Good day and thank you for standing by. Welcome to the Pharming Group Fourth Quarter and Full-year 2024 Results Conference Call and Webcast. [Operator Instructions] Please be advised that today's conference is being recorded. I'd now like to hand the conference over to your first speaker today, Fabrice Chouraqui, CEO. Please go ahead, sir.

Thank you very much. Hello, everyone, and welcome to the Pharming’s full-year and Q4 2024 financial results Call. I'm Fabrice Chouraqui, CEO of Pharming, and I'll be joined on this call today by Stephen Toor, our Chief Commercial Officer, Anurag Relan, our Chief Medical Officer, and Jeroen Wakkerman, our Chief Financial Officer. We'll be making forward-looking statements in this call that are based upon our current insights and plans. As you know, this may differ from future results. First of all, let me say that I'm really excited to be joining Pharming, and it's an honor to succeed Sijmen de Vries. I'm passionate about progressing medical sciences and bringing innovation to patients, and naturally I feel deeply connected with Pharming's mission to serve the unserved rare disease patients. Over the past 25 years, I've developed an experience across the business spectrum, from preclinical research and clinical development to commercial leadership, business development, and capital formation, having able to experience the best of the two worlds, the rigor and sophistication of big pharma and the value creation mindset and agility of venture capital and biotech. In light of this experience, I'm impressed with the development of Pharming over the past 15 years and its significant growth prospects. RUCONEST has become one of the cornerstone on-demand treatments for HAE. Joenja is already approved and launched in the US for the treatment of APDS, with a second number of patients already on treatment, and it is due to be launched in other key markets around the world. And last but not least, the recent completion of the acquisition of Abliva is another stepping stone in the development of the company. We have a clear vision for Pharming, which is to develop a leading global rare disease company with a diverse portfolio and presence…

Thank you, Fabrice. Good morning, everybody. As Fabrice just alluded to, we've delivered another strong performance in 2024. On RUCONEST, we increased the prescriber base by 11% and new patient enrollments by 24%. This translated to a strong Q4, growing 9% over prior year and hitting almost $80 million for the quarter. We ended 2024 with sales of $25 million, 11% up on 2023. In the next two slides, I'll review why RUCONEST continues to show such strength and growth and why we're confident it will continue to grow in the years to come, even as the market becomes more competitive. On Joenja, we continue to build our patient pipeline and transition eligible patients to paid therapy. And as you would expect, our team delivered significant growth over the first year of launch, ending Q4 65% up on prior year at $13.1 million, up for 2024, plus 147% or $45 million. Of note, in addition to 96 patients plus five pending on paid therapy in the US, we have an additional 188 patients on therapy globally under various access programs and in clinical trials that can all move to commercial therapy when the necessary registrations are received. In the forthcoming slides, I'll also outline the opportunities we see in the coming months and years that will both build the Joenja business for APDS and with new potential indications for the molecule, create a strong high growth franchise. Looking first at u RUCONEST, as I just stated, RUCONEST is and will continue to be a growth driver for Pharming and an important treatment option for US patients and their doctors, which is why it's already the second most prescribed acute product in the US. And one of the key reasons for this is its mode of action. As you can see…

Thanks, Steve. And here we can see our growing pipeline. For someone who's been at Pharming for many years, it is incredibly impressive to see how this has expanded from only RUCONEST for HAE to now include multiple products and indication which can support the vision you heard Fabrice lay out that we have for Pharming. Since APDS is a primary immune deficiency with immune dysregulation and there are other more prevalent PIDs with similar features, we're especially excited for the work that we have started here, with two Phase 2 studies underway, including a new program in CVID, or common variable immune deficiency. And last but not least, we have on this slide KL1333 in a pivotal study with the recent acquisition of Abliva. Before turning to development, as you know, the VUS project has been a focus of our patient-finding work. A significant challenge in diagnosing APDS patients occurs when a patient's genetic test result shows a VUS, or a variant of unknown significance. This happens because a variant is novel and there isn't enough information to determine if the variant is disease-causing. In fact, there are over 1,200 patients in the US alone who have received a VUS result in the genes associated with APDS. Over the past year, we have been supporting a project to gain additional insights into these VUSes. The recently concluded study, which will be published soon, has shown there are many new variants that lead to hyperactivity in this pathway. The next step in the process is for genetic testing labs to review these data and determine which variants can now be reclassified as causing APDS. We expect by mid-year these efforts will lead to the identification of many new APDS patients. Now, let's turn to the work going on in pediatrics…

Thank you very much, Anurag. Q4 was a very robust quarter for Pharming. Revenues grew by 14%, 1-4, versus a very strong fourth quarter in 2023. RUCONEST growth was 9% and Joenja 66%. Gross profit grew by 9%, and that is lower than the revenue growth and that was driven by a one-off inventory impairment following a RUCONEST production issue at one of our CMOs. The OpEx was fairly stable and largely as expected in the quarter. The small increase was caused by one-off costs, including a full impairment of a lease contract and just over $1 million of Abliva acquisition cost. Operating profit increased by $5.6 million, driven by higher gross profit as a consequence of strong sales and active OpEx management. This was the second quarter in a row that we generated operating profit. And the net results went from a loss in Q4 2023 to a net profit in Q4 2024. We had a positive operating cash flow in the quarter, and in fact, for the second quarter in a row. The cash and marketable securities reduced slightly due to interest costs and currency effects. Now looking at the full year results, full-year results in 2024 were good. Revenue was up 21%, which was driven by both RUCONEST, with a strong growth of 11%, and leniolisib that grew by 147%. OpEx increased by 10% due to investments in Joenja, which is at a rate well below the revenue increase. Operating profit on a like-for-like basis improved, and that's when taking out the big one-offs that we had in 2023 our cash position reduced and that was driven by the refinancing of our convertible bonds earlier in 2024 for a lower amount than the previous bonds. A quick update on the Abliva acquisition process and timeline. The $66.1…

Thank you, Jeroen. As you've heard, our inline portfolio has generated strong growth in 2024, and we are exiting Q4 with a solid momentum. With its unique profile and strong patient experience, RUCONEST is well positioned to remain one of the treatment of choice for HAE attacks. In APDS, after an initial strong Joenja uptake, we are now working to identify and enroll new patients before capturing two well-defined opportunities with the VUS and the expected pediatric indication. We continue to invest in our long-term growth, with the objective to generate two blockbuster assets. First, the potential new indication of PID with immune dysregulation is a great opportunity to continue to expand Joenja sales potential. Second, the acquisition of Abliva's pivotal stage program in mitochondrial disease, brings another asset with significant revenue potential. Our 2025 revenue guidance of $315 million to $335 million illustrates our momentum, and obviously we look forward to updating you on our progress. Let me now open the line for questions.

[Operator Instructions] And your first question comes from the line of Jeff Jones from Oppenheimer. Please go ahead.

Good morning, guys, or afternoon, I guess. And Fabrice, welcome to the team and congratulations on a fantastic first earnings update here. I guess two questions for us. First, with respect to KL133 in the targeted primary mitochondrial disease, could you speak a little bit to how this patient population breaks down, and what portion of that population you think would be treatable and or eligible for treatment based on the likely label? There are a lot of sort of mutations within that group. And then just a clarification for our second question. For the 188 patients you mentioned that are on the expanded access program, which includes clinical trials, are any of those patients paid? And perhaps could you provide some breakdown in terms of the territories where those patients are? Thanks.

Thank you, Jeff. Let us elaborate actually on your question. So, I'll hand over to Anurag first to tell you more about the addressable population with the ongoing trial on KL1333.

Hi, Jeff. So, with respect to primary mitochondrial diseases, when we talk about the 30,000 number of patients that are in the US and the large European markets, this actually is - we've already limited it to the group of patients that have the mutations that are going to be enrolled in this study. So, specifically the mitochondrial DNA mutation, which already represent 80% of all PMDs. And then we broke that down further and looked at the mutations that are specifically being enrolled in this study. So, that's how we came up with this estimate of 30,000. So, in essence, all of those 30,000 are the addressable population.

Appreciate that. Thank you.

And then I'll turn it to Steve now to answer your question about the access program.

Hi, Jeff. Morning. So, of the 188, we actually have those patients in multiple countries around the world, including many of the key markets that I listed earlier. Those patients are predominantly in either the early access program or compassionate use and also in clinical trials. And we do have a number on paid therapy through name patient programs. But as you can appreciate, that's not a specific number or a revenue line that we would discuss publicly.

Appreciate that, guys. Thank you.

Thank you. Your next question comes from the line of Ben Jackson from Jefferies. Please go ahead.

Great. Thank you for the question. Just two for me, first to start on one that's not too exciting. So, the $30 million anticipated additional OpEx from the Abliva acquisition, are you able just to touch on how much of that is recurring? Apologies if you've noted that already in the call. And then the second one, just interestingly, do you see any theoretical exposure to potential US tariffs there are to apply to drugs? Again, at this point that it's very unclear what's going to happen and we don't necessarily know where it's going. And then I guess as a result of that, have you noticed any kind of level of changing inventories or stocking or patient interest in a measure to hedge against a potential short-lived trade war or anything like that? Your thoughts or color around that would be great. Thank you.

Thank you, Ben. So, let me take your first question about the $30 million of OpEx spent on Abliva in 2025 as announced by Jeroen. About $17 million will be R&D and the rest will be non-recurring transaction and integration costs. Now, when it comes to the tariff, obviously we are monitoring the situation and we're doing some homework in the background, looking how we can minimize the impact of potential tariffs if they were decided by the US administration. We're looking at some adaptation that we could make to our supply chain. This is obviously ongoing. I cannot share any details. And we can tell you more in due time, but this is obviously something on which we are proactive and monitoring very, very closely.

Perfect, thank you.

I think there was a question on whether there's any stocking or inventory buildup in anticipation of the tariffs.

No, we have enough stock already for our needs within the US, and there's no planned inventory buildups at this point in time until we have a clearer picture of the situation.

Very clear. Thank you very much.

Thank you. Your next question comes from the line of Alistair Campbell from RBC. Please go ahead.

Hi there. Thanks very much for taking the questions today. And actually, let me start with RUCONEST. It's great to see level of confidence that this product will continue to grow. Just very briefly in the Q4 number just for modeling purposes, were there any stocking effects in there or is that largely driven by underlying demand? And then thinking about the outlook for 2025, I mean, clearly you feel very confident that you will continue to grow despite new competition. Is that sort of based on your internal thinking? Or just intrigued if you've done any sort of market research to underpin that in terms of trying to assess what physicians think of the new product as it comes to market. Then finally, maybe turning to CVID, just a sense of the timeframe for those trials, should Phase 2 trials be sufficient for approval and how you think those trials will likely be scoped in terms of size and duration? Thank you.

So, thank you so much for your question, Alistair. I'll start answering some of them and hand over to Steve and Anurag for the last one on CVID. I want to reinforce that actually there's not been much talking actually in Q4 and the result, a very, very, very strong result that you saw actually on RUCONEST were in large, by in large, actually driven by strong demand. So, that should be very clear. When it comes to the positioning of RUCONEST, again, as we've said, I mean, because of the unique profile of the drug and the very strong patient experience that we've been able to generate years after years since the launch of the drug more than 10 years ago, we feel confident that RUCONEST will remain a treatment of choice for HAE attacks despite new other entrants. As we've seen in other categories, there will probably actually be - the new orals will be help to develop the market. They'll be able to position themselves for specific categories of patients based on our experience with RUCONEST and on the feedback we are gathering from doctors and more general marketing sites. This is our strong belief. And I'll ask Steve, obviously, to comment, given his experience with the drug.

Certainly. The only thing I would add to that, Alistair, and you asked about market research, is we've obviously pressure-tested that through a number of advisory boards and steering committees over the past year. And the resounding conclusion of those interactions is exactly what Fabrice said, which is this is a relatively unique drug in terms of its mode of action. The patients we serve are severe and they attack frequently, and they have a positive experience. And for those reasons, and as I say, validated externally, we believe that RUCONEST has a place both in the short term and the long term and will continue to be a growth driver for Pharming.

Thank you.

And then Alistair, on the question about the CVID studies, we'll have some more details after we dose the first patient, but this will be a Phase 2 study, of course, and we will talk a little bit more about what those results and the timing of those results would look like once we begin the program formally. And we'll also then be able to talk to you about what the development path might look like.

Thank you. Your next question comes from the line of Joe Pantginis from H.C. Wainwright. Please go ahead.

Hey guys. Joe Pantginis from H.C. Wainwright. Thanks for taking the questions. Fabrice, obviously good luck at the helm here, very successful company. So, I think you're taking over at a great time as well. So, first question is, with regard to RUCONEST and building the new prescriber base in the US, how would you sort of describe the yes versus no dynamic as you're trying to convince physicians to be new prescribers to support the core growth of the asset?

All right, thank you Joe, for your kind words. When it comes to RUCONEST, I've actually over the past few days actually met a few RUCONEST prescribers. And so, got a first-hand experience of what's happening in daily medical practice. I think we see a grow - an increased number of prescribers with RUCONEST as they can see that the drug has a unique profile. And as a consequence, it has a unique value proposition for a specific segment of the patient, those difficult-to-treat patients who are experiencing actually a number of breakthrough attacks. And those doctors, I think are reinforced by their experience of the drug. I mean, some of them have spoke to me about a drug which is transformative. I'm using, again, the word transformative, to the life of their patients. And so, I think that that's very meaningful. Given my experience, I mean, when you hear a clinician who is actually treating patient with such a deviating disease, you've seen, I mean, the picture actually of a patient suffering from an attack, that means a lot. Steve, you want to elaborate a bit?

Sure. Thank you, Fabrice. Hey Joe. I think to answer your question of the yes versus no dynamic, we’re 10 years post-launch, and obviously this is a well-developed market. And even in year 10, we were able to grow the prescriber base by 11%. And the reason for that is if you get outside of the centers of excellence where they have large numbers of patients and experience, many physicians haven't had to consider RUCONEST because they've simply not had a patient or they've had their first one. So, what we find, especially with those physicians, is they're very open to the concept of RUCONEST because they're now having to treat these severe frequently attacking patients that they haven't before. So, as I said, we have a strong base of prescribers, but as the market expands over time and as we go deeper into them, we are very confident that more and more physicians will need to prescribe and will use and be open to it.

That's really helpful, Steve. Thanks for that. And then I guess, Fabrice, I certainly acknowledge this is a very early time to ask this question. Anything you could share with regard to changes you might or might not envision for the company's growth? Example, is there any further rightsizing of the sales force, the impact of new assets or even further in licensing of assets to look forward to?

It's very early actually to tell you about what will really be my vision and the roadmap for the company. I believe, again, given what you've heard today about the momentum that clearly we will continue to move forward. I mean, I've tried to share a bit about my vision for the company, which is actually very similar to what you heard from Sijmen in the past. I think our success will come from great ambition, a relentless focus on execution, rigorous P&L management and OpEx management specifically. And then the continued expansion of our pipeline, looking how we can expand our pipeline with the current assets. And you've seen that there are a number of great opportunities with our current assets, but also continue to look at value deals that could actually drive shareholder value in the mid. I'll be very happy to tell you more in the coming weeks and months as I'm becoming more and more knowledgeable with the intricacies of it.

Of course. I had to ask, and thanks for that. And thanks for all the color, guys.

[Operator instructions]. We'll now go to the next question. And the question comes from the line of Simon Scholes from First Berlin. Please go ahead.

Yes, good afternoon. Thanks for taking my questions. I've got two. Just to follow up on the Abliva costs, I was wondering if you could give us an indication of how those costs might evolve during 2026 and 2027. And then on CVID, my understanding is that on PI3K Delta, you will require a Phase 3. I was just wondering if you could give us an indication of why you might not require a Phase 3 on CVID.

All right, so let me quickly answer your question about the spend on the Abliva program. So, as I said and you heard it from Jeroen, about $30 million this year, $17 million R&D, the rest non-recurring transaction and integration costs. When we announced the deal at the end of last year, we've estimated the total cost of the program to be around $120 million to 125 million. So, you do the deduction with the $30 million, that's - we still in that dock. Obviously, we'll refine this as we complete the integration, resume the trial, but today we don't have any data that tells us that actually this will be any different. Now, when it comes to CVID, I'll let Anurag actually clarify perhaps some misunderstanding.

Yes. Hi, Simon. So, we do anticipate, and again, this is early days, not having even dosed the first patient yet, but we do anticipate that there would be a need for a Phase 3 study as we've done with APDS. We're not anticipating - these are rare diseases. So, these are still relatively small programs. The Phase 2 program in the first PID with immune dysregulation is 12 patients. The CVID indication Phase 2 program will be slightly larger, but we still anticipate a Phase 3 requirement to enable registration. Of course, as the Phase 2 readout, we’ll be able to tell you more what those Phase 3s look like, but that's our current plan.

Okay. And just one last one. I mean, do you also expect CVID to get an FDA fast-track designation at some stage?

We will certainly look at all of those types of options. These are severe diseases. They have a similar course. As APDS, there's early mortality associated with them. These are sick patients who have these conditions. So, we do anticipate being able to work with the regulators to try to expedite the development.

Okay. Thanks very much. That's really helpful.

Thank you. There are currently no further questions. I will hand the call back to Fabrice for closing remarks.

Thank you very much, operator. Thank you very much to those of you who attended the call, and those of you who are on the webcast. As I said, I'm very excited to be joining Pharming. I believe that we are exiting 2024 with a very solid momentum, that there are very clearly identified growth opportunities ahead of us. And as per my answer to the question, our success will come from our ability to realize and manage our P&L rigorously and maintain a very high level of ambition given clearly the growth prospect that we can have with our inline brands, with Abliva. And also, I think the capabilities and the unique infrastructure that we have created that can really position the company as a leading rare disease company in the future. Thank you very much.

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