Arcturus Therapeutics Holdings Inc (ARCT) 2023 Q2 法說會逐字稿

Greetings, and welcome to Arcturus Therapeutics Second Quarter 2023 Earnings Call. (Operator Instructions) As a reminder, this conference is being recorded.

您好，歡迎參加 Arcturus Therapeutics 2023 年第二季財報電話會議。 （操作員指示）謹此提醒，本次會議正在錄製中。

It is now my pleasure to introduce your host, Neda Safarzadeh, Vice President, Head of Investor Relations, Public Relations and Marketing. Please go ahead.

現在我很高興向您介紹主持人 Neda Safarzadeh，她是副總裁、投資者關係、公共關係和行銷主管。請繼續。

Thank you, operator.

謝謝你，接線生。

Good afternoon, and welcome to Arcturus Therapeutics Second Quarter 2023 Financial Update and Pipeline Progress Call. Today's call will be led by Joseph Payne, our President and CEO; and Andy Sassine, our CFO; Dr. Pad Chivukula, our CSO and COO, will join in for the Q&A session.

下午好，歡迎參加 Arcturus Therapeutics 2023 年第二季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 Joseph Payne 主持；和我們的財務長安迪·薩辛 (Andy Sassine)；我們的首席策略長兼營運長 Pad Chivukula 博士將參加問答環節。

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. 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 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.

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。前瞻性陳述不屬於前瞻性陳述。性能保證。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結果、績效和成就有重大差異。請參閱今天稍早發布的公司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 SEC 提交的文件中的風險因素部分。

In addition, any forward-looking statements represent our view only as of the date such statements are made. Arcturus specifically disclaims any obligation to update such statements to reflect further information, events or circumstances.

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。 Arcturus 特別聲明不承擔更新此類聲明以反映更多資訊、事件或情況的義務。

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

現在，我將把電話轉給喬。

Thank you, Neda, and it's good to be with you again, everybody. We look forward to providing our updates today on our quarterly investor call. I will begin my remarks by highlighting our progress with our ARCT-154 COVID-19 vaccine Phase III program.

謝謝你，內達，很高興再次和大家在一起。我們期待今天在季度投資者電話會議上提供最新消息。我將首先強調我們在 ARCT-154 COVID-19 疫苗 III 期計劃方面取得的進展。

We're pleased with the rapid development and regulatory process -- progress recently made with our alliance partner, Meiji Pharma, toward the approval of ARCT-154 by the Japanese regulatory authorities. The ARCT-154 submission is supported by an active controlled Phase III booster vaccine study that was executed during a period when multiple COVID variants were circulating. Initial ARCT-154 Phase III booster study results were released as preprint last month in med archive.

我們對快速的開發和監管流程感到高興——最近與我們的聯盟合作夥伴明治製藥在日本監管機構批准 ARCT-154 方面取得了進展。 ARCT-154 提交得到了一項主動對照 III 期加強疫苗研究的支持，該研究是在多種新冠病毒變種流行期間進行的。 ARCT-154 III 期加強研究的初步結果於上個月在醫學檔案庫中作為預印本發布。

The study achieved its primary endpoint, demonstrating non-inferiority of neutralizing antibody response against the SARS-CoV-2 ancestral strain when compared to Comirnaty. The study also demonstrated superiority of ARCT-154 in neutralizing antibody response against the Omicron BA.4/5 variant as a key secondary endpoint. The results of this trial indicate increased immunogenicity associated with ARCT-154 at 28 days following booster at administration.

該研究達到了其主要終點，證明與 Comirnaty 相比，針對 SARS-CoV-2 祖先株的中和抗體反應並不遜色。該研究還證明了 ARCT-154 在中和針對 Omicron BA.4/5 變異體的抗體反應方面的優越性，作為關鍵的次要終點。該試驗的結果表明，在加強給藥後 28 天，與 ARCT-154 相關的免疫原性增加。

For the ancestral strain, the geometric mean ratio of neutralizing antibodies between ARCT-154 and Comirnaty was 1.43-fold, indicating elevated neutralizing antibodies against the vaccine strain versus the comparator. Based on available Phase III clinical data at the time of interim analysis, ARCT-154 continues to demonstrate a favorable safety and tolerability profile with no additional safety concerns identified.

對於祖先株，ARCT-154 和 Comirnaty 之間的中和抗體幾何平均比率為 1.43 倍，顯示與比較株相比，針對疫苗株的中和抗體有所升高。根據中期分析時可用的 III 期臨床數據，ARCT-154 繼續表現出良好的安全性和耐受性，沒有發現其他安全性問題。

In today's earnings release, we also included new ARCT-154 Phase I/II clinical data, which suggests a durable immune response up to 1 year following booster administration. Notably, neutralizing antibody levels remained greater than tenfold above baseline across a panel of variants, including Omicron. During the 1-year -- and this is during the entire 1-year observation period.

在今天的財報中，我們還納入了新的 ARCT-154 I/II 期臨床數據，該數據表明在加強注射後長達 1 年的持久免疫反應。值得注意的是，包括 Omicron 在內的一組變異體的中和抗體水平仍然高於基線十倍以上。在一年內——這是在整個一年的觀察期內。

In summary, ARCT-154 has shown broad neutralizing capability against multiple variants of concern, and has the potential to offer not only effective but also a longer-lasting immune response that may suggest durable protection against COVID-19. We're very pleased with the ARCT-154 clinical data, and now believe that this next-generation self-amplifying mRNA platform is meaningfully different than conventional, currently-approved mRNA vaccines.

總之，ARCT-154 已表現出針對多種關注變體的廣泛中和能力，並且有可能提供不僅有效而且更持久的免疫反應，這可能表明對 COVID-19 具有持久的保護作用。我們對 ARCT-154 的臨床數據非常滿意，現在相信這種下一代自放大 mRNA 平台與目前批准的傳統 mRNA 疫苗有很大不同。

I will note that the ARCT-154 dose is very much lower. In our head-to-head study, ARCT-154 was dosed at only 5 micrograms. This is an 83.3% lower dose than Comirnaty and at least 90% lower than other approved mRNA vaccines.

我會注意到 ARCT-154 的劑量要低得多。在我們的頭對頭研究中，ARCT-154 的劑量僅為 5 微克。這比 Comirnaty 的劑量低 83.3%，比其他核准的 mRNA 疫苗低至少 90%。

As previously reported, in April, Meiji submitted a new drug application in Japan to support potential initial approval of ARCT-154 as a primary immunization vaccine. And in June, we were pleased to hear that Meiji filed the NDA for the booster and included the relevant data to support that booster application. The review process with the PMDA is ongoing, with Japanese NDA approval being our next targeted milestone. A positive PMDA decision would represent Arcturu's first product approval, a tremendous achievement for our company. And approval or unapproval, along with the promising data that we've collected, is indicative of the broader opportunity for Arcturus' mRNA technology platform.

正如先前報導的那樣，4月份，明治在日本提交了一份新藥申請，以支持 ARCT-154 作為初級免疫疫苗的潛在初步批准。六月，我們很高興聽到明治提交了加強劑的新藥申請，並包含了支持加強劑申請的相關數據。 PMDA 的審查流程正在進行中，日本 NDA 的批准將是我們的下一個目標里程碑。 PMDA 的積極決定將代表 Arcturu 的第一個產品獲得批准，這對我們公司來說是一項巨大的成就。批准或不批准，以及我們收集到的有希望的數據，都表明 Arcturus 的 mRNA 技術平台有更廣泛的機會。

I'll now move on to provide an update on ARCT-810. This is our messenger RNA therapeutic candidate for ornithine transcarbamylase, or OTC deficiency. This investigational medicine is designed to functionally replace the deficient OTC enzyme in the liver and thereby restore urea cycle activity and prevent metabolic crises that cause neurological damage. ARCT-810 could potentially reduce the need for ammonia scavengers and ease the rigid dietary protein restrictions that OTC patients face today, thus improving quality of life for those living with this disease.

我現在將繼續提供 ARCT-810 的更新。這是我們針對鳥氨酸轉氨甲酰酶或 OTC 缺乏症的信使 RNA 治療候選藥物。該研究藥物旨在功能性替代肝臟中缺乏的 OTC 酶，從而恢復尿素循環活性並預防導致神經損傷的代謝危機。 ARCT-810 可能會減少對氨清除劑的需求，並緩解非處方藥患者目前面臨的嚴格的飲食蛋白質限制，從而提高患有這種疾病的人的生活品質。

In June, we announced that the FDA had granted ARCT-810 with fast track designation. The company has also recently received Rare Pediatric Disease designation from the FDA for ARCT-810. Rare Pediatric Disease designation is designed to recognize those rare diseases in children in which serious or life-threatening manifestations primarily affecting patients from birth to 18 years of age. Now due to this designation, if ARCT-810 achieves approval for a pediatric indication, Arcturus will receive a voucher for priority review of a subsequent marketing application for a different product.

6 月，我們宣布 FDA 已授予 ARCT-810 快速通道資格。該公司最近還獲得 FDA 授予的 ARCT-810 罕見兒科疾病資格。罕見兒科疾病頭銜旨在識別那些兒童罕見疾病，這些疾病的嚴重或危及生命的表現主要影響從出生到 18 歲的患者。現在，由於此指定，如果 ARCT-810 獲得兒科適應症的批准，Arcturus 將收到一張憑證，用於優先審查不同產品的後續行銷申請。

ARCT-810 is currently being evaluated in 2 ongoing clinical studies in patients, a Phase Ib study in adults and a multi-dose Phase II study in adolescents and adults with OTC deficiency. The Phase Ib single-ascending dose study is being conducted in the United States and has completed dosing of all planned cohorts in a total of 16 subjects. The ARCT-810 Phase II study is being conducted in the United Kingdom and Europe, and plans to enroll up to 24 adolescents and adults with OTC deficiency. The ongoing study is evaluating 2 dose levels and includes up to 6 biweekly administrations for each participant. We expect to share interim data on biological activity from a subset of patients in the coming months.

ARCT-810 目前正在兩項正在進行的患者臨床研究中進行評估，一項是針對成人的 Ib 期研究，另一項是針對患有 OTC 缺乏的青少年和成人的多劑量 II 期研究。 Ib期單次劑量遞增研究正在美國進行，並已完成對總共16名受試者的所有計劃隊列的給藥。 ARCT-810 II 期研究正在英國和歐洲進行，計劃招募多達 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 2 個劑量水平，每位參與者每兩週最多接受 6 次給藥。我們預計在未來幾個月內分享部分患者生物活性的臨時數據。

Now I'll move on to ARCT-032. This is our inhaled messenger RNA therapeutic for cystic fibrosis. This program is designed to express fully functional CFTR protein in the lungs of individuals with CF, utilizing our LUNAR delivery technology that has been highly optimized for inhaled delivery to the lungs. Our approach is agnostic to the underlying mutations associated with the disease, and as a result, this program could provide clinical benefit across a wide range of those living with CF, including those that are not well served by currently-approved CFTR modulators.

現在我將繼續討論 ARCT-032。這是我們用於治療囊性纖維化的吸入式信使 RNA 療法。該計劃旨在利用我們針對吸入輸送至肺部進行了高度優化的 LUNAR 輸送技術，在 CF 患者的肺部表達功能齊全的 CFTR 蛋白。我們的方法不知道與該疾病相關的潛在突變，因此，該計劃可以為廣泛的 CF 患者提供臨床益處，包括目前批准的 CFTR 調節劑無法很好治療的患者。

In June, at the European CF Society Conference in Vienna, in collaboration with the University of Alabama Birmingham lab, we reported promising data demonstrating that ARCT-032 fully restore CFTR expression and function in vitro in bronchial epithelial cells from CF donors. In the past, improvement in chloride transport in these human bronchial epithelial cells treated with CFTR modulators has been associated with improved clinical outcomes.

6 月，在維也納舉行的歐洲CF 協會會議上，我們與阿拉巴馬大學伯明罕分校實驗室合作，報告了有希望的數據，表明ARCT-032 在體外完全恢復CF 供體支氣管上皮細胞中的CFTR 表達和功能。過去，使用 CFTR 調節劑處理的人類支氣管上皮細胞中氯離子轉運的改善與臨床結果的改善有關。

The ARCT-032 clinical development program continues to advance according to plan. We're pleased to report today the successful completion of dosing in our Phase I study. The study includes 32 healthy participants, including 8 subjects in each of 4 dose cohorts being tested. We look forward to reporting interim safety and tolerability study results later this year.

ARCT-032臨床開發項目繼續按計畫推進。今天，我們很高興地報告我們的第一階段研究已成功完成給藥。研究包括 32 名健康參與者，其中 4 個劑量組各有 8 名受試者進行測試。我們期待在今年稍後報告中期安全性和耐受性研究結果。

We received regulatory approval of a protocol amendment to allow the transition to a Phase Ib clinical study of ARCT-032 in up to 8 cystic fibrosis patients. The study will be conducted in New Zealand and continuing to advance this important investigational medicine. Our strategic collaboration with CSL Seqirus, this is Arcturus' exclusive global licensee, is focused on the development and commercialization of next-generation mRNA vaccines and continues to make strong progress. Our LUNAR-FLU program, for example, continues to progress with funding and operational support from CSL Seqirus. LUNAR-FLU utilizes Arcturus' validated next-generation STARR mRNA platform.

我們獲得了監管部門對一項方案修正案的批准，允許在最多 8 名囊性纖維化患者中過渡到 ARCT-032 的 Ib 期臨床研究。該研究將在新西蘭進行，並繼續推進這項重要的研究醫學。我們與 Arcturus 的全球獨家授權商 CSL Seqirus 進行策略合作，專注於下一代 mRNA 疫苗的開發和商業化，並持續取得強勁進展。例如，我們的 LUNAR-FLU 計劃在 CSL Seqirus 的資助和營運支援下繼續取得進展。 LUNAR-FLU 利用 Arcturus 經過驗證的下一代 STARR mRNA 平台。

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

現在我將把電話轉給安迪。

Thank you, Joe, and good afternoon, everyone.

謝謝喬，大家下午好。

The press release issued earlier today includes financial statements for the second quarter and 6 months ended June 2023, and provides a summary and analysis of year-over-year financial results. Please also reference our most recent Form 10-Q for more details on the financial performance.

今天稍早發布的新聞稿包括截至 2023 年 6 月的第二季和 6 個月的財務報表，並提供了同比財務表現的摘要和分析。另請參閱我們最新的 10-Q 表，以了解有關財務業績的更多詳細資訊。

We're very pleased with the ARCT-154 new drug application to the PMDA in Japan, and we believe that this product could represent an improved vaccine option for patients as well as an important source of potential future revenues for our organization. Furthermore, the development and manufacturing plan supporting ARCT-154 was carried out in a financially disciplined and efficient manner.

我們對 ARCT-154 新藥向日本 PMDA 的申請感到非常高興，我們相信該產品可以代表患者改進的疫苗選擇，也是我們組織未來潛在收入的重要來源。此外，支援 ARCT-154 的開發和製造計劃以財務上嚴格、高效的方式進行。

I will remind you that the Phase III Japanese booster study, as well as product manufacturing related to this collaboration, are being funded by Meiji Seika Pharma and the Japanese government. Also, in April, Meiji Seika Pharma entered into an agreement with CSL Seqirus, whereby Meiji will be responsible for the regulatory approval, marketing, distribution and sales of ARCT-154 in Japan, as well as coordinating manufacturing of COVID vaccine products with our catalyst for the Japanese market.

我想提醒您的是，日本 III 期加強研究以及與本次合作相關的產品製造均由明治精化製藥公司和日本政府資助。此外，今年 4 月，Meiji Seika Pharma 與 CSL Seqirus 簽訂了一項協議，根據該協議，Meiji 將負責 ARCT-154 在日本的監管審批、行銷、分銷和銷售，並協調使用我們的催化劑生產新冠疫苗產品面向日本市場。

We're thrilled to announce the completion of a state-of-the-art mRNA drug substance manufacturing facility in Japan with our partner, ARCALIS. A team of delegates from Arcturus led by our senior executives and scientific team attended a grand opening ceremony of the cutting-edge cGMP facility in Tokyo, Japan this past week. The ceremony was a celebration of collaboration and partnership as Arcturus joined forces with Japanese health care leaders and senior government officials to inaugurate the first mRNA manufacturing facility in Japan.

我們很高興地宣布與我們的合作夥伴 ARCALIS 在日本建成了最先進的 mRNA 藥物生產設施。上週，由我們的高階主管和科學團隊帶領的 Arcturus 代表團隊參加了在日本東京舉行的尖端 cGMP 設施的盛大開幕儀式。這場儀式是對合作與夥伴關係的慶祝，Arcturus 與日本醫療保健領導人和高級政府官員聯手為日本第一家 mRNA 製造工廠揭幕。

Located in a strategic hub for biomedical research and development, ARCALIS is poised to become a key player in the global mRNA drug manufacturing landscape. ARCALIS's new plant meets current good manufacturing practice and is equipped with the world's most advanced manufacturing control and quality control system to efficiently manufacture high-quality substance for mRNA pharmaceuticals.

ARCALIS 位於生物醫學研究和開發的策略中心，預計將成為全球 mRNA 藥物製造的關鍵參與者。 ARCALIS的新工廠符合目前的良好生產規範，並配備了世界上最先進的生產控制和品質控制系統，可高效生產高品質的mRNA藥物物質。

In April 2023, we received an advanced payment of $23.6 million for the manufacturing and supply of ARCT-154 booster vaccines from CSL. The advanced payment is for specified manufacturing runs of ARCT-154, which includes the drug substance as well as the reservation fees and related manufacturing requirements.

2023年4月，我們收到了CSL預付款2360萬美元，用於生產和供應ARCT-154加強疫苗。預付款用於 ARCT-154 的指定生產運行，其中包括原料藥以及預訂費和相關生產要求。

As Joe mentioned, the LUNAR-FLU program continued to progress with funding and operational support from CSL, and additional updates will be provided soon.

正如 Joe 所提到的，LUNAR-FLU 計劃在 CSL 的資金和營運支援下繼續取得進展，並將很快提供更多更新。

I will now provide a summary of our financial results for the second quarter of 2023.

我現在將總結 2023 年第二季的財務表現。

Our primary source of revenues were from license fees, consulting and related technology transfer fees, reservation fees and collective -- collaborative payments received from research and development arrangements with pharmaceutical and biotechnology partners. For the 3 months ended June 30, 2023, we reported revenues of $10.5 million compared with $27.1 million for the 3 months ended June 30, 2022. The decrease was primarily attributable to a decrease in revenues of $12.7 million related to the termination of the agreement with Vinbiocare and a decrease in revenue of $12.5 million related to the agreement with the Israeli Ministry of Health. The decrease was primarily offset by an increase in revenue of $8.6 million related to the collaboration agreement with CSL and the grant agreement with BARDA, which were both executed in the second half of 2020.

我們的主要收入來源是許可費、諮詢和相關技術轉移費、保留費以及與製藥和生物技術合作夥伴的研發安排中收到的集體合作付款。截至2023年6月30日的三個月，我們報告的收入為1,050萬美元，而截至2022年6月30日的三個月為2,710萬美元。收入減少的主要原因是與協議終止相關的收入減少1,270萬美元與 Vinbiocare 的合作以及與以色列衛生部的協議相關的收入減少 1,250 萬美元。這一下降主要被與 CSL 的合作協議和與 BARDA 的資助協議相關的 860 萬美元收入成長所抵消，這兩項協議均於 2020 年下半年簽署。

Revenue increased by $58.5 million during the 6 months ended June 30, 2023 compared to the prior year period. The increase was primarily attributable to an increase in revenue of $87.6 million related to the collaboration agreement with CSL Seqirus and the grant agreement with BARDA.

截至 2023 年 6 月 30 日的 6 個月內，營收較上年同期增加 5,850 萬美元。這一增長主要歸因於與 CSL Seqirus 的合作協議以及與 BARDA 的資助協議相關的收入增​​加 8,760 萬美元。

Total operating expenses for the 3 months ended June 30, 2023 was $65.9 million compared with $49.2 million for the 3 months ended June 30, 2022. Total operating expenses for the 6 months ended June 30, 2023 were $131.4 million compared with $104.8 million for the 6 months ended June 30, 2022.

截至2023年6月30日止三個月的總營運開支為6,590萬美元，而截至2022年6月30日止三個月的總營運開支為4,920萬美元。截至2023年6月30日止六個月的總營運開支為1.314億美元，而截至2022年6月30日止三個月的總營運開支為1.048億美元。截至 2022 年 6 月 30 日的 6 個月。

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. R&D expenses were $52.7 million for the 3 months ended June 30, 2023, compared with $38.2 million in the comparable period last year, primarily reflecting increased clinical research and manufacturing costs of $11.4 million and an increase of $2.9 million in personnel-related expenses.

我們的研發費用主要包括外部製造成本、合約研究組織、臨床和監管顧問進行的體內研究和臨床試驗、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。截至2023年6月30日的三個月，研發費用為5,270萬美元，去年同期為3,820萬美元，主要反映臨床研究和製造成本增加1,140萬美元，以及人事相關費用增加290萬美元。

R&D expenses were $104.4 million for the 6 months ended June 30, 2023, compared with $83.1 million in the comparable period last year, primarily reflecting increased manufacturing and personnel costs.

截至2023年6月30日的六個月，研發費用為1.044億美元，去年同期為8,310萬美元，主要反映了製造業和人員成本的增加。

General and administrative expenses primarily consist of salaries and related benefit of our executive, administrative, legal and accounting functions and professional service fees for legal and accounting services, as well as other general and administrative expenses. G&A expenses were $13.2 million and $27 million for the 3 and 6 months ended June 30, 2023, respectively, compared with $11 million and $21.7 million in the comparable period last year. The increase has resulted primarily from personnel expenses due to increased head count and salaries, increased travel and consulting expenses as well as an increased rent expense associated with the new headquarters facility.

一般和行政費用主要包括我們的執行、行政、法律和會計職能的薪資和相關福利以及法律和會計服務的專業服務費，以及其他一般和行政費用。截至 2023 年 6 月 30 日的 3 個月和 6 個月，一般管理費用分別為 1,320 萬美元和 2,700 萬美元，而去年同期為 1,100 萬美元和 2,170 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新總部設施相關的租金費用增加造成的人員費用。

For the 3 months ended June 30, 2023, Arcturus reported a net loss of approximately $52.6 million or $1.98 per diluted share compared with a net loss of $21.6 million or $0.82 per diluted share in the 3 months ended June 30, 2022. For the 6 months ended June 30, 2023, Arcturus reported a net loss of approximately $1.8 million or $0.07 per diluted share compared with a net loss of $72.7 million or $2.75 per diluted share in the 6 months ended June 30, 2022.

截至2023年6月30日的三個月，Arcturus報告的淨虧損約為5,260萬美元或稀釋每股1.98美元，而截至2022年6月30日的三個月淨虧損為2,160萬美元或稀釋每股0.82美元。截至2023年6月30日的幾個月，Arcturus報告的淨虧損約為180萬美元，即稀釋後每股0.07美元，而截至2022年6月30日的六個月，淨虧損為7270萬美元，即稀釋後每股2.75美元。

Cash and cash equivalents and restricted cash were $380.6 million as of June 30, 2023, and $394 million on December 31, 2022. We have collected approximately $300 million in upfront payments and milestones from CSL as of June 30, 2023. Additionally, in the second quarter, we received $23.6 million under the manufacturing and supply of ARCT-154 from CSL. We expect to continue receiving future milestone payments from CSL that will support the ongoing development of the COVID and FLU programs.

截至2023 年6 月30 日，現金及現金等價物以及限制性現金為3.806 億美元，截至2022 年12 月31 日為3.94 億美元。截至2023 年6 月30 日，我們已從CSL 收取了約3 億美元的預付款和里程碑。第二季度，我們從 CSL 獲得了 2360 萬美元的 ARCT-154 製造和供應費用。我們預計未來將繼續收到 CSL 的里程碑付款，這將支持 COVID 和 FLU 項目的持續開發。

Finally, I'm happy to report the cash run rate remains extended through the beginning of 2026, based on the current pipeline and programs.

最後，我很高興地報告，根據目前的管道和計劃，現金運行率仍將延長至 2026 年初。

In summary, we believe the company remains in a strong financial position and has the resources needed to achieve multiple near-term, value-creating milestones for the vaccine and therapeutic programs. Furthermore, with the anticipated ARCT-154 product approval later this year in Japan, we look forward to beginning to report potential commercial sales in the next few years.

總而言之，我們相信該公司仍保持強勁的財務狀況，並擁有實現疫苗和治療計畫多個近期、創造價值的里程碑所需的資源。此外，預計 ARCT-154 產品將於今年稍晚在日本獲得批准，我們期待開始報告未來幾年的潛在商業銷售情況。

I will now pass the call back to Joe.

我現在將把電話轉回給喬。

Thanks, Andy. We've continued to make excellent progress and advance our proprietary messenger RNA and LUNAR delivery platform technologies toward later stages in clinical development. It was great to hear the progress of our catalysts and our partner there on the manufacturing facility in Japan, and we're especially excited about the progress toward our first product approval potentially later this year with ARCT-154. The achievement would definitely mark a critical milestone for the platform and for Arcturus.

謝謝，安迪。我們繼續取得巨大進展，並將我們專有的信使 RNA 和 LUNAR 遞送平台技術推進到臨床開發的後期階段。很高興聽到我們的催化劑和我們的合作夥伴在日本製造工廠的進展，我們對 ARCT-154 可能在今年稍後獲得第一個產品批准的進展感到特別興奮。這項成就無疑將標誌著該平台和 Arcturus 的一個重要里程碑。

So with that, I'd like to turn the time over to the operator for questions.

因此，我想將時間交給接線員提問。

We will now be conducting a question-and-answer session. (Operator Instructions) Our first question comes from Yasmeen Rahimi with Piper Sandler.

我們現在將進行問答環節。 （操作員說明）我們的第一個問題來自 Yasmeen Rahimi 和 Piper Sandler。

And congrats on all the updates, especially on the manufacturing facility.

恭喜所有的更新，特別是製造設施的更新。

Team, could you maybe provide some color in terms of the timing of the approval in Japan, if that's still set for the fall?

團隊，如果仍定於秋季，您能否提供一些有關日本批准時間的資訊？

Second, maybe you could also provide us some thoughts around manufacturing capacity. Would you be able to, by the time you receive approval in Japan, to facilitate and produce over 70 million doses if needed?

其次，也許您也可以向我們提供一些關於製造能力的想法。當您在日本獲得批准時，您是否能夠根據需要促進和生產超過 7000 萬劑疫苗？

And then the third question is on the CF program. Are you planning to share the single ascending data? Could you comment how high you want a dosing? And then lastly, what are the doses you're moving forward into the [MAT] portion? I'll jump back into the queue and my apologies for so many questions.

第三個問題是關於CF程序的。您打算分享單一升序資料嗎？您能評論一下您想要多高的劑量嗎？最後，您進入 [MAT] 部分的劑量是多少？我將回到隊列中，並對這麼多問題表示歉意。

Sure. Well, with respect to the first question on the approval time line, I can address that. You can appreciate that the review process is ongoing with the PMDA, whether it's CMC and non-plan and clinical package insert and risk management plan questions, right? These are all standard and we're going through this ongoing process with the PMDA. So it means that we remain on track for later this year with respect to approval.

當然。嗯，關於批准時間線的第一個問題，我可以回答。您可以理解 PMDA 正在進行審查過程，無論是 CMC 還是非計劃和臨床說明書以及風險管理計劃問題，對吧？這些都是標準的，我們正在與 PMDA 一起完成這個持續的過程。因此，這意味著我們仍有望在今年稍後獲得批准。

With respect to capacity, I'm going to turn the time to Andy to address that.

關於容量，我將請安迪來解決這個問題。

Thanks. Yasmeen. With respect to capacity in Japan, we've clearly indicated that -- the fact we will not be operational in producing until next year. And furthermore, we will defer those kind of questions to our partner, ARCALIS and Meiji in Japan and CSL as well. So hopefully, you can appreciate they're in control of the commercial program here and have licensed out our ARCT-154 in future COVID products. So we're going to have to rely and depend on them for guidance with respect to capacity, but I'm sure they'll provide it when the time is appropriate.

謝謝。亞斯明。關於日本的產能，我們已經明確表示，我們要到明年才能投入生產。此外，我們會將此類問題轉交給我們的合作夥伴日本 ARCALIS 和 Meiji 以及 CSL。因此，希望您能理解他們控制著這裡的商業計劃，並已在未來的新冠產品中授權我們的 ARCT-154。因此，我們將不得不依賴並依賴他們在容量方面的指導，但我相信他們會在適當的時候提供指導。

And to address your final question about CF. We have not, and by intention, not disclosed any of the dose levels that we've evaluated given that the environment is competitive, but I can share with you that each patient will receive 2 doses in the Phase Ib amendment. So up to 8 CF patients and each will receive 2 doses, but the specific dose level, we're not disclosing at this time.

並解決您關於 CF 的最後一個問題。鑑於環境競爭激烈，我們並沒有有意透露我們評估過的任何劑量水平，但我可以與您分享的是，每位患者將在 Ib 期修正案中接受 2 劑劑量。因此，最多 8 名 CF 患者，每人將接受 2 劑劑量，但具體劑量水平，我們目前尚未透露。

Okay. Great. And I'll jump back into the queue.

好的。偉大的。我會跳回到隊列中。

Next question comes from Myles Minter with William Blair.

下一個問題來自邁爾斯·明特和威廉·布萊爾。

Congrats on the booster data as well. Nice to see that. Just on 154, if you do receive approval by year-end in Japan, do you think you've got the right strain in there to potentially deliver some doses in this current vaccination season? I just know one of your peers out there, Daiichi, they got approval and then clearly stated they'd be switching to an XBB strain to supply the current period. So that's the first question.

也祝賀助推器數據。很高興看到這一點。就 154 而言，如果您確實在年底前在日本獲得了批准，您認為您是否擁有合適的菌株，可以在當前的疫苗接種季節提供一些劑量？我只知道你的一位同行，Daiichi，他們獲得了批准，然後明確表示他們將改用 XBB 菌株來供應當前時期。這是第一個問題。

Yes. Myles, thanks for joining the call. It's good to hear you. You're absolutely right. All the regulatory agencies, including PMDA, are evaluating all the variants of interest in a particular region, in this case, Japan, and Arcturus is prepared to address whatever they request. So right now, you've seen the profile of ARCT-154, and it's broadly acting against a variety of variants. But if it's deemed by the PMDA for whatever reason to proceed with another variant of interest, whether that's XBB or something else, we're prepared to immediately respond and we're positioning the company strategically to do so, okay, with CSL and Meiji involved in this process.

是的。邁爾斯，感謝您加入通話。很高興聽到你的聲音。你是絕對正確的。所有監管機構，包括 PMDA，都在評估特定地區（在本例中為日本）感興趣的所有變體，而 Arcturus 已準備好滿足他們的任何要求。現在，您已經了解了 ARCT-154 的概況，它廣泛針對各種變體。但如果 PMDA 出於某種原因認為繼續進行另一種利益變體，無論是 XBB 還是其他，我們準備立即做出回應，我們正在對公司進行戰略定位，以便與 CSL 和 Meiji 合作參與這個過程。

Okay. And then the second question is just on duration. Thanks for supplying that Phase I/II data. Are we going to see duration of immunogenicity out of the Phase III booster trial? And what are your sort of predictions on the Comirnaty neutralizing antibodies sort of as we get into the 6 to 12-month period out of that trial?

好的。第二個問題是關於持續時間。感謝您提供第一階段/第二階段數據。我們會看到 III 期加強試驗的免疫原性持續時間嗎？當我們進入該試驗的 6 至 12 個月期間時，您對 Comirnaty 中和抗體有何預測？

Yes. No, I appreciate the question. Clearly, this data we shared today is very exciting. It's very promising. We're happy to see just a really strong durability signal from ARCT-154. It's a good representation of this next-generation self-amplifying mRNA platform. It's clearly different. So with respect to the Phase III data set, we intend to share that data for the 6-month time point later this year. And we'll be more than happy to share that at that time.

是的。不，我很欣賞這個問題。顯然，我們今天分享的這些數據非常令人興奮。這是非常有前途的。我們很高興看到 ARCT-154 發出非常強烈的耐用性訊號。它很好地代表了下一代自放大 mRNA 平台。顯然是不同的。因此，對於 III 期資料集，我們打算在今年稍後分享 6 個月時間點的數據。屆時我們將非常樂意分享這一點。

Next question comes from Seamus Fernandez with Guggenheim Securities.

下一個問題來自古根漢證券公司的謝默斯·費爾南德斯。

This is Evan Wang on for Seamus. I have 2 questions. First, on COVID. Just wondering if you could share some color on the Japanese COVID market? Really trying to figure out some of the opportunity for '23, '24, particularly with the, I believe, first 25 million vaccine purchase from Japan and expectations for additional orders.

這是 Seamus 的 Evan Wang。我有 2 個問題。首先，關於新冠病毒。只是想知道您是否可以分享一些有關日本新冠病毒市場的資訊？我真的很想找出「23」、「24」的一些機會，特別是我相信，從日本購買了第一批 2500 萬支疫苗，以及對額外訂單的預期。

Second, on OTC, wondering if you can provide enrollment updates there and what we can expect from an update later this year? Will that be specific to 810? Or should we expect a broader update as well?

其次，在 OTC 上，想知道你們是否可以在那裡提供註冊更新以及我們對今年稍後的更新有何期望？這是810特有的嗎？或者我們也應該期待更廣泛的更新嗎？

All right. So your first question is with respect to the opportunity for vaccine purchases in Japan, right? I guess I'll turn that over to Andy. Do you want to address that?

好的。那麼你的第一個問題是關於在日本購買疫苗的機會，對吧？我想我會把它交給安迪。你想解決這個問題嗎？

Yes. I think we obviously are very excited that the Japanese government continues to purchase the vaccines, the COVID-related vaccine for its population. And historically, they purchased about 80 million vaccines as of the last 12 months that we have record from the Japanese government. So certainly, the future orders that we're currently seeing and anticipating are certainly a testament to their concern about COVID during an endemic phase here. And certainly, the approval of Daiichi in Japan for a conventional mRNA vaccine made in Japan is certainly viewed as very favorable here for not only Arcturus but our partners, Meiji and CSL because the Japanese government is very committed to ensuring that in the future Japan will be vertically integrated and completely independent of any future manufacturers for any related pandemic type of viruses. And I think that's pretty exciting that the government had taken on this initiative to be self-sufficient. And hopefully, we can be a part of it and we'll certainly learn more soon.

是的。我認為我們顯然對日本政府繼續為其民眾購買疫苗（與新冠病毒相關的疫苗）感到非常興奮。從歷史上看，根據日本政府的記錄，截至過去 12 個月，他們購買了約 8,000 萬支疫苗。當然，我們目前看到和預期的未來訂單肯定證明了他們對新冠疫情流行階段的擔憂。當然，日本第一製藥公司批准日本製造的傳統 mRNA 疫苗無疑不僅對 Arcturus 有利，對我們的合作夥伴明治和 CSL 也非常有利，因為日本政府非常致力於確保未來日本將垂直整合並完全獨立於任何相關流行病類型病毒的未來製造商。我認為政府採取這項措施是為了實現自給自足，這非常令人興奮。希望我們能夠成為其中的一部分，並且我們一定會很快了解到更多。

But with respect to specific orders, we really cannot provide that at this time. It will certainly be developed and articulated by Meiji and CSL soon.

但對於具體的訂單，我們目前確實無法提供。明治和 CSL 肯定會很快開發和闡明它。

And then with respect to your second question on ARCT-810 enrollment, I think we haven't provided specific guidance there, but we encourage people to look to other rare liver disease companies on the pace of their enrollment as a basic guide as to what to anticipate.

關於 ARCT-810 註冊的第二個問題，我認為我們還沒有提供具體指導，但我們鼓勵人們關注其他罕見肝病公司的註冊進度，作為基本指南預見。

When we have finished enrollment of the Phase Ib portion of the trial, and as Joe mentioned in his remarks, that we intend to share some data around the 810 later on in the coming months.

當我們完成試驗的 Ib 期部分的註冊時，正如 Joe 在他的演講中提到的那樣，我們打算在未來幾個月晚些時候分享有關 810 的一些數據。

Yes.

是的。

Next question comes from Pete Stavropoulos with Cantor Fitzgerald.

下一個問題來自皮特·斯塔夫羅普洛斯和坎托·菲茨杰拉德。

Joe, Andy and team, congratulations on all the progress and the booster data presented in MedRx. It was nice to see the non-inferiority and superiority and non-neutralizing capabilities compared to an approved vaccine.

Joe、Andy 和團隊祝賀 MedRx 中呈現的所有進展和增強數據。很高興看到與已批准的疫苗相比的非劣效性和優越性以及非中和能力。

So first question, regarding the manufacturing capabilities in Japan, can you potentially leverage them for outside Japan with 154 and possibly other future candidates? Or will the facility be strictly focused on COVID vaccine?

那麼第一個問題，關於日本的製造能力，您是否有可能將其用於日本以外的地區，包括 154 以及未來可能的其他候選人？或者該設施會嚴格專注於新冠疫苗？

Absolutely, Peter. That's a really good question, and thanks for being on the call. We anticipate that ARCALIS will become a full-fledged mRNA facility with not only the capability of drug substance and drug product, but certainly going to be a world-class facility for any type of mRNA capability going forward. So it's up to ARCALIS to announce all this specifics with respect to their capability, and I'll leave it up to them. But they do have an exciting future, and we're a part of it. And certainly, we'll have more detail with our partner as soon as it becomes available.

當然，彼得。這是一個非常好的問題，感謝您接聽電話。我們預計 ARCALIS 將成為一個成熟的 mRNA 設施，不僅具有原料藥和藥品的能力，而且未來肯定會成為任何類型 mRNA 能力的世界一流設施。因此，由 ARCALIS 宣布有關其能力的所有細節，我將由他們決定。但他們確實擁有令人興奮的未來，而我們也是其中的一部分。當然，一旦有更多詳細信息，我們將立即與我們的合作夥伴聯繫。

All right. And for 032, I know that you have fully enrolled the Phase I in terms of healthy volunteers. And I know the focus is safety and tolerability. But now that you're expanding into patient population, what are some of the ways that you may evaluate the pharmacodynamic response?

好的。至於032，我知道你們已經在健康志工方面全面入組了一期。我知道重點是安全性和耐受性。但現在您正在擴展到患者群體，您可以透過哪些方法來評估藥效學反應？

Yes. There's -- we're going to be looking primarily at safety and tolerability in patients. I know we're very pleased with the results so far that we've seen in Phase I in healthy volunteers. This was the first time anyone has inhaled LUNAR technology. And so now that we transition to patients in Phase Ib, that is the primary objective here because we have a stellar preclinical data set of really positive data. So we just want to first see safety and tolerability in this Phase Ib set of patients.

是的。我們將主要關注患者的安全性和耐受性。我知道我們對迄今為止在健康志願者身上看到的第一階段結果非常滿意。這是第一次有人吸入月球技術。因此，現在我們過渡到 Ib 期患者，這是這裡的主要目標，因為我們擁有一組非常積極的臨床前數據。因此，我們只想先看看這群 Ib 期患者的安全性和耐受性。

Having said that, we're positioning ourselves to evaluate LCI or lung clearance index. And this is a sensitive measure of lung function. So we will look to see if after 2 doses, if we can see something. But the primary objective here is just to establish safety and tolerability in patients.

話雖如此，我們將自己定位為評估 LCI 或肺清除指數。這是肺功能的敏感指標。所以我們會看看兩次注射後是否能看到一些東西。但這裡的主要目標只是確定病患的安全性和耐受性。

All right. All right. And the last question is, I know you gave a brief sort of update on enrollment and how to look at other programs. But have you activated all the sites? And if not, how many more can you potentially activate to help enrollment move along?

好的。好的。最後一個問題是，我知道您簡要介紹了招生情況以及如何看待其他項目。但是您是否啟動了所有網站？如果沒有，您還可以啟動多少個來幫助註冊繼續進行？

We're essentially at capacity with respect to activating sites. Our team has been traveling through Europe and following up with all the principal investigators in this manner. So we're working hard to enroll patients. And that's the guidance we've provided and that we remain consistent on providing some data later this year or in the coming months.

我們在激活站點方面基本上已經達到了極限。我們的團隊一直在歐洲旅行，並以這種方式追蹤所有主要研究人員。因此，我們正在努力招募患者。這就是我們提供的指導，我們將在今年稍後或未來幾個月提供一些數據。

All right. Congrats on the progress once again.

好的。再次恭喜你們取得的進展。

Yes. Thanks, Pete.

是的。謝謝，皮特。

Next question comes from Yanan Zhu with Wells Fargo.

下一個問題來自富國銀行的朱亞楠。

Congrats on the progress. I wanted to get maybe a little more clarity on what might happen after a potential Japan approval? So I think Daiichi's decision, at least looking at the news release, is by itself, and it doesn't look like the PMDA instructed it not to supply the market with the original strain vaccine. So I was wondering what is your and your partner thinking once you receive the approval, what the thinking process in terms of whether to supply the market? And if you do supply the market, I was wondering who is the manufacturer? Is that you, your facility or the ARCALIS facility?

祝賀取得的進展。我想更清楚地了解日本潛在批准後會發生什麼？所以我認為第一第一的決定，至少從新聞稿來看，是其本身的決定，而且看起來不像 PMDA 指示它不要向市場供應原株疫苗。所以我想知道，當你獲得批准後，你和你的合作夥伴在想什麼，在是否供應市場方面的思考過程是怎麼樣的？如果你確實供應市場，我想知道製造商是誰？是您、您的工廠還是 ARCALIS 工廠？

Well, with respect to commercial guidance?

那麼，關於商業指導？

With respect to the second, obviously -- thanks for the question, Yanan. But certainly, our current manufacturing partners which represents Catalent and Aldevron in the U.S. and Recipharm in Europe would be the suppliers of any current supply. As you know, we've articulated the Japan facility, it won't come online until next year. So any kind of orders for Japan from that facility probably will not be until next year, late or the year after. So hopefully, you can appreciate that. We have a dual process in place to be able to provide the Japanese market with our vaccine as soon as possible. And certainly, once the factory is up and running in Japan, that they'll be able to supply going forward.

關於第二個問題，顯然──謝謝亞南的提問。但可以肯定的是，我們目前的製造合作夥伴（代表美國的 Catalent 和 Aldevron 以及代表歐洲的 Recipharm）將是任何當前供應的供應商。如您所知，我們已經明確了日本設施，它要到明年才會上線。因此，從該工廠向日本發出的任何訂單可能要到明年、年底或後年才會收到。所以希望你能欣賞這一點。我們制定了雙重流程，以便能夠盡快向日本市場提供我們的疫苗。當然，一旦工廠在日本建成並運營，他們將能夠繼續供應。

Hopefully, that helps clarify that situation, and Joe can address the first part of the question.

希望這有助於澄清這種情況，喬可以解決問題的第一部分。

Yes. With respect to the other vaccine or vaccines getting approved in Japan, we're very happy to see that Japan is following their domestic strategic plan. We've touched on this earlier in the call a little bit. We view this very positive because we feel like we're part of this domestic plan with Meiji and CSL.

是的。至於日本批准的其他疫苗，我們很高興看到日本正在遵循其國內戰略計劃。我們之前在電話會議中已經談到過這一點。我們認為這非常積極，因為我們覺得我們是明治和中超國內計劃的一部分。

But our -- what sets this vaccine technology apart from all other conventional mRNA vaccines that have been approved or soon to be approved is our dose level. So our dose level is significantly lower. Our serial response rates that we've observed seem to be differentiating. Clearly, people have to be taking this dose level into consideration when it comes to safety and reactogenicity that's potentially differentiating. And then finally, the data we showed today, the durability data is very promising. So -- and can set this technology apart.

但我們的——這種疫苗技術與所有其他已批准或即將批准的傳統 mRNA 疫苗的區別在於我們的劑量水平。所以我們的劑量水平明顯較低。我們觀察到的串行響應率似乎有所不同。顯然，當涉及到潛在的差異化安全性和反應原性時，人們必須考慮到這個劑量水平。最後，我們今天展示的數據，耐久性數據非常有希望。所以——並且可以使這項技術與眾不同。

So as we work with Japan and their strategy, we definitely see a way to fit in line with their objectives to address some of the key issues in protecting their people with a vaccine strategy.

因此，當我們與日本及其策略合作時，我們肯定會找到一種符合他們目標的方法，以解決透過疫苗策略保護其人民的一些關鍵問題。

Got it. And you touched on durability, congrats on the data. I was wondering, can you talk about the underlying biological basis for this durability? And your confidence that we could see this observation replicated in the longer follow-up for the Japan study?

知道了。您談到了耐用性，並祝賀您的數據。我想知道，你能談談這種持久性的潛在生物學基礎嗎？您是否有信心我們可以在日本研究的長期追蹤中看到這項觀察結果？

Yes. It's a great question. Self-amplifying mRNA is providing very encouraging durability data. And your question is why, and it's because the mechanism of how this -- the self-amplifying mRNA molecules make the antigen. Conventional mRNA make the antigen for a period of time and then degrades, right? But self-amplifying mRNA, this next-generation mRNA technology, extends the duration of making that antigen. So the body sees the antigen for a longer period of time. That means it is allowed to increase the antibody titer levels, and that's what we've seen in the Phase III comparison study.

是的。這是一個很好的問題。自我擴增 mRNA 提供了非常令人振奮的耐久性數據。你的問題是為什麼，這是因為自我擴增 mRNA 分子產生抗原的機制。傳統的mRNA會產生抗原一段時間然後降解，對嗎？但自我擴增 mRNA，這種下一代 mRNA 技術，延長了製造抗原的持續時間。因此，身體看到抗原的時間更長。這意味著它可以提高抗體滴度水平，這就是我們在 III 期比較研究中看到的。

And we've all -- because the body sees the antigen for a longer period of time, it allows a broader spectrum of antibodies to be made. And when you combine those 2 features of increased antibody titers with a broader spectrum of antibodies being created by the body, this translates into a longer lasting vaccine. And that would provide an explanation as to explaining what -- why we're seeing what we're seeing.

我們都知道—因為身體能在更長的時間內看到抗原，所以可以產生更廣泛的抗體。當您將抗體滴度增加的這兩個特徵與身體產生的更廣泛的抗體結合時，這就會轉化為更持久的疫苗。這將提供一個解釋，解釋為什麼我們會看到我們所看到的。

Got it. So we might -- we should be able to see something similar with the Japan study? Am I correct?

知道了。所以我們可能——我們應該能夠看到與日本研究類似的東西？我對麼？

Yes, well -- correct. Correct. That's what you would expect. And remember, previously, we've seen in our Phase I and Phase II studies that the antibody titer levels tend to increase beyond 1 month or beyond 4 weeks, so will we see that as well in Phase III is yet to be understood. But yes, our expectations are high and very optimistic.

是的，嗯——正確。正確的。這正是您所期望的。請記住，之前我們在 I 期和 II 期研究中發現，抗體滴度水平往往會在 1 個月或 4 週以上後增加，因此我們是否會在 III 期研究中看到這一點尚待了解。但是，是的，我們的期望很高而且非常樂觀。

Got it. And lastly, on the OTC deficiency program. I was wondering in the news release, you mentioned you may announce data from a subset of the patients. I was wondering, could we expect 1 or both cohorts of the patients' data being reported out? And what type of changes clinically or in terms of biomarkers can be expected with roughly a 3-month duration?

知道了。最後，關於 OTC 缺陷計劃。我想知道在新聞稿中，您提到您可能會公佈一部分患者的數據。我想知道，我們是否可以期望報告一組或兩組患者的數據？在大約 3 個月的時間內，臨床或生物標記方面預計會發生什麼類型的變化？

And lastly, would you be able to comment on any next steps that we can expect once you have reported the data?

最後，您能否對您報告數據後我們可以預期的後續步驟發表評論？

Well, I appreciate the question and wanting to understand additional detail on different dose levels in the OTC clinical trial. But the only guidance we're providing today is some biological proof of concept or some biological data that will provide in a subset of patients. So I can't provide any more detail than that.

嗯，我很欣賞這個問題，並想了解 OTC 臨床試驗中不同劑量水平的更多細節。但我們今天提供的唯一指導是將在一部分患者中提供的一些生物學概念證明或一些生物學數據。所以我無法提供更多細節。

With respect to any biomarkers that we're tracking, we will be tracking them for an extended period of time, and that includes ammonia and urea genesis. And other amino acids can be -- such as glutamate, for example, can be measured. Several amino acids are impacted by the urea cycle. And OTC itself can be measured, the ornithine transcarbamylase enzyme that's built or expressed in these liver cells. These liver cells, just so you're aware, can be sloughed off into the circulation and measured in the plasma. And so we can track OTC levels as well and over an extended period of time.

對於我們正在追蹤的任何生物標誌物，我們將長期追蹤它們，其中包括氨和尿素的生成。其他氨基酸也可以測量，例如穀氨酸。幾種胺基酸受到尿素循環的影響。 OTC 本身可以測量，即在這些肝細胞中構建或表達的鳥氨酸轉氨甲酰酶。如您所知，這些肝細胞可以脫落進入循環系統並在血漿中進行測量。因此我們也可以在很長一段時間內追蹤 OTC 水平。

Next question comes from Yigal Nochomovitz with Citi.

下一個問題來自花旗銀行的 Yigal Nochomovitz。

This is Carly on for Yigal. First, just curious if there's anything more you can say about CSL's progress on the seasonal flu vaccine? And if that work has maybe accelerated at all after the COVID data? Do you have a sense for time lines for potentially bringing a flu candidate into the clinic?

這是伊格爾的卡莉。首先，我想知道您對 CSL 在季節性流感疫苗方面的進展還有什麼要說的嗎？在新冠病毒數據公佈之後，這項工作是否可能有所加速？您是否知道可能將流感候選人帶入診所的時間線？

Well, I can provide 1 comment. You're absolutely right that the Meiji, CSL and Arcturus teams are all united in excitement over this recent data set. And that excitement bleeds into other programs, of course. It gives us more energy and more ambition and vigor in other programs.

好吧，我可以提供 1 則評論。你說得對，Meiji、CSL 和 Arcturus 團隊都對最近的數據集感到興奮。當然，這種興奮也會滲透到其他項目中。它給了我們更多的精力，讓我們在其他項目上更有雄心和活力。

And so your question about the flu is appropriate. We have to be very careful. It's -- I would consider, even though we're working closely with CSL, it is their program and there's -- their program to guide on. So it's very difficult for us to just give a candid response to your question on guidance. Having said that, we look forward to continuously update the market because this is an active program for us. We've reported milestones on this previously this year, and clearly, this is a program of high interest for CSL. And Andy, anything to add?

所以你關於流感的問題是恰當的。我們必須非常小心。我認為，儘管我們正在與中超聯賽密切合作，但這是他們的計劃，並且有他們的計劃可供指導。所以我們很難對你提出的指導性問題作出坦誠的答覆。話雖如此，我們期待不斷更新市場，因為這對我們來說是一個積極的計劃。今年早些時候，我們已經報告了這方面的里程碑，顯然，這是中超聯賽非常感興趣的計劃。安迪，還有什麼要補充的嗎？

Yes. In my comments, I obviously said that we will have update provided soon, so stay tuned. Thank you.

是的。在我的評論中，我顯然說過我們將很快提供更新，敬請期待。謝謝。

Yes.

是的。

Okay. Got it. That's helpful. And then just on OTC and CF. I know that the ongoing Phase II in OTC is active in the U.K. and Europe, and then you're also recruiting in New Zealand for the CF program. Just curious, any comments on potential time lines and plans for opening sites in the U.S. for those studies?

好的。知道了。這很有幫助。然後就是 OTC 和 CF。我知道正在進行的 OTC 第二階段在英國和歐洲很活躍，然後你們還在新西蘭招募 CF 計畫。只是好奇，對在美國開設這些研究地點的潛在時間表和計劃有什麼評論嗎？

Well, we already have active trial ongoing in -- for COVID and the vaccine enterprise in the U.S. already. So we already have an active effort in the United States. And for OTC, we have an active effort in the U.S. with our Phase Ib trial in patients.

嗯，我們已經在美國針對新冠病毒和疫苗企業進行了積極的試驗。所以我們已經在美國做出了積極的努力。對於 OTC，我們在美國積極進行針對患者的 Ib 期試驗。

With respect to CF, you can see that we have a very strong relationship with the CF Foundation, and they have considerable oversight and influence on the U.S. area, not just globally. But we haven't indicated any guidance as to when we'll be conducting any clinical trial efforts in CF in U.S. There will be an appropriate time to do so, but today is not that day.

關於CF，你可以看到我們和CF基金會有非常牢固的關係，他們對美國地區有相當大的監督和影響力，而不僅僅是在全球範圍內。但我們還沒有就何時在美國進行任何 CF 臨床試驗工作提供任何指導。會有適當的時間這樣做，但今天還不是那一天。

Next question comes from Ed Arce with H.C. Wainwright.

下一個問題來自 Ed Arce 和 H.C.溫賴特。

This is Thomas Yip asking a couple of questions for Ed. Congratulations on all the progress with Meiji in Japan. So first, perhaps looking a little bit into the future. Do you have any plans right now to expand 154's use in populations beyond adults in Japan? And if so, what can investors think about the estimated time line?

我是 Thomas Yip，向 Ed 問了幾個問題。祝賀明治在日本的所有進展。首先，也許要展望一下未來。您現在有計劃將 154 的使用範圍擴大到日本成年人以外的人群嗎？如果是這樣，投資人對預期的時間線有何看法？

Yes. The short answer is yes. There's a lot of activities we'd like to expand because our Phase III trial was in adults, right? So there's more than just adults in Japan, and CSL has a definite -- and Meiji has a clear interest in expanding the commercial opportunity beyond adults. So -- but I can't give specific guidance on that. It's theirs to provide.

是的。簡短的回答是肯定的。我們想要擴大很多活動，因為我們的 III 期試驗是在成年人中進行的，對吧？因此，日本不僅有成年人，CSL 也有明確的目標——而明治對擴大成人以外的商業機會有著明確的興趣。所以——但我無法就此給出具體指示。這是他們要提供的。

But outside of Japan, CSL is our exclusive partner for distribution and commercialization in U.S. and Europe, for example. So we'll be looking to them to provide guidance on those efforts.

但在日本以外，CSL 是我們在美國和歐洲等地區的分銷和商業化的獨家合作夥伴。因此，我們將尋求他們為這些努力提供指導。

Got it. Perhaps just 1 more question from us regarding 032 with the CF. A lot of interest on this and the OTC program, clearly. Perhaps for the Phase I study, when can we expect the first CF patients to be enrolling to the study? I know you just received clearance. And also, what -- when can we expect the initial data set with CF patients?

知道了。也許我們還有 1 個關於 032 與 CF 的問題。顯然，人們對此和 OTC 計劃很感興趣。也許對於 I 期研究，我們什麼時候可以預期第一批 CF 患者會參與研究？我知道你剛剛收到許可。而且，我們什麼時候可以期待 CF 患者的初始資料集？

Well, we've conservatively guided the initiation of enrollment in the second half of this year, and we'll allow that to unfold. And then with respect to data, that will be at a later time point. I think we're focused on the near-term objective of enrolling, initiating enrollment for these up to 8 CF patients in New Zealand in the second half of this year.

嗯，我們保守地指導了今年下半年的招生啟動，我們將允許這一進程展開。然後就數據而言，那將是稍後的時間點。我認為我們的近期目標是入組，今年下半年在新西蘭開始入組最多 8 名 CF 患者。

With respect to interim Phase I safety data, interim Phase I safety data is also expected later this year.

至於中期第一階段安全數據，中期第一階段安全數據也預計今年稍後公佈。

Okay. Got it. Looking forward to those data along with the COVID regulatory status in Japan as well.

好的。知道了。期待這些數據以及日本的新冠疫情監管狀況。

Next question comes from I-Eh Jen with Laidlaw & Company.

下一個問題來自 Laidlaw & Company 的 I-Eh Jen。

Congrats on all the progress in Japan at this moment. I appreciate the data you provided today in terms of the -- both the duration as well as the breadth of the vaccine 154 it covers.

祝賀日本目前所取得的所有進步。我很欣賞您今天提供的數據，包括疫苗 154 的持續時間和廣度。

My question to you is that does this have any read-through in terms of the application in Japan in terms of cover broader background of strain? Then I have another follow-up question.

我向您提出的問題是，就涵蓋更廣泛的菌株背景而言，這對在日本的應用有任何通讀嗎？然後我還有另一個後續問題。

Yes. It's a good question. The data we shared today was only using a validated assay. The new strains that are coming forward are only exploratory in nature and not validated yet. So we've remained consistent on sharing data that's only validated assays, right? So there will be a time and a place to provide that data once the assays are validated is the answer.

是的。這是一個好問題。我們今天分享的數據僅使用經過驗證的測定法。即將出現的新菌株本質上只是探索性的，尚未得到驗證。因此，我們一直堅持共享僅經過驗證的檢測的數據，對嗎？因此，一旦檢測得到驗證，就會有時間和地點提供數據。

With that referring you mentioned earlier that you might report a 6-month data in the future time, so maybe later this year. Are these 2 connected in any way?

您之前提到，您可能會在未來（也許是今年稍後）報告 6 個月的數據。這兩個有什麼關聯嗎？

All right. If you're referring to the Phase III Japanese comparator study, yes, we're guiding that we'll be able to share a 6-month durability data later this year. Correct.

好的。如果您指的是日本 III 期比較研究，是的，我們建議我們將能夠在今年稍後分享 6 個月的耐久性數據。正確的。

And -- this is Pad. And I just want to make sure that you understand, we're an mRNA platform company. And because of that, we can update our vaccine readily. So if there's a new strain that emerges, we can, of course, update our vaccine. And because the platform will be approved, we can quickly commercialize that as well. And our manufacturing process is very similar to a lot of the other mRNA players.

而且──這是帕德。我只是想確保您明白，我們是一家 mRNA 平台公司。正因為如此，我們可以輕鬆更新我們的疫苗。因此，如果出現新株，我們當然可以更新我們的疫苗。由於該平台將獲得批准，我們也可以快速將其商業化。我們的製造流程與許多其他 mRNA 生產商非常相似。

Keep in mind that with the trial being completed in February, you don't really have the 6-month completion of the data until August. So by the time they collect it and analyze it, you have to give us a few months for that. So hopefully, I give you some kind of runway to understand when conceivably the 6-month data could even be presented. Hopefully, it will be probably a fourth quarter event, if you can appreciate that. Does that make sense?

請記住，由於試驗已於 2 月完成，因此直到 8 月您才能真正獲得 6 個月的數據。因此，當他們收集並分析它時，您必須給我們幾個月的時間。因此，希望我能為您提供某種跑道，讓您了解何時可以呈現 6 個月的數據。希望這可能是第四季的活動，如果你能欣賞的話。那有意義嗎？

Absolutely. And I really appreciate the color. And 1 follow-up question here is in terms of the 032 in the CF. In your press release, you mentioned that there was some amendment being tested out, explored or being suggested for the Phase Ib study. Any color in terms of what specific amendment has been placed?

絕對地。我真的很欣賞這種顏色。這裡的 1 個後續問題是關於 CF 中的 032 的。在你們的新聞稿中，你們提到有一些修正案正在測試、探索或建議用於 Ib 期研究。就具體的修正案而言，有什麼顏色嗎？

Yes. The amendment is -- our Phase 1 was in healthy volunteers. And what we talked about was -- in Joe's comments that there's been an amendment that was filed, and it was recently approved to include patients in the study.

是的。修正案是－我們的第一階段是在健康志工中進行的。我們討論的是——在喬的評論中，已經提交了一項修正案，並且最近被批准將患者納入研究中。

So therefore, just adding the patient versus purely the healthy volunteers.

因此，只需將患者與純粹的健康志願者相加即可。

That's right.

這是正確的。

Okay. Great. Again congrats though.

好的。偉大的。不過再次恭喜。

Yes. Thank you. I-Eh.

是的。謝謝。我-呃。

That was all the time we had for today. I would like to turn the floor back over to Joe for closing comments.

這就是我們今天的全部時間了。我想把發言權交還給喬，讓他發表結束語。

Thanks for participating on the call today, everyone. If there's remaining questions, please reach out to the team, and we'll get back to you right away. Good night.

感謝大家參加今天的電話會議。如果還有其他問題，請聯絡團隊，我們會立即回覆您。晚安。

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation, and have a great day.

今天的電話會議到此結束。此時您可以斷開線路。感謝您的參與，祝您有美好的一天。