Clovis Oncology Inc (CLVS) 2021 Q4 法說會逐字稿

Good morning. My name is Chris, I'll be your conference operator today. At this time, I'd like to welcome everyone to the Clovis Oncology Fourth Quarter and Year-end 2021 Operating Results. (Operator Instructions) Thank you.

早安.我叫克里斯，今天我將擔任你們的會議操作員。此時此刻，我謹歡迎大家閱讀 Clovis Oncology 2021 年第四季和年底的營運表現。 （操作員說明）謝謝。

Anna Sussman, Vice President of Investor Relations.

安娜‧蘇斯曼 (Anna Sussman)，投資者關係副總裁。

Thank you, Chris. Good morning, everyone and welcome to the Clovis Oncology Fourth Quarter and Full Year 2021 Conference Call. Thank you for joining us. You've likely seen this morning's news release and if not, it's available on our website. As a reminder, this conference call is being recorded and webcast. Remarks may be accessed live on our website during the call and will be available in our archive for the next several weeks.

謝謝你，克里斯。大家早上好，歡迎參加克洛維斯腫瘤學 2021 年第四季和全年電話會議。感謝您加入我們。您可能已經看過今天早上的新聞稿，如果沒有，可以在我們的網站上找到。謹此提醒，本次電話會議正在錄製並進行網路直播。通話期間您可以在我們的網站上即時存取評論，並將在接下來的幾週內保存在我們的檔案中。

Today's agenda includes the following, corporate update and then Dr. Thomas Harding, our Chief Scientific Officer, will present an update on the 2286 and targeted radionuclide therapy development programs; Dr. Lindsey Rolfe, our Chief Medical Officer will discuss the anticipated upcoming clinical milestones for Rubraca and FAP-2286. Then Dan Muehl, our Chief Financial Officer will cover the financial results for the quarter and the year in greater detail. Patrick will then make a few closing remarks and then we will open the call for Q&A, during which time Pat, Dan, Tom and Lindsey will be available to answer questions.

今天的議程包括以下公司最新動態，然後我們的首席科學官 Thomas Harding 博士將介紹 2286 和靶向放射性核素治療開發計劃的最新動態；我們的首席醫療官 Lindsey Rolfe 博士將討論 Rubraca 和 FAP-2286 即將到來的臨床里程碑。然後，我們的財務長 Dan Muehl 將更詳細地介紹本季和本年度的財務業績。然後派崔克將做一些總結發言，然後我們將開始問答環節，在此期間帕特、丹、湯姆和林賽將回答問題。

Before we begin, please note that during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans. All of these statements are subject to risks and uncertainties and statements. Our actual results could differ materially due to a number of factors, including the extent and duration of the effects of the COVID-19 pandemic and the timing and extent of recovery from it. Please refer to our recent filings with the SEC for a full review of the risks and uncertainties associated with our business.

在開始之前，請注意，在今天的電話會議上，我們可能會做出聯邦證券法含義內的前瞻性聲明，包括有關我們的財務前景和預期業務計劃的聲明。所有這些陳述均受到風險和不確定性的影響。由於多種因素的影響，我們的實際結果可能會存在重大差異，包括 COVID-19 大流行影響的程度和持續時間以及從中恢復的時間和程度。請參閱我們最近向 SEC 提交的文件，以全面審查與我們業務相關的風險和不確定性。

Forward-looking statements speak only as of the date on which they are made and Clovis undertakes no obligation note that we'll be discussing cash burn, a non-GAAP financial measure during today's conference call. Required disclosures related to this are in today's news release, which can be found on our website.

前瞻性聲明僅代表截至其發布之日的情況，克洛維斯不承擔任何義務，說明我們將在今天的電話會議上討論現金消耗，這是一項非公認會計準則財務指標。與此相關的必要披露資訊包含在今天的新聞稿中，您可以在我們的網站上找到該新聞稿。

Now I'll turn the call over to Patrick Mahaffy.

現在我將把電話轉給帕特里克·馬哈菲。

Thanks, Anna, excuse me, good morning. Welcome, everybody, appreciate your time today. As usual, I'll start today's call with a review of Rubraca sales for the quarter. Sales in Q4 2021 were $36 million, 5% lower than the prior quarter and 17% lower year-over-year compared to Q4 2020. As seen over the previous quarters, this year-over-year decline is primarily due to fewer diagnoses and fewer patient starts in the US and Europe, primarily caused by the ongoing COVID-19 pandemic.

謝謝，安娜，對不起，早安。歡迎大家，非常感謝你們今天的時間。像往常一樣，我將首先回顧本季 Rubraca 的銷售情況。 2021 年第四季的銷售額為3,600 萬美元，比上一季下降5%，與2020 年第四季相比同比下降17%。從前幾季可以看出，同比下降主要是由於診斷數量減少和美國和歐洲的新冠患者數量減少，這主要是由於持續的 COVID-19 大流行造成的。

Despite the continuing impact of COVID-19, we believe we had maintained our US market share for Rubraca in the second-line maintenance ovarian cancer setting. We do expect that as patient visits begin to rise, diagnoses increase and the urgent need to more actively manage this often fatal disease growth, the maintenance treatment of ovarian cancer patients will increase, including the use of Rubraca for women with advanced disease.

儘管受到 COVID-19 的持續影響，我們相信我們仍保持了 Rubraca 在二線維持卵巢癌領域的美國市場份額。我們確實預計，隨著患者就診次數開始增加、診斷數量增加以及更積極地管理這種往往致命的疾病增長的迫切需要，卵巢癌患者的維持治療將會增加，包括對患有晚期疾病的女性使用Rubraca。

Perhaps even more importantly, we see a significant opportunity to move into earlier lines of therapy with Rubraca in both the US and Europe. We anticipate 3 Phase III readouts this year, ATHENA-MONO as monotherapy in the first-line ovarian cancer maintenance treatment setting now expected in Q2 based on a slower-than-expected pace of progression-free survival events or PFS events and ATHENA-COMBO in combination with Opdivo in the first-line ovarian cancer maintenance treatment setting in Q4 and TRITON3 in the second-line prostate cancer treatment setting for selected patients in Q2. These trials potentially allow Rubraca to address larger patient populations in earlier lines of therapy for both ovarian and prostate cancer and could drive growth in Rubraca sales in both the US and Europe. Lindsey will provide an update on these clinical programs.

也許更重要的是，我們看到了在美國和歐洲進行 Rubraca 早期治療的重大機會。我們預計今年將有3 項III 期試驗結果，其中ATHENA-MONO 作為一線卵巢癌維持治療的單一療法，基於無進展生存事件或PFS 事件的速度低於預期，預計將在第二季度進行，而ATHENA -COMBO 則預計將在第二季度進行。在第四季度的一線卵巢癌維持治療環境中與 Opdivo 聯合使用，在第二季度的選定患者的二線前列腺癌治療環境中與 TRITON3 聯合使用。這些試驗可能使 Rubraca 在卵巢癌和前列腺癌的早期治療中能夠滿足更多患者群體的需求，並可能推動 Rubraca 在美國和歐洲的銷售成長。 Lindsey 將提供這些臨床項目的最新資訊。

For FAP-2286, the Phase I portion of LuMIERE continues to enroll and we are committed to maintaining our lead in the clinical development of an FAP-targeted radionuclide therapeutic candidate. We and our investigators remain extremely enthusiastic about this program and look forward to presenting data at nuclear medicine meetings during 2022 and initiating the Phase II portion of the LuMIERE study later this year. Tom and Lindsey will speak in more detail to developments about the FAP-2286 program.

對於 FAP-2286，LuMIERE 的 I 期部分繼續入組，我們致力於維持在 FAP 標靶放射性核素治療候選藥物臨床開發的領先地位。我們和我們的研究人員對該計劃仍然充滿熱情，並期待在 2022 年期間的核子醫學會議上展示數據，並在今年稍後啟動 LuMIERE 研究的 II 期部分。 Tom 和 Lindsey 將更詳細地談論 FAP-2286 計劃的進展。

In fact to that end, I'll turn the call over to Tom, our Chief -- Thomas Harding, sorry Tom, our Chief Scientific Officer to discuss the FAP-2286 and targeted radionuclide therapeutic development programs. Tom?

事實上，為此，我將把電話轉給我們的首席科學官湯姆 - 托馬斯·哈丁，對不起，湯姆，我們的首席科學官，討論 FAP-2286 和靶向放射性核素治療開發計劃。湯姆？

Thanks, Pat. Hello. It's a pleasure to speak with you again today. As we've discussed in prior calls, a key strategy for Clovis is to be a leader in targeted radionuclide therapy. FAP-2286, our lead targeted radio therapeutic compound licensed as part of our ongoing collaboration with 3B Pharmaceuticals is the first peptide target radiotherapy candidate or PTRT targeting fibroblast activation protein, also known as FAP in clinical development. And as Pat mentioned, in 2022, we will report the first Phase I clinical data for the program and plan to advance the program into Phase II expansion cohorts. SAP is highly expressed on cancer associated fibroblasts or CAFs, which represent one of the most abundant cell components in tumors and they're found in the majority of solid tumor types.

謝謝，帕特。你好。很高興今天再次與您交談。正如我們在之前的電話會議中討論的那樣，克洛維斯的一個關鍵策略是成為標靶放射性核素治療的領導者。 FAP-2286 是我們與3B Pharmaceuticals 持續合作的一部分，獲得許可的領先靶向放射治療化合物，是第一個肽靶向放射治療候選藥物或PTRT 靶向成纖維細胞激活蛋白，在臨床開發中也稱為FAP。正如 Pat 所提到的，2022 年，我們將報告該計畫的第一個 I 期臨床數據，並計劃將該計畫推進到 II 期擴展隊列。 SAP 在癌症相關纖維母細胞或 CAF 上高度表達，它們代表腫瘤中最豐富的細胞成分之一，並存在於大多數實體瘤類型中。

CAFs play critical role in tumor initiation, progression, metastasis and therapeutic resistance. For example, recent studies have demonstrated FAP expressing CAFs exert a potent immunosuppressive activity that can promote tumor progression and confer resistance to immune-based therapies such as PD-1 and PD-L1 blockade. As we highlighted last quarter, we presented non-clinical data describing a high expression level of FAP across 9 of 16 solid tumor types screened using immunohistochemistry.

CAF 在腫瘤發生、進展、轉移和治療抗藥性中發揮關鍵作用。例如，最近的研究表明，表達 FAP 的 CAF 具有強大的免疫抑制活性，可以促進腫瘤進展並賦予對 PD-1 和 PD-L1 阻斷等免疫療法的抵抗力。正如我們在上季度所強調的那樣，我們提供了非臨床數據，描述了使用免疫組織化學篩選的 16 種實體瘤類型中的 9 種中 FAP 的高表達水平。

High FAP expression was observed in pancreatic ductal adenocarcinoma, cancer of unknown primary, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non-small cell lung as well as squamous head and neck cancers. In these tumor types, higher FAP expression detected in both primary and metastatic tumor samples was independent of tumor stage or grade. The analysis also demonstrate that in most tumor types, FAP expression, which predominantly localize the cancer-associated fibroblast surrounding the tumor cells and integrated into the tumor microenvironment.

在胰腺導管腺癌、原發灶不明的癌症、唾液腺癌、間皮瘤、結腸癌、膀胱癌、肉瘤、鱗狀非小細胞肺癌以及鱗狀頭頸癌中觀察到高FAP表達。在這些腫瘤類型中，在原發性和轉移性腫瘤樣本中檢測到的較高 FAP 表現與腫瘤分期或等級無關。分析還表明，在大多數腫瘤類型中，FAP 表達主要定位於腫瘤細胞周圍的癌症相關成纖維細胞，並整合到腫瘤微環境中。

In addition, in cancers of mesenchymal origin, including sarcoma and mesothelioma, FAP expression was observed in tumor cells in addition to the CAF population. These data support the investigation of FAP-2286 in multiple tumor types in the planned Phase II expansion cohorts of LuMIERE. Additional presentations of non-clinical data are anticipated at medical oncology and nuclear medicine meetings over the next few quarters.

此外，在間質來源的癌症（包括肉瘤和間皮瘤）中，除了 CAF 群體外，在腫瘤細胞中也觀察到 FAP 表現。這些數據支持在 LuMIERE 計劃的 II 期擴展隊列中對 FAP-2286 在多種腫瘤類型中的研究。預計未來幾季的腫瘤內科和核醫會議將介紹更多非臨床數據。

As interest in FAP as the target increases and the field grows larger, we are pleased to be in the first mover position with FAP-2286 to be the first peptide-targeted radionuclide therapeutic targeting FAP to enter into the clinic. Clinically, we are focused on 2286 monotherapy development in our ongoing LuMIERE study. However, preclinically, we are evaluating a number of 2286 drug combinations.

隨著人們對 FAP 的興趣隨著標靶的增加和領域的擴大而增加，我們很高興能夠成為先行者，FAP-2286 成為第一個進入臨床的針對 FAP 的勝肽靶向放射性核素治療藥物。臨床上，我們正​​在進行的 LuMIERE 研究重點關注 2286 單藥療法的開發。然而，在臨床前，我們正在評估 2286 種藥物組合。

Given the role of FAP expressing CAFs in [medium] to resistance to immune-based therapies such as PD-1 and PD-L1 blockade, combinations with these agents will be a priority. We are evaluating in non-clinical studies the efficacy and mechanism of action of FAP-2286 and a PD-1 monoclonal antibody in syngeneic mouse tumor models. In addition to immune checkpoint inhibitors, there are a number of publications reporting non-clinical data that support the combination targeted radiotherapy with PARP inhibitors to augment efficacy. This makes sense [radiotherapies] work by causing DNA damage via radioactive admission. If this damage is not repaired, the cell will eventually die.

鑑於表達 FAP 的 CAF 在抵抗基於免疫的療法（例如 PD-1 和 PD-L1 阻斷）中發揮的作用，與這些藥物的組合將是優先考慮的事項。我們正在非臨床研究中評估 FAP-2286 和 PD-1 單株抗體在同基因小鼠腫瘤模型中的功效和作用機制。除了免疫檢查點抑制劑之外，還有許多出版物報告了支持標靶放射治療與 PARP 抑制劑聯合治療以增強療效的非臨床數據。這是有道理的[放射療法]透過放射性進入造成 DNA 損傷來發揮作用。如果這種損傷得不到修復，細胞最終就會死亡。

One of the critical proteins for repairing radiation-induced damage is part and it's in addition augment efficacy in combination with multiple targeted radiotherapy agents. We are currently preclinically evaluating the combination of FAP-2286 with our own PARP inhibitor rucaparib in multiple tumor models.

修復輻射引起的損傷的關鍵蛋白質之一是一部分，它還可以與多種標靶放射治療藥物結合使用來增強療效。我們目前正在多個腫瘤模型中評估 FAP-2286 與我們自己的 PARP 抑制劑 rucaparib 的組合。

Lastly, radiation is known to synergize with a number of agents that are currently approved as a standard of care in specific cancer indications. For example, gemcitabine used as a first-line chemotherapy in pancreatic cancer and other carcinomas is a well-known radiosensitizer and could have utility in combination with FAP-2286. We are currently performing a high throughput screen of approved oncology drugs in combination with radiation to identify promising combinations for FAP-2286 development.

最後，眾所周知，放射可以與目前被批准作為特定癌症適應症的護理標準的許多藥物產生協同作用。例如，用作胰腺癌和其他癌症一線化療的吉西他濱是一種眾所周知的放射增敏劑，可與 FAP-2286 聯合使用。我們目前正在對已批准的腫瘤藥物與放射治療相結合進行高通量篩選，以確定有希望用於 FAP-2286 開發的組合。

We look forward to reporting the results of this preclinical work at upcoming scientific meetings. To support our commitment to this emerging field, we have created educational materials about targeted radiotherapy. The first of these materials are a microsite and an introductory video that provide more information about targeted radiotherapy FAP-2286 and Clovis' targeted radionuclide development program. To learn more, please visit targeted radiotherapy.com.

我們期待在即將召開的科學會議上報告這項臨床前工作的結果。為了支持我們對這一新興領域的承諾，我們製作了有關標靶放射治療的教育材料。第一個材料是一個微型網站和一個介紹性視頻，提供有關靶向放射治療 FAP-2286 和克洛維斯靶向放射性核素開發計劃的更多資訊。要了解更多信息，請訪問 Targeted Raditherapy.com。

Lastly, we are collaborating with 3B pharmaceuticals on a discovery program directed at 3 additional targets to targeted radionuclide therapeutic development to which we have global rights. And now with that, I'll turn the call over to Lindsey Rolfe for a clinical update.

最後，我們正在與 3B Pharmaceuticals 合作開展一項發現計劃，該計劃針對我們擁有全球權利的靶向放射性核素治療開發的另外 3 個目標。現在，我將把電話轉給林賽·羅爾夫 (Lindsey Rolfe)，以了解臨床最新情況。

Thanks, Tom. Good morning, everybody. I'm glad to be here with you today to highlight the key clinical milestones expected for Rubraca and FAP-2286 in 2022. For Rubraca, based on a slower-than-expected PFS event count, we are now expecting data from ATHENA-MONO in the second quarter of 2022. Patients from ATHENA-COMBO, the combination arm of Rubraca plus Opdivo versus monotherapy are expected in the fourth quarter of 2022.

謝謝，湯姆。大家早安。我很高興今天與大家一起強調 Rubraca 和 FAP-2286 預計在 2022 年實現的關鍵臨床里程碑。對於 Rubraca，基於慢於預期的 PFS 事件計數，我們現在期待來自 ATHENA-MONO 的數據預計將於2022 年第第二季度接受來自ATHENA-COMBO（Rubraca 合併Opdivo 與單一療法的聯合療法）的患者治療，預計將於2022 年第四季接受治療。

As a reminder, ATHENA is a Phase III 1,000-patient study in first-line newly diagnosed advanced ovarian cancer maintenance. With ATHENA, we believe we are uniquely positioned to evaluate Rubraca in terms of 2 independent outcomes, monotherapy versus placebo in the first-line maintenance setting as well as any potential advantage of the combination of Rubraca and Opdivo over Rubraca [low] in the same first-line maintenance setting.

提醒一下，ATHENA 是一項針對新診斷的晚期卵巢癌一線維持治療的 III 期研究，涉及 1,000 名患者。透過 ATHENA，我們相信我們具有獨特的優勢，能夠根據 2 個獨立結果（一線維持治療中的單一療法與安慰劑相比）以及 Rubraca 和 Opdivo 組合相對於 Rubraca [低] 的任何潛在優勢來評估 Rubraca。一線維護設定。

We believe this study offers an opportunity to truly differentiate Rubraca in the first-line maintenance setting. Once top line monotherapy results are available and should the data be supportive, we plan to file an sNDA and variation to the European MAA shortly thereafter. Continuing with near-term milestones for Rubraca, top line data from the TRITON 3 trial are expected in the second quarter of 2022. TRITON 3 is a Phase III study evaluating Rubraca versus physician's choice of chemotherapy or second-line androgen deprivation therapy in patients with mCRPC with BRCA or ATM mutations.

我們相信這項研究提供了一個機會，讓 Rubraca 在一線維護環境中真正脫穎而出。一旦獲得第一線單一療法結果並且如果數據具有支持性，我們計劃不久後向歐洲 MAA 提交 sNDA 和變更。繼續 Rubraca 的近期里程碑，預計 TRITON 3 試驗的頂線數據將於 2022 年第二季度獲得。TRITON 3 是一項 III 期研究，評估 Rubraca 與醫生選擇的化療或二線雄激素剝奪治療的患者俱有BRCA 或ATM 突變的mCRPC。

This trial is expected to serve as a complimentary study for Rubraca's current approval in the prostate indication as well as the potential second line label expansion and we plan to file an sNDA shortly after results are available. These 3 anticipated [both] readout, ATHENA-MONO, ATHENA-COMBO and TRITON 3 provide the potential to reach larger patient populations in earlier lines of therapy for both ovarian and prostate cancers.

該試驗預計將作為 Rubraca 目前在前列腺適應症方面獲得批准以及潛在的二線標籤擴展的補充研究，我們計劃在結果公佈後不久提交 sNDA。這 3 個預期的讀數，ATHENA-MONO、ATHENA-COMBO 和 TRITON 3 提供了在卵巢癌和前列腺癌的早期治療中接觸更多患者群體的潛力。

Beyond the opportunity for Rubraca in first-line ovarian cancer, the ATHENA-COMBO study represents the potential to introduce an anti-PD-1 containing regimen for the first time to a broad population of ovarian cancer patients. As a reminder, the timing for each data readout is contingent upon the occurrence of the protocol-specified progression-free survival events.

除了 Rubraca 在第一線卵巢癌中的機會之外，ATHENA-COMBO 研究還代表了首次向廣大卵巢癌患者引入含有抗 PD-1 療法的潛力。提醒一下，每次資料讀出的時間取決於方案指定的無進展生存事件的發生。

I'd like to discuss our FAP-2286 program next. Tom provided an overview of the non-clinical work and now I'll review the clinical work underway. In our ongoing Phase I/II LuMIERE study, FAP-2286 is used as both an imaging agent and a therapeutic agent, a concept often described as a theranostic. For the imaging agent, FAP-2286 is attached to the isotope for gallium-68 to allow positron emission tomography or PET imaging on selection of patients for inclusion in the study.

接下來我想討論一下我們的 FAP-2286 計畫。湯姆概述了非臨床工作，現在我將回顧正在進行的臨床工作。在我們正在進行的 I/II 期 LuMIERE 研究中，FAP-2286 既用作顯影劑又用作治療劑，這一概念通常被描述為治療診斷。對於顯影劑，FAP-2286 與鎵 68 同位素相連，以便對納入研究的患者進行正子斷層掃描或 PET 影像。

For the therapeutic agent, FAP-2286 is attached to the isotope lutetium-177 and a mixture of beta particle, ionizing radiation that causes DNA damage and cell death. The Phase I portion of the LuMIERE study continues to enroll patients and the second dose cohort is currently enrolling patients. As a reminder, for this first-in-man study, this is a dose escalation study with each of the 5 dose cohorts being enrolled sequentially with a 6-week safety follow-up period after the last patient in each cohort has enrolled to ensure it's safe to move the next dose cohort. While this 6-week period is longer than in Phase I trials of other oncology agents, it is standard for targeted radio therapies.

對於治療劑，FAP-2286 附著在同位素镥 177 和 β 粒子的混合物上，電離輻射會導致 DNA 損傷和細胞死亡。 LuMIERE 研究的 I 期部分繼續招募患者，第二劑量組目前正在招募患者。提醒一下，對於這項首次人體研究，這是一項劑量遞增研究，5 個劑量組中的每一個都按順序入組，並在每個組中的最後一位患者入組後進行6 週的安全追蹤期，以確保轉移下一個劑量組是安全的。雖然這 6 週的時間比其他腫瘤藥物的 I 期試驗要長，但它是標靶放射治療的標準時間。

Following the Phase I evaluation of the safety of FAP-2286 and determination of a recommended Phase II dose, expansion cohorts are planned in multiple tumor types and are expected to begin in 2021. In addition to our own program, a separate investigator-sponsored imaging study with FAP-2286 is underway at UCSF being led by Dr. Thomas Hope, who is also the principal investigator of the LuMIERE study. The imaging-only study is evaluating FAP expression in multiple tumor types and is currently enrolling patients.

在對FAP-2286 的安全性進行I 期評估並確定建議的II 期劑量後，計劃在多種腫瘤類型中進行擴展隊列，預計將於2021 年開始。除了我們自己的計劃外，還有一項由研究者贊助的單獨成像FAP-2286 的研究正在 UCSF 進行，由 Thomas Hope 博士領導，他也是 LuMIERE 研究的首席研究員。這項純成像研究正在評估多種腫瘤類型中的 FAP 表達，目前正在招募患者。

Results from this study, along with the preclinical data we are generating are expected to help in own selection of tumor types for our Phase II expansion cohorts. We look forward to Dr. Hope's presentation of his initial energy data from this study at the upcoming virtual SNMMI Mid-Winter meeting later this week. In addition to initiating LuMIERE Phase II expansion cohorts during 2022, we anticipate several key milestones for the program, including the first presentation of Phase I data for LuMIERE at Nutrient medicine-focused meetings, the launch of our combination study program to explore FAP-2286 in combination with other oncology compounds.

這項研究的結果以及我們正在產生的臨床前數據預計將有助於為我們的 II 期擴展隊列選擇腫瘤類型。我們期待著 Hope 博士在本週稍後即將舉行的 SNMMI 仲冬虛擬會議上介紹他從這項研究中獲得的初步能源數據。除了在 2022 年啟動 LuMIERE II 期擴展隊列外，我們預計該計劃將實現幾個關鍵里程碑，包括在營養醫學會議上首次展示 LuMIERE I 期數據、啟動探索 FAP-2286 的聯合研究計劃與其他腫瘤學化合物組合。

Given the role of FAP expressing CAFs in mediating immunosuppression, exploring the combination with PD-1 or PD-L1 blockade is a priority, augmented by Tom, we are exploring multiple combination studies in preclinical animal models to inform our choice of combinations for clinical development. Finally, a potential IND filing for FAP-2286 linked to an alpha emitting isotope in 2023. I'd like to recognize again the dedicated efforts of the teams involved in our clinical trials, both employees and investigators and the patient participants as our clinical programs advance.

鑑於表達FAP 的CAF 在介導免疫抑制中的作用，探索與PD-1 或​​ PD-L1 阻斷的組合是當務之急，在Tom 的推動下，我們正在臨床前動物模型中探索多種組合研究，以告知我們臨床開發組合的選擇。最後，可能會在 2023 年提交與 α 發射同位素相關的 FAP-2286 IND 申請。我想再次認可參與我們臨床試驗的團隊、員工和研究人員以及患者參與者作為我們的臨床項目的奉獻精神進步。

And with that, I'll turn the call over to Dan to discuss fourth quarter financial results.

接下來，我將把電話轉給丹，討論第四季的財務表現。

Thanks, Lindsey and hello, everyone. We reported net product revenues for Rubraca of $36 million for Q4 2021, which included US product revenues of $27.6 million and ex-US product revenues of $8.4 million respectively. This represents a sequential 5% decrease from Q3 2021 and a 17% decrease year-over-year, compared to Q4 2020 net product revenues of $43.3 million, which included US product revenues of $36.4 million and ex-US net product revenues of $6.9 million.

謝謝，林賽，大家好。我們報告稱，Rubraca 2021 年第四季的產品淨收入為 3,600 萬美元，其中美國產品收入分別為 2,760 萬美元，美國以外產品收入分別為 840 萬美元。這比 2021 年第三季季減 5%，年減 17%，而 2020 年第四季產品淨收入為 4,330 萬美元，其中美國產品收入為 3,640 萬美元，美國以外產品淨收入為 690 萬美元。

We reported net product revenue for Rubraca of $148.8 million for the full-year ended December 31, 2021, which included $115.7 million in US and $33.1 million in ex-US product revenues respectively. This represents a 10% decrease compared to 2020 net product revenues of $164.5 million, which included $146.3 million in the US and ex-US net product revenues of $18.2 million.

我們報告稱，截至 2021 年 12 月 31 日的全年，Rubraca 的產品淨收入為 1.488 億美元，其中美國產品收入分別為 1.157 億美元，美國以外產品收入為 3,310 萬美元。這與 2020 年 1.645 億美元的產品淨收入相比下降了 10%，其中包括美國的 1.463 億美元和美國以外的產品淨收入 1,820 萬美元。

Gross to net adjustments totaled 30.6% globally in Q4 2021 compared to 27% in Q3 2021. Increasing GTN in the ex-US and public health service discounts in the US were the main drivers. This metric fluctuates quarter-to-quarter and is difficult to estimate on future revenues, but the high 20% to low 30% level seems likely depending on the revenue and distribution mix for the US and Europe. As previously discussed, as European revenues increased in proportion to the US, global GTN will increase correspondingly.

2021 年第四季度，全球毛淨調整總額為 30.6%，而 2021 年第三季為 27%。美國以外地區 GTN 的增加和美國公共衛生服務折扣是主要驅動力。該指標按季度波動，很難估計未來的收入，但高 20% 到低 30% 的水平似乎可能取決於美國和歐洲的收入和分銷組合。如前所述，隨著歐洲收入相對於美國的比例增加，全球 GTN 將相應增加。

Research and development expenses totaled $41.8 million for Q4 2021 and $186.6 million for fiscal year 2021, down 26% and 28% respectively, compared to 56.7 and $257.7 million for the comparable periods in 2020. Research and development expenses decreased for the quarter and the year compared to the same periods in the prior year, primarily due to lower spending on Rubraca clinical trials.

2021 年第四季的研發費用總計為4,180 萬美元，2021 財年的研發費用為1.866 億美元，分別下降26% 和28%，而2020 年同期的研發費用為56.7 美元和2.577 億美元。研發費用季度和年度均有所下降與去年同期相比，主要是由於 Rubraca 臨床試驗支出減少。

Selling, general and administrative expenses totaled $33.3 million for Q4 2021 and $128.4 million for fiscal year 2021, down 18% and 22% respectively, compared to 40.8 and $163.9 million for the comparable periods in 2020. Selling, general and administrative expenses decreased during the quarter and the year compared to the prior periods -- the same periods in the prior year with savings due to the COVID-19 situation globally and overall cost reduction efforts.

2021 年第四季的銷售、一般和管理費用總計為 3,330 萬美元，2021 財年為 1.284 億美元，分別下降 18% 和 22%，而 2020 年同期分別為 40.8 和 1.639 億美元。與上一季和上一季相比，去年同期由於全球新冠肺炎(COVID-19) 疫情以及總體成本削減工作而節省了成本。

We reported a net loss for Q4 2021 of $64.4 million or $0.50 per share and a net loss of $264.5 million or $2.29 per share for fiscal year 2021. Net loss for Q4 2020 was $99 million or $1.02 per share and $369.2 million or a net loss of $4.38 per share for fiscal year 2020.

我們報告2021 年第四季的淨虧損為6,440 萬美元，即每股0.50 美元，2021 財年的淨虧損為2.645 億美元，即每股2.29 美元。2020 年第四季的淨虧損為9,900 萬美元，即每股1.02 美元，淨虧損為3.692 億美元，即每股淨虧損2020 財年每股收益為 4.38 美元。

Turning now to a discussion of cash and debt, Clovis had $143.4 million in cash and cash equivalents as of December 31, 2021. During Q4 2021, we raised $3 million in net proceeds and in Q1 2022 so far have raised $27.2 million in net proceeds through our previous established aftermarket equity offering program. We have capacity to issue additional shares of common stock under this ATM program.

現在轉向現金和債務的討論，截至2021 年12 月31 日，克洛維斯擁有1.434 億美元的現金和現金等價物。在2021 年第四季度，我們籌集了300 萬美元的淨收益，在2022 年第一季迄今已籌集了2,720 萬美元的淨收益透過我們先前製定的售後市場股權發行計畫。我們有能力根據該 ATM 計劃發行額外的普通股。

In addition, we paid off our 2.5% convertible senior notes due in 2021 at full maturity. Our next convertible debt maturity is August 1, 2024, and has a conversion price of $7.29 for a portion and a conversion price of $6.24 for the remainder. As of December 31, 2021, we had drawn $147.2 million under the Sixth Street Partners ATHENA clinical trial financing and had up to $27.8 million available to draw under the agreement to fund expenses of the ATHENA trial.

此外，我們還清償了 2021 年到期的 2.5% 可轉換優先票據。我們的下一個可轉換債務到期日是 2024 年 8 月 1 日，部分的轉換價格為 7.29 美元，其餘部分的轉換價格為 6.24 美元。截至 2021 年 12 月 31 日，我們已根據 Sixth Street Partners ATHENA 臨床試驗融資提取了 1.472 億美元，並根據協議可提取最多 2780 萬美元，用於資助 ATHENA 試驗的費用。

The first royalty payment to Sixth Street Partners will be in Q4 of this year after determination of Q3 2022 revenues subject to the applicable payment caps in the agreement. Net cash used in operating activities was $41.3 million for 4Q 2021, down from $56.1 million reported in 4Q 2020. Cash burn in Q4 2021 was $31.6 million, down 23% from Q4 2020 quarter cash burn of $40.9 million.

在根據協議中適用的付款上限確定 2022 年第三季收入後，將於今年第四季向 Sixth Street Partners 支付第一筆特許權使用費。 2021 年第四季經營活動使用的現金淨額為4,130 萬美元，低於2020 年第四季報告的5,610 萬美元。2021 年第四季的現金消耗為3,160 萬美元，比2020 年第四季的現金消耗4,090 萬美元下降23%。

Similarly, net cash used in operating activities for the full-year 2021 was $196.1 million compared with $252.7 million for the full-year 2020. Cash burn for the full year was $148.6 million, down 24% from the prior year cash burn of $195.6 million. We have and will continue to manage expenses carefully and we currently expect R&D and SG&A expenses in 2022 to be generally consistent with 2021. We remain focused on our liquidity position and recognize that we will need to raise additional capital in the near-term to fund our operating plans in the next 12 months and beyond.

同樣，2021 年全年經營活動使用的現金淨額為 1.961 億美元，而 2020 年全年為 2.527 億美元。全年現金消耗為 1.486 億美元，比上年現金消耗 1.956 億美元下降 24% 。我們已經並將繼續謹慎管理費用，目前預計 2022 年的研發和銷售、一般管理費用將與 2021 年基本一致。我們仍然關注我們的流動性狀況，並認識到我們需要在短期內籌集額外資本來資助我們未來12 個月及以後的營運計劃。

Now I'll turn the call back to Pat.

現在我將把電話轉回給帕特。

Thanks, Dan. In summary, we've set the stage for a very important year. We're on track to announce top line data from 3 Phase III Rubraca data readouts, ATHENA-MONO, ATHENA-COMBO and the TRITON 3 study that offer the potential for label expansions in ovarian and prostate cancers. This includes the ATHENA-COMBO readout that should definitively inform whether adding an anti-PD-1 to Rubraca monotherapy in the first-line maintenance treatment ovarian cancer setting extends Rubraca's progression-free survival.

謝謝，丹。總而言之，我們已經為非常重要的一年做好了準備。我們即將公佈 3 項 III 期 Rubraca 數據讀出、ATHENA-MONO、ATHENA-COMBO 和 TRITON 3 研究的主要數據，這些數據為卵巢癌和前列腺癌的標籤擴展提供了潛力。這包括 ATHENA-COMBO 讀數，該讀數應明確告知在卵巢癌一線維持治療中，在 Rubraca 單藥療法中添加抗 PD-1 是否會延長 Rubraca 的無惡化存活期。

In addition, our commitment to targeted radiotherapy is significant and offers the potential to be transformational in 2022 when we present data from the Phase I LuMIERE study of FAP-2286, the first peptide-targeted radionuclide therapy targeting FAP to enter clinical development. We intend to maintain our lead as we advance LuMIERE into Phase II and begin our combination development program. These anticipated pipeline events and our commitment to improving our balance sheet support our efforts to execute our 3 core strategies, expand the Rubraca label to drive revenue growth, emerge as a leader in targeted radionuclide therapy and achieve long-term financial stability.

此外，我們對標靶放射治療的承諾意義重大，並有可能在2022 年實現變革，屆時我們將展示FAP-2286 的I 期LuMIERE 研究數據，FAP-2286 是第一個進入臨床開發的針對FAP 的勝肽靶向放射性核素療法。當我們將 LuMIERE 推進到第二階段並開始我們的組合開發計劃時，我們打算保持領先地位。這些預期的管道事件以及我們對改善資產負債表的承諾支持我們努力執行 3 項核心策略，擴大 Rubraca 標籤以推動收入成長，成為靶向放射性核素治療的領導者並實現長期財務穩定。

With that, we're happy to answer any questions you may have.

因此，我們很樂意回答您可能提出的任何問題。

(Operator Instructions) Our first question is from Paul Choi with Goldman Sachs.

（操作員說明）我們的第一個問題來自高盛的 Paul Choi。

This is Charlie on for Paul. I just had a question on the FAP-2286 opportunity, it's exciting that we'll be seeing this data this year. And as we start to think about what the potential market opportunity is for this product. We're just wondering, are there any nuances in terms of considering the commercial potential for the imaging modality versus the therapeutic modalities, is there anything we should be considering there in terms of differences and how that might be priced or the potential patient populations that would be up for either the imaging or the therapeutic modality?

這是查理替保羅發言。我剛剛對 FAP-2286 機會有疑問，令人興奮的是我們今年將看到這一數據。當我們開始思考該產品的潛在市場機會是什麼時。我們只是想知道，在考慮影像方式與治療方式的商業潛力方面是否存在任何細微差別，我們是否應該在差異、定價方式或潛在患者群體方面考慮什麼？會選擇影像學還是治療方式？

I'll take a shot at that, Tom and then you may want to -- or Tom or Lindsey may want to add in. It's a really interesting and timely question for us. We have up to now primarily thought of the imaging opportunity with 2286 to be limited to its potential and necessity as a companion diagnostic. That is, as we seek to develop 2286 as a therapeutic, we would simultaneously be developing for a given indication the same peptide label with gallium to a -- as an imaging modality for patient selection.

我會嘗試一下，湯姆，然後你可能會想——或者湯姆或林賽可能想加入。這對我們來說是一個非常有趣且及時的問題。到目前為止，我們主要認為 2286 的成像機會僅限於其作為伴隨診斷的潛力和必要性。也就是說，當我們尋求開發 2286 作為治療劑時，我們將同時針對給定的適應症開發相同的鎵肽標記，作為患者選擇的成像方式。

We have been evaluating at the guidance and request of the clinical community with whom we interact, the nuclear medicine community whether or not FAP-2286 could be seen on its own as an imaging modality, particularly in tumor types where standard imaging for instance, FDG-PET are not as effective. And as we have evaluated this and we've looked at the reimbursement for a standalone imaging agent, it clearly has emerged as a potential opportunity.

我們一直在與我們互動的臨床界、核醫學界的指導和要求下評估 FAP-2286 是否可以單獨被視為一種成像方式，特別是在標準成像、FDG 等腫瘤類型中-PET 沒有那麼有效。當我們對此進行評估並研究獨立顯影劑的報銷時，它顯然已成為一個潛在的機會。

Haven't made a firm commitment yet to entering into this field, but we're getting there. The workup we've done suggest it's a pretty interesting opportunity financially. The cost of development is markedly lower than the cost of development for a therapeutic. And it is an earlier and quicker path to market for us as an opportunity to generate revenue for 2286 prior to when we would expect to see an accelerated approval for any given therapeutic opportunity. So interested, more to come on this, we'll probably be able to provide an update on our next quarterly call. Tom or Lindsey, anything you'd add to that?

尚未做出進入這一領域的堅定承諾，但我們正在實現這一目標。我們所做的調查表明，從財務角度來看，這是一個非常有趣的機會。開發成本明顯低於治療方法的開發成本。對我們來說，這是一條更早、更快的上市途徑，可以在我們期望看到任何給定治療機會加速批准之前為 2286 創造收入。我們很感興趣，對此還有更多內容，我們可能會在下一個季度電話會議上提供最新資訊。湯姆或林賽，你還有什麼要補充的嗎？

The only thing I've mentioned is to completely support what you're saying, there is some preliminary data that will be presented at the SNMMI Mid-Week winter meeting later this week from Thomas Hope. So take a look at that data.

我唯一提到的就是完全支持你所說的，托馬斯·霍普 (Thomas Hope) 將在本週晚些時候的 SNMMI 冬季周中會議上提供一些初步數據。所以看看這些數據。

Our next question is from Cory Kasimov with JPMorgan.

我們的下一個問題來自摩根大通的科里·卡西莫夫。

This is Gavin on for Cory. Just I had a question on data and then a follow-up to the previous question. I guess starting there, just curious on the process for the Gallium-68 inpatient selection. How efficient is that process? And how long does it take? And then just you mentioned some tumor types where standard is unable to meet the needs, what tumor types are those?

這是科里的加文。我只是有一個關於數據的問題，然後是上一個問題的後續問題。我想從這裡開始，只是對 Gallium-68 住院病患選擇的過程感到好奇。這個過程的效率如何？需要多長時間？那麼剛才您提到了一些標準無法滿足需求的腫瘤類型，那是哪些腫瘤類型？

Lindsey or Tom, do you want to talk about the kind of the logistical side? We have not yet determined exactly which tumors we would initially approach. We have a list, I probably don't want to share that yet. But again, we'll update on specific programs in the upcoming quarterly calls. On the logistics, Tom or Lindsey? Go ahead, Lindsey. Lindsey, I think we'll -- go ahead Lindsey.

Lindsey 或 Tom，您想談談後勤方面的情況嗎？我們還沒有確切地確定我們首先要治療哪些腫瘤。我們有一個清單，我可能還不想分享。但同樣，我們將在即將到來的季度電話會議中更新具體計劃。關於物流，湯姆還是林賽？繼續吧，林賽。 Lindsey，我想我們會—繼續，Lindsey。

So regarding the gallium scan -- the gallium scanning, because gallium has a very short half-life, the sites manufacture the imaging product on site on the day that it's used for the imaging. Our Phase I sites are all highly experienced in this kind of process. And so it's bread and butter for them again a new scanning agent setup. Does that answer your question?

因此，關於鎵掃描－鎵掃描，因為鎵的半衰期非常短，所以這些工廠在用於成像的當天現場生產成像產品。我們的一期工廠在此類過程中都擁有豐富的經驗。因此，新的掃描代理設定對他們來說又是麵包和黃油。這是否回答你的問題？

Great, yes. And then just quickly on the ATHENA-COMBO study, in your conversations with the community, is it possible to quantify how much you need to extend PFS for utilization in that setting?

太好了，是的。然後，在 ATHENA-COMBO 研究中，在您與社區的對話中，是否有可能量化您需要延長多少 PFS 才能在該環境中使用？

I'll try that -- go ahead, Lindsey, you go ahead and then I'll answer it.

我會嘗試——繼續，林賽，你繼續，然後我會回答。

That's obviously a difficult question to answer ahead of time, but we always expect the results to be clinically significant as well as statistically significant in order to drive uptake given that there are multiple options available now in frontline maintenance. I would expect the combination of Rubraca and Opdivo to be useful if the advantage over rucaparib is substantial, either in the whole population or in a sub-group.

這顯然是一個很難提前回答的問題，但我們總是期望結果具有臨床意義和統計意義，以便推動採用，因為目前一線維護中有多種選擇。如果 Rubraca 和 Opdivo 的組合相對於 rucaparib 的優勢很大，無論是在整個人群還是在一個亞組中，我預計 Rubraca 和 Opdivo 的組合將會有用。

I might add to that. The anticipation is growing now for that result. There's a great amount of interest in it and I think it speaks to the fact that, as is true for every tumor type now, hardly any patient fails to ask the question, can I get immunotherapy. It's on commercials, it's in the news, people are aware of it. And as you're probably aware, there are no immunotherapies approved today in ovarian except a very, very small subset. So I agree with Lindsey. Obviously, we have to show a benefit, it has to be statistically significant. I think the demand from the patient and from the prescribing community will be high. In particular, Lindsey said in subgroup populations and that's true, but I'd also add, as is true for a lot of IO, if the difference at the median is perhaps not substantial, but obviously needs to be statistically significant, but the tail for the combo looks to be providing significant benefit in a hard-to-identify subset, I think the demand for the combination would be quite high.

我可能會補充一點。現在人們對這結果的期望越來越高。人們對此非常感興趣，我認為它說明了這樣一個事實：就像現在每種腫瘤類型一樣，幾乎所有患者都會問這樣的問題：我可以接受免疫治療嗎？它出現在廣告中、出現在新聞中，人們都知道這一點。正如您可能知道的那樣，除了非常非常小的子集外，目前還沒有批准針對卵巢的免疫療法。所以我同意林賽的觀點。顯然，我們必須展示一個好處，它必須具有統計顯著性。我認為患者和處方界的需求將會很高。 Lindsey 特別指出，在亞組人群中，這是事實，但我還要補充一點，就像很多 IO 一樣，如果中位數的差異可能並不顯著，但顯然需要具有統計顯著性，但尾部由於該組合看起來在難以識別的子集中提供了顯著的好處，因此我認為對該組合的需求會相當高。

We have no further questions at this time. I'll turn the call back over to Ms. Sussman for any closing remarks.

目前我們沒有進一步的問題。我會將電話轉回蘇斯曼女士，讓她發表結束語。

Thank you, Chris. Thanks, everyone for your interest in Clovis Oncology today. If you have any follow-up questions, please call me at (303) 625-5022 or Breanna Burkart at (303) 625-5023. This call can be accessed via a replay of our webcast at clovisoncology.com, beginning in about an hour and will be available for 30 days. Again, we appreciate your interest and time. Thank you and have a good day.

謝謝你，克里斯。謝謝大家今天對克洛維斯腫瘤學的興趣。如果您有任何後續問題，請致電 (303) 625-5022 聯絡我，或致電 (303) 625-5023 Breanna Burkart。您可以透過 clovisoncology.com 上的網路廣播重播來觀看此電話會議，該電話會議將在大約一小時後開始，持續 30 天。再次感謝您的興趣和時間。謝謝你，有美好的一天。

Ladies and gentlemen, this concludes today's conference call. Thank you for participating and you may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝您的參與，您現在可以斷開連接。