Pharming Group NV (PHAR) 2025 Q4 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Pharming Group N.V. Fourth Quarter and Full Year 2025 Financial Results Conference Call and Webcast. (Operator Instructions) Please note that today's conference is being recorded.

各位好，感謝您稍候。歡迎參加 Pharming Group N.V. 2025 年第四季暨全年財務業績電話會議與網路直播。（接線員指示）請注意，今天的會議將被錄音。

I would now like to turn the conference over to your first speaker, Mr. Fabrice Chouraqui, CEO. Please go ahead, sir.

現在我想把會議交給第一位講者，執行長 Fabrice Chouraqui 先生。先生，請開始。

Thank you, operator. Good morning and good afternoon, everyone, and welcome to our Q4 and Full Year 2025 Earnings Call. I'll be joined on this call today by Leverne Marsh, our new Chief Commercial Officer; Anurag Relan, our Chief Medical Officer; and Kenneth Lynard, our Chief Financial Officer.

謝謝，接線員。各位早安、午安，歡迎參加我們 2025 年第四季暨全年財報電話會議。今天與我一同出席的還有：我們新任首席商務長 Leverne Marsh、首席醫療長 Anurag Relan，以及首席財務長 Kenneth Lynard。

On this call, we will be making forward-looking statements that are based upon our current insights and plans. As you know, these may differ from future results. As you saw in our press release, Pharming ended 2025 on a strong note, operationally and financially. Total revenues grew by 15% in the fourth quarter of 2025 and by 27% for the full year. Thanks to disciplined cost management, we delivered $26 million of operating profit in 2025 compared to a loss in 2024.

在本次電話會議中，我們將發表以前瞻性陳述為主的內容，這些陳述係基於我們目前的洞見與計畫。如各位所知，實際未來結果可能與之不同。正如您在新聞稿中所見，Pharming 在 2025 年以強勁表現作結，無論在營運或財務面皆然。2025 年第四季總營收成長 15%，全年成長 27%。受惠於嚴謹的成本管理，我們在 2025 年實現 2,600 萬美元的營業利益，相較 2024 年為虧損。

We also significantly increased our cash position. Operating cash flow came in at $55 million in 2025, putting our cash position at year-end above that of the end of 2024 level before the acquisition of Abliva.

我們也大幅提升了現金部位。2025 年營運現金流為 5,500 萬美元，使我們年末現金部位高於 2024 年底、在收購 Abliva 之前的水準。

2025 was marked by significant growth of our two commercial assets, RUCONEST and Joenja. RUCONEST grew 26% year-on-year and by 9% in the fourth quarter. With its efficacy, with its reliability and its rapid onset of action, RUCONEST is poised to remain an established on-demand treatment option for difficult-to-treat patients in an evolving HAE treatment landscape. Leverne will talk more about RUCONEST performance and its unique value proposition.

2025 年的亮點之一，是我們兩項商業化資產 RUCONEST 與 Joenja 的顯著成長。RUCONEST 年增 26%，第四季成長 9%。憑藉其療效、可靠性與快速起效，RUCONEST 有望在不斷演變的 HAE 治療格局中，持續作為難治型患者既有且成熟的按需治療選項。Leverne 將進一步說明 RUCONEST 的表現及其獨特的價值主張。

Joenja grew 29% year-on-year and by 53% in the fourth quarter, fueled by the acceleration of new patients on drug in the US, but also increased demand in international markets, including in the UK, where the drug was launched last spring and in other countries through purchases under government-supported access program. These results underscore Pharming's transformation from a single asset company into a highly profitable, high-growth biotech with two commercial products and a late-stage pipeline with two programs offering billion sales potential.

Joenja 年增 29%，第四季成長 53%，主要受美國用藥新患者加速增加所帶動，同時國際市場需求亦上升，包括英國（該藥於去年春季上市）以及其他國家透過政府支持的用藥可近性計畫採購。這些成果凸顯 Pharming 已從單一資產公司轉型為高度獲利、高成長的生技公司，擁有兩項商業化產品，以及具兩個計畫、具備十億美元銷售潛力的後期研發管線。

We highlighted these programs at our Investor Day last month, offering investors unique insights to our high-value pipeline. RUCONEST is the foundation of our portfolio and a reliable cash engine for the future, even in a more crowded HAE on-demand market, given its efficacy profile on the difficult-to-treat patient subpopulation. Joenja is just at the beginning of its life cycle with multiple growth catalysts in APDS, international geographic expansion and potential expansion into much larger PIDs. Napazimone, which we used to call KL1333 for primary mitochondrial disease is another $1 billion-plus opportunity with the registrational study now well underway. This combination of durable revenue, first-in-disease innovation and an advancing late-stage pipeline positions Pharming well for substantial near-term and long-term value creation.

我們在上個月的投資人日重點介紹了這些計畫，為投資人提供對我們高價值研發管線的獨到洞見。RUCONEST 是我們產品組合的基石，也是未來可靠的現金引擎；即使 HAE 按需市場更為擁擠，鑑於其在難治型患者亞族群的療效特徵，仍具競爭力。Joenja 的產品生命週期才剛開始，在 APDS、多國市場地理擴張，以及潛在拓展至更大規模的 PID 適應症方面，具備多項成長催化劑。Napazimone（我們過去稱為 KL1333，用於原發性粒線體疾病）是另一個超過 10 億美元的機會，目前註冊性研究已在穩步推進。這種「具韌性的營收、首創疾病創新、以及持續推進的後期研發管線」的組合，使 Pharming 在短期與長期的價值創造上都具備良好定位。

Let me now turn to our outlook for the remainder of 2026. As announced at our Investor Day in February, we expect 2026 revenue between $405 million and $425 million this year, representing an 8% to 13% growth with operating expenses increasing at a slower overall pace even with substantially higher R&D investment in our pipeline to fuel future growth. We expect continued RUCONEST growth for the reason mentioned earlier and accelerating Joenja growth, fueled by the uptake in APDS patients above 12 years in the US and potential future regulatory approval internationally.

接下來我談談 2026 年剩餘期間的展望。如同我們在 2 月投資人日所宣布，我們預期 2026 年營收介於 4.05 億至 4.25 億美元，代表 8% 至 13% 的成長；同時，即便我們將大幅提高研發投入以推動未來成長，營運費用的整體增速仍將較為緩和。基於前述原因，我們預期 RUCONEST 將持續成長；而 Joenja 的成長將加速，主要由美國 12 歲以上 APDS 患者的用藥採用提升，以及未來可能取得國際監管核准所帶動。

Regarding the US pediatric label extension, we've been working to address the FDA request, and we expect to have greater clarity on the resubmission requirements and timeline following the FDA Type A meeting, which is now scheduled at the end of March.

關於美國兒科適應症標籤延伸，我們一直在處理 FDA 的要求；在目前排定於 3 月底召開的 FDA Type A 會議之後，我們預期將更清楚了解重新提交的要求與時程。

2026 is an important year for our pipeline with the materialization of potential value inflection points. We have now completed the enrollment of two leniolisib Phase 2 trials for late larger prevalence PIDs, and we expect a top line data readout in the second half of this year. We also expect to complete enrollment in the napazimone pivotal study this year to be in a position for a data readout at the end of 2027.

2026 年對我們的研發管線而言是關鍵一年，潛在的價值拐點將逐步顯現。我們已完成兩項 leniolisib 第二期試驗的受試者招募，目標為較晚期、盛行率更高的 PID，我們預期今年下半年將取得主要（top line）數據讀出。我們也預期今年完成 napazimone 關鍵性試驗的受試者招募，以便在 2027 年底進行數據讀出。

We are clearly determined to maintain strong financial discipline to optimize capital allocation on our growth drivers. This is critical as we strive to build an efficient and scalable organization and make Pharming a leading rare, ultra-rare disease company and deliver sustainable value for our shareholders.

我們明確致力於維持強而有力的財務紀律，以最佳化資本配置並聚焦於成長驅動因素。這一點至關重要，因為我們力求打造高效率且可擴展的組織，將 Pharming 建設為領先的罕見與超罕見疾病公司，並為股東創造可持續的價值。

Let me now turn to Leverne Marsh for deeper insights on the performance of our commercial portfolio.

接下來我把時間交給 Leverne Marsh，請她更深入分享我們商業化產品組合的表現。

Good day, everybody. Let me start with RUCONEST, where the US business delivered another year of strong and resilient performance. In 2025, despite the first new wave of treatment options in the HAE market in almost five years, RUCONEST continued to grow as an essential therapy for patients living with severe high-frequency HAE attacks. Our strategy remains consistent, focused on high-attack patients who require fast, reliable on-demand treatment and ensure that we continue to execute against that differentiated value proposition even as new agents enter the market.

各位好。我先從 RUCONEST 談起，美國業務在過去一年再次交出強勁且具韌性的表現。2025 年，儘管 HAE 市場近五年來迎來第一波新的治療選項，RUCONEST 仍持續成長，成為嚴重且高頻率 HAE 發作患者不可或缺的治療。我們的策略始終如一，聚焦於需要快速、可靠按需治療的高發作頻率患者，並確保即使有新藥進入市場，我們仍能持續落實這一差異化的價值主張。

For the full year, RUCONEST delivered 26% global revenue growth and a volume growth in the US of 20%, a clear indicator of the strong and durable demand for RUCONEST in the acute segment. In quarter 4, we delivered 9% global revenue growth versus the prior year quarter and a 2% volume growth in the core US market, continuing the upward trajectory of RUCONEST. As expected, through Q4, we began to observe impact of newly launched therapies for HAE in the US market with some patients trialing and some already returning to RUCONEST. Despite these competitive dynamics, we welcomed over 60 new enrollments in the US in the fourth quarter, slightly above Q3. RUCONEST added both new patients and new prescribers in the quarter, underscoring the resilience of our position in the difficult-to-treat patient segments and the clinical trust placed in RUCONEST in real-world settings.

就全年而言，RUCONEST 全球營收成長 26%，美國銷量成長 20%，清楚顯示 RUCONEST 在急性治療領域具有強勁且持久的需求。在第四季，我們的全球營收較去年同期成長 9%，美國核心市場銷量成長 2%，延續 RUCONEST 的上升趨勢。如預期所示，至第四季期間，我們開始觀察到美國市場新上市 HAE 治療對我們的影響，部分患者正在試用，亦有部分患者已回到 RUCONEST。儘管存在這些競爭動態，我們在第四季於美國新增超過 60 位新加入（enrollments），略高於第三季。RUCONEST 在本季同時新增患者與新增開立處方醫師，凸顯我們在難治型患者族群中的地位韌性，以及 RUCONEST 在真實世界臨床情境中所獲得的臨床信任。

That said, the high burden of HAE matters for patients who have high-frequency attacks. Attacks are often unpredictable and potentially life-threatening and symptom severity often escalate within hours. Importantly, for patients experiencing multiple attacks per month or patients who experience suboptimal responses to other options, dependable rapid relief is not optional, it is essential. And this high-frequency attack segment is precisely where we have seen consistent durable use of RUCONEST over time and where we expect RUCONEST to remain highly relevant even as new treatments enter the market. To that end, a meaningful proportion of new patient enrollments in the US are switches to RUCONEST from other on-demand therapies, further emphasizing the continued need that high attack patients have for an effective, reliable one-and-done therapy like RUCONEST.

話雖如此，對於高頻率發作的患者而言，HAE 的高疾病負擔至關重要。發作往往難以預測，且可能危及生命，而症狀嚴重程度常在數小時內惡化。重要的是，對於每月多次發作的患者，或對其他選項反應不佳的患者而言，可靠且快速的緩解不是可有可無，而是必需。而這個高頻率發作族群，正是我們長期以來觀察到 RUCONEST 持續且穩健使用的領域；即使新療法進入市場，我們也預期 RUCONEST 仍將高度相關。因此，美國新患者加入中有相當比例是從其他按需療法轉換至 RUCONEST，進一步凸顯高發作頻率患者對於像 RUCONEST 這種有效、可靠、一次到位（one-and-done）療法的持續需求。

And so when you put this together, the unpredictability of the disease, the high burden carried by certain patient segments, the limitations of some other acute therapies and consistently strong clinical performance associated with RUCONEST, the unique value proposition for RUCONEST remains clear. Looking ahead, we foresee some pressure on our growth early in the year, but with no change in the need for an effective, rapid onset, reliable one-dose treatment like RUCONEST.

因此，當你把這些因素綜合起來——疾病的不可預測性、特定病患族群所承受的高負擔、部分其他急性治療的限制，以及與 RUCONEST 相關且一貫強勁的臨床表現——RUCONEST 的獨特價值主張依然十分清晰。展望未來，我們預期年初的成長可能會面臨一些壓力，但對於像 RUCONEST 這樣具備有效、快速起效、可靠且單次劑量治療的需求並不會改變。

With that in mind, let me turn to Joenja. For Joenja, we delivered a strong fourth quarter, building on the momentum we established throughout the year. Revenue grew 53% compared to the fourth quarter in 2024, reaching $19.8 million globally. For the full year, Joenja generated $58 million, representing 29% growth year-on-year and demonstrating both sustained utilization from patients and the expanding clinical recognition and treatment of APDS.

基於這一點，讓我轉到 Joenja。就 Joenja 而言，我們在第四季交出強勁表現，延續了我們全年建立的動能。營收較 2024 年第四季成長 53%，全球達到 1,980 萬美元。全年而言，Joenja 創造 5,800 萬美元營收，年增 29%，展現病患持續使用，以及 APDS 在臨床端的認知與治療正在擴大。

In the United States, patient growth remained a central driver of performance. By the end of 2025, we had 120 patients on paid therapy, representing a 25% increase over year-end 2024. This steady expansion of our treated population reflects strong physician confidence, consistent engagement with patient communities and a team that executes with discipline and with urgency. Equally important, we made significant progress in broadening the pool of identified APDS patients, one of the most critical leading indicators in an ultra-rare disease. In 2025, the number of US patients we identified diagnosed with APDS increased by 40, more than double the increase of 18 we saw in 2024. This growth in identified patients with APDS shows that our educational efforts, our diagnostic partnerships, and our medical engagement in the US are working.

在美國，病患成長仍是表現的核心驅動因素。截至 2025 年底，我們有 120 位病患接受付費治療，較 2024 年底增加 25%。受治療族群的穩定擴張，反映出醫師高度信心、與病患社群的持續互動，以及一支以紀律與緊迫感執行的團隊。同樣重要的是，我們在擴大已識別的 APDS 病患池方面取得顯著進展；在超罕見疾病中，這是最關鍵的領先指標之一。2025 年，我們在美國識別並確診為 APDS 的病患數增加 40 人，超過 2024 年增加 18 人的兩倍。已識別 APDS 病患的成長顯示，我們的教育推廣、診斷合作夥伴關係，以及在美國的醫學互動正在發揮作用。

Outside the US, we saw strengthening demand across international markets, including a solid first year uptake in the United Kingdom following the launch in April 2025. We also benefited from government-supported access programs, which allowed us to reach more patients who currently have limited therapeutic options. Taken together, these results give us a strong platform for Joenja in the years ahead.

在美國以外，我們看到國際市場需求走強，包括英國在 2025 年 4 月上市後的第一年即有穩健的採用。我們也受惠於政府支持的用藥可近性計畫，使我們能觸及更多目前治療選擇有限的病患。綜合而言，這些成果為 Joenja 未來數年的發展奠定了強勁平台。

Finally, we expect geographic expansion and the anticipated 4- to 11-year approval in the United States to be meaningful contributors to growth. These two catalysts remain materially important to increase the number of patients who can benefit from Joenja and expand the global footprint of the APDS business. Internationally, we've already demonstrated our ability to execute. In the UK, where Joenja launched in April 2025, we have seen solid early uptake and (inaudible). That success reinforces that our teams have the capability, the infrastructure and the strategic focus needed to deliver in new markets.

最後，我們預期地理版圖擴張，以及在美國預期取得 4 至 11 歲適應症核准，將成為重要的成長貢獻來源。這兩項催化劑對於增加可受惠於 Joenja 的病患人數、並擴大全球 APDS 業務版圖，仍具有實質重要性。在國際市場方面，我們已經展現出執行能力。在英國，Joenja 於 2025 年 4 月上市後，我們看到穩健的早期採用，並且(聽不清楚)。這項成功再次印證，我們的團隊具備在新市場交付成果所需的能力、基礎設施與策略聚焦。

In the United States, our commercial teams are fully prepared to launch Joenja for children ages 4 to 11 pending FDA approval. And importantly, we already have 52 eligible patients identified, 1/3 of them currently on therapy through our early access program ready to transition at approval. This will give us a running start and positions us for early momentum once the label is approved.

在美國，我們的商業團隊已全面準備就緒，待 FDA 核准後即可為 4 至 11 歲兒童推出 Joenja。更重要的是，我們已識別 52 位符合資格的病患，其中三分之一目前透過早期可近性計畫接受治療，核准後可立即轉換。這將讓我們一開始就具備良好起跑優勢，並在標籤核准後為早期動能奠定基礎。

Beyond the US, our international organization is deeply engaged in progressing regulatory submissions and ensuring that reimbursement discussions can start when approvals are granted across Europe, Japan, and Canada. Across these three regions, we have over 80 patients already receiving Joenja through early access mechanisms, awaiting full regulatory approval and commercial availability. This represents a significant built-in foundation for launch acceleration once those approvals are secured.

在美國以外，我們的國際組織正積極推進法規申請，並確保在歐洲、日本與加拿大取得核准後即可啟動給付／報銷討論。在這三個地區，我們已有超過 80 位病患透過早期可近性機制接受 Joenja，正等待完整法規核准與商業供應。一旦取得核准，這將構成顯著的內建基礎，有助於加速上市推進。

And as we're stepping into 2026, we do so with confidence. For Joenja, we have the right growth catalysts in front of us, and we have an organization that has demonstrated that it can execute launches with precision and continuity. This gives us confidence not just in the next quarter, but in the sustained global expansion of Joenja over the coming years.

而在邁入 2026 年之際，我們充滿信心。就 Joenja 而言，我們面前具備正確的成長催化劑，同時我們也擁有一個已證明能以精準與連續性執行上市的組織。這不僅讓我們對下一季有信心，也對未來數年 Joenja 的持續全球擴張充滿信心。

And with that, I'll now hand over to Dr. Anurag Relan, our Chief Medical Officer, who will walk you through our progress across the pipeline and the upcoming development and regulatory milestones.

接下來，我將把時間交給我們的首席醫學官 Anurag Relan 醫師，他將帶各位了解我們在研發管線上的進展，以及即將到來的開發與法規里程碑。

Thank you, Leverne. As we discussed at our Investor Day in February, PI3K delta is a master regulator of the immune system and imbalances here contribute to immune dysregulation in a number of primary immune deficiencies or PIDs. This understanding serves as the foundation and rationale for our Joenja development efforts. APDS, where Joenja is currently approved, is a primary immune deficiency caused by a genetic defect that leads to PI3K-delta hyperactivation. This results in the dysfunction of the immune system and is characterized by frequent and severe infections and a wide array of immune dysregulation consequences, as you see here. APDS is a progressive disease and leads to early mortality due to these complications with unfortunately about 25% of patients dying by the age of 30.

謝謝你，Leverne。如同我們在 2 月投資人日所討論的，PI3K delta 是免疫系統的主調控因子，而此處的失衡會導致多種原發性免疫缺陷（PID）出現免疫失調。這項理解構成我們 Joenja 開發工作的基礎與理據。APDS（Joenja 目前已核准的適應症）是一種由基因缺陷所致的原發性免疫缺陷，會造成 PI3K-delta 過度活化。這會導致免疫系統功能失常，其特徵為頻繁且嚴重的感染，以及如各位在此所見的多種免疫失調後果。APDS 是一種進行性疾病，並會因這些併發症而導致早期死亡；不幸的是，約有 25% 的病患在 30 歲前死亡。

Based on this understanding of APDS, we have two ongoing Phase 2 proof-of-concept clinical trials evaluating leniolisib in more prevalent PIDs, which share unmet medical needs, mechanisms, and disease pathology with APDS. These include the genetically identified primary immune deficiencies with immune dysregulation linked to altered PI3K-delta signaling and Common Variable Immune Deficiency or CVID with immune dysregulation, which is identified independently of genetics. And as Fabrice mentioned, both of these studies have now completed enrollment. And as you see here, APDS falls under the broader CVID umbrella diagnosis and Joenja, in fact, serves as a proof of concept for the work we are doing now in these much more prevalent PIDs.

基於對 APDS 的理解，我們目前有兩項進行中的第二期概念驗證臨床試驗，評估 leniolisib 在更常見的 PID 中的效果；這些疾病與 APDS 共享未被滿足的醫療需求、作用機制與疾病病理。這些包括：經基因鑑定、與 PI3K-delta 訊號改變相關之免疫失調型原發性免疫缺陷；以及具有免疫失調的常見變異型免疫缺陷（CVID），其鑑定不依賴基因資訊。如 Fabrice 所提到，這兩項研究目前都已完成收案。如各位所見，APDS 屬於更廣泛的 CVID 診斷範疇之下，而 Joenja 事實上也為我們目前在這些更常見 PID 上所進行的工作提供了概念驗證。

This slide highlights the opportunity now to broaden the use of Joenja. The prevalence figures here are for the US, but they illustrate the larger opportunity to serve patients and underpin peak sales potential above $1 billion. We're very excited about the work that I just discussed to study Joenja in these additional PIDs with immune dysregulation beyond APDS. These address significantly larger patient populations, which are 5 to 26 times the prevalence of APDS.

這張投影片凸顯了目前擴大 Joenja 使用範圍的機會。此處的盛行率數據以美國為例，但它們說明了服務病患的更大機會，並支撐超過 10 億美元的峰值銷售潛力。我們對我剛才所談到、在 APDS 之外針對其他具有免疫失調的 PID 研究 Joenja 的工作感到非常振奮。這些適應症涵蓋顯著更大的病患族群，其盛行率為 APDS 的 5 至 26 倍。

In APDS, Leverne already discussed progress with patient identification and our commercial preparations for geographic and pediatric expansion. But let me update you now on the variance of uncertain significance project and the opportunity there. Following various discussions over many months involving Columbia and genetic testing labs, it became clear that the labs require additional evidence to reclassify VUSs. Understanding the consequences of VUS has remain a significant unmet need and actually a public health problem for clinicians and patients. And as you see, the number of patients with VUS continues to grow.

在 APDS 方面，Leverne 已經談到病患識別的進展，以及我們在地理擴張與兒科擴張上的商業準備。但現在讓我向各位更新「意義未明變異」（VUS）專案的進展與其中的機會。在與 Columbia 及基因檢測實驗室歷經數月的多次討論後，我們已清楚了解到，實驗室需要更多證據才能重新分類 VUS。理解 VUS 的影響仍是一項重大的未被滿足需求，對臨床醫師與病患而言，實際上也是一個公共衛生問題。而如各位所見，具有 VUS 的病患人數仍在持續增加。

To complement the significant first batch of data, which were published in Cell, we are now planning new experiments to generate the data needed to allow genetic testing labs to evaluate VUSs. Following completion of these experiments, we plan to provide an estimate how many VUSs may be reclassified and how many patients may be ultimately diagnosed with APDS. In addition, the work published in Cell also suggests that the prevalence of APDS could be significantly higher than we currently estimate. We convened a global advisory board and are now initiating work to explore and better understand the prevalence of APDS as well as the spectrum of disease.

為了補充已在《Cell》發表的重要第一批資料，我們目前正規劃新的實驗，以產生遺傳檢測實驗室評估 VUS 所需的資料。在完成這些實驗後，我們計畫提供一項估計，說明可能有多少 VUS 會被重新分類，以及最終可能有多少患者會被確診為 APDS。此外，《Cell》發表的研究也顯示，APDS 的盛行率可能顯著高於我們目前的估計。我們已召集全球諮詢委員會，並正啟動相關工作，以探索並更深入了解 APDS 的盛行率以及疾病譜系。

I'll now cover the progress we are making in APDS, including some of our near-term regulatory milestones. Overall, we made good progress in APDS during 2025 and early this year. While we are disappointed in the complete response with letter we received from FDA in January regarding our regulatory submission for the pediatric label expansion for Joenja for the treatment of APDS in children ages 4 to 11, we believe we can address both the clinical pharmacology and analytical batch testing methodology issues outlined in the letter. A Type A meeting has now been scheduled with FDA for later this month, and we expect to discuss the agency's feedback and align on the path forward for resubmission.

接下來我將說明我們在 APDS 方面的進展，包括一些近期的法規里程碑。整體而言，我們在 2025 年以及今年年初於 APDS 領域取得了良好進展。儘管我們對 FDA 於 1 月就 Joenja 用於治療 4 至 11 歲 APDS 兒童之兒科適應症擴大申請所發出的完整回覆函（CRL）感到失望，但我們相信可以解決函中所列的臨床藥理以及分析批次檢測方法學問題。我們已安排於本月稍晚與 FDA 召開 Type A 會議，預期將討論主管機關的回饋，並就重新提交的後續路徑達成一致。

In Europe, we have filed a marketing authorization application for leniolisib for patients 12 years and older and now responded to CHMP's questions on manufacturing activities and quality controls and believe we have addressed their concerns. We now expect a CHMP opinion on the MAA to take place at their meeting later this month with potential EC approval in the first half of this year.

在歐洲，我們已就 leniolisib 用於 12 歲及以上患者提交上市許可申請（MAA），並已回覆 CHMP 對製造活動與品質管制的提問，且我們相信已解決其疑慮。我們目前預期 CHMP 將於本月稍晚的會議中就該 MAA 形成意見，並可能於今年上半年獲得歐盟執委會（EC）核准。

Regarding the Japan NDA for leniolisib for the treatment of APDS in patients four years of age and older, the Pharmaceutical Affairs Council meeting has recommended approval. This news was covered in The Pink Sheet, who importantly noted that this would represent the first approval for children with APDS ages 4 to 11. We now await the formal decision by the PMDA by the end of March.

關於 leniolisib 用於治療 4 歲及以上 APDS 患者的日本新藥申請（NDA），藥事審議會會議已建議核准。《The Pink Sheet》亦報導了此消息，並特別指出這將代表首個針對 4 至 11 歲 APDS 兒童的核准。我們目前正等待 PMDA 於 3 月底前做出正式決定。

I'll now turn to our next pipeline asset, napazimone or formerly known as KL1333. Napazimone has also progressed significantly in the past year. This is being developed for primary mitochondrial diseases, which is a group of rare disorders where mutations in mitochondrial DNA lead to significant fatigue and muscle weakness. Napazimone addresses this underlying disorder by normalizing the NAD+ to NADH ratio, which is abnormally low in these patients. There are a large number of these patients already diagnosed across the US and large European countries where they are treated at centers of excellence and part of strong advocacy groups. And here, we have a registration-enabling study underway with endpoints agreed upon with FDA.

接下來我將談到我們下一個研發管線資產 napazimone（先前稱為 KL1333）。Napazimone 在過去一年也取得了顯著進展。該藥物正用於原發性粒線體疾病的開發，這是一組罕見疾病，患者的粒線體 DNA 發生突變，導致嚴重疲勞與肌肉無力。Napazimone 透過使 NAD+ 與 NADH 的比值正常化來處理此基礎病理；在這些患者中，該比值異常偏低。在美國及歐洲主要國家，已有大量此類患者被確診，並在卓越中心接受治療，同時也有強而有力的倡議團體支持。在此方面，我們已啟動一項具註冊支持性的研究，且其終點已與 FDA 達成一致。

And importantly, there was a blinded interim analysis in which both endpoints passed utility. Since completing the acquisition of Abliva last year, we are making good progress in the second wave of the study and are on track to complete enrollment later this year with readout in 2027 and potential approval later in 2028.

更重要的是，在一次盲態期中分析中，兩個終點皆通過效用（utility）評估。自去年完成對 Abliva 的收購以來，我們在研究的第二波推進上進展良好，並按計畫於今年稍晚完成受試者入組，預計 2027 年讀出結果，並可能於 2028 年稍晚獲得核准。

And with that, I'll turn it over to Kenneth now to discuss our financial results.

接下來我把時間交給 Kenneth，請他說明我們的財務結果。

Thank you very much, Anurag. I'm pleased to now provide some color on our strong 2025 financial performance and our outlook for 2026.

非常感謝你，Anurag。我很高興接下來就我們 2025 年強勁的財務表現，以及 2026 年展望提供一些補充說明。

The fourth quarter was a strong finish with revenues of $106.5 million being 15% growth versus Q4 of 2024. This was driven by continued momentum across our portfolio, including a 9% growth for RUCONEST and a 53% growth for Joenja. Notably, Joenja annual revenues exceeded $50 million for the first time, triggering our first $5 million sales milestone payment in the quarter. As a reminder, this milestone is recorded in cost of goods sold and therefore, affected gross margin for the fourth quarter.

第四季表現強勁收官，營收為 1.065 億美元，較 2024 年第四季成長 15%。此表現主要由我們產品組合的持續動能所帶動，包括 RUCONEST 成長 9%，以及 Joenja 成長 53%。值得注意的是，Joenja 年度營收首次超過 5,000 萬美元，因而在本季觸發我們第一筆 500 萬美元的銷售里程碑付款。提醒一下，該里程碑款項列入銷貨成本，因此影響了第四季的毛利率。

Adjusted operating profit was broadly stable year-over-year after several offsetting one-off items. Fourth quarter 2025 expenses include $9.3 million in expenses related to Abliva and napazimone following the completion of the Abliva acquisition this year as well as the $5 million Joenja sales milestone payment just mentioned. Excluding these items to compare operating profit on a like-for-like basis to the fourth quarter of 2024, operating profit in the fourth quarter of '25 would have been $14 million higher.

在若干相互抵銷的一次性項目影響下，調整後營業利益與去年同期大致持平。2025 年第四季費用包含：於今年完成 Abliva 收購後，與 Abliva 及 napazimone 相關的 930 萬美元費用，以及前述 500 萬美元的 Joenja 銷售里程碑付款。若排除上述項目，以同口徑與 2024 年第四季比較，2025 年第四季的營業利益將高出 1,400 萬美元。

Finally, cash and marketable securities increased by $12.2 million from $168.9 million at the end of Q3 to $181 million at year-end, primarily driven by positive operating cash flow, reflecting the strength of our commercial performance. Turning to our full year 2025 results. Our financials shows the continued strong execution of our strategy. Total revenues increased 27% to $376.1 million, driven by robust double-digit growth from both RUCONEST and Joenja. Gross margin remained stable at approximately 88% despite the $5 million Joenja sales milestone recorded in the fourth quarter.

最後，現金及有價證券增加 1,220 萬美元，從第三季末的 1.689 億美元增至年末的 1.81 億美元，主要由正向營運現金流所帶動，反映我們商業表現的強勁。接著看 2025 年全年業績。我們的財務結果顯示策略持續強力執行。總營收成長 27% 至 3.761 億美元，主要由 RUCONEST 與 Joenja 皆呈現強勁的雙位數成長所驅動。儘管第四季認列 500 萬美元的 Joenja 銷售里程碑，毛利率仍維持穩定，約為 88%。

Operating expenses rose to $311.3 million, excluding $4.1 million of one-off restructuring costs related to our G&A reduction program announced in October, operating expenses were $307.2 million and within our previously communicated guidance range of $304 million to $308 million. Importantly, when also excluding the full $29.7 million of Abliva-related expenses, operating expenses increased only 2% on a like-for-like basis. This reflects disciplined cost management. In total, adjusted operating profit, which exclude nonrecurring Abliva acquisition-related costs and other offsetting items was $36.4 million compared with a loss of $8.6 million in 2024. Excluding recurring Abliva expenses and the $5 million Joenja sales milestone, operating profit for 2025 would have been $24.4 million higher.

營業費用上升至 3.113 億美元；若排除 10 月宣布之一般與行政（G&A）縮減計畫相關的 410 萬美元一次性重整成本，營業費用為 3.072 億美元，落在我們先前溝通的指引區間 3.04 億至 3.08 億美元之內。重要的是，若再排除全額 2,970 萬美元的 Abliva 相關費用，以同口徑計算，營業費用僅增加 2%。這反映了嚴謹的成本管理。總體而言，調整後營業利益（排除非經常性的 Abliva 收購相關成本及其他相互抵銷項目）為 3,640 萬美元，相較 2024 年為虧損 860 萬美元。若排除經常性的 Abliva 費用以及 500 萬美元的 Joenja 銷售里程碑，2025 年營業利益將再高出 2,440 萬美元。

Cash flow from operating activities totaled $54.7 million versus being slightly negative in 2024, showing the improved profitability and cash generation of the business. Cash and marketable securities increased $11.7 million to $181.1 million despite $68 million used for the Abliva acquisition, again, highlighting the strength of our underlying operational cash generation.

營運活動現金流合計 5,470 萬美元，相較 2024 年略為負值，顯示公司獲利能力與現金創造能力的改善。儘管收購 Abliva 使用了 6,800 萬美元，現金及有價證券仍增加 1,170 萬美元至 1.811 億美元，再次凸顯我們基礎營運現金創造能力的強勁。

Turning to our 2026 outlook. We reaffirm our expectation for total revenues of $405 million to $425 million, representing full year growth of approximately 8% to 13% versus 2025. The growth is expected to be driven by continued growth for RUCONEST in the US, partly offset by declining ex-US revenue as we exit those markets and accelerated growth for Joenja.

接著看 2026 年展望。我們重申對總營收 4.05 億至 4.25 億美元的預期，代表相較 2025 年全年約成長 8% 至 13%。預期成長將由 RUCONEST 在美國的持續成長所帶動，但部分將被我們退出美國以外市場所造成的境外營收下滑所抵銷，同時 Joenja 的成長將加速。

For RUCONEST, quarterly revenue typically fluctuates with patient ordering patterns and channel inventory movements with the first quarter usually being the lowest. In Q1 2026, inventory drawdowns are expected to impact US RUCONEST revenue growth by 7% to 9% year-on-year as market dynamics settle. This is factored into our full year guidance, which assumes mid-single-digit RUCONEST growth at the midpoint of the range. For Joenja, we expect growth to accelerate with annual growth approximately 10 percentage points higher than in 2025.

就 RUCONEST 而言，季度營收通常會隨患者訂購模式與通路庫存變動而波動，其中第一季通常為最低。在 2026 年第一季，預期庫存去化將影響美國 RUCONEST 營收年增率約 7% 至 9%，因市場動態逐步趨於穩定。此因素已納入我們全年指引中；以區間中點計算，假設 RUCONEST 呈現中個位數成長。就 Joenja 而言，我們預期成長將加速，年度成長率將較 2025 年高出約 10 個百分點。

The pediatric APDS indication remains an important future growth driver, and we look forward to clarity on the US approval timeline for patients aged 4 to 11 following the upcoming FDA Type A meeting. In the meantime, US pediatric revenues are excluded from our 2026 guidance. For operating expenses, we anticipate a range of $330 million to $335 million, including more than $60 million of incremental R&D investments. This guidance reflects -- also reflects the $9 million favorable impact from the 20% G&A headcount reduction program announced in October 2025, along with stable marketing and sales spending.

兒科 APDS 適應症仍是未來重要的成長驅動力，我們期待在即將召開的 FDA Type A 會議後，能更清楚了解 4 至 11 歲患者在美國的核准時程。在此期間，我們的 2026 年財測指引不包含美國兒科營收。在營業費用方面，我們預期介於 3.30 億至 3.35 億美元之間，其中包含超過 6,000 萬美元的新增研發投資。此指引亦反映了——也反映了——我們於 2025 年 10 月宣布的 G&A 人力縮減 20% 計畫所帶來的 900 萬美元正面影響，同時行銷與銷售支出維持穩定。

Overall, we remain committed to financial discipline, prioritizing investment that drive near- and long-term value creation for our shareholders. Because Joenja revenue is not expected to exceed $100 million in 2026, we do not assume the $10 million commercial milestone payments, which otherwise would be recorded in cost of goods sold. As communicated during our Investor Day in February and aligned with ex US rollout plans, no additional milestone payments are expected. We estimate cost of goods sold at 10% of revenues, corresponding to a gross margin of 90%. Finally, available cash and future operating cash flows are expected to fully support pipeline investments, including all prelaunch activities.

整體而言，我們仍致力於財務紀律，優先投入能為股東創造短期與長期價值的投資。由於預期 Joenja 於 2026 年的營收不會超過 1 億美元，我們不假設將發生 1,000 萬美元的商業里程碑付款；若發生，該款項原本會計入銷貨成本。如同我們在 2 月投資人日所傳達，並與美國以外的上市推進計畫一致，預期不會有額外的里程碑付款。我們估計銷貨成本為營收的 10%，對應毛利率為 90%。最後，現有現金與未來營運現金流預期將足以全面支持產品線投資，包括所有上市前活動。

With that, I will now hand over to Fabrice for his closing remarks.

接下來，我將把時間交給 Fabrice 作結語。

Thank you, Kenneth. So in summary, we are pleased to report another strong quarter and a record year for Pharming in 2025 with $376 million revenues and a shift to operating profitability and positive operating cash flow.

謝謝你，Kenneth。總結來說，我們很高興在 2025 年再度繳出強勁的一季與 Pharming 的創紀錄年度表現，營收達 3.76 億美元，並轉為營業獲利且營運現金流為正。

Looking ahead, RUCONEST is poised to remain a constant treatment for severe HAE patients, underpinning a strong revenue base. We see clear revenue catalysts ahead for Joenja with the product well positioned to generate a significant proportion of our revenues in the future. Our upcoming clinical data readouts, including the two leniolisib Phase 2 later this year and the napazimone pivotal study readout next year, each have the potential to unlock significant value and take the company to a whole new level.

展望未來，RUCONEST 可望持續作為重度 HAE 患者的穩定治療選項，支撐強勁的營收基礎。我們看到 Joenja 未來有明確的營收催化劑，該產品具備良好定位，未來可望貢獻我們營收中的相當比重。我們即將公布的臨床數據讀出，包括今年稍晚兩項 leniolisib 第 2 期試驗，以及明年 napazimone 關鍵性研究的讀出；每一項都有潛力釋放重大價值，並將公司帶到全新層級。

And finally, the decisive steps we have taken to improve financial discipline will support driving the positive bottom line. With strong commercial and development capabilities, a fit-for-purpose leadership team with strong new additions like Leverne and Kenneth and a scalable organization, we are committed to making 2026 another stepping stone in achieving our vision of becoming a leading global rare disease company.

最後，我們為提升財務紀律所採取的果斷措施，將有助於推動正向的最終獲利。憑藉強大的商業化與研發能力、適任且目的導向的領導團隊（包含 Leverne 與 Kenneth 等強力新成員），以及可擴展的組織架構，我們致力於讓 2026 年成為實現願景的另一個墊腳石——成為全球領先的罕見疾病公司。

Let me now open the line for questions.

現在我開放提問。

(Operator Instructions) Lucy Codrington, Jefferies.

（接線員指示）Lucy Codrington，Jefferies。

To begin with Joenja growth this year, how much of that are you expecting to come from the US market versus international markets? And then secondly, looking at the US market, of those 61 eligible patients that are not on treatment in the US, how many of these do you think could be converted to paid therapy? Or how many have been -- versus how many have been considered and ruled out?

先從今年 Joenja 的成長談起，你們預期其中有多少來自美國市場、多少來自國際市場？第二，聚焦美國市場，在美國那 61 位符合資格但尚未接受治療的患者中，你們認為有多少可能轉換為自費（付費）治療？或者其中有多少已被——相較之下，有多少已被評估後排除？

And then finally, in terms of RUCONEST dynamics, you mentioned that you have heard of patients coming back to treatment and having tried the orals. Do you have any -- I guess, it would be anecdotal commentary on how quickly the patients return having tried the orals?

最後，關於 RUCONEST 的動態，你提到你們聽說有患者嘗試口服藥後又回到治療。你們是否有任何——我想可能是一些軼事性的評論——關於患者在嘗試口服藥後多快會回來？

Very good. Thank you so much, Lucy, for those questions. I'll turn to Leverne in a minute, actually. Let me start with the last one on RUCONEST and then we can take your two questions on Joenja.

很好。非常感謝你，Lucy，提出這些問題。我等一下會把問題交給 Leverne。我先從最後一題 RUCONEST 開始，接著再回答你關於 Joenja 的兩個問題。

It is true that we've seen some patients trying and coming back. As you know, and as Leverne reinforced, HAE is a very severe disease and patients got to be controlled and especially patients who were used to highly reliable treatment. And so when those patients try another treatment and see that their crisis is not properly controlled, they tend to come back to their previous medication very quickly because not controlling a crisis could be life-threatening.

確實，我們看到有些患者嘗試後又回來。如你所知，也如 Leverne 所強調，HAE 是非常嚴重的疾病，患者必須被控制，尤其是那些習慣於高度可靠治療的患者。因此，當這些患者嘗試其他治療卻發現其發作未能被妥善控制時，他們往往會很快回到先前的用藥，因為若無法控制一次發作，可能危及生命。

Now when it comes to Joenja's growth, as we've said, we see the growth this year in 2026 being fueled both by the continued growth in the US as well as growth increasing in international markets. It's -- obviously, the growth in international markets will come from the UK where the drug has been launched, new launch countries. And this will happen in a staged fashion since once we receive marketing approval, we'll have to negotiate price and reimbursement. So ultimately, a bigger portion of the growth will come from international market, but that's going to be gradual.

至於 Joenja 的成長，如我們所說，我們看到 2026 年的成長將同時由美國持續成長以及國際市場加速成長所帶動。很明顯，國際市場的成長將來自已在英國上市，以及其他新上市國家。而這將以分階段方式發生，因為一旦取得行銷核准，我們仍需進行定價與給付（報銷）談判。因此，最終成長中較大的一部分將來自國際市場，但會是逐步發生。

When it comes to more specificities on Joenja's patient funnel, I'll ask Leverne to comment.

至於 Joenja 病患漏斗更具體的細節，我請 Leverne 來說明。

Thank you. Thank you, Lucy, for your question. How we would think about the patients considered for Joenja or eligible for Joenja in the US and the pull-through to patients on therapy, that there would be a lag there as patients are going through the patient journey, a fairly complicated patient journey, seeing multiple physicians, the enrollment and then the reimbursement process before we get to patients on paid therapy. And so how I would think about the delta there and the opportunity, there's still a substantial proportion of patients both eligible and potentially reimbursable that would drive growth for us in the US in 2026.

謝謝。謝謝你，Lucy，提出問題。我們看待美國 Joenja 的「被考慮」或「符合資格」患者，以及最終導入到實際用藥患者之間，會存在一段落差，因為患者正經歷其就醫旅程——這是一段相當複雜的旅程，包含看多位醫師、完成收案/登錄，接著是給付（報銷）流程，之後才會到達實際付費用藥的患者。因此，就這個差距與機會而言，仍有相當比例的患者既符合資格且可能取得給付，將在 2026 年推動我們在美國的成長。

Maybe, Lucy, this is Kenneth speaking. Maybe I can just add out of the expected Joenja growth in 2026, it will probably be around about 70%, 75% that will come from the US.

Lucy，我是 Kenneth。我補充一下：在 2026 年預期的 Joenja 成長中，可能大約有 70% 到 75% 會來自美國。

So 70%, 75% from the US.

所以 70%、75% 來自美國。

Of the growth in 2026 for Joenja, yes.

是的，指的是 Joenja 在 2026 年的成長。

Joe Pantginis, H.C. Wainwright.

Joe Pantginis，H.C. Wainwright。

So I know might not be able to give color here ahead of the Type A, but I'm going to ask anyway. Obviously, the reasons for your discussions, as Anurag said, were the clinical pharmacology and the analytical batches. Is there anything that you would consider sort of the lead rate-limiting step here? That's question number one.

我知道在 Type A 會議之前你們可能不便多做說明，但我還是想問。很明顯，如 Anurag 所說，你們討論的原因在於臨床藥理以及分析批次。這裡是否有任何你們認為是主要的瓶頸（限制速率步驟）？這是第一個問題。

Question number 2, regarding RUCONEST, you touched upon this a little bit, but I guess the RUCONEST case can be split into two components in my belief. So first, you have the medical component, which continues to make the case. And I'd like to touch upon the investor component and specifically your comments that patients are still seeing switches from the new therapies to RUCONEST. So I was hoping you can provide some additional color as to why those switches are taking place.

第二個問題，關於 RUCONEST，你稍早有提到一些，但我認為 RUCONEST 的論點可分成兩個部分。首先是醫學層面，這部分仍持續成立。我想談談投資人層面，特別是你提到患者仍在從新療法轉回 RUCONEST。因此我希望你能提供更多背景，說明為何會發生這些轉換。

Thank you, Joe, for these questions. So on the Type A meeting, it's very difficult to speculate. I think Anurag has been clear on the questions that were raised by FDA, and we are really looking forward to engage with the agency later this month to address their feedback and discuss a path forward. So too soon to tell. Clearly, given what they've raised, we feel actually that these questions are addressable. And once again, we look forward to engaging with them.

謝謝你，Joe，提出這些問題。關於 Type A 會議，現在很難推測。我想 Anurag 已清楚說明 FDA 提出的問題，我們非常期待在本月稍晚與主管機關進一步交流，以回應其回饋並討論後續推進路徑。所以現在還言之過早。很明顯，基於他們提出的事項，我們其實認為這些問題是可以被解決的。再次強調，我們期待與他們進一步溝通。

When it comes to RUCONEST, I'll let Leverne answer your question.

談到 RUCONEST，我會讓 Leverne 來回答你的問題。

So thanks for your question, an important one. So as we've seen new agents entering the HAE market in the US between June and August last year, as expected, we saw some trialing of both acute agents and new prophylactic agents in the US market. What we're observing in our data currently, and it's still early, is within about three to six months, some of these patterns may start to shift, and we've seen some return of RUCONEST patients that have originally adopted or trialed a different product coming back to RUCONEST.

所以謝謝你的提問，這是一個重要的問題。如同我們所見，去年 6 月到 8 月期間，美國 HAE 市場有新藥物進入；如預期，我們看到美國市場對急性用藥以及新的預防性用藥都有一些試用。我們目前在數據中觀察到的情況（而且仍屬早期）是，在大約三到六個月內，這些使用模式可能開始出現轉變；我們也看到一些原本採用或試用其他產品的 RUCONEST 病患回流到 RUCONEST。

But again, early days, and we're monitoring this closely, and we continue to execute competitively based on RUCONEST's very different value proposition for patients, specifically in the high attack segment, where they are increasingly concerned with reliability and a fast on-demand treatment like RUCONEST.

但再次強調，現在仍是早期階段，我們正密切監測；同時我們也持續以具競爭力的方式執行，依據 RUCONEST 對病患而言非常不同的價值主張，特別是在高發作族群，他們對可靠性以及像 RUCONEST 這樣快速、按需使用的治療愈來愈重視。

Jeff Jones, Oppenheimer.

Jeff Jones，Oppenheimer。

Congrats on the great year 2025. A couple of questions from us. You spoke a little bit to the cadence of moving patients from early access on to paid therapy. Any notable variations between Europe, Japan, Canada as you look to that? And then as you look at the other primary immune deficiencies for Joenja and the Phase 2 readouts that you're anticipating, can you speak a little bit about next steps? What types of additional trials might be needed and how to think about the path forward there?

恭喜 2025 年表現亮眼。我們有幾個問題。你提到了一些將病患從早期用藥（early access）轉換到自費/付費治療的節奏。就此而言，歐洲、日本、加拿大之間是否有任何值得注意的差異？另外，當你們看 Joenja 在其他原發性免疫缺陷（PID）適應症，以及你們預期的二期（Phase 2）讀出時，能否談談下一步？可能需要哪些額外試驗，以及該如何看待後續推進路徑？

Thank you, Jeff, for these questions. When it comes to access to paid therapies for Joenja in international markets, most of these markets are -- have access -- centrally driven access. So the dynamic is different compared to the US, where in a sense, each patient needs to deal with different payers. So in a centralized access system, things are slower at the beginning because you need to negotiate, obviously, with the authorities for reimbursement or the one you get reimbursement, then afterwards, the reimbursement process is extremely efficient. So we don't expect to see the same type of dynamic international. When it comes to higher prevalent PMDs, I'll ask Anurag to elaborate.

謝謝你，Jeff，提出這些問題。就 Joenja 在國際市場取得付費治療可近性而言，多數市場是——採取集中式驅動的可近性（centralized access）。因此其動態與美國不同；在美國，某種程度上每位病患都需要面對不同的保險支付方。在集中式可近性體系中，一開始進展較慢，因為你需要與主管機關協商給付；但一旦取得給付之後，後續的給付流程就會非常有效率。因此我們不預期國際市場會出現與美國相同的動態。至於盛行率較高的 PMD，我會請 Anurag 進一步說明。

Jeff, so on the question about the -- what happens next. So as I mentioned, the studies have completed enrollment. We expect results later this year. The results that we're looking for, again, the endpoints that we're evaluating are clinically relevant endpoints similar to the ones that we looked at in APDS as well as other clinically relevant endpoints. As we look at those endpoints, we'll plan to have a discussion with FDA and other regulators about the path forward.

Jeff，關於接下來會發生什麼。如我提到的，這些研究已完成收案。我們預期今年稍晚會有結果。我們要看的結果——同樣地，我們評估的終點是具臨床意義的終點，類似我們在 APDS 研究中所看的，以及其他具臨床意義的終點。在我們檢視這些終點後，我們會與 FDA 及其他監管機構討論後續推進路徑。

I think our base case here is that we would expect to do a Phase 3 randomized type of study. However, I think you've also seen from FDA some openness and willingness to look at alternative mechanisms and pathways for patients with rare diseases, especially those where there's a plausible mechanism and there's a mechanism that's understood. So those are the types of discussions that we would have with the FDA, again, once we have the data to be able to plan the path forward.

我認為我們的基本情境是，預期會進行一項第三期（Phase 3）隨機分派類型的研究。不過，你也看到 FDA 對於罕見疾病病患，在存在合理作用機轉且機轉已被理解的情況下，對替代性機制與審評途徑展現一定的開放與意願。因此，一旦我們有了數據，便會與 FDA 進行這類討論，以便規劃後續推進路徑。

Sushila Hernandez, VLK.

Sushila Hernandez，VLK。

On Joenja, you mentioned different launch dynamics for international markets. So what kind of timelines are you working with for getting these patients in Japan and Canada on paid therapy? And in the UK, will you also start reporting the numbers of patients on paid therapy? So currently, how many patients in the UK are on paid therapy and how many have you identified?

關於 Joenja，你提到國際市場的上市動態不同。那麼，讓日本與加拿大的這些病患轉為付費治療，你們目前規劃的時間表是什麼？另外在英國，你們也會開始揭露付費治療病患數嗎？所以目前英國有多少病患在付費治療上？你們已識別出多少病患？

So when it comes to timelines, so we've elaborated a bit on our expectations when it comes to regulatory timelines in the very near future. When it comes to CHMP opinion from Europe and PMDA approval in Japan. We'll in Japan, specifically since you asked the questions, we will be submitting a price very shortly for reimbursement, and it takes about three months actually for the price to be granted.

關於時間表，我們已就近期的法規時程預期做了一些說明。包括歐洲的 CHMP 意見以及日本的 PMDA 核准。就日本而言，既然你特別問到，我們將在很短時間內提交給付用的價格申請，而價格核定大約需要三個月。

So today, we have launch timelines planned for the summer. We will be reporting more information on the international market on Joenja in a full fashion as soon as we have launches in more than one country. So this should happen very soon it's absolutely essential and you can count on transparency here. For the second part of your question, I'll let Leverne elaborate.

因此，以今天來看，我們規劃的上市時程是在夏季。一旦我們在不只一個國家完成上市，我們就會以完整方式提供更多關於 Joenja 國際市場的資訊。這應該很快就會發生；這絕對至關重要，你可以期待我們在這方面保持透明。至於你問題的第二部分，我會讓 Leverne 進一步說明。

Certainly. As Fabrice has said prior, as we look at different approvals coming online at different times in this year, every country fundamentally will be a country-by-country process as the approval and reimbursement processes are quite unique for the countries that we discussed. So how we're thinking about conversion is conversion will depend on physician experience, diagnostic confirmation and testing and access, and we are building those enablers systematically with the international teams to make sure that we are able to execute upon approval.

當然。如 Fabrice 先前所說，隨著今年不同核准在不同時間點陸續到位，每個國家基本上都會是逐國推進的流程，因為我們所討論各國的核准與給付流程都相當獨特。因此我們對「轉換」的思考是：轉換將取決於醫師的使用經驗、診斷確認與檢測，以及可近性；我們正與國際團隊系統性地建立這些促成因素，以確保在核准後能夠有效執行。

Natalia Webster, RBC Capital Markets.

Natalia Webster，RBC Capital Markets。

My first one is a follow-up on Joenja and the patients on paid therapy in the US. You added 18 in H1 2025 and six in H2. I appreciate that this takes time, but are you expecting for this rate to pick up into 2026?

我的第一個問題是追問 Joenja 以及美國付費治療病患數。你們在 2025 年上半年新增 18 位、下半年新增 6 位。我理解這需要時間，但你們是否預期這個速度在 2026 年會加快？

Then the second question is just on costs. You're guiding to 6% to 8% growth in OpEx in 2026. And you mentioned some phasing considerations on the revenue side. Are there any particular phasing considerations for the costs through the year particularly around the higher R&D costs and G&A cost savings?

第二個問題是關於成本。你們指引 2026 年營業費用（OpEx）成長 6% 到 8%。你們也提到營收端有一些分期（phasing）考量。那成本端在全年是否也有任何特定的分期考量，特別是較高的研發成本以及一般與行政（G&A）成本節省方面？

And then just finally, on M&A. In the release, you mentioned continued focus on potential acquisitions and in-licensing opportunities. So any additional color on what your thoughts are there would be helpful.

最後是關於併購（M&A）。在新聞稿中，你們提到持續聚焦於潛在收購與引進授權（in-licensing）機會。因此若能補充一些你們在這方面的想法，會很有幫助。

Very good. Thank you so much, Natalia, for your question. So I'll start with the last one when it comes to M&A. We have clearly a number of growth catalysts, both in our commercial portfolio and in our pipeline in the years to come. So obviously, there is no urgency to do any transaction hastily to compensate for any sort of weakness. Yet we clearly aspire to leveraging proven capabilities and a great growth platform to take that to a whole new level and make Pharming a leading rare disease, ultra-rare disease player.

很好。非常感謝你，Natalia，提出問題。我先從最後一題——併購（M&A）談起。未來幾年，我們在商業化產品組合與研發管線上，都明確擁有多項成長催化劑。因此，顯然我們沒有急迫性去倉促進行任何交易，以彌補任何形式的弱點。但我們確實希望運用已被驗證的能力與優秀的成長平台，把公司帶到全新層級，讓 Pharming 成為罕見疾病與超罕見疾病領域的領先者。

And so we are constantly looking out for opportunities to expand our pipeline. Now it is absolutely essential that these opportunities, if they were to materialize, would be value accretive. And that's really our commitment to our shareholders. So it's not about actually leveraging any external growth opportunities, but making sure that anything that we would consider would be complementary, would fulfill our mission, and will be quickly accretive from a value perspective.

因此我們持續尋找擴充研發管線的機會。而且至關重要的是，若這些機會成形，必須能夠增厚價值（value accretive）。這也是我們對股東的承諾。所以重點不在於單純追求外部成長機會，而是確保我們所考慮的任何項目都具有互補性、能實現我們的使命，並且從價值角度能夠快速增厚。

From a cost perspective, I'll let Kenneth elaborate.

從成本角度來看，我會請 Kenneth 進一步說明。

Yes. Thanks for the question. I think the way to think about it is in the 2025 baseline, we obviously had also some one-off costs that were related to the transaction of the Abliva, so nonrecurring transaction cost of about $10 million. And we also communicated earlier that we had about $4 million in costs related to the G&A reduction program. But then when you're looking into the more than $60 million incremental investments in 2026, we, of course, see the $9 million of savings in G&A come fully through.

是的。謝謝你的提問。我認為可以這樣理解：在 2025 年的基準情境中，我們顯然也有一些與 Abliva 交易相關的一次性成本，因此非經常性的交易成本約為 1,000 萬美元。我們也先前溝通過，與 G&A（一般及行政）縮減計畫相關的成本約為 400 萬美元。但當你看到 2026 年超過 6,000 萬美元的增量投資時，我們當然也會看到 G&A 的 900 萬美元節省將完全反映出來。

And then we have seen the impact in our planning of the strengthened capital allocation, which has allowed us to keep also marketing and sales cost flat. So there are different dynamics that are playing in. But I think picture speaks for itself that we are fueling where we're seeing the opportunities to advance in this case, in 2026, the pipeline and are very diligent around spend discipline across all other areas.

此外，我們在規劃中也看到了強化資本配置所帶來的影響，這使我們也能將行銷與銷售成本維持持平。因此其中有不同的動態在發揮作用。但我認為整體圖像已不言自明：我們正把資源投入到我們看到有機會推進的地方——在這個案例中是 2026 年的研發管線——同時在其他所有領域都非常嚴謹地維持支出紀律。

And so lastly, coming to your question on Joenja, which is actually a very important question because, as I said, I really see Joenja taking a larger part of our revenues as the drug continue to grow significantly and realize its full potential.

最後，回到你關於 Joenja 的問題，這其實是一個非常重要的問題，因為如我所說，隨著該藥物持續顯著成長並實現其全部潛力，我確實看到 Joenja 將在我們營收中占比更大。

You heard that last year, we reaccelerated the uptake of the drug. We had more new paid patients on therapy in the US that we had in '24. Also, we've identified more APDS patients in the US in '25 than we did in '24. And so this is really fueling the growth. So this year, we expect to continue to accelerate patient enrollment on Joenja and as a consequence, accelerate our revenue growth.

你也聽到我們去年重新加速了該藥物的採用。我們在美國新增的付費治療患者數量比 2024 年還多。此外，我們在 2025 年於美國辨識出的 APDS 患者也比 2024 年更多。因此這確實正在推動成長。所以今年我們預期將持續加速 Joenja 的患者納入，並因此加速我們的營收成長。

Simon Scholes, First Berlin.

Simon Scholes，First Berlin。

I've just got two. So I was wondering if you could give us a timeline on the performance and collection of the results from these additional experiments you need to perform with regard to the variant of uncertain significance. And also, are you still confident that 20% of these VUSs will turn out to be APDS?

我只有兩個問題。我想請問，針對這些「意義未明變異」（VUS）所需進行的額外實驗，其表現與結果收集的時間表能否提供一下？另外，你們是否仍有信心其中 20% 的 VUS 最終會被證實為 APDS？

And then just on RUCONEST, you were talking about a possible inventory-related decline in -- or inventory-related effect on sales in Q1. Is this an unusually large inventory drawdown that you're expecting to see in Q1? I mean that was my impression. And if so, how did -- why do you think you saw such a large inventory buildup towards the tail end of last year?

另外關於 RUCONEST，你提到第一季銷售可能會出現與庫存相關的下滑——或庫存相關的影響。你們預期第一季會出現異常大幅的庫存去化嗎？我的印象是如此。如果是的話，那麼——你們為何認為在去年年底會看到如此大的庫存累積？

Thank you, Simon. So let me -- let's start with the US. Clearly, this is a sizable opportunity, and we are really committed to helping those patients accessing the right diagnostics. So Anurag?

謝謝你，Simon。那我——我們先從美國談起。很明顯，這是一個相當可觀的機會，我們也非常致力於協助這些患者取得正確的診斷。所以 Anurag？

So Simon, we are now planning these new experiments. These experiments, again, we're working with Columbia. They're actually going to be using new technology, new base editing technology to be able to generate different types of variants, generate more controls as they go through this process. It's too soon to tell in terms of the timelines as well as the actual number of patients that will actually be reclassified. But as this work gets underway over the coming months, we should be able to provide more details around it.

Simon，我們目前正在規劃這些新的實驗。這些實驗同樣是與 Columbia 合作。他們實際上將使用新技術——新的鹼基編輯（base editing）技術——以便產生不同類型的變異，並在此過程中產生更多對照組。就時間表以及實際會有多少患者被重新分類而言，現在還言之過早。但隨著這項工作在未來幾個月展開，我們應該能提供更多相關細節。

And Simon, on the inventory part, the way we're thinking about it is that there's always this quarterly fluctuation of the RUCONEST business given the patient ordering patterns and the general movements. And we have also historically, if you go back in the previous years, seen that similar dynamics in the early part of the year.

Simon，關於庫存的部分，我們的看法是：RUCONEST 業務一直都會因患者下單模式與一般變動而出現季度性的波動。而且從歷史來看，如果回顧前幾年，我們也在年初看到過類似的動態。

Now it's a little bit, let's say, higher in terms of inventory drawdown and dynamics this year, and we kind of attribute that simply to some of those market dynamics are kind of settling now and that inventory levels are just kind of returning to a little bit more of the normalized level. So impact-wise, it's a little bit higher, but the mechanics of how the quarters are fluctuating and the fact that the inventory impact in the first quarter are not new to us.

今年在庫存去化幅度與相關動態上，確實稍微高一些；我們將其歸因於部分市場動態目前正在趨於穩定，而庫存水位也正回到較為正常化的水平。因此就影響而言會稍高一些，但季度波動的運作機制，以及第一季出現庫存影響這件事，對我們來說並不新鮮。

Very good. So listen, I think with this, we are going to close our call. Thank you so much for these additional questions, and we look forward to keeping you closely informed on our plan. There is -- there are a number of important milestones coming up. And so we look forward to reconnecting with you very soon. Thank you so much. Thank you, operator.

非常好。那各位，我想我們將在此結束本次電話會議。非常感謝這些額外的提問，我們也期待持續就我們的計畫向各位提供最新資訊。接下來將有若干重要的里程碑。因此我們也期待很快再次與各位聯繫。非常感謝。謝謝，接線員。

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

謝謝。今天的電話會議到此結束。感謝各位的參與。現在您可以掛斷電話線。謝謝。