Arcturus Therapeutics Holdings Inc (ARCT) 2026 Q1 法說會逐字稿

Hello and welcome everyone joining today's Arcturus Therapeutics' first-quarter 2026 earnings call. (Operator Instructions) Please note, this call is being recorded. We are standing by if you should need any assistance.

各位好，歡迎所有加入今天 Arcturus Therapeutics 2026 年第一季財報電話會議的來賓。(接線員指示) 請注意，本通話將被錄音。如您需要任何協助，我們隨時待命。

It is now my pleasure to turn the meeting over to Neda Safarzadeh, Vice President, Head of Investor Relations, Public Relations and Marketing. Please go ahead.

現在我很榮幸將會議交給投資人關係、公共關係與行銷部門副總裁暨主管 Neda Safarzadeh。請開始。

Thank you, operator. Good afternoon, and welcome to Arcturus Therapeutics' quarterly financial update and pipeline progress call.

謝謝您，接線員。各位午安，歡迎參加 Arcturus Therapeutics 的季度財務更新與產品線進展電話會議。

Today's call will be led by Joe Payne, our President and CEO; Dr. Alan Cohen, our Chief Medical Officer; and Dennis Mulroy, our Chief Financial Officer. Dr. Pat Chivukula, our CFO and COO, will join them for the Q&A session.

今天的會議將由我們的總裁兼執行長 Joe Payne、首席醫務官 Alan Cohen 醫師，以及首席財務官 Dennis Mulroy 主持。首席科學官兼營運長 Pat Chivukula 博士將在問答環節加入。

Before we begin, I would like to remind everyone that the statements made during call regarding matters that are not historical facts are forward-looking statements within the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995.

在開始之前，我想提醒各位，本次通話中就非歷史事實事項所作之陳述，均屬於 1995 年《私人證券訴訟改革法》安全港條款所界定的前瞻性陳述。

Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by statements. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the risk factors section in our most recent Form 10-K and in subsequent filings with the SEC.

前瞻性陳述不保證未來表現。其涉及已知與未知的風險、不確定性與假設，可能導致實際結果、表現與成就與陳述所明示或暗示者存在重大差異。請參閱公司今日稍早發布之新聞稿中的前瞻性陳述免責聲明，以及我們最近一期 Form 10-K 與後續向美國證券交易委員會（SEC）提交文件中的風險因素章節。

In addition, any forward-looking statements represent our views only as of the date such statements are made. Arcturus specifically disclaims any obligation to update such statements.

此外，任何前瞻性陳述僅代表我們在作出該等陳述當日的觀點。Arcturus 明確聲明不承擔更新該等陳述的任何義務。

And with that, I will now turn the call over to Jeff.

接下來，我將把電話會議交給 Jeff。

Thank you, Neda. It's good to be with you again, everybody. The first quarter of 2026 was a period of solid execution for Arcturus as we continue to advance our rare disease pipeline and strengthen our leadership team. I'm very pleased to report that our CF program is now in new, uncharted territory. Our 12-week Phase 2 study began enrollment in Q1.

謝謝你，Neda。各位，很高興再次與大家相聚。2026 年第一季對 Arcturus 而言是執行穩健的一季，我們持續推進罕見疾病產品線並強化領導團隊。我非常高興地報告，我們的 CF 計畫目前已進入全新、前所未有的領域。我們的 12 週第 2 期研究已於第一季開始收案。

We are already well beyond one month of dosing. Continuous dosing beyond a month has never been successfully tolerated in the history of inhaled mRNA therapeutics, but this is a big deal. And why is that? Because Class I CF is a serious disease with serious unmet medical need, and we believe that the nested pulmonary congestion observed in Class I CF disease requires consistent chronic dosing that is reasonably well tolerated to be successful.

我們目前已完成超過一個月的給藥。在吸入式 mRNA 治療的歷史上，連續給藥超過一個月從未能成功被耐受，但這是一項重大里程碑。為什麼這麼重要？因為 I 類 CF 是一種嚴重疾病，存在重大的未被滿足醫療需求；我們相信，在 I 類 CF 疾病中觀察到的巢狀肺部阻塞/充塞（nested pulmonary congestion）需要一致的長期慢性給藥，且必須具備合理的耐受性，才能取得成功。

There are specific reasons why Arcturus has been able to achieve tolerable dosing beyond one month. Firstly, our inhaled LUNAR particle technology includes key delivery lipids that are chemically different from all other technologies competing in this space. Secondly, our messenger RNA manufacturing process to remove undesired impurities is unique, proprietary, and trade-secreted.

Arcturus 能夠達成超過一個月仍可耐受給藥，背後有特定原因。首先，我們的吸入式 LUNAR 顆粒技術包含關鍵的遞送脂質，其化學結構與此領域所有其他競爭技術皆不同。其次，我們用於去除不希望雜質的 mRNA 製造流程是獨特的、專有的，並以商業機密方式保護。

ARCT-032, this is our inhaled mRNA CF therapeutic candidate, continues to showcase these differences in its growing safety and tolerability profile. The CF community is aware of our safety and tolerability profile, which has contributed to the reason why we were able to initiate enrollment of our 12-week open-label Phase 2 study earlier than originally anticipated. This study is enrolling Class I CF participants and monitors lung function measures, including percent-predicted FEV1 and Lung Clearance Index or LCI.

ARCT-032（我們的吸入式 mRNA 囊性纖維化治療候選藥物）持續在其逐步累積的安全性與耐受性特徵中展現這些差異。CF 社群已了解我們的安全性與耐受性概況，這也促成我們能比原先預期更早啟動 12 週開放標籤第 2 期研究的收案。本研究收納 I 類 CF 受試者，並監測肺功能指標，包括預測值百分比 FEV1（percent-predicted FEV1）與肺清除指數（Lung Clearance Index，LCI）。

We believe there is increasing recognition across the field of both the significant unmet medical need in Class I CF and the importance of achieving a well-tolerated, repeat-dose therapeutic approach to enable durable clinical benefit. Our program is designed with these principles in mind and we are encouraged by the opportunity to generate meaningful clinical data in a patient population that continues to have no effective treatment options.

我們相信，整個領域對 I 類 CF 的重大未被滿足醫療需求，以及達成可良好耐受之重複給藥治療策略以帶來持久臨床效益的重要性，正獲得越來越多的認同。我們的計畫即以這些原則為設計核心；對於能在一個至今仍缺乏有效治療選項的病患族群中產出具意義的臨床數據，我們深受鼓舞。

We look forward to collecting this clinical data, including lung function measures, during and throughout this open-label Phase 2 study. Arcturus remains committed to advancing our inhaled mRNA therapy for people living with CF Class I mutations who continue to face significant unmet medical needs.

我們期待在此開放標籤第 2 期研究期間及全程收集臨床數據，包括肺功能指標。Arcturus 仍致力於推進吸入式 mRNA 治療，服務帶有 CF I 類突變且仍面臨重大未被滿足醫療需求的患者。

Now moving on to our flagship liver program, ARCT-810. This is our mRNA therapeutic candidate to treat ornithine transcarbamylase or OTC deficiency. We met with the FDA to discuss the pediatric clinical development strategy for ARCT-810. Following this Type C meeting, we're pleased to receive clear regulatory direction on a path toward a pivotal pediatric study. In line with that direction, we are collecting additional exploratory data and look forward to further alignment with the FDA at the end of Phase 2 meeting planned for the second half of 2026.

接著談到我們的旗艦肝臟計畫 ARCT-810。這是我們用於治療鳥胺酸氨甲醯轉移酶（ornithine transcarbamylase，OTC）缺乏症的 mRNA 治療候選藥物。我們已與 FDA 會面，討論 ARCT-810 的兒科臨床開發策略。在此次 Type C 會議後，我們很高興獲得明確的監管指引，指向一條邁向關鍵性兒科研究的路徑。依循該指引，我們正在收集額外的探索性數據，並期待在預計於 2026 年下半年舉行的第 2 期結束（End-of-Phase 2）會議上與 FDA 進一步對齊。

Beyond our clinical rare disease programs, our partner Meiji in Japan is actively manufacturing KOSTAIVE, this is our self-amplifying mRNA COVID vaccine for the upcoming 2026-2027 season using a two-dose vial presentation. All commercial guidance for KOSTAIVE in Japan will be provided by Meiji.

除我們的臨床罕見疾病計畫外，我們在日本的合作夥伴明治（Meiji）正積極生產 KOSTAIVE，也就是我們用於 2026-2027 季度的自我擴增 mRNA COVID 疫苗，採用雙劑量小瓶（two-dose vial）包裝形式。KOSTAIVE 在日本的所有商業指引將由明治提供。

We also expanded our executive leadership team with the appointments of Dennis Mulroy as Chief Financial Officer and Dr. Alan Cohen as Chief Medical Officer. I'm pleased that they are both on the call with us today, and we will get to hear from them shortly. Both bring extensive and relevant experience that will play important roles as we continue executing across clinical, regulatory, and corporate priorities. Many of you will have the opportunity to meet with these gentlemen, and I encourage you to do so.

我們也透過任命 Dennis Mulroy 擔任首席財務官，以及 Alan Cohen 醫師擔任首席醫務官，擴充了高階管理團隊。我很高興他們今天都與我們一同參與電話會議，稍後各位也將聽到他們的分享。兩位都具備豐富且高度相關的經驗，將在我們持續推進臨床、監管與公司層面優先事項的執行上扮演重要角色。各位之中許多人將有機會與兩位先生會面，我也鼓勵大家把握機會。

Overall, we believe Arcturus is well positioned to advance our pipeline toward meaningful clinical and regulatory milestones for patients and for our shareholders.

整體而言，我們相信 Arcturus 已具備良好條件，能推動產品線邁向對患者與股東皆具意義的臨床與監管里程碑。

With that, I'll now turn the time over to our Chief Medical Officer, Dr. Cohen.

接下來，我把時間交給我們的首席醫務官 Cohen 醫師。

Thank you, Joe, and good afternoon, everyone. From a clinical development perspective, the first quarter reflected meaningful progress across our key programs. Starting with cystic fibrosis, ARCT-032 is currently enrolling people with CF with Class I mutations in a larger and longer open-label Phase 2 study over a 12-week period.

謝謝你，Joe，各位午安。從臨床開發角度來看，第一季在我們的關鍵計畫上取得了具意義的進展。先從囊性纖維化談起，ARCT-032 目前正在一項規模更大、時間更長的 12 週開放標籤第 2 期研究中，收納帶有 I 類突變的 CF 患者。

The study is designed to monitor safety, tolerability, and assess evidence of early clinical benefit, including two pulmonary functional measures, including changes in percent predicted FEV1 and lung clearance index. We've intentionally designed this study to generate a more comprehensive understanding of safety and tolerability, along with early signs of clinical efficacy, which are critical to advancing inhaled messenger RNA therapies in the lung.

本研究旨在監測安全性與耐受性，並評估早期臨床受益的證據，其中包含兩項肺功能指標的評估，包括預測值百分比 FEV1 的變化與肺清除指數的變化。我們刻意將本研究設計為可更全面理解安全性與耐受性，同時觀察早期臨床療效訊號；這些對推進肺部吸入式信使 RNA（mRNA）療法至關重要。

We are also evaluating two validated quality of life outcome measures, along with changes in high-resolution CT imaging to support a comprehensive assessment of potential clinical effects. Taken together, these endpoints are intended to provide a robust data package to inform both the therapeutic potential and the feasibility of repeat dosing. Our goal is to establish not only early evidence of activity, but also the feasibility of repeated dosing, which is fundamental to unlocking durable benefit in this patient population.

我們也正在評估兩項已驗證的生活品質結果量測指標，並結合高解析度 CT 影像的變化，以支持對潛在臨床效果的全面評估。綜合而言，這些終點旨在提供一套扎實的數據組合，用以判斷治療潛力以及重複給藥的可行性。我們的目標不僅是建立早期活性證據，也要證實重複給藥的可行性；這是為此患者族群解鎖持久效益的根本關鍵。

Turning to OTC deficiency, our ARCT-810 program continues to broaden its development strategy to address the unmet medical needs of newborns and young children affected by the most severe forms of the disease. Following our recent Type C meeting, the FDA provided clear direction toward a pivotal pediatric development path. We are actively collecting additional exploratory data to help establish the optimal dose and therapeutic effect as we prepare for the end of Phase 2 meeting planned later this year.

談到 OTC 缺乏症，我們的 ARCT-810 計畫持續擴大其開發策略，以滿足受該疾病最嚴重型態影響之新生兒與幼兒的未被滿足醫療需求。在我們近期的 Type C 會議之後，FDA 就關鍵性兒科開發路徑提供了明確指引。我們正積極蒐集額外的探索性資料，以協助在今年稍晚規劃召開的第二期結束（End of Phase 2）會議前，確立最佳劑量與治療效果。

Across both programs, our focus remains on generating high-quality clinical and regulatory data to support thoughtful decision-making and efficient advancement through development. We believe this disciplined approach is particularly important in emerging modalities where careful characterization of safety, tolerability, delivery, and clinical effect is essential to long-term success.

在兩項計畫中，我們的重點仍是產出高品質的臨床與法規資料，以支持審慎決策並有效率地推進開發進程。我們相信，這種嚴謹的方法在新興治療模式中特別重要，因為對安全性、耐受性、遞送方式與臨床效果進行仔細特性描述，是長期成功的關鍵。

I'm excited to be part of the Arcturus team, look forward to working closely with our investigators, regulatory partners, and internal team members as we continue moving these important programs forward.

我很高興能成為 Arcturus 團隊的一員，並期待在我們持續推進這些重要計畫的同時，與研究者、法規合作夥伴以及內部團隊成員密切合作。

With that, I'll now pass the call to Dennis.

接下來，我把電話交給 Dennis。

Thanks, Alan, and good afternoon, everybody. Our press release issued earlier today includes financial statements for the first quarter ending March 31, 2026, and provides a summary and analysis of our year-over-year performance. Please also reference our most recent Form 10-Q for more details on our financial performance.

謝謝你，Alan，各位下午好。我們今天稍早發布的新聞稿包含截至 2026 年 3 月 31 日止第一季的財務報表，並提供我們年對年表現的摘要與分析。也請參考我們最新的 Form 10-Q，以取得更多關於財務表現的細節。

Cash, cash equivalents and restricted cash totaled $213.4 million on March 31, 2026; and $232.8 million on December 31, 2025. Year-over-year quarterly revenue decreased by $27.3 million. The decline was driven by reductions in revenue from our CSL collaboration as Arcturus refocuses on our rare disease clinical programs.

截至 2026 年 3 月 31 日，現金、約當現金及受限制現金合計為 2.134 億美元；而截至 2025 年 12 月 31 日為 2.328 億美元。年對年季度營收減少 2,730 萬美元。此下降主要由於我們與 CSL 合作帶來的營收減少，因 Arcturus 重新聚焦於罕見疾病臨床計畫。

Quarterly research and development expenses decreased year over year by $13.4 million, which was driven primarily by lower manufacturing costs related to LUNAR, COVID, and BARDA as well as reduced clinical trial costs associated with the LUNAR COVID program. Additional decreases were attributable to lower payroll and benefit costs associated with lower stock-based compensation expense and a reduction in headcount. Overall reductions were partially offset by higher manufacturing costs related to LUNAR OTC.

季度研發費用年對年減少 1,340 萬美元，主要原因為與 LUNAR、COVID 及 BARDA 相關的製造成本降低，以及與 LUNAR COVID 計畫相關的臨床試驗成本下降。其他下降因素包括因股票基礎給付費用降低及人力編制縮減而導致的薪資與福利成本下降。整體降幅部分被與 LUNAR OTC 相關的較高製造成本所抵銷。

General and administrative expenses decreased year over year by $1.8 million due to reduced share-based compensation expense, as well as payroll and benefits associated with reductions in headcount. Through continued execution and strategic refocusing on our existing rare disease clinical programs and therapeutic platform in the first quarter of 2026, Arcturus has maintained a cash runway extending beyond the second quarter of 2028.

一般及行政費用年對年減少 180 萬美元，原因為股份基礎給付費用降低，以及因人力編制縮減而降低的薪資與福利。透過在 2026 年第一季持續執行並策略性重新聚焦於既有罕見疾病臨床計畫與治療平台，Arcturus 已維持現金可支撐期延伸至 2028 年第二季之後。

The company remains in a strong financial position and has cash runway needed to achieve multiple near-term, value-creating milestones in both therapeutic programs.

公司仍維持強勁的財務狀況，並具備所需的現金可支撐期，以在兩項治療計畫中達成多項近期可創造價值的里程碑。

With that, I'll now pass the call back to Joe.

接下來，我把電話交回給 Joe。

Thanks, Dennis. Arcturus continues to make steady progress across our rare disease mRNA therapeutic programs while strengthening the foundation of the company.

謝謝你，Dennis。Arcturus 在罕見疾病 mRNA 治療計畫方面持續穩健推進，同時也在強化公司的基礎。

With enrollment now underway in our 12-week open-label Phase 2 study of ARCT-032 in cystic fibrosis, and clear regulatory direction from the FDA on the pediatric development strategy for ARCT-810 and OTC deficiency, we remain focused on advancing toward important clinical and regulatory milestones throughout 2026. Supported by a strong balance sheet and an expanded, experienced leadership team, we believe Arcturus is low positioned to execute on our priorities.

隨著 ARCT-032 囊性纖維化 12 週開放標籤第二期研究已開始收案，以及 FDA 就 ARCT-810 與 OTC 缺乏症的兒科開發策略提供明確的法規方向，我們仍專注於在 2026 年推進多項重要的臨床與法規里程碑。在強健的資產負債表與擴充且經驗豐富的領導團隊支持下，我們相信 Arcturus 已具備良好條件來執行我們的優先事項。

So with that, let's turn the call over to the operator for questions.

那麼，接下來我們把電話交給接線員進行提問。

(Operator Instructions) Seamus Fernandez, Guggenheim.

（接線員指示）Guggenheim 的 Seamus Fernandez。

Hey guys, thanks for taking the question. This is Evan Wang on for Seamus. Two for me, one on OTC deficiencies and one on cystic fibrosis. Just on first on OTC deficiency, can you share specific FDA feedback on the glutamine and ureagenesis assay specifically? Curious also the discussion between infants and adults since I don't know if I saw -- you mentioned a path forward in the adult setting.

各位好，謝謝讓我提問。我是代 Seamus 發言的 Evan Wang。我有兩個問題，一個關於 OTC 缺乏症，一個關於囊性纖維化。先談 OTC 缺乏症，能否分享 FDA 對麩醯胺酸與尿素生成（ureagenesis）檢測的具體回饋？也想了解嬰兒與成人之間的討論，因為我不確定是否看到——你們提到在成人族群有一條前進路徑。

And second, cystic fibrosis, just curious, anything you can share in terms of patient enrollment and progress there and, what's the potential for a potential interim there? Thanks.

第二個，關於囊性纖維化，想請問在病人收案與進度方面是否能分享一些資訊，以及是否有可能進行期中分析？謝謝。

Hey, thanks, Evan. I can turn the time over to Alan to address some of the FDA feedback questions pertaining to infants and adults and the biomarker question to him. And then I can -- we'll go to that point. I can address the CF question.

嗨，謝謝你，Evan。我可以把時間交給 Alan，請他回應一些與嬰兒與成人相關、以及生物標記問題有關的 FDA 回饋。然後我可以——我們再接著談。我可以回應 CF 的問題。

Right, thanks, Joe. So we've successfully, as you mentioned, completed the first of two Type C meetings with the FDA, and it's clear that we have greater clarity now as to what we need moving forward.

好的，謝謝你，Joe。如你所提，我們已成功完成與 FDA 的兩場 Type C 會議中的第一場，且很明顯我們現在對後續所需事項有更清楚的認識。

And as you mentioned, the utility of the biomarkers, most notably ammonia and glutamine in particular, have been historically highlighted and were identified as areas of greater focus and attention for us moving forward. So greater clarity on which biomarkers to use.

如你所提，生物標記的效用，尤其是氨與麩醯胺酸，過去一直被強調，並被認定為我們後續需要更聚焦與更重視的領域。因此，我們對應使用哪些生物標記有了更清楚的方向。

Urogenesis is still a biomarker in development, and we're continuing to advance that. But our dependence upon it, I think, will depend on the additional data that we're currently in the process of generating.

尿素生成（ureagenesis）仍是一項正在開發中的生物標記，我們會持續推進。但我們對它的依賴程度，我認為將取決於我們目前正在產生的額外資料。

And then with respect to your CF questions and the cadence of enrollment, I think the cadence of enrollment is being determined in the upcoming weeks. We just started this study in the first quarter, but we'll be able to give a more accurate enrollment completion timing later this year.

至於你關於 CF 的問題以及收案節奏，我認為收案節奏將在未來幾週內確定。我們在第一季才剛啟動這項研究，但我們將能在今年稍晚提供更準確的收案完成時間。

We do remind people that we enrolled approximately 13 subjects in 2025 over sequential three cohorts, first, second, and third cohort. And that was limited to the United States. We are expanding enrollment not just in the U.S., but also outside the US or abroad.

我們也提醒大家，我們在 2025 年於連續的三個隊列（第一、第二與第三隊列）中共收納約 13 名受試者。而當時僅限於美國。我們正在擴大收案，不僅在美國，也包括美國以外或海外地區。

Thank you.

謝謝。

Thanks, Evan.

謝謝你，Evan。

Lili Nsongo, Leerink Partners.

Leerink Partners 的 Lili Nsongo。

Hi, good afternoon. Thank you for taking the question. Maybe just a quick question regarding the OTC program. So could you tell us what is the type of exploratory data that the FDA is looking for and also whether it would require for you to initiate studies in the pediatric population? Thank you.

嗨，下午好。謝謝讓我提問。我想快速問一個關於 OTC 計畫的問題。所以你們能否說明 FDA 想要的探索性資料類型是什麼，以及是否會要求你們在兒科族群啟動研究？謝謝。

Go ahead, Alan.

Alan，你來回答。

Sure. So great question and thank you for asking. The first Type C meeting that we had, as you alluded to, focused exclusively on what will it take for us to be able to take the adult data that we're still in the process of generating in our current open Phase 2 study into pediatrics.

好的。這是個很好的問題，謝謝你的提問。我們進行的第一場 Type C 會議，如你所指，完全聚焦於：我們需要做到什麼，才能把目前這項開放性第二期研究中仍在產生的成人資料，推進到兒科。

The results of that meeting suggested that we have a clear path forward. We're continuing to collect additional enrollment data for the 0.3 and the 0.5 dosing groups. Our plan is to then have an end of Phase 2 meeting with the FDA. The intent there is to do sort of the usual necessary tasks, which is to reaffirm and continue to show safety and tolerability. And of course, if you're going to go into young children and newborns, the goal would be to also show enough evidence of clinical efficacy to justify going into such a young, vulnerable population.

該次會議的結果顯示，我們有一條明確的前進路徑。我們將持續蒐集 0.3 與 0.5 劑量組的額外收案資料。接著我們的計畫是與 FDA 召開第二期結束（End of Phase 2）會議。其目的在於完成一般必要的工作，也就是再次確認並持續證明安全性與耐受性。當然，如果要進入幼兒與新生兒族群，目標也會是展現足夠的臨床療效證據，以合理化進入如此年幼且脆弱的人群。

We have greater clarity now as a result of that meeting. We're in the process of completing that data set and we should have sufficient data later this year to take that total data set, bring it forward to the FDA, and continue our conversations and hopefully get into a pediatric study sometime in the months and years ahead.

由於那次會議，我們現在有更清晰的了解。我們正在完成該資料集，並且預期在今年稍晚會有足夠的數據，屆時可將完整資料集提交給 FDA，並持續與其溝通，期望在未來幾個月到幾年內的某個時間點進入兒科研究。

Yanan Zhu, Wells Fargo.

Yanan Zhu，富國銀行。

Hi. Thanks for taking our question. This is Kuanan for Yannan. So our question is around cystic fibrosis. Since there is no placebo control for the 12-week study, can you talk about the variability of FEV1 and LCI, and how should we prepare to interpret the data without placebo control? Thank you.

你好。謝謝讓我們提問。我是代替 Yannan 的 Kuanan。我們的問題是關於囊性纖維化。由於這項 12 週研究沒有安慰劑對照組，能否談談 FEV1 與 LCI 的變異性，以及在沒有安慰劑對照的情況下，我們應該如何準備解讀數據？謝謝。

Yeah, that's correct. There's no placebo arm in the present study. Maybe Alan can comment on the [REACH] study and placebo strategy going forward. With respect to variability of FEV, that's well understood. We are collecting two lung function parameters, FEV and LCI, and maybe Alan can comment on the value of doing that.

是的，沒錯。目前這項研究沒有安慰劑組。也許 Alan 可以就 [REACH] 研究以及未來的安慰劑策略做些說明。至於 FEV 的變異性，這點已相當清楚。我們正在收集兩個肺功能參數，FEV 與 LCI，也許 Alan 可以談談這樣做的價值。

Sure, great question and an important question. As you know, the requirements for percent-predicted FPV1 and spirometry is active performance characteristics and reproducibility with the person performing the task. The good news about cystic fibrosis patients is that they've been accustomed, unfortunately, to doing spirometry since they're in school.

當然，這是個很好的問題，也是個重要的問題。如你所知，預測百分比（percent-predicted）FEV1 與肺量計檢測的要求，取決於受試者執行測試時的主動表現特性與可重複性。關於囊性纖維化患者的好消息是，他們不幸地從在學時期起就已習慣做肺量計檢測。

And since most of the adults that we're enrolling are well into their 20s and beyond, they have decades of experience performing spirometry almost daily. We have set in this Cohort 4 study parameters from screening and baseline to allow for a small variation from the two measures, but not an excessive amount so that there is enough consistency between screening and baseline that we feel confident that an individual is producing reproducible, reliable tests throughout the course of the study. That was something we didn't have in place before. I think it's necessary. I believe that it's going to mitigate any concerns that we may have moving forward.

而且我們納入的大多數成人受試者都已二十多歲甚至更年長，他們幾乎每天做肺量計檢測，累積了數十年的經驗。在這項第 4 隊列研究中，我們在篩選與基線之間設定了參數，允許兩次測量之間有小幅變動，但不允許過度變動，以確保篩選與基線之間具有足夠一致性，讓我們有信心個體在整個研究期間都能產出可重複、可靠的測試結果。這是我們以前沒有建立的機制。我認為這是必要的。我相信這將能減輕我們未來可能有的任何疑慮。

Now in terms of LCI, the challenge with LCI in adults is that there just simply has not been a very large natural history database of people with cystic fibrosis. The good news is that the Cystic Fibrosis Foundation, recognizing the sensitivity of that tool, in particular for measuring changes in small airways, which is likely to be the place where early demonstration of clinical efficacy is most likely to be, they are currently completing a large prospective, open-label study in exactly the same population that we're targeting for our Cohort 4 and subsequent studies.

至於 LCI，在成人族群的挑戰在於：針對囊性纖維化患者，確實一直缺乏非常大型的自然病程資料庫。好消息是，囊性纖維化基金會（Cystic Fibrosis Foundation）認知到該工具的敏感性，特別是在衡量小氣道變化方面——而這很可能是最早能展現臨床療效的部位——他們目前正在完成一項大型前瞻性、開放標籤研究，研究族群正是我們第 4 隊列及後續研究所鎖定的同一族群。

And that data should be shared later this year going into 2027 by the CF Foundation at the upcoming NACFC meeting. So we're looking forward to seeing that data starting to be presented, and they have assured all sponsors, including us, that we'll have access to that data moving forward.

而該數據預計將在今年稍晚、邁入 2027 年之際，由 CF 基金會在即將召開的 NACFC 會議上分享。因此我們很期待看到這些數據開始被發表；他們也向所有贊助方（包括我們）保證，未來我們將能取得這些數據。

So we'll have a normative data set, which we hope to use as we bring forward the data we'll be generating on our study drug in the months and years ahead as well.

因此我們將會有一套常模（normative）資料集；我們希望在未來幾個月到幾年內，當我們推進並提交本研究藥物所產生的數據時，也能一併運用該資料集。

The only thing I would add is that I just want to remind everyone on the call that the FDA has not defined a threshold of success for FEV or LCI, at least for our program.

我唯一想補充的是：我想提醒各位與會者，至少就我們的計畫而言，FDA 尚未為 FEV 或 LCI 定義成功門檻。

In the modulator space, they have. But for a new modality like inhaled mRNA, for Class 1CF, there's no minimum threshold that we must observe. Anything positive would be viewed seriously. And like what Alan mentioned, the REACH study will be very likely to be very helpful as well. Anyway, thanks for the question.

在調節劑（modulator）領域，他們有定義。但對於像吸入式 mRNA 這種新型態療法、用於第 1 類囊性纖維化（Class 1 CF），並沒有我們必須觀察到的最低門檻。任何正向結果都會被嚴肅看待。而且如 Alan 所提到的，REACH 研究也很可能會非常有幫助。總之，謝謝你的提問。

Thank you for all the colors.

謝謝你提供這麼多補充說明。

Myles Minter, William Blair.

Myles Minter，William Blair。

Hi, this is Jake on for Myles. Thanks for taking our question. One of your competitors recently discontinued its inhaled CFTR mRNA trial. We were just wondering if you've seen any of the manifestations that were described there and led to the discontinuation and whether you've had any discussions with the CF Foundation or regulators regarding patient enrollment of this new cohort now that that trial has been discontinued? Thank you.

你好，我是代替 Myles 的 Jake。謝謝讓我們提問。你們的一家競爭對手最近停止了其吸入式 CFTR mRNA 試驗。我們想了解你們是否看到了該試驗中所描述、並導致其終止的任何表現（manifestations）；以及在該試驗終止後，你們是否就這個新隊列的病患招募，與 CF 基金會或監管機構進行過任何討論？謝謝。

Yeah, the short answer is no. There's significant differences between the technology that we use to deliver the RNA molecule then versus our competitors. And we touched that on in the script earlier on today's call. But I would like to also highlight that we have utilized no steroids as a co-treatment before, during, or after the dosing period. And that's a point of differentiation and there's reasons for that that are safety and tolerability related.

是的，簡短回答是沒有。我們用來遞送 RNA 分子的技術，與競爭對手的技術有顯著差異。我們在今天電話會議較早的講稿中也提到過。但我也想強調，我們在給藥期之前、期間或之後，都沒有使用類固醇作為合併治療。這是一個差異化重點，而背後原因與安全性及耐受性相關。

And also we've been approved by regulators for unsupervised dosing at home, and that's not been the case for some of the other companies in this field. And those are -- that's another point of differentiation. And the reason behind that, again, is all because we're using a different technology. It's a different chemistry, and it also includes a different manufacturing process to purify the mRNA molecule, which could be a contributor to remove the impurities that cause those undesired immunogenicities and immune responses.

此外，我們已獲監管機構核准可在家中進行無監督給藥，而這在本領域的某些其他公司並非如此。這也是另一個差異化重點。而其背後原因同樣是因為我們採用不同的技術。這是不同的化學設計，也包含不同的製造流程來純化 mRNA 分子；這可能有助於去除會導致那些不希望出現的免疫原性與免疫反應的雜質。

But anything else to add, Alan?

Alan，還有什麼要補充的嗎？

No, I think Joe covered the majority of it. The only thing I would add is that it's worth pointing out that at the completion of our Cohort 3 study, which went up from 5 to 10 to 15 milligrams daily for 28 days that we were given the ability to move forward with a longer study, allowing for either 10 or 15 milligrams daily in cohort four.

沒有，我想 Joe 已涵蓋大部分內容。我唯一要補充的是：值得指出的是，在我們第 3 隊列研究完成後——該研究為期 28 天、每日劑量從 5 提升到 10 再到 15 毫克——我們獲准可以推進到更長期的研究，並允許在第 4 隊列中採用每日 10 或 15 毫克。

So our safety monitoring committee saw nothing clinically worrisome and have allowed us to not only go up to 15 milligrams if we choose to daily, but we also have the freedom and ability to take those patients out to 12 weeks, which we are currently embarking on right now, initiating at a 10-milligram dose once daily.

因此，我們的安全監測委員會沒有看到任何臨床上令人擔憂的訊號，並允許我們不僅在需要時可將每日劑量提高到 15 毫克，同時也讓我們有自由與能力將受試者治療期延長到 12 週；我們目前正著手進行，並以每日一次 10 毫克劑量啟動。

Mayank Mamtani, B. Riley Securities.

Mayank Mamtani，B. Riley Securities。

Yes. Good afternoon, team. Thanks for taking your questions and good to hear 032 studies progressing ahead of plan. Did I hear that you've had certain patients move past the one-month exposure window? And just curious if the Vortex study, there are any go/no-go decisions in trust study on duration of treatment, because those studies were kind of comparable on timelines and how further along they were. There are mechanisms built in your study that informs continuation based primarily on tolerability reasons, but also obviously efficacy reasons also and then I have a follow-up.

是的。各位下午好。謝謝回答問題，也很高興聽到 032 研究進展超前於原計畫。我是否聽到你們已有部分病患已超過一個月的暴露期？另外想請教，在 Vortex 研究中，是否有任何針對治療期間的 go/no-go 決策點，因為那些研究在時間線上有點可比，且進度也更往前。你們的研究內建了一些機制，主要基於耐受性因素來決定是否繼續，但顯然也會考量療效因素；然後我還有一個追問。

Yes, it's a good question. With respect to the first, we have initiated the 12-week study in the first quarter. So that means that we are well beyond a month of dosing already in the study. We are continuing to enroll at a pace that's going to be understood in the next in in the coming weeks. But yes, we're well beyond that one-month study.

是的，這是個好問題。就第一點而言，我們已在第一季啟動了為期12週的研究。這表示在該研究中，我們的給藥已經進行超過一個月了。我們仍在持續招募，招募速度在接下來幾週會更清楚。但沒錯，我們已經遠遠超過那個一個月的研究進度。

With respect to intermediate go/no-go opportunities and decisions that are built into the protocol, I'll have Alan comment on that.

至於方案中內建的中期繼續/停止（go/no-go）機會與決策，我會請Alan來說明。

Yes, I mean, the good news about an open-label clinical trial is that we're going to be able to, in an active way, monitor patient progress and look for safety signals as well as early signs of efficacy. It's our impression that before the end of this calendar year, we should have enrolled and have sufficient enough data in hand that we will be able to speak a little bit more clearly to the future longevity of the program as well as the direction of the program moving forward.

是的，我的意思是，開放標籤臨床試驗的好消息在於，我們能以主動的方式監測病患進展，並同時觀察安全性訊號以及早期療效跡象。我們的看法是，在今年曆年結束前，我們應該能完成招募並取得足夠的數據，使我們能更清楚地談談該計畫未來的持久性，以及後續推進的方向。

And then on the REACH data that you're looking to learn at [NACFC], I was just curious on the LCI, what, according to you, start up good looks like and what correlations that you're curious about?

另外，關於你在[NACFC]想了解的REACH數據，我只是好奇在LCI方面，依你看，啟動後「良好」的表現應該是什麼樣子，以及你特別想看的相關性有哪些？

Yeah. There's several reasons why we've included Lung Clearance Index into this new protocol for the fourth cohort. The first, of course, is to add an additional measure of lung function that is respected, understood, and can be a potential endpoint for us in the study.

是的。我們之所以在第四隊列的新方案中納入肺清除指數（Lung Clearance Index, LCI），有幾個原因。第一，當然是增加一項受尊重、被理解、且可作為本研究潛在終點的肺功能量測指標。

With respect to the correlation of LCI to other parameters, maybe you can comment on that.

至於LCI與其他參數之間的相關性，也許你可以評論一下。

Yeah, I mean, the interesting thing about LCI is that I mentioned earlier, one of the questions that we got earlier was talking about the variability of the performance characteristics of spirometry. The nice thing about Lung Clearance Index and why it was used almost exclusively in young children who can't perform spirometry is that it's a passive maneuver. It doesn't require active involvement of the patient itself to perform it.

是的，我的意思是，LCI有趣之處在於我先前提到過，我們之前收到的一個問題談到肺量計（spirometry）表現特性的變異性。肺清除指數的優點，以及它幾乎專門用於無法進行肺量計檢查的幼童的原因，是因為它是一種被動操作。它不需要病患主動配合去完成。

So it's actually very reproducible and highly reliable. So all you really have to do is form a seal around the mouthpiece, and then the equipment does the rest. So right now, the only outstanding information we have is what the CF Foundation is generating right now with the REACH study, which is what's the normal rate of decline of Lung Clearance Index within the population that we're studying. So we have a comparative group.

因此它其實非常可重現且高度可靠。你真正需要做的只是讓口含器周圍形成密封，接著設備就會完成其餘部分。所以目前我們唯一尚待取得的資訊，是CF基金會正在透過REACH研究產出的資料，也就是在我們所研究的人群中，肺清除指數的正常下降速率是多少。如此我們就有一個可比較的對照組。

So really right now, it's not only a more sensitive measure. And by the way, it's also, as you may know, been an approvable endpoint for some of the modulators, in particular in Europe and rest of the world. So we know it's reliable, we know it's reproducible. It has really not been used in adults just simply because it wasn't perceived as necessary. But I think increasingly, it's being appreciated for the sensitive way with which it measures a more distinct, more peripheral, more acutely portion of the airway that may prove to be much more useful for purposes of a study like this in these patients moving forward.

所以目前它不僅是一個更敏感的量測指標。順帶一提，如你所知，它也曾作為某些調節劑（modulators）的可核准終點，特別是在歐洲及世界其他地區。因此我們知道它可靠、也知道它可重現。它之所以在成人中沒有被廣泛使用，單純是因為過去不被認為有必要。但我認為，越來越多人開始重視它以敏感方式量測更明確、更周邊、且更急性（更即時）反映的氣道區段；對於像這樣的研究、以及未來在這些病患中的研究目的，可能會更有用。

And LCI also has a correlation between mucus plug reduction and insomuch that that's the encouraging data we saw in our second cohort that we've shared.

而且LCI也與黏液栓（mucus plug）減少具有相關性；就我們在第二隊列所分享的令人鼓舞數據而言，正是如此。

We'd like to see that correlate with the lung function measure and Lung Clearance Index has nice correlation to these reductions of mucus plugs and other studies.

我們希望看到這能與肺功能量測相互對應，而在其他研究中，肺清除指數與黏液栓減少及其他變化之間也有良好的相關性。

Got it. And lastly, any insight on your plans for combining with a modulator or maybe non-responder population? Is there anything you could do in the ongoing protocol? Thanks for taking my question.

了解。最後，關於你們與調節劑合併使用，或是針對無反應族群（non-responder population）的計畫，有沒有任何見解？在進行中的方案裡，有沒有什麼你們可以做的？謝謝你回答我的問題。

Did you understand the question now?

你現在理解這個問題了嗎？

Yes, I think I did, and if I didn't, please correct me. I guess the question as I understood it was, obviously the highest unmet medical need population are those with null mutations and those who are unable to tolerate or are unable to get access to modulators. That's obviously the patient population that we're focused on now.

是的，我想我理解了；如果我沒有理解，請糾正我。我理解的問題是：顯然，未被滿足醫療需求最高的族群，是那些帶有無功能突變（null mutations）的人，以及那些無法耐受或無法取得調節劑治療的人。這顯然就是我們目前聚焦的病患族群。

Is our therapeutic potentially beneficial to a broader population of patients who may be on modulators? Yes, the answer is yes. And that would obviously be the next place we'd want to go. But obviously, we're going to need to generate sufficient data to make that justifiable and we look forward to hopefully getting that data in the years ahead.

我們的治療是否可能對更廣泛、可能正在使用調節劑的病患族群也有益？是的，答案是肯定的。而那顯然會是我們下一步想前往的方向。但很明顯，我們需要產出足夠的數據來使其具備正當性；我們也期待在未來幾年能取得那些數據。

Adam Walsh, ROTH Capital Partners.

Adam Walsh，ROTH Capital Partners。

Hi, good afternoon and thanks for taking my questions. On the adult Type C meeting timing, when would we expect to hear about that outcome?

嗨，午安，謝謝你回答我的問題。關於成人Type C會議的時程，我們何時可以預期聽到結果？

Sure. We've shared previously that both of these Type C meetings would be completed in the first half of this year, and we're well on track for that. So the second would be sometime this quarter. That's a near-term. It's on the near-term horizon here very soon.

當然。我們先前已分享，這兩場Type C會議都會在今年上半年完成，而我們進度完全符合預期。因此第二場會在本季的某個時間點。這是近期事項。很快就會在近期視野內發生。

Wonderful. And then how's the team segmenting pediatric versus adolescent versus adult for OTC? And what is the realistic enrolled patient number for the pediatric pivotal given the targeted severity?

太好了。那團隊如何針對OTC在兒科、青少年與成人之間做分層？另外，考量目標嚴重程度，兒科關鍵性試驗（pivotal）在現實上可招募的病患人數是多少？

Sure. Great questions. I'll take this one. This is Alan. The population that we believe has the highest unmet need are those who tend to be under the age of six, so preschool age up to early school age. By the time -- unfortunately, most of these kids with OTC deficiency who manifested in the birth period, by the time they get to school age, they're either unfortunately having a liver transplant or if they're unable to be stable enough for that, they die.

好的。很好的問題。我來回答這題。我是Alan。我們認為未被滿足需求最高的族群，是那些通常年齡在六歲以下的孩子，也就是學齡前到小學低年級。不幸的是，多數在出生期就發病的OTC缺乏症孩子，等到他們到了學齡時，不是已經需要肝臟移植，就是如果狀況不夠穩定而無法進行移植，就會死亡。

So the segmentation for the pediatric population would almost exclusively be focused on that exact population, children in the first weeks and months of life up through probably age six.

因此，兒科族群的分層幾乎會專注在那個確切族群：從出生後最初幾週與幾個月，一直到大約六歲的兒童。

Excellent. And then one more, if I may, just on 032 and CF. How is the team approaching interim versus full disclosure, given the open-label design? I know this was touched upon on the last call, and you may not be advanced enough to comment on it. But will you be anticipating any disclosure on interim, given the open-label study?

非常好。如果可以的話我再問一題，關於032與CF。在開放標籤設計下，團隊如何看待期中揭露（interim）與完整揭露（full disclosure）的取捨？我知道上次電話會議有提到，你們可能還沒進展到能評論的程度。但在這項開放標籤研究中，你們是否預期會做任何期中揭露？

Yes, the language we've used on this call today, Adam, is that you're right, it's an open-label study. It's already started. And we're expressing confidence on today's call that later this year we should have sufficient enrollment and data to inform our next steps. So I think we're going to be in a really good place to understand where we are with this program later this year.

是的，Adam，我們今天在電話會議上使用的措辭是：你說得對，這是一項開放標籤研究。它已經開始了。而我們今天也表達信心，認為在今年稍晚，我們應該會有足夠的招募與數據來指引我們的下一步。所以我認為，今年稍晚我們會處於非常好的位置，能理解這個計畫目前的狀況。

That's great. Thank you.

太好了。謝謝。

Whitney Ijem, Canaccord.

Whitney Ijem，Canaccord。

Hi, thank you for taking your questions. This is [Angela Chan] on for Whitney. Can you remind us what preclinical data you have of LUNAR CF to penetrate the mucus and any data around like endosomal escape or production of functional protein?

嗨，謝謝讓我們提問。我是代替 Whitney 的 [Angela Chan]。可以請您提醒一下，LUNAR CF 在穿透黏液方面有哪些臨床前數據？以及是否有關於內體逃逸或產生功能性蛋白的相關數據？

And then can you also remind us what cells are you reaching within the lung?

另外，也請您提醒一下，你們在肺部目前能觸及到哪些細胞？

Sure. So we have Pat here with this. He can comment on the ferret data, et cetera.

當然。我們這裡有 Pat 來回答這部分。他可以評論雪貂數據等等。

Yeah. Well, first of all, we worked for many years with the CF Foundation to develop our preclinical package. And we've done quite a bit of work on looking at LNP stability in sputum. And then we've also done a lot of work preclinically in mouse, rodents, and ferrets, as well as non-human primates.

是的。首先，我們與 CF Foundation 合作多年，來建立我們的臨床前資料套件。我們做了相當多工作來觀察 LNP 在痰液中的穩定性。此外，我們也在小鼠、囓齒類與雪貂，以及非人靈長類中做了大量臨床前研究。

And what we see is in the CF mouse model, for example, that we can get to various bronchial apathy cells. We have a pretty broad distribution, and some of this data was recently published with some of our collaborators, and I think that's available. And we can provide that to you.

我們看到的是，例如在 CF 小鼠模型中，我們可以到達多種支氣管上皮細胞。我們的分佈相當廣泛，其中部分數據最近已與一些合作夥伴共同發表，我想那是可取得的。我們也可以提供給你。

Did we address your question?

這樣有回答到你的問題嗎？

Great, yeah, if you could send that would be great. And then maybe a follow-up is on dosing currently, are you doing anything to address kind of the distribution of drug into the lower lobes? Like, is there a way you can try to impact the distribution of drugs?

很好，有的，如果你們能寄給我就太好了。另外一個追問是，目前在給藥方面，你們是否有做任何事情來改善藥物分佈到下葉？例如，有沒有方法可以影響藥物的分佈？

Right now, our anticipation is we won't have to modify the position of the patient or anything like that to access different lobes or parts of the lungs, so that's not our anticipation, but --.

目前我們預期不需要調整病人的姿勢或做任何類似處置來進入不同肺葉或肺部不同區域，所以這不是我們的預期，不過--。

I can also this this is Pat again, we can also when we did our initial preclinical evaluation of the nebulizer that we were going to use, we've optimized the particle size of the nebulizer so that it does get distributed throughout the lump.

我也補充一下，我是 Pat。當我們對將要使用的霧化器進行初步臨床前評估時，我們已最佳化霧化器的粒徑，使其能分佈到整個肺部。

Yeah, and this is Alan. Just to add one more piece to that, I think your question is probably coming from the high-resolution CT data that we shared and generated in our last cohort, which showed a preponderance of effect mostly in the lower segments of the thoracic cage and within the lower segments of the lung.

是的，我是 Alan。再補充一點，我想你的問題可能是來自我們在上一個隊列分享並產生的高解析度 CT 數據；該數據顯示效果主要集中在胸廓下段以及肺部下段。

We know that ventilation, perfusion, and ventilation in general differs with aerosols in particular in the lower and upper segments of the lung. One of the things that we're hoping to achieve if we're going now from a four-week dosing strategy to 12-week strategy is a much more thorough application of our therapy throughout the lung. And we hope to see that manifest as the study goes beyond the four-week period. So we think this is more so a byproduct of time and not necessarily dose.

我們知道，特別是對於氣霧劑而言，通氣、灌流以及整體通氣在肺的下段與上段之間有所不同。我們希望達成的一件事是，若我們現在從四週給藥策略改為 12 週策略，能讓我們的治療在整個肺部更全面地發揮作用。我們希望隨著研究超過四週期間而看到這點呈現出來。因此我們認為這更像是時間的副產品，而不一定是劑量的問題。

Got it. Thank you so much.

了解。非常感謝。

Yigal Nochomovitz, Citigroup.

Yigal Nochomovitz，Citigroup。

Hi, this is [Won Kim] on for you all. Thanks for taking our questions. Maybe two quick ones from us. Just to confirm, firstly, do you need to enroll more patients at the 0.3 or 0.4, 0.5 mgs per kg dose for the exploratory data that needs to be generated? Or is that just from longer follow-up?

嗨，我是代替各位的 [Won Kim]。謝謝讓我們提問。我們這邊可能兩個簡短問題。首先確認一下，為了需要產生的探索性數據，你們是否需要在 0.3 或 0.4、0.5 mg/kg 劑量再納入更多病人？還是只是需要更長的追蹤？

The short answer is we just need to complete the scheduled study as dictated and communicated at the Type C meeting. So there's nothing too extraordinary. We just need to complete that data set and also analyze it and then present it in a way that they requested. It was just a re-analysis of the data that they wanted to appreciate and we said that we'd provide that to them at the EOP2 meeting.

簡短回答是：我們只需要依照 Type C 會議所規定並已溝通的內容，完成既定研究。所以沒有什麼特別不尋常的。我們只需要完成那個資料集、進行分析，並以他們要求的方式呈現。他們只是希望我們對數據做重新分析，我們也表示會在 EOP2 會議提供給他們。

Got you. And also, CF, I believe that you noted that you're planning on conducting the HRCT scans in the 12-week study. Can you provide additional detail on how frequently the assessment, as well as LCI and FEV-1 measurements, might be conducted? And are you seeking to enroll a certain number of patients ex US? Thank you very much.

了解。另外，關於 CF，我記得你們提到計畫在 12 週研究中進行 HRCT 掃描。能否提供更多細節，例如評估的頻率，以及 LCI 與 FEV-1 測量可能會以多頻繁的節奏進行？另外，你們是否希望在美國以外招募一定數量的病人？非常感謝。

Yeah, with respect to high-res CT scan, it's before and after. We typically do not propose to take several of these high-res CT scans during a study. It's typically before and after. With respect to the other lung function measurements and the cadence of that throughout the 12-week study, maybe, Alan, you can comment on that, what you're comfortable sharing?

是的，關於高解析度 CT 掃描，是在治療前與治療後各做一次。我們通常不會在研究期間做多次高解析度 CT 掃描。一般就是前後各一次。至於其他肺功能測量，以及在 12 週研究期間的執行頻率，Alan，也許你可以就你方便分享的部分評論一下？

Yeah, we haven't really shared that kind of level of granularity. But I think it's appropriate to just consider that. Every time a patient comes back to a clinic to get evaluated and to get another scheduled amount of drug, that's a perfect time, particularly at a CF center, to repeat testing in a controlled setting.

是的，我們還沒有分享那麼細的層級。但我想可以這樣理解：每次病人回到診所接受評估並取得下一次排程的藥量時，尤其是在 CF 中心，那就是在受控環境下重複檢測的最佳時機。

We are not using home monitoring nor home spirometry or Lung Clearance Index equipment in the household or in the home. So we want consistent measures being performed in an appropriate skilled center so that we can have reliable data. So we're collecting data at every time point that the patient's coming back. So it's at a regular cadence over the course of 12 weeks.

我們不使用居家監測，也不使用居家肺量計或在家中使用 Lung Clearance Index 設備。因此我們希望在合適且具專業能力的中心進行一致的測量，以便取得可靠數據。所以我們會在病人每次回診的每個時間點收集數據。因此在 12 週期間會以固定節奏進行。

Got it. Thank you. And are you looking to enroll? Is there a number of patients next to US?

了解。謝謝。另外你們是否打算招募？美國以外的病人數量會是多少？

Yeah, for 20 subjects, up to 20 subjects is what we're -- what's presently in the protocol for CF. Or were you asking about OTC?

是的，針對 CF，目前方案中規劃的是 20 名受試者，最多到 20 名。還是你在問 OTC？

Oh, no, I just went -- amongst those 20 patients, is there a specific number that you're looking to get, ex-US versus US?

喔不是，我是想問——在那 20 位病人之中，你們是否有特定希望的美國以外 vs 美國的比例或人數？

Go ahead, Alan. Comment on that.

Alan，你來回答一下。請評論。

Yeah, no, another great question. We added ex-US sites in large part because there are jurisdictions in the world that happen to have higher preponderances of people with null mutations. And we're trying to take advantage of the fact that there are high unmet medical needs in parts of the world where the level of care, the nature of care, and the clinical course of the disease is commensurate and consistent with what we observe here in the US, Canada, and other parts of the world.

是的，這也是個很好的問題。我們新增美國以外的研究中心，很大一部分原因是世界上有些司法管轄區恰好有較高比例的無功能突變（null mutations）患者。我們希望利用這個事實：在世界某些地區存在高度未被滿足的醫療需求，而那裡的照護水準、照護型態以及疾病的臨床病程，與我們在美國、加拿大及世界其他地區所觀察到的是相稱且一致的。

So we haven't set a high or low bar in terms of the number of patients to be enrolled in the United States and outside of the United States. It's in our anticipation that it's going to be, perhaps an equal mix, but it really shouldn't matter at this point.

因此，就在美國境內與美國境外要納入的病患人數而言，我們並沒有設定很高或很低的門檻。我們預期可能會是大致各半的組合，但在現階段其實不應該有太大影響。

Great. Thank you very much. Appreciate the call.

很好。非常感謝。感謝這通電話。

Thank you.

謝謝。

Thomas Shrader, BTIG.

Thomas Shrader，BTIG。

Hi, good afternoon. This is Ginny on for Tom Schrader. Thank you for taking our questions, and thank you for all the updates. I had a couple of questions on the OTC program.

嗨，午安。我是 Ginny，代替 Tom Schrader 發言。感謝你們回答我們的問題，也謝謝你們提供所有更新。我有幾個關於 OTC 計畫的問題。

For OTC, you're now pursuing late onset adult and severe pediatric populations, which is a meaningful broadening. But could you help us understand how you're thinking about resource and capital allocation between these two tracks? Is there a scenario where an adult program generates registrational data first and helps the pediatric program? Or do you view these as truly independent developmental paths that need to run in parallel?

就 OTC 而言，你們現在同時推進晚發型成人與重症兒科族群，這是相當有意義的擴展。但能否協助我們理解，你們如何在這兩條路徑之間思考資源與資本配置？是否存在一種情境：成人計畫先產出可用於註冊申請的數據，進而幫助兒科計畫？或者你們認為這兩者是真正獨立的開發路徑，需要並行推進？

And as you think about your end of Phase 2 meeting in the second-half of the year, could you walk us through your best case versus based case outcome and what that looks like from that interaction? Thank you.

另外，當你們思考今年下半年與主管機關進行第二期結束（EOP-2）會議時，能否帶我們了解一下你們所認為的最佳情境與基準情境的結果，以及那次互動可能呈現的樣貌？謝謝。

Okay. A lot there, but I think Alan got it. With respect to pediatric and adult regulatory paths, we can comment on that. And then expectations for the EOP-2 meeting, go ahead.

好的。內容很多，但我想 Alan 都記下來了。關於兒科與成人的法規路徑，我們可以回應。至於對 EOP-2 會議的預期，請繼續。

Just the path for what percentage of the budget is allocated or energies and resources to the pediatric path versus the adult path, is there more prioritization to the pediatrics?

就是在預算配置、投入的精力與資源方面，兒科路徑相對於成人路徑各占多少比例？是否更優先投入兒科？

Well, yeah. So, okay, understood. So rather than getting into granularity on the budgetary likelihood of expenditure, right now, our pediatric program is predicated on the successful completion, sufficient end of Phase 2 data, and a general agreement that we've generated sufficient safety, tolerability, and clinical efficacy data to be able to then go into children.

嗯，是的。好的，了解。與其深入到預算支出可能性的細節層級，目前我們的兒科計畫是以成功完成、並取得足夠的第二期結束數據為前提，且需要在我們已產生足夠的安全性、耐受性與臨床療效數據方面達成整體共識，之後才能進入兒童族群。

Our expectation and hope is that the pediatric opportunity and unmet medical need is the greatest and the one that we feel we need to be spending our greatest attention to once we're given the opportunity to do so.

我們的期待與希望是：兒科的機會與未被滿足的醫療需求最大；一旦我們獲得推進的機會，這也會是我們認為需要投入最多關注的方向。

Our adult program is almost completed. So right now, we're just finishing up enrollment on a small number of patients to complete the grid that Joe was just referring to a moment ago. It's five doses. And then once we complete five doses and have time to analyze the totality of that data and prepare it for our end of Phase 2 meeting, our hope is that we're given the green light to move forward with a pediatric program, and that would, in large, part our focus moving forward.

我們的成人計畫幾乎已完成。所以目前我們只是完成少數病患的收案，以完成 Joe 剛才提到的那個劑量矩陣。一共是五個劑量。一旦完成五個劑量並有時間分析全部數據、並為第二期結束會議準備資料後，我們希望能獲得綠燈推進兒科計畫，而那將在很大程度上成為我們後續的重點。

Great, thank you.

很好，謝謝。

(Operator Instructions) Yale Jen, Laidlaw and Company.

（接線員指示）Yale Jen，Laidlaw and Company。

Good afternoon, and thanks for taking the questions. In terms of the pediatric OTC programs, you mentioned most of those patients need transplantation of the treatment.

午安，謝謝讓我提問。就兒科 OTC 計畫而言，你提到多數這些病患需要接受移植治療。

I just wonder whether you're thinking that the drug currently you're developing was mainly for a stopgap for those patients before they can ultimately get transplantation or this is potentially disease modifying the patient can be treated for a long time without the need for transplantation.

我想請教，你們是否認為目前正在開發的藥物主要是作為這些病患在最終能接受移植前的過渡性治療？還是它可能具有疾病修飾效果，使病患可以長期治療而不需要移植？

Well, first to comment is that the OTC deficiency is definitely a pediatric centric disease. That's usually when it's diagnosed and there is a significant unmet need to prevent the undesired liver transplantation that occurs in these young children. So engaging them prior to the severity getting to that point is the timing we're talking about.

首先要說的是，OTC 缺乏症確實是一個以兒科為主的疾病。通常是在那個時期被診斷出來，而且在這些年幼兒童中，避免不希望發生的肝臟移植存在顯著的未被滿足醫療需求。因此，我們所談的時機，是在病情嚴重到那個程度之前就介入。

But is there any other comments?

還有其他補充嗎？

Yeah, no, I think your question is actually a really good one. Our hope and expectation would be that we're not only forestalling the need for a liver transplant, but we should hopefully be able to keep these children from requiring liver transplants lifelong if we intervene and do so in as pronounced a way as we hope and expect to do as early as possible in the course of their disease.

是的，我認為你的問題其實非常好。我們的希望與預期是：我們不僅能延後肝臟移植的需求；如果我們能在疾病進程中盡可能早期介入，並以我們希望且預期能達到的顯著程度進行治療，那麼我們應該有機會讓這些孩子終其一生都不需要肝臟移植。

Okay, great. That's very helpful and congrats on all the progress.

好的，很好。這非常有幫助，也恭喜你們取得所有進展。

Great. Thank you. Great question.

很好。謝謝。很好的問題。

Thank you. And at this time, there are no further questions in queue. I will now turn the call back to Joe Payne for closing comments.

謝謝。目前問題佇列中已沒有其他提問。我現在把電話交回給 Joe Payne 作結語。

Just thanks, everyone, for participating on the call. We appreciate everyone's time. Please don't hesitate to reach out to our team for any remaining questions. We will always get back to you as soon as we can. Thanks again.

感謝各位參與這通電話會議。我們很感謝大家的時間。若仍有任何問題，請隨時與我們團隊聯繫。我們一定會在可行的情況下盡快回覆。再次感謝。

Thank you. This brings us to the end of today's meeting. We appreciate your time and participation. You may now disconnect.

謝謝。今天的會議到此結束。感謝各位的時間與參與。您現在可以掛線。