Arcturus Therapeutics Holdings Inc (ARCT) 2025 Q3 法說會逐字稿

Good afternoon, everyone. Welcome to the Arcturus Therapeutics third-quarter 2025 earnings call. (Operator Instructions) Also, today's call is being recorded, (Operator Instructions)

大家下午好。歡迎參加 Arcturus Therapeutics 2025 年第三季財報電話會議。（操作員指示）另外，今天的通話將被錄音。（操作說明）

Now, at this time, I'd like to turn things over to Neda Safarzadeh, Vice President, Head of Investor Relations, Public Relations, and Marketing. Please go ahead, ma'am.

現在，我想把發言權交給副總裁兼投資者關係、公共關係和行銷主管內達·薩法扎德。請便，女士。

Thank you, operator. Good afternoon, and welcome to Arcturus Therapeutics' quarterly financial update and pipeline progress call. Today's call will be led by Joe Payne, our President and CEO; and Andy Sassine, our CFO. Dr. Pad Chivukula, CSO and COO, will join them for the Q&A session.

謝謝接線生。下午好，歡迎參加 Arcturus Therapeutics 的季度財務更新和研發管線進度電話會議。今天的電話會議將由我們的總裁兼執行長喬·佩恩和我們的財務長安迪·薩辛主持。首席科學官兼首席營運長帕德·奇武庫拉博士將加入他們的問答環節。

Before we begin, I would like to remind everyone that statements made during this 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. 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 the statements. Please see the forward-looking statement disclaimer in 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. 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.

在開始之前，我想提醒大家，本次電話會議中關於非歷史事實的陳述屬於1995年《私人證券訴訟改革法案》安全港條款所界定的前瞻性陳述。前瞻性陳述並非業績保證。它們涉及已知和未知的風險、不確定性和假設，可能導致實際結果、績效和成就與聲明中明示或暗示的內容有重大差異。請參閱本公司今天稍早發布的新聞稿中的前瞻性聲明免責聲明，以及我們最新的 10-K 表格和隨後向美國證券交易委員會提交的文件中的「風險因素」部分。此外，任何前瞻性陳述僅代表我們截至作出該等陳述之日的觀點。Arcturus明確聲明不承擔更新此類聲明的任何義務。

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

接下來，我將把電話交給喬。

Thank you, Neda. It's good to be with you again, everybody. I will begin today with an update on our ARCT-032 program. This is our messenger RNA therapeutic candidate for cystic fibrosis, or CF. ARCT-032 utilizes Arcturus's LUNAR lipid-mediated aerosolized platform to deliver CFTR messenger RNA to the lungs. Expression of a functional copy of the CFTR mRNA in the lungs of people with CF has the potential to restore CFTR activity and mitigate the downstream effects that cause progressive lung disease.

謝謝你，內達。很高興再次見到大家。今天我將先報告我們的 ARCT-032 計畫的最新進展。這是我們針對囊性纖維化（CF）的信使RNA治療候選藥物。ARCT-032 利用 Arcturus 的 LUNAR 脂質介導氣溶膠平台將 CFTR 信使 RNA 輸送到肺部。在囊性纖維化患者的肺部表達功能性 CFTR mRNA 拷貝有可能恢復 CFTR 活性，並減輕導致進行性肺部疾病的下游效應。

In October, the company announced interim data from its ongoing Phase 2 clinical trial of ARCT-032. Treatment with inhaled 10-milligram doses daily over 28 days in six Class I CF adults was generally safe and well tolerated. A protocol prespecified analysis of high-resolution computed tomography lung scans, or HRCT lung scans, using FDA 501(k)-cleared AI technology revealed reductions in mucus burden in 4 of the 6 Class I CF participants in our second cohort.

10 月，該公司公佈了其正在進行的 ARCT-032 2 期臨床試驗的中期數據。六名 I 類 CF 成年患者每天吸入 10 毫克劑量，持續 28 天接受治療，整體而言安全且耐受性良好。使用 FDA 501(k) 批准的 AI 技術對高解析度電腦斷層掃描肺部掃描 (HRCT) 進行預先規定的分析，結果顯示，我們第二組 6 名 I 類 CF 患者中有 4 名的黏液負荷有所減少。

The ongoing third cohort is enrolling up to six subjects to assess the safety and tolerability of the 15-milligram dose daily over 28 days and the impact on the efficacy endpoints. The company intends to evaluate daily dosing of ARCT-032 over a 12-week duration in up to 20 CF participants. Safety and preliminary efficacy data will be collected in this study, which is planned to begin in the first half of 2026 after the third cohort top-line data is understood.

正在進行的第三組試驗招募了多達六名受試者，以評估每天服用 15 毫克劑量 28 天的安全性和耐受性，以及對療效終點的影響。該公司計劃在最多 20 名 CF 患者中，對 ARCT-032 進行為期 12 週的每日給藥評估。本研究將收集安全性和初步療效數據，計劃在了解第三組主要數據後，於 2026 年上半年開始進行。

Two weeks ago, I, along with our team, had the privilege of attending the North American Cystic Fibrosis Conference in Seattle. It was great to meet with the CF Foundation leadership team and share our enthusiasm for the Class I population based on our encouraging data. I met with the physicians and principal investigators involved in our ongoing clinical trials and was very pleased to hear their anecdotes, positivity, and encouragement. I enjoy meeting with multiple CT scan experts and and felt their passion as they described the present and future importance of HRCT imaging data in lung disease trials.

兩週前，我和我們的團隊有幸參加了在西雅圖舉行的北美囊性纖維化大會。很高興能與 CF 基金會領導團隊會面，並根據我們令人鼓舞的數據，分享我們對 I 類人群的熱情。我與參與我們正在進行的臨床試驗的醫生和主要研究人員會面，很高興聽到他們的軼事、積極態度和鼓勵。我很高興能與多位 CT 掃描專家會面，並感受到了他們在描述 HRCT 影像數據在肺部疾病試驗中當前和未來的重要性時的熱情。

I affirmed my appreciation of the significant unmet medical need represented by Class I CF and other CFTR modulator nonresponders here in the United States. There's an even higher prevalence of people with Class I CF in countries outside the US especially in Europe, India, the Middle East, and Israel. All in all, the conversations with the CF Foundation, people with Class I CF, their physicians, investigators, CT scan experts, and global CF representatives, all reinforced Arcturus' commitment to advance ARCT-032 further into development.

我再次強調，我非常重視美國 I 類 CF 和其他 CFTR 調節劑無反應者所代表的重大未滿足的醫療需求。在美國以外的國家，尤其是歐洲、印度、中東和以色列，I 類囊性纖維化患者的盛行率更高。總而言之，與 CF 基金會、I 類 CF 患者、他們的醫生、研究人員、CT 掃描專家和全球 CF 代表的對話，都強化了 Arcturus 進一步推進 ARCT-032 開發的決心。

The safety and tolerability profile data along with the before and after treatment HRCT scan images showing mucus plug reduction were well received by the CF community. We look forward to collecting additional and potentially meaningful clinical data in 2026 for our CF program.

安全性和耐受性概況數據以及治療前後 HRCT 掃描影像顯示黏液栓減少，受到了囊性纖維化 (CF) 群體的好評。我們期待在 2026 年為我們的 CF 計畫收集更多可能具有重要意義的臨床數據。

Moving on to the ARCT-810 program. This is our messenger RNA therapeutic candidate for ornithine transcarbamylase deficiency or OTC deficiency. With positive interim Phase 2 data in hand, the company is diligently preparing for meetings with regulatory agencies in the first half of 2026 to discuss pivotal trial strategy for both pediatric and adult populations. Understanding what the FDA requires for ARCT-810's path to approval is the next key milestone for this program. We aim to provide more details pertaining to these regulatory alignment meetings in the first half of 2026.

接下來是 ARCT-810 計畫。這是我們針對鳥氨酸轉氨甲酰酶缺乏症或OTC缺乏症的信使RNA治療候選藥物。憑藉積極的二期中期數據，該公司正積極準備在 2026 年上半年與監管機構舉行會議，討論針對兒童和成人人群的關鍵性試驗策略。了解 FDA 對 ARCT-810 獲得批准的要求是該計畫的下一個關鍵里程碑。我們計劃在 2026 年上半年提供有關這些監管協調會議的更多細節。

I will now provide regulatory updates for our partnered COVID-19 vaccine program, also known as KOSTAIVE. Our Japanese partner, Meiji Seika Pharma, had launched the two-dose vial of KOSTAIVE updated for the JN.1 variant XEC in Japan. This is the first time the two-dose vial presentation is being distributed in Japan. Meiji received approval from the Pharmaceuticals and Medical Devices Agency or PMDA in August.

接下來，我將介紹我們合作的 COVID-19 疫苗計畫（也稱為 KOSTAIVE）的最新監管動態。我們的日本合作夥伴明治製果製藥在日本推出了 JN.1 變體 XEC 的 KOSTAIVE 雙劑量小瓶裝。這是雙劑量小瓶包裝首次在日本上市。明治於8月獲得了日本藥品和醫療器材管理局（PMDA）的批准。

Also in August, the company published the Phase 3 manuscript on the immunogenicity and safety of our self-amplifying mRNA COVID-19 vaccine, ARCT-2303. The study shows that ARCT-2303 induces a robust immune response against SARS-CoV-2 and can be co-administered with licensed influenza vaccines in adults with no impact on safety or immunogenicity of either vaccine. The results were published in eClinical medicine.

同樣在 8 月，該公司發表了關於我們自擴增 mRNA COVID-19 疫苗 ARCT-2303 的免疫原性和安全性的 3 期臨床試驗手稿。研究表明，ARCT-2303 可誘導針對 SARS-CoV-2 的強效免疫反應，並且可以與已獲許可的流感疫苗一起用於成人，而不會影響任何一種疫苗的安全性或免疫原性。研究結果發表在《eClinical medicine》期刊。

Moving on to ARCT-2304. This is our next-gen star vaccine candidate for pandemic A/H5N1 influenza virus. This is the program contracted with and funded in part by BARDA. We conducted a Phase 1 study in 132 young adults and 80 older adults. ARCT-2304 induced a humoral immune response after a single dose in all tested dose levels. The administration of a second dose of ARCT-2304 further increased immune responses.

接下來是 ARCT-2304。這是我們針對甲型H5N1流感病毒的下一代明星候選疫苗。這是由生物醫學高級研究與發展局 (BARDA) 承包並部分資助的計畫。我們對 132 名青年和 80 名老年人進行了 1 期研究。ARCT-2304 在所有測試劑量下，單次給藥後即可誘導體液免疫反應。給予第二劑 ARCT-2304 後，免疫反應進一步增強。

ARCT-2304 at dose levels of 1.5, 5, and 12 micrograms induced a hemoglutinin-specific immune response similar to or higher than the MF59-adjuvanted pandemic vaccine in both young and older adults. No safety or tolerability concerns were raised from available data. These data further validate our STARR sa-mRNA platform. The study results support the further development of the self-amplifying mRNA pandemic influenza vaccine candidate.

ARCT-2304 的劑量值為 1.5、5 和 12 微克時，在年輕人和老年人中均誘導了與 MF59 佐劑大流行疫苗相似或更高的血凝素特異性免疫反應。根據現有數據，未發現任何安全性或耐受性方面的問題。這些數據進一步驗證了我們的 STARR sa-mRNA 平台。該研究結果支持進一步開發自擴增 mRNA 大流行性流感疫苗候選物。

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

接下來，我會把電話轉給安迪。

Thank you, Joe, and good afternoon, everyone. The press release issued earlier today includes financial statements for the third quarter of 2025 and provides a summary and analysis of year-over-year performance. Please also reference our most recent Form 10-Q for more details on the financial performance.

謝謝你，喬，大家下午好。今天稍早發布的新聞稿包含了 2025 年第三季的財務報表，並對同比業績進行了總結和分析。有關財務績效的更多詳情，請參閱我們最新的 10-Q 表格。

The KOSTAIVE BLA filing had been delayed indefinitely. Due to the sudden regulatory changes by the FDA, combined with uncertain commercial visibility of KOSTAIVE in the United States, we have decided to reduce additional expenses to extend the runway for the Cystic Fibrosis and OTC programs. The company expects continued support from CSL to commercialize KOSTAIVE in Asia and Europe and will provide additional detail on our year-end call in March.

KOSTAIVE BLA 的申請被無限期推遲。由於 FDA 突然改變監管政策，加上 KOSTAIVE 在美國的商業前景不明朗，我們決定減少額外支出，以延長囊性纖維化和非處方藥計畫的營運時間。該公司期待 CSL 繼續支持 KOSTAIVE 在亞洲和歐洲的商業化，並將在 3 月的年終電話會議上提供更多細節。

Revenues for the three and nine months ended September 30, 2025, was $17.2 million and $74.8 million, respectively, representing a decrease of $24.5 million and $54.7 million compared to the same period in 2024. These declines were primarily driven by reduced revenues from the CSL collaboration, reflecting lower supply agreement activity and lower amortization of the upfront payment as KOSTAIVE became a commercial product. Total operating expenses for the three months ended September 30, 2025 were $33.7 million compared with $52.4 million for the three months ended September 30, 2024. Total operating expenses for the nine months ended September 30, 2025 were $119.8 million compared with $191.8 million in the prior year.

截至 2025 年 9 月 30 日的三個月和九個月期間的收入分別為 1,720 萬美元和 7,480 萬美元，與 2024 年同期相比分別減少了 2,450 萬美元和 5,470 萬美元。這些下降主要是由於與 CSL 合作的收入減少所致，反映出供應協議活動減少以及隨著 KOSTAIVE 成為商業產品，預付款攤提減少。截至 2025 年 9 月 30 日止三個月的總營運支出為 3,370 萬美元，而截至 2024 年 9 月 30 日止三個月的總營運支出為 5,240 萬美元。截至 2025 年 9 月 30 日的九個月，總營運支出為 1.198 億美元，而去年同期為 1.918 億美元。

R&D expenses were $23.3 million for the three months ended September 30, 2025 compared with $39.1 million in the prior year. The decrease was primarily driven by lower manufacturing cost for the COVID, flu, and CF program as well as reduced clinical trial expenses for COVID and Cystic Fibrosis. Lower payroll and employee benefits further contributed to the decrease. R&D expenses were $87.7 million for the nine months ended September 30, 2025, compared with $151.4 million in the prior year. The decrease was primarily driven by lower manufacturing and clinical costs related to the COVID program, reflecting the program's transition from a development program to the commercial phase.

截至 2025 年 9 月 30 日止的三個月內，研發費用為 2,330 萬美元，而去年同期為 3,910 萬美元。下降的主要原因是 COVID、流感和 CF 項目的製造成本降低，以及 COVID 和囊性纖維化臨床試驗費用減少。工資和員工福利的降低進一步促成了這一下降。截至 2025 年 9 月 30 日的九個月，研發費用為 8,770 萬美元，而去年同期為 1.514 億美元。下降的主要原因是與 COVID 項目相關的製造和臨床成本降低，這反映出該項目從研發階段過渡到商業化階段。

Additional decreases were attributable to lower manufacturing costs for the Cystic Fibrosis and flu program. These reductions were partially offset by higher clinical costs for Phase 2 of the Cystic Fibrosis program. Payroll and benefits expenses also decreased primarily due to lower stock-based compensation expense. G&A expenses were $10.4 million and $32.1 million for the three and nine months ended September 30, 2025, compared with $13.3 million and $40.4 million in the comparable period last year.

囊性纖維化和流感項目的製造成本降低，也導致了其他方面的下降。囊性纖維化計畫第二階段較高的臨床成本部分抵消了這些減少。薪資和福利支出也減少，主要原因是股票選擇權費用降低。截至 2025 年 9 月 30 日止的三個月及九個月期間，一般及行政費用分別為 1,040 萬美元及 3,210 萬美元，而去年同期分別為 1,330 萬美元及 4,040 萬美元。

The decrease in both periods were primarily due to reduced share-based compensation expense as well as reduced payroll and benefits. We expect general and administrative expenses to continue to decrease slightly in fiscal year '26.

這兩個時期的下降主要歸因於股權激勵支出減少以及工資和福利支出減少。我們預計 2026 財年一般及行政費用將繼續小幅下降。

For the three months ended September 30, 2025, Arcturus reported a net loss of approximately $13.5 million or $0.49 per diluted share, compared with a net loss of $6.9 million or $0.26 per diluted share in the three months ended September 30, 2024. Cash, cash equivalents, and restricted cash were $237.3 million as of September 30, 2025 and $293.9 million on December 31, 2024. Based on the additional planned cost reductions in Q4 and the delay in the Phase 3 Cystic Fibrosis clinical trial commencement, the cash runway remained extended into 2028. More details regarding our cost reduction and runway will be provided on our year-end call in March.

截至 2025 年 9 月 30 日止的三個月，Arcturus 報告淨虧損約 1,350 萬美元，即每股攤薄虧損 0.49 美元，而截至 2024 年 9 月 30 日止的三個月淨虧損為 690 萬美元，即每股攤薄虧損 0.26 美元。截至 2025 年 9 月 30 日，現金、現金等價物及受限現金為 2.373 億美元；截至 2024 年 12 月 31 日，現金、現金等價物及受限現金為 2.939 億美元。鑑於第四季度計劃進一步削減成本以及 3 期囊性纖維化臨床試驗啟動的延遲，現金流得以維持到 2028 年。我們將在三月的年終電話會議上提供更多關於成本削減和資金周轉情況的詳細資訊。

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

總而言之，公司財務狀況依然穩健，擁有足夠的現金儲備，可以實現兩個治療項目在近期內多個創造價值的里程碑。

I will now pass the call back to Joe.

現在我將把電話轉回給喬。

Thanks, Andy. Arcturus continues to make progress across our mRNA therapeutics and vaccines pipeline. We look forward to initiating the planned 12-week CF study for ARCT-032 in the first half of 2026. And engaging regulatory agencies regarding the pivotal trial designs for ARCT-810.

謝謝你，安迪。Arcturus 在 mRNA 療法和疫苗研發管線方面持續取得進展。我們期待在 2026 年上半年啟動計畫中的 ARCT-032 為期 12 週的 CF 研究。並與監管機構就 ARCT-810 的關鍵試驗設計進行溝通。

With that, let's turn the time over to the operator for questions.

那麼，接下來就交給接線員回答問題吧。

(Operator Instructions) Yasmeen Rahimi, Piper Sandler.

（操作說明）Yasmeen Rahimi，Piper Sandler。

I guess the first question is, given this data, have you been able to do some PK/PD modeling to help us understand the expectations as you are initiating the third dose cohort and what you hope to gain and how we should be thinking about that? That's question one.

我想第一個問題是，根據這些數據，您是否能夠進行一些 PK/PD 建模，以幫助我們了解您在啟動第三劑量組時的預期結果，以及您希望獲得什麼，以及我們應該如何看待這個問題？這是第一個問題。

And then question two is, as you are preparing for the meeting with the agency to discuss your OTC pivotal programs, what are some of the optionalities of base case, best case, both in development for the pediatric population as well as development in the adult population. And thank you so much, and I'll jump back in the queue.

第二個問題是，當您準備與監管機構開會討論您的 OTC 關鍵項目時，在兒科人群和成人人群的開發中，基本情況和最佳情況有哪些選擇？非常感謝，我會重新排隊。

With respect to PK/PD modeling, well, the third cohort, which is being evaluated at a dose level of 15 milligrams is being conducted in a very similar manner to the first two cohorts at 5 and 10 milligrams, respectively. So all of the activities with respect to data collection are going to be in line with the first two cohorts. With respect to the fourth cohort or I guess you would say this planned 12-week safety and preliminary efficacy study. This is an expanded study.

關於 PK/PD 模型，第三組受試者正在接受 15 毫克劑量等級的評估，其評估方式與前兩組受試者分別接受 5 毫克和 10 毫克劑量的評估方式非常相似。因此，所有與資料收集相關的活動都將與前兩批人群保持一致。關於第四組，或者我猜你會說是這項計劃中的為期 12 週的安全性和初步療效研究。這是一項擴展研究。

So in addition from extending the duration of the study from 4 weeks to 12 weeks, we're also increasing the population up to 20, but a large amount of the data that's being collected is very similar to what we're doing in the first three cohorts. There is some noted differences that we're intending to conduct this trial under. First of all, we're going to be adding an extra screening visit which to establish a more stable FEV1 baseline.

因此，除了將研究持續時間從 4 週延長至 12 週外，我們還將人口增加到 20 人，但收集到的大量數據與我們在前三個隊列中所做的非常相似。我們打算根據一些顯著的差異進行這項試驗。首先，我們將增加一次額外的篩檢訪視，以建立更穩定的 FEV1 基線。

We're also going to be, of course, looking at the high-res CT scan before the study, but at 12 weeks this time instead of at 4 weeks. So we'll allow those two additional months to occur before we take an imaging scan. We're also going to be looking at adding questions to the questionnaire that there's what's called an EQ-5D-5L general health questionnaire, where we're going to be looking at mobility and self-care and usual activities, pain and discomfort, anxiety depression. We're going to be adding this general health questionnaire to the standard validated CFQR questionnaire that people are familiar with CF, but with respect to PK and PD markers, it would be very similar to the first three cohorts.

當然，我們也會查看研究之前的高解析度 CT 掃描結果，但這次是在 12 週時進行，而不是 4 週時。所以，我們會再給這兩個月的時間，然後再進行影像掃描。我們還將考慮在問卷中添加一些問題，例如 EQ-5D-5L 一般健康問卷，我們將調查行動能力、自我照顧和日常活動、疼痛和不適、焦慮和憂鬱。我們將把這份一般健康問卷添加到人們熟悉的、經過驗證的標準 CFQR 問卷中，但在 PK 和 PD 標誌物方面，它將與前三個隊列非常相似。

With respect to your second question, you were asking about OTC, we're looking at two separate populations, the adult population and then the more severe disease in children. And these will likely are requiring two separate conversations with regulatory agencies to gain alignment on a pivotal study. The adults will likely be involving glutamine as a biomarker because that's where we captured success already, and we've learned -- we've collected some positive data already in our trials to date with respect to glutamine in adults. With respect to children that are suffering of more severe disease, the focus will be more on pneumonia itself and getting alignment with the FDA on that, and can we do a single-arm study, for example, in children to capture approval? But these sorts of conversations are separate and distinct enough to have separate meetings to address them as our expectation.

關於你的第二個問題，你問的是非處方藥，我們關注的是兩個不同的群體，一個是成年人群體，另一個是患有更嚴重疾病的兒童群體。而這可能需要與監管機構進行兩次單獨的對話，以就一項關鍵研究達成一致。成年人可能會採用麩醯胺酸作為生物標記物，因為我們已經在這方面取得了成功，而且我們已經了解到——到目前為止，我們在試驗中已經收集到了一些關於麩醯胺酸對成年人的積極數據。對於患有更嚴重疾病的兒童，重點將更多地放在肺炎本身以及與 FDA 就此達成一致上，例如，我們能否在兒童中進行單臂研究以獲得批准？但這些類型的對話是獨立且不同的，因此我們預期會單獨召開會議來討論它們。

The best case scenario, of course, is that we gain alignment with both adults and pediatrics, and that would be very exciting for this program to have line of sight in a broader population to get this approved as soon as possible. And any different scenarios would be if one of these were approved to proceed, for example. But anyway, thanks for your question.

當然，最好的情況是我們能夠同時獲得成人和兒科的支持，這將使該計畫能夠覆蓋更廣泛的人群，從而盡快獲得批准，這令人非常興奮。例如，如果其中一項獲得批准，就會出現不同的情況。不過，還是謝謝你的提問。

Myles Minter, William Blair.

邁爾斯·明特，威廉·布萊爾。

This is Jake on for Myles. Just reflecting back on the imaging data you showed for CF. Do you expect that the improvements you see in mucus over time, especially in that 20-week study, will be bronchial- or alveolar-specific as you sort of showed in that initial dataset? And is that what you saw in the mucus burden from the ferret model preclinically?

這是傑克替麥爾斯報道。我只是回顧一下你展示的關於囊性纖維化的影像數據。您是否預期，隨著時間的推移，尤其是在為期 20 週的研究中，黏液的改善情況會像您在最初的資料集中顯示的那樣，具有支氣管特異性或肺泡特異性？你在雪貂模型臨床前研究中觀察到的黏液負荷情況也是如此嗎？

And then just wanted to also check in on cost saves and see if you've updated your guidance as to when you're going to start realizing revenue from that program?

另外，我還想了解成本節約情況，以及你們是否更新了關於何時能從該專案中獲得收益的指導意見？

Okay. So the first question is with respect to mucus plug reduction, one of the key observations that we've observed and is familiar with the field is mucus plugs form in the smaller airways, right? So as you resolve that, you measure smaller changes in airway improvement. FEV on the other hand is mainly a measure of larger airways. So they're complementary, but they do not measure the same thing. And given enough time, we believe that both of these will improve. And so that's one of the purposes of the 12-week study.

好的。所以第一個問題是關於減少黏液栓的，我們觀察到的一個關鍵現象，也是該領域所熟悉的，就是黏液栓形成於較小的氣道中，對吧？因此，在解決這個問題的過程中，你會測量到氣道改善的較小變化。另一方面，FEV 主要衡量的是較大氣道的功能。所以它們是互補的，但它們衡量的並不是同一件事。我們相信，假以時日，這兩方面都會有所改善。所以，這就是這項為期 12 週的研究的目的之一。

Before I move on to the KOSTAIVE commercial question, did I address your question, Jake?

在我回答 KOSTAIVE 廣告問題之前，傑克，我回答了你的問題嗎？

I guess I wanted to know whether you expect those mucus reductions to occur across the entirety of the lung or whether a specific bronchial or specific alveoli are going to be resolved given that you sort of boxed specific bronchials in your presentation, denoting that because potentially LNPs are directed there primarily that that's where you're going to see an effect. I just wanted to know that. And whether you also saw sort of bronchial specific reductions in the lungs of the ferrets when you dosed those.

我想知道，您是否預期整個肺部的粘液減少情況會發生變化，還是只會影響特定的支氣管或肺泡，因為您在演示文稿中用方框標出了特定的支氣管，表明 LNP 可能主要作用於這些支氣管，所以您會在那裡看到效果。我只是想知道這一點。以及，當你給雪貂服用藥物時，是否也觀察到雪貂肺部支氣管特異性減少的情況。

No. Great question. So first of all, with respect to the data that we collected in the images, you do see in the lower register, the lower lobes that they are first to resolve and show a reduction of mucus plugs and that's simply because this is an inhaled therapeutic. We've talked to now several pulmonologists that view this as confirmational that that we see, first, the lower register, the lower lobes being addressed simply because this is an inhaled therapeutic. We expect over time that the effect will continue to improve. And that's one of the primary purposes of the 12-week study is through an extended duration that will continue to address not only the lower lobes, but the upper lobes as well.

不。問得好。首先，就我們在影像中收集的數據而言，你可以看到在下部區域，下葉首先出現，黏液栓減少，這只是因為這是一種吸入療法。我們已經和幾位肺科醫生談過，他們認為這證實了我們所看到的現象，首先是下肺葉的問題，因為這是一種吸入療法。我們預計隨著時間的推移，這種效果會持續改善。這項為期 12 週的研究的主要目的之一，就是透過延長研究時間，不僅繼續研究下葉，也繼續研究上葉。

With respect to your question about ferrets, this is a different lung type entirely. They're not a vertical animal. So gravity is not -- and this was an injected process. This wasn't a traditional inhaled therapeutic like humans experience, so we didn't expect to see a similar dataset, and we didn't do CT scans in these ferrets as well. We analyze the data separately through mucociliary clearance.

關於你提到的雪貂的問題，這是一種完全不同的肺部類型。它們不是垂直生活的動物。所以重力不是——這是一個人為注入的過程。這不是像人類經歷的那樣傳統的吸入療法，所以我們沒有期望看到類似的數據集，我們也沒有對這些雪貂進行 CT 掃描。我們透過黏液纖毛清除功能對資料進行單獨分析。

Now with respect to the second question on KOSTAIVE guidance. Andy, do you want to provide maybe an answer there?

現在來回答關於 KOSTAIVE 指導的第二個問題。安迪，你想提供一些答案嗎？

Yeah. Thank you for the question. Typically, we do not provide guidance with respect to KOSTAIVE commercial revenue. And the last comment that came in press release that came from Meiji, they did order about 1 million doses for the fourth quarter, and that was delivered to them in October, November. So they're in the process of selling those doses in Japan.

是的。謝謝你的提問。通常情況下，我們不提供 KOSTAIVE 商業收入的指導。明治公司在新聞稿中最後一次表示，他們為第四季度訂購了約 100 萬劑疫苗，這些疫苗已於 10 月或 11 月交付給他們。所以他們正在日本銷售這些劑量的疫苗。

We don't really have an update subsequent to that, but probably look for an update sometime at the end of the year call in next March. Hope that helps.

此後我們還沒有確切的更新，但可能會在年底或明年三月收到更新通知。希望對您有幫助。

Seamus Fernandez, Guggenheim.

西莫斯·費爾南德斯，古根漢美術館。

This is Evan Lang on for Seamus. Just two questions on Cystic Fibrosis with the upcoming 15 mg dose. Can you just talk about the metrics that will drive to know your decision reflect 10 or 15 mg in the subsequent Phase 2, whether it's FEV1, CT scan, or both and what specifically you may be looking for? And then with the subsequent 12-week study, curious what you define as success then with longer treatment in terms of either FEV1 or high-res CT as you think about data relative to the interim value shown so far?

這是埃文·朗代替西莫斯報道。關於即將開始的 15 毫克劑量，我只有兩個關於囊性纖維化的問題。您能否談談在後續的 2 期臨床試驗中，哪些指標將決定您選擇 10 毫克還是 15 毫克的劑量？這些指標是 FEV1、CT 掃描，還是兩者都有？您具體會關注哪些方面？在接下來的 12 週研究中，您如何定義更長時間治療的成功？您是根據 FEV1 或高解析度 CT 數據，結合目前為止顯示的期中位數來考慮治療效果的嗎？

Yeah. With respect to the 15-milligram cohort, we want to gain additional confidence in the dose response. We did not see any mucus plug reduction at 5 milligrams, yet we saw four out of fix in the second cohort at 10 milligrams exhibit mucus plug reduction. So one of the things we're looking for at 15 milligrams is, is there a continued or elevated response? And is that a dose response? But the most important dataset that we're collecting from this third cohort is really safety and tolerability. If it's well tolerated, then I think we have our dose that we will select for this 12-week study coming up in the first half of next year.

是的。對於 15 毫克劑量組，我們希望進一步增強對劑量反應的信心。我們沒有看到 5 毫克劑量組的黏液栓減少，但在第二組 10 毫克劑量組中，我們看到 4 例失禁病例出現了​​黏液栓減少。因此，我們觀察 15 毫克劑量時的結果之一是，是否有持續或增強的反應？這是劑量反應關係嗎？但我們從第三批受試者收集的最重要的數據集實際上是安全性和耐受性。如果耐受性良好，那麼我認為我們就能確定明年上半年即將開始的為期 12 週的研究的劑量。

With respect to what we would define as success is if we see continued or further reduction of mucus plugs, and that translates into additional benefits that can be either imaged or or experienced in terms of lung function improvements, and that would be fantastic, given that this is a first-in-line therapy for a considerable unmet medical need in Class I subjects and modulator nonresponders. So anything positive for FEV would be viewed positively if we see an improvement with the extended duration or elevated dosing in this 12-week study with respect to the mucus plug reduction and mucus burden being decreased, that would be also very promising to encourage the Board and our company to advance this into a Phase 3 trial.

我們對成功的定義是，如果看到黏液栓持續或進一步減少，並且轉化為額外的益處，這些益處可以透過影像學檢查或肺功能改善來體現，這將是非常棒的，因為這是針對 I 類患者和調節劑無反應者的巨大未滿足醫療需求的一線療法。因此，如果在這項為期 12 週的研究中，隨著治療時間的延長或劑量的增加，FEV 指標有所改善，並且粘液栓減少和粘液負荷降低，那麼任何對 FEV 指標產生積極影響的結果都將被視為積極信號。這將非常有希望鼓勵董事會和我們公司將此研究推進到 3 期試驗階段。

And if I could ask one follow-up. Just curious in terms of the CT scan and mucus plugs, what commissions you as clinically meaningful? And what in terms of some of the regulatory discussions you've had, especially as an approach to include CT scan as an exploratory end point, what they might view as a potentially approvable endpoint or whether focus would be on FEV1?

如果可以的話，我想問一個後續問題。我只是好奇，關於CT掃描和黏液栓，您認為哪些檢查結果具有臨床意義？那麼，就您進行的一些監管討論而言，特別是關於將 CT 掃描作為探索性終點的方法，他們認為什麼是潛在的可批准終點，或者重點是否會放在 FEV1 上？

Well, we'll be the first company in CF to establish that. That's one of the key tasks at hand here as a group. As we share this data with the FDA, we need to determine what's clinically meaningful. What we know now is that the more optimized mature modulators out there after a year of treatment, you can see near-complete resolution of mucus plugs. And at an interim time point, you'll see not a complete resolution of mucus plugs.

我們將成為CF領域第一家實現此目標的公司。這是我們團隊目前面臨的關鍵任務之一。在與 FDA 分享這些數據時，我們需要確定哪些數據具有臨床意義。我們現在知道，經過一年的治療，使用目前市面上更優化的成熟調節劑後，黏液栓幾乎可以完全消除。在某個階段，你會發現黏液栓還沒完全消退。

Unfortunately, we're the first -- well, unfortunately, we're the first company in therapeutic to evaluate CT scan measurements after only 28 days of treatment. So the fact that we saw some of these subjects responding 30%, 40% mucus reduction after just 28 days is encouraging. But the question you asked is what is meaningful?

遺憾的是，我們是第一家——好吧，很遺憾，我們是第一家在治療僅 28 天後就評估 CT 掃描測量結果的治療公司。因此，我們看到部分受試者在短短 28 天內黏液減少了 30%、40%，令人鼓舞。但你提出的問題是：什麼是有意義的？

I think we're already in that phase of a meaningful reduction. We just now need to extend treatment to see if that translates into other benefits and lung function improvements over an extended term. But the specific number, we're not prepared to share right now, no one is. That is something that we can discuss at a later time with the agency.

我認為我們已經進入了實質減排階段。我們現在需要延長治療時間，看看能否在更長的時間內帶來其他益處和肺功能改善。但具體數字，我們現在不方便透露，誰也不方便透露。這是我們之後可以和相關機構討論的問題。

Whitney Ijem, Canaccord.

Whitney Ijem，Canaccord。

This is Angela on for Whitney. So you're planning to start this 12-week study starting in the first half of next year. Any idea when we should expect to see data from the 15-milligram cohort? And any thoughts on what endpoints you would show for the 15 milligrams?

這裡是安琪拉，替惠特尼報道。所以你們計劃從明年上半年開始這項為期 12 週的研究。請問大概什麼時候能看到15毫克劑量組的數據？對於15毫克劑量，您有什麼終點指標的想法嗎？

Well, for the 15-milligram cohort, if you're referring to the third cohort, that's the 28-day study. It's the same data being collected under the same protocol for the first two cohorts. And that data is expected likely in the first quarter of next year. And as soon as that top-line data is understood, we will be able to quickly then transition to the 12-week study. And focus on that.

嗯，對於 15 毫克劑量組，如果你指的是第三組，那就是為期 28 天的研究。前兩組受試者均依照相同的方案收集相同的數據。預計這些數據將在明年第一季公佈。一旦我們了解了這些初步數據，我們就可以迅速過渡到為期 12 週的研究。專注於此。

There -- but the parameters and the efficacy endpoints and safety and tolerability investigations are all identical to what we did for the first two cohorts for the 15-milligram third cohort. Did I address --

但是，對於 15 毫克劑量的第三組，其參數、療效終點、安全性和耐受性研究都與我們前兩組所做的完全相同。我是否已經談過--

Yeah. Maybe just one quick follow-up. Any chance you would show the analysis of the CT scans for patients who might not have responded and seen the decrease in mucus plugs? Or do you expect it to be similar?

是的。或許只需要一個簡短的後續問題。您能否展示一下那些可能沒有療效但粘液栓減少的患者的CT掃描分析結果？還是你認為情況會類似？

Well, there's going to be a time for us to share the complete data package for the first three cohorts, right? We do have a 5-, 10- and 15-milligram cohort, I'm sure that will be a nice presentation or publication at some point. We haven't determined exactly when, but that would be an appropriate time to to just share all the data we've collected to determine if there's a dose response and provide those details.

嗯，我們會找個時間分享前三組的完整資料包，對吧？我們確實有 5 毫克、10 毫克和 15 毫克劑量組，我相信這在某個時候會是一個很好的報告或出版物。我們還沒有確定具體時間，但那將是分享我們收集的所有數據以確定是否存在劑量反應並提供這些細節的合適時機。

I've already shared on this call already that at 5 milligrams, we did not see any mucus plugs reduction. There was none observed. And at 10 milligrams, we saw four out of six. So the 15-milligram cohort, we'll see if that recapitulates or gets better, and we'll have the opportunity to see if there's a dose response at that time.

我之前在這次電話會議上已經提到過，5毫克的劑量並沒有減少黏液栓。未觀察到任何異常。服用 10 毫克時，我們看到了六個人中的四個。所以，對於 15 毫克劑量組，我們將看看結果是否會重現或改善，屆時我們將有機會觀察是否有劑量反應。

Yanan Zhu, Wells Fargo.

朱亞楠，富國銀行。

This is Kuan on for Yanan. So our question is also around CF. We are wondering, have you seen any data from 15 mg? And if so, any update on the safety? And will you be planning to evaluate any dose higher than that? And I have a quick follow-up.

這是關為亞楠報到。所以我們的問題也跟囊性纖維化有關。我們想知道，您是否見過 15 毫克劑量的相關數據？如果屬實，安全方面有任何最新進展嗎？你們是否計劃評估高於該劑量的任何劑量？我還有一個後續問題。

Yeah. 15 milligram will be the highest dose that we're evaluating. We intend to choose either 10 or 15 milligrams or something in between, perhaps, for the 12-week study in next year. When the 15-milligram cohort data is completed in the first quarter of next year, that's when we'll be able to make that decision. In terms of when we share data around that third cohort, that hasn't been guided. We'll first collect it and then make a determination how and when to share it. Did I address your question?

是的，15毫克將是我們正在評估的最高劑量。我們打算在明年為期 12 週的研究中，選擇 10 毫克或 15 毫克，或介於兩者之間的劑量。等到明年第一季完成 15 毫克劑量組的試驗數據後，我們才能做出決定。至於何時分享第三批人群的數據，目前還沒有明確的指導方針。我們會先收集這些訊息，然後再決定如何以及何時分享這些資訊。我回答你的問題了嗎？

Yes. And I'm wondering, do you need to show a clear correlation between mucus plug reduction and FEV1? I'm wondering hypothetically, for example, only mucus or plug reduction data is positive and FEV1 is not, would that affect how you view the program and how you make (inaudible)

是的。我想知道，是否需要證明黏液栓減少與 FEV1 之間有明確的相關性？我假設一下，例如，如果只有痰液或鼻塞減少的數據呈陽性，而FEV1呈陰性，這是否會影響您對該項目的看法以及您的決策？（聽不清楚）

I had great conversations with a lot of the experts here at the NACFC in Seattle last month. And yes, CT imaging has been a primary endpoint previously. However, that's not our present expectation. The FDA may not yet consider CT imaging as a surrogate endpoint at this time. But I think it's safe to assume that it will be a supportive endpoint for like a Phase 3 or a pivotal trial.

上個月在西雅圖舉行的北美足球教練協會（NACFC）會議上，我與這裡的許多專家進行了很好的交流。是的，CT成像以前一直是主要終點指標。然而，這並非我們目前的預期。目前，FDA可能尚未將CT影像視為替代終點指標。但我認為可以肯定的是，它將成為 3 期臨床試驗或關鍵性試驗的一個支持性終點。

We first have to collect the data from the 12-week study and then share it with the FDA to have that conversation. If the data is convincing, yes, we'll look at primary or a co-primary endpoint that involves CT scan. But the present expectation is that CT imaging will be a supportive endpoint, very similar to what or can be had to go through where they have their primary being FEV, but the support of data played a key role in getting that approved as the first modulator or one of the early modulators.

我們首先需要收集為期 12 週的研究數據，然後將其提交給 FDA 進行討論。如果數據令人信服，是的，我們會考慮 CT 掃描作為主要終點或共同主要終點。但目前的預期是，CT 影像將成為一個輔助終點，與 FEV 的主要終點非常相似，但數據支援在將其批准為第一個調節劑或早期調節劑之一的過程中發揮了關鍵作用。

Yigal Nochomovitz, Citi.

Yigal Nochomovitz，花旗集團。

This is Joohwan Kim on for Yigal. Regarding the extra screening visit that you had mentioned for the 12-week study, can you just provide additional clarity on whether you're planning on averaging the screening business together to get a more reliable baseline? And also, are you planning on just doing the one extra measurement? And I guess, why not multiple?

這裡是 Joohwan Kim 為 Yigal 報告。關於您之前提到的為期 12 週的研究中的額外篩檢訪視，您能否進一步說明一下，您是否計劃將篩檢業務平均起來，以獲得更可靠的基線？另外，您是否只打算進行一次額外的測量？我想，為什麼不多選呢？

Yeah, and why not do multiple? It's a great question. We haven't had that conversation with the FDA yet. But our present thinking around designing the trial is not only increasing the duration from 4 to 12 weeks and increasing the number of participants from 6 to 20, but it's also strengthening the baseline. And whether that's an additional FEV previsit or a second one? And do we average screening and to FEV pretreatments or not, that conversation will be one of the key questions that we'll have with the FDA.

是啊，為什麼不做多個呢？這是一個很好的問題。我們還沒有和FDA進行過這方面的討論。但我們目前對試驗設計的想法不僅是將試驗持續時間從 4 週增加到 12 週，並將參與者人數從 6 人增加到 20 人，而且還加強了基線。是需要額外進行一次 FEV 預檢，還是需要進行第二次 FEV 預檢？至於是否要對篩檢和 FEV 預處理進行平均，這將是我們與 FDA 討論的關鍵問題之一。

Once we have aligned on that, I can provide more clarity. But the present expectation is just an additional pretreatment value that can be averaged and strengthening the baseline twofold.

一旦我們達成共識，我就可以提供更清晰的解釋。但目前的預期只是一個額外的預處理值，可以取平均值，並將基線強度提高一倍。

Got it. And if I could just follow up with one more. I believe you had mentioned previously that the quality of life assessment for the Phase 2 for the CFQ RSS was also variable, and so you have decided not to share that. But I guess, is there a strategy in mind to reduce the variability there, so you could better interpret its meaning implied to the future, or is the EQ-5D-5L questionnaire just less subject to variability?

知道了。如果可以的話，我再補充一點。我相信您之前提到過，CFQ RSS 第二階段的生活品質評估結果也存在差異，因此您決定不分享該結果。但我想，是否有策略來減少其中的變異性，以便更好地解釋其對未來的潛在意義，或者 EQ-5D-5L 問卷本身就不太容易受到變異性的影響？

Yeah. So just to catch everybody up, the validated questionnaire that's used in the modulator space is well validated and quite comprehensive and it addresses multiple organs in the body. Our CFQ-R is truncated and focused on just the lungs because it's an inhaled therapeutic, so there's questions in the pulmonary section. And because of that and for other reasons and because of the smallness of the nature of our of 6 cohorts. The variability is just -- these questionnaires are more powerful and larger Phase III studies, but it's still variable to address that.

是的。為了讓大家了解情況，這裡介紹一下，在調節劑領域使用的經過驗證的問卷調查是經過充分驗證的，內容相當全面，並且涵蓋了身體的多個器官。我們的 CFQ-R 是簡化版，只關注肺部，因為它是吸入式治療藥物，所以肺部部分有一些問題。正因為如此，也因為其他原因，以及我們這 6 個班級規模較小的性質。差異性就在於——這些問卷調查是更有效的、規模更大的 III 期研究，但仍有差異，需要考慮。

In our upcoming 12-week study, we do intend to add additional general health questions, what's called an EQ-5D. And I touched on this earlier, but when we look at mobility and self-care and pain, discomfort, anxiety depression, and this general health questionnaire will be coupled with this truncated CFQ-R that's more validated just to add weight to the questionnaire, and we'll see what we can glean from that. And to what extent we modify it or keep it for the Phase 3 trial will also be helpful in this upcoming 12-week study.

在我們即將進行的為期 12 週的研究中，我們計劃增加一些一般健康問題，即 EQ-5D。我之前也提到過這一點，當我們審視行動能力、自我照顧、疼痛、不適、焦慮和憂鬱時，這份一般健康問卷將與經過更多驗證的簡化版 CFQ-R 相結合，以增加問卷的權重，看看我們能從中獲得什麼資訊。在即將到來的為期 12 週的研究中，我們將在多大程度上修改它或將其保留到 3 期試驗中，也將對我們有所幫助。

Tom Shrader, BTIG.

湯姆·施拉德，BTIG。

I'm wondering in the next CF cohort if there's any interest or thoughts about adding slightly less impacted patients where the lungs might be a little cleaner and delivery might be easier. And then I appreciate you at arm's length on Kostaive. But can you comment, are there ongoing discussions? Or has the FDA kind of made a statement and there's no room to discuss anything?

我想知道在下一批 CF 患者中，是否有人有興趣或考慮加入一些病情較輕的患者，他們的肺部可能更乾淨一些，分娩也可能更容易一些。然後，我會在 Kostaive 上與你保持一定距離地欣賞你。您能否透露一下，目前是否有正在進行的討論？或者說，FDA已經發表了聲明，沒有討論的空間了嗎？

There's definitely room to discuss that they, of course, are interested in this first-in-line therapy for such a huge unmet medical need in the CF space. So there is still flexibility to discuss. With respect to your first question about less impacted individuals, we did -- you'd have to go to our website, but we enabled the cohort patient 5 -- cohort 2, patient 5. This is someone who had more advanced disease and much more numerous plugs and even larger plugs.

當然，他們肯定對這種針對囊性纖維化領域巨大未滿足醫療需求的首選療法很感興趣，這一點值得探討。所以還有討論的空間。關於您提出的第一個問題，即受影響較小的個體，我們已經啟用了隊列 2 中的第 5 位患者（您需要訪問我們的網站）。這位患者的病情更為嚴重，腦栓塞的數量更多，體積也更大。

And we just got considerable positive feedback from the subject even though their mucus plug reduction was only 9%. And because the size of the plugs that were reduced were meaningful, were larger. So we found -- we had just a success, I would call it, with one particular more advanced subject. So the short answer to your question is, no. We're not refining the list of who's going to be getting the drug for this upcoming 12-week study because we found success in less advanced and more advanced disease.

儘管受試者的黏液栓減少量僅為 9%，但我們仍然收到了相當正面的回饋。而且，因為縮小的插頭尺寸更大，所以意義重大。所以我們發現——或者說，我們在一個比較高級的科目上取得了成功。所以，對於你的問題，簡短的回答是：不。由於我們發現該藥物對病情較輕和較重的患者都有效，因此我們不會縮小即將進行的為期 12 週的研究的用藥人群名單。

Yale Jen, Laidlaw & Company.

耶魯‧詹，萊德勞公司。

I apologize, I missed the earlier part of the conversation. Just a quick question about CSL in terms of the -- I understand the initial contract or deal with them, there's sort of four target infectious disease treatments via treatment. So I wonder any progress on those two other than the influenza and COVID. Any comment on that?

抱歉，我錯過了前面那部分對話。關於 CSL，我有個小問題——我了解與他們簽訂的初始合約或協議，他們透過治療針對四種目標傳染病進行治療。所以我想知道除了流感和新冠肺炎之外，其他兩種疾病（流感和新冠肺炎）方面是否有任何進展。對此有何評論？

Yeah, it's a great question. CSL and Seqirus are considering a demerging process, and they've publicly disclosed that. The timing of that is -- it remains uncertain. But if CSL and Seqirus demerge, then Seqirus will be focused on the vaccine enterprise going forward, especially the flu enterprise. So with respect to the future of the program, the collaboration will come through that arm of the company.

是的，這是一個很好的問題。CSL 和 Seqirus 正在考慮分拆，他們已經公開披露了這一點。具體時間—目前尚不確定。但如果 CSL 和 Seqirus 分拆，那麼 Seqirus 今後將專注於疫苗業務，尤其是流感疫苗業務。所以，關於該專案的未來，合作將透過公司的該部門進行。

As of right now, COVID is, of course, still very active. Any guidance on the flu program will come from them going forward and likely the Seqirus branch if they demerge. With respect to any new programs, we have communicated in the past that those are being considered or active in certain degrees. But we haven't disclosed any of those details that they will be the right time and place to do it and it will likely be coinciding with any updates we hear from a CSL-Seqirus demerger.

當然，目前新冠疫情仍然非常活躍。今後有關流感防治計劃的任何指導都將來自他們，如果 Seqirus 分拆出來，也可能來自 Seqirus 分部。關於任何新項目，我們過去曾表示，這些項目正在考慮中或已在一定程度上實施。但我們尚未透露任何細節，何時何地才是合適的時機，而且很可能會與我們從 CSL-Seqirus 分拆中聽到的任何最新消息同時發生。

Lili Nsongo, Leerink.

莉莉·恩松戈，Leerink。

Two questions. First, on the Cystic Fibrosis program. So the program -- the study was initiated in January, about nine patients were dosed by September. You had mentioned initially that the three additional patients for Cohort 3 would be dosed by year-end. How should we think about the enrollment pace? Is 3 patients a quarter what we should expect moving forward? And does that also apply going into the 12-week study?

兩個問題。首先，我們來看囊性纖維化項目。該計畫——這項研究於 1 月啟動，到 9 月已有大約 9 名患者接受了治療。您最初曾提到，第三組新增的三名患者將在年底前接受給藥。我們該如何看待招生速度？我們未來每季應該預期會有 3 位病患嗎？那麼，這是否也適用於為期 12 週的研究呢？

Yeah. We've expanded the third cohort from 3. At our last quarterly call, we indicated that we -- or estimated that we would have three subjects in our third cohort. We've now communicated that that could be expanded up to six, and that would take us into the first quarter of next year. With respect to -- did I address that question first?

是的。我們將第三批學員人數從 3 人增加到 3 人。在上一次季度電話會議上，我們表示——或者說估計——我們的第三批受試者將有三名。我們現在已經宣布，這個數字可能會增加到六個，這將持續到明年第一季。關於這個問題——我是否首先回答了這個問題？

I mean, this wasn't the question, but based on that pattern of having about three patients enrolled per quarter, should we also think about the pace of enrollment for the 20 patients for the 12-week study to be similar?

我的意思是，雖然這不是問題所在，但根據每季招募約三名患者的模式，我們是否也應該考慮以類似的速度招募參加為期 12 週的研究中的 20 名患者？

Yeah. No, we're looking to add a considerable amount of sites in different countries as well to facilitate enrollment for this 12-week study. I alluded to this previously. But when we were at the Seattle conference or at the NACFC, we got to meet with a variety of investigators globally, not just limited to the US. So the percentage and prevalence of Class I and modulator nonresponders in other countries is extraordinary and untapped.

是的。不，我們還計劃在不同國家增加大量站點，以方便參與者參與這項為期 12 週的研究。我之前已經提到過這一點。但是，當我們在西雅圖會議或北美基督教研究大會 (NACFC) 上時，我們有機會與來自世界各地的各種研究人員會面，而不僅限於美國。因此，其他國家 I 類和調節劑無反應者的比例和盛行率非常高，而且尚未充分開發。

So in addition to the dozen or so sites that we have opened here in the US, I believe that we'll be adding additional sites outside of the US. And that will -- is intended to accelerate the enrollment pace to support the end of 20 rather than the end of 6 for this upcoming 12-week study. So the short answer to your question is that we anticipate enrollment rate to increase with these additional sites and additional access to Class I and modulator nonresponders. To what extent that increases, we'll be the first to find out.

因此，除了我們在美國開設的十幾個站點之外，我相信我們還會在美國以外的地方增加更多站點。這樣做是為了加快招募速度，以便支持在即將到來的 12 週研究結束前完成招募，而不是在 6 月底完成。因此，對於您的問題，簡而言之，我們預計隨著這些新增站點的設立以及對 I 類藥物和調節劑無反應患者的更多治療機會，註冊率將會提高。至於成長幅度有多大，我們將第一時間得知。

And is the global expansion and the additional sites? Is that captured in the current cash runway guidance?

全球擴張和新增站點的情況如何？目前的現金流預期是否反映了這一點？

Yes. But Andy, you can confirm that that's captured in the runway guidance, correct?

是的。但是安迪，你能確認一下跑道引導系統中是否包含了這些資訊嗎？

Yeah, that is all captured in the runway guidance. And the good news is that we had produced additional material for the CF clinical trials and consequently, the additional cost of expanding the trial is pretty much de minimis. So we're in very good shape there financially. Thank you.

是的，這些都包含在跑道引導系統中。好消息是，我們已經為 CF 臨床試驗生產了額外的材料，因此，擴大試驗的額外成本幾乎可以忽略不計。所以，我們在那裡的財務狀況非常好。謝謝。

Second question regarding the OTC program. So can you give us an age range in terms of what your pediatric population target would be? Because the data we've seen so far is in 12 and older. And I was wondering what would it take to go to the younger patient? Or would you solely focus on pediatric patients that are 12 to 18?

關於OTC專案的第二個問題。那麼，您能否給出一下您的兒科目標族群的年齡範圍？因為我們目前看到的數據都是針對 12 歲及以上族群的。我想知道要怎麼樣才能接觸到更年輕的病人？或者您會只關注 12 至 18 歲的兒科患者？

That's one of the agenda-related questions that we expect for these Type C type meetings with the regulatory agency. Pertaining to pediatrics is what the cutoff age is. Whether it's 5 years old or 8 years old is going to be determined and finalized as part of that meeting. And then adults as well, is it going to be 12 and above or 16 and above are -- that will be -- that's one of the purposes of these meetings to get aligned with the pivotal trial protocol. And that clarity will be provided in the first half of next year is our anticipation.

這是我們預計在與監管機構舉行的 C 類會議中會提出的議程相關議題之一。兒科領域指的是年齡分界點。是 5 歲還是 8 歲，將在那次會議上確定並最終確定。那麼成年人呢，是 12 歲及以上還是 16 歲及以上——這將是——這些會議的目的之一是為了與關鍵試驗方案保持一致。我們預計明年上半年情況將會明朗。

Do you expect to be able to go into pivotal in pediatric patients without an additional study needed to reach between the dynamic team?

您是否期望無需額外的研究即可在兒科患者中進行關鍵性研究，而無需動態團隊之間的溝通協調？

Well, if we can accomplish that, that would be fantastic. But yes, that's the intent. To what extent we can accomplish that, we'll find out. And all I know is there's a much more considerable unmet medical need in these young, specially X-linked males or boys. And the younger they are, the more severe the disease. And the less the requisite or requirement that we have to track glutamine as a primary driver, like it is in the adults. Adults is likely going to be more closely associated with glutamine as a biomarker.

如果我們能做到這一點，那就太好了。是的，這正是我們的意圖。我們能在多大程度上實現這個目標，我們拭目以待。我只知道，這些年輕的，特別是患有 X 染色體連鎖疾病的男性或男孩，存在著相當大的未滿足的醫療需求。年齡越小，病情越嚴重。因此，我們就不需要像在成年人中那樣，將麩醯胺酸作為主要驅動因素進行追蹤了。成年人可能與麩醯胺酸作為生物標記的關係更為密切。

So there are two separate discussions.

所以這是兩個獨立的討論。

And Mr. Payne, it appears we have no further questions this afternoon. Sir, I'd like to turn the conference back to you for any closing comments.

佩恩先生，看來今天下午我們沒有其他問題了。先生，我想把會議交還給您，請您作總結發言。

Thanks, everyone, for participating on the call. And if there are remaining questions by those that weren't able to pose them, don't hesitate to reach out to our team, and we'll get back to you as soon as we can. Thanks again.

感謝各位參加本次電話會議。如果還有其他問題未能提出，請隨時聯絡我們的團隊，我們會盡快回覆您。再次感謝。

Thank you very much, Mr. Payne. Again, ladies and gentlemen, that will conclude the Arcturus Therapeutics third-quarter earnings conference call. Again, thanks so much for joining us, everyone, and we wish you all a great afternoon. Goodbye.

非常感謝您，佩恩先生。女士們、先生們，Arcturus Therapeutics 第三季財報電話會議到此結束。再次感謝各位的參與，祝大家下午愉快。再見。