Spero Therapeutics Inc (SPRO) 2022 Q4 法說會逐字稿

Good afternoon, and welcome to Spero Therapeutics Fourth Quarter and Year-End 2022 Financial Results Conference Call.

下午好，歡迎來到 Spero Therapeutics 第四季度和 2022 年底財務業績電話會議。

(Operator Instructions)

（操作員說明）

Please be advised that this call is being recorded, and the replay will be available. You can find information on the replay and further information related to today's announcement on the Spero Therapeutics website at www.sperotherapeutics.com.

請注意，此通話正在錄音中，並且可以重播。您可以在 Spero Therapeutics 網站 www.sperotherapeutics.com 上找到有關重播的信息以及與今天的公告相關的更多信息。

At this time, I would like to turn the call over to Ted Jenkins, Vice President, Investor Relations and Strategic Finance at Spero Therapeutics. Mr. Jenkins, please go ahead.

此時，我想將電話轉給 Spero Therapeutics 投資者關係和戰略財務副總裁 Ted Jenkins。詹金斯先生，請繼續。

Thank you, operator, and thank you all for participating in today's conference call. This afternoon, Spero Therapeutics released financial results and provided a pipeline update for the fourth quarter and full year 2022. Our press release is available on the Investor page of the Spero Therapeutics website.

謝謝接線員，也感謝大家參加今天的電話會議。今天下午，Spero Therapeutics 發布了財務業績，並提供了第四季度和 2022 年全年的管道更新。我們的新聞稿可在 Spero Therapeutics 網站的投資者頁面上獲取。

Before we begin, I'd like to remind you that some of the information presented on this conference call contains forward-looking statements based on our current expectations, including statements about the future development and commercialization of SPR720, SPR206 and tebipenem HBr, and the design, initiation, timing, progress and results of the company's preclinical studies and clinical trials and its research and developmental programs, management's assessment of the results of such preclinical studies and clinical trials, the company's cash forecast and anticipated expenses and the sufficiency of its cash resources.

在我們開始之前，我想提醒您，本次電話會議中提供的一些信息包含基於我們當前預期的前瞻性陳述，包括關於 SPR720、SPR206 和替比培南 HBr 的未來開發和商業化的陳述，以及公司臨床前研究和臨床試驗及其研發項目的設計、啟動、時間、進展和結果，管理層對該等臨床前研究和臨床試驗結果的評估，公司的現金預測和預期費用以及現金充足性資源。

Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those contained in such statements. Several factors that could cause or contribute to such differences are described in detail in Spero Therapeutics' filings with the SEC, including in the Risk Factors section of our annual report on Form 10-K for the year ended December 31, 2022, filed with the SEC today. These forward-looking statements speak only as of the date of this conference call, and the company undertakes no obligation to publicly update any forward-looking statements or supply new information regarding the company after the date of today's call.

此類前瞻性陳述不是業績保證，公司的實際結果可能與此類陳述中包含的結果存在重大差異。 Spero Therapeutics 向美國證券交易委員會提交的文件中詳細描述了可能導致或促成此類差異的幾個因素，包括我們提交給美國證券交易委員會的截至 2022 年 12 月 31 日止年度 10-K 表格年度報告的風險因素部分。美國證券交易委員會今天。這些前瞻性陳述僅在本次電話會議召開之日有效，公司沒有義務在今天的電話會議之後公開更新任何前瞻性陳述或提供有關公司的新信息。

Participating in today's call are Dr. Ankit Mahadevia, Chief Executive Officer; Dr. Kamal Hamed, Chief Medical Officer; and Sath Shukla, Chief Financial Officer.

參加今天電話會議的有首席執行官 Ankit Mahadevia 博士；首席醫療官 Kamal Hamed 博士；和首席財務官 Sath Shukla。

And with that, I'd like to turn the call over to Dr. Ankit Mahadevia. Please go ahead, Ankit.

有了這個，我想把電話轉給 Ankit Mahadevia 博士。請繼續，Ankit。

Thanks, Ted, and thanks to everyone listening. Spero's off to a strong 2023, thanks to recent achievements that have provided us with a strong balance sheet and world-class partners to support the advancement of our multi-program pipeline of differentiated medicines. We remain committed to developing a pipeline of medicines that marry unmet need with high commercial potential, and we continue to do so while placing a premium on capital efficiency and complementing our efforts with those of our partners in pharma and in public agencies.

謝謝，泰德，感謝大家的聆聽。 Spero 的 2023 年表現強勁，這要歸功於最近的成就為我們提供了強大的資產負債表和世界級的合作夥伴，以支持我們差異化藥物的多項目管道的發展。我們仍然致力於開發一系列藥物，將未滿足的需求與高商業潛力結合起來，我們將繼續這樣做，同時重視資本效率，並與我們在製藥和公共機構的合作夥伴的努力相輔相成。

Kamal will be providing an update on SPR720 and SPR206. So I'll focus my part of the call on tebipenem HBr, which we are developing as potentially the first oral carbapenem antibiotic for the treatment of complicated urinary tract infections or cUTI. As a reminder, tebipenem HBr is the subject of an exclusive license agreement with GSK, which closed last quarter. This agreement came with a $66 million upfront payment to us as well as a $9 million equity investment in our common stock, both of which have now been received.

Kamal 將提供 SPR720 和 SPR206 的更新。因此，我將把我的部分重點放在替比培南 HBr 上，我們正在開發它作為潛在的第一種口服碳青黴烯類抗生素，用於治療複雜的尿路感染或 cUTI。提醒一下，替比培南 HBr 是上個季度與 GSK 達成獨家許可協議的對象。該協議包括向我們支付 6600 萬美元的預付款以及對我們普通股的 900 萬美元股權投資，目前均已收到。

In addition, we are eligible for up to $525 million in development, sales and milestone payments as well as single-digit to low double-digit royalties on net product sales. In exchange for all this, GSK was granted an exclusive license for tebipenem HBr's development and commercialization in all territories except Japan and certain other Asian countries, where rights are being retained by our partner, Meiji Seika. Per the agreement, we hold responsibility for an upcoming Phase III trial of tebipenem HBr, while GSK will be responsible for additional development and commercialization activities outside of the Meiji Seika territory.

此外，我們有資格獲得高達 5.25 億美元的開發、銷售和里程碑付款，以及產品淨銷售額的個位數到兩位數的特許權使用費。作為這一切的交換，葛蘭素史克獲得了氫溴酸替比培南在所有地區的獨家開發和商業化許可，但日本和某些其他亞洲國家/地區除外，我們的合作夥伴明治精化保留了這些國家/地區的權利。根據協議，我們負責即將進行的氫溴酸替比培南 III 期試驗，而葛蘭素史克將負責明治制果領域以外的額外開發和商業化活動。

We're engaged with the FDA on the planned protocol for tebipenem HBr's upcoming clinical trial. As you may recall, we had a Type A Meeting with the agency in 2022, during which we aligned on high-level aspects of the trial design and received feedback indicating the positive results from the trial, together with confirmatory, nonclinical evidence of efficacy could be sufficient to support tebipenem's approval in cUTI, including pyelonephritis for a limited use indication.

我們與 FDA 就替比培南 HBr 即將進行的臨床試驗的計劃方案進行了接觸。您可能還記得，我們在 2022 年與該機構舉行了一次 A 類會議，在此期間我們就試驗設計的高級方面進行了調整，並收到了反饋，表明試驗的積極結果，以及確認性非臨床療效證據可以足以支持替比培南在 cUTI 中的批准，包括腎盂腎炎的有限使用適應症。

We still anticipate providing an update on our engagement with the FDA in the first half of this year. This update will include details of the clinical trial design as well as granularity on the specific regulatory and development activities over the coming months that will trigger milestone payments from our GSK partnership. We'll continue to anticipate initiating the Phase III trial in the second half of 2023. And if all goes well with the program, we believe tebipenem HBr could reach commercialization by 2026, as noted by GSK on their earnings call last month.

我們仍然預計在今年上半年提供我們與 FDA 合作的最新情況。本次更新將包括臨床試驗設計的詳細信息以及未來幾個月具體監管和開發活動的詳細信息，這些活動將觸發我們 GSK 合作夥伴的里程碑付款。我們將繼續預計在 2023 年下半年啟動 III 期試驗。如果該計劃一切順利，我們相信 tebipenem HBr 可以在 2026 年實現商業化，正如 GSK 在上個月的財報電話會議上指出的那樣。

I'd like to thank GSK for their role in what's been a very productive partnership to date. As we work to advance tebipenem HBr through the regulatory process and complete the Phase III trial, it's the program's strong foundation that fuels our enthusiasm. This foundation consists of 3 key pillars. The first of these pillars is the extensive data set supporting tebipenem's safety and efficacy. Between our work and that of Meiji Seika, tebipenem has been evaluated in 24 clinical trials that have been collectively enrolled over 2,500 subjects. These are highlighted by our double-blind placebo-controlled Phase III trial ADAPT-PO.

我要感謝葛蘭素史克在迄今為止非常富有成效的合作夥伴關係中發揮的作用。在我們努力通過監管流程推進氫溴酸替比培南並完成 III 期試驗時，正是該計劃的堅實基礎激發了我們的熱情。該基金會由 3 個關鍵支柱組成。這些支柱中的第一個是支持替比培南安全性和有效性的廣泛數據集。在我們和 Meiji Seika 的工作之間，替比培南已在 24 項臨床試驗中進行了評估，這些試驗總共招募了 2,500 多名受試者。我們的雙盲安慰劑對照 III 期試驗 ADAPT-PO 突出了這些。

Moreover, post-marketing surveillance efforts on tebipenem in Japan where it's approved for pneumonia, otitis media and sinusitis have demonstrated its efficacy while noting no safety issues in a review of more than 3,300 patients. The second key pillar of tebipenem's foundation is its potential to address a clear and pressing unmet need. There are currently no oral carbapenem antibiotics available for millions of cUTI patients in the U.S., many of whom have no other option other than to receive an IV therapy in a hospital setting.

此外，在日本批准替比培南治療肺炎、中耳炎和鼻竇炎的上市後監測工作已經證明了它的有效性，同時在對 3,300 多名患者的審查中沒有發現安全問題。替比培南基礎的第二個關鍵支柱是它有可能解決一個明確而緊迫的未滿足需求。美國目前沒有可供數百萬 cUTI 患者使用的口服碳青黴烯類抗生素，其中許多人除了在醫院接受靜脈注射治療外別無選擇。

By successfully developing tebipenem, we believe we can provide these patients with an at-home oral treatment that could provide health and economic benefits for them, while also improving costs for the health care system. The last key pillar making up tebipenem's foundation for success comes from the support of our partners. We believe GSK is the ideal partner to lead tebipenem's commercialization, if approved, given its well-established commercial organization and commitment to serving patients with infection, including urinary tract infections. We're also grateful for the continued support of BARDA for the advancement of tebipenem.

通過成功開發替比培南，我們相信我們可以為這些患者提供居家口服治療，為他們帶來健康和經濟效益，同時還能降低醫療保健系統的成本。構成替比培南成功基礎的最後一個關鍵支柱來自我們合作夥伴的支持。我們相信葛蘭素史克是領導替比培南商業化的理想合作夥伴，如果獲得批准，鑑於其完善的商業組織和為包括尿路感染在內的感染患者服務的承諾。我們也感謝 BARDA 對替比培南進步的持續支持。

With that, I'll turn the call over to Kamal to discuss SPR720 and SPR206.

有了這個，我會把電話轉給 Kamal 來討論 SPR720 和 SPR206。

Thanks, Ankit. I'll begin by providing a brief update on SPR720, our novel oral drug candidates being developed as a first-line treatment for the orphan-designated nontuberculous mycobacterial pulmonary disease or NTM-PD for short. An important aspect of our SPR720 program is a target patient population, which consists of patients who are treatment-naive or those who have received treatment but have nonrefractory disease. This is noteworthy because patients with NTM-PD who progress to refractory disease often suffer irreversible lung damage limiting the potential for pharmacotherapy to improve how they even function.

謝謝，安吉特。我將首先簡要介紹 SPR720，這是我們正在開發的新型口服候選藥物，作為孤兒指定的非結核分枝桿菌肺病或簡稱 NTM-PD 的一線治療藥物。我們的 SPR720 計劃的一個重要方面是目標患者群體，其中包括初治患者或接受過治療但患有非難治性疾病的患者。這是值得注意的，因為進展為難治性疾病的 NTM-PD 患者通常會遭受不可逆的肺損傷，這限制了藥物療法改善其功能的潛力。

With quite the inherent challenges of treating patients with refractory disease, there remain no FDA-approved first-line therapy for NTM-PD. Instead, patients were early in their disease journey are frequently treated with combinations of off-label therapies with limitations related to tolerability and effectiveness. In fact, published estimates indicate that 75% of patients with NTM-PD who receive standard-of-care treatment discontinue such treatment after about a year, mainly due to tolerability and effectiveness concerns.

由於治療難治性疾病患者存在相當大的固有挑戰，目前尚無 FDA 批准的 NTM-PD 一線療法。相反，處於疾病早期的患者經常接受與耐受性和有效性相關的限制的標籤外療法的組合治療。事實上，已公佈的估計表明，接受標準護理治療的 NTM-PD 患者中有 75% 在大約一年後停止了此類治療，這主要是出於對耐受性和有效性的擔憂。

Even when they complete their course of therapy, a relatively large proportion of patients experience recurrent disease. Through SPR720 development, we hope to improve the first line standard of care for patients with NTM-PD. Towards this end, we initiated a Phase IIa clinical trial designed to establish proof of concept. We recently completed the successful investigator meeting, and we are conducting the appropriate development activities for the program, working to eventually advance SPR720 into clinicals.

即使他們完成了療程，仍有相當大比例的患者會出現疾病復發。通過 SPR720 的開發，我們希望提高 NTM-PD 患者的一線護理標準。為此，我們啟動了 IIa 期臨床試驗，旨在建立概念驗證。我們最近完成了成功的研究者會議，我們正在為該項目進行適當的開發活動，努力最終將 SPR720 推向臨床。

I'll jump in for Kamal. I think he's having technical difficulties. These activities include ongoing toxicology work, CMC and quality initiatives, engagement with FDA and activities to expand into Japan as there is a large prevalence of Japanese patients with NTM-PD. Importantly, we are also actively progressing with the development and validation of relevant patient-reported outcomes for NTM-PD as part of the clinical endpoint work for follow-on clinical studies.

我會加入 Kamal。我認為他有技術上的困難。這些活動包括正在進行的毒理學工作、CMC 和質量計劃、與 FDA 的合作以及擴展到日本的活動，因為日本 NTM-PD 患者患病率很高。重要的是，作為後續臨床研究的臨床終點工作的一部分，我們還在積極推進相關患者報告的 NTM-PD 結果的開發和驗證。

The Phase II trial was designed to enroll approximately 35 patients with NTM-PD due to mycobacterium avium complex, implicated in approximately 80% of NTM-PD cases. Eligible participants are either treatment-naive or have received prior treatment but have nonrefractory disease. The study will compare 2 doses of oral SPR720 monotherapy of 500 and 1,000 milligrams versus placebo.

II 期試驗旨在招募約 35 名因鳥分枝桿菌複合體而患有 NTM-PD 的患者，這些患者約佔 80% 的 NTM-PD 病例。符合條件的參與者要么未接受過治療，要么接受過既往治療但患有非難治性疾病。該研究將比較兩種劑量的 500 毫克和 1,000 毫克口服 SPR720 單一療法與安慰劑。

The primary endpoint is slope change of weekly sputum bacterial burden from day 1 to the end of the trial's 56-day treatment period. We aim to see SPR720 treatment leading to a weekly sputum bacterial slope change, which is both negative and significantly better than placebo. Achieving this goal would make SPR720 the only agent in development that we're aware of with a demonstrated ability to drive early microbiological response against NTM as a stand-alone agent versus placebo.

主要終點是從第 1 天到試驗 56 天治療期結束時每週痰液細菌負荷的斜率變化。我們的目標是看到 SPR720 治療導致每週痰液細菌斜率變化，這既是負面的，又明顯優於安慰劑。實現這一目標將使 SPR720 成為我們所知道的唯一開發中的藥物，作為一種獨立藥物與安慰劑相比，它具有推動針對 NTM 的早期微生物學反應的能力。

Pairing this result with safety data that are consistent with the favorable safety findings observed in SPR720's prior Phase I trial would strongly support advancement of the program. More broadly speaking, the goal of our Phase IIa proof-of-concept studies to inform the design of a later stage and longer-term trial evaluating SPR720 in combination with current standard-of-care agents. Although we do not expect to comment on enrollment this trial progresses, 10 U.S. sites are currently active and more sites are expected to come onboard in the coming months.

將這一結果與與 SPR720 之前的 I 期試驗中觀察到的有利安全結果一致的安全數據相結合，將有力地支持該項目的推進。更廣泛地說，我們 IIa 期概念驗證研究的目標是為評估 SPR720 與當前標準護理藥物相結合的後期和長期試驗的設計提供信息。儘管我們不希望就此試驗的進展發表評論，但美國有 10 個站點目前處於活動狀態，預計未來幾個月將有更多站點加入。

This progress is in line with our target time lines and we remain on track to report top-line results from this Phase IIa trial in the first half of 2024. On behalf of Kamal, I'll now briefly discuss SPR206, our investigational next-generation polymyxin candidate being developed to treat multidrug-resistant gram-negative infections in the hospital setting. This program is supported by multiple collaborations, including Pfizer, Everest Medicine and the National Institute of Allergy and Infectious Disease and the U.S. Department of Defense.

這一進展符合我們的目標時間表，我們仍有望在 2024 年上半年報告該 IIa 期試驗的主要結果。我現在將代表 Kamal 簡要討論 SPR206，我們的下一步研究-新一代多粘菌素候選藥物正在開發中，用於治療醫院環境中的多重耐藥革蘭氏陰性菌感染。該計劃得到了多項合作的支持，包括輝瑞、Everest Medicine 和美國國家過敏和傳染病研究所以及美國國防部。

A major limitation of currently available polymyxins is the nephrotoxicity associated with these agents. With that as a premise, our team leveraged the understanding of the structure activity relationships to design 206 in a way that minimizes in vitro cytotoxicity in vivo kidney exposure. In animal models, this led to a substantial reduction of the nephrotoxicity profile compared to currently available polymyxins. Subsequent Phase I trials indicated that 206 was generally well tolerated at dose levels of both predictive therapeutic exposures in key tissues such as the lungs. These data, together with in vitro data demonstrating its potent activity against multidrug-resistant pathogens supports our belief that 206 has the potential to be a best-in-class polymyxine.

目前可用的多粘菌素的一個主要限制是與這些藥物相關的腎毒性。以此為前提，我們的團隊利用對構效關係的理解來設計 206，從而最大限度地減少體內腎臟暴露的體外細胞毒性。在動物模型中，與目前可用的多粘菌素相比，這導致腎毒性特徵顯著降低。隨後的 I 期試驗表明，在關鍵組織（如肺）中，206 在兩種預測治療暴露的劑量水平下通常具有良好的耐受性。這些數據連同證明其對多重耐藥病原體的有效活性的體外數據支持我們的信念，即 206 有潛力成為一流的多粘菌素。

Supported by encouraging clinical and preclinical results we have seen to date, we're now working to advance SPR206 into an externally funded Phase II trial in patients with hospital-acquired or ventilator-associated bacterial pneumonia. We expect to submit an IND application to the FDA to support this Phase II trial in the fourth quarter of this year.

在我們迄今為止看到的令人鼓舞的臨床和臨床前結果的支持下，我們現在正在努力將 SPR206 推進到一項由外部資助的 II 期臨床試驗中，該試驗用於治療醫院獲得性或呼吸機相關性細菌性肺炎患者。我們預計在今年第四季度向 FDA 提交 IND 申請以支持該 II 期試驗。

With that, I'll pass the call over now to Sath to review our financial results. Sath?

有了這個，我現在會把電話轉給 Sath 來審查我們的財務結果。薩特？

Thank you, Ankit, and good afternoon to all listening. It is my pleasure to now provide an overview of Spero's financial results for the fourth quarter and full year ended December 31, 2022. Total revenues for the fourth quarter of 2022 were $47.4 million compared with revenues of $2.7 million for the fourth quarter of 2021. The revenue increase for the fourth quarter of 2022 was primarily due to $46.1 million in collaboration revenue related to our agreements with GSK and Pfizer.

謝謝 Ankit，大家下午好。我很高興現在概述 Spero 截至 2022 年 12 月 31 日的第四季度和全年的財務業績。2022 年第四季度的總收入為 4740 萬美元，而 2021 年第四季度的收入為 270 萬美元。 2022 年第四季度的收入增長主要是由於與我們與葛蘭素史克和輝瑞達成的協議相關的 4610 萬美元合作收入。

Total revenue for the year ended December 31, 2022, was $53.5 million compared to $18.3 million for the year ended December 31, 2021. The revenue increase for the year ended December 31, 2022, was primarily due to the aforementioned partnership collaboration revenue. Research and development expenses for the fourth quarter of 2022 were $15.1 million compared to $17.2 million of research and development expenses for the same period in 2021. This year-over-year decrease was primarily due to a reduction in personnel-related costs following the strategic restructuring announced in May 2022.

截至 2022 年 12 月 31 日止年度的總收入為 5350 萬美元，而截至 2021 年 12 月 31 日止年度的總收入為 1830 萬美元。截至 2022 年 12 月 31 日止年度的收入增長主要是由於上述合作夥伴協作收入。 2022 年第四季度的研發費用為 1510 萬美元，而 2021 年同期的研發費用為 1720 萬美元。同比下降的主要原因是，在實施戰略後，人事相關成本有所減少2022 年 5 月宣布重組。

Research and development expenses for the year ended December 31, 2022, were $47.6 million compared to $64.5 million for the year ended December 31, 2021. The lower expenses in 2022 compared to 2021 primarily due to reduced program activity for tebipenem HBr as a result of the strategic restructuring last year. General and administrative expenses for the fourth quarter of 2022 were $6.5 million compared to $13 million of G&A expenses for the same period in 2021. This year-over-year decrease was primarily due to reduced headcount costs in our commercial, general and administrative functions as a result of the strategic restructuring.

截至 2022 年 12 月 31 日止年度的研發費用為 4,760 萬美元，而截至 2021 年 12 月 31 日止年度的研發費用為 6,450 萬美元。2022 年的費用低於 2021 年的主要原因是氫溴酸替比培南的項目活動減少，原因是去年的戰略重組。 2022 年第四季度的一般和行政費用為 650 萬美元，而 2021 年同期的一般和行政費用為 1300 萬美元。同比下降的主要原因是我們的商業、一般和行政職能部門的人員成本減少，因為戰略重組的結果。

General and administrative expenses for the year ended December 31, 2022 were $36.5 million compared to $41.7 million for the year ended December 31, 2021. The lower expenses in 2022 compared to 2021, again, primarily as a result of the strategic restructuring. Restructuring expenses of $11.6 million were incurred during the year ended December 31, 2022. These expenses primarily comprised of $8.6 million of severance and other employee costs, $2.4 million of discontinuation costs such as contract termination fees and $0.6 million of lease impairment expenses.

截至 2022 年 12 月 31 日止年度的一般和行政費用為 3650 萬美元，而截至 2021 年 12 月 31 日止年度為 4170 萬美元。2022 年的費用低於 2021 年，這再次主要是由於戰略重組。截至 2022 年 12 月 31 日止年度發生了 1,160 萬美元的重組費用。這些費用主要包括 860 萬美元的遣散費和其他員工費用、240 萬美元的終止合同費用（例如合同終止費）和 60 萬美元的租賃減值費用。

Spero reported net income of $26.8 million for the fourth quarter and a full year net loss of $46.4 million for the year ended December 31, 2022 or net income of $0.55 and net loss of $1.23 per share of common stock, respectively. Net losses for the fourth quarter and year ended December 31, 2021, were $29.2 million and $89.8 million or $0.90 and $2.91 per share of common stock, respectively.

Spero 報告第四季度淨收入為 2680 萬美元，截至 2022 年 12 月 31 日止年度全年淨虧損為 4640 萬美元，每股普通股淨收入分別為 0.55 美元和淨虧損 1.23 美元。截至 2021 年 12 月 31 日的第四季度和年度的淨虧損分別為 2920 萬美元和 8980 萬美元，即普通股每股虧損 0.90 美元和 2.91 美元。

As of December 31, 2022, Spero had cash and cash equivalents of $109.1 million. Based on its current operating plan, Spero believes that its cash and cash equivalents, together with other nondilutive funding commitments, will be sufficient to fund its operating expenses and capital expenditure requirements beyond 2024. For further details on our financials, please refer to our 10-K filed with the SEC today. We will now open the call for questions.

截至 2022 年 12 月 31 日，Spero 擁有現金和現金等價物 1.091 億美元。根據其目前的運營計劃，Spero 認為其現金和現金等價物以及其他非稀釋性資金承諾將足以為其 2024 年以後的運營費用和資本支出需求提供資金。有關我們財務狀況的更多詳細信息，請參閱我們的 10 -K 今天向美國證券交易委員會提交了文件。我們現在將開始提問。

Operator?

操作員？

(Operator Instructions)

（操作員說明）

Our first question comes from Louise Chen with Cantor.

我們的第一個問題來自 Louise Chen 和 Cantor。

Congratulations on all the progress this quarter. So I'm going to ask a few questions. First, on your cash balance, will it take you to the 720 Phase II readout? And then the other question I wanted to ask you was, if your drug, the 720 is approved for NTM, where do you expect to fit into the treatment paradigm? And then last question is just on OpEx. How we should think about that relative to 2022 and then with the potential increase in R&D expense, I guess, given the new programs that you're working on, how we should phase that in?

祝賀本季度取得的所有進展。所以我要問幾個問題。首先，關於您的現金餘額，它會帶您到 720 Phase II 讀數嗎？然後我想問你的另一個問題是，如果你的藥物 720 被批准用於 NTM，你希望在治療範式中適應什麼？最後一個問題是關於 OpEx 的。相對於 2022 年，我們應該如何考慮這一點，然後隨著研發費用的潛在增加，我想，鑑於您正在開展的新計劃，我們應該如何分階段實施？

Thanks, Louise, for the questions. Your first and third question relates to some of our financials. So I'll have Sath answer those. But perhaps I'll start with the treatment paradigm for 720. So just to zoom out to 100,000 feet, NTM is a debilitating chronic disease. It affects about 0.25 million patients worldwide, half in the U.S., half in the rest of the world. It's a slow-growing, debilitating disease where patients would lose their quality of life slowly and the longer a patient has the disease, the more long term and lasting damage the lungs have.

謝謝，路易絲，提出問題。你的第一個和第三個問題與我們的一些財務有關。所以我會讓 Sath 回答這些問題。但也許我會從 720 的治療範例開始。所以只要縮小到 100,000 英尺，NTM 就是一種使人衰弱的慢性疾病。它影響全球約 25 萬患者，其中一半在美國，一半在世界其他地區。這是一種生長緩慢、使人衰弱的疾病，患者的生活質量會慢慢下降，患者患病時間越長，肺部受到的損害就越長期和持久。

So we believe that the treatment paradigm for NTM drugs generally and also 720 is to be a solution for patients early in their disease journey. Now certainly, the drug has the microbiological characteristics to be useful throughout a patient's disease journey. We're starting with first line because it's 75% of the current patient population, number one. And number two, as we've looked at published literature suggests that 75% of patients that are on the current options they have discontinue within a year. And of the patients that actually stick with it, half of them don't find any relief.

因此，我們認為 NTM 藥物和 720 的治療範例將成為患者疾病早期的解決方案。現在可以肯定的是，該藥物具有微生物學特性，可在患者的整個疾病過程中發揮作用。我們從一線開始，因為它佔當前患者人數的 75%，排名第一。第二，正如我們查看已發表的文獻表明，75% 的接受當前選擇的患者在一年內停止了治療。在真正堅持下去的患者中，有一半沒有找到任何緩解。

So the major unmet need right now is first-line treatment and something that patients can take throughout their disease journey to avoid becoming refractory patients that's where we'll start, and then we'll explore how we expand the story from there as we continue to generate clinical data. So that's perhaps the first part of your question. For the financial components of your question, I'll turn it to Sath.

因此，目前未滿足的主要需求是一線治療，以及患者在整個疾病旅程中可以採取的治療措施，以避免成為難治性患者，這是我們的起點，然後我們將探索如何在繼續的過程中從那裡擴展故事生成臨床數據。所以這可能是你問題的第一部分。對於你問題的財務部分，我會把它交給 Sath。

Thanks for the question, Louise. So your first question on whether the cash balance will take us through the top-line data readout for 720. That is indeed the case our expected top-line data readout is in the first half of next year. Our expected cash runway is to beyond 2024, meaning beyond the end of 2024. So we expect to have this data readout with still a healthy balance of cash sitting on our books when it becomes available. So that -- unless you had questions on the cash, I can move on to the operating expense question.

謝謝你的問題，路易絲。所以你的第一個問題是現金餘額是否會讓我們通過 720 的頂線數據讀數。我們預計明年上半年的頂線數據讀數確實是這種情況。我們預計的現金跑道將超過 2024 年，也就是超過 2024 年底。因此，我們預計在數據可用時，我們的賬簿上仍有健康的現金餘額。所以——除非你對現金有疑問，否則我可以繼續討論運營費用問題。

Yes, that makes sense.

是的，這是有道理的。

Great. On the operating expenses, Louise, if you look at our financials for this quarter, other than a onetime payment made to Meiji as disclosed in our 10-K, the run rate for OpEx is virtually the same as our burn on OpEx for 3Q of last year. So for 3Q of last year, we've been in the early teens in terms of dollars. If you extrapolate that early teens burn on (inaudible) expenses on a $109 million cash balance that would give you the support for our disclosed cash runway to beyond 2024.

偉大的。關於運營費用，Louise，如果你看一下我們本季度的財務數據，除了我們 10-K 中披露的向明治支付的一次性付款外，OpEx 的運行率幾乎與我們第三季度的 OpEx 燃燒率相同去年。因此，對於去年的第三季度，我們在美元方面一直處於十幾歲的早期。如果你推斷出青少年在 1.09 億美元的現金餘額上消耗（聽不清）費用，這將為你提供對我們披露的現金跑道到 2024 年以後的支持。

For the in between R&D, you are, of course, right that we expect to scale that up and we start Phase III trials, but those will be funded by the milestones we received from GSK on development through that process. So indeed, R&D expenses will go up, but so will the cash and milestones coming in from our partners. And therefore, for GSK, we expect that to be a wash. Prior run rate will give you the calculations that would support our disclosed cash runway.

對於中間的研發，你當然是對的，我們希望擴大規模並開始 III 期試驗，但這些將由我們從葛蘭素史克通過該過程獲得的開發里程碑資助。因此，研發費用確實會增加，但來自我們合作夥伴的現金和里程碑也會增加。因此，對於葛蘭素史克，我們希望這是一次洗禮。先前的運行率將為您提供支持我們披露的現金跑道的計算。

This concludes our question-and-answer session. I will now turn the call back to Dr. Mahadevia.

我們的問答環節到此結束。我現在將電話轉回 Mahadevia 博士。

Thank you, operator, and thanks to everyone who joined us on the call today to hear about our recent progress. We look forward to the continued advancement of our programs and wish everyone a nice evening.

謝謝你，接線員，並感謝今天加入我們的電話會議以了解我們最近的進展的每一個人。我們期待著我們的計劃不斷取得進展，並祝大家度過一個愉快的夜晚。

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation. 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。祝你有美好的一天。