Xenon Pharmaceuticals Inc. (XENE) 2026 Q1 法說會逐字稿

Thank you for standing by. My name is Rebecca, and I will be your conference operator today. At this time, I would like to welcome everyone to the first-quarter 2026 Xenon Pharmaceuticals earnings conference call. (Operator Instructions)

感謝您耐心等候。我叫 Rebecca，今天將擔任本次電話會議的接線員。此刻，我謹代表主辦方歡迎各位參加 Xenon Pharmaceuticals 2026 年第一季財報電話會議。（接線員指示）

I will now turn the call over to Colleen Alabiso, Senior Vice President of Corporate Affairs at Xenon. Please go ahead.

現在我將把電話交給 Xenon 企業事務資深副總裁 Colleen Alabiso。請開始。

Good afternoon. Thank you for joining us on our call and webcast to discuss Xenon's first-quarter 2026 financial and operating results. Joining me today are Ian Mortimer, President and Chief Executive Officer; Dr. Chris Kenney, Chief Medical Officer; Darren Cline, Chief Commercial Officer; and Tucker Kelly, Chief Financial Officer.

各位下午好。感謝各位參加我們的電話會議與網路直播，一同討論 Xenon 2026 年第一季的財務與營運成果。今天與我一同出席的有：總裁兼執行長 Ian Mortimer；首席醫療官 Chris Kenney 醫師；首席商務官 Darren Cline；以及首席財務官 Tucker Kelly。

After completing our prepared remarks today, we will open the call up for your questions.

在我們完成今天的事先準備發言後，將開放提問。

Please be advised that during this call, we will make a number of statements that are forward-looking, including statements regarding the timing of and potential results from clinical trials, the potential efficacy, safety profile, future development plans and current and anticipated indications, addressable market, regulatory success and commercial potential of our and our partners' product candidates, the strength of our clinical trial designs, our ability to successfully develop and achieve milestones in our clinical development programs, including the anticipated filing of INDs and NDAs, the timing and results of those filings and our interactions with regulators, our ability to successfully obtain regulatory approvals, anticipated timing of top-line data readouts for our clinical trials of azetukalner and other candidates and our expectation that we will have sufficient cash to fund operations in 2029.

請注意，在本次電話會議中，我們將作出若干前瞻性陳述，包括關於臨床試驗時程及潛在結果、我們及合作夥伴產品候選藥物的潛在療效、安全性特徵、未來開發計畫以及目前與預期適應症、可觸及市場、法規核准成功與商業化潛力、我們臨床試驗設計的強健性、我們在臨床開發計畫中成功開發並達成里程碑的能力（包括預期提交 IND 與 NDA）、上述申報的時程與結果以及我們與監管機關的互動、我們成功取得監管核准的能力、azetukalner 及其他候選藥物臨床試驗的主要（top-line）數據讀出之預期時程，以及我們預期擁有足夠現金以支應營運至 2029 年。

Today's press release summarizing Xenon's first quarter financial results and the accompanying quarterly report on Form 10-Q will be made available under the Investors section of our website at xenon-pharma.com and filed with the SEC on SEDAR+.

今日發布、彙總 Xenon 第一季財務結果的新聞稿，以及隨附的 Form 10-Q 季度報告，將於 xenon-pharma.com 網站的投資人（Investors）專區提供，並將向 SEC 提交並於 SEDAR+ 申報。

I'll now turn the call over to Ian.

現在我將把電話交給 Ian。

Thanks, Colleen, and good afternoon to everyone joining us today. We are excited to recap an exceptional quarter for Xenon, where we made tremendous progress toward our goal of becoming a fully integrated neuroscience company, delivering life-changing medicines to patients.

謝謝你，Colleen，也向今天加入我們的各位致上下午好。我們很高興回顧 Xenon 表現卓越的一季；我們在朝向成為一家完整整合的神經科學公司、為病患帶來改變人生的藥物之目標上，取得了重大進展。

In March, we reported results from our Phase 3 X-TOLE2 study of azetukalner, or AZK, in focal onset seizures that exceeded our expectations. Now with these positive data in hand, we are focused on our NDA submission to the FDA expected in the third quarter of 2026, and we also continue to work on increasing AZK awareness and education through our scientific engagement amongst HCPs as well as our commercial readiness activities.

3 月，我們公布 azetukalner（或稱 AZK）用於局灶性發作（focal onset seizures）的第三期 X-TOLE2 研究結果，表現超出我們的預期。在取得這些正面數據後，我們正專注於預計於 2026 年第三季向 FDA 提交 NDA；同時也持續透過與醫療照護專業人員（HCPs）的科學交流，以及我們的商業化準備活動，提升 AZK 的認知與教育。

In addition, we continue to broaden the therapeutic opportunities for AZK beyond epilepsy with potential neuropsychiatric indications where we have strong preclinical, clinical and genetic evidence. Our three Phase 3 depression studies in major depressive disorder and bipolar depression continue to enroll, and we're on track to deliver top-line results from X-NOVA2 in the first half of 2027. Successful studies in MDD, BPD, or both would serve to benefit patients and substantially expand the commercial opportunity for AZK.

此外，我們也持續拓展 AZK 在癲癇以外的治療機會，涵蓋具潛力的神經精神適應症；在這些領域我們擁有強而有力的臨床前、臨床與遺傳學證據。我們在重度憂鬱症（MDD）與雙相憂鬱（bipolar depression）的三項第三期憂鬱症研究持續收案，並按計畫於 2027 年上半年公布 X-NOVA2 的主要（top-line）結果。若在 MDD、BPD 或兩者皆取得成功，將可造福病患，並大幅擴大 AZK 的商業機會。

Finally, we remain focused on expanding our pipeline through the advancement of our promising earlier-stage ion channel programs, with exciting candidates that provide the potential to drive our long-term growth. This includes completion of our first-in-human studies for XEN1701, targeting Nav1.7, and XEN1120 targeting Kv7 later this year, with the intent to advance both programs to Phase 2 proof-of-concept studies in pain.

最後，我們仍專注於推進具前景的早期離子通道計畫，以擴充產品線；這些令人振奮的候選藥物有望驅動我們的長期成長。其中包括今年稍晚完成 XEN1701（靶向 Nav1.7）與 XEN1120（靶向 Kv7）的首次人體試驗，並計畫將兩項計畫推進至疼痛領域的第二期概念驗證（proof-of-concept）研究。

As we continue to execute our clinical programs and prepare for the anticipated approval and launch of AZK, we also continue to prioritize maintaining a strong balance sheet. So today, I'm going to focus most of my comments on AZK and epilepsy, and then I'll turn the call over to Chris, Darren and Tucker.

在我們持續執行臨床計畫並為 AZK 的預期核准與上市做準備之際，我們也持續優先維持強健的資產負債表。因此，今天我將把大部分發言聚焦在 AZK 與癲癇，接著把電話交給 Chris、Darren 與 Tucker。

As you all know, in Q1, we announced positive top-line results from the X-TOLE2 study in focal onset seizures, which exceeded our expectations by surpassing the already strong results from the Phase 2b X-TOLE study, and to our knowledge, demonstrated the highest placebo-adjusted median percent change in monthly focal seizure frequency ever seen in a pivotal FOS study. Similar to X-TOLE, we observed a rapid onset of efficacy, strong and dose-dependent responder rates and a consistent safety and tolerability profile.

各位都知道，在第一季我們公布了 X-TOLE2 研究於局灶性發作的正面主要（top-line）結果；其表現超出我們的預期，不僅優於第二期 b X-TOLE 研究已相當強勁的結果，且據我們所知，顯示了在關鍵性（pivotal）FOS 研究中迄今最高的、相較安慰劑校正後的每月局灶性發作頻率中位數百分比變化。與 X-TOLE 類似，我們觀察到療效起效迅速、反應者比例強勁且呈劑量依賴性，以及一致的安全性與耐受性特徵。

Following the top-line announcement, we were excited to present the data as a late-breaking oral presentation at the American Academy of Neurology Annual Meeting in Chicago. Around these two milestones, we have engaged with hundreds of epileptologists and neurologists and the feedback we've received has been incredibly positive.

在公布主要結果後，我們很高興於芝加哥舉行的美國神經學學會（AAN）年會上，以最新突破（late-breaking）的口頭報告形式發表這些數據。圍繞這兩個里程碑，我們已與數百位癲癇專科醫師與神經科醫師交流，而我們收到的回饋極為正面。

HCPs are enthusiastic about the magnitude of the efficacy benefits seen in our two randomized trials, the breadth and consistency of our safety and tolerability data, the impressive rates of seizure freedom in the OLE and the key differentiating attributes of AZK, and this includes novel Kv7 targeting mechanism of action, no titration, once-daily dosing and no dose adjustments for other ASMs. If approved, this profile would add a meaningful new medicine to their toolkit and provide the opportunity for rational polytherapy.

醫療照護專業人員對我們兩項隨機試驗中觀察到的顯著療效幅度、廣泛且一致的安全性與耐受性數據、開放標籤延伸（OLE）中令人印象深刻的無發作比例，以及 AZK 的關鍵差異化特徵感到振奮；這些特徵包括新穎的 Kv7 靶向作用機轉、無需滴定、每日一次給藥，以及不需針對其他抗癲癇藥物（ASMs）進行劑量調整。若獲核准，這樣的特徵將為其治療工具箱增添一項具意義的新藥，並提供合理的多重治療（rational polytherapy）機會。

We feel increasingly confident in AZK's potential to become a preferred ASM for the significant number of patients who do not achieve seizure freedom with initial treatment. We are working hard to submit our new drug application to the US Food and Drug Administration in the third quarter of 2026. Our base case assumption is a standard review period followed by DEA scheduling, which would put us -- which would put the anticipated launch timing at the end of 2027 or early 2028.

我們對 AZK 有望成為許多在初始治療下仍無法達到無發作的病患之首選抗癲癇藥物（ASM），愈發有信心。我們正全力以赴，力求於 2026 年第三季向美國食品藥物管理局提交新藥申請（NDA）。我們的基本情境假設為標準審查期，之後進行 DEA 排程（scheduling），因此預期上市時點將落在 2027 年底或 2028 年初。

At the same time, we are focused on building out our commercial infrastructure and finalizing our go-to-market strategy, and Darren will speak to this a little bit later on the call. Beyond FOS, we're encouraged by the potential of AZK in primary generalized tonic-clonic seizures, and our Phase 3 X-ACKT study continues to enroll. Positive results in X-ACKT would enable us to submit a supplemental NDA for an additional epilepsy indication, which would meaningfully increase our addressable patient population.

同時，我們也專注於建置商業化基礎設施並敲定上市策略；Darren 稍後會在電話會議中進一步說明。除局灶性發作外，我們也看好 AZK 在原發性全身性強直-陣攣發作（primary generalized tonic-clonic seizures）上的潛力，而我們的第三期 X-ACKT 研究仍在持續收案。若 X-ACKT 取得正面結果，我們將可就額外的癲癇適應症提交補充 NDA，並可顯著擴大我們可觸及的病患族群。

Outside of epilepsy, we're making good progress enrolling our three ongoing neuropsychiatry studies, X-NOVA2 and X-NOVA3 in major depressive disorder and X-CEED in bipolar depression. There is strong rationale for Kv7 openers in depression. Several preclinical and clinical studies, including our own X-NOVA study, have shown promising signals of antidepressive effects for the Kv7 mechanism.

在癲癇以外，我們在三項進行中的神經精神研究收案方面也取得良好進展，包括重度憂鬱症的 X-NOVA2 與 X-NOVA3，以及雙相憂鬱的 X-CEED。Kv7 開啟劑（openers）用於憂鬱症具有強而有力的理論基礎。多項臨床前與臨床研究（包括我們自己的 X-NOVA 研究）已顯示 Kv7 機轉具有具前景的抗憂鬱效果訊號。

Additionally, in bipolar depression, there are genetic links with Kv7, including evidence of Kv7 downregulation. We look forward to sharing our first top-line Phase 3 data set in MDD in the first half of next year.

此外，在雙相憂鬱方面，Kv7 亦存在遺傳學關聯，包括 Kv7 下調（downregulation）的證據。我們期待在明年上半年分享我們在 MDD 的第一套第三期主要（top-line）數據。

We also continue to progress our early-stage programs, including our first-in-human studies with XEN1701 targeting Nav1.7 and XEN1120 targeting Kv7. These are both compelling targets to treat pain with non-opioid approaches. These programs are exciting as they leverage our deep expertise in ion channel science and the strength of our discovery capabilities and would address large unmet medical needs.

我們也持續推進早期計畫，包括靶向 Nav1.7 的 XEN1701 與靶向 Kv7 的 XEN1120 之首次人體試驗。這兩者皆為以非鴉片類方式治療疼痛的具吸引力靶點。這些計畫令人振奮，因其運用我們在離子通道科學上的深厚專業與強大的藥物發現能力，並可滿足龐大未被滿足的醫療需求。

Acute and chronic pain affects more people than diabetes, heart disease and cancer combined, yet effective non-opioid options are scarce. There is a significant opportunity for Xenon to be a leader in unlocking the next generation of pain therapeutics.

急性與慢性疼痛影響的人數，超過糖尿病、心臟病與癌症三者合計，然而有效的非鴉片類選項仍然稀缺。Xenon 有重大機會成為引領者，解鎖下一代疼痛治療藥物。

We're also excited about our early-stage epilepsy programs, including our Nav1.1 program in Dravet syndrome. IND-enabling studies are ongoing, and we continue to showcase our encouraging preclinical findings at large congresses, such as the recent AAN meeting. Our collaborators at Neurocrine are also progressing a Phase 1b study for NBI-921355.

我們也對早期階段的癲癇專案感到振奮，包括我們在 Dravet 症候群的 Nav1.1 專案。IND 申請前（IND-enabling）研究正在進行中，我們也持續在大型學術會議（例如近期的 AAN 年會）展示令人鼓舞的臨床前發現。我們在 Neurocrine 的合作夥伴也正在推進 NBI-921355 的第 1b 期研究。

This is an investigational selective inhibitor of voltage-gated sodium channels Nav1.2 and Nav1.6, which is being investigated as a potential treatment for certain types of epilepsy. Data from this study are expected next year.

這是一種研究用的選擇性電壓門控鈉通道 Nav1.2 與 Nav1.6 抑制劑，正被評估作為某些類型癲癇的潛在治療。預期明年將取得此研究的數據。

Finally, I want to highlight another major accomplishment for Q1, which was the completion of our $747.5 million financing. It significantly extends our cash runway into 2029, allowing us to transition to a commercial stage company and advance our depression and pain programs to key data milestones.

最後，我想強調第一季的另一項重大成就，也就是完成 7.475 億美元的融資。這大幅延長我們的現金可支撐期至 2029 年，使我們得以轉型為商業化階段公司，並推進憂鬱症與疼痛專案至關鍵數據里程碑。

So now with that overview, I'll provide -- I'll turn it over to Chris to provide an update on our activities at AAN and our broader clinical program. Chris?

在以上概述之後，我將把時間交給 Chris，請他更新我們在 AAN 的活動以及更廣泛的臨床計畫進展。Chris？

Okay. Thanks a lot, Ian. It's been a really exciting time at Xenon since we reported our top-line X-TOLE2 data. As you would imagine, there's a great deal of enthusiasm in the epilepsy community with the prospect of a new antiseizure medicine that could address many of the gaps in today's treatment paradigm, including the limited number of mechanisms available.

好的。非常感謝，Ian。自從我們公布 X-TOLE2 的主要（top-line）數據以來，Xenon 一直處於非常令人振奮的時刻。如你所想，癲癇領域對於一款新的抗癲癇發作藥物（antiseizure medicine）抱持高度熱情，因為它有望補足當今治療模式中的許多缺口，包括可用機轉的數量有限。

With the strong X-TOLE2 data that exceeded all expectations, coupled with the long-term OLE data showing sustained effects and impressive seizure freedom, I'm incredibly excited about the potential for AZK to positively impact the lives of patients in the near future and for decades to come.

憑藉超出所有預期的強勁 X-TOLE2 數據，再加上長期 OLE 數據顯示效果持續且達到令人印象深刻的無發作（seizure freedom），我對 AZK 在不久的將來以及未來數十年能為病患生活帶來正面影響的潛力感到無比興奮。

Recently, our team spent a week in Chicago at the American Academy of Neurology Annual Meeting, where we gave several important clinical, preclinical and real-world data presentations, which collectively underscored the significant opportunity for AZK and our growing leadership within epilepsy. I'll start by highlighting the X-TOLE2 data that were featured as a late-breaking science presentation.

近期，我們團隊在芝加哥參加美國神經學學會（AAN）年會一週，發表了多項重要的臨床、臨床前與真實世界數據報告，整體凸顯了 AZK 的重大機會，以及我們在癲癇領域日益增長的領導地位。我先從作為「最新突破科學」（late-breaking science）報告重點呈現的 X-TOLE2 數據談起。

Every year, AAN receives more than 300 late-breaking science submissions. And this year, they selected just 18 abstracts for data that they viewed as warranting expedited presentation and publication to their neurologists. Dr. Jackie French of NYU and Chair of the X-TOLE2 Steering Committee presented the X-TOLE2 data in both an oral platform presentation as well as a poster.

每年，AAN 都會收到超過 300 件最新突破科學投稿。而今年，他們僅選出 18 篇摘要，認為其數據值得加速向神經科醫師進行報告與發表。紐約大學（NYU）的 Jackie French 醫師、同時也是 X-TOLE2 指導委員會主席，以口頭平台報告與海報兩種形式呈現 X-TOLE2 數據。

The reactions were very positive with the session moderator from Harvard University and Massachusetts General Hospital characterizing the data as outstanding. And Dr. French highlighting rapid onset of efficacy and no titration as key differentiating aspects of AZK that will appeal to physicians. Our X-TOLE2 presentation reinforced the positive top-line data we announced in March, including that the study met its primary endpoint of median percent change in monthly FOS frequency from baseline to week 12 in both the 25-milligram and 15-milligram AZK dose groups compared to placebo.

反應非常正面，來自哈佛大學與麻省總醫院的場次主持人將該數據形容為「傑出」。French 醫師也強調，療效起效快速且無需滴定（titration）是 AZK 的關鍵差異化特點，將對醫師具有吸引力。我們的 X-TOLE2 報告強化了我們在 3 月公布的正向主要數據，包括研究達成主要終點：在 25 毫克與 15 毫克 AZK 劑量組，相較安慰劑，從基線至第 12 週每月 FOS 頻率的中位數百分比變化（median percent change, MPC）。

Specifically, we observed an MPC reduction of 53.2% for 25 milligrams, 34.5% for 15 milligrams and 10.4% for placebo, results that were highly statistically significant and actually outperformed the Phase 2b X-TOLE study. We also observed early dose-dependent MPC reductions in weekly FOS from baseline to week one, which were sustained through the double-blind period with both AZK doses, reinforcing AZK's rapid and sustained antiseizure activity.

具體而言，我們觀察到 25 毫克的 MPC 降幅為 53.2%，15 毫克為 34.5%，安慰劑為 10.4%；結果具有高度統計顯著性，且實際上優於第 2b 期 X-TOLE 研究。我們也觀察到從基線至第 1 週，每週 FOS 的 MPC 降幅呈現早期且具劑量依賴性，並在雙盲期間以兩個 AZK 劑量皆維持，進一步支持 AZK 具快速且持續的抗癲癇發作活性。

These efficacy results are even more impressive when you consider that X-TOLE and X-TOLE2 included the most treatment-resistant FOS population ever trialed. At baseline, patients in X-TOLE2 were experiencing a median of 13 seizures per month, had been treated with a median of five prior ASMs and more than half were already using three concomitant antiseizure medications. About 60% were on or had already tried and stopped cenobamate and still they had not achieved seizure control.

當你考量到 X-TOLE 與 X-TOLE2 納入的是迄今試驗中治療抗性最高的 FOS 族群時，這些療效結果更顯得令人印象深刻。在基線時，X-TOLE2 病患每月癲癇發作中位數為 13 次，既往接受過的抗癲癇發作藥物（ASM）中位數為 5 種，且超過一半的病患已同時使用 3 種抗癲癇發作藥物。約 60% 的病患正在使用或曾嘗試後停用 cenobamate，但仍未達到發作控制。

We also provided additional data from our responder rate analysis, where we observed dose-dependent increases in the proportion of participants with at least 75% and 90% reductions in monthly seizure frequency through the double-blind period.

我們也提供了反應者比例（responder rate）分析的額外數據，觀察到在雙盲期間，每月癲癇發作頻率至少降低 75% 與 90% 的受試者比例，隨劑量增加而上升。

We also presented 100% responder rate data, which demonstrated that a 100% reduction in seizures over the double-blind period was attained by a greater proportion of participants with AZK 25 milligrams than placebo, results which were highly consistent with the results of X-TOLE.

我們也呈現了 100% 反應者比例數據，顯示在雙盲期間癲癇發作降低 100%（即無發作）者，在 AZK 25 毫克組的比例高於安慰劑；該結果與 X-TOLE 的結果高度一致。

While AZK has a rapid onset of efficacy, it also takes a few weeks to reach steady-state levels. And we've seen in other instances such as the X-TOLE OLE that efficacy continues to build over time. Therefore, we also conducted a post-hoc analysis of the X-TOLE2 data to see if a greater proportion of participants experienced a 100% reduction in seizures over time. Indeed, 100% responder rate increased steadily over the last eight, six, and four weeks.

雖然 AZK 的療效起效快速，但仍需要數週才能達到穩態濃度。而我們也在其他情境（例如 X-TOLE 的 OLE）看到療效會隨時間持續累積。因此，我們也對 X-TOLE2 數據進行事後（post-hoc）分析，以評估隨時間推移，是否有更高比例的受試者達到癲癇發作 100% 降低。確實，100% 反應者比例在最後 8 週、6 週與 4 週期間皆呈穩步上升。

For example, the 100% responder rate over the 12-week double-blind period for 25 milligrams was 6.5%. But over the last 6 weeks, it increased to 11.3% and over the last four weeks, it increased further to 13.7%. We're looking forward to continuing to follow this trend in the Phase 3 OLE.

例如，在 25 毫克組，12 週雙盲期間的 100% 反應者比例為 6.5%。但在最後 6 週期間，該比例上升至 11.3%，而在最後 4 週期間，進一步上升至 13.7%。我們期待在第 3 期 OLE 中持續追蹤此趨勢。

This brings me to our other key AZK presentation at AAN, our 48-month X-TOLE OLE data, where the trend of efficacy building over time is even more compelling. The OLE is also where we are best positioned to evaluate whether patients are truly achieving seizure freedom, which has been a consensus definition of no seizures for 12 months or more. This definition also aligns to practical real-world outcomes for patients, as in many states 12 months without seizures means they're able to drive again.

這也帶到我們在 AAN 的另一項 AZK 重點報告：48 個月的 X-TOLE OLE 數據，其中療效隨時間累積的趨勢更具說服力。OLE 也是我們最能評估病患是否真正達到無發作的地方；無發作的共識定義為 12 個月或更久沒有癲癇發作。此一定義也符合病患在真實世界的實際結果，因為在許多州，連續 12 個月無發作意味著他們可以再次開車。

Our long-term OLE data demonstrated continued reductions in focal seizures with a 91% reduction in monthly seizure frequency for those treated for at least 48 months. Those who entered the study taking one or two ASMs demonstrated a 100% reduction in monthly seizure frequency compared with an 82% reduction in seizure frequency among those taking three ASMs at baseline.

我們的長期 OLE 數據顯示，局灶性癲癇發作持續下降；對於至少治療 48 個月者，每月癲癇發作頻率降低 91%。入組時使用 1 或 2 種 ASM 的受試者，其每月癲癇發作頻率降低 100%；相較之下，基線時使用 3 種 ASM 者的癲癇發作頻率降低 82%。

With regards to seizure freedom, the patients treated for at least 48 months, almost 40% were seizure-free for at least 12 months and one in four were seizure-free for at least two years. If you consider how treatment-resistant the overall patient population was at baseline, this is truly remarkable.

就無發作而言，在至少治療 48 個月的病患中，近 40% 已連續至少 12 個月無發作，且每 4 人就有 1 人已連續至少 2 年無發作。若考量整體病患族群在基線時的治療抗性程度，這確實非常了不起。

Based on feedback from our investigators, we understand some of these patients have never experienced seizure freedom before taking AZK, and their stories fuel our desire to bring AZK to patients and clinicians as quickly as possible.

根據我們研究人員的回饋，我們了解到其中一些患者在服用 AZK 之前從未曾達到過癲癇發作完全控制，而他們的故事更激勵我們希望盡快將 AZK 帶給患者與臨床醫師。

Finally, I'll also note that our AZK data at AAN continued to support a general well-tolerable profile. The safety data are remarkably consistent between X-TOLE and X-TOLE2 in terms of types of treatment-emergent adverse events, the frequency at which they occurred, the number and types of serious adverse events and the events that led to discontinuations.

最後，我也要指出，我們在 AAN 發表的 AZK 數據持續支持其整體具有良好耐受性的特徵。就治療期間出現的不良事件類型、發生頻率、嚴重不良事件的數量與類型，以及導致停藥的事件而言，X-TOLE 與 X-TOLE2 的安全性數據高度一致。

The most common treatment-emergent adverse events across both studies in the AZK dose groups were dizziness, somnolence, headache and fatigue. With more than 800 patient years of safety and exposure data, we are comfortable that this profile is consistent with other well-tolerated ASMs and with a drug that is potent and active in the central nervous system.

在兩項研究的 AZK 劑量組中，最常見的治療期間出現不良事件為頭暈、嗜睡、頭痛與疲勞。累積超過 800 個病人年（patient-years）的安全性與暴露數據後，我們有信心此一特徵與其他耐受性良好的抗癲癇藥物（ASM）一致，也符合一種在中樞神經系統具高效力且具活性的藥物之特性。

We will continue to add to these robust safety and tolerability data with our ongoing Phase 2 and Phase 3 OLEs in epilepsy.

我們將透過正在進行的癲癇第 2 期與第 3 期開放標籤延伸試驗（OLE），持續累積這些強而有力的安全性與耐受性數據。

Another focus for Xenon at AAN was education around unmet needs in epilepsy care, including the impact that titration has on both patients and HCPs and the opportunity for no titration options to improve treatment experiences, outcomes and health care resource utilization. We presented real-world data that captured the challenges reported by patients around medication schedules, daily life and quality of life during titration periods, while physicians reported challenges related to treatment complexity and cross titration.

Xenon 在 AAN 的另一個重點是針對癲癇照護中尚未被滿足的需求進行教育，包括劑量滴定（titration）對患者與醫療照護專業人員（HCP）的影響，以及「無需滴定」選項在改善治療體驗、結果與醫療資源使用方面的機會。我們展示了真實世界數據，呈現患者在滴定期間對用藥時程、日常生活與生活品質所回報的挑戰；同時，醫師也回報了與治療複雜性及交叉滴定（cross titration）相關的挑戰。

When questioned on the perceptions of ASMs without titration, most patients noted that they either agree or strongly agree that initiating an ASM without needing to titrate to a stable dose would boost their confidence, reduce anxiety and improve adherence. Physicians noted that no titration options would increase simplicity as many patients are already on complex drug regimens.

在被問及對「無需滴定」的抗癲癇藥物（ASM）的看法時，多數患者表示他們同意或非常同意：在不需要滴定至穩定劑量的情況下開始使用 ASM，將能提升信心、降低焦慮並改善用藥依從性。醫師則指出，鑑於許多患者已在使用複雜的用藥方案，無需滴定的選項將可提升治療的簡便性。

These findings suggest using ASMs that do not require titration may reduce stress and simplify FOS management. And we heard this echoed in our discussions at AAN as well, especially for general neurologists who value the ease-of-use attributes in prescribing decisions.

這些發現顯示，使用不需要滴定的抗癲癇藥物（ASM）可能降低壓力並簡化局灶性發作（FOS）的管理。我們在 AAN 的討論中也聽到相同的回饋，尤其是重視處方決策中「易用性」特質的一般神經科醫師。

We rounded out our AAN scientific program with an oral presentation of preclinical data from our Nav1.1 program in Dravet syndrome. These data demonstrated that selective potentiation of Nav1.1 channels in Dravet mice improved motor function, suppressed spontaneous seizures, preventing sudden unexpected death from epilepsy, increased long-term potentiation, which is a potential cellular correlate of learning and memory, and produced more mature dendritic spine morphology.

我們以一場口頭報告，發表了 Nav1.1 計畫在德拉維特症候群（Dravet syndrome）的臨床前數據，為 AAN 的科學議程畫下句點。這些數據顯示，在德拉維特小鼠中選擇性增強 Nav1.1 通道可改善運動功能、抑制自發性癲癇發作、預防癲癇猝死（SUDEP）、增加長期增強作用（long-term potentiation；可能是學習與記憶的細胞層面相關指標），並產生更成熟的樹突棘形態。

The data continued to support our belief that targeting Nav1.1 with a small molecule could potentially address the underlying cause and symptoms of Dravet syndrome. IND-enabling studies for this program are currently ongoing. All in all, we're very proud of our scientific contributions at AAN as well as how positively they were received by the community.

這些數據持續支持我們的看法：以小分子藥物靶向 Nav1.1，可能有機會同時處理德拉維特症候群的根本原因與症狀。此計畫的 IND 申請前（IND-enabling）研究目前正在進行中。總而言之，我們對在 AAN 的科學貢獻以及社群對其正面回應感到非常自豪。

Moving on to our other clinical programs. We've had a lot of activity as we continue to enroll three Phase 3 studies in depression and two Phase 1 programs in pain. Depression is an area where the differentiated profile of AZK, including its novel mechanism of action, rapid onset of action and potential benefits on anhedonia could meaningfully benefit patients. Like epilepsy, the depression landscape has experienced a dearth in innovation for some time and new mechanisms are urgently needed.

接下來談談我們其他的臨床計畫。隨著我們持續招募三項憂鬱症第 3 期研究，以及兩項疼痛領域第 1 期計畫，我們近期有相當多的進展。憂鬱症是一個 AZK 具差異化特徵的領域，包括其新穎作用機轉、快速起效，以及對快感缺失（anhedonia）的潛在益處，可能為患者帶來實質幫助。如同癲癇領域，憂鬱症治療版圖也已一段時間缺乏創新，迫切需要新的作用機轉。

Our clinical development team has made great progress with X-NOVA2 and X-NOVA3, which are ongoing and enrolling patients with major depressive disorder. As Ian previously stated, we anticipate sharing top-line data from X-NOVA2 in the first half of 2027.

我們的臨床開發團隊在 X-NOVA2 與 X-NOVA3 方面取得重大進展；這兩項研究目前正在進行中，並持續招募重度憂鬱症（MDD）患者。如 Ian 先前所述，我們預期將於 2027 年上半年分享 X-NOVA2 的主要（top-line）數據。

In addition, X-CEED, a Phase 3 clinical study evaluating AZK in patients with bipolar I and bipolar II depression, also continues to enroll. This is another area where there is significant unmet need for safe and effective therapies due to nonadherence related to side effects and other factors. The physicians that we've spoken with are keenly interested in AZK's novel selective Kv7 mechanism of action, potential benefit on anhedonia, rapidity of onset and differentiated safety profile.

此外，X-CEED（第 3 期臨床研究），用以評估 AZK 在第一型與第二型雙相情感障礙憂鬱症患者中的療效，也持續招募中。由於副作用及其他因素導致的不依從性，此領域對安全且有效的治療仍存在顯著未被滿足的需求。我們交流過的醫師對 AZK 新穎且具選擇性的 Kv7 作用機轉、對快感缺失的潛在益處、起效速度，以及差異化的安全性特徵表現出高度興趣。

To round out my remarks, pain continues to be an area of growing focus, and we're looking forward to completing our first-in-human studies for our novel pain programs this year. There remains a strong desire for non-opioid pain therapies given the limited efficacy of current options and substantial risk of abuse and dependency tied to opioids.

作為我發言的收尾，疼痛仍是我們日益聚焦的領域，我們期待在今年完成新穎疼痛計畫的首次人體試驗（first-in-human）。鑑於現有選項療效有限，且鴉片類藥物伴隨顯著的濫用與依賴風險，市場對非鴉片類止痛療法仍有強烈需求。

We know that analgesics can act along multiple different points of the pain pathway and interrupt the pain signal on its way to the brain, and we believe in the potential for Nav1.7 inhibitors and Kv7 potentiators to play important roles at multiple points in this pathway, including in the initial transduction of pain stimuli into pain signals, the transmission of those pain signals along nociceptive neurons and the relay from peripheral sensory neurons to spinal cord neurons in the central nervous system.

我們知道，鎮痛藥可在疼痛傳導路徑的多個不同節點發揮作用，並在疼痛訊號傳往大腦的過程中加以中斷；我們相信 Nav1.7 抑制劑與 Kv7 增強劑有潛力在此路徑的多個節點扮演重要角色，包括將疼痛刺激初始轉換為疼痛訊號、沿傷害感受神經元（nociceptive neurons）傳遞疼痛訊號，以及在中樞神經系統中由周邊感覺神經元向脊髓神經元進行中繼傳遞。

We believe Nav1.7 is the best genetically validated pain target with striking genetic data in patients with loss of function mutations that have no ability to feel pain. Pain of function mutations have also been identified that drive pain disorders, further underscoring the critical role Nav1.7 plays in pain signaling. With XEN1701 as well as other Xenon programs in preclinical development, we believe we have solved for some of the critical limitations of prior Nav1.7 compounds.

我們認為 Nav1.7 是目前基因層面驗證最充分的疼痛靶點；在帶有功能缺失（loss-of-function）突變的患者中，有非常顯著的基因數據顯示其完全無法感受疼痛。此外，也已辨識出會驅動疼痛疾病的功能獲得（gain-of-function）突變，進一步凸顯 Nav1.7 在疼痛訊號傳遞中的關鍵角色。透過 XEN1701 以及 Xenon 其他處於臨床前開發階段的計畫，我們相信已解決先前 Nav1.7 化合物的一些關鍵限制。

Kv7 is also a compelling pain target to modulate neuronal hyperexcitability at multiple points along the pain pathway. And we believe Kv7 potentiators have the potential to treat a range of pain conditions. This is supported by high levels of Kv7 expression throughout the pain pathway and our preclinical data shows that Kv7 is enriched in the C and A delta subtypes of sensory neurons.

Kv7 也是一個極具吸引力的疼痛靶點，可在疼痛路徑的多個節點調節神經元過度興奮。我們相信 Kv7 增強劑有潛力治療多種疼痛狀況。這一點受到疼痛路徑中 Kv7 高表現量的支持，而我們的臨床前數據顯示 Kv7 在感覺神經元的 C 型與 Aδ 型亞型中更為富集。

In addition, Kv7 openers can block action potential firing in both DRG and spinal cord neurons, thereby significantly inhibiting pain signals from reaching the brain. Evidence supports that dysfunction or downregulation of Kv7 activity has been observed in altered pain states.

此外，Kv7 開啟劑可阻斷背根神經節（DRG）與脊髓神經元的動作電位放電，從而顯著抑制疼痛訊號傳達至大腦。證據顯示，在疼痛狀態改變時，已觀察到 Kv7 活性功能失調或下調。

We're excited to be advancing an optimized Kv7 opener with our XEN1120 program. We're really encouraged by our Nav1.7 and Kv7 work in pain and look forward to providing more details later in the year.

我們很興奮能透過 XEN1120 計畫推進一款經最佳化的 Kv7 開啟劑。我們對 Nav1.7 與 Kv7 在疼痛領域的研究成果深受鼓舞，並期待在今年稍晚提供更多細節。

With that, I'll turn it over to Darren to provide an update on our path to commercialization, including interactions and discussions at AAN. Darren?

接下來，我將把時間交給 Darren，請他就我們的商業化路徑提供最新進展，包括在 AAN 的互動與討論。Darren？

Thank you, Chris. I would like to reinforce the comments from Ian and Chris regarding the strong interest in our X-TOLE2 data since we first reported the results in early March. Since then, we have seen sustained engagement and interest from a broad group of epileptologists and neurologists attending AAN. Across these interactions, they reiterated the strength of our X-TOLE2 and OLE data sets and AZK's differentiated profile, and we consistently heard enthusiasm about the potential to use AZK in clinical practice.

謝謝你，Chris。我想再次強調 Ian 與 Chris 的評論：自我們在 3 月初首次公布結果以來，市場對我們的 X-TOLE2 數據展現出強烈興趣。此後，我們看到參與 AAN 的廣泛癲癇專科醫師與神經科醫師持續投入與關注。在這些互動中，他們重申我們的 X-TOLE2 與 OLE 數據集的強度，以及 AZK 的差異化特徵；我們也一再聽到大家對 AZK 在臨床實務中應用潛力的熱忱。

Physicians highlighted the importance of efficacious therapies that are also straightforward to incorporate into routine patient care. AZK's unique mechanism and its expected profile of once-daily dosing, an effective starting dose, no drug interactions and no dose adjustments with other ASMs remains among the most frequently cited and most compelling attributes.

醫師強調，療效確切且也能夠容易納入日常病患照護流程的治療方案之重要性。AZK 的獨特作用機制，以及其預期具備每日一次給藥、有效起始劑量、無藥物交互作用且與其他抗癲癇藥物（ASM）併用時無需調整劑量的特性，仍是最常被提及且最具說服力的優勢之一。

Looking ahead, we plan to increase our understanding through primary research, advisory boards and one-on-one meetings as we continue to deepen our insight of AZK in advance of potential approval and launch. Based on our growing engagements with this audience, we believe AZK has the potential to become the preferred branded ASM for general neurologists.

展望未來，我們計畫透過主要研究、諮詢委員會及一對一會議來提升我們的理解，並在潛在核准與上市前持續加深對 AZK 的洞察。基於我們與此族群日益增加的互動，我們相信 AZK 有潛力成為一般神經科醫師偏好的品牌抗癲癇藥物（ASM）。

We also continue to hear that AZK's profile may support greater confidence in treating a broader range of epilepsy patients within community practices rather than referring patients to a Level 3 or 4 epilepsy center after exhausting existing available options, which could contribute to broader adoption, improved patient outcomes and meaningful prescription growth over time.

我們也持續聽到，AZK 的特性可能有助於提升在社區診所治療更廣泛癲癇病患族群的信心，而非在既有可用選項用盡後才將病患轉介至第 3 或第 4 級癲癇中心；這可能促進更廣泛的採用、改善病患結果，並隨時間帶來具意義的處方成長。

Launch readiness remains a key enterprise priority. Over the past several months, we have focused on increasing our scientific engagement with epilepsy specialists, neurologists and advanced practice providers, while continuing to expand our field-based capabilities, including the recent addition of several medical science liaisons. In parallel, we have initiated discussions with payers to introduce Xenon, better understand unmet needs and communicate potential value proposition of AZK.

上市準備度仍是公司層級的關鍵優先事項。過去數月，我們著重提升與癲癇專科醫師、神經科醫師及進階實務提供者的科學互動，同時持續擴充我們的外勤能力，包括近期新增數位醫學科學聯絡員（MSL）。同時，我們已啟動與付款方的討論，以介紹 Xenon、更深入了解未被滿足的需求，並溝通 AZK 的潛在價值主張。

In March, we attended the Pharmaceutical Care Management Association, or PCMA, meeting for the first time and held a number of productive introductory discussions with pharmacy benefit managers and payers. The timing of these conversations alongside our X-TOLE2 data release helped drive interest and momentum. We plan to participate in several national payer meetings this year.

3 月，我們首次參加藥品照護管理協會（Pharmaceutical Care Management Association，PCMA）會議，並與藥局福利管理機構（PBM）及付款方進行多場富有成效的初步交流。這些對話的時點與我們發布 X-TOLE2 數據相互呼應，有助於帶動興趣與動能。我們計畫今年參與數場全國性付款方會議。

And in the coming months, we expect to expand our field-based payer team to continue dialogue with this important constituency and further strengthen our launch preparedness. As we execute on these launch readiness priorities, we remain focused on building an experienced launch and life cycle management organization, advancing innovation across channels and patient services and increasing awareness across our customer universe.

在接下來幾個月，我們預期將擴編外勤付款方團隊，持續與這個重要利害關係人對話，並進一步強化我們的上市準備。在推進這些上市準備優先事項的同時，我們仍專注於建立具經驗的上市與產品生命週期管理組織、推動跨通路與病患服務的創新，並提升我們整體客戶群的認知度。

Our commercial objective is to establish Xenon as a leader in epilepsy, and we believe we are making meaningful progress towards that goal. We are highly motivated by the opportunity to deliver meaningful benefits to patients and the physicians who care for them.

我們的商業目標是將 Xenon 打造成癲癇領域的領導者，我們相信正朝此目標取得具意義的進展。能為病患及照護他們的醫師帶來實質效益的機會，讓我們深受激勵。

With that, I'll turn the call over to Tucker to review our financial results.

接下來，我把電話交給 Tucker，請他回顧我們的財務結果。

Thanks, Darren. As Ian mentioned, the exceptional results in X-TOLE2 allowed us to complete a highly successful public offering of nearly $750 million, which fortified our balance sheet as we move to a potential approval and launch. We ended Q1 with cash, cash equivalents and marketable securities of $1.3 billion compared to $586 million as of December 31, which, based on our current operating plans, provides cash to fund operations into 2029.

謝謝，Darren。如 Ian 所提到，X-TOLE2 的卓越結果使我們得以完成一項非常成功、規模近 7.5 億美元的公開發行，並在我們邁向潛在核准與上市之際強化了資產負債表。我們在第一季末的現金、約當現金及可出售證券為 13 億美元，相較於 12 月 31 日的 5.86 億美元；依據我們目前的營運計畫，這可提供資金支應營運至 2029 年。

Given our strong balance sheet and fiscal management, we are well positioned to support AZK's US launch, multiple registrational programs for AZK and the continued maturation of our early-stage pipeline. I would refer you to our press release and our 10-Q filed today for further details on our financial results.

憑藉我們強健的資產負債表與財務管理，我們具備良好條件以支持 AZK 在美國的上市、AZK 的多項註冊性計畫，以及我們早期研發管線的持續成熟。關於財務結果的更多細節，請參閱我們的新聞稿以及今日提交的 10-Q。

Overall, it's a very exciting time at Xenon as we continue to build momentum in our pipeline spanning epilepsy, depression and pain, and make progress against our critical priorities, with our first target being the submission of our NDA for AZK to the FDA in the third quarter of 2026 as well as the advancement of our commercial readiness activity to support a strong launch in FOS.

整體而言，對 Xenon 來說這是一個非常令人振奮的時刻；我們持續在涵蓋癲癇、憂鬱症與疼痛的研發管線上累積動能，並在關鍵優先事項上取得進展。我們的首要目標是在 2026 年第三季向 FDA 提交 AZK 的 NDA，同時推進商業化準備活動，以支持在 FOS 的強勁上市。

We also remain focused on broadening the therapeutic opportunities for AZK beyond epilepsy, and we continue to make good progress enrolling our studies in major depressive disorder and bipolar depression, with the readout of our first depression study anticipated in the first half of 2027.

我們也仍專注於將 AZK 的治療機會拓展至癲癇以外領域；我們在重度憂鬱症與雙相憂鬱症研究的收案方面持續取得良好進展，並預期於 2027 年上半年讀出我們第一項憂鬱症研究結果。

And lastly, we are pleased with the momentum in our early-stage pain program, and we anticipate completing the first-in-human studies for 1701 targeting Nav1.7 and 1120 targeting Kv7 later this year, and we seek to advance both programs to Phase 2 proof-of-concept studies.

最後，我們對早期疼痛計畫的動能感到滿意；我們預期於今年稍晚完成 1701（靶向 Nav1.7）與 1120（靶向 Kv7）的首次人體試驗，並希望將兩項計畫推進至第 2 期概念驗證研究。

We are in an excellent position to execute our priorities due to our strong cash position, and we are feeling very optimistic about a bright future as we begin to transition to a commercial stage company, delivering meaningful medicines to patients. And with that, we can open the call up for questions. Operator?

憑藉強勁的現金部位，我們處於極佳位置以執行各項優先事項；隨著我們開始轉型為商業化階段公司、為病患提供具意義的藥物，我們對光明的未來感到非常樂觀。接下來，我們可以開放提問。接線員？

(Operator Instructions) Paul Matteis, Stifel.

(接線員指示) Stifel 的 Paul Matteis。

Congratulations on everything from the first quarter. I wanted to ask a couple of questions on the pain programs, if that's okay. First, as it relates to the Nav1.7 compound, I was wondering if you could talk about where you've gotten to in your Phase 1 program at this point? And how much you feel like you've derisked some of the safety issues that have plagued other drugs?

恭喜第一季的各項成果。如果可以的話，我想就疼痛計畫問幾個問題。首先，關於 Nav1.7 的化合物，我想請你談談目前你們第 1 期計畫進展到哪個階段？以及你們覺得在多大程度上已降低其他藥物曾受困擾的一些安全性風險？

And then separately, can you maybe just speak to more specifics around these Phase 2 plans in acute pain? And what would sort of the size and scope of those studies potentially look like, assuming the Phase 1 data later this year lets you advance?

另外，能否請你更具體談談在急性疼痛方面的第 2 期計畫？假設今年稍晚的第 1 期數據讓你們能夠推進，這些研究在規模與範疇上可能會是什麼樣子？

Chris, I'm happy to start, and then provide your perspective, especially on the future clinical development. So Paul, we announced at JPMorgan earlier this year in January, I think some of the progress we had made on both Nav1.7 and Kv7.

Chris，我很樂意先開始，然後也請你補充觀點，特別是未來的臨床開發。Paul，我們在今年 1 月的 JPMorgan 會議上宣布了我們在 Nav1.7 與 Kv7 兩個項目上的一些進展。

You asked specifically around Nav1.7. At that time, we said that we already felt that we were at high enough exposures to get receptor occupancy that would mimic the human genetics. So we had already made good progress in those early cohorts of dose escalation. If we kind of bring forward to today, we've continued to enroll additional healthy volunteers in that Phase 1 study.

你特別問到 Nav1.7。當時我們表示，我們已覺得達到足夠高的暴露量，可取得能模擬人類遺傳學的受體佔有率。因此，我們在那些早期劑量遞增隊列中已取得良好進展。若把時間推進到今天，我們已持續在該第 1 期研究中納入更多健康受試者。

So I think sitting today, we feel really good that we can safely dose, have the appropriate therapeutic index and give this mechanism a real shot to show proof-of-concept data in Phase 2. So based on what we know today, our plans are to move forward into a Phase 2 acute pain proof-of-concept study. I can start on how we're thinking about it, and then Chris can add some details.

因此，以目前來看，我們對於能夠安全給藥、具備適當的治療指數，並讓此機制在第 2 期真正有機會展現概念驗證數據感到非常有信心。所以基於我們目前所知，我們的計畫是推進至第 2 期急性疼痛概念驗證研究。我可以先談談我們的思考方向，接著 Chris 再補充一些細節。

Obviously, on the acute pain side, we're looking at studies like bunionectomy or abdominoplasty. We haven't yet fully designed the studies. We would want to have them of sufficient size and power, obviously, to show -- and these would be placebo-controlled studies to show a difference between active and placebo. The question really that we continue to think about internally is just how many arms, active comparators, how many doses, all of those things we're still planning.

顯然，在急性疼痛方面，我們會考慮像拇囊炎切除術（bunionectomy）或腹部整形術（abdominoplasty）這類研究。我們尚未完全完成研究設計。我們希望研究具備足夠的樣本數與統計力；而且這些將是安慰劑對照研究，用以顯示活性治療與安慰劑之間的差異。我們內部持續思考的核心問題是：需要多少個治療組別、是否納入主動對照、多少個劑量等，這些都仍在規劃中。

And that will become clear as we finish Phase 1 and we have a really good idea of what we're seeing in terms of the dose response and safety profile in those Phase 1 healthy volunteer studies.

隨著我們完成第 1 期，並對第 1 期健康受試者研究中所觀察到的劑量反應與安全性特徵有非常清楚的掌握後，這些將會變得更明確。

Chris, any color to add on additional details for future development?

Chris，對於未來開發的更多細節，還有什麼可以補充的嗎？

No, I'll just double down on your point that we think we have what we need to go forward into Phase 2 on both programs. And we just -- we haven't worked out exactly what the plan would be after the proof-of-concept that would be with abdominoplasty and/or bunionectomy.

沒有，我只是再強調一次你的觀點：我們認為在兩個專案上，我們已具備進入第二期（Phase 2）所需的一切。而且我們只是——我們還沒有把概念驗證（proof-of-concept）之後的計畫完全定案，那會是在腹部整形術（abdominoplasty）和／或拇囊炎切除術（bunionectomy）上。

Tessa Romero, JPMorgan.

Tessa Romero，摩根大通（JPMorgan）。

Congratulations from us on all the progress. Ian, Chris, I was wondering if tonight you could provide your perspective on how the seizure freedom data that you have shared at 12 weeks from X-TOLE2 compares to what we know about XCOPRI on a cross-trial basis numbers-wise.

我們也恭喜你們取得所有進展。Ian、Chris，我想請教今晚你們是否能分享一下，你們在 X-TOLE2 12 週所公布的無發作（seizure freedom）數據，若以跨試驗（cross-trial）比較、就數字而言，與我們對 XCOPRI 的了解相比如何。

How do you think doctors will approach thinking through the seizure freedom data that we have for these two assets, given that nearly 60% of the patient population were taking or had already discontinued XCOPRI and X-TOLE2 and, of course, that XCOPRI has to be titrated?

考量到將近 60% 的病人族群正在使用或已經停用 XCOPRI（在 X-TOLE2 中），當然 XCOPRI 又需要滴定（titration），你們認為醫師會如何看待並評估這兩個資產的無發作數據？

I'll start. Chris can provide his perspective. But I also want Darren to weigh in because we've had a huge amount of interaction with HCPs and the feedback that they're providing us. And Chris touched upon some of this in the prepared remarks, but maybe I'll give a little bit more detail. So Chris mentioned in the prepared remarks that the consensus definition of seizure freedom is really having no seizure for 12 months.

我先開始。Chris 也可以分享他的觀點。但我也希望 Darren 一起補充，因為我們與醫療照護專業人員（HCPs）有大量互動，也收到他們提供的回饋。Chris 在事先準備的講稿中提到了一部分，不過我也許可以再多給一些細節。Chris 在準備講稿中提到，對於「無發作」的共識定義，其實是 12 個月沒有任何發作。

And so when we talk about our seizure freedom data with prescribers, we focus more on our open-label data than our double-blind data. So you'll hear us use terms like RR100 in the double-blind period, which is the percentage of those patients that had 100% reduction over the double-blind.

因此，當我們與開立處方者討論無發作數據時，我們更聚焦於開放標籤（open-label）數據，而不是雙盲（double-blind）數據。所以你會聽到我們在雙盲期間使用像 RR100 這樣的術語，指的是在雙盲期間達到 100% 降幅的病人比例。

You've asked for a comparison between azetukalner and cenobamate. It is a cross-trial comparison and it is challenging, but I will make a couple of comments.

你問到 azetukalner 與 cenobamate 的比較。這屬於跨試驗比較，確實具有挑戰，但我會提出幾點看法。

One, it was a materially different patient population. So Chris walked you through and you've seen in our publications, in our posters and in our disclosure that we believe that both in X-TOLE and X-TOLE2, this was the most refractory population ever trialed in a pivotal FOS study. And when we look at the cenobamate data and the double-blind data trials that they did over a decade ago, this was a significantly less refractory population. So we are comparing actually two different clinical populations within FOS.

第一，病人族群有實質差異。如 Chris 帶你回顧的，以及你在我們的論文、海報與揭露資料中看到的，我們認為無論在 X-TOLE 或 X-TOLE2，這都是在關鍵性 FOS 研究中曾納入過最難治（最具抗藥性）的族群。而當我們看 cenobamate 的數據，以及他們十多年前所做的雙盲試驗，那是一個明顯較不難治的族群。因此，我們其實是在 FOS 範疇內比較兩個不同的臨床族群。

You also mentioned another key factor, which is, because cenobamate is titrated, when they look at their RR100 during their double blind, they only report over the maintenance period, which is the last six weeks of dosing. One of the reasons why we had a breakdown of that last eight, six, and four weeks.

你也提到另一個關鍵因素：由於 cenobamate 需要滴定，他們在雙盲期間看 RR100 時，只報告維持期（maintenance period）的結果，也就是最後六週的給藥期間。這也是我們為什麼把最後八週、六週與四週做了拆分呈現。

Maybe the last comment on the cross-trial comparison is that often they show their data at their 400-milligram dose, which the feedback we get, and we see it both in data, but also in feedback from prescribers is that patients rarely get to 400 milligrams.

關於跨試驗比較的最後一點是：他們常常展示 400 毫克劑量的數據；但我們收到的回饋——不論是從數據上看到的，或是處方醫師的回饋——都顯示病人很少會用到 400 毫克。

So if you look at their 200-milligram dose and you look at the last period within our double-blind period -- within the last six weeks or four weeks of our data, I would actually say that our RR100 is higher than the cenobamate data seen at their 200-milligram dose.

所以如果你看他們 200 毫克劑量的數據，並且看我們雙盲期間最後一段——也就是我們數據的最後六週或四週——我會說，我們的 RR100 實際上高於 cenobamate 在 200 毫克劑量下所見的數據。

Then the last point you made, which I think is an important one, is we actually have a cenobamate refractory population in our trial when -- as we mentioned, about close to 40% of patients were on background cenobamate and approximately another 20% of patients had tried it and had failed it either for efficacy or tolerability and were no longer on the drug.

接著你提到的最後一點，我認為也很重要：我們的試驗中其實包含了對 cenobamate 反應不佳（refractory）的族群——如我們所提，約接近 40% 的病人以 cenobamate 作為背景用藥，另外約 20% 的病人曾嘗試但因療效或耐受性失敗而停藥。

So overall, I wanted to provide a little bit more of that background because I think our data stack up really well. And I haven't even talked about the open-label data. That's just a cross-trial comparison during the double-blind period.

總之，我想補充這些背景，因為我認為我們的數據表現非常好。而且我甚至還沒談到開放標籤數據。以上只是雙盲期間的跨試驗比較。

So I'll pass it to Chris to talk about the open-label seizure freedom data and then to Darren on how that's really being pulled through into the real world.

所以我先交給 Chris 談開放標籤的無發作數據，接著再請 Darren 談談這些結果如何在真實世界中被延伸與落地。

Yes. I mean, it's interesting, in the epilepsy field, I think there's a little bit of a disconnect. And what I mean by that is that if you talk to epileptologists and neurologists and you ask them what they're hoping to achieve, they talk about seizure freedom on a long time horizon, like at least six months, more like a year, sometimes more. And yet in the same conversation, they'll ask what was your seizure freedom over a month or two or three months.

是的。我的意思是，很有趣的是，在癲癇領域我覺得存在一點落差。我所說的落差是：如果你和癲癇專科醫師（epileptologists）與神經科醫師談，問他們希望達成什麼，他們會談到長期的無發作目標，例如至少六個月，更常是一年，有時甚至更久。但在同一段對話裡，他們又會問你在一個月、兩個月或三個月內的無發作情況如何。

And so there's this sort of inconsistency there that I just want to kind of note. I think that as you make the comparisons -- Ian's already commented on the details matter here, if you're talking about seizure freedom with cenobamate at 400 milligrams with hardly anybody taking 400 milligrams. And really, it's -- 40% of patients are treated with cenobamate at 200 milligrams and the rest of them are treated at lower doses. I think it's important to think about dose.

所以我只是想指出，這裡存在某種不一致。我認為在做比較時——Ian 已經評論過，細節在這裡很重要——如果你談的是 cenobamate 400 毫克的無發作，但幾乎沒有人用到 400 毫克。而實際上——40% 的病人使用 cenobamate 200 毫克，其餘則使用更低劑量。我認為把劑量納入考量很重要。

Also, in the label, when they talk about seizure freedom and cenobamate, they're excluding the first six months -- excuse me, six weeks of the trial period, which is why we've provided sort of these different cuts of seizure freedom to allow a better comparison.

另外，在標籤（label）中，當他們談到 cenobamate 的無發作時，他們排除了試驗期間的前六個月——抱歉，是前六週——這也是我們提供不同切分的無發作數據，以便更好比較的原因。

But I mean, let me just zoom out for a second. I was prescribing when levetiracetam Keppra was approved. And what people want, especially general neurologists, is something easy to use. And with azetukalner, you don't have to worry about titration. You don't have to worry about drug-drug interactions and manipulating other medications to get therapeutic dose and so forth.

不過，我先把視角拉遠一點。我在 levetiracetam（Keppra）獲批時就已經在開立處方。而大家想要的——尤其是一般神經科醫師——是容易使用的藥。使用 azetukalner，你不需要擔心滴定。你也不需要擔心藥物—藥物交互作用，或為了達到治療劑量而去調整其他藥物等等。

So it's easy to use. But then just to kind of wrap it up with the seizure freedom. I mean, I really think that we should be talking about what's happening in the long term. And what we're seeing in the long term with the data that we just presented at AAN is that of the patients who've been treated for four years or more, we're seeing 40% of patients with seizure freedom for a year or more. That's what really matters, not so much what happened over one month or two months.

所以它很容易使用。但回到無發作這件事做個總結。我的意思是，我真的認為我們應該談長期發生了什麼。而我們在剛於 AAN 發表的長期數據中看到的是：在已治療四年或更久的病人中，有 40% 的病人達到一年或更久的無發作。那才是真正重要的，而不是一個月或兩個月發生了什麼。

Darren?

Darren？

Maybe Darren -- yes, can weigh in here as well.

也許 Darren——是的，也可以在這裡補充一下。

Yes. I'll just reiterate what Ian and Chris said. When we engage with physicians, both epileptologists and general neurologists at AAN and other forums, this is largely -- XCOPRI is an epileptologist drug. And when we query about the seizure freedom as it relates to the 400 milligram, I'll just put a finer point on what Ian and Chris said, very, very few, if any, patients get to the 400-milligram dose.

是的。我只是重申 Ian 和 Chris 所說的。當我們在 AAN 與其他場合和醫師互動時——不論是癲癇專科醫師或一般神經科醫師——整體而言，XCOPRI 主要是癲癇專科醫師用藥。而當我們詢問與 400 毫克相關的無發作情況時，我再更精確地補充 Ian 和 Chris 的說法：非常、非常少（如果有的話）病人會用到 400 毫克的劑量。

So as it relates to their own experience with the seizure freedom, it's not as compelling as in the real world. Now XCOPRI does have benefit, but they're not seeing anywhere near what they see at the 400 milligram. And I make this comment about it being epileptologist drug because when we talk to general neurologists, they have really struggled with using it and they're pretty much -- they try it once and they're done.

因此，就他們自身對於「無發作」的體驗而言，並不像真實世界那麼有說服力。目前 XCOPRI 確實有益處，但他們看到的效果遠遠不及 400 毫克劑量時的表現。我之所以評論它像是癲癇專科醫師（epileptologist）的藥，是因為當我們與一般神經科醫師交流時，他們在使用上確實很吃力，基本上就是——試一次就不再用了。

And this is as what Chris said, what differentiates AZK and what we believe will make this a tremendous opportunity is with the general neurologist. The ease-of-use attributes, the lack of titrations, daily dosing and no DDIs really, really ring true with them and they look forward to incorporating in their practice.

而正如 Chris 所說，AZK 的差異化之處、以及我們相信能使其成為巨大機會的關鍵，就在於一般神經科醫師端。其易用性特點、無需滴定、每日一次給藥，以及幾乎沒有藥物交互作用（DDIs），對他們而言非常、非常有感，他們也期待把它納入臨床實務。

Cory Kasimov, Evercore.

Cory Kasimov，Evercore。

This is [Adi] on for Cory. Just on the earlier question asked on the pain assets, I just wanted to ask that can you confirm if investors should anticipate any data this year? I believe earlier it was mentioned that maybe Phase 1 SAD/MAD data might be presented. I just wanted to get if we should anticipate that data.

我是代 Cory 發言的 [Adi]。就先前關於疼痛資產的提問，我想再追問一下：你們能否確認投資人今年是否應該期待任何數據釋出？我記得先前提到可能會公布第一期 SAD/MAD 的數據。我想確認我們是否應該期待那份數據。

Yes, we're very comfortable in saying that the Phase 1 healthy volunteer studies for both 1701 and 1120 will complete this year. So in terms of how much of those data we provide publicly, for competitive reasons, I think -- obviously, we'll talk about that we believe we have enough receptor occupancy and exposure and coverage to have a really good shot at seeing an analgesic effect in a proof-of-concept study.

是的，我們很有把握地說，1701 與 1120 這兩個項目的第一期健康受試者研究都會在今年完成。至於我們會在公開場合披露多少數據，基於競爭因素，我認為——當然，我們會談到：我們相信我們已具備足夠的受體佔有率、暴露量與覆蓋度，因此在概念驗證（proof-of-concept）研究中看到鎮痛效果的機會相當大。

But really to be determined right now whether we're going to broadly show the Phase 1 data publicly. But we are comfortable that those studies will wrap up this year.

但目前仍未決定我們是否會廣泛地公開展示第一期數據。不過我們確定的是，這些研究會在今年結束。

Peyton Bohnsack, TD Cowen.

Peyton Bohnsack，TD Cowen。

This is Peyton on for Joe. I guess, have you scheduled or had a pre-NDA meeting yet? And if you have had the meeting, can you talk about any feedback you've received from the FDA?

我是代 Joe 發言的 Peyton。我想問，你們是否已經安排或已經進行過 pre-NDA 會議？如果已經開過會，能否談談你們從 FDA 收到的任何回饋？

And then I guess the schedule. Can you walk us through the timelines and your expectations for what kind of schedule you would have for that?

另外我想問時程。你們能否帶我們走一遍時間線，以及你們對於整體時程安排的預期？

Chris, do you want to address the regulatory interaction?

Chris，你要不要回應一下法規互動的部分？

Yes, sure. So just the second part of that was the timeline on that meeting. Was it just a reiteration of the other part of the question? Or was there something different there?

好的，當然。所以你剛剛第二部分是問那場會議的時間線。那只是重述前面問題的另一部分嗎？還是你指的是不同的事情？

I was more referring to the DEA scheduling and natural time lines to be approved.

我比較是指 DEA 的分級（scheduling）以及核准所需的自然時間線。

DEA scheduling. Okay. Yes, so -- yes, so what we're sharing is that -- what we've guided on, we just had top-line X-TOLE2 in March. We've guided that we're expecting about a six-month period of time between that and submitting the NDA. We're expecting a standard review of 12 months and then DEA scheduling is expected to be three months. Which is why Ian stated in his comments that we expect approval end of 2027 or early 2028.

DEA 分級。好的。是的，所以——我們分享的是——依我們給出的指引，我們在 3 月拿到 X-TOLE2 的頂線（top-line）結果。我們指引為：從那之後到提交 NDA，預期約需六個月。我們預期標準審查期為 12 個月，接著 DEA 分級預期為三個月。這也是 Ian 在評論中提到我們預期在 2027 年底或 2028 年初獲批的原因。

We have, obviously -- I mean, pre-NDA meetings are standard. We're expecting for that to occur in between the top-line data, which has already occurred in the NDA submission, obviously, in the fall. But we haven't gone into specifics about when exactly that's going to take place.

當然——我的意思是，pre-NDA 會議是標準流程。我們預期它會發生在頂線數據（已經出來）與 NDA 提交（顯然是在秋季）之間。但我們尚未就確切何時舉行提供具體細節。

I will tell you that we've had thoughtful and timely interactions with FDA, and we think we have a decent reputation with them, and we don't -- we haven't foreseen any problems up until at this point in time. So we're looking forward to more interactions with them in the future.

我可以告訴你的是，我們與 FDA 的互動一直很周到且及時；我們也認為我們在他們那裡有不錯的口碑，而且——截至目前我們沒有預見任何問題。因此我們也期待未來能與他們有更多互動。

Andrew Tsai, Jefferies.

Andrew Tsai，Jefferies。

This is Matt Barcus on for Andrew Tsai. I just wanted to see if you can give us a little bit of flavor on one of the Phase 3 data analysis that you might share later this year, especially at AES conference in December, which can further showcase AZK's potential differentiation.

我是代 Andrew Tsai 發言的 Matt Barcus。我想請你們稍微分享一下：今年稍晚你們可能會分享的某些第三期數據分析（尤其是 12 月的 AES 會議），哪些內容能進一步展現 AZK 潛在的差異化。

Chris, do you want to walk through maybe some of our thinking around AES and additional analysis?

Chris，你要不要談談我們對 AES 與額外分析的一些想法？

Yes. So we've -- as you can imagine, we spent a lot of time trying to understand what's going on with the Phase 3 and understanding all the data. And so we're sort of working through exactly what we intend to submit as potential abstracts at AES. As you know, you submit those and they may or may not be approved. We've had a pretty good acceptance rate, but you don't know for sure. We're focusing on looking at kind of the combination.

好的。所以——如你所想像，我們花了很多時間試圖理解第三期到底發生了什麼，並理解所有數據。因此我們正在梳理，究竟打算向 AES 提交哪些可能的摘要（abstracts）。如你所知，你提交後可能會被接受也可能不會。我們的接受率一直不錯，但你無法百分之百確定。我們目前聚焦在看某種「合併」的分析。

Now we have two -- what we consider two pivotal trials for FOS. And so we're interested in kind of combining that data and sharing with the world what that efficacy and safety data looks like combined. We're also -- you may remember from the X-TOLE study that we looked at seizure subtypes, and so we're probably likely to look into that and share that.

目前我們有兩項——我們認為是兩項針對 FOS 的關鍵性試驗（pivotal trials）。因此我們有興趣把這些數據做某種合併，並向外界分享合併後的療效與安全性數據長什麼樣子。另外——你可能還記得在 X-TOLE 研究中我們看過發作亞型（seizure subtypes），所以我們很可能也會再深入分析並分享。

And then, of course, we're -- every year, we update the X-TOLE OLE data. And so those are the things that for sure will happen. And then we're just kind of working through whether there'll be anything else there.

然後當然——我們每年都會更新 X-TOLE OLE 的數據。所以這些事情肯定會做。至於是否還會有其他內容，我們正在進一步評估。

Ian, you want to add anything to that?

Ian，你要補充什麼嗎？

No, that was great.

沒有，剛剛講得很好。

Brian Skorney, Baird.

Brian Skorney，Baird。

This is Charlie on for Brian. So just thinking about your Nav1.1 in Dravet, obviously, a pretty crowded space. How do you see this compound and mechanism differentiating from the field, especially considering there are some other therapies out there addressing this issue in epilepsy?

我是代 Brian 發言的 Charlie。談到你們在 Dravet 的 Nav1.1，顯然這是一個相當擁擠的領域。你們如何看待這個化合物與作用機制相對於同業的差異化，尤其考量到癲癇領域已有其他療法在處理這個問題？

And just one more if I could ask on pain. What are you thinking about long term in terms of chronic pain versus acute pain and how each asset might fit into that paradigm?

另外如果可以再問一題關於疼痛。從長期來看，你們如何思考慢性疼痛相對於急性疼痛？以及各個資產可能如何融入這個治療框架？

Chris, I can start on Nav1.1 and then feel free to add, and then we can talk about the pain, although we talked about earlier that we're still working on kind of the development strategy for the pain assets. On Nav1.1, so these children that have Dravet syndrome are haploinsufficient for Nav1.1, so they have 50% of the protein. The drugs that are currently approved address the seizures.

Chris，我可以先談 Nav1.1，你也可以再補充；接著我們再談疼痛——雖然我們先前也提到，我們仍在制定疼痛資產的開發策略。就 Nav1.1 而言，這些患有 Dravet 症候群的孩子在 Nav1.1 上屬於單倍體不足（haploinsufficient），因此他們只有 50% 的蛋白表現量。目前已核准的藥物主要是針對發作本身。

So drugs that are used like clobazam or Epidiolex or Fintepla are really trying to prevent the seizures that these children are having. Really, where we believe the field is going in addition to those therapies is to see if we can start to correct the underlying genetics. And so there's ASO approaches that I'm sure you're aware of.

因此，像 clobazam、Epidiolex 或 Fintepla 這類使用中的藥物，主要是在嘗試預防這些孩子出現的癲癇發作。而我們認為，除了這些療法之外，這個領域接下來的走向，是看看能否開始矯正其底層的遺傳問題。因此也有反義寡核苷酸（ASO）的策略，我相信你也有所了解。

And what we think is the opportunity to have a small molecule that can be orally administered and can really be titrated or appropriate weight-based dosing for these patients that have a wide variety of weights as they're diagnosed generally within the first 6 to 18 months of life. And so if there's an opportunity to have an oral small molecule, where we potentiate the channel so we can increase current through the wild-type channel as the opportunity potentially to correct the underlying challenges of this disease.

而我們認為的機會在於，能有一種可口服給藥的小分子，並且能夠真正進行滴定，或針對這些患者採用合適的按體重劑量調整；這些患者的體重差異很大，且通常在出生後前 6 到 18 個月內被確診。因此，如果有機會提供一種口服小分子，透過增強該通道的功能，使野生型通道的電流增加，便有可能從根本上矯正這種疾病的核心挑戰。

And the preclinical data that Chris walked through and you've seen in poster presentations, and we had an oral presentation, standing room only oral presentation at AAN this year, those data are quite remarkable. And these are in genetic animals. So these are in animals that are haploinsufficient and very much look like the human phenotype in terms of the spontaneous seizures and the SUDEP.

Chris 剛才帶大家回顧的臨床前數據，以及你們在海報展示中看到的內容——而且我們今年在 AAN 還做了一場口頭報告，現場座無虛席——那些數據相當令人驚豔。而且這些是在基因改造動物中取得的。也就是在單倍體不足（haploinsufficient）的動物中，牠們在自發性癲癇發作與 SUDEP（癲癇猝死）方面，與人類表型非常相似。

And not only is the seizure reduction impressive in our preclinical studies, but also really the potential for disease modification. We're protecting these animals from death and really helping them in terms of the long-term potentiation. So we've showed some of those data historically. I think they're really interesting.

我們在臨床前研究中看到的不僅是顯著的發作減少，還包括真正具有疾病修飾的潛力。我們正在保護這些動物免於死亡，並且在長期增強（long-term potentiation）方面確實對牠們有幫助。因此我們過去已展示過其中一些數據。我認為它們非常有意思。

We're now in tox studies. But I think there's a huge opportunity and need for better therapies for Dravet, and I think this will fit in really nicely. But it's early days.

我們目前正在進行毒理（tox）研究。但我認為 Dravet 症候群在更佳療法方面存在巨大的機會與需求，而我認為這項療法會非常契合。不過目前仍屬早期階段。

Chris, anything to add on the 1.1? Or do you want to move to just thinking about longer-term development in the pain portfolio?

Chris，關於 1.1 還有什麼要補充的嗎？或者你想轉到更長期的疼痛產品組合開發思路？

A couple of things. Maybe slightly crowded, but if you think about -- this is a really devastating disorder. And so I think it's good that multiple people are working on this. The reason why we think we're differentiated is because we're coming along with a small molecule that we think will deal with the underlying pathophysiologies in a similar manner to what Stoke's ASO was doing.

有幾點。可能這個領域稍微擁擠，但如果你想想——這是一種非常具毀滅性的疾病。因此我認為有多個團隊投入是好事。我們之所以認為自己具差異化，是因為我們帶來的是一種小分子，我們認為它能以類似於 Stoke 的 ASO 所做的方式，處理其根本病理生理機制。

But obviously, an ASO is being delivered through the intrathecal route, and this would be an oral therapy. So I would just draw kind of an analogy with what happened in spinal muscular atrophy, where gene therapy came along, ASOs came along and then oral therapies came along, and you know how that went. So we do think that we have something to offer these patients.

但很明顯，ASO 是透過鞘內（intrathecal）途徑給藥，而這將會是一種口服治療。所以我會用脊髓性肌肉萎縮症的發展作類比：先有基因治療、再有 ASO，接著出現口服療法，而你也知道後來的發展。因此我們確實認為，我們能為這些患者提供一些價值。

And then, yes, we're still working through the pain. So we're focused on getting out of first-in-human into proof-of-concepts, and then we still need to figure out chronic versus acute and a whole sorts of different things in the coming months and years.

另外，是的，我們仍在推進疼痛領域的工作。因此我們的重點是從首次人體試驗（first-in-human）推進到概念驗證（proof-of-concept），接著在未來幾個月與幾年內，我們仍需要釐清慢性對比急性，以及各種不同面向的問題。

And maybe I can just add on the pain side. Obviously, the first proof-of-concept studies will be in acute pain, and we've talked about bunionectomy or abdominoplasty. There's nothing in the underlying genetics in Nav1.7 or the mechanism of Kv7 that should suggest or support that these mechanisms should only work in acute chronic or nociceptive or neuropathic pain.

我也許可以在疼痛方面補充一下。顯然，最初的概念驗證研究會在急性疼痛中進行，我們也談過拇囊炎切除術（bunionectomy）或腹部整形（abdominoplasty）。Nav1.7 的基礎遺傳學或 Kv7 的作用機制，並沒有任何理由暗示或支持這些機制只會在急性或慢性、或只在傷害性（nociceptive）或神經病理性（neuropathic）疼痛中有效。

So if these programs continue to look promising and we can get good proof of concept, the plan would be to go quite broad in terms of the late-stage clinical development.

因此，如果這些專案持續展現良好前景，且我們能取得良好的概念驗證結果，計畫是在後期臨床開發上採取相當廣泛的布局。

Myles Minter, William Blair.

Myles Minter，William Blair。

One on the commercial side, I find it interesting that we're all comparing XCOPRI when that's not the number one branded product, BRIVIACT is. And I think that, that had gone generic at the start of the year. So the question is, is that a headwind to marketing of a newly branded ASM there because costs are coming down in the general neurology practice?

關於商業面，我覺得有趣的是，我們都在拿 XCOPRI 來比較，但其實排名第一的品牌產品是 BRIVIACT。而我認為它在今年年初已經轉為學名藥。所以問題是：這是否會成為新品牌 ASM（抗癲癇藥物）在一般神經科診所推廣上的逆風，因為整體成本正在下降？

Or is that actually a tailwind because you no longer have to compete for that branded slot against BRIVIACT kind of coming in and taking the market specifically within that general neurologist population?

或者這其實是順風，因為你不再需要在那個品牌名額上與 BRIVIACT 競爭——BRIVIACT 之前在一般神經科醫師族群中進入並占據了市場？

No, I think on the contrary, I think when you look at AZK, all the attributes, particularly the novel mechanism after generations of SV2A channel blockers, sodium channel blockers, SV2As and GABA, the novel Kv7 is a benefit. All our ease-of-use attributes that we've outlined on the call and that we get positive feedback from both epileptologists and general neurologists.

不，我認為恰恰相反。當你看 AZK 的所有特性，尤其是在一代又一代的 SV2A 通道阻斷劑、鈉通道阻斷劑、SV2A 與 GABA 之後，這種新穎的作用機制——新穎的 Kv7——是一項優勢。以及我們在電話會議中概述的所有易用性特點，我們也從癲癇專科醫師與一般神經科醫師那裡得到正面回饋。

And you look at the timing of when we ultimately launch. It will be almost a decade of really what I would characterize as kind of a stagnation of development in focal epilepsy. And so we really think that's the backdrop along with our clinical data and profile that we can really, really have a great opportunity here.

再看我們最終上市的時間點。那將會是將近十年——我會形容為局灶性癲癇開發某種程度的停滯。因此我們確實認為，在這樣的背景之下，加上我們的臨床數據與產品特徵，我們在這裡有非常、非常好的機會。

And again, I think if you look at the case with XCOPRI, we've talked about that. But even I think BRIVIACT, it was another kind of me-too mechanism on top of a wildly successful parent in Keppra. And so I think that's a completely different market and opportunity than what we have with AZK as we look in the future and we prepare to launch this.

再者，我認為如果你看 XCOPRI 的案例，我們已經談過。但即便是 BRIVIACT，它也是在 Keppra 這個極為成功的母品牌之上，另一種某種程度的「me-too」機制。因此我認為那是完全不同的市場與機會，與我們在展望未來並準備推出 AZK 時所面對的情況不同。

David Hoang, Deutsche Bank.

David Hoang，德意志銀行。

So maybe first, again, on the commercial side, given the strong balance sheet you have now, how can you think about leveraging that to perhaps ensure the best commercial launch you can for AZK in focal epilepsy? For example, would you think about maybe increasing the number of sales reps that you would field?

那麼也許先從商業面再問一次：鑑於你們目前強勁的資產負債表，你們會如何思考運用它，來確保 AZK 在局灶性癲癇的商業上市能做到最好？例如，你們會考慮增加你們配置的業務代表人數嗎？

And then just thinking about different angles out there in the focal epilepsy market, a competitor of yours is doing a monotherapy study, I believe, and they think that by weaning patients off background meds and having them on a monotherapy, that may be will also allow them to get into earlier lines of treatment. I was curious if you've ever thought of a study designed like that and if you think that would be helpful for AZK?

另外，從局灶性癲癇市場的不同角度來看，你們的一個競爭對手我相信正在做單藥治療（monotherapy）研究，他們認為透過讓患者逐步停用背景用藥、改為單藥治療，可能也能讓他們進入更早的治療線。我想知道你們是否曾考慮過這樣設計的研究，以及你們是否認為這對 AZK 會有幫助？

I'm happy to start just because I think a little bit of historical context is important here, and then Darren will go through kind of the details of preparing for launch. And then, Chris, do you want to address the question just on monotherapy and the label, at least how we think about that? Really since the X-TOLE data in 2021, David, we have really moved to investing in commercial preparation at risk. I think this is a generational type opportunity, paradigm shifting.

我很樂意先回答，因為我認為這裡需要一些歷史背景，接著 Darren 會說明上市準備的細節。然後 Chris，你要不要回應一下關於單藥治療與標籤（label）——至少我們如何看待這件事——的問題？自 2021 年的 X-TOLE 數據以來，David，我們確實已經轉向在風險承擔下投資商業化準備。我認為這是一個世代型的機會，將改變既有典範。

As Darren mentioned, it will be almost a decade since we've seen a branded launch in FOS. But it's been ages since we've seen this kind of mechanistic diversity and the profile of something like azetukalner. So given our confidence going into the Phase 3 readout in X-TOLE2, we started that commercial preparation already.

如 Darren 所提到的，距離我們在 FOS（局灶性起始性癲癇）看到一次品牌上市，將近已經十年。但更久的是，我們已經很久沒有看到像 azetukalner 這樣在機制多樣性與產品特徵方面的組合。因此，基於我們對 X-TOLE2 第三期讀出結果的信心，我們已經開始進行商業化準備。

So not only was Darren hired almost a year ago, but we've had field medical out -- MSL speaking with prescribers and engaging in medical and scientific exchange. This summer, it will be two years since we've had that team out there. Darren's already got his leadership team in place. We've had people on the access side in place for years.

因此不僅 Darren 在將近一年前就加入，我們也已經有外勤醫學團隊——MSL 與處方醫師交流，並進行醫學與科學層面的互動。到今年夏天，我們派出該團隊到市場上已經滿兩年。Darren 也已經把他的領導團隊建置完成。而在市場准入（access）方面，我們多年來也一直有人員到位。

So we really believe that early investment was going to be an opportunity here to have real success in those early days of commercialization. But Darren can give you a little bit more detail on that.

因此，我們確實相信，早期投資將會是在商業化初期取得真正成功的一個機會。不過 Darren 可以就此提供更多細節。

Yes, I think -- and if you kind of -- and Ian hit it on it. You look at successful launches, and some of that I've been a part of, there's a few ingredients. One is the early investment, which I was very pleased joining Xenon that, that was in place.

是的，我認為——如果你稍微——Ian 也提到了。你看成功的上市案例，其中一些我也參與過，通常有幾個要素。其一是早期投資；我很高興加入 Xenon 時，這一點已經到位。

Second is the team that you can put -- yourself put together. And I think from a commercial leadership perspective, we have folks with deep epilepsy experiences and relationships, launch experience, which provide us, I think, a leg up.

第二是你能——自己能組建的團隊。我認為從商業領導的角度來看，我們有在癲癇領域具備深厚經驗與人脈、以及上市經驗的人才，這讓我們，我想，佔有優勢。

Third, and also part of that is, we will be a variable desirable place for professionals that have dedicated their careers to epilepsy. As we pointed out, there's been really nothing new. And so I think when we start posting positions, we're going to get the best available people.

第三，而且也是其中一部分是，我們將會成為那些把職涯奉獻給癲癇領域的專業人士非常嚮往的去處。如我們所指出的，市場上真的很久沒有新東西了。因此我認為當我們開始發布職缺時，我們會吸引到最優秀、最合適的人才。

Then you turn to the product that we have available to us. And from a brand marketing positioning perspective, the clinical data is, some would argue, the best in focal seizure. I think as we think about the opportunity to price this and extract the value that we think the asset deserves.

接著你再看我們手上可用的產品。從品牌行銷定位的角度，臨床數據——有人會說——在局灶性發作領域是最好的。我認為當我們思考這項產品的定價，以及擷取我們認為該資產應得的價值時，機會很大。

And then also, too, the services, the distribution model, I think we're thinking of it in a very creative way. That again will extract the most value. But most importantly, have the best patient and physician experience, because as we know, while it takes a lot of effort and investment to create the demand, converting that prescription to paid scripts and persistency and compliance, that's the entire equation.

另外，服務與配送模式方面，我認為我們正以非常有創意的方式來思考。這同樣將能擷取最大的價值。但最重要的是，提供最佳的病患與醫師體驗；因為如我們所知，雖然創造需求需要大量努力與投資，但把處方轉化為已付費處方、並提升持續用藥與依從性，才是整個方程式的全部。

And so when we think about our commercial team and our launch preparation, all those variables are being put in place. And again, with the backdrop of the clinical profile that we have with AZK, we're extremely, extremely excited and bullish on this launch.

因此，當我們思考商業團隊與上市準備時，這些變數都正在到位。再加上我們在 AZK 上所具備的臨床特徵作為背景，我們對這次上市感到非常、非常興奮，並且相當看多。

And Chris, you want to talk on the monotherapy?

Chris，你要談一下單藥治療（monotherapy）嗎？

Yes. I mean, it's hard to not be blunt. I don't see the upside of doing it, frankly. So from a labeling perspective, the current labels don't say that these drugs are approved for adjunctive. They just say that they're approved for the indication. So I don't see any upside from a labeling perspective per se. I'll defer to Darren on the commercial side.

好的。我的意思是，很難不直說。坦白講，我看不出做這件事的上行空間。就標示（labeling）而言，目前的標示並沒有寫這些藥物核准用於加成治療（adjunctive）。它們只是寫核准用於該適應症。所以我不認為在標示層面本身有任何上行空間。商業面的部分我交給 Darren。

I will say this, though, if for whatever reason I did see an upside with doing a monotherapy study, I would do a monotherapy study drug versus placebo from the very beginning. I think if you're manipulating other ASMs and trying to back off and then interpret that efficacy and safety data, it's probably very challenging.

不過我會這麼說：如果不論出於什麼原因，我確實看到了做單藥治療研究的上行空間，那我會從一開始就做「單藥治療用藥」對照安慰劑的研究。我認為如果你在調整其他抗癲癇藥物（ASMs）、嘗試逐步減量，然後再去解讀其療效與安全性數據，可能會非常具挑戰性。

Ben Burnett, Wells Fargo.

Ben Burnett，富國銀行（Wells Fargo）。

This is [Orpheus] on for Ben. Congrats on the progress. Maybe just a quick one on our end. As we look forward to X-TOLE3 data and a potential ex-US launch, how are you thinking about commercialization in ex-US territories? I know that in the past, you have shared you would look to partner in such geographies.

我是代 Ben 提問的 [Orpheus]。恭喜你們的進展。我們這邊可能快速問一個。展望 X-TOLE3 數據以及潛在的美國以外（ex-US）上市，你們如何思考在美國以外地區的商業化？我知道過去你們曾分享，會在這些地理區域尋求合作夥伴。

So is that still your latest thinking? And are there any updates you can share on that front?

這仍然是你們目前最新的想法嗎？在這方面有沒有任何更新可以分享？

Sure. I'm happy to address that. So we are doing the clinical development that we think will meet regulatory requirements around the world. So we've been talking for some time that the clinical program should meet requirements in Europe.

當然。我很樂意回應。因此，我們正在進行我們認為能滿足全球各地監管要求的臨床開發。我們談了一段時間，這個臨床計畫應該能符合歐洲的要求。

And then an update over the last couple of quarters for us was interaction with PMDA and the incorporation of Japanese sites and subjects into X-TOLE3 to meet the requirements in Japan without having to run a completely separate Phase 3 program in Japan. So I think we've done everything kind of across the board to continue to drive the global clinical development and drive value.

另外，過去幾個季度我們的一項更新是：與日本 PMDA 的互動，以及將日本的試驗中心與受試者納入 X-TOLE3，以在不必於日本另外執行一個完全獨立的第三期（Phase 3）計畫的情況下，滿足日本的要求。所以我認為我們已在各方面都做了該做的事，持續推動全球臨床開發並提升價值。

We've also been really clear that we're not going to build infrastructure, market access and commercial infrastructure outside of the US. And so when the appropriate time is right, that would be when we would engage with potential partners to access those markets. But right now, we're really focused on the global clinical development.

我們也非常清楚地表示，我們不會在美國以外建立基礎設施、市場准入以及商業化基礎設施。因此在適當的時點，我們會與潛在合作夥伴接洽，以進入那些市場。但目前我們真正聚焦的是全球臨床開發。

I will now turn the call back over to Ian Mortimer for closing remarks.

我現在把電話交回給 Ian Mortimer 作結語。

Thanks very much, operator, and thanks to everyone for joining us today. I know there were other questions in the queue. So if we didn't get to your question, we will reach out to you directly to connect. And we look forward to providing continued updates as we advance our programs and we deliver on important milestones throughout the remainder of the year.

非常感謝，接線員，也感謝各位今天加入。我知道佇列中還有其他問題。因此如果我們沒有回答到你的問題，我們會直接與你聯繫以便進一步交流。隨著我們推進各項計畫，並在今年剩餘時間內達成重要里程碑，我們也期待持續提供最新進展。

So operator, we can now end the call.

那麼接線員，我們現在可以結束電話會議。

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

各位女士、先生，今天的電話會議到此結束。感謝各位參與。您現在可以掛線。