Praxis Precision Medicines, Inc. (PRAX) 2026 Q1 法說會逐字稿

Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Praxis Precision Medicines first quarter 2026 financial results conference call. (Operator Instructions)

各位女士、先生，大家好，感謝各位稍候。歡迎參加 Praxis Precision Medicines 2026 年第一季財務業績電話會議。（接線員指示）

As a reminder, this conference call is being recorded. At this time, I would like to turn the conference over to Mr. Dan Ferry of LifeSci Advisors.

提醒各位，本次電話會議將被錄音。現在我想把電話會議交給 LifeSci Advisors 的 Dan Ferry 先生。

Sir, please begin.

先生，請開始。

Good morning, and welcome to Praxis Precision Medicines first quarter 2026 financial results and business update conference call. This call is being webcast live and can be accessed on the Investors section of Praxis website @www.praxismedicines.com.

各位早安，歡迎參加 Praxis Precision Medicines 2026 年第一季財務業績與業務更新電話會議。本次會議將進行線上即時網路直播，可於 Praxis 官網 www.praxismedicines.com 的投資人專區收看。

Please note that remarks made during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about the company's future expectations and plans, clinical development timelines, and financial projections. While these forward-looking statements represent Praxis views as of today, they should not be relied upon as representing the company's views in the future.

請注意，本次會議中的發言可能包含符合 1995 年《私人證券訴訟改革法》定義的前瞻性陳述。其中可能包括關於公司未來預期與計畫、臨床開發時程，以及財務預測的陳述。雖然這些前瞻性陳述代表 Praxis 截至今日的觀點，但不應被依賴為代表公司未來的觀點。

Praxis may update these statements in the future, but is not taking on an obligation to do so. Please refer to Praxis's most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with the company's business.

Praxis 未來可能更新這些陳述，但不承擔必須更新的義務。請參閱 Praxis 最近向美國證券交易委員會（SEC）提交的文件，以了解與公司業務相關的若干風險與不確定性之討論。

Joining the call today are Marcio De'Souza, President and Chief Executive Officer of Praxis; and Tim Kelly, Chief Financial Officer. After providing updates on our key programs, we'll move to a brief Q&A session where Marcio and Tim will be joined by Steve Petrou, President of Research and Development; and Megan Sniecinski, Chief Operating Officer.

今天參與會議的有 Praxis 總裁兼執行長 Marcio De'Souza，以及財務長 Tim Kelly。在提供我們主要專案的最新進展後，我們將進入簡短的問答環節，屆時 Marcio 與 Tim 將與研發總裁 Steve Petrou 以及營運長 Megan Sniecinski 一同參與。

With that, it's my pleasure to turn the call over to Marcio.

接下來，我很高興把電話會議交給 Marcio。

Thank you, Dan, and good morning, everyone, and thanks for joining Praxis first quarter 2026 conference call. Building on a remarkable 2025, we have continued executing across our portfolio in our journey to become a commercial company with strong momentum building across four late-stage assets, representing more than $20 billion in peak sales potential.

謝謝你，Dan，各位早安，也感謝各位參加 Praxis 2026 年第一季電話會議。在卓越的 2025 年基礎上，我們持續在產品組合上推進執行，朝著成為商業化公司邁進；目前四項後期資產動能強勁，峰值銷售潛力合計超過 200 億美元。

With the NDAs for ulixacaltamide and relutrigine accepted by the FDA and PDUFA date set, we're ramping up commercial efforts to support the two potential US launches within the next 8 months while also making significant progress with our other clinical programs.

隨著 ulixacaltamide 與 relutrigine 的新藥申請（NDA）已獲 FDA 受理並設定 PDUFA 日期，我們正在加速商業化準備，以支援未來 8 個月內兩項潛在的美國上市，同時也在其他臨床專案上取得重大進展。

It's also incredibly exciting to announce that we have completed recruitment for the EMBOLD study in the broad DEE population, with top-line results expected in the fourth quarter of this year, which we expect to support a potential supplemental NDA next year.

同時也非常令人振奮地宣布，我們已完成針對廣泛 DEE 族群的 EMBOLD 研究受試者招募，預計今年第四季公布主要結果（top-line results），我們預期這將支持明年提出潛在的補充新藥申請（sNDA）。

We're also on track to report results from our POWER1 study for lamotrigine later this quarter. Also made exciting progress with our solids ASO platform with the positive results from the EMBRAVE Part A showing a disease-modifying effect of easinersen in SCN2A early onset DEE and substantial reduction in monthly seizures, amongst many other results.

我們也按計畫將於本季稍晚公布 lamotrigine 的 POWER1 研究結果。此外，我們在固體 ASO 平台方面也取得令人振奮的進展：EMBRAVE A 部分的正面結果顯示 easinersen 在 SCN2A 早發型 DEE 中具有疾病修飾效果，並使每月癲癇發作次數大幅下降，且還有許多其他成果。

With key hires made in our commercial organization and a strong financial foundation, we're accelerating the delivery of life-altering treatments to patients with CNS disorders. Let me provide a bit more detail on each one of our programs. Let's start with Ulixa.

隨著商業組織完成關鍵人才招募，並具備穩健的財務基礎，我們正加速將改變人生的治療帶給中樞神經系統（CNS）疾病患者。接下來我將更詳細說明我們各項專案。先從 Ulixa 開始。

FDA acceptance for Ulixa's NDA marks a meaningful step forward for the 7 million Americans living with essential tremor who currently have no ET-specifically developed treatments approved. We estimate that about 2 million of those people living with ET are in immediate need of a therapy that can clinically improve their daily lives, representing a potential for over $10 billion in peak sales.

Ulixa 的 NDA 獲 FDA 受理，對於目前缺乏任何專為原發性顫抖（ET）開發且獲核准治療的 700 萬名美國患者而言，是一項重要的進展。我們估計其中約有 200 萬名 ET 患者迫切需要能在臨床上改善日常生活的治療，對應的峰值銷售潛力超過 100 億美元。

To unlock the benefit for patients and the value, we have been diligently preparing for our commercial launch based on the PDUFA date of January 29, next year. The commercial leadership team is in place with our field force plan to be hired and trained in advance of the launch, and we continue to expand and build the commercial infrastructure across multiple areas, like operations, marketing, access, and compliance. We have also successfully established a distribution network to ensure drug availability at launch at successful levels.

為了讓患者受益並釋放價值，我們一直依據明年 1 月 29 日的 PDUFA 日期，積極且審慎地為商業上市做準備。商業領導團隊已就位，我們的外勤團隊（field force）計畫將在上市前完成招募與訓練；同時我們也持續在營運、行銷、給付可近性（access）與法規遵循（compliance）等多個領域擴充並建置商業基礎設施。我們也已成功建立配送網路，以確保上市時藥品供應可達到適當水準。

Earlier this year, we conducted a very comprehensive observational study with physicians to understand their view of ET and ulixacaltamide. We surveyed more than 2,300 US physicians who collectively manage tens of thousands of patients. The results were beyond encouraging. They validated the ulixacaltamide profile across efficacy, the breadth of benefits, and tolerability, reinforcing the more than $10 billion peak sales potential and the need for a drug like Ulixa in the market.

今年稍早，我們與醫師進行了一項非常全面的觀察性研究，以了解他們對 ET 與 ulixacaltamide 的看法。我們調查了超過 2,300 位美國醫師，他們合計管理數以萬計的患者。結果令人非常振奮。研究驗證了 ulixacaltamide 在療效、效益廣度與耐受性方面的特徵，進一步強化其超過 100 億美元的峰值銷售潛力，以及市場對 Ulixa 這類藥物的需求。

Importantly, we also wanted to hear more details from patients and conduct a similar work with over 1,300 ET patients, which further validated the agreement between the needs of patients in terms of their functional benefits and the results of the Essential3 program. It's truly exciting to be in a place of such alignment amongst treating physicians, patients, and the results of our program.

同樣重要的是，我們也希望從患者端獲得更多細節，因此對超過 1,300 名 ET 患者進行了類似研究，進一步驗證患者在功能性改善需求與 Essential3 計畫結果之間的一致性。能看到治療醫師、患者需求與我們專案結果之間如此高度一致，確實令人振奮。

We're also very pleased with our robust presence at the American Academy of Neurology Annual Meeting last month. With 15 scientific presentations, including a plenary presentation highlighting the Essential3 program results, which received the AAN's abstract of Distinction and Movement Disorder Awards, which underscore the strong interest and engagement of the medical community. To further enhance our engagement with health care professionals, we have launched the Essential 2 Me disease state campaign.

我們也很高興上個月在美國神經學學會（AAN）年會上展現了強而有力的能見度。我們共進行 15 場科學發表，其中包括一場全體會議（plenary）發表，重點呈現 Essential3 計畫結果；該摘要獲得 AAN 的「傑出摘要」（Abstract of Distinction）與「運動障礙獎」（Movement Disorder Awards），凸顯醫學界的高度興趣與投入。為進一步提升我們與醫療專業人員的互動，我們已啟動 Essential 2 Me 疾病狀態宣導活動。

Let's now move to our epilepsy programs. As we shared in March, in another pivotal moment for practice and patients, the FDA has accepted with priority review the NDA for relutrigine for seizures associated with SCN2A &8A-DEE. Those are severe patients affected early in life, and where the seizures are intractable from the very beginning.

接下來談談我們的癲癇專案。如同我們在 3 月分享的，對 Praxis 與患者而言又一個關鍵時刻：FDA 已以優先審查（priority review）受理 relutrigine 用於治療與 SCN2A 與 8A-DEE 相關之癲癇發作的 NDA。這些患者在生命早期即受到嚴重影響，且癲癇發作從一開始就難以控制。

It's important to highlight that if approved, relutrigine would be eligible for a pediatric review voucher. With the PDUFA date of September 27, preparation for launch is moving full steam ahead with continued hiring of commercial roles, building sufficient inventory, establishing a comprehensive patient support program, and engaging with payers to ensure timely access upon potential approval.

需要特別強調的是，若獲核准，relutrigine 將符合兒科審查憑證（pediatric review voucher）的資格。隨著 PDUFA 日期訂於 9 月 27 日，上市準備正全速推進，包括持續招募商業職位、建立足夠庫存、建立完整的患者支持計畫，並與保險給付方（payers）互動，以確保在潛在核准後能及時取得用藥。

We remain confident in the clinical potential for relutrigine and the benefits to the broader DEE population. With recruitment in the EMBOLD study now completed in record time, it's clear that patients and investigators share our view.

我們對 relutrigine 的臨床潛力以及其對更廣泛 DEE 族群的效益仍充滿信心。EMBOLD 研究如今以創紀錄的速度完成招募，清楚顯示患者與研究者與我們有相同看法。

The potential launch in SCN2A and 8A will build the foundation and the results of the EMBOLD later this year if positive, it will significantly expand the commercial potential for relutrigine by several folds, considering the broad DEE population is comprised of over 200,000 patients in the United States.

在 SCN2A 與 8A 的潛在上市將奠定基礎；而若今年稍晚 EMBOLD 的結果為正面，考量廣泛 DEE 族群在美國超過 20 萬名患者，將使 relutrigine 的商業潛力成倍大幅擴張。

Let's now talk about vormatrigine, the most potent and selective sodium channel modulator ever developed for the 3.5 million people living with epilepsy in the United States. We have three key milestones in the near future for the program.

接下來談 vormatrigine，這是迄今為止為美國 350 萬名癲癇患者所開發、效力最強且選擇性最高的鈉離子通道調節劑。此專案在近期有三個關鍵里程碑。

The first is the readout of the 401 Phase 3 study later this quarter. Then the initiation of the POWER3 study, a milestone in the community, using all the exciting features of vormatrigine to deliver on what the majority of the market really needs. And then later in the year, the completion of the POWER2 Phase 2 study, which is evaluating doses of 20, 30, and 40 milligrams once daily.

第一個是本季稍晚公布 401 第三期研究的結果。接著是啟動 POWER3 研究，這將是社群的一項里程碑，運用 vormatrigine 的各項令人振奮特性，來滿足市場多數真正需要的目標。然後在今年稍晚，完成 POWER2 第二期研究，該研究正在評估每日一次 20、30 與 40 毫克的劑量。

Enrollment is progressing well, and we're on track to finalize the study this year and report early next year. Lastly, let's talk about Elsunersen, the first ASO on our platform. also has a rare pediatric drug designation and is being developed for the treatment of early seizure onset patients with SCN2A mutations.

受試者招募進展順利，我們正按計畫在今年完成該研究，並於明年年初公布結果。最後，我們來談談 Elsunersen，這是我們平台上的第一個 ASO。它也獲得罕見兒科用藥資格認定，並正開發用於治療帶有 SCN2A 突變、早發性癲癇發作的患者。

We have recently reported the results of EMBRAVE Part A, which enrolled 9 children aged 2 to 12 who were randomized 3:1 to elsunersen or sham over 24 weeks. We are thrilled with the impressive 77% placebo-adjusted reduction in monthly seizures and the disease-modifying components seen across multiple domains in those patients, while maintaining the generally safe and well-tolerated profile.

我們近期已公布 EMBRAVE A 部分的結果；該研究納入 9 名 2 至 12 歲兒童，並以 3:1 隨機分派接受 elsunersen 或假處置，治療期為 24 週。我們對於每月癲癇發作次數達到令人印象深刻的 77%（經安慰劑校正後）下降，以及在多個面向觀察到的疾病修飾成分感到非常振奮，同時整體仍維持一般而言安全且耐受性良好的特徵。

The overall data from both the EMBRAVE program, open-label extension, and emergency use program globally highlight durable seizure reduction and meaningful global gains, which further underscore the transformational potential of this drug.

EMBRAVE 計畫（含開放標籤延伸試驗）以及全球緊急使用計畫的整體數據，凸顯癲癇發作降低的持久性與具意義的整體改善，進一步強調此藥物的變革性潛力。

In conclusion, we're off to a great start with our momentum continuing to accelerate across our clinical portfolio, preparations for the commercial launch of ulixacaltamide and lamotrigine well underway, the completion of the EMERALD study enrollment, POWER1 top line readout coming up, and many other achievements to come.

總結而言，我們已取得良好開局，臨床產品組合的動能持續加速；ulixacaltamide 與 lamotrigine 的商業上市準備工作正順利推進；EMERALD 研究已完成受試者招募；POWER1 的主要結果讀出即將到來，且未來還有許多其他里程碑可期。

Backed by a strong balance sheet and a long, multilayer IP portfolio across the programs, we're focused on rigorous execution and driving progress across our innovative first and best-in-class portfolio of CNS therapies.

在強健的資產負債表以及涵蓋各項計畫、長期且多層次的智慧財產權組合支持下，我們專注於嚴謹執行，並推動我們創新、同類首創與同類最佳的中樞神經系統（CNS）治療產品組合持續進展。

I'll now hand over the call to our CFO, Tim Kelly.

接下來我把電話交給我們的財務長 Tim Kelly。

Tim?

Tim？

Thank you, Marcio. Good morning, everybody, and thank you for joining today's call. I'll provide a quick summary of our first quarter financials. In Q1, our operating expenses were approximately $106 million, with $78 million of that for R&D and the remaining $28 million for SG&A, driven by ramping activities and hiring related to commercial launch preparations.

謝謝你，Marcio。各位早安，感謝大家參加今天的電話會議。我將快速摘要我們第一季的財務表現。第一季我們的營運費用約為 1.06 億美元，其中 7,800 萬美元用於研發（R&D），其餘 2,800 萬美元為銷售、一般及行政費用（SG&A），主要受商業上市準備相關活動加速與招募人員所帶動。

During the first quarter, Praxis spent $86 million in operating cash compared to $53 million in the first quarter of 2025, reflecting greater clinical trial activity, headcount growth, and commercial launch preparations. As of March 31, 2026, Praxis had $1.4 billion in cash, cash equivalents, and marketable securities compared to $926 million as of December 31, 2025.

第一季 Praxis 的營運現金支出為 8,600 萬美元，相較於 2025 年第一季的 5,300 萬美元，反映臨床試驗活動增加、人力擴編，以及商業上市準備。截至 2026 年 3 月 31 日，Praxis 持有現金、約當現金及有價證券共 14 億美元，相較於 2025 年 12 月 31 日的 9.26 億美元。

This increase of approximately $474 million was primarily attributable to net proceeds from Praxis's January 2026 follow-on public offering and interest income on marketable securities, partially offset by the previously mentioned cash used in operations. The company's cash, cash equivalents, and marketable securities as of March 31, 2026, are expected to fund operations into 2028.

約 4.74 億美元的增加，主要來自 Praxis 於 2026 年 1 月後續公開發行（follow-on public offering）的淨募資款，以及有價證券的利息收入；部分被前述營運現金使用所抵銷。公司截至 2026 年 3 月 31 日的現金、約當現金及有價證券，預期可支應營運至 2028 年。

With that, I will hand the call back to Marcio.

接下來我把電話交回給 Marcio。

Thank you, Tim. I appreciate the review. We're going to move now to Q&A. Howard, maybe you can provide the queue for us.

謝謝你，Tim。感謝你的回顧。我們現在進入問答（Q&A）環節。Howard，也許你可以為我們提供提問順序。

(Operator Instructions)

（接線員指示）

Yasmeen Rahimi, Piper Sandler.

Yasmeen Rahimi，Piper Sandler。

Good morning, team. Thank you so much for all the great updates. Maybe also congrats on EMBOLD bringing to the finish line enrollment and data in 4Q as it's an important readout this year. Maybe remind us, what is the data that we have to support relutrigine working in a broader DEE population, both across preclinical and clinical data?

各位早安，團隊。非常感謝你們帶來這麼多最新進展。也恭喜 EMBOLD 在第四季完成受試者招募並取得數據，因為這是今年一個重要的讀出。想請你們再提醒一下：有哪些數據支持 relutrigine 能在更廣泛的 DEE 人群中發揮作用，包含臨床前與臨床數據？

And then also, what do you see on a blinded basis across safety and efficacy that continues to give you confidence in the high success in the EMBOLD study? And I'll jump back in the queue.

另外，在盲態（blinded）的安全性與療效觀察上，你們看到了什麼，讓你們對 EMBOLD 研究的高成功率仍持續有信心？我會回到隊列中。

Sounds good. Thanks, Yas. I'll take a step back here and maybe talk a little bit about the genesis of going to the broad DE population. When you look into seizure activities, particularly on those intractable conditions like DEEs, we know full well just how difficult those patients are to control.

好的。謝謝你，Yas。我先退一步，談談我們為何會走向更廣泛 DE 人群的起源。當你檢視癲癇發作活動，特別是在像 DEE 這類難治性病況中，我們非常清楚這些患者有多難控制。

I know that when they can have at least some partial control for the most part, it is because that is a way to inhibit the block, better modulate their sodium channel activity, like you simply cannot have seizure activity without participation of those channels.

我知道，多數情況下若能達到至少部分控制，是因為這是一種抑制（阻斷）並更好地調節其鈉離子通道活性的方式；因為沒有這些通道的參與，基本上不可能出現癲癇發作活動。

So when we were conducting the EMBOLD program for SCN2A and SCN8A, the number 1 question we're getting from physicians back then was, when are you going to expand this [key outlets]?

因此，當我們針對 SCN2A 與 SCN8A 進行 EMBOLD 計畫時，當時醫師問我們的第一個問題是：你們什麼時候要把這個擴展到[關鍵管道]？

So we'll take that into mind in terms of the overall clinical proof of concept, payer idea, and the needs that we're seeing. But we had to slow down a little bit and do a lot of work. And you might have seen, and it's available on our website, a fair bit of the work in terms of different animal models, which are incredibly predictive in epilepsy.

所以我們把這點納入考量，從整體臨床概念驗證、支付方（payer）的觀點，以及我們所看到的需求來看。但我們必須稍微放慢腳步，做大量工作。你們可能已經看到（我們網站上也有），我們在不同動物模型上做了不少研究，而這些模型在癲癇領域具有非常高的預測性。

On understanding whether or not there was a good scientific rationale on top of the electrophysiology rationale, on top of the molecular rationale to go to this. Then, in the last part, we had to make sure that the FDA was in agreement that we could study in this population. Safety is paramount, making sure that we're actually understanding the populations we're in.

用以理解：除了電生理學的理據、分子層面的理據之外，是否還有良好的科學理據支持我們往這個方向推進。接著在最後一部分，我們必須確保 FDA 同意我們可以在這個族群中進行研究。安全性至關重要，必須確保我們確實理解所研究的族群。

So when we checked all those boxes, we're able to initiate the study. I think what is incredible, I would say, is just the level of interest. If you look into ourselves, if you look into other studies indeed before, if you look into competitive, and I'm going to put that very loosely, there were studies that are going right now, there was no interest in those others. It's pretty obvious by the pace of enrollment that is happening with us and with others out there. And the number 1, reason why is that physicians are very confident in the Ada here, just like we are.

當我們把這些條件都確認到位後，就能啟動研究。我認為非常令人驚訝的是其關注度之高。如果你看我們自己、看之前其他研究、再看競品（我用這個詞很寬鬆），目前也有一些研究正在進行，但其他研究並沒有受到關注。從我們以及外部其他人的招募速度就很明顯。而最主要的原因是，醫師對這裡的數據非常有信心，就像我們一樣。

So it gave us, of course, this extra ability to move things forward. But if I can turn to the business for a second, we are in the business of helping patients. But at the same time, the only way to continue to help them is to continue to generate proper positive returns to invest in the future.

因此，這當然也讓我們更有能力把事情往前推進。但如果我從商業角度談一下，我們的業務是幫助患者。但同時，能夠持續幫助他們的唯一方式，是持續創造適當的正向報酬，以投資未來。

The expansion towards the DEE is like 20-fold what the initial indication for SCN2 and 8A is, which is incredibly important. But the second part makes not only scientific sense, but it's a tremendous upside in terms of the potential of this drug.

擴展到 DEE 的規模，大約是 SCN2 與 8A 初始適應症的 20 倍，這非常重要。而第二部分不僅在科學上合理，從該藥物的潛力來看也具有巨大的上行空間。

Then lastly, I know we keep piling catalysts throughout the year, and you guys might be tired of us having so many readouts. But we thought it was very important to get that, shortly thereafter, to really, with a fresh, hopefully, approval at that point in time, give the FDA a lot of flexibility to actually look into just the additional data and potentially even qualify for certain accelerated mechanisms that have been available. So all in all, we see this as a tremendous and maybe the key updates today that we're giving in terms of value inflection for investors.

最後，我知道我們今年不斷堆疊催化劑，你們可能也會覺得我們有太多讀出而感到疲乏。但我們認為，在那之後不久就取得該結果非常重要，如此一來，屆時若能（希望）獲得核准，也能讓 FDA 有更大的彈性去檢視額外數據，甚至可能符合某些已可用的加速機制。因此整體而言，我們認為這是非常重大的進展，也可能是我們今天提供、對投資人而言具有價值拐點的關鍵更新。

Thank you. Ritu Baral, TD Cowen

謝謝。Ritu Baral，TD Cowen

Good morning, guys. Thanks for taking the question. A lot of client questions are just around the upcoming power readout and what our expectations should be. Knowing the baseline and knowing the relative baseline of other competitive therapies, how should investors, how should we be looking at placebo-adjusted seizure reduction, the safety profile? And then how might that data then frame the POWER2 and POWER3 studies, given the different doses in those studies and the different dosing paradigms?

各位早安。謝謝讓我提問。很多客戶的問題都圍繞著即將公布的 POWER 數據，以及我們應該抱持什麼樣的預期。在了解基線、也了解其他具競爭性的療法相對基線的情況下，投資人應該如何看待經安慰劑校正後的癲癇發作減少幅度、以及安全性概況？另外，考量到 POWER2 與 POWER3 研究中不同的劑量與不同的給藥模式，這些數據又可能如何為 POWER2 與 POWER3 的研究提供框架？

Great set of questions there, Ritu. So, I think let's start with the baseline, that's what you mentioned. So if you look historically, at least in recent history, baseline for focal seizures in the refractory population, so 1 to 3 ASMs, and you know the drill there on the other criteria, have been hovering around like 9 to 11, 12 countable seizures on the previous 28 days.

Ritu，這是一組很棒的問題。我想先從你提到的基線開始。如果回顧歷史資料，至少在近期，針對難治性族群的局灶性癲癇發作基線（也就是使用 1 到 3 種抗癲癇藥物 ASMs，且符合你也熟悉的其他條件），在前 28 天可計數的發作次數大約落在 9 到 11、12 次左右。

And I think we're probably a little higher than that, a tiny bit here for POWER1, which was what we're aiming for. We knew these patients were fairly refractory or very confident about the drug. We also wanted to make sure that once we establish there and have very clear efficacy as we expect, allow us to move incredibly quickly as well towards the ultimate goal of this drug that's being widely available for any patients with focal seizures and in the future, other types of seizures as well.

我想在 POWER1 這裡我們可能會略高一些，這也是我們的目標。我們知道這些病人相當難治，或者說我們對藥物非常有信心。我們也希望一旦在此建立基礎並如預期展現非常清楚的療效，就能讓我們也非常快速地朝這個藥物的最終目標前進：讓任何局灶性癲癇患者都能廣泛取得，未來也涵蓋其他類型的癲癇發作。

That brings us to the second part of your question, which is the expectations. And I think that it's always dangerous to talk about expectations and setting bars, artificial bars, this late in the game, in terms of like literally like weeks, I would say, before readouts.

這就帶到你問題的第二部分，也就是預期。我認為在這個階段談預期、或設定門檻（人為的門檻）總是有風險的，尤其是距離讀出結果可能只剩下幾週的時候。

But we've been fairly consistent on the expectation here throughout the years is, number 1, as the severity increases, I think this is one of the few areas, and we're going to be very excited about science that the new drugs still deliver a lot. We just saw that recently with another program, we expect to see the same, like here, a drug delivered despite being piled up with a lot of other drugs.

但我們多年來對此的預期一直相當一致：第一，隨著疾病嚴重度增加，我認為這是少數幾個領域之一，新藥仍然能帶來很大的改善；我們也會對這樣的科學結果感到非常興奮。我們最近在另一個專案也看到了這點，我們預期在這裡也會看到同樣的情況：即使病人已經合併使用許多其他藥物，這個藥仍能帶來效果。

It is at a higher baseline, so more severity. And we've historically been giving that adjusted by placebo around 30% or so as quite meaningful because when we talk to physicians, when you look into the active prescription pattern, that seems to be a number that lands incredibly well.

在較高的基線下，也就是更高的嚴重度。而從歷史經驗來看，我們一直認為經安慰劑校正後約 30% 左右的改善就相當有意義，因為當我們與醫師交流、並觀察實際處方模式時，這個數字似乎非常能被接受、也很有說服力。

And then the last part is safety, as you mentioned. And we're very confident about the safety profile of this drug, both what we're seeing in the blinded, based on POWER1, or also what we are seeing on a blinded basis, POWER2, which was the very last topic you mentioned. So fairly comprehensively, I think we're excited about the upcoming readouts, another card to flip, another program to hopefully accelerate to bring to patients.

最後一部分是你提到的安全性。我們對這個藥物的安全性概況非常有信心，不論是我們在 POWER1 盲態試驗中看到的，或是我們在 POWER2 盲態資料中看到的（也就是你最後提到的主題）。所以整體而言，我們對即將公布的讀出結果感到興奮；又是一張要翻開的牌、又一個希望能加速推進、帶給病人的專案。

POWER2 is going really well. So, as you saw as well in the press release, we reiterated finalizing the study by the end of the year and reading out early next year. So all in all, to think about a potential third or fourth drug or a potential third submission of an NDA or account for this NDA in 12 months is no joke, and we are very, very proud of that.

POWER2 進展得非常順利。如同你在新聞稿中也看到的，我們重申會在年底前完成研究，並在明年初讀出結果。總體來說，在 12 個月內可能迎來第三或第四個藥物、或第三次 NDA 送件，或把這個 NDA 納入 12 個月的規劃，這絕非小事，我們對此非常、非常自豪。

Given that baseline, what about seizure-free, Marcio? Last question, I promise.

在那樣的基線下，Marcio，那無發作（seizure-free）呢？最後一個問題，我保證。

Yeah, no, like Nick -- one there. I think, again, we should unblind it. I do feel the number 1, thing is really to make sure we have a very solid reduction. But of course, we want to see seizure freedom here as well. It's important.

對，沒錯，就像 Nick——那個問題。我想，再次強調，我們應該等到解盲之後再看。我確實覺得第一要務是確保我們有非常扎實的發作減少幅度。但當然，我們也希望看到無發作。這很重要。

It's something we saw on the RADIANT data, that when you treat patients longer, by week 10, 12, your median seizure gets to 100% reduction. So of course, we want to see the more we treat, the longer we treat patients, a very deepening of effect, that's what started seeing. And I'll leave like that, but we're excited with the overall profile.

我們在 RADIANT 的數據中看到，當治療病人的時間更長時，到第 10、12 週，你的中位數癲癇發作可以達到 100% 的減少。所以當然，我們希望看到隨著治療越久、病人接受治療的時間越長，效果會更深化，這也是我們開始看到的趨勢。我就先說到這裡，但我們對整體概況感到興奮。

Thank you. Tiago Fauth, Raymond James.

謝謝。接下來是 Raymond James 的 Tiago Fauth。

Great. Thanks so much for taking the question. I had just one quick one on Ulixa. It's also related to the communication plan for the Street on the regulatory interactions still a huge area of focus with investors. So I'm curious what's the level of detail that the Street can expect around mid-cycle review, labeling discussions, CMC inspection scheduling, or anything related to that?

很好。非常感謝讓我提問。我只有一個關於 Ulixa 的快速問題。這也與對華爾街的溝通計畫有關，因為監管互動仍是投資人高度關注的重點。所以我想了解，針對期中審查（mid-cycle review）、標示（labeling）討論、CMC 稽查排程，或任何相關事項，市場可以期待你們提供到什麼程度的細節？

Thank you.

謝謝。

Thanks, Tiago. So maybe, again, I'll take another step back here as well. So we are, of course, being communicated by the FDA when the expected mid-cycle meetings are going to happen for both programs, their communication pattern with us, when label negotiation is expected to start and be completed, and the entire cycle.

謝謝你，Tiago。我想我也再退一步說明。當然，FDA 會與我們溝通兩個專案預期的期中會議何時舉行、他們與我們的溝通節奏、何時預期開始並完成標示協商，以及整個審查週期的安排。

So we have very good visibility from the agency's goals and from the conversations with us in relation to that. I can tell you that throughout this process, I think a very good shift, I would say, on the FDA is just the ability to really try to keep communicating with the companies throughout the process, and we are seeing that in both programs, which gives us -- I'm going to be cautiously optimistic here about a good level of comfort on how the process is moving on both drugs.

因此，對於主管機關的目標、以及與我們相關的對話內容，我們有非常好的能見度。我可以告訴你，在整個過程中，我認為 FDA 有一個很好的轉變：他們更有能力、也更願意在流程中持續與公司溝通；我們在兩個專案上都看到了這點。

Having said that, I think it would not be appropriate for us to give play-by-play. And at the mid cycle, I think the expectation on our end is that they're going to be like no major concerns, keep reviewing, keep like finalizing, crossing the Ts and dotting the Is.

話雖如此，我認為我們不適合逐項逐步（play-by-play）對外說明。而在期中階段，我們這邊的預期是：不會有重大疑慮，繼續審查、繼續把細節收尾，把該補的都補齊。

And if that's the case, I think we should expect very little from ourselves. Of course, if something meaningful happens on those meetings, either on the view of like maybe they want to see something or the opposite. They are moving faster, and maybe they want to accelerate things.

如果真是如此，我認為我們自己對外應該也不會有太多可更新的內容。當然，如果在那些會議上發生了有意義的事情，不論是他們可能想看某些額外資料，或相反地，他們進度更快、也許想加速一些事項。

I think it would be appropriate for us to have a discussion. But we need to get to that point with both publications to be able to have a discussion. I know you asked Ulixa, but I want to make sure our equally lost child gets some attention here with relutrigine.

我認為那時我們就適合進行說明與討論。但我們需要等兩個案子都走到那個節點，才有辦法討論。我知道你問的是 Ulixa，但我也想確保我們那個同樣有點被忽略的孩子 relutrigine 也能在這裡得到一些關注。

Thank you. Francois Briesbois, LifeSci Capital.

謝謝。接下來是 LifeSci Capital 的 Francois Briesbois。

Hey, thanks for the question and congrats on the EMBOLD recruitment there. I was just wondering, maybe if you can help us understand, obviously, the patient population size is quite different between 2A and 8A, and then going to broader. But I was just wondering on the broad side, how different are these patients?

嗨，謝謝讓我提問，也恭喜 EMBOLD 的招募進度。我想請教的是，也許你們可以幫我們理解：很明顯 2A 與 8A 的病人族群規模差異很大，接著再往更廣泛的族群延伸。但我想問的是，在「廣泛」那一端，這些病人到底有多不同？

And my question is geared towards expectations. Is it that the 2A and 8A are so severe that if we look at that data, that kind of sets these artificial bars or whatnot on expectations for the broad DEEs? Or is that a dangerous game based on maybe the heterogeneity of the patients? Just a little more understanding of who you are going after with these broad DEEs?

我的問題是針對預期。是否因為 2A 與 8A 的病情非常嚴重，所以如果我們看那邊的數據，就會在對廣泛 DEEs 的預期上形成某種人為門檻之類的？或者，基於病人異質性，這其實是個危險的推論？想再多了解一些，你們在這些廣泛 DEEs 中鎖定的是哪些病人？

Yeah. And thanks. I'll split that question into two parts. So, one, it is kind of insane to think this way, but it is the reality of the market. When you go to these patients and to the physicians, and we understand their clinical course and just how the disease is a downward slope, it only gets worse over time for those patients, unfortunately, leading to all sorts of complications and SEP and so on.

是的。也謝謝。我會把這個問題拆成兩個部分。所以，第一，這樣想其實有點不可思議，但這就是市場的現實。當你去接觸這些病患和醫師，我們了解他們的臨床病程，以及這個疾病如何一路下滑——不幸的是，病患只會隨時間惡化，進而導致各種併發症、SEP 等等。

It is very clear that improvement, any improvement, would be the bar, meaning stat sig is the bar for the ERL study. Of course, we want to deliver the best possible results for those patients, but I also think we have to be very careful about setting up the bar. And as I said, in relation to the previous study with POWER1 on Ritu's question. So here we are in a situation that is a very large market, but that is nothing. It's the end of the line.

很明確的是，改善——任何改善——就是門檻，也就是說，對 ERL 研究而言，統計顯著性（stat sig）就是門檻。當然，我們希望為這些病患帶來盡可能最好的結果，但我也認為我們必須非常謹慎地設定門檻。正如我先前在回應 Ritu 關於 POWER1 的問題時所說。所以我們現在處於一個市場非常大的情境，但那其實也不算什麼。這是最後一線。

If you think about the patients, then over time, we expect to give them a lot. But I think for this study, we need to be happy if we see statistical significance as we expect to and some improvements. Now, to go to the other side of the question, how heterogeneous is this population? Our recruitment strategy was very clear as to what we want these patients to be diagnosed with.

如果你從病患角度來看，隨著時間推移，我們預期要給他們很多幫助。但我認為就這項研究而言，只要如我們預期看到統計顯著性以及一些改善，我們就應該感到滿意。接著談問題的另一面：這個族群有多異質？我們的招募策略非常清楚，界定我們希望這些病患被診斷為什麼。

So that's very serious, has to be early, has to have a developmental impact together with seizure onset and a number of countable seizures at baseline. Having said that, we want the most diverse group of patients possible because that's what we're going after. That's what no other drug can do right now. And we accomplished that.

所以必須是非常嚴重、必須是早期、必須在癲癇發作起始的同時對發展造成影響，並且在基線時有一定數量、可計數的發作次數。話雖如此，我們希望病患組成盡可能多元，因為這就是我們要攻克的目標。這也是目前沒有其他藥物能做到的。而我們做到了。

By definition, one could argue that 2A and 8A are harder to treat, but this is more heterogeneous to treat. So if you can see even half, I would say, what we're seeing on EMBOLD would be just doing -- it's even hard to imagine how big a market that would be. But if we see just stabilization and improvement in these patients, that would be incredibly meaningful. So, on setting it up, what is meant to be a really major opportunity for all of us?

按定義來說，有人可能會認為 2A 和 8A 更難治療，但這裡的族群在治療上更為異質。所以如果你能看到哪怕只有一半——我會說——我們在 EMBOLD 看到的效果，那就已經是……甚至很難想像那會是多大的市場。但即便我們只在這些病患身上看到穩定與改善，那也會非常有意義。所以，在設定門檻這件事上，什麼才算是對我們所有人而言真正重大的機會？

And maybe if I could sneak in on AAN, obviously, I think the plenary was passed, like about 8,000 people attending. And so can you just talk about your interactions with neurologists and movement disorder specialists, does that trigger any interest for ex US? Can you share what you guys are thinking on the ex-US stage for ulixacaltamide?

另外也許我可以順便問一下 AAN 的部分，顯然我想全體大會（plenary）通過了，出席人數大概 8,000 人。那你能談談你們與神經科醫師以及動作障礙專科醫師的互動嗎？這是否會引發美國以外（ex US）的興趣？你能分享一下你們對 ulixacaltamide 在美國以外市場（ex-US）階段的想法嗎？

Yeah. Thanks for reminding us of something that I think we get so excited and so wanting to move forward as always, that sometimes we only stop, slow down, and smell the roses. Yes, being on that plenary at AAN in Chicago a couple of weeks back, and with about 8,000 physicians attending, being the first one to recognize the most important clinical study presented at the meeting.

是的。謝謝你提醒我們一件事：我想我們總是很興奮、很想往前推進，以至於有時候我們需要停下來、放慢腳步，享受一下成果。是的，幾週前在芝加哥的 AAN 全體大會上，約有 8,000 位醫師出席，而我們是第一個被認可為在會議上呈現最重要臨床研究的團隊。

It was very emotional for some of us, for me, certainly. But the cort the most cort was actually the number of people who came afterwards to us and wanted us to go to their practice with our medical affairs team and present to the entire practice and [our dentist] start thinking and so on.

對我們其中一些人來說非常感動，對我當然也是。但最讓人感觸深的是，會後有很多人來找我們，希望我們的醫藥事務團隊到他們的診所，向整個團隊做簡報，並且讓[我們的 dentist]開始思考等等。

So it just reinforced now there's a huge interest in ex-US as you can imagine, we believe and to be very clear, this is, first and foremost, a US opportunity right now. We're putting our heads down, and we're executing the US. There are multiple implications of current policies in the

所以這再次強化了：如你所想，美國以外（ex-US）的興趣非常大；但我們也相信並要非常清楚地說，這首先、最重要的是一個美國的機會。我們會埋頭把美國市場執行好。目前政策在美國有多重影響，特別是定價政策方面，我會說這並不太讓我們有興趣去探索在美國以外採取分拆策略。

United States, particularly the pricing policies that I would say don't excite us too much to explore split strategies outside of the US. We wouldn't put at risk the US business. So this is something that someone has to do globally. And of course, we're planning to eventually get there. But we're not really too excited about splitting the geographies with anyone else.

我們不會讓美國業務承擔風險。所以這需要有人在全球層面來做。當然，我們計畫最終會走到那一步。但我們並不太熱衷於把不同地理區域拆分給其他任何人。

Thank you. Yatin Suneja, Guggenheim.

謝謝。Yatin Suneja，Guggenheim。

Hey, guys.

嗨，各位。

Can you hear me?

你們聽得到我嗎？

Yeah.

聽得到。

Perfect. Hey guys, congrats. A very nice update. Maybe two questions for me. Marcio, you addressed the expectations for POWER1. So the follow-up question I have there is that at least in POWER1, we're going to get data on the 30-milligram QD dose.

太好了。嗨，各位，恭喜。這次更新很不錯。我這邊可能有兩個問題。Marcio，你談到了對 POWER1 的預期。所以我接著想問的是，至少在 POWER1，我們會拿到 30 毫克 QD 劑量的數據。

So could you maybe talk about the potential to capture additional efficacy with the 40-milligram in POWER2? Just love to hear from you, how should we think about the 30 and the 40 if there is any potential there? And then a broader question on the commercial side. I mean, obviously, you are undertaking two big launches in the next, let's say, 6-months or so. So could you talk about the manufacturing, supply chain, all of that stuff, where do you stand there?

那你能否談談在 POWER2 使用 40 毫克是否有機會捕捉到額外療效？很想聽你說說，我們應該如何看待 30 與 40（毫克），如果其中存在任何潛力的話？然後是一個更廣泛的商業面問題。我的意思是，很明顯你們在接下來大概 6 個月左右要進行兩個大型上市。所以你能談談製造、供應鏈等各方面的情況嗎？你們目前進展到哪裡了？

Thank you so much.

非常感謝。

No, of course, yeah, maybe even starting with that. So we imagine when we are planning these launches, we're like, okay, what is likely to happen? And that's how we set our base and how we set the financial expectations, and you see in our forward-looking statements, and overall, you are saying that.

當然可以，是的，也許就從那個開始。所以我們在規劃這些上市時，會想：好，最可能發生什麼？我們就是這樣設定基準情境（base case），以及設定財務預期；你也在我們的前瞻性陳述中看到，我們整體就是這樣在說的。

And then we go, and we talk to the market, and we start to be maybe a little conservative on some of those. And what if we're wrong on the upper side of that?

然後我們會去跟市場溝通，並且在其中一些假設上可能會稍微保守一點。那如果我們在上行方面判斷錯了呢？

And then what if we are wrong by several folds on the upper side of that? And that's how we have to plan supply in our view. And that's what we've been doing. We're glad for Ulixa, for example, to have dual like two completely independent drug substance manufacturers. They are being rock and rolled for us to have inventory.

那如果我們在上行方面錯得更多、甚至是好幾倍呢？在我們看來，這就是我們必須如何規劃供應的方式。而這正是我們一直在做的。例如對 Ulixa 而言，我們很高興擁有雙來源——兩家完全獨立的原料藥（drug substance）製造商。它們正在全力運轉，為我們建立庫存。

We're talking about metric tons of drugs here, of Ulixa, just to give you an idea of scale. This is not like a small scale in general, but a very large scale. And we're also quite happy with the fact that the process is relatively, I'm going to say, in the grand scheme of things, simple, and we've been able to align that with the FDA before the submission. So we're good there. Relutrigine, of course, the scale is smaller for 288, but it's not small for GE.

我們談的是以公噸計的藥量——以 Ulixa 來說——只是讓你了解規模。整體而言這不是小規模，而是非常大的規模。我們也很高興這個製程相對而言——我會說在大局觀下——算是簡單，而且我們在送件前已能與 FDA 對齊。所以這部分沒問題。至於 relutrigine，當然 288 的規模較小，但對 GE 來說也不算小。

So we're thinking about that as well, and we're preparing for that for the launch, too. Very different distribution strategies, as you can imagine, a much more full white glove-like one-on-one interactions all the way to the point of use with the relutrigine, and we are building like that. And then on the Ulixa, we want to do a one-to-one as well. But of course, there's a little bit less downstream here. So both the inventory and management of the patient taking the drug have been quite sorted out.

所以我們也在思考這點，並且也在為上市做準備。如你所想，這會是非常不同的配送策略：對 relutrigine 會採取更完整、類似白手套服務（white glove）的方式，從一對一互動一路到實際使用端，我們正在依此建置。而在 Ulixa 方面，我們也希望做一對一。但當然在下游環節會少一些。因此，無論是庫存，或是病患用藥管理，都已經相當完善。

If I go back to your POWER1, POWER2 interrelatedness question, 20-milligrams, 30-milligrams of POWER1, we believe we're going to see very, very strong results there. But that begs the question, is there even more to come?

如果我回到你關於 POWER1、POWER2 相互關聯性的問題，POWER1 的 20 毫克、30 毫克，我們相信會看到非常、非常強勁的結果。但這也引出了問題：是否還會有更多進展？

So if you look into recent history, very, very recent history, what we're seeing is companies dabbling with the issue of even a little bit more drug, and you trip the wire, and then the drug becomes completely useless from a clinical practice perspective.

所以如果你回顧近期歷史、非常非常近期的歷史，我們看到的是，有些公司在嘗試把藥量再多加一點點，結果就踩到紅線，從臨床實務的角度來看，該藥物就變得完全沒有用。

We saw that in our results a few weeks back, when there are two dose and the top dose cannot be used at all by patients despite delivering a little bit more efficacy on paper. But that is not the case here. We know that that is not a limitation with Uoraserene. So when you think about the need of patients and the 3.5 million, not the 30,000 that maybe others are going after, that is the real market we're going after, and it requires understanding the heterogeneity of all those patients.

我們在幾週前的結果中也看到了這點：有兩個劑量，而最高劑量即使在紙面上帶來一點更多療效，患者也完全無法使用。但這裡不是這種情況。我們知道這不是 Uoraserene 的限制。所以當你想到患者需求，以及那 350 萬人——而不是可能其他人鎖定的 3 萬人——那才是我們要攻的真正市場，而這需要理解所有這些患者的異質性。

That's why having the ability to deliver meaningful either 20, 30, or 40, you name it, is so important. So as not to create expectations that it could be even better. But of course, by definition, it could be even better there on POWER2. So we'll get there soon, and we're going to be able to review it.

這就是為什麼能夠提供有意義的 20、30 或 40（你說得出來的劑量）如此重要。以免造成「可能還能更好」的期待。但當然，按定義來說，在 POWER2 上確實可能更好。所以我們很快就會走到那一步，也將能夠回顧相關結果。

I hope I answered your questions.

希望我回答了你的問題。

Thank you. Kambiz Yazdi, BTIG

謝謝。Kambiz Yazdi，BTIG

Good morning, team. Thank you so much for the question. Three for me. On Ulixa, with the Essential to Me disease education campaign launched in April, can you give us a sense for the early response from health care providers and how you think this initiative is going to translate into the top of the patient funnel heading into the PDUFA, maybe briefly on relutrigine.

各位早安，團隊。非常感謝讓我提問。我有三個問題。關於 Ulixa：4 月啟動了「Essential to Me」疾病教育活動後，能否談談醫療照護提供者的早期回饋，以及你們認為這項計畫在 PDUFA 前將如何轉化為患者漏斗上游的成長？也請簡要談一下 relutrigine。

I know you touched base on Mario, but how were you able to enroll EMBOLD so rapidly compared to competitors in the DEE space? And lastly, on vormatrigine, you commented a little bit about blinded POWER1, POWER2 safety. How are you handling the investigator's option to reduce the dose of background medication in POWER1 relative to the RADIANT study?

我知道你提到過 Mario，但相較於 DEE 領域的競爭對手，你們是如何能如此快速地完成 EMBOLD 的入組？最後，關於 vormatrigine：你提到了一些關於盲態 POWER1、POWER2 的安全性。相較於 RADIANT 研究，你們在 POWER1 中如何處理研究者可選擇降低背景用藥劑量的做法？

Thank you so much.

非常感謝。

Sounds good. I'll try to tackle all of them so I can move on. So Essential to me was something we developed with patients and the way they see themselves. And I think once the reaction from the providers is fantastic. Like, people really love it.

好的。我會盡量把問題都回答到，這樣我就可以往下進行。「Essential to Me」是我們與患者一起開發的，反映他們看待自己的方式。我認為醫療端的反應非常好。大家真的很喜歡。

They see their patients. It reminds them to act, and so we're very happy with this. It will, and it's already doing a great job on building further our database prelaunch to understand really who would be the first in line here, both on the providers and on the patient. We're going to give more of an update next quarter as well. How did we enroll EMBOLD?

他們看見了自己的患者。這也提醒他們採取行動，所以我們對此非常滿意。它將會、而且已經在發揮很大作用：在上市前進一步建立我們的資料庫，以真正了解誰會是第一批使用者——不論是醫療提供者端或患者端。我們也會在下個季度提供更多更新。至於我們如何完成 EMBOLD 入組？

I would say to go back in time, and people would ask, and maybe I'm going to be criticized by the comments, but I'm going to give it a try. We would ask Jordan how it could be Jordan. They would go back to the court, and would train and would understand the shots that worked and the ones that didn't.

我想回到過去談談。人們會問——也許我會因為這些評論而被批評——但我想試著回答。我們會問 Jordan 為什麼能成為 Jordan。他會回到球場訓練，並理解哪些投籃有效、哪些無效。

And it wouldn't take any wins as a win, but as an opportunity for the next win to work. I think we're never going to be as good as Jordan was, but I think we're pretty serious about every single day asking ourselves, how can we do better, because these patients need us.

他不會把任何一次勝利只當作勝利，而是把它當作為下一次勝利做準備的機會。我想我們永遠不會像 Jordan 那麼厲害，但我認為我們每天都很認真地問自己：我們如何做得更好，因為這些患者需要我們。

We're pretty good as well on actually getting sites that have a large number of patients and therefore, have the ability to enroll, and they understand us from the beginning, meaning they understand that our expectation is the highest quality, first and foremost. But also high speeds in terms of you don't sit on queries. We don't sit on the eligibility form. You don't sit on a meeting that's going to happen next week. You need us, we're there immediately.

我們也很擅長選擇那些患者數量多、因此具備入組能力的研究中心；而且他們從一開始就理解我們——也就是理解我們的期望是：首先是最高品質。但同時也要有很高的速度，例如不要拖著不回覆查詢（queries）。我們不會拖著資格審查表不處理。你也不該拖著等下週才開的會議。你需要我們，我們會立刻到位。

And I think our team is, if I were to say fantastic, they will be fantastic at doing all of this because everyone is here for one single reason is to help these patients. So that's as simple as that. And I think there was a last question that I actually forgot now.

我認為我們的團隊——如果我說「非常棒」——他們確實非常擅長把這些都做到位，因為大家在這裡只有一個原因：幫助這些患者。就這麼簡單。我想還有最後一個問題，但我現在其實忘了。

Yeah. Just briefly, on vormatrigine, you talked a little bit about blinded POWER1, POWER2 tolerability. How are you handling the investigator option to reduce dose and background in POWER1 relative to what was observed in RADIANT?

對。簡單問一下 vormatrigine：你談到一些關於盲態 POWER1、POWER2 的耐受性。相較於在 RADIANT 觀察到的情況，你們在 POWER1 中如何處理研究者可選擇降低劑量與背景用藥的做法？

Thank you so much.

非常感謝。

Yeah, absolutely. So what we learned from RADIANT, we've got both pragmatic and programmatic reduction systems in POWER1. One must be very confident in what the investigational drug does to allow for the background to be reduced. Others reduce the investigational drug, as you know, because they don't trust the drug so much, not in our case. So we allow that to happen.

好的，當然。我們從 RADIANT 學到的是：在 POWER1 中我們同時設置了務實（pragmatic）與程式化（programmatic）的減量系統。要允許降低背景用藥，必須對試驗用藥的作用非常有信心。如你所知，其他人會降低試驗用藥，因為他們不太信任該藥——但我們不是這樣。所以我們允許降低背景用藥發生。

I will tell you, it happens partially, which is obviously very important. But I think it was very effective as well. It's the same algorithm for POWER2. I think physicians are very happy with how it's done. It's very safely done, although very logical, the way it's done, considering the fact that the background, sometimes on a placebo, creates circumstances as well, which is required.

我可以告訴你，這種情況確實有部分發生，而這顯然非常重要。但我認為這也非常有效。POWER2 使用相同的演算法。我認為醫師對這樣的做法非常滿意。執行上非常安全，也非常合乎邏輯；考量到背景用藥有時即使在安慰劑組也會造成一些狀況，而這樣的處理是必要的。

So it keeps the blinds, keeps the integrity, but at the same time, manages the study in general. So super happy with that as well.

因此它能維持盲態、維持研究完整性，同時也能管理整體試驗。我們對此也非常滿意。

Thank you so much

非常感謝

Thank you. Ami Fadia, Needham & Company.

謝謝。Ami Fadia，Needham & Company。

This is [Puna] on for Ami. For focal onset epilepsy, are there any first-to-market dynamics you see if Xenon's product is first to market? Our KOL checks have been overwhelmingly positive for vomacigine, but I just wanted to understand if there are any other factors that may have an impact here? And also, have you had any early discussions with payers on what data you need to generate to support earlier line use?

我是代 Ami 提問的 [Puna]。針對局灶性起始癲癇（focal onset epilepsy），如果 Xenon 的產品率先上市，你們是否看到任何「先行者」的市場動態？我們對 vomacigine 的 KOL 訪談結果非常正面，但我想了解是否還有其他可能影響的因素？另外，你們是否已與支付方（payers）進行任何早期討論，了解需要產出哪些數據來支持更早線別的使用？

Thank you.

謝謝。

Yeah. So I think when you look into the overall market, and we did a lot of work on this, it's very sad in a sense that when you go outside of the very small number of patients that are treated at Level four epilepsy centers, and you go to a much larger market outside of that, these patients are failing at very high proportions.

是的。我認為當你看整體市場——我們在這方面做了很多工作——某種程度上很令人難過：當你走出那一小部分在第四級癲癇中心（Level four epilepsy centers）接受治療的患者，進入更大的外部市場時，這些患者的治療失敗比例非常高。

They are like switching medications, like they're adding on top of that, and so on. So I said this before, I don't believe that it is a one-winner game here that if we had 10 other drugs for focal seizures, that would be needed. What we have right now is completely inadequate.

他們不斷換藥、在既有用藥上加藥等等。所以我之前說過，我不認為這是一個「一個贏家通吃」的局面；就算我們有另外 10 種治療局灶性發作的藥物，市場也仍然需要。我們目前擁有的治療選項完全不足。

Having said that, the biggest complication throughout the years is when you get a drug, and you really can't allow the physician to have the flexibility to tailor for their patients needs. And I think what we're seeing with vormatrigine is that it gives a lot of flexibility in terms of what can be done, as we just discussed on the previous question, for example, and it's not the case for other potential competitors here.

話雖如此，多年來最大的複雜之處在於，當你拿到一個藥物時，你其實無法讓醫師有彈性去依照病患需求進行個別化調整。而我認為我們在 vormatrigine 上看到的是，它在可採取的作法上提供了很大的彈性，正如我們在上一個問題中討論的例子；但對於這裡其他潛在競爭者而言，情況並非如此。

But also pretty confident about our overall pace. Being a few months behind, and reminding all of you, we were way more than several months behind the other DEE study not that long ago, and now we're reading out soon, and the other study is not even reading out until late next year. So I'm not sure if a few months is really a first-mover advantage.

不過，我們對整體進度也相當有信心。即便落後幾個月，也提醒各位，不久之前我們相較於另一項 DEE 研究落後的可不只是幾個月；而現在我們很快就要讀出結果，反觀另一項研究要到明年年底才會讀出。所以我不確定落後幾個月是否真的構成先行者優勢。

And I don't believe there was ever a mechanistic sodium channel modulator removed from the market, but there certainly was for the other mechanism that you mentioned, and all the safe signals are showing up there as well.

而且我不認為曾有任何以機轉為基礎的鈉離子通道調節劑被下市；但你提到的另一種機轉確實曾發生過，而且所有的安全性訊號也都在那裡出現。

So, I think the physicians we talk to are happy about having more options, but cautious about things that they've seen before not happening too well or working so well for patients on the safety side. So we'll play that. We'll play our press on the market, and I have no doubt we're going to win.

所以，我認為我們接觸到的醫師很樂見有更多選擇，但也會對他們過去看過、在安全性面向表現不佳或對病患效果不如預期的事情保持謹慎。所以我們會照這個方向來應對。我們會在市場上推進我們的策略，我毫不懷疑我們會贏。

Thank you. Andrew Tsai, Jefferies.

謝謝。Andrew Tsai，Jefferies。

Hi, good morning. Appreciate all the updates. I know we've talked a lot about the EMBOLD study. I did have one small pointed question about it. When you guys shared the [2aAA] data, 53% placebo-adjusted reduction overall, curious if you saw a consistent seizure reduction in both or each of the two DEE subgroups. Maybe that can give investors confidence that you'll see robust and consistent efficacy across the broader DEE subgroup.

嗨，早安。感謝所有更新。我知道我們談了很多關於 EMBOLD 研究。我確實有一個比較聚焦的小問題。你們分享 [2aAA] 數據時，整體安慰劑校正後下降 53%；想請教在兩個 DEE 亞組中，是否都觀察到一致的發作（癲癇）降低？也許這能讓投資人更有信心，相信你們在更廣泛的 DEE 亞組中會看到強勁且一致的療效。

So, would it be possible to share the seizure reduction in both subgroups? And then for ET, I appreciate all the AAN analyses and so forth. And maybe based on your ongoing work on a friendlier titration schedule, ultimately, should this be approved, what kind of compliance rate do you expect to see in the real world? How long do you think Ulixa responders could be on the drug for?

所以，是否可以分享兩個亞組各自的發作降低幅度？另外關於 ET，我很感謝你們所有 AAN 的分析等等。也許基於你們正在進行、讓滴定（titration）時程更友善的工作，最終若獲核准，在真實世界中你們預期會看到什麼樣的用藥依從率？你們認為 Ulixa 的反應者可能會在這個藥上維持多久？

Thank you.

謝謝。

Thanks, Andrew. Maybe I'll start with ET, and then we can move back to 2A on EOL and in general. So when you ask physicians, and we had a number of advisory boards and this insanely large overall observational study, we asked them how they would manage and what the expectation is.

謝謝你，Andrew。也許我先從 ET 開始，然後我們再回到 2A 的 EOL 以及整體情況。所以當你去問醫師——我們做了多場諮詢委員會（advisory boards），以及一個規模極其龐大的整體觀察性研究——我們問他們會如何管理，以及他們的預期是什麼。

I think the positive surprise for us was just like how comfortable they were in managing what we know to be a tolerability concern that happens on the first few days and first few weeks of this drug. We're going into this launch fully aware of that being the single most important driver of retention of patients in the long run, and they're incredibly comfortable, and we're actually telling them the things that we thought they could do in terms of like calling these patients and then advising them better, and so on and so forth.

我想對我們而言正面的驚喜是，他們在處理我們所知、會在用藥最初幾天到最初幾週出現的耐受性疑慮時，竟然如此自在。我們在準備上市時完全清楚，這會是長期病患留存（retention）的最重要單一驅動因素；而他們非常有把握。我們其實也在告訴他們一些我們原本以為他們可以做的事，例如主動打電話關懷這些病患、給予更好的建議等等。

So very comfortable with that. Now, how does that translate to overall retention over time and financials? There are two approaches here that we can take. One is saying what the things we're thinking about, and that is your classical oral chronic therapy compliance and retention. So starts anywhere from the 60%s to 80%.

所以在這方面非常有信心。那麼，這如何轉化為隨時間推移的整體留存率與財務表現？這裡我們有兩種做法。一種是談我們正在思考的事情，也就是典型的口服慢性治療的依從性與留存。通常大約落在 60% 到 80% 之間。

That's just overall numbers out there. And then what is the minimum to sustain the forecast we put in front of you all to be over $10 billion? That number is way smaller. So I'm not saying the number will be smaller. I'm saying I'm going to have to believe in something to go into a forecast, and we don't need to believe a lot to go to $10 billion plus.

這只是外部的整體數字。那要支撐我們呈現給各位、超過 100 億美元的預測，最低需要多少？那個數字要小得多。所以我不是說實際數字會更小。我的意思是，我要進行預測就必須相信某些假設，而要達到 100 億美元以上，我們不需要相信太多。

And that gives us insane comfort. We also have hundreds, hundreds of patients in the safety database, as you know, that have been on this drug for 6 months, 1 year, 2 years. So that gives us a very good indicator of how persistent all these patients are.

這讓我們非常安心。此外，如各位所知，我們的安全性資料庫中有數百、數百名病患已使用這個藥 6 個月、1 年、2 年。因此這也給了我們一個很好的指標，了解這些病患的持續用藥（persistence）程度。

The second question is actually very appropriate to be asked right now, the results on 2A and 8A, despite the fact that the manifestations, the electrophysiology, and the overall clinical manifestation of NAV 1.2 deregulations and NAV 1.6 deregulations are very different. The results are quite similar and very good in terms of the overall reduction, developmental gains, and seizure freedom. So it gives us insane comfort that it is so similar across 2A and has all very good points.

第二個問題其實非常適合在此刻提出：2A 與 8A 的結果——儘管 NAV 1.2 失調與 NAV 1.6 失調在表現型、電生理以及整體臨床表現上非常不同——但在整體降低幅度、發展性增益以及無發作（seizure freedom）方面，結果相當類似且非常好。所以這讓我們非常有信心：在 2A 上的表現如此相近，而且各項指標都非常正面。

Thanks for reminding us to make the highlights.

謝謝你提醒我們把重點整理出來。

Thank you. David Hoang, Deutsche Bank.

謝謝。David Hoang，Deutsche Bank。

Great, thanks for taking my questions.

很好，謝謝讓我提問。

So I just had a couple here. Maybe back to vormatrigine in focal epilepsy across POWER1 and POWER2, I know you're looking at three doses, 20, 30, 40 mg. How many of those doses would you like to actually take to market? And what do you think would be the best number for commercial viability?

我這裡有幾個問題。先回到局灶性癲癇中 vormatrigine 的 POWER1 與 POWER2；我知道你們在看三個劑量：20、30、40 mg。你們實際上希望把其中幾個劑量推向市場？你們認為就商業可行性而言，最理想的數量是多少？

And then in terms of the POWER 3 study, the monotherapy study that you also intend to conduct, could you talk a little bit about how that fits into your broader plans for vormatrigine? And why aren't other sponsors pursuing monotherapy studies like that?

另外就 POWER 3 研究而言，也就是你們打算進行的單藥治療（monotherapy）研究，你能否談談它如何融入你們對 vormatrigine 更廣泛的規劃？以及為什麼其他公司不做這類單藥研究？

Thanks a lot.

非常感謝。

Thanks so much for the question, Dave. So 20, 30, 40, when you started S20 for POWER1, and the part is like normally, people start, if you go to the public documents for like other sponsors, for example, everyone is going to be like, how close to the MESCC50 can I get when you translate that to humans?

非常感謝你的問題，Dave。所以 20、30、40；當你在 POWER1 以 S20 開始時，通常大家會——如果你去看其他公司公開文件，例如——每個人都會想：把它換算到人體後，我能多接近 MESCC50？

And I'm going to be pretty close to that because I can go much higher. We can go much higher here. So we're like, where we started the drug is going to be clearly effective. So that's where we started. And where do we end for now, when we believe that's kind of the maximum efficacy?

而我會相當接近，因為我可以用到更高。我們在這裡可以用到更高。所以我們認為起始劑量就會明顯有效。因此我們從那裡開始。那目前我們要到哪裡結束——在我們相信那大概是最大療效的地方？

And I think that's the bull that we are seeing. But a pretty big feedback from the thousands of neurologists that treat this patient is that flexibility is important for them as they're going through different patient types and different comorbid conditions. And so we intend to bring all of those to the market because we believe that gives the highest flexibility to physicians and our largest ability to obtain and keep market share.

我想這就是我們看到的趨勢。但來自數千位治療這類病患的神經科醫師的一個很重要回饋是：在面對不同病患類型與不同共病狀況時，彈性對他們很重要。因此我們打算把這些劑量都帶到市場上，因為我們相信這能給醫師最大的彈性，也讓我們有最大的能力取得並維持市占。

Now, POWER3 is a different animal. POWER3 requires the profile of vormatrigine. So the answer to your question is that others are not doing it because they cannot. Because you need to be able to use this drug as monotherapy. Now there are steps towards monotherapy.

至於 POWER3 則是另一種情況。POWER3 需要 vormatrigine 的特定特性。所以你問題的答案是：其他人不做，是因為他們做不到。因為你必須能把這個藥作為單藥治療來使用。當然也有一些邁向單藥治療的步驟。

It's not an immediate reduction to monotherapy. It has to be done pretty safely, pretty thoughtfully. But patients fail because they can't be on one mechanism. The only mechanism that can, if tolerated, as we believe here, vormatrigine can truly stop any seizures is by acting on the IS and by modulating these channels. And we're the only ones that do that right now.

這不是立即就降階到單一療法。必須以相當安全、相當審慎的方式來進行。但病人之所以治療失敗，是因為他們無法只靠單一作用機轉。我們在此相信，唯一一個在可耐受的前提下、vormatrigine 透過作用於 IS 並調節這些通道，確實能夠阻止任何癲癇發作的機轉。而目前只有我們能做到這一點。

Everything else is upstream of that mechanism. So that's why the confidence when you have a drug like vormatrigine, as I said in my prepared remarks, this is the most potent and most selective ever developed. So we have this data publicly available for anyone to scrutinize.

其他所有藥物都在那個機轉的上游。所以這就是為什麼當你擁有像 vormatrigine 這樣的藥物時會有信心；正如我在事先準備的發言中所說，這是迄今開發過最強效、最具選擇性的藥物。因此我們把這些數據公開提供，任何人都可以檢視與審閱。

So that is the confidence there. What it does is to move from what has been in a little bit of the definition of insanity on how these drugs are developed to get more and more severe patients, smaller pools of patients, and they no longer represent the broader market in those refractory studies.

所以信心就在這裡。它所做的是，讓我們從過去那種在藥物開發上有點像「瘋狂定義」的做法中走出來——不斷去找更嚴重的病人、更小的病人池，而在那些難治性研究中，他們已不再代表更廣泛的市場。

And you're never really addressing the true market, the true unmet needs that are those patients who are struggling to go back to work, struggling to stay driving, struggling to concentrate. A significant number of patients with epilepsy experience disabilities. They cost themselves, the health care system, and the social security system an insane amount of resources because the drugs they were putting are compounding the issue with the condition.

而你其實從未真正觸及真正的市場、真正未被滿足的需求——那些病人正努力重返工作、努力維持開車、努力專注。相當多的癲癇患者會出現失能。他們讓自己、醫療體系以及社會安全體系耗費極其龐大的資源，因為他們被使用的藥物反而在原有疾病之上加劇了問題。

And I think we have an obligation as a company with such a potent, interesting drug to go there and change and revolutionize, as we say, the treatment of epilepsy. That is the long answer to the question.

我認為，作為一家擁有如此強效且有趣藥物的公司，我們有義務走向那裡，去改變並且如我們所說，去革新癲癇的治療。這就是對這個問題的長答案。

Jay Olson, OpCo.

Jay Olson，OpCo。

Hi. Thanks for taking the question. Congrats on all the progress. This is Cheng on the line for Jay. Maybe a couple of us. First, on the Ulixa commercialization. Just curious about the feedback from A and the market research you conducted, what do you view as the most important driver of adoption?

嗨。謝謝讓我提問。恭喜你們取得所有進展。我是 Cheng，代 Jay 在線上。我這邊可能有兩個問題。首先，關於 Ulixa 的商業化。想請教你們從 A 以及你們所做的市場研究得到的回饋是什麼？你們認為採用（adoption）最重要的驅動因素是什麼？

And then I think at the end, you also presented some data on the cerium channel modulator in pain. So I'm just also curious about your latest thinking around this opportunity and if there's anything we should expect in the near term?

另外我想在最後，你們也展示了一些關於疼痛領域的 cerium 通道調節劑數據。所以我也想了解你們對這個機會最新的想法，以及短期內我們是否應該期待有任何進展？

Yeah, of course. Thanks, Jay. So the most important thing for physicians, when we rank -- and as I mentioned before, and I appreciate you bringing up the question, was very extensive testing and really understanding the details from them. And there are a number of things they really like.

好的，當然。謝謝，Jay。所以對醫師而言，當我們做排序——如我先前提到的，也謝謝你提出這個問題——我們做了非常廣泛的測試，並真正去理解他們的細節看法。而他們非常喜歡的點有好幾個。

They really like the fact that they have never had something targeted for essential tremor. So, having something that the most fundamental mechanism is C-type calcium modulation, and now they have something for that, or soon they're going to have something for that.

他們非常喜歡的一點是：他們從來沒有一個專門針對原發性顫抖（essential tremor）的治療。因此，現在有一個其最根本機轉是 C 型鈣通道調節的療法，讓他們有了這樣的選項，或很快就會有這樣的選項。

The second was actually a little bit surprising to all of us. They absolutely lost the fact that in 2 weeks, for the majority of the patients, you have the ability to have a conversation with the patients and they really have an effect. They just don't have that right now in a sustainable manner. They like the fact that we tested the durability of the effect in Study two.

第二點其實讓我們所有人都有點意外。他們非常喜歡的是：在兩週內，對多數病人而言，你就能夠與病人進行對話，而且他們確實有反應、有效果。他們目前並沒有一個可持續的方式做到這一點。他們也喜歡我們在第二項研究中測試了效果的持久性。

And I would say all those things together, and there are many others, really are going to be key drivers of adoption. And as I mentioned on one of the previous calls about like inventory and building, if anything, they're giving us indications they're going to prescribe to more patients than we originally thought they would.

我會說，這些因素加在一起——當然還有很多其他因素——都將成為採用的關鍵驅動力。而且如我在之前某次電話會議提到的，例如庫存與備貨等，如果有什麼訊號的話，他們給我們的指引是：他們會開立給比我們原先預期更多的病人。

And then the second part of your question about our pain program. Well, I think we've been, as you can imagine, we're a CNS company. We need to look into areas of science that make sense for us based on our technology, on the one hand.

接著是你第二個問題，關於我們的疼痛計畫。如你所想像的，我們是一家中樞神經系統（CNS）公司。一方面，我們必須基於我們的技術，去看對我們而言合理的科學領域。

On the other hand, we do have a fair bit of things that are moving forward as we discussed today, and many more catalysts to come. So we've been taking a measured approach in terms of exploring a number of other areas in science where our molecules and our platforms can play a significant role. And at AAN, we did present some of the work we've been doing in pain. And you will hear more from us in the future about how we are advancing quite significantly in that regard as well.

另一方面，正如我們今天討論的，我們確實有相當多項目正在推進，且未來還會有更多催化劑。因此，我們在探索其他科學領域時採取了審慎、循序漸進的方式，評估我們的分子與平台能在哪些領域扮演重要角色。在 AAN 上，我們確實展示了我們在疼痛方面所做的一些工作。未來你們也會聽到我們更多消息，關於我們在這方面同樣正在相當顯著地推進。

Douglas Tsao, H.C. Wainwright.

Douglas Tsao，H.C. Wainwright。

Hi, good morning. Thanks for taking my question. Hello, can you hear me?

嗨，早安。謝謝讓我提問。哈囉，你們聽得到我嗎？

Yeah, we can, Doug.

可以的，Doug。

Sorry about that. Marcio, just starting with EMBOLD, I'm just curious, congrats on completion of enrollment. Obviously, demand was very strong. I'm just curious if you have insight into the subsets of patients that you received?

抱歉。Marcio，先從 EMBOLD 開始，我只是好奇，也恭喜完成收案。顯然需求非常強勁。我想請教你們是否對收到的病人子族群有任何洞見？

And were there any particular ones where you saw very strong demand to reflect sort of the magnitude of unmet need, because obviously, for so many of these, there's no approved therapy, and physicians are just basically trying to figure out as they go along, using sort of off-label ASMs.

以及是否有任何特定子族群的需求特別強，足以反映未被滿足需求的程度？因為很明顯，對其中很多情況而言，根本沒有核准的治療，醫師基本上只能邊做邊摸索，使用一些適應症外（off-label）的抗癲癇藥物（ASM）。

Yeah. Doug, I'm going to be honest, when we went to the sites, and we talked to physicians who presented the protocol. Maybe what I haven't said in the call so far is that we disappointed a lot of physicians by telling them, no, no, no, you've got to stop. You can't enroll more patients in this study. We really got there pretty fast, and it seems like we have a deep understanding of this, exactly what you just said.

是的。Doug，我老實說，當我們到各研究中心，與呈現試驗方案的醫師交流時，或許我在這通電話裡還沒提到的是：我們告訴很多醫師「不、不、不，你們得停下來」，其實讓他們很失望。你不能再把更多病人納入這項研究。我們很快就達標了，而看起來我們對這件事有很深的理解——正如你剛才所說的。

There are so many patients out there that there is very little or nothing they can do, even patients who have other drugs technically approved, but they have failed already, or they try to have a suboptimal response. So it is very broad. Both the phenotype and genotype of patients we got here. And it is within what we expected.

外面有非常多病人，幾乎沒有什麼、甚至完全沒有什麼他們能做；即便是那些理論上已有其他藥物獲批的病人，也可能早已治療失敗，或只能得到不理想的反應。所以涵蓋面非常廣。我們在這裡納入的病人，不論表型或基因型都很廣泛。而且都在我們的預期範圍內。

And unfortunately, maybe this is a [coup] in apology, we couldn't get all the patients that wanted to be on this study. But I think our promise is if the drug works, we're going to get this drug to them in the near future. So really, really happy with everything and all the dynamics here.

而且很遺憾——也許這算是一種帶著歉意的「好問題」——我們無法讓所有想參加這項研究的病人都納入。但我想我們的承諾是：如果藥物有效，我們會在不久的將來把這個藥帶給他們。所以對這裡的一切以及所有動態都非常、非常滿意。

Okay, great. And if I can, on a follow-up in terms of vormatrigine. With POWER1, I'm just curious, do you have any insight in terms of the discontinuation rate so far? Because obviously, I think in RADIANT, there were some discontinuations.

好的，很好。如果可以的話，我想追問一下 vormatrigine。關於 POWER1，我想了解你們目前對停藥率（discontinuation rate）是否有任何洞見？因為很明顯，在 RADIANT 中有一些停藥。

But we certainly heard from clinicians that they had patients who maybe dropped out, who they would have provided some additional counseling, just given the robustness ultimately of the drug, they would maybe encourage them to stay in.

但我們也確實聽臨床醫師說，有些病人可能中途退出；如果當時能提供更多諮詢與衛教，考量到這個藥最終展現的強勁效果，他們或許會鼓勵病人繼續留在試驗中。

Additionally, given the fact that you titrate up in POWER1, if we're seeing any evidence that that is having an effect?

另外，鑑於你們在 POWER1 中是逐步滴定加量（titrate up），我們是否看到任何證據顯示這樣做正在產生影響？

Thank you.

謝謝。

Yeah, absolutely. So we're pretty happy with how we got reduced, I would say, the overall discontinuation here in terms of the historical with the program. I think some of the points you mentioned, people get more experience with the studies, and so on, they get more comfortable managing.

是的，當然。所以我會說，我們對於在此計畫中、相較於過往，整體停藥率能夠降低的成果感到相當滿意。我想你提到的一些重點是，大家對研究更有經驗等等，因此在管理上也更得心應手。

So I'll say I think we're very comfortable with that. I think we're very comfortable with the new benchmark as well, when you consider that drugs people are excited about have like 22% to 25% discontinuation with a further 25% dose reduction on the top dose. That's definitely not what we are seeing. So we think we are very, very competitive here, considering recent competitive events.

所以我會說，我們對此非常有信心。同時，當你考量到一些讓人興奮的藥物，其停藥率大約有 22% 到 25%，而且在最高劑量上還會再有 25% 的劑量下調，我想我們對新的基準也非常有信心。這絕對不是我們所看到的情況。因此，考量到近期競品的動態事件，我們認為我們在這裡非常、非常具有競爭力。

Thank you. Danielle Brill, Truist Securities.

謝謝。Truist Securities 的 Danielle Brill。

Hi, Tyler here for Danielle. My question is regarding the total addressable market in essential tremor. So up to 7 million patients have essential tremor, but you recently said that there are approximately 1 million actively seeking treatment.

嗨，我是 Tyler，代 Danielle 發問。我的問題是關於特發性顫抖（essential tremor, ET）的總可服務市場。大約有多達 700 萬名患者有特發性顫抖，但你們最近表示，約有 100 萬人正在積極尋求治療。

So what's this gap between the predicted prevalent population and those seeking treatment? And with that, is education still needed in the field for more accurate diagnosis? And do higher volume academic centers typically have a more accurate diagnosis?

那麼，在推估的盛行人口與實際尋求治療者之間，這個落差是什麼原因造成的？另外，臨床端是否仍需要更多教育，以利更精準的診斷？而高量能的學術中心通常會有更準確的診斷嗎？

Yeah. So there's about like 2 million to 2.5 million patients right now, either who are being treated and seeing a physician at this moment or just done it and are sitting on the sidelines. So when you go from 7 to, let's say, two to three, it is a drop that is not unheard of. I'll say there are many, many reasons here. It is not a misdiagnosed problem, and I want to clarify that.

是的。所以目前大約有 200 萬到 250 萬名患者，要嘛正在接受治療、此刻正在看醫師，要嘛曾經看過、目前暫時觀望。所以當你從 700 萬降到、比方說 200 萬到 300 萬，這樣的落差並不罕見。我會說這裡有非常、非常多原因。這不是誤診的問題，我想澄清這一點。

This is mostly something they know and they're either not speaking publicly or disclosing or discussing because they know there's a stigma, there's effect I think we just saw this week, Senator Collins speaking about her diagnose of essential tremor in the sense of people attacking that she might not be fit, which obviously is absurd, because this is a progressive disease only of movement, for example, but people are afraid of talking about things like that.

這多半是他們自己知道，但因為知道有汙名化，所以不太願意公開談論、揭露或討論。我想我們本週剛看到參議員 Collins 談到她被診斷為特發性顫抖，結果有人攻擊她可能不適任；這顯然很荒謬，因為這是一種例如僅影響動作的進行性疾病，但人們會害怕談論這類事情。

It is a disease that, for the most part, runs in the family. So people are aware. It is a combination of two factors. One is the progress. It's how quickly and how far in the disease patients are. We call that the level of feasibility, and that's what gives us about $3 million. And the other is society, sometimes not being too ready for someone to raise their hand and say they have a condition.

這種疾病在多數情況下有家族性。所以人們是知道的。這是兩個因素的組合。其一是疾病進展。也就是患者處於疾病的哪個階段、進展多快、到什麼程度。我們稱之為可行性（feasibility）層級，而這讓我們估算大約有 300 萬人。另一個因素是社會有時候還沒那麼準備好，讓某個人舉手說自己有這個狀況。

I think the last one is one where you have two or three family members, and a physician tells the first one, there's nothing I can do right now because there are no good alternatives available. You did engage the other family members with ulixacalamide coming to the market hopefully, soon those dynamics will change. So we bring this to the forefront. One of the reasons why our campaign is called Essential to Me because it's really what is essential for the patients death. That's what we want to awaken to that.

我想最後一點是：當你有兩到三位家族成員，而醫師對第一位說，目前我無能為力，因為沒有好的替代方案可用。但隨著 ulixacalamide 希望很快上市，你就能帶動其他家族成員參與，這些動態將會改變。所以我們把這件事帶到台前。我們的宣導活動之所以叫做「Essential to Me」，其中一個原因是，這真的關乎患者生活中最重要的事。這正是我們想喚醒大家去重視的。

Thank you. Brian Skorney, Baird.

謝謝。Baird 的 Brian Skorney。

Hey, good morning, team. Thanks for fitting me in here. You alluded to the opportunity to develop Ulixa and the oral T-type calcium channel antagonist in indications beyond ET. Obviously, you're pretty full with NDA reviews and running another few pivotal studies.

各位團隊早安。謝謝讓我插進來提問。你們提到有機會在 ET 之外的適應症，開發 Ulixa 以及這款口服 T 型鈣離子通道拮抗劑。顯然你們目前在 NDA 審查以及再跑幾項關鍵性試驗方面已經相當忙碌。

So maybe it's a little bit in the background. But just wondering if you had any updated thoughts on the exploration of other indications where Ulixa could have an impact? And if there's any time frame you can provide, where we might hear an update on that?

所以這可能比較在背景進行。但我想請問，你們對於探索其他 Ulixa 可能產生影響的適應症，是否有任何更新的想法？以及你們是否能提供任何時間表，讓我們知道何時可能會聽到相關更新？

Yeah. Brian, we selected two other indications we're going to be going through. We're just going through the last, I would say, checking everything here, taking the time, and making sure that we can discuss a little bit more publicly.

是的。Brian，我們已選定另外兩個適應症會往下推進。我們正在做最後的、我會說是全面檢查，花時間把所有事情確認清楚，並確保我們能更公開地多談一些。

We're discussing the format of that as well, whether it's an R&D Day or if it's a series of calls and experts with us. So sight just for a bit, and you're going to be able to talk about that. We are very excited, both scientifically, on the patient side, and market potential for either of those indications.

我們也在討論呈現形式，是辦一場研發日（R&D Day），或是一系列我們與專家一起的電話會議。所以再稍等一下，你們就能聽到我們談這件事。無論從科學面、患者面，或是這兩個適應症的市場潛力來看，我們都非常興奮。

Thank you. That's all the time we have for Q&A at this time. I would like to turn the conference back over to Mr. Marcio D'Souza for any closing remarks.

謝謝。目前問答時間就到這裡。我想把電話會議交回給 Marcio D'Souza 先生做結語。

So thank you very much, everyone. I'm sorry for the questions we couldn't take on today's call. I think we're running a little bit ahead here. An incredibly exciting way to start the year. As you think back over the last 12 months, so much happened in really moving the needle for so many patients.

非常謝謝各位。很抱歉今天的電話會議有些問題我們無法回答。我想我們時間有點超前。這是一個令人無比振奮的開年方式。回顧過去 12 個月，發生了很多事情，確實為許多患者帶來了實質進展。

Yet, another study they're finalizing, making sure that we flip the card, make sure that if there is a benefit, we're going to get that as quickly as possible. This year, with EMBRAVE Part A being positive, EMBRAVE 3 recruiting really well, EMBOLD coming up, POWER1 coming up, POWER2 coming up, new indications, as Brian just asked.

此外，還有另一項研究正在收尾，確保我們把牌翻開；如果確實有療效，我們就會盡可能快地把它拿到。今年，EMBRAVE A 部分結果為正向、EMBRAVE 3 招募進展非常順利、EMBOLD 即將到來、POWER1 即將到來、POWER2 即將到來，還有新的適應症，就像 Brian 剛剛問到的。

So we're full steam ahead. The focus is very clear, is to deliver as much value for everyone, including our shareholders. And we promise you we'll have our heads down on the execution here and get everything done.

所以我們將全速前進。焦點非常清楚，就是為所有人交付最大價值，包括我們的股東。我們也向各位承諾，會專注執行，把所有事情完成。

Thanks for the interest, and we're going to be talking to you soon.

謝謝各位的關注，我們很快會再與各位交流。

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone, have a wonderful day.

各位女士、先生，感謝參與今天的電話會議。本次會議到此結束。您現在可以掛線。祝各位有美好的一天。