we'll report at the end of this year. So, in other words, we expect a significant inflow of patients in the U.S. from that experiment that will overdose more than 1,100 patients with the VUS. Then you heard about the ex-U.S. increasing revenues from the commercial availability through the named patient program, which we expect to continue to increase during the remainder of this year, the clinical trials, the pediatric trial. And of course, the Japan trial continue. We also expect regulatory action you heard this year from the various jurisdictions where we have regulatory files that are under review. We're very excited, of course, and expect in the very near future to be able to announce that the Phase II proof-of-concept clinical trial in PID with immune dysregulation is actually -- will be started to significantly expand our commercial potential of leniolisib, but you heard Anurag outlining the details about. And then last not least, we have an active business development group that looks for primarily in-licensing opportunities, but also we look at acquiring opportunities that are in clinical stage of development or later in those areas that I mentioned here on the slide, immunology, hematology respiratory and gastroenterology preferably. So, in other words, we have a very busy remainder of the year ahead of us, and we look forward, of course, to updating you on that later on. But let's switch over now to the operator first, because there may be some questions that we happily answer. Over to you, operator.

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

Thank you and thanks, guys for taking the question. Three questions, please. The first one would be on Joenja in the U.S. Just to understand a bit better the sort of potential moving parts here in terms of patient numbers. You talked about 83 being on treated therapy as of 31st March, but that compares to 81 at the end of December. So just a net two additional, but maybe there's some additional patients that have come on, but then some have dropped off and then maybe some come in around the duration of treatment that you've seen so far, given that you will now have some patients potentially you've been on this since they've launched 12 months ago. So, just a better understanding of the patient dynamics there, and what to expect through the rest of the year?

Steve, would you be so kind?

Sure. Thanks, Christian. Good morning. So yeah, the -- so we actually with 81, and we added four group patients in the quarter. There were two now that dropped out. One was post-transplant. Unfortunately, that patient passed away unrelated to Joenja. And then secondarily, a patient with an unknown adverse event. So, the net of that is 83. We also diagnosed or have diagnosed 15 more patients during that quarter, and those are currently being processed, obviously, and will be additive to the current patient load. So, as things stand right now, our outlook as much as same as Sijmen said we are on track to get to where we need to by year-end.

I think you refer to that -- thanks, Steve, for that. I think as with all these sort of ultra-rare therapies, you will see, of course -- especially in the beginning, you'll see some lumpiness in the sales, right, that -- that's why we say quarterly fluctuations, Christian.

Yeah. Okay. Thank you. And then have you got -- I mean, is the working assumption that the majority of patients continue to be on therapy or if you've got an average duration of treatment that you can quote at the moment?

I think you're right. I mean, people stopping therapies are as far a few -- between what we see, right? Anurag, do you want to say something on that?

Yeah. Thanks, Sijmen. Hi, Christian. We see continued very high compliance with the product. We've seen that throughout the clinical development program and we see infrequent discontinuation.

Okay. Thank you. And then, the second one would be on lenoi, Joenja in Europe, flagging ongoing review with the AMA and obviously expecting a CHMP. Just wanted to try and understand a little bit as much as you can tell what some of these issues could be or relate to? Do you have any outstanding issues there? And when you say you expect to be on the agenda for May is that's not necessarily the same thing as being up for an opinion in May. I just want to clarify what your expectation is for the May Committee?

Anurag, would you be happy to answer that question?

Sure. So, we do expect to be on the CHMP agenda that for their meeting at the end of May on the MAA. So that's our expectation. Of course, we'll wait for the CHMP feedback to confirm that.

Okay. So, we should be expecting Joenja -- that's your expectation, Joenja will be up for an opinion in May?

That's correct.

And then, just finally on the named patient rollout, obviously, 1.1 million. You said that will continue to grow. Can you give us a sense for the growth there through the rest of the year? And also, kind of the number of patients and the sort of that the prices that you're getting for these patients? Thank you.

Steve, would you like to comment on that?

So, the prices are generally in line with the U.S. price, sometimes with a slight discount to that, so generally in a ballpark way. In terms of numbers, we don't necessarily forecast NPP out just because that's driven obviously by the doctor and their discussions with both the patient and local authorities in the country. But we would expect to see as the product is -- becomes better known and the effect that it has a positive effect on patients becomes more widely understood that as we await approvals, more patients do benefit from that. But there is no specific target as such as very much doctor driven, Christian.

Okay. Thank you.

Thank you. We will now take the next question from the line of Sushila Hernandez from Van Lanschot Kempen. Please go ahead.

Yes. Thank you for taking my question. Also one on Joenja and patient findings. You see that there are 15 diagnosed patients in Q1. So, how many of these patients do you expect to be converted to paid patients? And also on operating expenses, are these the levels that we can expect throughout the year? Or are you foreseeing any increases or decreases compared to this quarter? Thank you.

Okay. So, may I suggest, Stephen, you answered the first one. Is that all right?

Yeah, absolutely. So, thanks for the question. We expect the majority of those patients if not all of them to be converted on to paid therapy. We have not as yet had a rejection. So, I would expect to -- and the course of business of all those patients come online.

Would you like to comment on the operating expenses, Jeroen, what do we expect for that?

As I said last year on the OpEx, where it was in the Q4 was $73 million that we expected it to go down. It has gone down now. And I would expect it to be slightly up in the next quarters, because we keep investing in Joenja, both in the U.S. and ex-U.S. And so, I don't expect a sharp drop or anything in OpEx in the next few quarters.

Does that answer your question, Sushila?

Yes. Thank you.

My pleasure.

Thank you. We will now take the next question from the line of Joe Pantginis with H.C. Wainwright. Please go ahead.

Good morning and good afternoon, gentlemen. Thanks for taking the questions. So, a couple please. I just want to start at the end of your written comments today because more on curiosity. I mean, obviously, it's not impactful of your investment case. But you did disclose that OTL-105 with Orchard is being discontinued. So, just curious if -- two things. Is there anything technical or science that impacted the decision to discontinue for the program? And are there any payments either way for the termination? And will you be potentially looking for an additional or an alternative gene therapy approach for the future? Thanks.

All right, Joe. First, no significant payments. Secondly, yes, there was always a high hurdle, of course, involved in the high technical hurdle. And when you look at it, it's associated with the -- both the ability to generate sufficient C1 inhibitor protein by means of the blood organ and so on. And then, of course, the non-toxic conditioning regimen developments. So, those were the high hurdles. And then, of course, last but not least, but very importantly, we -- at the time, we did not have the opportunity to develop and that's the main reason -- to develop leniolisib. We were not expecting that to be able to develop leniolisib for two subsequent indications. So, we're now about to kick off that Phase II study for leniolisib for the next indication. You heard from Anurag is a very, very significant indication, which is fairly near by the market compared to also a product like OTL-105. Obviously, no competition around with a long exclusivity guaranteed for leniolisib. Secondly, we are looking at an even more and bigger PID indication going further forward. So, in other words, we have a lot of opportunities now that are more nearby, more derisked without any competitive threats here. So, we decided, given all the things together that it is the best way forward to focus ourselves now on this with regards to our internal portfolio, and of course, to continue to look for leveraging the infrastructure, the commercial infrastructure further. We are active in licensing/acquisition quest. So, I hope it's a bit long-winded, I hope I answered your question, Joe.

No, absolutely. Thank you. And then, on RUCONEST, sort of a two-pronged question. How would you describe sort of the first quarter impact with regard to insurance resets that are usually expected? How much did that impact at least just for the first quarter to be able to get back on trajectory? And secondly, how would you describe the balance, because obviously, it's very nice to see the continued addition of new physicians to the program and refill rates? Thanks a lot.

Yeah. Of course, it's always part of the lumpiness or the first quarter is always part and parcel of that renewals of the of the prior authorization. But let's just go to Steve, give a bit more insight in these things, right, Steve?

Yeah. Absolutely. Hi, Joe. So actually, the things went well, Joe. As you know, we've been doing this now for a number of years. So, we were able to prepare in Q4. And the prior authorizations in Q1 actually went pretty smoothly, and we have completed almost all of them by the end of February. Now what complicated last year was some issues, as you know, that were external which you've hit the market for government patients. We saw that impact decline quite significantly this year as patients out-of-pockets also came down in the Medicare space. And certainly, for us, it was a significant decline in impact. So, overall, I would say Q1, while you expect lumpiness in Q1, it was pretty successful reauthorization period for us.

Excellent. Thanks for all the details, guys.

Pleasure, Joe.

Thank you. We will now take the next question from the line of Hartaj Singh from Oppenheimer. Please go ahead.

Great. Thank you. And thanks for the questions. I just have a couple. Really nice launch going on with Joenja. But I just want to kind of go back to a previous question on the first quarter fluctuations. Two years in a row now, we've had them and they seem to be pretty extreme. I mean, is it other companies, they talk about payment into government programs, there's patient system programs, et cetera, et cetera. I mean, what exactly happened in the first quarter where you have this pretty large drop-off from the fourth quarter to the first quarter seems mostly sales? And then is that the expectation going forward? Is that the way we should model this going forward? In that in future first quarters, on a quarter-on-quarter sequential we should expect a pretty significant decrease in the sales and then that will pick up going on later. I mean, is it the way to think about it? So that's my first question. I just got a couple of others. Thank you.

Yeah. Hartaj, I think it's been the case, right, for all those years and was aggravated last year by this special situation there. But it seems to be the case, right? Do you want to comment any further on this, Stephen?

Sure. Morning, Hartaj. So, I think it's certainly the case that in most Q1s, you've seen over the years, RUCONEST sees a slight decline due to the reauthorization. Reauthorization of most of our patients in that period of time, and that does affect most companies. Last year was exacerbated by an impact to government patients. It was external. It was in an effect of the whole HA space. That came down significantly this year as patient out-of-pockets declined. So, we saw about half the impact that we saw last year. And next year, that stabilizes completely. I think with patient out-of-pocket is coming down to around $2,000. So, I think you can say by the time we get to next year, it's steady state. So yeah, perhaps we should expect a decline as we always have year-on-year, but I don't expect what's happened last year and this year to continue. That's the result of a very specific event affecting government patients.

Yeah. No, Stephen, that makes sense. And we've heard that from other companies also. I think the IRA, Inflation Reduction Act, has exacerbated this first quarter fluctuations. The other question I would just have is on OpEx, really like all the color there. But let me put the -- there's a question asked previously, let me put it in this way, which is that if you're expecting -- your guidance suggests a pretty significant increase in revenues this year. Is OpEx expected to grow at the same rate? I mean -- or can we hope for some operating leverage, which would mean OpEx growing at a slower rate than revenues? And I've got one last question after that.

Yeah, sure. No, I think Jeroen already commented on that, Hartaj, about the -- still to be expected a slight increase in the operating expenses for the coming quarters. Having said that, it's not the spectacular increase anymore before, because we did the U.S. launch, of course, but that is carrying capital intensive. On the other hand, we continue to invest in all those things in the U.S. market. And of course, we're preparing for, as Jeroen has already alluded to, all the preparations for the launch of Joenja outside of the U.S. And in addition to that, you also see that gradually, R&D costs will not spectacularly, but will continue to go up as well, because of the fact that we are starting the clinical trial programs for leniolisib in the subsequent indications. So, all in all, we're not at this point in time, of course, aiming for profitability per se in this year, because it's still a launch year, right, and it takes time. And you already heard that, for instance, did the leverage, I think the real leverage. If you look at the patient growth in APDS as you heard Stephen say there that conclusive VUS MAVE experiment that Anurag was talking about, will or should be bringing a very significant bolus of patients to the U.S. -- in the U.S. market towards becoming available for paid therapy next year. So, this is typically -- when you have a new disease that's not fully describes. It is typically when you are -- you're dealing in ultra-rare diseases that it takes time and it takes a lot of investment. But eventually, it will be a very, of course, profitable operation. I hope that answers your question a little bit, Hartaj.

Yeah. No, absolutely. And in line with what you've said before also previously, Sijmen, I just wanted to get more color on it. My last question is just on Phase II design. Anurag, you might have mentioned this already, but can you just kind of walk us through roughly how long would it take for you to sort get all the sites open, recruiting. When could we see -- essentially what I'm trying to get to is when could we see a sort of a readout -- would that be a 2025 event or 2026? And thank you for all the questions.

Thank you, Hartaj. Anurag, please.

Hi, Hartaj. So we -- this next Phase II dose finding study is being conducted at a single center, and that's at the NIH. So with that and the fact that they've -- we're anticipating 12 patients in this study, this is a center that has actually already identified, which patients they anticipate being able to enroll. We believe that they'll be able to enroll the study in a relatively rapid fashion once we get going, and we expect to be able to readout the results probably in the course of 2025.

Great. Thank you, all.

Thank you, Hartaj.

Thank you. We will now take the next question from the line of Alistair Campbell from Royal Bank of Canada. Please go ahead.

Thanks so much for taking the questions. I've got three, if that's okay. Just first of all, looking at Joenja. I mean, obviously, you've seen more diagnosis through Q1, but we haven't seen progression in terms of patients on therapy. I just want to ask, get a sense of that. I mean, just check, we're not seeing an underlying dynamic here or perhaps what you've done in the first instance is kind of hoovered [ph] up the most severe patients and maybe now we're moving into patients who are diagnosed, but don't have quite a severe disease and they're potentially harder to pick up. So maybe some commentary on that in terms of what's happening with severity in patients on drug? And then if I do some quick mathematics, I'm assuming you had about 80 patients on paid therapy through the quarter, that was sort of point me to U.S. number based on the WAC, a chunk higher than reported sales and sort of indicates something like a 25% gap in the system. Is that a good proxy for how much kind of discounting there might be from the WAC price in the system? And then finally, just on the PID trials. Is there any reason to think that PIDs need a different dose from APDS, and you may perhaps need stronger suppression of the pathway? Just any sort of feedback on that would be interesting. Thank you.

Okay. Let's maybe start with -- thanks, Alistair. Maybe start with two questions from Anurag about severity and the PID dosing. Anurag, would you like to comment on that?

Sure. So, I think, Alistair, the first comment is correct that the patients that we initially able to convert over to paid therapy. These were patients, of course, that were in the clinical trial program in the expanded access program. So, there was, of course, a bolus of those patients. And many of those patients were quite severely ill. Now APDS, in general, is a serious disease. So, there's -- there aren't a large number of, let's say, asymptomatic patients that were floating around out there, but all of these patients are sick. Most of these patients are on IG replacement therapy, for example. So, this is a serious disease and a progressive disease. So, I think it's just a matter of continuing to reach out to these doctors and educate them, as well as patients about their condition and the potential effects of Joenja. On to the question about the dosing in this study as well as any future studies, and I think that it's really an open question. We're starting with a lower dose than we have approved for Joenja currently. So, we're starting at the 10-milligram dose, which is the same dose that we used initially with APDS, and we'll progress these patients through. Based on everything that we know so far about the activation of the pathway in these patients and measurements that have been done about that activation relative to APDS patients, we feel like we're in the right dosing range. So, we don't believe that we're going to need a higher dose to so-called suppress the pathway, but really trying to normalize and sort of balance the pathway. I think that's probably a better way to think of.

Okay. Thanks. And then maybe, Jeroen, you want to comment on -- Alistair's question about the discounting or the absence of it in Joenja.

Yeah, absolutely. So basically, it's not just discounting like in other drugs. It's mainly because of the mix with the Medicaid, Medicare patients and mainly Medicare. And so, we did have, for that reason, a discount of around 12%.

Does that answer your question, Alistair?

Yes.

There is no other discount on that, Alistair.

Yeah, that's good. It's very clear. And is that broadly what you should be thinking about carrying on going forward, or do you think the mix will change over time?

Good growth.

It really depends on the patient mix. So, it's very difficult to say. But other than that, it's been relatively stable so far.

You should realize, Alistair, it's a relatively young population we're treating right here in this case.

Very good. Very clear. Thank you.

Thank you. [Operator Instructions] There are no further questions at this time. I would like now to turn the conference back to Sijmen de Vries for closing remarks. End of Q&A:

Thank you, Sandra. Yes. Thank you very much. Yes. So, you heard our total revenue guidance continues to be between $280 million and $295 million. You heard about the progress of finding the additional APDS patients in the U.S. and outside of the U.S., of course, and then bringing also relevant part of the revenues for Joenja. You heard about the expectations towards the big effort that's ongoing during the remainder of the year to clarify the full description of the disease by means of the MAVE experiment, so which will we expect deliver a significant new bolus of patients next year becoming available for therapy. Obviously, the clinical trials are ongoing, an especially here the pediatric label expansion trial progresses very well. At that trial with 4, 11-year-olds has the majority or the vast majority of the pediatric patients in it. And that, of course, will be delivering a significant bolus of patients in addition to that. You heard about the regulatory actions that are ongoing in the various territories outside the U.S. and where we expect to see some progress there continuing. And then, of course, last but not least, we are very excited about the start of our Phase II clinical trial, proof-of-concept trial in PID with immune dysregulation that will very significantly expands long-term commercial opportunity of leniolisib. And very lastly, we continue to look for in-licensing opportunities of clinical stage, rare disease opportunities to be either in-licensed preferably or acquired. So, with that, I would like to all thank you for being present at our conference, and we look forward to updating you on our next call, which will be our half year results in the beginning of August. Thank you very much, and goodbye.

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