Good day, and thank you for standing by. Welcome to the Pharming Group NV Q3 2026 Results Conference Call and Webcast. At this time, all participants are in listen only mode. After the speakers' presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one and one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one and one again. Please be advised that today's conference is being recorded.
I would now like to hand the conference over to your speaker today, Kenneth Lynard. Please go ahead.
Thank you, operator. Good morning and good afternoon, everyone, and thank you for joining Pharming's third quarter 2026 call. I am joined today by Leverne Marsh, my fellow interim Co-CEO and our Chief Commercial Officer, and Dr. Anurag Relan, our Chief Medical Officer. After my opening remarks, Leverne will review our commercial performance, Anurag will cover R&D, and I will return to take you through the financials and outlook before we open the line for questions. As you know, on September 29th, Fabrice Chouraqui stepped down as CEO, and the board appointed Leverne and me as interim co-CEOs while it conducts a formal search for permanent successor. As of now, there are no additional updates to report, and despite these changes, our strategy, pipeline, and commitment to patients remain unchanged.
Before we begin, please note that we will be making forward-looking statements on this call. These are based on our current expectations and plans, and actual results may differ materially. Please refer to the full statement on this slide. We are pleased to report a strong third quarter performance. Before I go further, I want to comment on why we decided to report results today rather than on November 5th, as originally scheduled. Because our third quarter results came in above analyst consensus, we did so on October 22nd in a pre-release with top-line revenues and operating expenses only. We appreciated that once these numbers were public, investors would want to see the full details behind the numbers as soon as possible and have the opportunity to ask questions.
As a result, we moved the date up for our full third quarter disclosure to today. The change in date is not related to any transaction or restructuring of the company. Getting back to this slide, as many of you have followed Pharming know, our strategy rests on three pillars. RUCONEST continues to provide a durable source of cash flow, and I am pleased to report it has returned to growth this quarter. Joenja, a high-growth asset still early in its life cycle, is expanding geographically and with a new pediatric indication. A high-value clinical pipeline with two potential billion-dollar opportunities, leniolisib in broader primary immune deficiencies, including CVID, and napazimone in mitochondrial DNA-driven primary mitochondrial disease.
Turning to the quarter in more details, total revenue grew 21% to $117.6 million ahead of market expectations. This quarter, RUCONEST returned to revenue growth, Joenja sales grew 58%, and our operating profit increased by 89%. We are also tightening our full year revenue guidance to $380 million-$390 million and lowered our operating expense guidance to $310 million-$315 million. Both of our commercial products contributed to growth. RUCONEST returned to growth in the quarter with U.S. demand back to prior year levels in volume terms. Joenja continued to grow strongly in the U.S. and internationally. That performance carried through to a significant increase in operating profit and strong operating cash flow.
Leverne will take you through each product shortly, and I'll come back to the full financials and our guidance later in the call. At the start of the second half, we laid out three goals for 2026, and I'm happy to report that we made notable progress on each of these during the quarter. First, RUCONEST. We stabilized demand and returned revenue to growth in the quarter ahead of our own projections, and furthermore, saw stabilization in underlying demand. Second, Joenja and APDS. Geographic and pediatric expansion continued.
We launched in Germany in July and Japan in August, with Japan becoming the first market where Joenja is commercially available for children aged 4- 11. In the U.S., the FDA approved our pediatric label expansion on September 11, ahead of the PDUFA date, and shipments for this newest market segment began this month. Third, advancing leniolisib in conditions beyond APDS. On October 14, we presented positive phase II top-line data in genetic PIDs with immune dysregulation, and we expect to report top-line data from our CVID study in November. These updates represent substantial growth for leniolisib in the years ahead.
With that, I'll hand the call over to Leverne to discuss our commercial performance. Leverne?
Thank you, Kenneth. Good morning. Good afternoon, everyone. I'll provide an update on our third quarter commercial performance and the growth opportunities ahead for RUCONEST and Joenja. Starting with RUCONEST. The third quarter marked a return to revenue growth for RUCONEST. As you heard from Kenneth, RUCONEST revenue reached $93.8 million, an increase of 14% year-over-year. Importantly, we have stabilized underlying U.S. demand with volume returning to prior year levels. This compares favorably to declines we reported in Q1 and Q2, and we expect this positive trend in demand to continue into Q4. We're encouraged by the stabilization that came only one year after the introduction of the first oral on-demand treatment. As we communicated previously, RUCONEST demand has not been impacted by any new prophylaxis treatments that were launched in 2025.
We continue to maintain the overwhelming majority of our active patient base, with particularly strong retention amongst patients experiencing more frequent or severe HAE attacks. We continue to attract new patients and new prescribers. To put our revenue performance into context, there's one additional factor worth highlighting. RUCONEST third quarter revenue benefited from a seasonal increase in channel inventory that came a quarter earlier than expected. This contributed approximately 9 percentage points of the quarter's 14% year-over-year growth. While these inventory levels can fluctuate, the underlying patient demand remains our most meaningful indicator of the franchise performance. The stabilization that we've seen in RUCONEST demand reinforces our confidence in its resilient and differentiated position within the HAE treatment landscape. While treatment options are expanding choices for patients, we know that HAE is not a one size fits all disease.
Patients who are experiencing more frequent or more severe attacks often have very distinct treatment needs, and RUCONEST continues to play an important role for this population. By replacing deficient or dysfunctional C1 esterase inhibitor, RUCONEST targets the root cause of HAE across all pathways, offering high efficacy and a fast, complete resolution of attacks. We believe that these attributes are particularly important for patients with a higher disease burden and helps explain the strong patient retention that we've seen. More than a year after the launch of the first oral on-demand competitor, the overwhelming majority of RUCONEST patients have remained on therapy, and physicians continue to prescribe RUCONEST for new patients with more severe disease. In addition, RUCONEST's highly specialized manufacturing process may present challenges for direct biosimilar competition, and these factors combined further support our confidence in its long-term commercial position.
Now turning to Joenja. We continued to build on our commercial momentum in the third quarter, with global revenue increasing 58% year-over-year to $23.8 million. This is driven by continued U.S. patient growth and an increased contribution from international markets. In the U.S., revenue increased 19% to $15.9 million, supported by continued growth in patients on therapy. We ended the quarter with 136 U.S. patients on paid therapy, up 17% year-over-year. Also an increase of four patients from the end of the second quarter. Internationally, our revenue increased to $7.9 million compared to $1.7 million a year ago. Now the international business represents approximately 1/3 of Joenja's global revenue. This growth reflects our expanding international presence, including launches in Germany and Japan, alongside continued penetration in the U.K.
At quarter end, 75 patients were receiving paid therapy internationally, including 30 patients in launch markets and 45 patients through paid access programs in other markets. It's worth noting that international revenue for Joenja also benefited from ordering patterns in certain markets that we consider temporary. As a result, there is a $2 million-$3 million in earlier revenue recognition that benefited Q3 that we originally expected in Q4. Importantly, the growing number of patients receiving treatment across markets demonstrates continued progress in expanding Joenja's global commercial reach. Additionally, our third quarter results do not yet reflect any revenue contribution from the newly approved U.S. pediatric doses, which began shipping in October. This brings me to our next slide. A notable next phase of Joenja's U.S. growth is now underway following FDA approval of the new pediatric doses in September.
This approval expands access to Joenja for eligible children aged 4- 11, an important population that was previously outside of the approved age range. On September 11, as Kenneth mentioned, the FDA approved our supplemental New Drug Application for the 40 and 50 mg twice-daily doses for children aged 4 - 11, weighing at least 27 kilograms. This happened ahead of the anticipated October 24 PDUFA date. Our shipments began in October, marking a significant milestone in our efforts to expand treatment across younger patients with APDS. We're also pursuing further expansion of our pediatric label, and in July, we submitted a separate supplemental application for the lower doses for children aged 4 - 11, between 13 and less than 27 kg. The FDA has accepted the application with Priority Review, and we have an assigned PDUFA date of January 30, 2027.
To date, we've identified over 60 children aged 4- 11 with APDS in the United States. The newly approved doses address 38 of these patients, with remaining children potentially becoming eligible under the lower dose application if approved. We've seen a strong start to the pediatric launch in the U.S., and we are expecting an initial bolus of new patients on therapy throughout Q4, in the range of 15- 20 patients on therapy. We look forward to providing an update on patients receiving treatment when we report our full-year results early in 2027. Looking ahead, we see several growth drivers that can build on Joenja's established commercial foundation in APDS. In the U.S., we expect continued patient finding, increased genetic testing, and expanded treatment access for younger pediatric patients.
As of September 30th, we had identified 304 patients with APDS in the United States and 1,056 globally, reflecting continued progress in identifying individuals living with this rare disease. Internationally, our focused geographic expansion can result in a doubling of the addressable APDS opportunity. Joenja is now approved in all our target launch markets, with Germany launching in July, Japan in August, building on our established presence in the U.K. Beyond APDS, our clinical development programs are exploring leniolisib's potential in significantly larger populations of patients with immune dysregulation. For common variable immune deficiency, or CVID, with immune dysregulation, where we plan to pursue a registrational trial, there are more than 13,000 patients in the United States, a 26x prevalence compared to APDS. Anurag will review our clinical programs with leniolisib in just a few minutes.
While this remains investigational, it certainly represents a potentially significant expansion of Joenja's addressable opportunity. Together, these growth drivers provide a clear path to build on Joenja's existing commercial foundation with continued expansion in APDS to the potential treatment of substantially larger patient populations in CVID. Our ambition is to establish Joenja as a broader immunology franchise with blockbuster potential.
With that, I'll turn the call over to Anurag to discuss our clinical development programs.
Thank you, Leverne. Before turning to our new PID programs, let's quickly review some background, specifically that PI3Kδ is a central regulator of immune cell development and activity. In APDS, where the pathway is overactive, Joenja has shown durable reductions in lymphoproliferation and has a well-established safety profile with up to seven years of treatment. Now let's turn to what's new. Our first clinical data for leniolisib beyond APDS, and what to expect from our CVID readout in November. The rationale for going beyond APDS is that there are other genetically defined PIDs and CVID patients with immune dysregulation who show similar PI3Kδ -driven biology. As a result, these populations share the same clinical manifestations we see in APDS, namely lymphoproliferation, autoimmunity, gastrointestinal disease, and pulmonary disease.
The two phase II studies we are running cover patient populations that are substantially larger than APDS, as Leverne just mentioned, but they share a similar unmet need. The prevalence, as you heard, is 26x greater than the APDS prevalence, and this includes the overlap with the genetic PID population. The two phase II studies that I've described have similar endpoints and objectives that we've discussed previously, and you can see here on this slide. They include spleen and lymph node size, blood cell counts, lung and liver involvement, and patient and clinician-reported outcomes, as well as biomarkers. Together, these studies will inform our plans for a potential registrational study. Because PI3Kδ is a shared driver across these populations, we continue to anticipate a single phase III study in this broader CVID indication, incorporating patients from both studies.
Here's an overview of the genetic PID study results we presented at a late-breaking abstract at the European Society for Immunodeficiencies conference two weeks ago. As you can imagine, we are excited by these results as they are the first clinical data establishing proof of concept for leniolisib in primary immune deficiencies beyond APDS. The study enrolled 13 participants, 12 of whom completed treatment. The mean age in the study was 32.5 years, and importantly, nine of the 13 participants also had a CVID diagnosis, which is relevant as we look ahead to the CVID readout. The data showed that treatment with leniolisib resulted in improvements across a number of objective measures consistent with the PI3Kδ mechanism, including spleen volume, lymph node size, lung gas exchange, and liver stiffness. Leniolisib was well-tolerated with no new safety signals.
Infections were the most common adverse event, as would be expected in a PID population, and two patients had serious adverse events considered unrelated to leniolisib. Also important, all 12 participants who completed the study chose to continue to enter the three-year long-term extension study, which we see as a meaningful signal from both patients and physicians. Looking ahead to the CVID readout, which we expect to report top-line results from next month. This is a 20-patient, single-arm, open-label, multi-center study in CVID with immune dysregulation, with or without a genetically identified cause. We will report across the same measures as in the previous PID study, including lymphoproliferation, cytopenias, lung and liver disease, biomarkers, and safety. The CVID population is more heterogeneous and many patients have no identified genetic cause.
We will be looking for a consistent direction of benefit across measures and a dose to take forward. Together with the genetic PID data, the CVID results will inform a potential registrational study. In fact, we've already planned several regulatory interactions to discuss the endpoints and design of a phase III study, including an End-of-Phase II meeting with FDA. Turning to napazimone or KL1333, which is being developed to treat mitochondrial DNA-driven primary mitochondrial disease, which is in a registrational enabling study. This is a rare disorder in which mutations in mitochondrial DNA cause debilitating fatigue and muscle weakness. With more than 30,000 diagnosed patients in the U.S., EU4, and the U.K., there is no approved disease-modifying treatment. Napazimone targets the underlying pathology by normalizing the NAD+ to NADH ratio and mitochondrial function.
The primary endpoints of our pivotal FALCON study are improvements in fatigue and a measure of muscle weakness called a sit-to-stand test. Both endpoints have cleared a futility analysis at the interim look at the data, which was conducted after 40 patients had gone through 24 weeks of treatment. The study continues to enroll patients with more than 50 sites now recruiting and where there has been a significant expansion in the U.S. Based on the patients already screened, we expect that 145 of the planned 180 participants to be enrolled by the end of this year, and we expect enrollment to be complete during the first half of 2027. Top-line results are therefore expected approximately one year after enrollment is complete.
With that, I will turn it back to Kenneth.
Thanks, Anurag. I would now like to take a moment to walk you through the financial highlights of Q3 2026 versus Q3 2025. Our third quarter revenue was $117.6 million, up 21%, with Joenja up 58% and RUCONEST up 14% year-over-year and 30% sequentially. Operating profit was $29.9 million, up 89%. Excluding a $5.1 million one-time manufacturing-related inventory impairment, adjusted operating profit increased significantly to $35 million compared to $16 million a year ago. Operating expenses were $74.6 million, in line with a year ago, and the result also benefited from higher other income, mainly received R&D tax incentives. Net profit was $22.4 million compared to $7.5 million last year, including a favorable foreign exchange result.
Operating cash flow was $32.4 million, and cash and marketable securities rose $31.4 million in the quarter to $190.9 million, driven by profitability and partially offset by normal activity-driven working capital movements, including increase in trade and other receivables. For the first nine months of the year, revenue was $280.2 million, up 4%. Joenja grew 45% to $55.7 million, and RUCONEST was 3% lower at $224.5 million. Adjusted operating profit was $38 million compared with $29.7 million, driven by higher revenue and total operating expenses 2.8% below the prior year. Operating cash flow was $24.7 million year to date, with cash and marketable securities increased $9.8 million since year-end to $190.9 million after the $12.3 million settlement for the early termination of the DSP facility lease in the first quarter.
For the full year 2026, we have tightened our revenue guidance to $380 million-$390 million, representing 1%-4% growth, and lowered our operating expenses guidance to $310 million-$315 million, representing 0%-1% growth. That includes approximately $35 million incremental R&D investment and about $9 million of structural G&A savings. Our full year guidance continues to assume that RUCONEST revenue will stabilize and return to growth in the second half of 2026, and that Joenja will deliver significant and accelerating growth for the year. At the midpoint of our guidance range, RUCONEST U.S. revenue is expected to decline approximately 3% for the full year. For Joenja, we continue to expect annual revenue growth in the mid 30% as compared to 29% growth in 2025, with international launches and the U.S. pediatric revenues in the fourth quarter contributing.
For the full year, we expect cost of goods sold to be approximately 12% of revenue, including the $10 million manufacturing inventory impairments recorded in Q2 and Q3, corresponding to a gross margin of around 88%. With nine months revenue of $280.2 million, our guidance implies fourth quarter revenue of roughly $100 million-$110 million. As Leverne noted, third quarter RUCONEST revenue included an early seasonal increase in channel inventory, and fourth quarter revenue may reflect inventory timing. For Joenja, the $2 million-$3 million early international revenue recognition we saw in Q3 was pulled forward from Q4. Finally, our cash position of $190.9 million, together with future operating cash flows, is expected to cover our current pipeline and pre-launch costs.
In closing, this quarter showed what our business can deliver. RUCONEST returned to growth in the quarter with stable U.S. demand and a resilient patient base and remains a durable source of cash flow. Joenja grew 58% and is still early in its life cycle. New pediatric doses began shipping in the U.S. earlier this month. With a strong start to the launch, we have a PDUFA date of January 30th, 2027 for lower pediatric doses, and our launches in Germany and Japan are well on the way. Moving to our pipeline, leniolisib delivered positive data in genetic PIDs, and we expect top line CVID data in November, which will shape our path to potential registrational study.
FALCON enrollment continues to progress towards completion in the first half of 2027. We are running the company with discipline. Operating expenses were flat in the quarter. Operating profit rose 89%, and we ended the quarter with $190.9 million in cash. Leverne and I, together with the leadership team and the board, are focused on execution consistent with our strategy.
With that, operator, please open the line for questions.
Thank you. As a reminder, to ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Our first question comes from the line of Benjamin Jackson from Jefferies. Please go ahead. Your line is open.
Great. Thank you for the question, or thanks for the presentation. Very clear, across the full spectrum, I guess. Just a couple from me. The first, I just wanted to touch on the RUCONEST patient initiations you saw during 3Q. I guess when we look historically, the third quarter is typically seasonally lower. But relative to historical, still probably a lower value than perhaps we anticipated, and we made a fairly big deal about it being a leading indicator back at 2Q. Perhaps you could provide a little bit of color around the, I think it was the 43 patient additions you saw this quarter and how that is tracking in the first month of the fourth quarter.
Secondly, any color you can provide in and around the CEO search and how the board is thinking about a profile for this individual. Are they looking both internally and externally and kind of what. Just making that profile a little bit more clear to us in terms of what they're looking for. Then the third and final one from me, just if you could add any color behind the slower FALCON recruitment, just be interested if there's something specifically about patient identification or competing trials running at the same time that perhaps has impacted the timelines versus your prior expectation. Thank you.
Great. Thanks, Ben, for the question. I think your first remark is important, right? Because we do see new patient enrollments naturally vary from quarter to quarter. Exactly as you said, we typically see Q3, if we look back, somewhat softer than Q2. So that pattern certainly continues. However, we don't necessarily view a single quarter as a reliable indicator of the long-term demand trend. So what I'm asking everyone to pay attention to is that RUCONEST is a combination of new enrollments, the retention that we've seen, and we've maintained over 90% of our active patient base still one year after an oral competitor.
We also review the retention amongst high-burden patients, which tend to be our high vial users. In this area, we disproportionately retain high-burden patients who suffer from severe attacks. That supports what we see in the volume growth. When we talk about stabilizing demand for RUCONEST and vial volumes returning to the same level it was in Q3, those are all the aggregate factors that are contributing to demand. So new enrollments, a disproportionate retention of high-burden patients, and patients returning back to RUCONEST. Based on what we've seen in Q3, on the back of declines that we reported in Q1, Q2 in volume demand. Q3 then returned to volume stabilization prior year levels, and we expect that strong momentum in demand to continue into Q4.
Ben, thanks for the question regarding the CEO, the leadership transition. Let me take the opportunity to reiterate that despite the leadership transition announced, there are no changes to our strategy, pipeline or the commitment to patients. That all remain unchanged. Leverne and I are as interim Co-CEOs, driving the organization to execute on all the priorities that we have talked about earlier and which we have given an update today on the progress on, and that we will continue to do. Meanwhile, the board is conducting a formal search for a permanent successor, and we don't really have any further updates on that at this point of time. But with the commitment that, in due time, of course, the company will provide updates as to the progress and the conclusion of that process.
Hi, Ben. On the question of FALCON enrollment. As I mentioned, we have more than 50 sites now recruiting, with many of those sites in the U.S. And the year-end estimate is actually based on patients who've already gone through or entered the screening process. The main bottleneck really was site activation, and that's largely now behind us. Investigator engagement and patient engagement actually remains very high. The sites that we've gotten up and running just in the past few months are very active, and we've seen a very high number of enrollments or screenings come just in the past couple of months. I think we really have this main bottleneck now largely behind us.
Great. Thank you for all of that.
Thank you. We will now move on to our next question. Our next question comes from the line of Sushila Hernandez from Van Lanschot Kempen. Please go ahead. Your line is open.
Yes. Thank you for taking my questions. I also have a few. At the moment, there are 30 patients on paid therapy in international launch markets. What is the Joenja opportunity for Japan, Germany, and the U.K., and could there be a trigger for further acceleration? Then a second question on the CVID study. What should we expect from this study to read out? What would be meaningful reduction in spleen volume? Then the third, just to clarify, you mentioned available cash covers pre-launch costs. Is it for KL1333, or would you need additional cash? Thank you.
I will take the first question. Thanks, Sushila, on the Joenja question. As you say, we have 30 patients on therapy in our launch markets, and that is in addition to 45 patients in non-launch markets, so other international markets on a named patient basis. In terms of the breakdown by country, because the launch is in Japan and Germany is still early, we will not be disclosing country-level patients on therapy quite as yet. What I can say is that we have seen a really, really healthy uptake, both in Germany and in Japan, on the back of established presence in the U.K. Future catalysts for growth in these three launch markets in particular are, A, for the U.K., an expansion in the pediatric population and the pediatric indication for the higher doses similar to what we have now in the U.S., so that is one growth catalyst.
Then continued progress both in Germany and Japan, as we engage physicians, as we educate physicians on the positioning of Joenja for patients with APDS. Those two key elements for Germany and Japan is going to be really, really critical.
Hi, Sushila. On the question of CVID and what we're looking for here is, we're looking to see if there's a consistent direction of benefit across lymphoproliferation, cytopenias, and the end organ measures. Take a look back at what we've done in APDS, and what we've seen is that there have been consistent improvements in lymphoproliferation. We've seen spleen volumes decrease, we've seen lymph nodes decrease in size, and of course, lymph node reduction was the primary endpoint in the APDS study. Obviously important from a regulatory standpoint, too. We've also seen now in the genetic PID study that just read out, we've seen a consistent improvement there also in lymphoproliferation. Seeing an improvement in lymphoproliferation would be important. Of course, it's expected based on this mechanism, but we need to establish that that can also be seen in patients with CVID.
I think that's probably one of the most important things that we'll be looking for. Obviously, these patients, as I said earlier, are heterogeneous, so they have other manifestations of the disease. The cytopenias and other end organ measures we'll be looking at. We'll also be looking at clinician-reported and patient-reported measures because we know these are important, obviously to patients, but also to regulators. Then lastly, we're looking at tolerability and safety and trying to determine what the dose should be to move forward in a larger study.
Sushila , maybe just on the cash aspect. No, we don't need to raise additional financing. The cash position end of September, together with the future cash flows that we are projecting, are covering, let's say, all our current pipeline costs, and also pre-launch costs related to those assets. Thanks for the questions.
Okay. That's clear. Thank you.
Thank you. We will now move on to our next question. Our next question comes from the line of Joe Pantginis from H.C. Wainwright. Please go ahead. Your line is open.
Hey, everybody. Good morning. Thanks for taking the questions and all the details today. I have a question. How would you envision the integration of Joenja when PID and CVID indications potentially get approved? Namely, could this be a potentially easier integration because of the current physician base, and also what kind of physicians or specialties could be expanded into? Thank you.
Great question, Joe. In fact, the doctors that diagnose and see APDS patients are largely the same physicians that see patients with CVID and these genetic PIDs. These are primarily immunologists, and they have a lot of experience in immune deficiency. It is really the same group of doctors that are seeing all three groups of patients.
Thank you.
And then in terms of execution, Joe, obviously with Joenja, we have established commercial medical affairs, market access, patient services capabilities in the U.S. with a very successful Joenja launch in APDS. All of those capabilities will be transferable to CVID. So calling on the same physicians, engaging payers with the value proposition for CVID, expanding our patient services program to accommodate for these CVID patients, and then continued commercial and medical affairs execution. Excited to be able to build on those capabilities that have served us well for Joenja and APDS.
Great. Thanks for the color.
Thank you. We will now move on to our next question. Our next question comes from the line of Simon Scholes from First Berlin. Please go ahead. Your line is open.
Yes. Good morning and good afternoon. Thanks for taking my questions. I have just got one, actually. So you have mentioned that in Q3, your numbers benefited from early inventory build by one specialty pharmacy. Might it not be the case that in Q4, your numbers benefit from inventory build by other specialty pharmacies?
Hi, Simon. Thanks for the question and astute observation. Yes. What we are expecting to see typically in Q4 is specialty pharmacies increasing inventory before year-end. We see that across the industry. You are 100% right, we have seen one specialty pharmacy pull that forward into Q3. While we are expecting, again, additional seasonal adjustments as the rest of the channel adjusts in Q4, I would think about it exactly as you say. RUCONEST components, as you look forward to Q4, would be demand. As we have stabilized our demand to prior year levels, recovering from the first and second quarter declines, we are expecting that momentum on demand to continue in Q4.
We are expecting some seasonal adjustment of inventory from the remainder of the channel, including the specialty pharmacy who have just bought in. Then finally, as you think about revenue, accommodate for price increases and some gross to net adjustments, and that will make up RUCONEST for Q4.
Okay, thanks very much. That is very helpful.
Thank you.
Thank you. Once again, to ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Our next question comes from the line of Fanyi Zhong from OpCo. Please go ahead. Your line is open.
Thanks for taking my question. This is Fanyi on for Jeff Jones from Oppenheimer. For the question about RUCONEST. Given the guidance of 2026 revenues, it looks like you estimate a softer 4Q revenue for RUCONEST versus 3Q. Should we expect a similar revenue pattern next year with a softer first half followed by a stronger second half? For leniolisib, what do you define as a successful November CVID readout? I probably have one follow-up. Thank you.
All right. For RUCONEST, thanks so much for the question, Fanyi . For RUCONEST, we are at midpoint of guidance, forecasting a 3% annual decline. You remember the Q1, Q2 declines. We have now seen a return to revenue growth in Q3 and a stabilization of demand in Q3. For Q4, the components will be as what I have discussed before. We are expecting demand growth to continue. We are expecting that momentum on demand to continue, but we are expecting inventory adjustments in the fourth quarter that will impact revenue, and that is the biggest factor now. From a seasonality perspective into next year, we are anticipating a new oral competitor that to date has a PDUFA date at the end of April.
What we are planning for is a similar pattern of impact that we have seen with the first oral competitor. As we look at how the quarters have evolved since the sebetralstat introduction, we are planning for a similar impact going forward. But the underlying business for us is really important. We have maintained more than 90% of our active patient base since the introduction of that first oral competitor. We have built back volumes to the previous year levels, and that is on the back of a disproportionate retention of high-burden patients that tend to use more vials. We continue to start new patients and engage new prescribers. Those are the different components that I would take into account for 2027 for RUCONEST.
Yeah. Fanyi, thanks for the question on CVID. I think it's important to remember that within CVID, we're enrolling patients with immune dysregulation, so not all CVID. The population that we've selected for the study is really enriched for a specific endotype. Immune dysregulation and CVID converges on this endotype, which includes this expanded population of certain B cells called CD21- low B- cells, elevated levels of CXCL13, and most importantly, lymphoproliferation. Lymphoproliferation is manifest as enlarged lymph nodes and a big spleen. What we've seen from the genetic PIDs data, as well as the data, of course, originally in APDS, is that leniolisib can positively impact lymphoproliferation.
We've seen that, and so that's obviously going to be one of the important things that we're going to be looking for in the CVID data. But we know that these CVID patients have other manifestations, too. We're also going to be looking at the response to those manifestations, including in the lung, as well as in the liver. So, lots of things to look at and try to see if we can positively impact and have a, like I said earlier, sort of a consistent direction of benefit in these patients.
Got it. Thank you so much.
There are no further questions at this time, so I'll hand the call back to Kenneth for closing remarks.
Thank you very much. Yes, this indeed concludes our Q&A. Thank you all for joining us today and for your questions. We look forward to sharing our CVID results in November and updating you further with our full year results. Thank you, everyone, for joining, and have a good day.
This concludes today's conference call. Thank you for participating. You may now disconnect.