Spero Therapeutics Inc (SPRO) 2022 Q3 法說會逐字稿

Good afternoon, and welcome to the Spero Therapeutics Third Quarter 2022 Financial Results Conference Call. (Operator Instructions) Please be advised that this call is being recorded, and a replay will be available.

下午好，歡迎參加 Spero Therapeutics 2022 年第三季財務業績電話會議。 （操作員指示）請注意，此通話將會被錄音，並可重播。

You can find information on the replay and further information related to today's announcement on the Spero Therapeutics website, www.sperotherapeutics.com.

您可以在 Spero Therapeutics 網站 www.sperotherapeutics.com 上找到有關重播的資訊以及與今天的公告相關的更多資訊。

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

現在，我想將電話會議交給 Spero Therapeutics 投資者關係和策略財務副總裁 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 third quarter of 2022. A press release is available on the Investor page of the Spero Therapeutics website.

謝謝接線員，也謝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 2022 年第三季的研發管線更新。新聞稿可在 Spero Therapeutics 網站的投資者頁面上查閱。

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 development programs; management's assessment of the results of such preclinical studies and clinical trials; the company's cash forecast and anticipated expenses and its sufficiency of its cash resources. 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.

在我們開始之前，我想提醒您，本次電話會議中提供的一些資訊包含基於我們目前預期的前瞻性陳述，包括有關 SPR720、SPR206 和氫溴酸替比培南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計劃的設計、啟動、時間安排、進展和現金結果管理對此類臨床資源此類前瞻性陳述並不構成績效保證，本公司的實際結果可能與此類陳述中的結果有重大差異。

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 Factor section of our quarterly report on Form 10-Q for the quarter ended September 30, 2022, filed 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.

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，包括我們今天提交的截至 2022 年 9 月 30 日的季度 10-Q 表季度報告中的風險因素部分。這些前瞻性陳述僅代表本次電話會議召開之日的觀點，本公司不承擔在今天電話會議召開之日後公開更新任何前瞻性陳述或提供有關本公司的新資訊的義務。

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

參加今天電話會議的有執行長 Ankit Mahadevia 博士；首席醫療官 Kamal Hamed 博士；以及我們的財務長 Sath Shukla。

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

說到這裡，我想把電話轉給 Ankit Mahadevia 博士。請繼續，Ankit。

Thank you, Ted, and good afternoon to everyone who's joined us for a discussion of our third quarter financial results and company highlights. The third quarter was an exciting time for Spero as we successfully executed on our new strategic direction that we set forward in the second quarter.

謝謝你，泰德，祝所有參加我們第三季財務業績和公司亮點討論的人下午好。第三季對 Spero 來說是令人興奮的時刻，因為我們成功執行了第二季制定的新策略方向。

When it became clear that tebipenem would not receive FDA approval on its first cycle of review, the strategy we laid out was to move forward with SPR720 as our lead asset and advanced tebipenem HBr and SPR206 as our designated partnership-directed programs. We made this decision because we felt it would position us for future growth, allow us to maintain good stewardship of our capital and ensure the medicines that we develop continue to advance towards potential regulatory approval.

當明確替比培南不會在第一輪審查中獲得 FDA 批准時，我們制定的策略是繼續推進 SPR720 作為我們的主導資產，並將替比培南氫溴酸鹽和 SPR206 作為我們指定的合作夥伴指導計畫。我們做出這項決定是因為我們認為這將為我們未來的成長奠定基礎，使我們能夠很好地管理我們的資本，並確保我們開發的藥物繼續獲得潛在的監管部門批准。

In addition, our long track record of establishing creative partnerships with leading organizations gave us confidence that we will be able to successfully execute our new strategic approach.

此外，我們與領先組織建立創造性合作夥伴關係的長期記錄使我們有信心能夠成功執行我們的新策略方針。

Our confidence and our approach were validated this past September when we entered into an exclusive license agreement with GSK for tebipenem HBr. As delineated in last week's press release, we have now closed this transaction. Spero has already received the $9 million associated with GSK's equity investment and will soon receive the $66 million upfront payment and will be eligible for up to $525 million in additional milestone payments as well as low single-digit to low double-digit tiered royalties on net product sales.

去年 9 月，我們與葛蘭素史克公司達成了氫溴酸替比培南的獨家授權協議，證明了我們的信心和方法的有效性。正如上週新聞稿中所述，我們現已完成此交易。 Spero 已經收到了與 GSK 股權投資相關的 900 萬美元，並將很快收到 6600 萬美元的預付款，並有資格獲得高達 5.25 億美元的額外里程碑付款以及淨產品銷售額的低個位數到低兩位數分級特許權使用費。

This collaboration adds even more strength to our balance sheet and shareholder base. In exchange for the upfront payment and potential milestones and royalties, GSK is being granted an exclusive license to develop and commercialize tebipenem HBr in all territories, except Japan and certain other Asian countries, which will be retained by Spero's partner, Meiji Seika.

此次合作將進一步增強我們的資產負債表和股東基礎。作為預付款和潛在里程碑及特許權使用費的交換，葛蘭素史克被授予在除日本和某些其他亞洲國家以外的所有地區開發和商業化氫溴酸替比培南的獨家許可，而這些許可將由 Spero 的合作夥伴明治制果保留。

Under the agreement, Spero is responsible for the execution of an upcoming Phase III study and GSK is responsible for the execution and cost of additional development and commercialization activities for tebipenem HBr outside of the Meiji Seika territory.

根據協議，Spero 負責執行即將進行的 III 期研究，而 GSK 負責在明治製果地區以外執行氫溴酸替比培南的額外開發和商業化活動並承擔相關費用。

Given GSK's global reach and history as a leader in infectious diseases, we believe they are the ideal partner to fully unlock tebipenem's value and expeditiously delevered the medicine to patients following regulatory approval. We therefore view the new partnership as our key step towards potentially providing millions of complicated urinary tract infection patients with an at-home oral option that may also reduce hospital resource utilization.

鑑於葛蘭素史克的全球影響力和作為傳染病領域領導者的歷史，我們相信他們是充分釋放替比培南價值的理想合作夥伴，並在獲得監管部門批准後迅速將藥物交付給患者。因此，我們認為新的合作關係是我們向數百萬複雜尿路感染患者提供家庭口服治療選擇的關鍵一步，這也可能減少醫院資源的使用率。

It's our hope that tebipenem HBr may provide an alternative to the intravenous therapies which currently are often a patient's only option. Extensive clinical and market research data suggests that such an option would improve clinical care while delivering substantial economic benefits to patients, physicians and payers alike. We are eager to continue developing tebipenem as the potential first oral carbapenem antibiotic for the development of cUTI and are thrilled to be supported in this endeavor by our world-class partners at GSK.

我們希望氫溴酸替比培南可以提供一種替代靜脈注射療法的方案，因為目前靜脈注射療法往往是患者唯一的選擇。大量臨床和市場研究數據表明，這種選擇將改善臨床護理，同時為患者、醫生和付款人帶來巨大的經濟效益。我們渴望繼續開發替比培南，將其作為治療 cUTI 的潛在首個口服卡巴培南類抗生素，並很高興得到葛蘭素史克世界級合作夥伴的支持。

Looking ahead for tebipenem HBr, we expect to initiate a new Phase III clinical trial in 2023. Prior to entering our agreement with GSK, we aligned with the FDA on key components of the trial design in a recent Type A meeting. Feedback from this meeting indicated that positive results from this single additional trial, together with confirmatory non-clinical evidence of efficacy, could be sufficient to support tebipenem HBr's approval for the treatment of complicated urinary tract infections, including pyelonephritis for a limited use indication.

展望氫溴酸替比培南，我們預計 2023 年啟動新的 III 期臨床試驗。在與 GSK 達成協議之前，我們在最近的 A 類會議上與 FDA 就試驗設計的關鍵要素進行了協調。本次會議的回饋表明，此額外試驗的積極結果，加上非臨床療效的確證，足以支持批准氫溴酸替比培南用於治療複雜的泌尿道感染，包括有限用途的腎盂腎炎。

This upcoming pivotal trial will build upon the extensive clinical and non-clinical data previously generated with tebipenem HBr, which include the results of our prior Phase III clinical trial, ADAPT-PO. The results of this clinical trial, which were published in the New England Journal of Medicine, demonstrated that oral tebipenem HBr was well tolerated and non-inferior to IV ertapenem in the treatment of adult patients with complicated urinary tract infections or acute pyelonephritis as per the prespecified statistical protocol. We are currently working to finalize the design of our upcoming trial, which will be the subject of a special protocol assessment request.

這項即將進行的關鍵試驗將以先前使用氫溴酸替比培南產生的大量臨床和非臨床數據為基礎，其中包括我們先前的 III 期臨床試驗 ADAPT-PO 的結果。這項臨床試驗的結果發表在《新英格蘭醫學雜誌》上，結果表明，口服氫溴酸替比培南耐受性良好，且在治療患有複雜性尿路感染或急性腎盂腎炎的成年患者方面，按照預先設定的統計方案，其療效不劣於靜脈注射厄他培南。我們目前正在努力完成即將進行的試驗的設計，這將成為特殊協議評估請求的主題。

With a review of our newly forged partnership complete, I'd like to now introduce Spero's recently appointed Chief Medical Officer, Dr. Kamal Hamed. Kamal joined Spero in September, bringing with him an impressive range of experience within the biotech industry, global pharmaceutical companies and as a practicing physician caring for patients with infectious diseases. He has a long track record in infectious disease drug development, including multiple drug approvals. He's integrated seamlessly into his new role at Spero and has displayed the expertise and commitment to our Spero values that made him the ideal candidate to serve as our CMO.

在回顧我們新建立的合作夥伴關係之後，我現在想介紹 Spero 新任命的首席醫療官 Kamal Hamed 博士。卡馬爾於 9 月加入 Spero，帶來了他在生物技術行業、全球製藥公司以及作為傳染病患者護理執業醫師方面的豐富經驗。他在傳染病藥物開發方面擁有長期的經驗，包括多項藥物的批准。他完美地融入了 Spero 的新角色，並展示了專業知識和對 Spero 價值觀的承諾，這使他成為擔任我們 CMO 的理想人選。

With the added strength Kamal brings to our management team, our clinical pipeline and our GSK partnership, we've laid the foundation for sustained growth into 2023 and beyond. We have cash runway through key milestones for each of our clinical programs and have a deeply talented team in place. All of our programs are supported by clinical and non-clinical data that provide clear differentiation over competing approaches, and each has demonstrated the potential to deliver clear clinical and economic benefits.

卡邁勒為我們的管理團隊、臨床管線和葛蘭素史克合作夥伴關係增添了實力，我們為 2023 年及以後的持續成長奠定了基礎。我們為每個臨床項目的關鍵里程碑提供了現金支持，並且擁有一支才華橫溢的團隊。我們的所有項目都得到了臨床和非臨床數據的支持，這些數據與競爭方法有明顯的區別，並且每個項目都顯示出提供明顯臨床和經濟效益的潛力。

With that, I will now turn the call over to Kamal to speak about his decision to join us here at Spero and to provide an update on the SPR720 and SPR206 programs. I'll hand it over to you, Kamal.

說完這些，我現在將電話轉給卡馬爾，讓他談談他加入 Spero 的決定，並提供有關 SPR720 和 SPR206 計劃的最新進展。我會把它交給你，卡馬爾。

Thank you very much, Ankit, for the kind introduction. The core drivers behind my decision to join Spero were the clear strength of its pipeline, the integrity and expertise of the management team as well as the guiding principles behind Spero's drug development strategy, which I view as the ideal approach for the antibiotic field.

非常感謝 Ankit 的熱情介紹。我決定加入 Spero 的核心驅動力是其產品線的明顯優勢、管理團隊的誠信和專業知識以及 Spero 藥物開發策略背後的指導原則，我認為這是抗生素領域的理想方法。

This approach focuses on developing medicines that, first and foremost, address the mathematical needs of patients while simultaneously providing clear benefits to the health care system more broadly. While successfully executing on this approach, I believe we can develop anti-infectives that are positioned for rapid and widespread uptake following regulatory approval.

這種方法專注於開發藥物，首先滿足患者的數學需求，同時為更廣泛的醫療保健系統提供明顯的好處。在成功執行這種方法的同時，我相信我們可以開發出在獲得監管機構批准後能夠迅速廣泛應用的抗感染藥物。

Since Ankit walked you through how we believe tebipenem HBr meets these criteria, I'll focus on SPR720 and SPR206.

由於 Ankit 向您介紹了我們如何認為氫溴酸替比培南符合這些標準，因此我將重點放在 SPR720 和 SPR206。

I'll start with SPR720, our novel oral candidate being developed as a first-line treatment for non-tuberculous microbacterial pulmonary disease, or NTMPD for short which is an orphan disease. NTMPD is an area of high unmet medical need as there are currently no FDA-approved options for first-line treatment.

我首先要介紹的是 SPR720，這是我們開發的新型口服候選藥物，用於治療非結核性微細菌性肺病（簡稱 NTMPD，一種罕見疾病）的第一線治療。 NTMPD 是一個醫療需求未被滿足的領域，因為目前尚無 FDA 批准的一線治療方案。

SPR720 is the stable prodrug that's rapidly converted to the active moiety SPR719. In vitro studies have demonstrated SPR719's potent activity against the broad spectrum of NTM species, which is a result of its ability to inhibit ATPase located on the [dried ASP] subunit of the tetrameric (inaudible) A2B2 protein. This mechanism of action is importantly distinct from that of fluoroquinolones, thus avoiding cross resistance with fluoroquinolones and other marketed antibiotics, which has been corroborated with in vitro surveillance data from recent anti-M clinical isolates. It's important to note that SPR719 is highly concentrated in microphages, a size where NTM survive and replicate.

SPR720 是一種穩定的前驅藥物，可快速轉化為活性部分 SPR719。體外研究表明，SPR719 對廣譜 NTM 物種具有強效活性，這是因為它能夠抑制位於四聚體（聽不清楚）A2B2 蛋白的 [乾燥 ASP] 亞基上的 ATPase。這種作用機轉與氟喹諾酮類藥物有重要區別，從而避免了與氟喹諾酮類藥物和其他市售抗生素的交叉抗藥性，這已得到最近抗 M 臨床分離株的體外監測數據的證實。值得注意的是，SPR719 在微噬細胞中濃度很高，而微噬細胞的大小適合 NTM 存活和複製。

In vivo data supporting SPR720's development come mainly from a newly in chronic infection model, where it displayed pulmonary activity against the most prevalent slowly growing and the most prevalent rapidly growing NTM species and an approximately 100-subject Phase I first-in-human study supporting its safety and tolerability at exposures above predicted therapeutic levels.

支持 SPR720 開發的體內數據主要來自一種新近的慢性感染模型，其中它對最常見的緩慢生長和最常見的快速生長 NTM 物種表現出肺部活性，並且大約 100 名受試者的 I 期首次人體研究支持其在高於預測治療水平的暴露下的安全性和耐受性。

These data fuel my optimism for the program Note, there are just one component of SPR's sound value proposition. A second key component is the clinical development strategy that we are pursuing. This strategy aims to maximize SPR720's therapeutic and commercial potential by addressing patients with NTMPD who are early in their disease journey, in the treatment naive or treatment in experienced stages.

這些數據增強了我對該計劃的樂觀情緒。請注意，這只是 SPR 合理價值主張的一個組成部分。第二個關鍵組成部分是我們正在推行的臨床發展策略。此策略旨在透過針對處於疾病早期、初治階段或已接受過治療階段的 NTMPD 患者，最大限度地發揮 SPR720 的治療和商業潛力。

The off-label therapy is currently available for these patients have poor risk/benefit profile and are frequently unable to prevent the progression for late-stage refractory disease, even when administered continuously for 1 to 2 years. In some instances, because physicians view the risk/benefit profiles of the antibiotic combinations currently employed as poor, they choose to delay for microtherapy and instead initially only suggest steps to improve bronchial hygiene.

目前針對這些患者可用的非說明書療法具有較差的風險/效益特徵，即使連續用藥 1 至 2 年也常常無法阻止晚期難治性疾病的進展。在某些情況下，由於醫生認為目前使用的抗生素組合的風險/益處狀況不佳，他們選擇推遲微療法，而是最初僅建議採取改善支氣管衛生的措施。

Unfortunately, this approach does not prevent disease progression. Patients who progress to refractory disease will often suffer irreversible lung damage, leading to debilitating symptoms that may prevent them from performing routine daily activities.

不幸的是，這種方法並不能阻止病情進展。發展為難治性疾病的患者通常會遭受不可逆的肺損傷，導致衰弱症狀，可能使他們無法進行日常活動。

Our recent virtual R&D event featured an NTMPD patient testimonial and expert perspective from a key opinion leader describing both the devastating effects of these symptoms as well as the stark limitations of currently available therapies. I'd highly encouraged all of those who are interested to view the replay of our event on the Spero website.

我們最近的虛擬研發活動以 NTMPD 患者的證詞和關鍵意見領袖的專家觀點為特色，描述了這些症狀的破壞性影響以及目前可用療法的明顯局限性。我強烈鼓勵所有有興趣的人在 Spero 網站上觀看我們活動的重播。

Despite the permanent lung damage that comes with progression to refractory NTMPD, most other agents in development only seek to treat the disease at this late stage. We however are taking a different approach. Our goal is to develop SPR720 to intervene before patients progress to refractory disease so that we can help prevent irreversible lung damage from the infection. We believe that this will allow SPR720 to elicit more meaningful improvement in clinical outcomes and quality of life.

儘管難治性 NTMPD 的進展會帶來永久性的肺損傷，但大多數其他正在研發的藥物僅尋求治療晚期疾病。然而，我們採取了不同的方法。我們的目標是開發 SPR720，在患者病情發展為難治性疾病之前進行幹預，從而幫助防止感染造成不可逆轉的肺部損傷。我們相信這將使 SPR720 在臨床結果和生活品質方面帶來更有意義的改善。

In addition, focusing on treatment-naive and treatment-inexperienced patients provides a larger addressable patient population for SPR720 and as 75% of NTMPD patients fall within these classifications.

此外，專注於初治和缺乏治療經驗的患者為 SPR720 提供了更大的可尋址患者群體，因為 75% 的 NTMPD 患者屬於這些分類。

As referenced in today's press release, we have initiated the SPR Phase IIa clinical trial designed to achieve early and robust proof-of-concept for this investigational medicine.

正如今天的新聞稿中所提到的，我們已經啟動了 SPR IIa 期臨床試驗，旨在為該研究藥物提供早期和強大的概念驗證。

Top line data are expected in the first half of 2024, and we no longer plan to announce interim data. Given that the trial will be relatively focused with a planned enrollment of 35 patients, we believe announcing data from all patients at once will allow us to make a disclosure that's more impactful from both a scientific and value-creation perspective, given our newly extended cash runway due to the GSK agreement.

預計收入數據將在 2024 年上半年公佈，我們不再計劃公佈中期數據。鑑於該試驗將相對集中，計劃招募 35 名患者，我們相信，一次性公佈所有患者的數據將使我們能夠做出更具影響力的披露，從科學和價值創造的角度來看，考慮到我們因與 GSK 的協議而新延長的現金流。

The trial design remains unchanged from what was discussed on Spero's last earnings call. The study will compare 2 doses of oral SPR720 monotherapy, 500 and 1,000 milligrams, versus placebo in treatment-naive or treatment-inexperienced patients. The primary endpoint is slow change of weekly sputum bacterial burden from day 1 to day 56. Specifically, we hope to observe a negative slope with SPR720 treatment that's significantly better than that observed with placebo.

試驗設計與 Spero 上次收益電話會議上討論的內容保持不變。該研究將對初治或未接受過治療的患者，比較兩種劑量的口服 SPR720 單一療法（500 毫克和 1,000 毫克）與安慰劑的效果。主要終點是從第 1 天到第 56 天每週痰液細菌負擔的緩慢變化。具體來說，我們希望觀察到 SPR720 治療的負斜率明顯優於安慰劑。

This methodology for assessing monotherapy activity of an anti-microbacterial agent is both well-established and validated, having previously been employed in the evaluation of drugs approved for mycobacterium tuberculosis.

這種評估抗菌藥物單一療法活性的方法已經成熟並得到驗證，之前曾用於評估批准用於治療結核分枝桿菌的藥物。

Demonstrating SPR720's ability to drive an early microbiological response as a stand-alone agent versus placebo would be a potential key catalyst for the program. It would clearly differentiate SPR720 from other therapy. There are currently no existing agents that have accomplished this feat. It would also provide clear proof of concept for SPR720's long-term development as a component of combination regimens for NTMPD.

證明 SPR720 作為獨立藥物而非安慰劑能夠推動早期微生物反應的能力將成為該計劃的潛在關鍵催化劑。它將明顯區分 SPR720 與其他療法。目前尚無現存特工完成這項壯舉。它還將為 SPR720 作為 NTMPD 聯合方案的組成部分的長期發展提供明確的概念證明。

I'll next discuss what I find most exciting about SPR206, our Phase II ready IV polymyxin antibiotic candidate being developed to treat multidrug-resistant Gram-negative bacterial infections within the hospital setting.

接下來，我將討論我發現的 SPR206 最令人興奮的地方，SPR206 是我們準備進入 II 期 IV 期的多粘菌素抗生素候選藥物，用於在醫院環境中治療多重抗藥性革蘭氏陰性細菌感染。

For background, the development of treatments for Gram-negative bacterial infections is an area of research that has been relatively stagnant with a number of novel approval for these infections, sharply decreasing over the past 40 years. A major reason for this has been the field inability to generate agents that can maintain antimicrobial activity while also penetrating the negatively charged [alpha membrane] of Gram-negative bacteria.

背景是，革蘭氏陰性菌感染的治療方法的開發是一個相對停滯的研究領域，針對這些感染的新療法的批准數量在過去 40 年裡急劇減少。造成這種情況的一個主要原因是，該領域無法產生既能保持抗菌活性又能穿透革蘭氏陰性細菌帶負電荷的 [α 膜] 的藥劑。

This lack of innovation has left patients with extensively drug-resistant, Gram-negative infections with suboptimal therapeutic options that consist of combination regimens, including older polymyxins, such as colistin, which is one of the most widely used polymyxins today. Unfortunately, colistin and other polymyxins are associated with remarkable nephrotoxicity, creating a need for next-generation agents that can take their place in combination regimens.

缺乏創新導致患有廣泛抗藥性革蘭氏陰性菌感染的患者只能採用由聯合療法組成的次優治療方案，包括較老的多粘菌素，例如粘菌素，它是當今使用最廣泛的多粘菌素之一。不幸的是，粘菌素和其他多粘菌素具有顯著的腎毒性，因此需要可以在聯合治療方案中取代它們的下一代藥物。

In addition, (inaudible) Colistin bronchoalveolar lavage (inaudible) study showed that colistin was unable to penetrate patients lungs with levels being undetectable as a conclusion for the study. This highlights another key limitation of the agent as about half of the patients infected with multidrug-resistant Gram-negative pathogens suffered from lung infections, i.e., pneumonia. Given its mechanism of action, we believe that SPR206 can overcome the resistance and Gram-negative bacteria to other classes of antibiotics as well as the limitations of currently available polymyxins.

此外，（聽不清楚）粘菌素支氣管肺泡灌洗（聽不清楚）研究表明，粘菌素無法滲透到患者的肺部，其水平無法檢測到，這是該研究的結論。這凸顯了該藥物的另一個關鍵局限性，因為大約一半感染多重抗藥性革蘭氏陰性病原體的患者患有肺部感染，即肺炎。鑑於其作用機制，我們相信 SPR206 可以克服革蘭氏陰性菌對其他類別抗生素的抗藥性以及目前可用的多粘菌素的局限性。

This belief is supported by preclinical data demonstrating that SPR206 given its potent intrinsic activity and ability to cannibalize Gram-negative bacterial membrane, when combined with beta lactams and carbapenem, is very effective in the profound killing of several extensively drug-resistant Gram-negative pathogens, including carbapenem-resistant Acinetobacter baumannii, which have a mortality rate of 40% to 50%.

這一信念得到了臨床前數據的支持，臨床前數據表明，鑑於 SPR206 強大的內在活性和蠶食革蘭氏陰性細菌膜的能力，當與β-內酰胺類和卡巴培南類藥物結合時，能夠非常有效地殺死幾種廣泛耐藥的革蘭氏陰性病原體，包括耐卡巴培南類藥物結合鮑曼的死亡率為 50%。

Further clinical data show that SPR206 can achieve exposures above predictive therapeutic levels, including concentrations in the lungs sufficient for killing these pathogens.

進一步的臨床數據表明，SPR206 可以達到高於預測治療水平的暴露量，包括足以殺死這些病原體的肺部濃度。

In clinical studies to date, SPR206 has been well tolerated and there has been no evidence of nephrotoxicity doses with exposures above therapeutic levels. When taken together, we believe these clinical and preclinical data clearly highlight SPR206 as a potentially best-in-class polymyxin.

在迄今為止的臨床研究中，SPR206 耐受性良好，且沒有證據表明暴露量超過治療水平會導致腎毒性。綜合起來，我們相信這些臨床和臨床前數據清楚地表明 SPR206 是一種潛在的同類最佳多粘菌素。

This best-in-class potential has helped SPR206 gained the support of partners, including Pfizer, who recently made a $5 million payment of our previously announced ex U.S. ex Asia license agreement. Thanks to the support from Pfizer and other partners SPR206 is fully funded by external non-dilutive sources through Phase II development. The upcoming Phase II study is designed to enroll patients with multidrug-resistant pathogens and is expected to begin in the fourth quarter of 2023.

這種一流的潛力幫助 SPR206 獲得了包括輝瑞在內的合作夥伴的支持，輝瑞最近根據我們先前宣布的美國以外亞洲許可協議支付了 500 萬美元。感謝輝瑞和其他合作夥伴的支持，SPR206 在第二階段開發過程中完全由外部非稀釋性來源資助。即將進行的 II 期研究旨在招募具有多重抗藥性病原體的患者，預計將於 2023 年第四季開始。

I'm pleased to announce that the U.S. Patent and Trademark Office has issued a composition of a patent with formulations thereof, and methods of use in treating bacterial infections with SPR206. The patent is assigned to Spero and has the lifespan extending into at least June 2039.

我很高興地宣布，美國專利商標局已經發布了一項專利組合物及其配方，以及使用 SPR206 治療細菌感染的方法。該專利已轉讓給 Spero，有效期限至少延長至 2039 年 6 月。

So this completes my pipeline review. I'll now turn the call over to our Chief Financial Officer, Sath Shukla to review our financial results. Sath?

這樣我的管道審查就完成了。現在我將把電話轉給我們的財務長 Sath Shukla，來審查我們的財務結果。薩斯？

Thank you, Kamal. As of September 30, 2022, Spero has approximately $50.4 million in cash, cash equivalents and marketable securities. This does not include the $75 million in total gross proceeds from the upfront payment and equity investment being made by GSK in connection with the exclusive license agreement for tebipenem HBr.

謝謝你，卡馬爾。截至 2022 年 9 月 30 日，Spero 擁有約 5,040 萬美元的現金、現金等價物和有價證券。這還不包括葛蘭素史克根據氫溴酸替比培南獨家許可協議支付的預付款和股權投資總額 7,500 萬美元。

Given that the GSK transaction is now closed, these expected payments have been invoiced, the $9 million in equity investment has been received, and the remaining $66 million upfront payment is expected to be delivered in November.

鑑於GSK交易現已完成，這些預期付款已開立發票，900萬美元的股權投資已收到，剩餘的6,600萬美元預付款預計將於11月交付。

Based on our current projections, we believe our existing cash, cash equivalents and marketable securities, together with the other non-dilutive funding commitments and the anticipated proceeds from the GSK license agreement, equity investment and milestones, will be sufficient to fund our planned operating expenses and capital expenditures beyond 2024.

根據我們目前的預測，我們相信我們現有的現金、現金等價物和有價證券，加上其他非稀釋性融資承諾以及葛蘭素史克許可協議、股權投資和里程碑預期的收益，將足以資助我們2024年以後計劃的運營費用和資本支出。

This anticipated runway is expected to take us through key clinical milestones, including: Final top line Phase II data for SPR720, the initiation of a Phase III clinical trial of tebipenem HBr and the initiation of a Phase II clinical trial for SPR206.

這條預期的跑道預計將帶領我們實現關鍵的臨床里程碑，包括：SPR720 的最終 II 期頂線數據、氫溴酸替比培南 III 期臨床試驗的啟動以及 SPR206 II 期臨床試驗的啟動。

Turning now to our remaining financial results. Total revenues for the third quarter of 2022 were $2 million compared with revenues of $3.1 million in the third quarter of 2021. The revenue decrease was primarily due to a $1.5 million decrease in funding under our DoD agreement relating to SPR206. a $0.2 million decrease in qualified expenses under the BARDA contract for tebipenem HBr; partially offset by an increase of $0.2 million under the NIAID agreement relating to SPR206, and recognition of $1.1 million in collaboration revenue relating to the Pfizer agreement.

現在來談談我們剩餘的財務表現。 2022 年第三季的總收入為 200 萬美元，而 2021 年第三季的營收為 310 萬美元。收入減少主要是由於我們與 SPR206 相關的國防部協議下的資金減少了 150 萬美元。 BARDA 合約項下氫溴酸替比培南的合格費用減少了 20 萬美元；部分抵消了與 SPR206 相關的 NIAID 協議下 20 萬美元的增加，以及與輝瑞協議相關的 110 萬美元的合作收入。

Research and development expenses for the third quarter of 2022 were $7.4 million compared with $14.4 million of research and development expenses for the same period in 2021. This year-over-year decrease was primarily due to a $4.5 million reduction in direct costs associated with program activity for tebipenem HBr, a $1.2 million decrease due to reduced clinical activity during the period for SPR206 and a decrease in personnel-related costs of $2.7 million related to a reduction in research and development headcount due to the May 2022 strategic restructuring; partially offset by $1.3 million of increased costs due to increased clinical and preclinical activity for SPR720.

2022 年第三季的研發費用為 740 萬美元，而 2021 年同期的研發費用為 1,440 萬美元。同比下降主要是由於與氫溴酸替比培南計畫活動相關的直接成本減少 450 萬美元，由於 SPR206 期間臨床活動減少導致的直接成本減少 120 萬美元，以及由於 2022 年 5 月戰略重組導致研發人員減少導致的人員相關成本減少 270 萬美元；由於 SPR720 的臨床研發人員減少導致的人員相關成本減少 270 萬美元；由於 SPR720 的臨床開發

General and administrative expenses for the third quarter of 2022 of $6.6 million were lower than the $11.2 million reported in the same period in 2021, primarily as a result of a decrease in personnel-related costs arising from a reduction in headcount in commercial, general and administrative functions due to our strategic restructuring, and a decrease in professional and consultant fees of $2.6 million.

2022 年第三季的一般及行政支出為 660 萬美元，低於 2021 年同期的 1,120 萬美元，主要原因是由於我們的策略重組導致商業、一般及行政職能部門員工人數減少，從而導致人員相關成本減少，以及專業及顧問費用減少 260 萬美元。

Spero reported a net loss for the third quarter ended September 30, 2022, of $11.7 million or $0.33 per common share compared to a net loss of $22.5 million or $0.70 per common share reported for the same period in 2021. For further details on our financials, please refer to our 10-Q filed with the SEC today.

Spero 報告稱，截至 2022 年 9 月 30 日的第三季淨虧損為 1,170 萬美元，即每股普通股 0.33 美元，而 2021 年同期的淨虧損為 2,250 萬美元，即每股普通股 0.70 美元。有關我們財務狀況的更多詳細信息，請參閱我們今天向美國證券交易委員會 (SEC) 提交的 10-Q 報表。

We will now open up the call for questions. Operator?

我們現在開始提問。操作員？

(Operator Instructions) Our first question is from Gavin Clarke-Gartner from Evercore ISI.

（操作員指示）我們的第一個問題來自 Evercore ISI 的 Gavin Clarke-Gartner。

I was just hoping with all the recent political updates, if you could frame where the PASTEUR Act stands, since this could potentially be relevant to SPR206.

我只是希望，結合最近的政治動態，您能否闡明《巴斯德法案》的立場，因為這可能與 SPR206 有關。

Thanks, Gavin, for the question. You're right that the PASTEUR Act, which just as a brief review would provide a very large 9-figure subscription payment to drug developers that develop medicines that meet certain criteria, such as those that potentially SPR206 could need. Could be a nice addition to the value proposition for 206.

謝謝 Gavin 提出這個問題。您說得對，巴斯德法案只是進行了簡要審查，將向開發符合特定標準（例如 SPR206 可能需要的標準）的藥物開發商提供高達 9 位數的訂閱費用。可能會對 206 的價值主張起到很好的補充作用。

Right now, the bill has made bipartisan progress, it has bipartisan sponsorship. And it's in a form where it could be appended to some of the larger vehicles for legislation. Certainly, with the midterms coming, where the prospects for the bill, I think, will depend on ultimately who's in control of the house now that the Senate is locked in on the Democratic side. So we'll see in the coming days, though, in terms of from a content perspective, PASTEUR is in a good position to be attended to something to potentially pass.

目前，該法案已取得兩黨進展，並得到了兩黨的支持。它的形式可以附加到一些較大的立法手段。當然，隨著中期選舉的到來，我認為，該法案的前景將最終取決於誰將控制眾議院，因為參議院目前已經被民主黨牢牢控制。因此，我們將在未來幾天看到，從內容角度來看，巴斯德處於有利地位，有可能獲得通過。

Maybe you could just give us a little more color around the rationale to [knock] interim analysis for SPR720.

也許您可以給我們更詳細地解釋一下對 SPR720 進行中期分析的理由。

Yes, Gavin, sure. So a couple of points there. First, we decided to focus on top line data because -- for a couple of reasons. First is that the study is relatively focused. So it lends itself to the second reason, which is that we wanted to make sure that the data we do deliver is fulsome and clear about what 720 can do for patients. There's even been very recent examples in the marketplace where interim data can sometimes paint a murky picture for a program in a study that's in progress.

是的，加文，當然可以。這裡有幾點。首先，我們決定專注於頂線數據，因為——出於幾個原因。一是研究比較集中。所以這就引出了第二個原因，那就是我們希望確保我們提供的數據充分且清楚地表明 720 可以為患者做些什麼。市場上最近甚至出現了這樣的例子，中期數據有時會給正在進行的研究項目描繪出一幅模糊的圖景。

And the final reason is that with the -- our newly extended cash runway after our partnership with GSK, we do have the runway and the opportunity to allow the study to get to a more robust point. And then finally, operationally, there's some efficiencies in being able to push forward into top line data rather than focus on an interim result.

最後一個原因是，與葛蘭素史克合作後，我們新延長的現金跑道讓我們擁有了跑道和機會，可以讓研究達到更穩健的水平。最後，從營運角度來看，能夠推動頂線數據而不是專注於中期結果可以提高效率。

The next question is from Louise Chen with Cantor.

下一個問題來自 Cantor 的 Louise Chen。

Congratulations on all the progress this quarter. So first question I have for you is if you could give more color on that $525 million in sales, in commercial milestones, and how those can get triggered or what will trigger them and when?

恭喜本季取得的所有進展。所以我想問您的第一個問題是，您能否詳細介紹一下 5.25 億美元的銷售額、商業里程碑以及這些里程碑是如何實現的，或者什麼會何時實現？

And then secondly, I wanted to ask you about OpEx in fourth quarter and 2023. Should we use the third quarter as a run rate? Or is there something else that we should think about as nuance there?

其次，我想問您有關第四季和 2023 年的營運支出的問題。我們應該使用第三季作為運行率嗎？或者我們還應該考慮其他細微差別嗎？

And then last question is you've got a lot going on in a very busy end of the year and then busy 2023, so I'm just curious. If we were going to frame it, what are the key catalysts and events you'll be looking out for, but let's say the next 12 to 18 months?

最後一個問題是，您在年底非常忙碌，2023 年也有很多事情要做，所以我很好奇。如果我們要建造它，那麼您將關注的關鍵催化劑和事件是什麼，例如未來 12 到 18 個月？

Yes. Thanks, Louise, for the great questions. I'll answer number 3 first in terms of the overall calendar. And then the other 2 questions you asked, I will hand to Sath.

是的。謝謝路易絲提出的這些精彩問題。我先從整體行程的角度回答第三個問題。然後，您問的另外兩個問題，我將交給 Sath。

So you're right that it's going to be a very eventful '23 and '24. You should expect us going program by program. Number one, as we mentioned, we're going to be going through the special protocol assessment process with tebipenem and starting that Phase III trial which will trigger milestones within the GSK agreement.

所以你說得對，2023年和2024年將會是多事之秋。你應該期待我們逐一程序進行。首先，正如我們所提到的，我們將對替比培南進行特殊方案評估流程，並開始第三階段試驗，這將觸發 GSK 協議中的里程碑。

Secondly, for SPR206, you'll look for us to do the work to advance 206 into the clinic again in a Phase II study.

其次，對於 SPR206，您會期待我們進行工作，將 206 再次推進到 II 期臨床研究。

And then number 3, for 720, we've gone through where the trial currently is, will be actively enrolling patients there, looking to the first half of '24 for a clinical readout. So in other words, each of our programs will be in the clinic during that period of time, and we'll be looking for several important readouts as well as milestones from our collaborations.

第三，對於 720，我們已經完成了目前的試驗，將在那裡積極招募患者，並期待 24 年上半年獲得臨床讀數。換句話說，我們的每個項目都將在那段時間內進入臨床階段，我們將從合作中尋找幾個重要的讀數以及里程碑。

For the other 2 questions, I'll hand it over to you, Sath.

另外兩個問題，我將交給你，Sath。

Great. So thanks for the questions, Louise. For milestones, we've laid out some detail for the development and commercial milestones when we announced the transaction. But in rough terms, roughly $150 million of those milestones are associated with the Phase III development program. We haven't disclosed exactly when those payments come in, but the expectation is that they will come in, in and actually fund the activities for the program.

偉大的。謝謝你的提問，路易絲。對於里程碑，我們在宣布交易時已經列出了開發和商業里程碑的一些細節。但粗略地說，其中約 1.5 億美元與第三階段開發計畫有關。我們尚未透露這些款項的具體到賬時間，但預計它們將會到賬，並真正為該計劃的活動提供資金。

So if you look at the next few quarters, as we engage in running that trial again, those -- that funding will come in through that period at certain points in time. That's the $150 million in development milestones.

因此，如果你看一下接下來的幾個季度，當我們再次進行該試驗時，那些資金將在那個時期的某個時間點到達。這就是 1.5 億美元的開發里程碑。

We've also disclosed $150 million in first patient for sale-associated milestones. Now this is a U.S. and also ex U.S. program. So part of that is ex U.S. But if you were to assume that the majority of that amount comes in on the first patient, first sale in the U.S., you wouldn't be wrong. So that's the majority of our entirety of the $150 million of that first patient commercial milestone.

我們也揭露了與首位患者銷售相關的 1.5 億美元里程碑。這是一個美國項目，也是一個前美國項目。因此，其中一部分來自美國以外。但如果你假設這筆錢的大部分來自美國的第一位病人、第一次銷售，那你就錯了。這就是我們為第一位患者實現商業化里程碑所籌集的 1.5 億美元中的大部分。

And then after that, as laid out in our PR, there are milestones associated with degrees of revenues. So the first time the product sales hit $200 million, Spero or gets a milestone. The first time they hit $300 million, Spero gets a milestone.

然後，正如我們的公關中所述，會有與收入程度相關的里程碑。因此當產品銷售額首次突破2億美元時，Spero或將獲得一個里程碑。首次突破 3 億美元，Spero 取得了里程碑式的成就。

In the [inner] sections of that (inaudible), the sales milestones continue to be allocated to Spero. Higher levels of sales, as we transition more into the royalties, which as Ankit described earlier, increased from low single digits at the lower end of sales to low double digits on the higher end.

在該（聽不清楚）的[內部]部分中，銷售里程碑繼續分配給Spero。隨著我們更多地轉向版稅，銷售額水平更高，正如 Ankit 之前所描述的，銷售額從低端的低個位數增長到高端的低兩位數。

Let me pause there, and I first confirm. Did that answer your question? Before I move to your run rate question.

讓我在這裡暫停一下，先確認一下。這回答了你的問題嗎？在我回答您的運行率問題之前。

Yes, it does.

是的。

Great. For the run rate, Louise, for 4Q, a 3Q number, but slightly higher is probably the appropriate measure for what you should model in. We will be investing a little bit in obviously the start of our SPA activities and preparing for the Phase III tebipenem trial when we restart that next year. But in the interim, if progressing 720 and 206, just as we did in this quarter, those funds will be actually pretty similar we experienced in this [quarter] so if you applied a slight markup but assume that be much more reflective of this quarter as opposed to Q2, for example. That would probably be the appropriate area to go.

偉大的。對於第四季度的運行率，Louise，與第三季度的數字相同，但略高一些，這可能是您應該建模的適當衡量標準。我們顯然會在 SPA 活動的開始上投入一些資金，並為明年重新開始的第三階段替比培南試驗做準備。但在此期間，如果像我們在本季度所做的那樣，進展到 720 和 206，這些資金實際上將與我們在本季度經歷的非常相似，因此，如果您應用了輕微的加價，但假設這更能反映本季度而不是第二季度的情況。那可能是適合去的地方。

You mean for R&D or SG&A also?

您指的是研發費用或銷售、一般及行政費用嗎？

For both.

對兩者而言。

(Operator Instructions) The next question is from Ritu Baral with Cowen.

（操作員指示）下一個問題來自 Cowen 的 Ritu Baral。

(inaudible) Ask about the final Phase III that was agreed upon following the Type A meeting and the minutes. Can you just talk about the major differences between the upcoming study on your prior study? Specifically, how any patients, I think with the (inaudible) will be handled, whether you have the full P value 0.05 for this study? And if you'll be using the same sites.

（聽不清楚）詢問 A 類會議和會議記錄後商定的最終第三階段。您能談談即將進行的研究與您先前的研究之間的主要差異嗎？具體來說，我認為（聽不清楚）將如何處理任何患者，您是否有這項研究的完整 P 值 0.05？如果您將使用相同的網站。

Thanks, Ritu. I'll hand this question over to Kamal.

謝謝，Ritu。我將這個問題交給卡邁勒。

Yes. Thank you for the question. So we're still in discussions about the final -- the design of the final Phase III, of course, we have the Type A meeting with FDA, and that provided clarity on the on how to approach the next Phase II study, but we are currently in discussions with our partner, GSK. And the final protocol design will be disclosed after we've reached agreement with GSK.

是的。謝謝你的提問。因此，我們仍在討論最終的 III 期最終設計，當然，我們與 FDA 舉行了 A 類會議，這明確瞭如何開展下一期 II 期研究，但我們目前正在與我們的合作夥伴 GSK 進行討論。最終的協議設計將在我們與GSK達成協議後公佈。

Got it. But that's -- the trial is still on track to start in 2023. Is that correct?

知道了。但那是——試驗仍按計劃於 2023 年開始。對嗎？

It is correct.

這是正確的。

This concludes the question-and-answer session. I'd now like to turn the conference back over to Dr. Mahadevia for any closing remarks.

問答環節到此結束。現在，我想將會議交還給 Mahadevia 博士，請他作最後發言。

Thank you, operator, and thanks to everyone that listened today. We will (inaudible) to our pipeline's continued advancement, and I wish everyone a nice evening.

謝謝接線員，也謝謝今天收聽節目的所有人。我們將（聽不清楚）繼續推進我們的管道建設，祝大家晚上愉快。

This concludes today's conference call. You may disconnect your lines. Thank you for participating, and have a pleasant day.

今天的電話會議到此結束。您可以斷開線路。感謝您的參與，祝您有個愉快的一天。