Arcturus Therapeutics Holdings Inc (ARCT) 2023 Q4 法說會逐字稿

Greetings, and welcome to Arcturus Therapeutics Fourth Quarter and Full Year 2023 conference call. At this time, all participants are in a listen only mode. A question and answer session will follow the formal presentation. (Operator Instructions) As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Neda Safarzadeh, Vice President, Head of Investor Relations, Public Relations and Marketing. Thank you. You may now begin.

您好，歡迎參加 Arcturus Therapeutics 2023 年第四季和全年電話會議。此時，所有參與者都處於只聽模式。正式演講後將舉行問答環節。（操作員指示）謹此提醒，本次會議正在錄製中。現在我想將會議交給東道主 Neda Safarzadeh，她是副總裁兼投資者關係、公共關係和行銷主管。謝謝。你現在可以開始了。

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 Andrew Sassine, our CFO, Padmanabh Chivukula, our CSO and COO, will join them for the Q&A session. Before we begin, I would like to remind everyone that the 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.

謝謝你，接線生。下午好，歡迎來到 Arcturus Therapeutics 季度財務更新和管道進度電話會議。今天的電話會議將由我們的總裁兼執行長 Joe Payne 主持；我們的財務長 Andrew Sassine、我們的 CSO 兼營運長 Padmanabh Chivukula 將與他們一起參加問答環節。在我們開始之前，我想提醒大家，本次電話會議中就非歷史事實的事項所做的陳述屬於 1995 年《私人證券訴訟改革法案》安全港條款範圍內的前瞻性陳述。

Forward-looking statements are not guarantees of performance and 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 statement 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. In addition, any forward-looking statements represent our views only as of the date such statements are made. I'm curious specifically disclaims any obligation to update such statements and with that. I will now turn the call over to Joe Payne.

前瞻性陳述並非業績的保證，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、業績和成就與陳述中明示或暗示的結果有重大差異，請參閱本公司的前瞻性陳述免責聲明今天早些時候發布的新聞稿，以及我們最新的 10 K 表格和隨後向 SEC 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做出此類陳述之日的觀點。我很好奇，明確否認有任何更新此類聲明的義務。我現在將把電話轉給喬·佩恩。

It's good to be with you again, everybody, and we look forward to providing our updates today on our quarterly investor call. I will begin my remarks with an update on progress regarding our co state COVID-19 vaccine program following favorable clinical results from several coastal studies, including a 16,000 subject efficacy study performed in Vietnam as well as a Phase three COVID-19 booster trial in Japan, Japan's Ministry of Health, Labor and Welfare MHLW granted approval for Costa. Dave, a self-amplifying mRNA COVID-19 vaccine for primary vaccination and booster for adults 18 years and older. This approval marks a historic milestone as the first self-amplifying mRNA product in the world to be registered and we are increasingly confident about the future applications of our now proven innovative STARR self-amplifying messenger RNA vaccine platform.

大家很高興再次與大家見面，我們期待在今天的季度投資者電話會議上提供最新消息。在幾項沿海研究取得良好的臨床結果之後，我將首先介紹我們的州COVID-19 疫苗計劃的最新進展，其中包括在越南進行的16,000 名受試者功效研究以及在日本進行的第三階段COVID -19 加強試驗日本厚生勞動省 MHLW 批准了 Costa。Dave，一種自放大 mRNA COVID-19 疫苗，適用於 18 歲及以上成年人的初級疫苗接種和加強疫苗接種。這項批准標誌著世界上第一個註冊的自擴增 mRNA 產品的歷史性里程碑，我們對現在已經過驗證的創新 STARR 自擴增信使 RNA 疫苗平台的未來應用越來越有信心。

We look forward to expanding our vaccine platform alongside our global exclusive partner CSL and CSL's partner in Japan, Meiji Seika Pharma, Costain Japan approval is further supported by an active controlled Phase three boosters vaccine study conducted in 11 sites in Japan. The study included healthy adults initially immunized with two doses of an mRNA vaccine, whether that was commonality or spike backs and then a third dose of commonality. The study was conducted in partnership with CSL's partner, Meiji Seika Pharma. This is a global health company based in Japan. New analysis at six months post vaccination shows that cause Steve induces a broader and more durable immune response compared to common equity for both the original Wuhan strain and the ARM Akron PA four slash five variant and and an advantage in antibody persistence posting results were achieved with one six.

我們期待與我們的全球獨家合作夥伴CSL 以及CSL 在日本的合作夥伴Meiji Seika Pharma 一起擴大我們的疫苗平台，Costin Japan 的批准得到了在日本11 個地點進行的主動對照三期加強疫苗研究的進一步支持。該研究包括健康成年人，最初接種了兩劑 mRNA 疫苗，無論是通用疫苗還是尖峰疫苗，然後是第三劑通用疫苗。該研究是與 CSL 的合作夥伴 Meiji Seika Pharma 合作進行的。這是一家總部位於日本的全球健康公司。疫苗接種後六個月的新分析表明，與原始武漢菌株和ARM Akron PA 四斜線五變體的普通股相比，史蒂夫引起了更廣泛和更持久的免疫反應，並且在抗體持久性發布結果方面取得了優勢一六。

The dose of commonality based on the totality of clinical data collected to date, Arcturus anticipates that the advantages of self-amplifying mRNA should provide superior protective efficacy against COVID-19 disease caused by future emerging variants of Star COV to the coast. A booster study is ongoing and will continue to collect safety data and assess durability of the immune response and participants up to 12 months post vaccination. We are very pleased to report that Costain remains on track to launch in Japan this year, Meiji Seika Pharma as the party responsible for distributing the vaccine in Japan will be providing updates and further details pertaining to the launch of Dave in official press releases in April, the WHO is expected to announce the updated COVID variant in due course, manufacturing runs and the subsequent distribution of coast. Dave in Japan will follow.

基於迄今為止收集的臨床數據總量，Arcturus 預計，自我擴增 mRNA 的優勢應該能夠對未來由海岸出現的 Star COV 變種引起的 COVID-19 疾病提供卓越的保護功效。一項加強研究正在進行中，並將繼續收集安全數據並評估免疫反應的持久性以及疫苗接種後 12 個月內的參與者。我們非常高興地報告，Costin 仍有望於今年在日本上市，明治精化製藥公司作為負責在日本分銷該疫苗的一方，將在 4 月份的官方新聞稿中提供有關 Dave 上市的最新信息和更多細節預計世界衛生組織將在適當的時候宣布更新的新冠病毒變種、生產運行以及隨後的海岸分佈。日本的戴夫也將緊跟在後。

The commercial case for Costain is becoming clear, a significantly stronger and broader immune responses. Preferred DACIPE. and other regulatory agencies are presently recommending to boosters each year for the approved conventional mRNA vaccines. Thus, it's very apparent that there's a clear need for a more durable once a year. Covid vaccine and Costain has the potential to address this important global health need. Covid is here to stay and the longer lasting cause Dave is also here to stay.

Costain 的商業案例正在變得清晰，其免疫反應明顯更強、更廣泛。優選 DACIPE。和其他監管機構目前每年都會向加強者推薦已批准的傳統 mRNA 疫苗。因此，很明顯，每年一次更耐用的需求是顯而易見的。新冠疫苗和 Costain 有潛力滿足這項重要的全球健康需求。新冠疫情將繼續存在，更持久的事業戴夫也將繼續存在。

So moving on to ARCT. two one three 8 million or flu program. This is our quadrivalent self-amplifying mRNA vaccine candidate for seasonal influenza. I'm pleased to announce that the Company, along with our partner, CSL, initiated a Phase one dose finding study in January 2024, with the intention of assessing the dose response of the investigational vaccine and comparing the safety and immunogenicity with the licensed standard of care. Overall, 132 healthy individuals, which includes 84 younger adults and 48 older adults are planned to be recruited in this Phase one clinical study.

那麼繼續 ARCT。二一三八百萬或流感計畫。這是我們針對季節性流感的四價自擴增 mRNA 候選疫苗。我很高興地宣布，該公司與我們的合作夥伴 CSL 於 2024 年 1 月啟動了第一階段劑量探索研究，旨在評估研究疫苗的劑量反應，並將安全性和免疫原性與許可標準進行比較的照顧。總體而言，該一期臨床研究計畫招募 132 名健康個體，其中包括 84 名年輕人和 48 名老年人。

I'm now excited to announce that Arcturus has initiated new vaccine discovery programs for Lyme disease and gonorrhea. This decision is supported by the clinical and regulatory validation of LUNAR and Star technologies provided by our first regulatory approval. Of course, Dave, our technologies are ideally suited for these infectious disease vaccine opportunities. Our validated vaccine platform is now being applied to seven global infectious diseases, five with our partner, CSL secures and two wholly owned vaccine discovery programs, Lyme disease and gonorrhea. The total estimated global market opportunity for these new vaccine discovery programs exceeds 4 billion.

我現在很高興地宣布 Arcturus 已啟動針對萊姆病和淋病的新疫苗發現計畫。這項決定得到了我們首次監管批准所提供的 LUNAR 和 Star 技術的臨床和監管驗證的支持。當然，戴夫，我們的技術非常適合這些傳染病疫苗機會。我們經過驗證的疫苗平台現已應用於七種全球傳染病，其中五種是與我們的合作夥伴 CSL secures 合作的，還有兩個全資擁有的疫苗發現項目：萊姆病和淋病。這些新疫苗發現計畫的全球市場機會總數估計超過 40 億。

I'll now move on to ARCT. eight 10. Our messenger RNA therapeutic candidate for ornithine transcarbamylase or OTC deficiency. This investigational medicine is designed to functionally replace the deficient or missing OTC. enzyme in the liver, restoring urea cycle activity and preventing metabolic crises that cause neurological damage ARCT. eight 10 could reduce the need for ammonia scavengers and ease for the rigid dietary protein restrictions that OTC patients face today, thus improving the quality of life for those with this disease, our Phase 1b single ascending dose study in the United States has completed enrollment and dosing of all cohorts with 16 patients.

我現在將轉向 ARCT。八 10.我們針對鳥氨酸轉氨甲酰酶或 OTC 缺乏症的信使 RNA 候選治療藥物。該研究藥物旨在功能上取代缺陷或缺失的 OTC。肝臟中的酶，恢復尿素循環活性並預防導致神經損傷的代謝危機 ARCT。 8 10 可以減少對氨清除劑的需求，並緩解OTC 患者當今面臨的嚴格飲食蛋白質限制，從而改善患有這種疾病的人的生活質量，我們在美國的1b 期單劑量遞增研究已完成入組，並且對 16 名患者的所有隊列進行給藥。

The Phase two study in the United Kingdom and Europe is enrolling up to 24 adolescents and adults with OTC deficiency. The ongoing study is evaluating two dose levels and includes up to six biweekly administrations for each participant. The Company expects to share Phase two interim study data by the end of Q2 2024. Moving now to our ARCTO. 32 program ARCTO. 32 is in an inhaled messenger RNA therapeutic candidate for cystic fibrosis. Formulated with Arcturus is LUNAR delivery technology. This investigational medicine is designed to functionally replace the deficient or missing CFTR transporter in the lung and thus restoring the balance of salt and water.

英國和歐洲的第二階段研究招募了多達 24 名患有 OTC 缺乏症的青少年和成年人。正在進行的研究正在評估兩種劑量水平，包括每位參與者每兩週最多給藥六次。公司預計在 2024 年第二季末分享第二階段中期研究數據。現在轉向我們的 ARCTO。 32 程序ARCTO。 32 是一種治療囊性纖維化的吸入式信使 RNA 候選藥物。LUNAR 輸送技術採用 Arcturus 配製而成。該研究藥物旨在功能性替代肺部缺陷或缺失的 CFTR 轉運蛋白，從而恢復鹽和水的平衡。

We have now completed dosing in a Phase one study in New Zealand of 32 healthy subjects across four ascending single dose cohorts. In addition, we have dosed patients in a Phase Ib clinical study in New Zealand. The Phase 1b study is designed to enroll up to eight adults with cystic fibrosis with each participant receiving two administrations of ARCT. or 32. We remain on track to share interim Phase Ib data in Q2 2024. In November 2023 ARCTO. 32 received orphan drug designation from the FDA. That designation provides significant incentives to promote the development of the drug, including the potential for market exclusivity for seven years upon FDA approval, eligibility for tax credits for qualified clinical trials, waiver of Prescription Drug User Fee Act.

我們現已在新西蘭完成了一項第一階段研究的給藥，該研究對 4 個遞增單劑量隊列中的 32 名健康受試者進行了給藥。此外，我們還在新西蘭的 Ib 期臨床研究中對患者進行了給藥。1b 期研究旨在招募最多 8 名患有囊性纖維化的成年人，每位參與者接受兩次 ARCT 治療。或 32。我們仍有望在 2024 年第二季分享 Ib 期中期數據。2023 年 11 月 ARCTO。 32 種藥物獲得 FDA 孤兒藥資格認定。該頭銜為促進該藥物的開發提供了重大激勵措施，包括獲得 FDA 批准後七年市場獨佔權的潛力、合格臨床試驗的稅收抵免資格、處方藥使用者費用法案的豁免。

Application fee and eligibility to receive regulatory guidance from the FDA and the design of an overall drug development plan in February 2020 for ARCTO. 32 received orphan medicinal product designation from the European Commission, which will give Arcturus access to protocol assistance, centralized authorization process fee reductions and 10 years of market exclusivity. And with that, I'll now pass the call to Andrew.

申請費和獲得 FDA 監管指導的資格以及 2020 年 2 月 ARCTO 的整體藥物開發計劃的設計。 32 獲得了歐盟委員會的孤兒藥產品指定，這將使 Arcturus 獲得協議援助、集中授權流程費用減少和 10 年市場獨佔權。現在我將把電話轉給安德魯。

Thank you, Joe, and good afternoon, everyone. The press release issued earlier today includes financial statements for the fourth quarter and fiscal year ending December 31st, 2023, and provides a summary and analysis of year over year financial results. Please also reference our Form 10 K, which will be filed early next week for more details on the financial performance.

謝謝喬，大家下午好。今天稍早發布的新聞稿包括截至 2023 年 12 月 31 日的第四季和財年的財務報表，並提供了同比財務業績的摘要和分析。另請參閱我們將於下週初提交的 10 K 表格，以了解有關財務業績的更多詳細資訊。

Before we begin the financial review, I wanted to give you some highlights from our recent trip to Tokyo where Joe pain patch. You have a cooler and I met with the executive teams from Meiji Seika Pharma and actually our JV partner in our catalyst manufacturing venture. I am happy to report that everyone was very excited about the approval of Costa in Japan and the opportunity to manufacture the world's first self-amplifying mRNA vaccine in Japan under the MAG. brand. All of our partners are working very closely with the Japanese and local government officials to prepare for the launch of Costain in the second half of 2024. We are deeply grateful to the Japanese government for their financial support of Costain and our manufacturing partner R-CALIF.

在我們開始財務審查之前，我想向您介紹我們最近的東京之行的一些亮點，喬的疼痛補丁在那裡。你有一個冷卻器，我會見了明治精化製藥公司的執行團隊，實際上是我們催化劑製造企業的合資夥伴。我很高興地向大家報告，每個人都對 Costa 在日本獲得批准以及有機會在 MAG 的領導下在日本製造世界上第一個自擴增 mRNA 疫苗感到非常興奮。品牌。我們所有的合作夥伴正在與日本和地方政府官員密切合作，為 2024 年下半年推出 Costain 做準備。我們非常感謝日本政府對 Costain 和我們的製造合作夥伴 R-CALIF 的財政支持。

Going forward, official from Meiji Seika Pharma will provide regular updates on the launch of Costain in official press releases this year. I will now provide a quick summary of our financial results. We reported revenues of $169.9 million during 2023 compared to revenues of $206 million during 2022. Revenue recognized from CSL in 2023 was $157.4 million, which slightly increased by $3 million compared to 2022. We also made significant progress with the Barda pandemic flu vaccine agreement that led to an increase in revenue of $8.8 million. The majority of the decrease in FY 23 revenue were driven by the discontinuation of our collaboration agreements with them Biocare and J&J and 2022.

展望未來，明治精果製藥官方將在今年的官方新聞稿中定期提供 Costain 上市的最新資訊。我現在將簡要概述我們的財務表現。我們報告 2023 年的收入為 1.699 億美元，而 2022 年的收入為 2.06 億美元。2023年中超聯賽確認的收入為1.574億美元，較2022年小幅增加300萬美元。我們也在 Barda 大流行流感疫苗協議方面取得了重大進展，收入增加了 880 萬美元。23 財年收入下降的主要原因是我們與 Biocare 和強生的合作協議在 2022 年終止。

In the fourth quarter of 2023, Arcturus achieved $29.2 million in milestones from CSL milestone payments will continue to be used to fund development activity for the LUNAR COVID-19 vaccine and self-amplifying mRNA flu programs with CSL. Total operating expenses for the year ended December 31st, 2023, with $245 million compared with $193.8 million for the year ended December 31st, 2022. For the three months ended December 31st, 2023, operating expenses were $49.1 million compared with $38.8 million for the three months ended December 31st, 2022. I want to highlight that total operating expenses declined by $15.4 million sequentially for the third fiscal quarter of 2023 due to lower manufacturing expenses.

2023 年第四季度，Arcturus 透過 CSL 實現了 2,920 萬美元的里程碑，里程碑付款將繼續用於資助 LUNAR COVID-19 疫苗的開發活動以及與 CSL 的自我放大 mRNA 流感計畫。截至2023年12月31日止年度的總營運支出為2.45億美元，而截至2022年12月31日止年度的營運支出為1.938億美元。截至2023年12月31日止三個月，營運費用為4,910萬美元，截至2022年12月31日止三個月為3,880萬美元。我想強調的是，由於製造費用下降，2023 年第三財季的總營運費用較上季下降了 1,540 萬美元。

Our research and development expenses consist primarily of external manufacturing costs in vivo research studies and clinical trial performed by contract research organization, clinical and regulatory consultants, personnel related expenses, facility related expenses and laboratory supplies related to conducting R&D activities research and development expenses were $192.1 million for the year ended December 31st, 2023, compared to $147.8 million for the year ended December 31st, 2022. The increase in research and development expenses were attributable to our continued efforts to progress the CSL and barter programs as well as our internal OTC and cystic fibrosis program. Additionally, we have increased investments in early-stage and discovery technologies.

我們的研發費用主要包括外部製造成本、合約研究組織進行的體內研究和臨床試驗、臨床和監管顧問、人員相關費用、設施相關費用以及與進行研發活動相關的實驗室用品研發費用為 192.1 美元截至2023年12月31日的年度為1.478億美元，而截至2022年12月31日的年度為1.478億美元。研發費用的增加歸因於我們持續努力推進 CSL 和以物易物項目以及我們的內部 OTC 和囊性纖維化項目。此外，我們也增加了對早期和發現技術的投資。

The company initiated pre-clinical research related to its Lyme disease and gonorrhea vaccine discovery program. Gna expenses were $52.9 million during 2023 compared with $46.1 million in 2022. The increase resulted primarily from personnel expenses due to increased headcount and salaries, increased travel and consulting expenses as well as an increased rent expense associated with the new headquarters facility in San Diego. We anticipate total G&A expenses for 2024, we'll remain consistent with 2023 totals. For the year ended December 31st, 2023, Arcturus reported a net loss of approximately $26.6 million or $1 per diluted share compared with net income of $9.3 million $0.35 per diluted share for the year ended December 31st, 2022.

該公司啟動了與其萊姆病和淋病疫苗發現計劃相關的臨床前研究。2023 年 Gna 支出為 5,290 萬美元，而 2022 年為 4,610 萬美元。這一增長主要是由於員工人數和工資增加、差旅和諮詢費用增加以及與聖地亞哥新總部設施相關的租金費用增加造成的人員費用。我們預計 2024 年的一般管理費用總額將與 2023 年的總金額一致。截至2023年12月31日的年度，Arcturus報告的淨虧損約為2,660萬美元，即稀釋後每股1美元，而截至2022年12月31日的年度淨利潤為930萬美元，稀釋後每股0.35美元。

For the three months ended December 31st, 2023, we reported a net loss of approximately $8.6 million or $0.32 per diluted share compared with a net income of $117.4 million or $4.33 per diluted share for the three months ended December 31st, 2022, prior year quarter included a $200 million upfront payment from our CSL collaboration, cash, cash equivalents and restricted cash were $348.9 million as of December 31st, 2023 and $394 million as of December 31st, 2022. Since the beginning of our deal with CSL in November 2022, we have achieved approximately $396 million in upfront payments and milestones as of December 31st, 2023.

截至2023 年12 月31 日的三個月，我們報告的淨虧損約為860 萬美元或稀釋每股0.32 美元，而截至2022 年12 月31 日的三個月淨利潤為1.174 億美元或稀釋每股4.33 美元（去年同期）包括我們與CSL 合作的2 億美元預付款，截至2023 年12 月31 日，現金、現金等價物和限制性現金為3.489 億美元，截至2022 年12 月31 日為3.94 億美元。自 2022 年 11 月開始與 CSL 達成協議以來，截至 2023 年 12 月 31 日，我們已實現約 3.96 億美元的預付款和里程碑。

We expect to continue to receive future milestone payments from CSL that will support the ongoing development of the COVID and flu programs and three additional vaccine programs by CSL. Finally, I'm happy to report the expected cash runway now extends through the first quarter of 2027 based on the current pipeline and program. I would also like to highlight that total shares outstanding on a fully diluted basis have remained relatively consistent for three years in a row at approximately 26.6 million shares. This demonstrates management's commitment to continually improving shareholder value as we execute our strategic business plan.

我們預計未來將繼續收到 CSL 的里程碑付款，這將支持 CSL 持續開發的新冠病毒和流感計畫以及另外三個疫苗計畫。最後，我很高興地報告，根據當前的管道和計劃，預期的現金跑道現已延伸至 2027 年第一季。我還想強調的是，完全稀釋後的流通股總數連續三年保持相對穩定，約 2,660 萬股。這顯示管理階層在執行策略性業務計畫時致力於不斷提高股東價值。

In summary, we believe the Company remains in a strong financial position. It has the resources to achieve multiple near-term value-creating milestones for the vaccine and therapeutic program. Furthermore, with the Costain product approval in December in Japan. We look forward to beginning to report potential commercial sales in the next few years. I will now pass the call back to Joe.

總而言之，我們相信公司的財務狀況仍然強勁。它擁有資源來實現疫苗和治療計劃的多個近期價值創造里程碑。此外，Costain 產品於 12 月在日本獲得批准。我們期待在未來幾年開始報告潛在的商業銷售。我現在將把電話轉回給喬。

Thanks, Andrew. We continue to make excellent progress, and we are incredibly excited about our first product approval with Costain. This achievement is an important validation of our mRNA technology and delivery platform. With that, let's turn the time over to the operator for questions.

謝謝，安德魯。我們繼續取得出色的進展，我們對於我們的第一個產品獲得 Costain 的批准感到非常興奮。這項成果是對我們的mRNA技術和遞送平台的重要驗證。接下來，我們將時間交給接線員提問。

(Operator Instructions) Evan Wang, Guggenheim Securities, LLC.

（操作員指示）Evan Wang，Guggenheim Securities, LLC。

Great. Thanks for taking the question guys, too for me first, it was encouraging to see the ACA fee recognition on revaccination of elderly last week. I'm wondering if we've seen similar recommendations internationally and additionally, what kind of regulatory feedback you've gotten on, how a much more durable vaccine may be implemented if you could talk both FDA internationally and markets like Japan in Europe and second, and looking forward to some updates in 2Q from OTC and CF as we're getting closer to data. Wondering if you can share how many patients we can expect from each trial? Thanks.

偉大的。感謝大家提出這個問題，首先對我來說也是如此，上週看到 ACA 對老年人重新接種疫苗的費用認可是令人鼓舞的。我想知道我們是否在國際上看到類似的建議，此外，您得到了什麼樣的監管反饋，如果您可以與國際上的FDA 以及日本等歐洲市場和第二個市場進行交談，那麼如何實施更耐用的疫苗，隨著我們越來越接近數據，期待 OTC 和 CF 在第二季度的一些更新。想知道您是否可以分享我們預計每次試驗將有多少患者？謝謝。

It's a seventh of Yes, first time I can address the question about the recent recommendations by ECIP. We're very happy to see that they recommended regular COVID vaccination, especially in the elderly and the fact that they've recommended two boosters annually. We, of course, because we're approved in Japan, we wanted to provide some updated new information to the people on this call that they may not appreciate, but Japan government has also now communicated that starting April 2024, that routine COVID-19 vaccinations for the elderly will be recommended.

這是「是的，我第一次回答有關 ECIP 最近建議的問題」的第七次。我們很高興看到他們建議定期接種新冠疫苗，尤其是老年人，他們建議每年接種兩次加強疫苗。當然，因為我們在日本獲得了批准，所以我們希望在這次電話會議上向人們提供一些他們可能不欣賞的最新信息，但日本政府現在也表示，從2024 年4 月開始，例行的COVID- 19建議老年人接種疫苗。

And if you just go to the MHLW. website, another new update that they recommend twice a year vaccination for the elderly, but also and I'll quote from the at the actual website in Japan that people age 65 and older, those with underlying medical conditions and health care workers. So each of these three sets of people will be vaccinated twice a year. While all of the others will be vaccinated once a year, the vaccinations remain free of charge as well, and that's clearly communicated.

如果你去厚生勞動省。網站上的另一個新更新是，他們建議老年人每年接種兩次疫苗，而且我還要引用日本實際網站上的內容，即 65 歲及以上的人、患有基礎疾病的人和醫護人員。所以這三組人每年都會打兩次疫苗。雖然所有其他疫苗每年都會接種一次，但疫苗接種仍然是免費的，這一點已明確傳達。

So these developments, of course, are very good news for us because we're addressing a need of durability for the field. But also that there's elevated support for the for those the elderly and those with underlying medical conditions and health care workers in Japan and that their vaccinations remain free of charge, which of course, is going to be helpful to us commercially. With respect to Europe, there's been no second vaccination recommendation for the elderly there by the by the European CDC, but that those discussions are ongoing, and we'll be looking for those updates shortly.

當然，這些進展對我們來說是非常好的消息，因為我們正在解決該領域的耐用性需求。而且日本對老年人、有基礎疾病的人和醫護人員的支持增加，而且他們的疫苗接種仍然是免費的，這當然對我們的商業有幫助。就歐洲而言，歐洲疾病預防控制中心尚未針對那裡的老年人提出第二次疫苗接種建議，但這些討論仍在進行中，我們很快就會尋找這些更新。

And now you also asked additional questions about just enrollment processes for the the two therapeutic programs corrective and we remain on track. That's that's something that we want to. We clearly communicate that we're on track to communicate some interim data for Phase Ib in our CF program, and that's recruiting all patients, no placebo in that group, six to eight patients is what we're estimating. And we're still guiding interim data to be shared in the second quarter. So that's a relatively near term milestone. And likewise, we maintain our guidance on the OTC. program for the end of Q2. With respect to specific updates and specific numbers, we haven't provided those details. Thank you for your questions.

現在，您也詢問了有關兩個矯正治療計劃的註冊流程的其他問題，我們仍處於正軌。這就是我們想要的。我們明確表示，我們正在按計劃傳達 CF 項目 Ib 期的一些中期數據，這將招募所有患者，該組中沒有安慰劑，我們估計有 6 到 8 名患者。我們仍在指導第二季度共享中期數據。所以這是一個相對近期的里程碑。同樣，我們維持對場外交易的指導。第二季末的計劃。至於具體的更新和具體數字，我們尚未提供這些細節。謝謝您的提問。

[Joe], Piper Sandler.

[喬]，派珀·桑德勒。

And good afternoon, team. This is Joe on for Yas contract. Taking our questions we have to first would you say is the rate-limiting step for orders in Japan and for cystic fibrosis and RGC? What type of data should we expect the top line and what would you say like the bar for success?

下午好，團隊。這是喬的亞斯合約。在回答我們的問題時，我們首先要回答的是，您認為日本訂單以及囊性纖維化和 RGC 的速率限制步驟是嗎？我們應該期待頂行什麼類型的資料以及您認為成功的標準是什麼？

Sure. I can speak to the data for the top line, the top line data for the therapeutic programs, but the first question, I'll turn the time over to Andy with respect to what's the what's rate limiting on getting orders in Japan, Andy, and I think we articulated earlier in the call that, you know, we had some very positive meeting with all the majors, take a pharma official and executives.

當然。我可以談談頂線數據，治療計劃的頂線數據，但第一個問題，我將把時間交給安迪，關於在日本獲得訂單的速率限制是什麼，安迪，我認為我們早些時候在電話會議中明確表示，我們與所有專業人士（包括製藥公司官員和高階主管）進行了一些非常積極的會議。

And then I think, you know, they're going to be driving the bus here and we'll be announcing in making press releases, you know, as appropriate. So please stay tuned and come in and be patient. That is certainly, you know, the encouragement was kind of articulated by Joe, just now that and this is kind of a recent development that the government is going to continue to financially support from the population over 65 which is about 32 to 36 million people, right?

然後我想，你知道，他們將在這裡開公車，我們將在適當的時候發布新聞稿來宣布。所以請大家繼續關注並耐心等待。當然，你知道，喬剛剛表達了這種鼓勵，這是最近的一項發展，政府將繼續為 65 歲以上人口（約 32 至 3600 萬人）提供財政支持， 正確的？

And that's not including the people that have compromised immune issues and so forth, so or chronic illnesses. So you're looking at, you know that you multiply that by two, somewhere in the vicinity of, you know, 60 plus million dollars potential doses, right? If everyone gets two shots to boosters, right of conventional mRNA. So we're just kind of reiterating what's in the public domain, what's available in MEG. We'll certainly give you more concrete information as soon as they can.

這還不包括患有免疫問題等、慢性疾病的人。所以你看，你知道你將其乘以二，大約在 60 多百萬美元的潛在劑量附近，對嗎？如果每個人都注射兩次加強劑，就傳統的 mRNA 而言。所以我們只是重申公共領域的內容、MEG 中可用的內容。我們一定會盡快向您提供更具體的資訊。

So stay tuned and then pertaining to the top-line data for CF and OTC. for OTC. We're looking for biomarkers to change in these patients, specifically ammonia to be adjusted to at or near normal levels. Many of these patients are on ammonia scavengers. So if that is indeed the case, there's other biomarkers that we can evaluate and measure, including erratic acid in urine and glutamate has another amino acid impacted by the urea cycle. And then OTC. itself can be measured.

因此，請繼續關注 CF 和 OTC 的頂線數據。用於場外交易。我們正在尋找可以改變這些患者的生物標記物，特別是將氨調整至正常或接近正常水平。其中許多患者正在服用氨清除劑。因此，如果情況確實如此，我們還可以評估和測量其他生物標記，包括尿液中不穩定的酸和谷氨酸，還有另一種受尿素循環影響的氨基酸。然後是場外交易。本身是可以測量的。

So plenty of biomarkers to measure in these trials in terms of top line data with respect to the CF program that we're going to be looking primarily at safety for Phase Ib. These are the first time that this therapeutic has been administered as two administrations in actual patients. And so it will be very meaningful for us to establish some sort of track record of safety and tolerability in a spectrum of CF patients anything to add to that pad for other program?

在這些試驗中，根據 CF 項目的頂線數據，需要測量大量生物標記物，因此我們將主要關注 Ib 期的安全性。這是該療法首次在實際患者中分兩次給藥。因此，對我們來說，在一系列囊性纖維化患者中建立某種安全性和耐受性的記錄是非常有意義的，有什麼可以為其他項目添加到該記錄中嗎？

You know, I think for the CF, I think what we're going to be looking at is mainly as a safety of your rights?

你知道，我認為對CF來說，我認為我們要考慮的主要是保障你的權利？

Well, it's going to be looking at various respiratory function to making sure that those that this dose is well tolerated in a patient population. So I think we will be happy to see some of those results. And then with regard to OTC. We just obviously want to reiterate that the Phase Ib that we we talked about was primarily a safety study. So we will be presenting that data at a conference coming up also. So thanks.

嗯，它將關注各種呼吸功能，以確保患者群體對該劑量的耐受性良好。所以我認為我們會很高興看到其中的一些結果。然後關於OTC。我們顯然只是想重申，我們談論的 Ib 期主要是一項安全研究。因此，我們也將在即將召開的會議上展示這些數據。那謝謝啦。

Thank you so much for the detail.

非常感謝你的詳細資料。

Whitney Ijem, Canaccord Genuity.

惠特尼·艾傑姆，Canaccord Genuity。

Hey, guys. Congrats on all the progress. First one from me is on COVID in Japan. I think you stand to benefit from from orders there kind of on two fronts, both from a our revenue sharing perspective as well as our catalyst. So can you help us understand and how those two will flow through your P&L or balance sheet when the orders and the manufacturing do start? So yes, with respect to revenue sharing and any sort of additional financial elements due to the our catalyst joint venture. And Andy, do you want to address those?

大家好。祝賀所有的進展。我的第一篇文章是關於日本的新冠疫情。我認為您將從兩個方面的訂單中受益，無論是從我們的收入分享角度還是從我們的催化劑角度來看。那麼，您能否幫助我們了解當訂單和製造開始時，這兩者將如何流經您的損益表或資產負債表？所以，是的，關於收入分享和由於我們的催化劑合資企業而產生的任何額外財務因素。安迪，你想解決這些問題嗎？

Yes. Certainly, Whitney, thanks for the question. We typically have not provided detailed with respect to revenue sharing opportunity, but if you look at the CSL and Arcturus, you know, 60 40 joint gross profit split and you can tried to extrapolate what would a three headed or three Musketeers type of partnership. Look like. So it'll obviously be very significant and meaningful for us. And we're excited about the partnership to be working with all three people in Japan, especially may decent. They're the number one flu vaccine company in Japan and CSL, who you know, number two in the world. So you're dealing with two very strong commercial powerhouses in their respective categories. So we're kind of fortunate with respect to that end.

是的。當然，惠特尼，謝謝你的提問。我們通常沒有提供有關收入分享機會的詳細信息，但如果你看看 CSL 和 Arcturus，你就會知道，60:40 聯合毛利分成，你可以嘗試推斷三頭或三劍客類型的合作夥伴關係。看起來像。所以這對我們來說顯然是非常重要和有意義的。我們很高興能夠與日本的所有三個人合作，尤其是可能體面的。他們是日本第一大流感疫苗公司，而 CSL，你知道，是世界第二大流感疫苗公司。因此，您正在與各自類別中的兩個非常強大的商業巨頭打交道。因此，我們在這方面是幸運的。

And we're pretty excited. Of course, having it being made in Japan is kind of something that the government and the people in Japan are very proud of and it's going to be under the major brand name. So keep in mind that this is going to be a Japanese vaccine, and that's what I think excites and then the government. And we're very fortunate that they gave us this opportunity and to compare our vaccine to Pfizer night.

我們非常興奮。當然，在日本製造是日本政府和人民感到非常自豪的事情，並且它將以主要品牌的名義生產。因此請記住，這將是一種日本疫苗，我認為這會讓政府感到興奮。我們非常幸運，他們給了我們這個機會，並將我們的疫苗與輝瑞之夜進行比較。

And if we didn't have that opportunity, we would not have this kind of data to share with the world and the fact that they financially supported the factory. So the bet on the right horse, and I think it's going to be an exciting future, and European approval is coming this year, too. So we're highly excited about that too and anticipating it as well.

如果我們沒有這個機會，我們就不會與世界分享此類數據以及他們為工廠提供經濟支持的事實。因此，押注於正確的馬，我認為這將是一個令人興奮的未來，歐洲的批准也將在今年到來。所以我們對此也感到非常興奮並期待它。

So there's a lot on the plate and hopefully that gives you some perspective. But unfortunately, we can't really go into too many details at this point in time, but hopefully soon we'll be able to reveal those.

因此，有很多事情要做，希望這能為您提供一些視角。但不幸的是，我們目前還不能透露太多細節，但希望很快我們就能透露這些細節。

Myles Minter, William Blair.

邁爾斯·明特，威廉·布萊爾。

Hi. Thanks for taking the questions. And how important is that the strain for your COVID vaccine actually gets adapted to expedite a 1.5. I know you have in collaboration with CSL one in a Phase three immunogenicity trial. And I think there was some guidance that maybe we might hear about something in the first quarter. So just want to make sure that that's on track and is that also a gain our guiding factor for the first sale in Japan. Thanks.

你好。感謝您提出問題。重要的是，您的新冠病毒疫苗株實際上已經適應以加快 1.5 的速度。我知道您與 CSL one 合作進行了第三期免疫原性試驗。我認為我們可能會在第一季聽到一些指導。因此，我只想確保一切步入正軌，這是否也是我們在日本首次銷售的指導因素。謝謝。

Yes, thanks for bringing those programs up. There's a lot of there's a considerable amount of late-stage clinical data that's being collected for this platform. I know you touched on a couple of these trials. That one was the Biovail it Phase three trial where we're comparing Biovail and Coast, Dave to Biovail and commonality. And that data is forthcoming soon. So that something that will help us be able to communicate how we perform in a multivalent or by Valence setting to other technologies out there.

是的，感謝您提出這些計劃。該平台正在收集大量後期臨床數據。我知道您談到了其中一些試驗。那是 Biovail it 第三階段試驗，我們正在比較 Biovail 和 Coast、Dave 與 Biovail 以及共性。該數據即將發布。這樣，這將幫助我們能夠將我們在多價或價設定中的表現與其他技術進行交流。

With respect to the monovalent XPB. trial. That one is designed to incorporate the southern hemisphere flu season cycle, and we'll be able to share data for that program later this year as well. So you did ask whether these programs are prerequisite for certain regulatory discussions. The answer is no for Japan and Europe, and we'll find out for the United States, but we are collecting it in any case. And CSL, our partners are are funding these programs just to strengthen the data packages for each of these programs. And Pad, anything to add?

相對於單價 XPB。審判。該計劃旨在納入南半球流感季節週期，我們也將能夠在今年稍後分享該計劃的數據。所以你確實問過這些計劃是否是某些監管討論的先決條件。對於日本和歐洲來說答案是否定的，對於美國我們會找到答案，但無論如何我們都會收集它。CSL，我們的合作夥伴正在資助這些項目，只是為了加強每個項目的資料包。還有 Pad，有什麼要補充的嗎？

Yes, just I'll just add one other thing is that you might be aware the current circulating strain, the it seems to be a Gen one. So So ultimately for the fall fall season, we will be once the platform has been approved, we will update it and be ready to supply whatever circulating strain is needed, correct. The WHO will be coming out with the updated variant announcement next month in April. And subsequent manufacturing runs and distribution work will be forthcoming and messaging guided through official press releases by Meiji.

是的，我要補充的另一件事是，你可能知道目前流行的菌株，它似乎是第一代。因此，最終在秋季，一旦平台獲得批准，我們將對其進行更新，並準備好提供所需的任何循環菌株，正確的。世界衛生組織將於下個月四月發布更新的變種公告。隨後的生產和分銷工作將很快展開，並透過明治官方新聞稿傳遞訊息。

Okay. And then secondly, just on the CF program, I know you mentioned you'd be looking at respiratory function data from a safety perspective. I mean, would you obviously look at FA one from a safety perspective and then have to report that data anyway offers for CF. We are we're collecting on standard eight-well pad money. You address that.

好的。其次，就 CF 計劃而言，我知道您提到您會從安全角度查看呼吸功能資料。我的意思是，您顯然會從安全角度考慮 FA ，然後必須報告為 CF 提供的數據嗎？我們正在收集標準八孔墊錢。你解決這個問題。

Yes, no, we of course, we will we're going to be cutting a lot of the safety signals, then we're going to be looking at a few one in lung clearance index as well. But we again, just to reiterate, you are going to be recruiting relatively relatively stable patients. And there was there could potentially be no patients in volume recorded in the population as well. But this is an all-comers study. So just so you're aware.

是的，不，我們當然會，我們將削減許多安全訊號，然後我們還將關注肺部清除指數中的一些訊號。但我們再次重申，您將招募相對穩定的患者。而且人口中也可能沒有記錄的患者數量。但這是一項面向所有人的研究。所以只是讓你知道。

Helpful. Thanks very much.

有幫助。非常感謝。

Yanan Zhu, Wells Fargo.

朱亞楠，富國銀行。

Well, great. Thanks for taking our questions. I have a couple for Costain and a couple of for the CF program until Steve was wondering how many booster doses were distributed last year and purchased by the Japan government, what percentage of that volume is for the three groups of people that you touched upon earlier on the call? And how would you expect that number to change this year?

嗯，太好了。感謝您回答我們的問題。我為Costain 準備了幾劑，為CF 計劃準備了幾劑，直到史蒂夫想知道去年分發並由日本政府購買了多少加強劑，該劑量中用於您之前提到的三組人的百分比是多少正在通話中？您預計今年這個數字會發生什麼變化？

No, it's a good question. First, of all I can speak to what is readily available in 2020 to over 82 million messenger RNA COVID vaccine boosters were distributed in Japan that number's not tightly understood for 2023, but it was a significant number as you can appreciate for 2024. We now as we touched on just moments ago that the Japanese government is has indicated and communicated to the clear recommendation that the elderly care you get to booster shots a year and the elderly population is 32 to $36 million in Japan. So it's a significant number of people and it was very good to hear that the government of Japan is going to be on providing these vaccinations to the elderly for elderly free of charge.

不，這是一個好問題。首先，我可以說的是，2020 年，日本已分發了超過8,200 萬份信使RNA COVID 疫苗加強劑，這個數字在2023 年還沒有得到嚴格的了解，但在2024 年，這是一個重要的數字，您可以理解。正如我們剛才提到的，日本政府已經表示並傳達了明確的建議，即日本每年獲得加強注射的老年人護理費用和老年人口為 32 至 3600 萬美元。因此，人數相當多，很高興聽到日本政府將免費為老年人提供這些疫苗。

So that speculating what that how that impacts the market is going to be difficult for me to do more appropriate for and analysts on this call to do that, thanks for the information in prior years in Japan were the average booster doses per person under two and in Japan as well known to have a high rate of vaccinations per person, many would say that they have the highest rate of vaccinations for any country in the world, especially relative to US and Europe. So they have a high prevalence for getting vaccinated and the elderly is even higher. So a very high rate of vaccination.

因此，猜測這對市場有何影響對我來說很難做更合適的事情，本次電話會議的分析師也很難做到這一點，感謝日本前幾年提供的信息，即每人2 歲以下和2 歲以下的人的平均加強劑量日本以人均疫苗接種率高而聞名，許多人會說他們的疫苗接種率是世界上最高的，尤其是相對於美國和歐洲。所以他們的疫苗接種率很高，老年人的比例也更高。所以疫苗接種率非常高。

How we project this into 2024, I think it's reasonable to expect a very high percentage of these people will fill out these cards that they receive in the mail setup times to go to the clinic to get their free vaccination. But what number that is I mean it would be inappropriate for me to guide.

我們如何預測到 2024 年，我認為可以合理地預期這些人中很大一部分人會填寫他們在郵件設定時間內收到的這些卡片，前往診所免費接種疫苗。但我的意思是，我不適合指導這個數字。

Sorry, I go My question was the prior recommendation or the default number boosters, a person get per year.

抱歉，我走了 我的問題是之前的推薦或預設數量的助推器，一個人每年獲得的。

Is that and not twice a year with that once last year, doctors don't know what the previous recommendation was. All I can comment on is what's clearly communicated on the MHLW website, which is two boosters annually for everyone over 65 in Japan gone.

是不是一年兩次，去年一次，醫生不知道之前的建議是什麼。我能評論的就是 MHLW 網站上明確傳達的內容，即每年為日本 65 歲以上的每個人提供兩次助推器。

Okay, thank you. And on the CF program, the Phase 1b portion on those patients caught two administrations of ARCTOC. two was wondering what's the interval between those two demonstrations? And also, I think you mentioned on a call that FEV. one lung clearance, these measures will are being collected perhaps mostly for from a safety standpoint. But the question is will you be presenting those data at the readout? Thank you.

好的謝謝。在 CF 計畫中，這些患者的 1b 期部分接受了兩次 ARCTOC 治療。兩個人想知道這兩次示威之間的間隔是多少？而且，我想您在電話會議上提到了 FEV。就肺部清除而言，收集這些措施可能主要是出於安全的角度。但問題是您會在讀數時呈現這些數據嗎？謝謝。

Well, first comment was the the primary purpose of this Phase Ib data is to ascertain safety and tolerability. We will be looking at severe adverse events and also more specifically side effects associated with the lung as this is a CF program, and there's increased sensitivity to lung related side effects and coughing, et cetera. So that's where we're going to be much more focused on in terms of externally communicating our Phase Ib interim data is severe adverse events and more lung centric side effects. And just summarizing the safety and tolerability in a spectrum, a small spectrum of a relatively small group of CF patients.

嗯，第一個評論是 Ib 期數據的主要目的是確定安全性和耐受性。我們將關注嚴重的不良事件，更具體地說，是與肺部相關的副作用，因為這是一個 CF 項目，並且對肺部相關副作用和咳嗽等的敏感性增加。因此，在對外傳達 Ib 期中期數據方面，我們將更加關注嚴重的不良事件和更多以肺部為中心的副作用。只是總結了一個範圍內的安全性和耐受性，一小部分相對較小的 CF 患者群體。

The other parameters are secondary or even exploratory in nature. We're not expecting in a small cohort like this, where many of these people are already on CFTR modulators that will see some efficacy readouts or anything like that. But we definitely will have an opportunity to present that data of the Phase Ib data later this year when we have a better idea which conference of great and the dosing interval that takes the dosing interval, we have not shared publicly.

其他參數是次要的，甚至是探索性的。我們並不期望在這樣一個小群體中，其中許多人已經在使用 CFTR 調節劑，他們會看到一些功效讀數或類似的東西。但我們肯定會有機會在今年稍後展示 Ib 期數據，當時我們對哪次會議有更好的了解以及服用給藥間隔的給藥間隔，我們還沒有公開分享。

This is a competitive environment. We've made it very clear that these are two administrations, their inhaled. We haven't disclosed the dose levels if they're the same are on are different. And how far apart they are. We had considerable learnings from the 32 subjects of data in the four cohorts evaluated in Phase one. So we wanted to and we've applied those learnings to the design of this Phase Ib trial, and we just wanted to keep those cards close to our chest at this time.

這是一個競爭的環境。我們已經非常明確地表明，這是兩屆政府，他們都被吸入了。我們沒有透露劑量水平是否相同或不同。以及他們之間的距離有多遠。我們從第一階段評估的四個隊列的 32 名受試者的數據中獲得了大量的經驗教訓。所以我們想要並且已經將這些知識應用到了 Ib 期試驗的設計中，我們只是想此時將這些卡片放在我們的胸前。

Got it. Thank you.

知道了。謝謝。

Yigal Nochomovitz, Citi.

伊格爾·諾霍莫維茨，花旗銀行。

Hi, this is Alan on for Yigal. Thank you for taking our questions. I have two related to cystic fibrosis. First and the upcoming CF readout? And should we expect a significant further clarify, should we expect any data from the healthy volunteers as though and except long capacity or lung function have you took and by high biopsy to look at the CFTR expression there?

大家好，我是伊格爾的艾倫。感謝您接受我們的提問。我有兩個與囊性纖維化有關的。首先是即將到來的 CF 讀數？我們是否應該期待進一步的重大澄清，我們是否應該期待來自健康志願者的任何數據，除了長容量或肺功能外，您還通過高活組織檢查來觀察那裡的 CFTR 表達？

And also what have you seen so far in the healthy volunteer that's suggesting a better tolerability of this drug versus the prior MRNA studies aside from the yes, the CF readout outcome is simply going to be focused on severe adverse events or any sort of on adverse events associated with the lung, like I just mentioned, I don't think we're going to be sharing any outside data from that with respect to samples being directly taken from the lung pad. You have a comment there.

到目前為止，您在健康志願者中看到的情況表明，與先前的mRNA 研究相比，該藥物具有更好的耐受性，除了是的，CF 讀數結果只是集中於嚴重不良事件或任何類型的不良事件。與肺部相關的事件，就像我剛才提到的那樣，我認為我們不會分享任何與直接從肺墊採集的樣本相關的外部數據。你在那裡有評論。

There's nothing that we're doing, but anything to comment now, again, just to reiterate some of the early, we haven't seen any SAEs or severe AEs associated with Phase one of our Phase Ib to date, and obviously, we're monitoring that closely. And in terms of lung biopsies, we are not currently or we're looking at the actual function in patients. So we're not done with respect to the Phase one data. There is a European CF Conference in June that we're preparing to present.

我們沒有做任何事情，但現在有任何評論，再次重申一下早期的一些，迄今為止，我們還沒有看到任何與我們的 Ib 期第一階段相關的 SAE 或嚴重 AE，顯然，我們'正在密切監視這一點。就肺活檢而言，我們目前還沒有或正在研究患者的實際功能。所以我們還沒有完成第一階段的數據。我們正準備在 6 月召開歐洲 CF 會議。

Okay. Got it. That makes sense. And just one quick follow-up on the OTCD. data that you're going to present and what do you need to see there to make it go?

好的。知道了。這就說得通了。這只是 OTCD 上的一個快速跟進。您要展示的數據以及您需要在那裡看到什麼才能使其順利進行？

No-go, go no-go decision there a go no-go decision for the Phase Ib readout for the OTCD. or into both for the OTC. readout? Sorry. Yes, we'd like to make sure we maintain a safety and tolerability of multiple doses that's going to be of utmost importance because that's one of the challenges that many a bunch of other competitors and people that have tried to do lipid nanoparticle mRNA therapeutics for OTC deficiency have failed in the past due to toxicity. So this is going to be a significant hurdle too, to jump through but that would be the primary objective.

不通過、通過、不通過決定 對於 OTCD 的 Ib 階段讀數，有一個通過或不通過的決定。或兩者都適用於 OTC。讀出？對不起。是的，我們希望確保保持多劑量的安全性和耐受性，這將是最重要的，因為這是許多其他競爭對手和嘗試進行脂質奈米顆粒 mRNA 療法的人們面臨的挑戰之一OTC 缺乏過去因毒性而失敗。因此，這也將是一個需要跨越的重大障礙，但這將是主要目標。

Something that we'd be very encouraged by is to show safety and tolerability of multiple treatments in a spectrum of OTC deficient patients. Having said that do we also want to see some biomarker changes? Absolutely. It is a placebo-controlled trial. So there would be increased confidence in these readouts as long as we have sufficient numbers we would be looking for for that sort of detail as well to give us confidence going to the next step.

我們非常鼓舞的是，在一系列非處方藥缺乏的患者中展示多種治療的安全性和耐受性。話雖如此，我們是否也希望看到一些生物標誌物的變化？絕對地。這是一項安慰劑對照試驗。因此，只要我們有足夠的數據來尋找此類細節，就會對這些讀數更有信心，從而讓我們有信心進行下一步。

Okay, got it. Great. Thank you very much for taking our questions. Thank you.

好，知道了。偉大的。非常感謝您接受我們的提問。謝謝。

Pete Stavropoulos, Cantor Fitzgerald.

皮特·斯塔夫羅普洛斯，康托·菲茨傑拉德。

Hi, Joe and Andy. On. So just had a question about catalysts on can you leverage that facility for other pipeline candidates and perhaps a distribution outside of Japan? And if not already, I don't know if you mentioned it or if I missed it when do you expect the facility to be operational and what will be the manufacturing capacity and if you want to grab that?

嗨，喬和安迪。在。因此，我有一個關於催化劑的問題，您是否可以將該設施用於其他候選管道，甚至可能在日本境外進行分銷？如果還沒有的話，我不知道你是否提到過，或者我是否錯過了，你預計該設施何時投入運營，製造能力是多少，以及你是否想抓住它？

Yes, sure.nThanks, Pete. Yes, we do know we've kind of highlighted the time line for our catalysts in terms of drug substance, you know, they're currently in production right now in getting GMP qualified. So that is pretty exciting and there will be some news coming out of them to update the status of what they're doing.And are they going to be participating, you know, in the orders from Japan you know, for this year. So those all the things you want to listen for carefully and obviously the drug product is going to be online probably either later on this year. Early next year.

是的，當然。謝謝，皮特。是的，我們確實知道我們已經強調了我們的催化劑在原料藥方面的時間表，您知道，它們目前正在生產以獲得 GMP 資格。所以這是非常令人興奮的，他們將發布一些消息來更新他們正在做的事情的狀態。他們是否會參與今年來自日本的訂單。因此，您想要仔細聆聽的所有內容，顯然該藥品可能會在今年稍後上線。明年初。

And then the plasma business should be on within a couple of years. So within 2.5 year, they should be vertically completely integrated. But in the meantime, we can certainly fill the void with our global CDMO partner in terms of Scotland in the United States and Albuferon and rescue farm in Paulinia and in Europe. So we have a really strong core of partners to help us fill the void where you know, until locality is able to get up to speed. Obviously, if they can make up to 1 billion doses.

然後血漿業務應該會在幾年內啟動。所以在2.5年內，它們應該完全垂直整合。但同時，我們當然可以透過我們的全球 CDMO 合作夥伴來填補美國蘇格蘭、保利尼亞和歐洲的 Albuferon 和救援農場的空白。因此，我們擁有非常強大的合作夥伴核心，可以幫助我們填補您所知道的空白，直到當地能夠跟上步伐。顯然，如果他們能生產出10億劑的話。

They CSL and Meiji have certainly a lot of opportunity to determine whether it's going to be and I have a chance to export, you know, the vaccine to other countries. And so that will be a decision that will be made by certainly CSL in major with respect to Japan. Hopefully, that helps if it does.

他們 CSL 和明治當然有很多機會來確定是否會這樣做，而且我有機會將疫苗出口到其他國家。因此，這將是中超聯賽針對日本隊做出的主要決定。如果確實如此，希望這會有所幫助。

Thank you. And so a question on the CF program. So you're having two doses. Just curious on the perspective of how much do those is actually be derisked. And I guess from a safety perspective, the drug. That's one question. And the other one is any learnings from the cystic fibrosis program that you can potentially develop an inhaled vaccine to a respiratory virus, either alone or in partnership with OCSL.

謝謝。還有一個關於CF程序的問題。所以你要服用兩劑。只是好奇這些實際上有多少風險。我想從安全角度來看，藥物。這是一個問題。另一個是從囊性纖維化計畫中獲得的經驗教訓，您可以單獨或與 OCSL 合作開發針對呼吸道病毒的吸入疫苗。

Yes, good follow-on questions there. Pete, with respect to the the you want to address those questions later that, you know, in terms of CF in the safety, what we really want to see is even with the single or two doses, we want to make sure that there is no respiratory side effects like Iraq, coughing, chest discomfort, et cetera, and we also want to look at some secondary safety endpoints like fever for examples, right? So I think we can tell of all those things from just two doses. So we're looking forward to cost cutting that data.

是的，後續問題很好。皮特，關於你想稍後解決這些問題，你知道，就 CF 的安全性而言，我們真正希望看到的是，即使是單劑或兩劑，我們也希望確保沒有呼吸道副作用，如伊拉克、咳嗽、胸部不適等，我們還想看看一些次要安全終點，例如發燒，對嗎？所以我認為我們只需服用兩劑就可以說出所有這些事情。因此，我們期待削減這些數據的成本。

And the reason why this is significant to us in our internal team has been doing inhaled therapeutics for decades. They do have a lot of experience here. And what they've shared with us is that if you do see challenges or problems in toxicology with inhaled therapeutics, it's in the first two administrations. So if we get through this trial successfully, the probability of success for this trial has meaningfully moved, moved up. And so that's why this is important.

這對我們內部團隊來說意義重大，因為我們幾十年來一直在進行吸入療法。他們在這裡確實有很多經驗。他們與我們分享的是，如果您確實看到吸入療法毒理學的挑戰或問題，那是在前兩次給藥中。因此，如果我們成功地通過了這次試驗，那麼這次試驗成功的可能性就會顯著上升。這就是為什麼這很重要。

And in the second part of your question, you know what the data is positive, what will it mean for the platform? I mean, obviously, if the data is positive and we do get proof-of-concept, we will expanding potentially the I'm thinking about other respiratory or other rare diseases or other diseases that need nebulization. But also this platform, of course, can be applied as potentially a vaccine as well.

在你問題的第二部分，你知道哪些數據是正面的，這對平台意味著什麼？我的意思是，顯然，如果數據是積極的並且我們確實得到了概念驗證，我們將有可能擴大我正在考慮的其他呼吸道疾病或其他罕見疾病或其他需要霧化的疾病。當然，這個平台也可以用作潛在的疫苗。

Great, thank you for taking my questions.

太好了，謝謝你回答我的問題。

Thanks, Pete.

謝謝，皮特。

[Thomas Yip] , H.C. Wainwright.

[葉偉雄] , H.C.溫賴特。

Hi, good afternoon, everyone. This is Thomas Yip asking a couple of questions for asked. Thank you for taking the question. So first question regarding coal staple and buy forward. So with the proven Japan and I believe Andy mentioned that have regulatory decisions expected. And from Europe this year, are there any plans by either some, you know, a book from the tourists or from CSL from Asia and the other plans to expand into additional territories?

嗨，大家下午好。這是Thomas Yip 提出的幾個問題。感謝您提出問題。第一個問題是關於煤炭主食和遠期購買。因此，隨著日本的成熟，我相信安迪提到了監管決策的預期。今年，歐洲的一些人是否有任何計劃，你知道，來自遊客的書或來自亞洲的 CSL 以及其他人計劃擴展到其他地區？

Yes, yes. Yes, Europe is we're intending on getting that approved this year and also the United Kingdom shortly thereafter after that, the next big market, of course, is the United States. Csl will be driving that those regulatory efforts, and they'll be providing guidance as to when that's going to be filed and approved. But what we can say at this point is we expect first approvals in Europe and then UK and then the United States.

是的是的。是的，我們打算今年在歐洲獲得批准，不久之後英國也將獲得批准，當然，下一個大市場是美國。Csl 將推動這些監管工作，他們將提供有關何時提交和批准的指導。但目前我們可以說的是，我們預計首先會在歐洲獲得批准，然後是英國，然後是美國。

And is that. Thank you. And then and then perhaps one question or actually two a 10 in OTC. And as we recall in the past, the Phase two study in Europe enrollment was slightly delayed. Can you discussed briefly, you know, how is the study enrolling so far in the Phase two study.

就是這樣。謝謝。然後然後也許是一個問題，或者實際上是兩個 10 的 OTC 問題。正如我們過去所記得的那樣，歐洲的第二階段研究入組略有延遲。您能否簡要討論一下，到目前為止，第二階段研究的招募情況如何。

But yes, how that survey and we provided guidance that we remain on track for the end of Q2, and that's the status of that program with respect to some interim interim data readout is at the end of Q2.

但是，是的，該調查和我們如何提供指導，使我們在第二季末保持正常運行，這就是該計劃在第二季末公佈的一些臨時中期數據的狀態。

Okay. Got it. And then and then perhaps one final question. This one's for Andy on cash runway. And just was there a does it include any projected revenue from a coal state in Japan or now perhaps 1.4 and Europe as well?

好的。知道了。然後也許還有最後一個問題。這是給現金跑道上的安迪的。它是否包括來自日本或現在可能 1.4 以及歐洲煤炭國家的任何預計收入？

Thanks, for asking that question of the guidance for the three year of cash runway at least did not include any revenues from Costain and did not include any commercial milestones from CSL So as soon as you know, we're able to discuss those as well. We'll update the guidance with respect to the cash runway. And so hopefully we will be able to do that soon. But at this point in time, we certainly have a long enough runway to be able to achieve a number of milestones this year, which are very critical to the opportunity to expand the pipeline within the company.

感謝您提出關於三年現金跑道的指導問題，至少不包括 Costain 的任何收入，也不包括 CSL 的任何商業里程碑，所以一旦您知道，我們也可以討論這些問題。我們將更新有關現金跑道的指導。希望我們能夠盡快做到這一點。但目前，我們當然有足夠長的跑道，能夠在今年實現許多里程碑，這對於擴大公司內部管道的機會非常關鍵。

So we're pretty excited and certainly have the resources to be able to address the CDF opportunity in the OTC opportunity. And now we're going to be launching two additional vaccines and hopefully be able to see some progress in that in the next few years. So pretty exciting year with respect to a number of milestones that are going to be forthcoming and hopefully we'll be able to it enhance shareholder value.

因此，我們非常興奮，當然有資源能夠解決 OTC 機會中的 CDF 機會。現在我們將推出另外兩種疫苗，希望在未來幾年內能看到一些進展。對於即將到來的許多里程碑來說，這是非常令人興奮的一年，希望我們能提高股東價值。

Thank you again for taking my questions.

再次感謝您回答我的問題。

Thank you.

謝謝。

Yale Jen, Laidlaw & Company.

耶魯‧詹 (Yale Jen)，萊德勞公司。

Thanks for taking the question. In terms of Japan, our COVID market, is that still mostly government or is that also what it is also a commercial aspect to evolve maybe in this year or in the future? Are you guys seeing, but it's a good question.

感謝您提出問題。就日本而言，我們的新冠病毒市場仍然主要是政府的，還是今年或未來可能會在商業方面發展？你們看到了嗎，但這是個好問題。

Yes, I mean, the good news is that the government has, you know, given kind of the guidance for what they're going to support, right? And so if you look at just the population of the people over 65, that's pretty substantial, 32 to 36 million people, right. And then that doesn't include people that are immunocompromised or would have chronic illnesses right, that certainly are going to be in a position to want to be vaccinated as well.

是的，我的意思是，好消息是政府已經為他們將要支持的項目提供了指導，對嗎？所以如果你只看 65 歲以上的人口，這個數字相當可觀，有 3200 到 3600 萬人，對吧。這還不包括免疫功能低下或患有慢性疾病的人，他們也肯定想接種疫苗。

So when you look at that, you know, that's a pretty significant part of the population at least something in the 30 to 40, maybe 50% of 125 million people. So that's quite substantial, right? And so it we're very excited about the opportunity and it's not trivial in remember, it's going to be a major vaccine made in Japan. So there's a lot you know that I think the government is very proud of and Meiji, very proud of CSL. Certainly, we are excited to be supporting this program and in launching it globally now also. So there's a lot of good news behind it.

所以，當你看到這一點時，你就會知道，這是人口中相當大的一部分，至少是 1.25 億人中的 30 到 40 人，也許是 50%。所以這相當可觀，對吧？因此，我們對這個機會感到非常興奮，記住這不是一件小事，它將成為日本製造的主要疫苗。所以你知道的很多事情我認為政府和明治都為中超感到非常自豪。當然，我們很高興能夠支持該計劃並在全球範圍內啟動它。所以這背後有很多好消息。

In terms of what it's going to be a private pay versus government pay in a major will make all those announcements when the time is right. But, you know, it's something that we're we're not really concerned about at this point.

至於私人薪酬與政府薪酬在重大項目中的區別，將在適當的時候宣布所有這些公告。但是，你知道，我們目前並不真正關心這一點。

And only thing I would add to that is that Meiji has a strong track record with working with the government to help with the subsidized vaccines in the flu space. So they've been doing this for years, and we're working with the ideal partner. I've done this before.

我唯一要補充的是，明治在與政府合作幫助流感領域補貼疫苗方面有著良好的紀錄。他們多年來一直這樣做，而我們正在與理想的合作夥伴合作。我以前做過這個。

All right.

好的。

We've reached the end of the question-and-answer session. I would now like to turn the call back over to Joe Payne for closing comments.

我們的問答環節已經結束了。我現在想將電話轉回喬·佩恩以徵求結束意見。

Yes. Thanks, everyone, for participating on the call. And if there's any remaining questions, don't hesitate as always to reach out to the team. We'll get back to you as soon as we can. All right.

是的。感謝大家參與此次電話會議。如果還有任何疑問，請一如既往地與團隊聯繫。我們會盡快回覆您。好的。

Thanks, everyone.

感謝大家。

This concludes today's conference. You may disconnect your lines at this time, and we thank you for your participation.

今天的會議到此結束。此時您可以斷開線路，我們感謝您的參與。