Afternoon, everyone, welcome back to Oppenheimer's 36th Annual Healthcare Conference. I'm Jeff Jones, one of the senior analysts here on the biotech team. I am delighted to welcome the team from Pharming to walk us through their story. We have Anurag Relan, Chief Medical Officer, Kenneth Lynard, CFO, and Michael Levitan from their IR team. Gentlemen, welcome, and I will let you take it away.
Thank you very much for the warm introduction, and good morning and good afternoon to you all. First and foremost, thanks for your interest in Pharming and for participating in our, you know, session today, with the updates that we would like to give you. Before we are heading into our presentation, I would like to send the apologies from our CEO, Fabrice Chouraqui, who due to the snowstorm on the U.S. East Coast, had his plane back to the U.S. rescheduled from Monday to Wednesday. He's right now somewhere up in the air on his way back to the U.S., where he's based and close to our business operations in the United States. I want to kind of first draw the attention to
Obviously, we will be making some forward-looking statements, I'm sure you're familiar with all the call-outs here, but, you know, be mindful of that. Just coming into a few highlights about the company. Pharming is unique in the sense that we're having a combination of, you know, commercial, already commercialized products and pipelines assets that are really poised to deliver a strong value creation in the years to come. On the commercial side, we're having RUCONEST with a differentiated value proposition, a highly specific manufacturing process. Been to the market for, or been in the market for about 10 years, and continued, as I will show you in a moment, also in 2025, to deliver strong growth.
We have Joenja for APDS, which was launched in 2023, and which we consider a significant near-term catalyst for growth, with opportunities for significantly higher prevalence than what we have seen up until now. We have a strong pipeline with extension for leniolisib into new indications with ongoing phase II trials, and we have the Abliva acquisition, or the acquisition of the company Abliva, and the KL-1333, which we're now calling napazimone, that are kind of, you know, making really good progress in the trials that are ongoing. Anurag Relan will speak more to the assets and give specific details and insights in a moment. I wanted to call out, you know, especially the ongoing commercial activities and the growth we're generating, combined with the pipeline.
You see to the very right here, each asset, with a peak sales potential of above $1 billion. Pharming is in a really good position, also in terms of future growth and value creation. Now, our vision remains that we want to develop a leading global rare disease company with a diverse portfolio and presence in large markets, leveraging really proven and efficient clinical development in the company, as well as the supply chain and commercial infrastructure that we already have in place. In 2025, we took a good step forward. We delivered $376 million in sales, a growth of 27% versus 2024. On the left-hand side here, you really see that we continue to grow RUCONEST strongly and accelerated the uptake for Joenja in APDS.
We have also, more recently, reiterated that, for 2025, our operating expenses will be in the range of $304 million-$308 million, in line with what was communicated earlier, and that we remain committed to continued cost discipline and really kind of optimizing, how we deploy capital, towards high-growth initiatives. We also announced that we expect revenues in 2026 to be between $405 million-$425 million, or between 8%-13% growth. That excludes any growth that would come, from Joenja sales to the pediatric population between four-11 years old in the US, as that's subject to the approval by the FDA and could offer a potential upside to the numbers that are presented here.
Last but not least, I want to draw your attention here to the fact that, you know, for the first nine months of the year, we were generating an operating profit of $30 million and an operating cash flow of $44 million. You know, something that is a really significant step forward versus prior years, for Pharming as well. Our full year numbers, with all details, we will disclose in the earnings call on March 12th, so tomorrow in two weeks, hope that many of you will have the opportunity to listen and hear us communicate the details there as well. With that, let me hand over to Anurag Relan for a more detailed insight to our products and the pipeline in particular.
Thanks, Kenneth. Let's spend the next few minutes talking about our products, RUCONEST and Joenja, and then also a little bit about why we're so excited about the pipeline. Let's jump right into RUCONEST. RUCONEST, again, is a product approved for the treatment of acute attacks of hereditary angioedema. There are other products out there to treat HAE, but RUCONEST really offers a unique value proposition. First of all, it's the only recombinant C1 inhibitor replacement therapy available, and as such, it treats the underlying cause of HAE across these multiple pathways that lead to these HAE attacks.
Of note, it's an IV-administered product, labeled for self-administration, in fact, that offers this unique attribute of being able to be immediately bioavailable because it's IV, and as such, it has a rapid onset of action, and it has a dose that really restores the therapeutic levels of C1 inhibitor in these patients. You see on the right some of the data showing that one dose was sufficient to treat 97% of attacks in the clinical trial setting. That one dose importantly offers a sustained response, meaning that patients who took RUCONEST had no symptoms in 93% of attacks that they treated that lasted for at least three days. This was also a very important finding as we treated patients with HAE type, called HAE with normal C1 inhibitor.
These are patients typically who have more severe attacks. These are patients who are having more frequent attacks despite prophylaxis, and oftentimes, these are patients who've already failed other on-demand therapies. It also has a very unique manufacturing process. It's a protein that's made in the milk of transgenic rabbits, and as such, really, is not susceptible or prone to being easily made into a biosimilar. Next slide. You know, recently we did a comparison to look at RUCONEST as how it compares to sebetralstat, one of the more recently available on-demand HAE therapies. This is not a head-to-head comparison, but what's called a indirect treatment comparison, and this data was presented at the American College of Allergy, Asthma and Immunology meeting back in November.
I'll focus in on the next slide, where you can see the time to complete resolution when attacks were treated with RUCONEST versus sebetralstat. Not a head-to-head study, but an indirect treatment comparison, which shows that a significantly greater proportion of attacks achieved complete resolution by the 24-hour time point when treated with RUCONEST versus sebetralstat. In fact, patients were four and a half times more likely to achieve complete symptom resolution when treated with RUCONEST versus sebetralstat. I think this unique value proposition is highlighted by data such as this, showing how RUCONEST is very beneficial for patients who have HAE. Next slide. Let's turn to Joenja and some of the programs that we have in terms of leniolisib Joenja managing its life cycle.
PI3K delta, which is a enzyme involved in signaling in immune cells, is a master regulator, in fact, of numerous processes that influence the growth and proliferation of immune cells. When this process becomes disrupted and specifically becomes hyperactive, that leads to the complications that you see in the middle here, where you have enlarged lymph nodes and enlarged spleen, autoimmune complications, gut disease, as well as lung disease. What we've seen is that these complications, when they're caused by a mutation in the genes that code for this enzyme pathway, leads to a condition called APDS or activated PI3K delta syndrome. In addition, we have seen that there are other conditions that are also under the influence of this same PI3K pathway.
There are other genetic diseases, that have, that lead to primary immune deficiencies that are also linked to this pathway, and there's also a condition called common variable immune deficiency that results from this, dysregulation in this pathway and leading to a lot of the same complications. Really, we see a lot of similarities between APDS and these other conditions, which makes sense given that they're really under the same influence of this pathway. Next slide. What we've seen with APDS, which is again, where Joenja is initially approved for the treatment of APDS in patients who are 12 years and older, we've seen significant improvements in patients' lives.
Here's an example where you have a patient who has significant fatigue, is on immunoglobulin replacement therapy, impaired quality of life, recurrent infections, needing antibiotics, has numerous clinical manifestations, including low blood counts, has damage in their lung, again, due to those same things that we were just talking about, as well as in their GI tract. This patient was actually treated in the clinical trial for leniolisib Joenja, and actually has been on therapy now for more than six years, and you see a range of improvements that this patient has had since starting treatment with Joenja. Specifically, they've been able to stop their immunoglobulin replacement therapy, their fatigue has improved, no hospitalizations, and again improvements also in their blood counts.
Really, the, this story that we see here, illustrated here, echoes what we see, it with the broader use of Joenja. On the next slide, you can see how we are taking Joenja even further. First of all, you know, when we think about APDS, we think about a prevalence of approximately one-two patients per million. About 30% of those patients are actually pediatric, so currently outside of the label, and I'll talk to you a little bit about that. In addition, there are many patients who get a genetic test for these, for these two genes, but they come back with an inconclusive result, and there's efforts going on now to help be able to reclassify these patients, and we think that eventually, a significant portion of patients could be eventually reclassified as having APDS.
Last year, there was also a publication in Cell that suggested that the prevalence of APDS could be significantly higher when they found that there were many other gene mutations or gene variants that led to hyperactivity. There's work going on there to explore how those patients could also eventually benefit from treatment with leniolisib. We have two phase II programs going on in the middle and the right column there. The first again, is in primary immune deficiencies with immune dysregulation related to this abnormal signaling. You see the number of patients there, which is significantly higher than we think with APDS. On the far right, that's even greater number of patients. These are those patients with common variable immune deficiency leading to immune dysregulation.
We'll talk a little bit about that. Next slide. In fact, what we found is that doctors came to us requesting access for leniolisib for use in these patients with other primary immune deficiencies. These are patients who didn't have APDS, but had similar features to APDS, specifically what we call immune dysregulation. Again, because of this shared biology that's driving that immune dysregulation, it was a rational approach to offer leniolisib to these patients. In fact, six patients have been treated in this expanded access program, and we've seen general improvements across a number of endpoints, including biomarkers, lymphoproliferation, and organ disease, as well as overall sense of well-being and fatigue.
Again, this is not a clinical trial, but this gave us the interest and confidence to say, "Okay, this is something that should be formally studied, given that we've seen these improvements in these patients." On the next slide, we can talk a little bit about what we're dealing with here. Again, is again, on the far left is APDS, and you see those clinical features in terms of infections and all of the autoimmune and autoinflammatory complications. In the middle and third columns, you see those other two programs that we have with very similar disease manifestations, but in this case, they don't have a treatment option available to manage all of the features of immune dysregulation. These two programs are on well underway.
They have phase II proof-of-concept studies going on, where we expect to read out in the second half of this year. Next slide. Now, turning on to our third asset, which is called napazimone, formerly known as KL-1333. This is being developed for primary mitochondrial disease that is driven by mutations in patients with mitochondrial DNA mutations. This could be the first disease-modifying treatment for these patients. Here also, we see that napazimone targets this underlying problem that these patients have, and specifically, because of these mutations in their mitochondrial DNA, they have an abnormal NAD+ to NADH ratio, which impairs their mitochondrial function.
We've seen that napazimone is able to correct that, and we've seen this in in vitro data, animal models, as well as in patients treated with KL-1333, and I'll share some of that data with you shortly. This is a significant patient population. You see there are more than 30,000 patients who are diagnosed with mtDNA disorders in the U.S. and Europe, and the vast majority of these patients are treated in centers of excellence. There is a registrational study underway here. This is a phase II program, where there have been discussions with FDA, including on endpoints. These are clinically relevant endpoints of fatigue and muscle strength, and these are endpoints that have been supported again, by the regulators.
There was a positive interim analysis in which both endpoints, in fact, cleared futility, and on that basis, the study continues, and we expect readout to be at the end of 2027, with approval the following year. Let's go to the next slide and talk a little bit about the study. Actually, first about the results. This is the results from the phase I-A/I-B program with patients showing how napazimone was able to improve patient fatigue, and you see that on the left, and then in the middle column, you can see how this also improved muscle function. This was being assessed by what's called a sit-to-stand test, and in fact, it's the same endpoint that's being used in the pivotal study.
Lastly, we saw improvements in their lactate to pyruvate ratio, which is an important measure of target engagement. We see that because these patients have impairment with oxidative phosphorylation, excuse me, these patients have high levels of lactate, and we see that by treating with KL1333 or napazimone, we're able to correct that ratio and bring that down in patients treated, again, even in the short duration of a two-week study. Let's turn to the ongoing study, which is called the FALCON Study. The FALCON Study was conducted in two parts. The first part, or wave one, was 40 patients who were treated across six countries, and there was an interim futility analysis conducted after those 40 patients were treated for six months.
That futility analysis showed that both endpoints, in fact, both primary endpoints, passed futility, suggesting that there were promising differences between these groups, and that if these trends continue, we could expect a successful result at the completion of the study. The data monitoring committee also reviewed safety and tolerability and allowed the study to continue without any changes to study design. There was an increase in the sample size or a sample size re-estimation that was performed, and a total number of 180 patients was confirmed for the study. That part of the study now is enrolling, so there will be a total of 180 patients, so that includes the 40 that were already treated, and these will be patients who are treated for a total of 48 weeks.
We already have the original sites up and running, and we've actually opened several new sites, and we're, in fact, planning more than a doubling of the total number of sites, including in the U.S. We're expecting to complete enrollment this year, which would enable us to read out the study at the end of next year. Next slide. Now just a quick update on some of the other developments. As we announced earlier this month, we did receive a Complete Response Letter on the supplemental NDA application to expand the use of leniolisib to APDS patients who are between the ages of four and 11 years old. We have now requested a Type A meeting to discuss the path forward with FDA. Some good news on the EMA front or the front in Europe.
We have responded to the questions from CHMP. Originally there was a oral explanation scheduled. EMA has now cancelled that oral explanation, deeming it to be unnecessary. We now expect a March opinion from the CHMP, with a potential approval two months later, landing us in the first half of this year. In addition, we have several reviews ongoing, including in Japan, which are also on track for approval later this year. As I mentioned, we're very excited about these two phase II programs, these proof of concept programs, and we're on track to be able to read out these studies in the second half of this year.
Lastly, the napazimone program, we have more than 20 sites actively recruiting, as I said, with a quick increase in the number of sites, which will enable us to read out the study at the end of next year. With that, I will turn it back over to Kenneth to review our financials.
Thank you very much, Anurag Relan, for all the insights. We just wanted to put up in front of you know, a positive rolling 12 months financial trend. When you look across revenues, and we already spoke about our 27% growth during 2025, but you also see here from a 12-months rolling basis, how the operating profit and operating cash flow, based on the first nine months of the year, are trending in a very favorable way. We are quite positive about the improvement in the financial performance of Pharming in 2025. Let's just kind of, you know, spend a moment on reiterating what we communicated about a month ago in terms of financial guidance for 2026.
We do expect, as I mentioned in the beginning of this presentation, revenues between $405 million-$425 million, or an 8%-13% growth, with continued RUCONEST growth around the mid-single digit and significant and accelerating growth for Joenja. We will continue to have the financial discipline and prioritize our investments. Operating expenses are, we are guided to be between $330 million-$335 million, and that compares, just for reference, to the $304 million-$308 million that we have said for 2025. In 2026, we expect to have about $60 million of incremental R&D investments to advance our pipeline.
Obviously that means that, you know, the $9 million of structural G&A cost reductions that we announced in October 2025, as well as other optimizations, are helping us here to reduce the overall growth in operating expenses and really focus on the advancement of the pipeline. We expect or continue to expect that the available cash and future cash flows are expected to cover, you know, current pipeline and pre-launch cost, and therefore financing needs, not necessary to assets that are already part of what we have in Pharming. Just before opening up to Jeff for any potential questions, you know, we are building momentum across commercial, financial, and, you know, our pipeline.
We already talked about and want to leave with all of you know, the strong revenue performance in 2025, with high double-digit growth for both products, significant operating profit and cash flows, and the guidance that we just spoke about. You know, we have a sustained growth of the commercial portfolio, which we continue to work towards. We have significant growth catalyst for Joenja. We have a very, let's say, strong and enhanced capital allocation, you know, approach that we are driving within the company.
We have a high-value pipeline, you know, that Anurag just spoke about, and we really feel that we are on a strong journey to build a leading rare disease company with a growth-oriented leadership team, proven commercial and development capabilities, and that we now have an organization that is scalable to also being able to take on more growth and really realize the potential, the full potential of the, of the company. With that, we're kind of, you know, handing back, I think, to Jeff. We have about five minutes left, and we'll be pleased to answer any questions you may want to ask us.
Great. Thank you guys very much.
Mm-hmm.
the detailed presentation, I guess maybe starting out with RUCONEST. Obviously, there's been the launch of Actemra into the market as an oral. Folks expected it to have perhaps a bigger impact than we're certainly seeing. RUCONEST seems to be very sticky, maintaining your revenues and continuing to grow your revenues within your target population. What do you think, and what do you hear from patients that's really keeping those patients on RUCONEST versus an oral option?
Do you want to speak to that, Anurag?
Sure. Jeff, I think, you know, HAE patients, and there's a good portion of them that are not well controlled with existing therapies, and these are patients who are on prophylaxis but still having attacks. What we find is that the typical RUCONEST patient is one of these patients that has had a long journey to get to RUCONEST. They've typically been on multiple prophylactic agents, usually have been on at least one, if not more than one, acute agent. Given that long journey and then finally arriving at RUCONEST, which seems to help with their disease, you can imagine that that type of patient is probably less willing or interested in trying something that may not be effective for them.
I think that's really the driver here in terms of that stickiness, is that long path that these patients take to get to RUCONEST, in terms of being able to manage their disease.
Okay. I know you guys made a bit of a commercial strategic change for RUCONEST in Europe relatively recently. You're now looking at Joenja becoming available in Europe with those ongoing discussions. How does this impact your commercial operations and planning? Do you need to invest more in commercial operations for Europe for Joenja, or is that something that's still been left in place following the adjustments you made?
I think the overall way of thinking about it is the company has indeed made the strategic decision to, should say, withdraw from commercial activities related to RUCONEST outside of the US. you know, we have not taken out all the infrastructure, so we can leverage parts of that as we are now building out on the Joenja franchise. There'll always be investments as we grow the business, but this is not starting from scratch.
Okay. you know, the acquisition of napazimone, still getting my head around that one.
Mm-hmm
La st year was really interesting. It's a very interesting indication, obviously a late-stage asset. Are you guys continuing to look at business development opportunities and building, you know, adding to your pipeline?
I mean, absolutely. It's part of Pharming strategy, in terms of, you know, the ability to deliver on our vision that we have spoken about. We have a very active business development team that are scouting the market for in-licensing as well as M&A opportunities, and are taking them through a very thorough, let's say, assessment in terms of strategic fit and scientific profile, and, you know, financial viability, return on investment, et cetera. That remains a very important part. You will continue to see that we are, on a selective basis, you know, doing activities in that field.
All right. Well, gentlemen, I think we are up on time, so thank you very much for the presentation today. Looking forward to the further update in a few weeks, when you report out full year. Hope you have some great meetings today, and we'll be talk soon.
Thank you very much, and thanks, everyone, for joining the presentation.
Thank you, guys.
Thank you.