Seres Therapeutics Inc (MCRB) 2024 Q2 法說會逐字稿

Good day, and thank you for standing by. At this time, I would like to welcome everyone to Seres Therapeutics second quarter 2024 earnings conference call.

美好的一天，感謝您的支持。此時此刻，我歡迎大家參加 Seres Therapeutics 2024 年第二季財報電話會議。

(Operator Instructions)

（操作員說明）

I would now like to turn the conference over to Dr. Carlo Tanzi, Investor Relations. Please go ahead.

現在我想將會議交給投資者關係部門的 Carlo Tanzi 博士。請繼續。

Thank you, and good morning. Our press release with the company's second quarter 2024 financial results and a business update became available at 7:00AM Eastern Time this morning and can be found on the Investors & News section of the company's website. The company has also posted an updated corporate presentation to the website.

謝謝你，早安。我們的新聞稿包含公司 2024 年第二季財務業績和業務更新，於東部時間今天早上 7:00 發布，您可以在公司網站的投資者與新聞部分找到。該公司還在網站上發布了更新的公司介紹。

I'd like to remind you that we'll be making forward-looking statements, including related to the financial terms, timing and completion of the sale of VOWST assets to Nestle Health Science. The receipt of future payments and the use of proceeds of the transaction, the timing and results of clinical studies and data readouts, development plans and commercial opportunities, operating plans and our future cash runway, our planned strategic focus and other statements, which are not historical fact. Actual results may differ materially.

我想提醒您，我們將做出前瞻性聲明，包括與將 VOWST 資產出售給雀巢健康科學的財務條款、時間安排和完成情況相關的聲明。未來付款的收到和交易收益的使用、臨床研究和數據讀出的時間和結果、發展計劃和商業機會、營運計劃和我們未來的現金跑道、我們計劃的戰略重點和其他陳述，這些陳述不屬於歷史事實。實際結果可能存在重大差異。

On today's call with prepared remarks, I'm joined by Eric Shaff, Seres' President and CEO; Marella Thorell, CFO; Dr. Lisa von Moltke, Chief Medical Officer; Dr. Matthew Henn, Chief Scientific Officer; and Dr. Terri Young, Chief Commercial and Strategy Officer.

Seres 總裁兼執行長 Eric Shaff 參加了今天的電話會議並發表了事先準備好的演講。馬雷拉‧索雷爾，財務長； Lisa von Moltke 博士，首席醫療官； Matthew Henn 博士，首席科學官；以及首席商務和策略長 Terri Young 博士。

With that, I'll pass the call to Eric.

這樣，我會將電話轉給艾瑞克。

Thank you, Carlo, and good morning, everyone. Last week, we announced our agreement to sell Seres VOWST assets of commercial rights to Nestle Health Science in exchange for substantial immediate and future financial consideration. We held a call at that time to review the agreement and the deal terms and to provide a high-level view of our planned corporate strategy to advance our live biotherapeutics drug candidates, which are consortia bacterial strains cultivated from clonal master cell banks and rationally design and optimize target disease-relevant pathways.

謝謝你，卡洛，大家早安。上週，我們宣布同意將 Seres VOWST 資產的商業權出售給雀巢健康科學，以換取近期和未來的大量財務考量。我們當時舉行了電話會議，審查了協議和交易條款，並提供了我們計劃的企業策略的高層視圖，以推進我們的活生物治療候選藥物，這些候選藥物是從克隆主細胞庫中培養並合理設計的聯合體細菌菌株並優化目標疾病相關途徑。

Today's call will focus on our SER-155 program, and the clinical data we look forward to obtaining next month and more broadly, our strategy moving forward. Later in the call, we will provide a review of our second quarter financial results.

今天的電話會議將重點討論我們的 SER-155 項目，以及我們期待下個月獲得的臨床數據，更廣泛地說，我們的策略進展。稍後在電話會議中，我們將回顧第二季的財務表現。

I'll begin with a recap of the VOWST asset sale and how this helps to support advancement of our pipeline. We expect the transaction to close in the next 90 days. As we discussed last week, the VOWST asset sale provides Seres with a meaningful capital infusion. Upon deal close, pending stockholder approval, we will receive $155 million in cash, which includes an upfront payment, a prepaid milestone payment and an equity investment, net of operational obligations we pay Nestle at close. The capital provided will strengthen our balance sheet, enable us to retire our existing debt facility and certain other operational liabilities and, most importantly, support the development of our pipeline of wholly owned live biotherapeutics that build upon our previous successes and represent the next generation of our drug technology.

我將首先回顧 VOWST 資產出售以及這如何有助於支持我們管道的進展。我們預計交易將在未來 90 天內完成。正如我們上週所討論的，VOWST 資產出售為 Seres 提供了有意義的資本注入。交易完成後，等待股東批准，我們將收到 1.55 億美元現金，其中包括預付款、預付里程碑付款和股權投資，扣除我們在交易結束時向雀巢支付的營運義務。所提供的資本將加強我們的資產負債表，使我們能夠償還現有的債務融資和某些其他營運負債，最重要的是，支持我們全資擁有的活生物治療藥物管道的開發，這些管道建立在我們先前的成功基礎上，代表著下一代我們的藥物技術。

We are proud to have developed VOWST as the first ever FDA-approved oral live microbiome therapy. VOWST has transformed the lives of thousands of patients with recurrent C. difficile infections, preventing devastating recurrences of infections for individuals who have limited FDA-approved therapeutic options. In developing VOWST, we created numerous capabilities including entirely new manufacturing methods, and we collaborated with the FDA to secure regulatory approval for a product in an entirely new class of oral biotherapeutics.

我們很自豪能夠將 VOWST 開發為 FDA 批准的第一個口服活微生物療法。VOWST 改變了數千名復發性艱難梭菌感染患者的生活，防止 FDA 批准的治療方案有限的患者出現毀滅性的感染復發。在開發 VOWST 的過程中，我們創造了許多能力，包括全新的製造方法，並且我們與 FDA 合作，確保了全新口服生物治療產品類別的監管批准。

Looking ahead, we believe that the capabilities, know-how and core intellectual property that we have developed over the last decade and our underlying technology platforms position Seres to continue to successfully advance new biotherapeutics to address significant unmet medical needs in additional medically vulnerable patient populations.

展望未來，我們相信，我們在過去十年中開發的能力、專業知識和核心知識產權以及我們的基礎技術平台使Seres 能夠繼續成功地推進新的生物治療藥物，以解決其他醫療脆弱患者群體中未滿足的重大醫療需求。

We believe that there are near-term opportunities to apply our drug technology to prevent serious bacterial infections and related conditions such as bloodstream infections and febrile neutropenia in high-risk patients, such as allo-HSCT patients. In the longer term, we plan to leverage our acquired capabilities and other diseases and conditions. More specifically, we believe we can develop our biotherapeutics to prevent infection in multiple medically vulnerable patient groups and we could address also GI immune-related diseases such as inflammatory bowel disease.

我們相信，近期有機會應用我們的藥物技術來預防高風險患者（例如異體造血幹細胞移植患者）的嚴重細菌感染和相關病症，例如血流感染和發燒性嗜中性白血球減少症。從長遠來看，我們計劃利用我們獲得的能力和其他疾病和狀況。更具體地說，我們相信我們可以開發生物治療藥物來預防多個醫學上脆弱的患者群體的感染，我們還可以解決胃腸道免疫相關疾病，例如發炎性腸道疾病。

In summary, we believe the VOWST asset sale will enable Seres to create meaningful new biotherapeutics for diseases that are not able to be effectively addressed with conventional approaches thereby creating value for patients and other stakeholders. The transaction enables us to transform Seres into a nimble and more streamlined organization, deploying our financial and human capital to advance in pipeline assets through discovery and clinical development, core competencies of Seres. We will be well positioned to build upon our extensive technical capabilities and to advance the development of potentially transformative new treatments for many serious diseases.

總之，我們相信 VOWST 資產出售將使 Seres 能夠針對傳統方法無法有效解決的疾病創造有意義的新生物療法，為患者和其他利害關係人創造價值。這項交易使我們能夠將 Seres 轉變為一個靈活、更精簡的組織，部署我們的財務和人力資本，透過發現和臨床開發（Seres 的核心能力）來推進管道資產。我們將充分利用我們廣泛的技術能力，推動許多嚴重疾病的潛在變革性新療法的開發。

Our lead program, SER-155 is being evaluated in an ongoing Phase 1b study, and we are looking forward to obtaining important clinical data next month in the placebo-controlled cohort 2. We anticipate this readout will extend the positive results observed in Cohort 1 and further highlight the potential for our novel therapeutic approach, expanding our prior clinical successes. Seres is also developing another proprietary live biotherapeutic composition, SER-147 to improve clinical outcomes in patients with metabolic disease, including those with chronic liver disease and those at high risk of bacterial infections.

我們的主導計畫 SER-155 正在一項正在進行的 1b 期研究中進行評估，我們期待下個月在安慰劑對照隊列 2 中獲得重要的臨床數據。我們預計這一結果將擴展在隊列 1 中觀察到的積極結果，並進一步突出我們的新型治療方法的潛力，擴大我們先前的臨床成功。Seres 也正在開發另一種專有的活生物治療組合物 SER-147，以改善代謝性疾病患者的臨床結果，包括慢性肝病患者和細菌感染高風險患者。

Matt will discuss this program shortly. I'll now pass to Lisa to discuss SER-155 in more detail.

馬特很快就會討論這個計劃。現在我將請 Lisa 更詳細地討論 SER-155。

Thank you, Eric. SER-155 is a live biotherapeutic that was specifically designed to target the unmet medical needs of gastrointestinal derived infections, including bloodstream infections, as well as infection associated negative clinical outcomes such as fever during periods of neutropenia. SER-155 is being evaluated in a Phase 1b study in patients undergoing allo HSCT following a diagnosis of AML or other hematologic malignancy. As a result of the extensive exposure to antibiotics and the effects of HSCT conditioning regimens, these patients often develop disruptive gastrointestinal microbiome resulting in functional deficiencies that often lead to pathogen overgrowth and domination in the GI tract.

謝謝你，埃里克。SER-155是一種活體生物治療藥物，專門針對胃腸道源性感染（包括血流感染）以及感染相關的陰性臨床結果（例如中性粒細胞減少症期間的發燒）未得到滿足的醫療需求而設計。SER-155 正在一項 1b 期研究中對診斷為 AML 或其他血液惡性腫瘤後接受異體 HSCT 的患者進行評估。由於廣泛接觸抗生素和 HSCT 調理方案的影響，這些患者經常會出現破壞性胃腸道微生物群，導致功能缺陷，導致病原體在胃腸道過度生長和主導。

These disruptions, coupled with diminished integrity of the GI epithelial barrier are associated with significantly increased risks of bloodstream infections, graft versus host disease and mortality.

這些破壞加上胃腸道上皮屏障完整性的降低，與血流感染、移植物抗宿主疾病和死亡率的風險顯著增加有關。

Last year, we reported promising Phase 1b cohort 1 clinical data with SER-155 being well tolerated in highly immunocompromised allo HSCT patients. In this open-label cohort, SER-155 was administered to 13 subjects with 11 continuing to transplant. Our data indicated that of the subjects administered SER-155, only a single patient had enteric pathogen domination within 30 days following stem cell transplant. This event was transient and the resulting incidence of domination in Cohort 1 was markedly lower than the incidents observed in a large reference cohort. These data provide strong mechanistic evidence supporting the clinical intent of SER-155 to prevent GI pathogen domination and related bloodstream infections.

去年，我們報告了令人鼓舞的 1b 期隊列 1 臨床數據，其中 SER-155 在高度免疫功能低下的異體 HSCT 患者中具有良好的耐受性。在這個開放標籤隊列中，13 名受試者接受了 SER-155，其中 11 名受試者繼續接受移植。我們的數據表明，在施用 SER-155 的受試者中，只有一名患者在幹細胞移植後 30 天內出現腸道病原體控制。該事件是短暫的，並且在隊列 1 中產生的支配發生率明顯低於在大型參考隊列中觀察到的事件。這些數據提供了強有力的機制證據，支持 SER-155 預防胃腸道病原體支配和相關血流感染的臨床意圖。

Next month, we will obtain data from study Cohort 2, which incorporates a randomized, double-blinded, placebo-controlled design and enrolled 45 subjects. I'd like to review several of the specific study endpoints that we will be evaluating. From a safety perspective, we would like to see continued evidence indicating that SER-155 is well tolerated. It is important to note that our biotherapeutics candidates are derived from bacteria isolated from the GI tract of healthy humans and only include bacterial strains that have not been associated with infection. As a result, we have reason to believe that the safety profile associated with our biotherapeutics will continue to be favorable as we have observed in our prior clinical studies.

下個月，我們將獲得第 2 組研究的數據，該研究採用隨機、雙盲、安慰劑對照設計，招募了 45 名受試者。我想回顧一下我們將評估的幾個具體研究終點。從安全角度來看，我們希望看到持續的證據表明 SER-155 具有良好的耐受性。值得注意的是，我們的候選生物療法藥物源自於從健康人體胃腸道分離的細菌，並且僅包括與感染無關的細菌菌株。因此，我們有理由相信，正如我們在先前的臨床研究中所觀察到的那樣，與我們的生物治療藥物相關的安全性將繼續良好。

From an efficacy perspective, we will be assessing the ability of SER-155 to decrease the incidence of GI-derived bloodstream infections within the first 30 and 100 days following HSCT, a period associated with a high rate of complications. We will also evaluate if SER-155 administration results in decreased rates of fever during neutropenia and subsequent rates of antibiotic initiation. In addition, we will examine if SER-155 is associated with the reduced incidence of acute graft-versus-host disease. However, given recent changes in standard treatment practices, we expect the overall rate of GvHD to be low during the study assessment period. The cohort 2 results and our subsequent discussions with FDA will inform next steps, but we expect our next study to be global and that there could be an opportunity for it to be a single pivotal study.

從功效角度來看，我們將評估 SER-155 在 HSCT 後前 30 和 100 天內降低胃腸道源性血流感染髮生率的能力，該時期是併發症發生率較高的時期。我們還將評估 SER-155 給藥是否會降低中性粒細胞減少症期間的發燒率以及隨後的抗生素起始率。此外，我們將檢查 SER-155 是否與急性移植物抗宿主疾病發生率降低有關。然而，鑑於最近標準治療實踐的變化，我們預計在研究評估期間 GvHD 的總體發生率會較低。組別 2 結果以及我們隨後與 FDA 的討論將為後續步驟提供信息，但我們預計我們的下一項研究將是全球性的，並且有機會成為一項單一的關鍵研究。

We believe positive data from the Cohort 2 readout would further validate the promise of our live biotherapeutics modality to address serious infection and infection-related negative clinical outcomes in medically vulnerable populations, including cancer patients with neutropenia, solid organ transplant recipients and individuals with chronic liver disease.

We believe positive data from the Cohort 2 readout would further validate the promise of our live biotherapeutics modality to address serious infection and infection-related negative clinical outcomes in medically vulnerable populations, including cancer patients with neutropenia, solid organ transplant recipients and individuals with chronic liver疾病.

Assuming supportive Cohort 2 data, we have already begun to plan further development steps for SER-155, including a potential global registrational study in allo-HSCT and potentially also initiation of development in other medically vulnerable groups, high rates of bacterial infections.

假設第二組數據支持，我們已經開始規劃 SER-155 的進一步開發步驟，包括異體造血幹細胞移植的潛在全球註冊研究，以及可能在其他醫學上脆弱的群體、高細菌感染率中啟動開發。

I'll now pass the call to Matt to discuss the pharmacology data that we will be collecting in the SER-155 study.

我現在將電話轉給 Matt，討論我們將在 SER-155 研究中收集的藥理學數據。

Thank you, Lisa. SER-155 is a consortium of 16 bacterial strains that was rationally designed and optimized based on the functional properties of the individual strains as well as clinical insights from across Seres portfolio of clinical studies. This biotherapeutic is designed to prevent and reduce pathogen colonization, abundance and overgrowth in the GI tract and to promote epithelial barrier to reduce the likelihood of harmful bacteria translating from the GI to the bloodstream.

謝謝你，麗莎。SER-155 是一個由 16 種細菌菌株組成的聯盟，根據各個菌株的功能特性以及 Seres 臨床研究組合的臨床見解進行合理設計和優化。這種生物療法藥物旨在預防和減少胃腸道中病原體的定植、豐富和過度生長，並促進上皮屏障，以減少有害細菌從胃腸道轉移到血液的可能性。

Additionally, there are bacteria included in SER-155 to modulate immune pathways to induce immune tolerance with the potential to impact GvHD. In Cohort 2 of the SER-155 allo-HSCT trial, we will evaluate a number of pharmacology parameters, including the kinetics and magnitude of drug species engraftment, meaning the outgrowth of bacteria in SER-155 in the gastrointestinal track and the abundance and overgrowth of harmful bacteria, including those that can harbor antimicrobial resistance in the GI.

此外，SER-155 中包含的細菌可以調節免疫途徑，誘導免疫耐受，並有可能影響 GvHD。在SER-155 allo-HSCT 試驗的第2 組中，我們將評估許多藥理學參數，包括藥物種類植入的動力學和程度，這意味著SER-155 中細菌在胃腸道中的生長以及豐度和過度生長有害細菌，包括那些在胃腸道中具有抗菌藥物抗藥性的細菌。

In addition, we will be evaluating changes in the GI microbiome and associated functions and a collection of host biomarkers to evaluate mechanisms of pathogen decolonization, epithelial barrier function and additionally, modulation of both local and systemic immune pathways that can induce immune tolerance.

此外，我們將評估胃腸道微生物組和相關功能以及宿主生物標記集合的變化，以評估病原體去定植、上皮屏障功能以及可誘導免疫耐受的局部和全身免疫途徑的調節機制。

Cohort 2 pharmacology data and endpoints will be examined in the context of the placebo control and the reference control cohort. The pending pharmacology data could provide additional support for clinical outcomes observed. In addition, these data will be important as we consider further development plans for SER-155 and targeting the prevention of infection in additional patient populations as well as GI-related immune diseases.

將在安慰劑對照和參考對照隊列的背景下檢查隊列 2 的藥理學數據和終點。待定的藥理學數據可以為觀察到的臨床結果提供額外的支持。此外，當我們考慮 SER-155 的進一步開發計劃並針對其他患者群體的感染以及胃腸道相關免疫疾病的預防時，這些數據將非常重要。

In addition to SER-155, we are developing SER-147 for compromised patients living with metabolic diseases. SER-147 is an oral live biotherapeutic product candidate consisting of a consortium of cultivated bacteria designed to prevent gut-seeded infections and associated downstream infections and spontaneous bacterial peritonitis, or SPP in chronic liver disease.

除了 SER-155 之外，我們也正在為患有代謝疾病的受損患者開發 SER-147。SER-147是一種口服活生物治療候選產品，由一組培養細菌組成，旨在預防腸道感染和相關下游感染以及慢性肝病中的自發性細菌性腹膜炎（SPP）。

In the advanced stages of chronic liver disease known as decompensated cirrhosis, patients can exhibit gastrointestinal microbiome disruption and associated functional deficiencies. This, combined with the frequent contact with the health care system can drive increased susceptibility to bacterial infections and other negative clinical outcomes such as hospitalization.

在慢性肝病（稱為失代償性肝硬化）的晚期階段，患者可能會表現出胃腸道微生物組破壞和相關的功能缺陷。再加上與醫療保健系統的頻繁接觸，可能會增加對細菌感染和其他負面臨床結果（例如住院）的敏感性。

SER-147 was designed and optimized using our reverse translational MbTx platform, enabling the data-driven selection of a unique set of bacterial strains with the desired functional properties. These strains were selected based on clinical insights and extensive preclinical in vitro and disease model screening of individual strains and lead consortia.

SER-147 使用我們的逆翻譯 MbTx 平台進行設計和最佳化，從而能夠以數據驅動方式選擇一組具有所需功能特性的獨特細菌菌株。這些菌株的選擇是基於臨床見解以及對單一菌株和主要菌群的廣泛臨床前體外和疾病模型篩選。

Our cultivated biotherapeutics are manufactured from single strain isolates through fermentation methods that allow for efficient, scalable processes. As with SER-155, we believe that SER-147 could represent another opportunity for Seres and we anticipate IND readiness in the second half of 2025.

我們的培養生物治療藥物是透過發酵方法從單一菌株分離物中生產出來的，可實現高效、可擴展的製程。與 SER-155 一樣，我們相信 SER-147 可能為 Seres 帶來另一個機會，我們預計 IND 將於 2025 年下半年準備就緒。

I'll now pass the call to Terri to provide further context around our pipeline strategy.

現在，我將把電話轉給 Terri，以提供有關我們的管道策略的更多背景資訊。

Thank you, Matt. To summarize our general path forward, we believe our approach has demonstrated unique clinical success with VOWST in preventing frequent, serious and extensive infection and we plan to build upon this success in additional medically vulnerable patients. Our next step in this journey is to substantiate a highly attractive profile for SER-155 in terms of safety and efficacy with a short oral dosing regimen.

謝謝你，馬特。總而言之，我們相信我們的方法在預防頻繁、嚴重和廣泛感染方面透過 VOWST 展現了獨特的臨床成功，並且我們計劃在其他醫療弱勢患者中取得這一成功。我們這趟旅程的下一步是透過短期口服給藥方案證實 SER-155 在安全性和有效性方面極具吸引力的特性。

With meaningful results next month from the Phase 1b study, we will begin to pursue additional therapeutic adjacencies for SER-155 as Lisa and Matt both outlined. Each adjacent patient population under consideration is significant in its own right, but together, they represent a substantial commercial opportunity.

隨著下個月 1b 期研究取得有意義的結果，我們將開始尋求針對 SER-155 的其他治療方法，正如 Lisa 和 Matt 所概述的那樣。所考慮的每個相鄰患者群體本身就很重要，但總的來說，它們代表著巨大的商業機會。

The allo-HSCT population is comprised of approximately 3,000 patients annually across the US and EU. Expansion across other hematologic malignancies would bring an additional 23,000 patients annually to the SER-155 patient pool from auto-HSCT and another 190,000 from hematologic cancer patients with high neutropenia rate. For example, AML, multiple myeloma and non-Hodgkin lymphoma. These patients are mainly treated at large centers across the developed world, and therefore, we would benefit from an efficient commercial model designed to reach a concentrated set of HCP.

美國和歐盟每年約有 3,000 名異體 HSCT 患者。擴展到其他血液惡性腫瘤將使每年透過自動 HSCT 增加 23,000 名患者進入 SER-155 患者庫，另外 19 萬名來自中性粒細胞減少症發生率高的血液癌症患者。例如，AML、多發性骨髓瘤和非何杰金氏淋巴瘤。這些患者主要在已開發國家的大型中心接受治療，因此，我們將受益於旨在接觸集中的 HCP 的高效商業模式。

We are also considering expansion into other transplants with the potential to avoid infections in the 65,000 patients across the US and EU each year to receive solid organ transplants like kidney and liver.

我們也考慮擴展到其他移植領域，以期避免美國和歐盟每年接受腎臟和肝臟等實體器官移植的 65,000 名患者出現感染。

Our next program, SER-147, provides the opportunity to prevent infections in chronic liver disease patients, another large patient. We also believe our approach can make a difference for patients beyond activity against infection by addressing immune modulation. This would enable us to pursue additional highly prevalent conditions such as inflammatory bowel disease. We remain excited about the breadth of opportunities in front of us. And it's worth reminding everyone that a key outcome of the VOWST asset sale to Nestle is that we will have full ownership of our entire next-generation of pipeline candidates providing strategic optionality as we move forward and positioning us to drive value for our key stakeholders.

我們的下一個計畫 SER-147 為預防慢性肝病患者（另一大患者）的感染提供了機會。我們也相信，除了透過解決免疫調節問題來對抗感染之外，我們的方法還可以為患者帶來改變。這將使我們能夠追蹤其他高度流行的疾病，例如發炎性腸道疾病。我們對面前的廣泛機會仍然感到興奮。值得提醒大家的是，VOWST 資產出售給雀巢的一個關鍵成果是，我們將擁有整個下一代候選產品的完全所有權，在我們前進的過程中提供策略選擇，並使我們能夠為我們的主要利益相關者創造價值。

Our pipeline prioritization has been informed by our knowledge of where microbiome disruption has been implicated in disease, thereby leaving patients vulnerable to serious and extensive infection.

我們的管道優先順序是基於我們對微生物組破壞與疾病的關係的了解，使患者容易受到嚴重和廣泛的感染。

We are also -- we also strongly consider diseases with high unmet needs, where a product with an attractive profile would bring a strong value proposition affording us pricing flexibility. In addition, as we develop our future plans, we will carefully consider the required development path for all indications under evaluation to ensure that we can demonstrate clinical proof of concept at modest cost and in a timely manner.

我們也強烈考慮需求未被滿足的疾病，具有吸引力的產品將帶來強大的價值主張，為我們提供定價彈性。此外，在製定未來計劃時，我們將仔細考慮評估中的所有適應症所需的開發路徑，以確保我們能夠以適度的成本及時展示概念的臨床證明。

In summary, we will continue to utilize a rigorous and data-driven approach to develop our pipeline strategy, which considers the strength of scientific rationale and commercial potential along with clinical development, feasibility, time and cost. The SER-155 clinical results that we receive next month will be a key input to our path forward and will allow us to refine our plans. We look forward to communicating more about our strategic path forward once we obtain and fully consider this important data set.

總而言之，我們將繼續採用嚴格和數據驅動的方法來製定我們的管道策略，該策略考慮科學原理和商業潛力的強度以及臨床開發、可行性、時間和成本。我們下個月收到的 SER-155 臨床結果將成為我們前進道路的關鍵投入，並使我們能夠完善我們的計劃。一旦我們獲得並充分考慮了這一重要數據集，我們期待就我們的策略路徑進行更多溝通。

Now I'll turn the call over to Marella to share our financial results.

現在我將把電話轉給 Marella 分享我們的財務表現。

Thanks, Terri, and good morning, everyone. I'd like to discuss our financial results for the second quarter, starting with VOWST. As a reminder, Seres does not recognize VOWST net sales in its financial statements, but instead under the terms of our prior agreements with Nestle, we share equally the product's commercial profits and losses, and we record our share in the collaboration profit and loss sharing related party line. VOWST profits and losses are determined based upon VOWST net sales, cost of goods sold and sales and marketing expenses. Net sales of VOWST for the second quarter were $14.4 million, reflecting an approximately 43% growth over the first quarter of this year.

謝謝，特瑞，大家早安。我想從 VOWST 開始討論我們第二季的財務表現。需要提醒的是，Seres 並未在其財務報表中確認VOWST 的淨銷售額，而是根據我們先前與雀巢達成的協議條款，我們平均分擔該產品的商業損益，並記錄我們在合作損益分攤中的份額關聯方線。VOWST 利潤和虧損根據 VOWST 淨銷售額、銷售成本以及銷售和行銷費用決定。VOWST 第二季淨銷售額為 1,440 萬美元，較今年第一季成長約 43%。

As discussed in our first quarter update, Nestle refined their call strategy and increased call points to broaden their prescriber reach. We remain confident in the potential of VOWST and Nestle continues to refine their launch execution to respond to market dynamics as they work to expand the business.

正如我們在第一季更新中所討論的，雀巢改進了他們的呼叫策略並增加了呼叫點，以擴大他們的處方者範圍。我們對 VOWST 的潛力仍然充滿信心，雀巢在努力擴大業務的同時，將繼續完善其上市執行，以應對市場動態。

Research and development expenses for the second quarter were $17.9 million, down from $46.8 million for the same period in 2023. The year-over-year decrease in R&D expenses was primarily driven by VOWST commercial manufacturing costs no longer being recognized in the Seres P&L, but instead being capitalized and recognized on our balance sheet.

第二季的研發費用為 1,790 萬美元，低於 2023 年同期的 4,680 萬美元。研發費用年減主要是由於 VOWST 商業製造成本不再在 Seres 損益表中確認，而是在我們的資產負債表中資本化和確認。

In addition, reductions in headcount and other expenses from the restructuring announced at the end of 2023, contributed to lower expenses. General and administrative expenses for the second quarter were $16.1 million, reduced from $28.1 million for the same period in 2023. Again, reflecting lower headcount following the restructuring actions as well as lower professional fees and other cost reduction efforts.

此外，2023年底宣布的重組導致員工人數和其他費用的減少，也導致費用下降。第二季的一般及管理費用為 1,610 萬美元，較 2023 年同期的 2,810 萬美元有所減少。再次反映重組行動後員工人數的減少以及專業費用和其他成本削減措施的降低。

We reported a net loss of $32.9 million for the second quarter of 2024 as compared to net income of $46.6 million for the same period in 2023. The change being a result of a $125 million milestone payment received from Nestle in the second quarter of 2023 upon the FDA approval of VOWST, along with other operating expense reductions noted between the periods.

我們報告 2024 年第二季淨虧損 3,290 萬美元，而 2023 年同期淨利為 4,660 萬美元。這項變更是由於 FDA 批准 VOWST 後，雀巢於 2023 年第二季度收到了 1.25 億美元的里程碑付款，以及在此期間注意到的其他營運費用減少。

More than a third of our employee base is expected to move to Nestle Health Science as part of the VOWST asset sale. Seres will be a more focused and streamlined organization upon the sale, and we will continue to manage expenses prudently. As a result, our cash burn will decline following the close of the transaction.

作為 VOWST 資產出售的一部分，我們超過三分之一的員工預計將轉移到雀巢健康科學。出售後，Seres 將成為一個更專注和精簡的組織，我們將繼續審慎管理費用。因此，交易結束後，我們的現金消耗將會下降。

Turning to our cash position. As of June 30, 2024, and we had $71.2 million in cash and cash equivalents. This does not include the cash infusion expected as part of the VOWST asset sale which we expect to close within 90 days of the August 5 signing. We expect that the capital obtained through the VOWST asset sale, if completed, to allow us to extend our cash runway, enabling Seres to meaningfully advance its pipeline. Based on our current cash, future operating plans, and the capital expected to be received at transaction close, plus the installment payments expected in 2025 and accounting for the ongoing transaction-related obligations, we anticipate a cash runway into the fourth quarter of 2025.

轉向我們的現金狀況。截至 2024 年 6 月 30 日，我們擁有 7,120 萬美元的現金和現金等價物。這不包括作為 VOWST 資產出售一部分的預計現金注入，我們預計該資產出售將在 8 月 5 日簽署後 90 天內完成。我們預計，透過 VOWST 資產出售獲得的資金如果完成，將使我們能夠擴大我們的現金跑道，使 Seres 能夠有意義地推進其管道。根據我們目前的現金、未來的營運計畫以及預計在交易結束時收到的資本，加上預計2025 年的分期付款以及對正在進行的交易相關義務的核算，我們預計2025 年第四季將有現金跑道。

I'll now pass the call back to Eric.

我現在將電話轉回給埃里克。

Thank you, Marella. And before we move forward, I'll just note that we have been made aware that there may be a technical issue with folks being able to access the call or at least the first part of the call from our website. So following the completion of this call, we will ensure that the full transcript from our remarks is posted and available to everybody.

謝謝你，瑪瑞拉。在我們繼續前進之前，我想指出的是，我們已經意識到，人們無法從我們的網站訪問通話或至少通話的第一部分，可能存在技術問題。因此，在本次電話會議結束後，我們將確保將我們的演講全文發布並提供給所有人。

Okay. Moving forward, Seres will pursue a focused corporate strategy where we will apply our experience with live biotherapeutics to improve patient outcomes in a variety of medically vulnerable patient populations. As discussed, our immediate strategy is focused on reducing the risk of bacterial infections in high-risk populations. In the future, we also believe that our biotherapeutics could be developed to address other large commercial opportunities, including the treatment of autoimmune diseases such as inflammatory bowel disease. As you've heard today, we are very excited to obtain the SER-155 clinical data and allo-HSCT in September.

好的。展望未來，Seres 將奉行專注的企業策略，我們將運用我們在活體生物治療方面的經驗來改善各種醫療弱勢患者群體的患者治療結果。如所討論的，我們目前的策略是降低高風險族群細菌感染的風險。未來，我們也相信，我們的生物治療藥物可以開髮用於解決其他巨大的商業機會，包括治療發炎性腸道疾病等自體免疫疾病。正如您今天所聽到的，我們非常高興能在 9 月獲得 SER-155 臨床數據和異基因造血幹細胞移植 (allo-HSCT)。

These data have the potential to highlight the tremendous opportunity we see in SER-155.

這些數據有可能突顯我們在 SER-155 中看到的巨大機會。

If we are successful, the medical and commercial opportunities for SER-155 could be very meaningful. Beyond SER-155, we are developing SER-147 for medically compromised patients with metabolic diseases, opening additional substantial opportunity. We've already shown that our therapeutic approach can yield highly efficacious and well-tolerated medicine that can change lives. We have the capabilities and with our recently announced transaction, we expect to have the capital to support the development of additional transformative new therapies for medically vulnerable patients.

如果我們成功，SER-155 的醫療和商業機會將非常有意義。除了 SER-155 之外，我們正在為患有代謝性疾病的醫學受損患者開發 SER-147，這開闢了額外的實質機會。我們已經證明，我們的治療方法可以產生高效且耐受性良好的藥物，從而改變生活。我們有能力，透過最近宣布的交易，我們預計將有資金支持為醫療弱勢患者開發更多變革性新療法。

Operator, with that, let's now open the call up to questions.

接線員，現在讓我們開始提問。

(Operator Instructions)

（操作員說明）

Tessa Romero, JPMorgan.

泰莎‧羅梅羅，摩根大通。

The first one from us what signal or signals you are specifically looking for in Cohort 2 for SER-155 around these key secondary endpoints that you've talked about today. And then zooming ahead a little bit, can you provide a framework for how we should think about what a potential pivotal study might look like if Cohort 2 is successful. Just trying to get at kind of how the risk that trial design might be on the backside of Cohort 2? And also how fast do you think you could get that pivotal study up and running?

我們的第一個訊號是您在 SER-155 的佇列 2 中圍繞您今天討論的這些關鍵次要終點特別尋找的訊號。然後稍微向前看一下，您能否提供一個框架，讓我們思考如果第二組成功的話，潛在的關鍵研究可能會是什麼樣子。只是想了解試驗設計在第 2 組的背面可能存在的風險有多大？您認為您能以多快的速度啟動並執行這項關鍵研究？

Tess, let me start and maybe I'll pass it over to Lisa. I think we lost a little bit of audio at the end there, but I think I heard most of the question. So the first question was around how do we think about quantifying signal in an endpoint, I assume, on the efficacy side in the upcoming readout. Second question was how quickly do we get to a next study?

苔絲，讓我開始吧，也許我會把它交給麗莎。我想我們最後丟失了一點音頻，但我想我聽到了大部分問題。因此，第一個問題是我們如何考慮量化端點中的訊號，我認為，在即將到來的讀數中的功效方面。第二個問題是我們要多快才能進行下一項研究？

And if it were pivotal, what does the kind of what smell and feel like in terms of time, cost and so forth. So if I didn't butcher your questions, Tess, maybe I can start and then Lisa can go from there. And I would start by just saying and reminding folks that this is a Phase 1b study. So the primary endpoints are, of course, safety and the pharmacology that I think we mentioned, we do have the benefit of having a placebo arm, roughly 25 patients per cohort so we are looking to see signals. And as always, our studies tend to be pretty data rich.

如果它是關鍵的話，那麼在時間、成本等方面，氣味和感覺是什麼樣的。所以，如果我沒有扼殺你的問題，苔絲，也許我可以開始，然後麗莎可以從那裡開始。首先我要提醒大家，這是 1b 期研究。所以主要終點當然是安全性和藥理學，我想我們提到過，我們確實有安慰劑組的好處，每個隊列大約有 25 名患者，所以我們正在尋找信號。像往常一樣，我們的研究往往數據相當豐富。

So maybe I can pass it to Lisa to talk about the parameters of the study and perhaps your questions about where we go with positive data.

因此，也許我可以將其傳遞給麗莎，討論研究的參數，也許還有您關於我們如何利用積極數據的問題。

Yes, Tess, we have not been specific about the actual deltas that we're looking for, but I think we can go through the endpoints and starting with something like neutropenia and fever, where rates are very, very high. We have a chance to be able to see a very meaningful decrement just because it's so prevalent. Something like bloodstream infections, which are less frequent, we still think we would be able to see a meaningful difference, but obviously, the delta would not be the same. Same thing for GI infection, Same thing for acute GvHD.

是的，苔絲，我們並沒有具體說明我們正在尋找的實際增量，但我認為我們可以通過端點並從中性粒細胞減少症和發燒等疾病開始，這些疾病的發生率非常非常高。我們有機會看到非常有意義的減少，因為它是如此普遍。像血液感染這樣的情況不太常見，我們仍然認為我們能夠看到有意義的差異，但顯然，三角洲不會相同。胃腸道感染也是如此，急性 GvHD 也是如此。

With regard to the infectious endpoint, the other thing we're looking for is consistency, right? We're wanting to see that we see a change in neutropenia and fever, we're also seeing a change in antibiotic starts as well as BSIs. So the consistency of that picture as well as then looking at the pathogen abundance data which mechanistically, we believe would underlie those findings will really be important. So it's the individual end points yes, but it's also the consistency of the picture that we see that paints the idea that we're doing what we want to do.

關於傳染性終點，我們正在尋找的另一件事是一致性，對嗎？我們希望看到中性粒細胞減少症和發燒的變化，我們也看到抗生素開始使用以及 BSI 的變化。因此，該圖片的一致性以及隨後查看的病原體豐度數據從機制上講，我們認為這些數據將成為這些發現的基礎，這確實很重要。因此，是的，這是各個終點，但也是我們所看到的畫面的一致性，描繪了我們正在做我們想做的事情的想法。

And the next question was around how do we think of the registration study.

下一個問題是我們如何看待註冊研究。

And I think what we would want is a study that builds on our experience with VOWST in that when you have a meaningful clinical delta, you can run an efficiently sized trial and that's what we'd be looking for. We have some idea of the kind of safety database that agency wants. So we would be using that experience to build a pivotal study, you could imagine on the same scale as the VOWST pivotal study as well as expecting a safety database requirement of about 300 total.

我認為我們想要的是一項建立在我們 VOWST 經驗基礎上的研究，因為當你有一個有意義的臨床增量時，你可以運行一個有效規模的試驗，這就是我們所尋求的。我們對機構想要的安全資料庫類型有所了解。因此，我們將利用這些經驗來建立一項關鍵研究，您可以想像與 VOWST 關鍵研究的規模相同，並且預計安全資料庫要求總計約為 300 個。

Ed Tenthoff, Piper Sandler.

艾德·騰索夫，派珀·桑德勒。

Looking forward to the data in September. Kind of looking forward a little bit as we were walking through the profile, I was thinking would it make sense for 155 in CAR T therapy? And could it help with some of the challenges in terms of CRS and GvHD that's seen, especially with some of the new allogeneic therapies that are coming down the pipe. Just a thought I had. I'm wondering what's your view of that opportunity is?

期待9月份的數據。當我們瀏覽該簡介時，我有點期待，我在想 155 在 CAR T 療法中是否有意義？它能否幫助解決 CRS 和 GvHD 方面的一些挑戰，尤其是一些即將推出的新同種異體療法。只是我的一個想法。我想知道您對這個機會有何看法？

Yes, Ed, great question. Let me hand it to Lisa.

是的，艾德，好問題。讓我把它交給麗莎。

Yes, we absolutely think there could be applicability in CAR T, both on -- from the infectious complications as well as the immunologic issues that you've just outlined. And I think that's the beauty of this trial, which is the ongoing trial, which is that we believe mechanistically, it applies to CAR T as well as auto transplants and other indications where there's chemotherapy.

是的，我們絕對認為 CAR T 可能適用於感染併發症以及您剛才概述的免疫學問題。我認為這就是這項試驗的優點，這是一項正在進行的試驗，我們相信從機制上講，它適用於 CAR T 以及自體移植和其他需要化療的適應症。

Ted, one additional point too, which is you've known us for a long time, and we've been really focusing on that core mechanisms and biologies, both around the ability to prevent pathogens from colonizing and then decolonize as well as the epi barrier and inducing immune tolerance. And I think something that's really important in the context of our technologies. We're bringing a novel approach forward that's not immunosuppressive. And I think that's particularly important in many of these different patient populations where we see the challenges such as infections and other immune responses.

特德，還有一點，那就是你認識我們很長時間了，我們一直在真正關注核心機制和生物學，包括防止病原體定植和去定植以及外延的能力。我認為這在我們的技術背景下非常重要。我們正在提出一種非免疫抑制的新方法。我認為這對於許多不同的患者群體尤其重要，我們在這些患者群體中面臨感染和其他免疫反應等挑戰。

So -- and Ted, just one more thing. There was a recent meta-analysis that came out in Nature Medicine that actually looked at the kinds of problems that CAR-T patients have that actually caused mortality. And the surprise in that paper was that infections are still an amazingly important issue and that more than 50% of the deaths are being attributed not to ICANs or to other things that are a bit more exotic, but to just infections. So there's still a lot of work to be done on just that kind of fundamental issue.

所以——還有特德，還有一件事。《自然醫學》最近發表了一項統合分析，實際上研究了 CAR-T 患者所面臨的導致死亡的問題。這篇論文中令人驚訝的是，感染仍然是一個極其重要的問題，超過 50% 的死亡不是由 ICAN 或其他更奇特的東西引起的，而只是由感染引起的。因此，在此類基本問題上仍有大量工作要做。

I'm looking forward to the data, and excited to hear more about the new 147 program.

我期待著這些數據，並很高興聽到有關新 147 計劃的更多資訊。

Peyton Bohnsack, TD Cowen.

佩頓·博恩薩克，TD·考恩。

This is Peyton on for Joe. I guess a real quick one on SER-155 pivotal time. I know that you mentioned it's going to most likely be a global trial. Could you talk about whether or not there are data sets for kind of the pathogen domination. Because I know there's a reference data set that you guys tend to use is from MSKCC and whether or not you think that there will be any difference in the types and amount of pathogens for globally?

這是佩頓替補喬。我想在 SER-155 關鍵時刻，這會是一次真正的快速行動。我知道你提到這很可能是全球試驗。您能否談談是否有關於病原體控制類型的資料集？因為我知道你們傾向於使用來自 MSKCC 的參考資料集，你們是否認為全球範圍內的病原體類型和數量會有任何差異？

And then I have a follow-up.

然後我有一個後續行動。

Maybe I'll ask Matt to comment. I mean, -- but before he does, just to make sure that we're level setting, right? One of the really interesting aspect of this study is the first cohort for those that might not be aware, where we looked at pathogen domination in comparison as Peyton mentioned, versus a reference cohort that we have established with the partnership of MSK.

也許我會請馬特發表評論。我的意思是，--但在他這樣做之前，只是為了確保我們處於平衡狀態，對嗎？這項研究真正有趣的方面之一是為那些可能不知道的人提供的第一個隊列，我們將佩頓提到的病原體控制與我們與 MSK 合作建立的參考隊列進行比較。

And with some really interesting initial early signals around lower pathogen incidents -- domination incidents that we might have thought based on that reference cohort, including one out of -- I think it was 11 subjects and it was actually a transitory event. So that's one of the reasons that we're so excited about this upcoming second cohort, particularly with the placebo control, but maybe Matt can comment further on your question.

圍繞較低病原體事件有一些非常有趣的初始早期訊號——我們可能根據參考隊列想到的支配事件，包括其中一個——我認為有 11 名受試者，這實際上是一個短暫的事件。這就是我們對即將到來的第二組感到如此興奮的原因之一，特別是安慰劑對照，但也許馬特可以對你的問題進一步發表評論。

So there is global data around pathogen abundance. And I'd point you to a New England Journal of Medicine article that was published. And obviously, we'd be happy to share that. But there was work conducted there across major transplant centers globally, including Asian as well as European centers and other centers in the US Seres actually helps support so that work and the data are consistent across the globe.

因此，存在有關病原體豐度的全球數據。我想向您推薦一篇發表在《新英格蘭醫學雜誌》上的文章。顯然，我們很樂意分享這一點。但全球主要移植中心都開展了工作，包括亞洲和歐洲中心以及美國的其他中心，Seres 實際上提供了支持，以便全球範圍內的工作和數據保持一致。

The reason we use the reference cohort data set that we've developed with MSK is because we've put a lot of energy and time into collection of that. And so it's a very, very high-quality data set that we feel highly reflects what those rates look like, but those trends are observed in the global data sets as well. And then you had a follow-up, Peyton?

我們之所以使用與 MSK 斯隆共同開發的參考隊列資料集，是因為我們投入了大量的精力和時間來收集這些資料。因此，這是一個非常非常高品質的數據集，我們認為它高度反映了這些比率的情況，但這些趨勢也在全球數據集中觀察到。然後你有後續行動嗎，佩頓？

Yes, I did. So I guess kind of could you go into any additional details about if -- when the Phase 1b cohort data -- that placebo control cohort data is positive. What are the next steps with the agency? What still needs to be required for actually initiating these studies. Do you have the (inaudible) put together?

是的，我做到了。因此，我想您能否詳細說明一下，當 1b 期隊列數據時，安慰劑對照隊列數據是否為陽性。該機構的下一步是什麼？實際啟動這些研究還需要什麼。你把（聽不清楚）放在一起了嗎？

Yes, I get the easy answer and then I can hand it to Lisa. The easy answer, of course, is it depends what the data shows, right? We always follow the data and that has been our experience, including with what was then 109. Now that was -- we were thrilled with the results then. And -- but of course, we follow the data, including our discussions with the agency.

是的，我得到了簡單的答案，然後我可以把它交給麗莎。當然，簡單的答案是這取決於數據顯示的內容，對嗎？我們始終遵循數據，這就是我們的經驗，包括當時的 109。現在，我們對當時的結果感到非常興奮。當然，我們會追蹤數據，包括我們與該機構的討論。

But maybe Lisa can comment a little bit more specifically around what the process looks like.

但也許麗莎可以對這個過程進行更具體的評論。

We would be going to them to actually discuss the data in the next study as well as for designations around orphan drug and breakthrough and obviously, we can't do too much until we actually get the data and then start to construct the argument. But you can imagine we've given all of that a lot of thought. And clearly, on the breakthrough side, and orphan drug, we've done that before. So we feel that, that's a fairly straightforward kind of request coming from our experience.

我們將與他們實際討論下一項研究中的數據，以及圍繞孤兒藥和突破的指定，顯然，在我們真正獲得數據並開始構建論點之前，我們不能做太多事情。但你可以想像我們已經對這一切進行了很多思考。顯然，在突破性藥物和孤兒藥方面，我們以前已經做到了。所以我們認為，根據我們的經驗，這是一個相當簡單的請求。

And the last question comes from the line of Jeff Jones with Oppenheimer.

最後一個問題來自傑夫瓊斯和奧本海默的台詞。

This is (inaudible) for Jeff. We have a couple of questions. First, can you share how you think of the pipeline post of VOWST, like what the criteria you are using to decide when programs to bring back online? And what drove you to select 147 at the first program to bring back? We have some to follow-up.

這是傑夫的（聽不清楚）。我們有幾個問題。首先，您能否分享一下您對 VOWST 管道貼文的看法，例如您使用什麼標準來決定專案何時恢復上線？是什麼促使你在第一個節目中選擇147帶回來？我們有一些需要跟進。

I think the question was around how do we decide to prioritize our programs perhaps in what we expect will be the closing of the Nestle transaction and our ability to focus more on the pipeline. And so I think there's some element of our process that Terri mentioned in her prepared remarks as we think about unmet need, as we think about where our technology has a, call it, an unshared advantage relative to other approaches and there's a lot of excitement that we have in terms of our technology based on our experience with VOWST.

我認為問題在於我們如何決定我們的計劃的優先順序，也許我們預計雀巢交易的完成以及我們更多地關注管道的能力。因此，我認為特里在她準備好的演講中提到了我們流程中的一些要素，因為我們考慮了未滿足的需求，當我們考慮我們的技術相對於其他方法具有不可共享的優勢時，我們感到非常興奮基於我們在 VOWST 的經驗，我們擁有的技術。

This is a disease where companies have for many years tried to innovate and has had limited success. We were successful in developing a therapeutic, which is highly efficacious, well-tolerated and oral. And we think that, that's really a precedent that we can take forward into adjacencies and SER-155 has been the next step for us, which is one of the reasons we're so excited about the upcoming readout.

這是一種疾病，企業多年來一直試圖創新，但收效甚微。我們成功開發了一種高效、耐受性良好的口服療法。我們認為，這確實是一個先例，我們可以將其推廣到鄰接領域，而 SER-155 是我們的下一步，這也是我們對即將發布的結果感到如此興奮的原因之一。

147, maybe I can ask Matt to talk about mechanistically why that's next on the list. But certainly, in our opinion, if we are successful with 155, it really opens up adjacencies where we can move, we think, quickly with 155 with 147 and based on the cultivated side of our manufacturing platform, where we have a backbone of bacterial strains that we utilize as part of our therapeutics and then can switch out additional strains based on what we're hoping to do functionally, we think we've got the opportunity to move quickly. So maybe I can ask Matt to comment further.

147，也許我可以請馬特從機制上談談為什麼這是清單中的下一個。但當然，在我們看來，如果我們在155 方面取得成功，它確實打開了我們可以快速移動的鄰接點，我們認為，我們可以在155 和147 的基礎上快速移動，並且基於我們製造平台的培養方面，我們在那裡有細菌的骨幹。所以也許我可以請馬特進一步發表評論。

Yes. So I mean, Seres as a company has always been data-driven and that's at the heart of how we make our decisions, whether it be the scientific data, the clinical data or the commercial data. And that's what we put into play as we think about prioritizing the various diseases. We are highly focused as a company in settings of medically compromised patients, where we know there is a highly disruptive microbiome in the gastrointestinal tract which leads to functional deficiencies that are linked to various different disease outcomes. And what we've done at the company is has done a lot of work to understand which of those functional pathways we can successfully target with our drugs and actually modulate.

是的。所以我的意思是，Seres 作為一家公司一直是數據驅動的，這是我們做出決策的核心，無論是科學數據、臨床數據還是商業數據。這就是我們在考慮優先考慮各種疾病時所扮演的角色。作為一家公司，我們高度關注醫療受損患者的環境，我們知道胃腸道中存在高度破壞性的微生物群，會導致與各種不同疾病結果相關的功能缺陷。我們在公司所做的就是做了大量的工作來了解我們可以成功地用我們的藥物瞄準並實際調節哪些功能途徑。

And that information is based on both preclinical and clinical data. And so when we looked across the spectrum of diseases, we saw real opportunities where basically the peer-reviewed literature had strong support for a microbiome connection. We've been able to confirm those kinds of results and we're moving those forward. So chronic liver disease is an example of that where we think there's a really nice lineup with basically what we believe our technology can do. We see a path clinically, and we see a meaningful commercial opportunity.

該資訊基於臨床前和臨床數據。因此，當我們縱觀各種疾病時，我們看到了真正的機會，基本上同行評審的文獻都對微生物組的聯繫提供了強有力的支持。我們已經能夠確認這些結果，並且正在推動這些結果。慢性肝病就是一個例子，我們認為有一個非常好的陣容，基本上我們相信我們的技術可以做到這一點。我們在臨床上看到了一條道路，我們看到了一個有意義的商業機會。

Last thing I'll just say is that with our ability to move quickly and we also bring a mindset of focus. We are deploying our capital and our resources in areas where we think there's the greatest opportunity for return and that, of course, is the idea behind the 155 readout and hopefully, what happens after that. So that is our approach.

我要說的最後一件事是，憑藉我們快速行動的能力，我們也帶來了專注的心態。我們正在將我們的資本和資源部署在我們認為回報機會最大的領域，當然，這就是 155 讀數背後的想法，希望這也是之後會發生的事情。這就是我們的方法。

And for 50-50 profit loss showing VOWST continues well, past the deal closing through fourth quarter 2025, as you mentioned. We note that, that one has turned profitable this quarter. So can you speak to whether this anticipated to continue? Or if the profit this quarter was associated with the any onetime like event?

正如您所提到的，50-50 的利潤損失表明 VOWST 在交易結束到 2025 年第四季後繼續表現良好。我們注意到，該公司本季已實現盈利。那麼您能談談這種情況是否會持續下去嗎？或者，本季的利潤是否與任何一次性類似事件相關？

Maybe I can ask Marella to comment on the parameters of this past quarter and maybe what we expect going forward.

也許我可以請 Marella 對上個季度的參數以及我們對未來的期望發表評論。

The profit this quarter was a combination of two things. Number one was the overall collaboration loss for the enterprise of VOWST, which is the net sales, less the COGS, less the marketing expenses incurred by Nestle, and that was a loss for the period. The component that put us into a profit was the profit that we recognized on the transfer of inventory to Nestle when they sell that on to a third party.

本季的利潤是兩件事的結合。第一個是VOWST企業的整體合作損失，即淨銷售額減去銷貨成本，再減去雀巢產生的行銷費用，這是該期間的損失。讓我們獲利的部分是我們在雀巢將庫存出售給第三方時將庫存轉移給雀巢時確認的利潤。

Going forward, that second component profit on inventory after the deal closes will no longer be an element. The manufacturing operations will transfer over to Nestle. We're providing some support through a transition services period, but we will no longer recognize profit. So that element will be gone from the results.

展望未來，交易結束後庫存的第二部分利潤將不再是要素。製造業務將轉移給雀巢。我們將在過渡服務期內提供一些支持，但我們將不再確認利潤。因此該元素將從結果中消失。

So it will really just be a matter of the product profit and loss that we will absorb. In the proxy, which we plan to publish in the coming days. We will include an estimates for what that collaboration profit or loss will be for the period in which we'll continue to share.

因此，這實際上只是我們將吸收的產品利潤和損失的問題。在我們計劃在未來幾天內發布的代理商中。我們將包括對我們將繼續分享的期間的合作利潤或損失的估計。

And then as of closing, in the closing balance sheet, we will record a liability for an estimate of what that profit or loss sharing for the period will be, and we'll adjust that each quarter. So you should think about the collaboration loss going forward in comparison to that one piece, that $6.6 million loss component of this quarter's results.

然後，截至收盤時，在期末資產負債表中，我們將記錄該期間利潤或損失分攤的估計負債，並且我們將每個季度進行調整。因此，您應該考慮與本季業績中 660 萬美元的損失部分相比，未來的合作損失。

There are no further questions at this time. I turn the call back over to the management for closing remarks.

目前沒有其他問題。我將電話轉回給管理層以供結束語。

Thank you, operator, and thanks to everyone for joining us this morning. We appreciate your time, and we look forward to keeping you updated as we go. Thanks very much, and have a great week.

謝謝您，接線生，也謝謝大家今天早上加入我們。感謝您抽出寶貴的時間，我們期待隨時向您通報最新情況。非常感謝，祝您有個愉快的一周。

This concludes today's conference call. You may now disconnect.

今天的電話會議到此結束。您現在可以斷開連線。