Seagen Inc (SGEN) 2022 Q4 法說會逐字稿

Good day, everyone, and welcome to the Seagen Fourth Quarter and Full Year 2022 Conference Call. (Operator Instructions) Please also note, today's event is being recorded.

大家好，歡迎參加 Seagen 2022 年第四季和全年電話會議。 （操作員指示）另請注意，今天的活動正在被記錄。

At this time, I'd like to turn the conference call over to Doug Maffei, Vice President, Investor Relations. Sir, please go ahead.

現在，我想將電話會議交給投資人關係副總裁 Doug Maffei。先生，請繼續。

Thank you, operator, and good afternoon, everyone.

謝謝接線員，大家下午好。

I'm pleased to welcome you to Seagen's Fourth Quarter 2022 Financial Results Conference Call.

我很高興歡迎您參加 Seagen 2022 年第四季財務業績電話會議。

This afternoon, we issued a press release with our results. The press release and supporting slides are available on our website in the Investors section, Events and Presentations page. Speakers on this call will be David Epstein, Chief Executive Officer; Chip Romp, Executive Vice President Commercial U.S.; Todd Simpson, Chief Financial Officer; and Roger Dansey, President of Research and Development.

今天下午，我們發布了一份新聞稿，公佈了我們的研究結果。新聞稿和支援幻燈片可在我們網站的「投資者」部分、「活動和簡報」頁面上找到。本次電話會議的發言人將是執行長 David Epstein； Chip Romp，美國商業執行副總裁；托德辛普森 (Todd Simpson)，財務長；以及研發總裁 Roger Dansey。

Following our prepared remarks, we'll open the line for questions. We aim to keep this call to 1 hour and ask that you limit yourself to 1 question to give everyone an opportunity to participate in Q&A during our call today.

在我們準備好發言之後，我們將開放提問熱線。我們計劃將本次通話時間控制在 1 小時內，並要求您將問題限制在 1 個，以便每個人都有機會在今天的通話中參與問答。

Today's conference call will include forward-looking statements regarding future or anticipated events and results, including the company's 2023 financial outlook, anticipated products, used costs and expenses, potential clinical and regulatory milestones, including data readouts and regulatory submissions, potential marketing approvals and commercial performance. Actual results or developments may differ materially from those projected or implied in these forward-looking statements.

今天的電話會議將包括有關未來或預期事件和結果的前瞻性陳述，包括公司 2023 年的財務展望、預期產品、使用的成本和費用、潛在的臨床和監管里程碑（包括數據讀數和監管提交）、潛在的營銷批准和商業表現。實際結果或發展可能與這些前瞻性陳述中預測或暗示的結果或發展有重大差異。

Factors that may cause such a difference include the difficulty in forecasting sales, revenues, costs and expenses and the uncertainty associated with the pharmaceutical development and regulatory approval process. More information about the risks and uncertainties faced by Seagen is contained under the caption Risk Factors included in the company's quarterly report for the quarter ended September 30, 2022, filed with the Securities and Exchange Commission and the company's subsequent reports filed with the SEC.

可能導致這種差異的因素包括預測銷售、收入、成本和費用的困難以及與藥品開發和監管審批流程相關的不確定性。有關 Seagen 面臨的風險和不確定性的更多信息，請參閱公司向美國證券交易委員會提交的截至 2022 年 9 月 30 日的季度報告以及公司向美國證券交易委員會提交的後續報告中的“風險因素”標題。

Now I'll turn the call over to David.

現在我將把電話轉給大衛。

Thank you, Doug, and good afternoon, everyone.

謝謝你，道格，大家下午好。

Today, we reported total 2022 revenue of nearly $2 billion, reflecting 25% growth over 2021. This included record net product sales of $1.7 billion, driven by meaningful uptick across our entire commercial portfolio. Our sales guidance for '23 reflects our optimism in our ability to gain market share in existing indications and grow into newly labeled indications.

今天，我們報告了 2022 年的總收入近 20 億美元，比 2021 年成長了 25%。其中包括創紀錄的 17 億美元淨產品銷售額，這得益於我們整個商業產品組合的顯著成長。我們對 23 年的銷售預期反映了我們對在現有適應症中獲得市場份額並發展到新適應症的能力的樂觀態度。

In a moment, I will take you through the strategy we presented at the JPMorgan Healthcare Conference last month. But first, I'd like to begin by reflecting on an exceptional year for Seagen and noting a few 2022 accomplishments.

稍後我將向您介紹我們上個月在摩根大通醫療保健會議上提出的策略。但首先，我想回顧 Seagen 不平凡的一年，並指出 2022 年所取得的一些成就。

Beginning with our commercial products, we received regulatory approvals and reimbursement decisions in multiple markets. We now have commercial presence in 17 countries. We delivered robust development progress across our approved brands, including positive results for 4 pivotal trials that have already resulted in 2 label expansions and completed enrollment for 2 potentially registration-enabling studies are PADCEV and TUKYSA franchises. We advanced a broad recently prioritized pipeline of differentiated assets, including potentially transformative programs like DV, SGN-B6A and SGN-B7H4V, while at the same time, initiating Phase I studies for multiple new drug candidates.

從我們的商業產品開始，我們在多個市場獲得了監管部門的批准和報銷決定。我們目前在 17 個國家都有商業業務。我們在所有獲批品牌中都取得了強勁的發展進展，包括 4 項關鍵試驗的積極成果，這些試驗已經導致 2 個標籤擴展，並完成了 2 項可能註冊的研究的註冊，即 PADCEV 和 TUKYSA 特許經營權。我們推進了近期優先發展的差異化資產管道，包括 DV、SGN-B6A 和 SGN-B7H4V 等具有潛在變革性的項目，同時啟動了多種新藥候選藥物的第一階段研究。

Seagen also entered into multiple corporate development agreements for new assets that are complementary to our expertise. For example, we secured global rights to an exciting preclinical gamma delta bispecific T cell engager for EGFR expressing solid tumors and entered into a collaboration with Sanofi for the development of multiple novel ADCs.

Seagen 也簽署了多項企業開發協議，以獲得與我們的專業知識互補的新資產。例如，我們獲得了針對錶達 EGFR 的實體腫瘤的激動人心的臨床前伽馬德爾塔雙特異性 T 細胞接合劑的全球權利，並與賽諾菲合作開發多種新型 ADC。

Looking ahead, we are focused on 3 strategic pillars. The first is focused on optimizing the full potential of our commercial portfolio of first or best-in-class products, demonstrated clinical and real-world benefits. Here, we are working to enhance our commercial execution and footprint as well. In parallel, we're executing robust clinical development programs, including 10 potentially registrational studies for our approved products and areas of opportunity spanning multiple tumor types. These new labels could unlock meaningful growth across our approved brands and broaden their reach to significantly more patients in need.

展望未來，我們將重點放在三大戰略支柱上。第一個重點是優化我們首創或一流產品商業組合的全部潛力，並展示臨床和現實世界的益處。在這裡，我們也正在努力提高我們的商業執行力和影響力。同時，我們正在執行強有力的臨床開發計劃，包括針對我們已獲批准的產品和涵蓋多種腫瘤類型的機會領域進行的 10 項潛在註冊研究。這些新標籤可以促進我們認可品牌的有意義的成長，並擴大其覆蓋範圍，涵蓋更多有需要的患者。

ADCETRIS further demonstrated its clinical value in 2022 with important data readouts, a label expansion and 3 sequential quarters of record sales. ADCETRIS is the U.S. standard of care in frontline Hodgkin lymphoma, has 7 U.S. indications following the approval of a pediatric label late last year and is expected to reach blockbuster status in our territories in 2023.

ADCETRIS 在 2022 年透過重要的數據讀數、標籤擴展和連續 3 個季度的創紀錄銷售額進一步證明了其臨床價值。 ADCETRIS 是美國治療霍奇金淋巴瘤一線的標準藥物，自去年年底兒科標籤獲批以來，已在美國擁有 7 個適應症，預計將於 2023 年在我們地區達到重磅藥物地位。

Outside of the U.S. and Canada, our partner, Takeda, continues to deliver ADCETRIS in international markets and their product was recently added to the National Reimbursement Drug List in China.

在美國和加拿大以外，我們的合作夥伴武田繼續在國際市場上推出 ADCETRIS，其產品最近被列入中國國家醫保藥品目錄。

I'll now turn to PADCEV, which we believe has the potential to become our second blockbuster brand. The FDA granted priority review for an application seeking accelerated approval for the combination of PADCEV and KEYTRUDA in first-line metastatic bladder cancer for patients that are cisplatin-ineligible with a target action date of April 21, 2023.

現在我來談談 PADCEV，我們相信它有潛力成為我們的第二個重磅品牌。 FDA 對一項申請給予優先審查，該申請尋求加速批准 PADCEV 和 KEYTRUDA 聯合用於治療不適合順鉑治療的轉移性膀胱癌患者的一線治療，目標作用日期為 2023 年 4 月 21 日。

Our goal is to advance PADCEV's utility into earlier stages of bladder cancer, and our robust clinical development program includes both muscle and non-muscle invasive forms representing even larger potential patient segments. We continue to evaluate PADCEV beyond bladder cancer and expect to report data from the solid tumor study later this year. We're also looking to expand PADCEV globally in partnership with Astellas following its approval in the EU and other countries, including Japan.

我們的目標是將 PADCEV 的效用提升到膀胱癌的早期階段，我們強大的臨床開發計劃包括肌肉和非肌肉侵入形式，代表更大的潛在患者群體。我們將繼續評估膀胱癌以外的 PADCEV，並預計在今年稍後報告實體腫瘤研究的數據。在 PADCEV 在歐盟和日本等其他國家獲得批准後，我們也希望與安斯泰來合作，在全球推廣 PADCEV。

Moving on to TUKYSA. This brand provides significant benefit for adults with HER2-positive metastatic breast cancer, particularly those with brain metastases. TUKYSA is now approved in 39 countries, and we continue to make progress expanding its use outside of the U.S. with multiple country launches planned in 2023.

繼續前往 TUKYSA。該品牌為 HER2 陽性轉移性乳癌成年患者（尤其是腦轉移患者）帶來了顯著益處。 TUKYSA 目前已在 39 個國家獲得批准，我們將繼續在美國以外擴大其使用範圍，並計劃於 2023 年在多個國家推出。

Last month, TUKYSA received an accelerated approval for patients with previously treated HER2-positive metastatic colorectal cancer, and it was subsequently added to the NCCN guidelines. This is a modest sized but important population as these patients typically have poor outcomes following progression on frontline therapy.

上個月，TUKYSA 獲得了先前接受過治療的 HER2 陽性轉移性大腸直腸癌患者的加速批准，隨後被添加到 NCCN 指南中。這是一個規模適中但很重要的群體，因為這些患者在接受第一線治療後通常預後不佳。

Our broad development program includes a combination of TUKYSA with ADCs such as KADCYLA, which is used in second-line+ metastatic breast cancer in a trial called HER2CLIMB-02. Our partnership with Merck also extends TUKYSA's reach outside of the U.S., Europe and Canada.

我們廣泛的開發計劃包括將 TUKYSA 與 ADC（例如 KADCYLA）相結合，後者在名為 HER2CLIMB-02 的試驗中用於治療二線+轉移性乳癌。我們與默克公司的合作也擴大了 TUKYSA 在美國、歐洲和加拿大以外的影響力。

TIVDAK is our newest commercial product and continues to receive recognition as an important treatment option for cervical cancer. TIVDAK is now a preferred regimen for second line or subsequent recurrent or metastatic cervical cancer per the NCCN guidelines. We and our partner, Genmab, are advancing a Phase III trial that could support international marketing authorizations as well as serve as a confirmatory trial in the U.S. with potential top line data expected by year-end 2023.

TIVDAK 是我們最新的商業產品，並繼續獲得認可，成為子宮頸癌的重要治療選擇。根據 NCCN 指南，TIVDAK 現在是第二線或後續復發或轉移性子宮頸癌的首選治療方案。我們和我們的合作夥伴 Genmab 正在推進一項 III 期試驗，該試驗可以支持國際行銷授權，並作為美國的確認性試驗，預計到 2023 年底將獲得潛在的頂線數據。

Our second strategic pillar is to prioritize the clinical development of assets that we believe will have the most transformative impact on patients and our business. We recently initiated a portfolio prioritization discipline to critically access data, chance of success, unmet medical need and potential patient opportunity. Based upon this analysis, we have prioritized the most promising assets and programs, optimizing the risk-benefit reward balanced across our entire portfolio. Examples of programs that will receive priority resourcing are DV, B6A and B7H4. These are ADCs with large potential indications and global or near full global rights and economics that flow to Seagen that could help transform our company.

我們的第二個策略支柱是優先考慮我們認為對患者和我們的業務產生最大變革影響的資產的臨床開發。我們最近啟動了一項投資組合優先排序規則，以嚴格存取資料、成功機會、未滿足的醫療需求和潛在的患者機會。基於此分析，我們優先考慮最有前景的資產和項目，以優化整個投資組合的風險收益平衡。將獲得優先資源的項目範例包括 DV、B6A 和 B7H4。這些 ADC 具有巨大的潛在適應症和全球或接近全球的權利和經濟效益，它們流向 Seagen，可以幫助我們公司轉型。

Importantly, we remain focused on the combination of adult ADCs and anti-PD-1s given the growing body of data demonstrating the clinical synergy through immunogenic cell death. As such, we have 9 trials underway exploring this combination.

重要的是，鑑於越來越多的數據證明透過免疫原性細胞死亡產生臨床協同作用，我們仍然專注於成人 ADC 和抗 PD-1 的組合。因此，我們正在進行 9 項試驗來探索這種組合。

Our third strategic pillar is to advance innovative next-generation ADC technologies to empower our pipeline for years to come. Several products utilizing our vedotin technology are now approved with many other pipeline assets in development. We believe the ADC market will in time be measured in the tens of billions of dollars.

我們的第三個策略支柱是推動創新的下一代 ADC 技術，為我們未來幾年的管道提供動力。採用我們的 vedotin 技術的幾種產品現已獲得批准，還有許多其他管道資產正在開發中。我們相信，ADC 市場規模最終將達到數百億美元。

In parallel, our teams are working on multiple waves of new ADC technologies that we believe will come to fruition at varying time points. For example, we're developing ADCs employing novel auristatin and camptothecin technologies as well as ADCs that incorporate new cytotoxic and immunostimulatory payloads. Further out, we expect ADCs to utilize novel drug conjugate technologies that employ other diverse mechanisms of action.

同時，我們的團隊正在研究多波新的 ADC 技術，我們相信這些技術將在不同的時間點上取得成果。例如，我們正在開發採用新型奧瑞他汀和喜樹鹼技術的 ADC 以及結合新型細胞毒性和免疫刺激有效載荷的 ADC。進一步來說，我們期望 ADC 能夠利用採用其他不同作用機制的新型藥物偶聯技術。

We continue to invest in cutting-edge technology to retain our leadership position and expand the number of approved ADCs in order to reach still more patients. We remain selective and opportunistic in supplementing our pipeline with complementary external assets that could also have exciting potential.

我們將繼續投資尖端技術，以保持我們的領導地位並擴大獲批的 ADC 數量，從而惠及更多患者。我們始終堅持選擇性和機會性，用也可能具有巨大潛力的互補外部資產來補充我們的產品線。

With that, I'll turn the call over to Chip, who will provide an update on our commercial performance. Then Todd will discuss our financial results and 2023 guidance. After that, Roger will detail our development activities and pipeline. Take it away, Chip.

說完這些，我將把電話轉給 Chip，他將提供有關我們商業表現的最新情況。然後托德將討論我們的財務表現和 2023 年指引。之後，Roger 將詳細介紹我們的開發活動和管道。把它拿走吧，奇普。

Thank you, David.

謝謝你，大衛。

The commercial team delivered another strong quarter to close out a very successful year for Seagen. Performance in Q4 underscores strong commercial execution across our portfolio. ADCETRIS' fourth quarter sales were a record $238 million, a 35% increase over the fourth quarter of 2021.

商業團隊又取得了一個強勁的季度業績，為 Seagen 非常成功的一年畫上了圓滿的句號。第四季的表現凸顯了我們整個投資組合強勁的商業執行力。 ADCETRIS 第四季銷售額創下 2.38 億美元的紀錄，較 2021 年第四季成長 35%。

Year-over-year growth reflects a return to pre-COVID diagnosis rates, favorable gross to nets and share point gains in frontline Hodgkin lymphoma. ADCETRIS is now a category 1 preferred agent in the NCCN guidelines, which has resulted in positive changes in treatment pathways and incremental share gains in the frontline setting. We are pleased with the performance of ADCETRIS, and we continue to see opportunities for incremental share gains in frontline HL in 2023.

同比增長反映了診斷率恢復到 COVID 之前的狀態、總收入與淨收入的良好增長以及一線霍奇金淋巴瘤的份額點數增加。 ADCETRIS 現在是 NCCN 指南中的 1 類首選藥物，這導致了治療途徑的積極變化和一線治療中份額的逐步增加。我們對 ADCETRIS 的表現感到滿意，並且我們繼續看到 2023 年一線 HL 份額增加的機會。

PADCEV's fourth quarter sales were $122 million, a 32% increase over the same quarter of last year. These sales included clinical trial supply orders of $6 million for the quarter. PADCEV remains a U.S. standard of care in the second-line setting. Underlying growth was primarily driven by patient flow into the second-line setting due to continued use of checkpoint inhibitors as frontline maintenance therapy.

PADCEV第四季銷售額為1.22億美元，比去年同期成長32%。這些銷售額包括本季 600 萬美元的臨床試驗供應訂單。 PADCEV 仍然是美國二線治療的標準。潛在的成長主要是由於檢查點抑制劑繼續用作一線維持療法，導致患者流入二線治療。

Meanwhile, our commercial teams are preparing for a potential launch into the frontline metastatic setting in combination with KEYTRUDA in cisplatin-ineligible patients. As a reminder, this is a sizable opportunity with approximately 20,000 total addressable patients in the frontline metastatic setting in the U.S. Around 18,000 of these patients are drug-treated and approximately 50% are ineligible for cisplatin-based chemotherapy. If approved, the PADCEV combination would represent an additional important new treatment option in the frontline setting.

同時，我們的商業團隊正在為將藥物與 KEYTRUDA 聯合用於不適合順鉑治療的患者的一線轉移性治療做準備。提醒一下，這是一個巨大的機會，美國第一線轉移性治療領域總共約有 20,000 名可治療患者。其中約 18,000 名患者接受藥物治療，約 50％ 的患者不適合接受以順鉑為基礎的化療。 如果獲得批准，PADCEV 組合將成為前線治療中另一個重要的新治療選擇。

Moving on to TUKYSA. Fourth quarter sales were $86 million, down 9% year-over-year. We have established TUKYSA's market position as a valuable treatment option for patients in the second-line+ setting, especially for those with active brain metastases. TUKYSA continues to perform well despite ongoing competitive headwinds related to Enhertu's increased use in the second-line+ setting. We expect to see stabilization of patient flow into the third line in the second half of this year.

繼續前往 TUKYSA。第四季銷售額為 8,600 萬美元，年減 9%。我們已經確立了 TUKYSA 的市場地位，使其成為二線+治療患者（尤其是活動性腦轉移患者）的寶貴治療選擇。儘管 Enhertu 在二線+環境中的使用增加帶來了持續的競爭阻力，但 TUKYSA 仍然表現良好。我們預計今年下半年三線病人流量將趨於穩定。

TUKYSA's performance continues to benefit from extended treatment duration of a year or longer in approximately 1/3 of patients, which underscores its efficacy and tolerability. After last month's FDA accelerated approval, our commercial team has now launched TUKYSA in the second-line+ setting in patients with HER2-positive metastatic colorectal cancer. This represents the first approved HER2-directed therapy in this setting. Although a modestly sized market of approximately 100 patients, this population represents a high unmet medical need as existing approved colorectal cancer therapies typically offer limited response rates. In addition, we estimate approximately half of colorectal cancer patients are currently screened for HER2 expression.

TUKYSA 的表現持續受益於約 1/3 患者的一年或更長時間的延長治療時間，凸顯了其療效和耐受性。在上個月獲得 FDA 加速批准後，我們的商業團隊現已在 HER2 陽性轉移性結直腸癌患者的二線+治療中推出了 TUKYSA。這是該領域首個獲準的 HER2 標靶療法。儘管該市場規模適中，約有 100 名患者，但由於現有核准的大腸直腸癌療法的反應率通常有限，因此該族群代表著巨大的未滿足醫療需求。此外，我們估計目前約有一半的大腸直腸癌患者接受了 HER2 表現篩檢。

A focus of our commercial efforts will be on increasing patient screening rates. Looking beyond the U.S., following successful pricing negotiations in the fourth quarter, we launched the TUKYSA in Italy and Norway and look forward to expanding access in the coming months. Merck is progressing regulatory submissions and reimbursement activities intended to expand TUKYSA's reach in their territory and have multiple launches planned this year.

我們的商業努力的重點是提高患者篩檢率。放眼美國以外，繼第四季度成功進行定價談判後，我們在義大利和挪威推出了 TUKYSA，並期待在未來幾個月內擴大其應用範圍。默克公司正在推動監管提交和報銷活動，旨在擴大 TUKYSA 在其領域的影響力，並計劃今年推出多款產品。

And finally, TIVDAK sales were $18 million for the fourth quarter, an increase of 7% from the third quarter of 2022. The Seagen and Genmab commercial teams remain focused on ensuring positive treatment experiences and driving further market penetration of this important treatment option. We also look forward to the outcome of the innovaTV 301 global Phase III trial later this year, which could result in full FDA approval if it demonstrates an OS benefit and other endpoints, while potentially serving as the basis for global submissions.

最後，TIVDAK 第四季的銷售額為 1,800 萬美元，較 2022 年第三季成長 7%。 Seagen 和 Genmab 商業團隊將繼續致力於確保積極的治療體驗，並推動這項重要治療方案進一步滲透市場。我們也期待今年稍後 innovaTV 301 全球 III 期試驗的結果，如果該試驗能證明 OS 優勢和其他終點，則可能獲得 FDA 的完全批准，同時可能成為全球提交的基礎。

With that, I'll pass the call over to Todd who will discuss our financial performance, including our outlook for 2023. Todd?

說完這些，我將把電話轉給托德，他將討論我們的財務業績，包括我們對 2023 年的展望。托德？

Great. Thanks, Chip, and thanks to everyone for joining us on the call.

偉大的。謝謝，Chip，也謝謝大家參加我們的電話會議。

Our financial results reflect significant progress made across the business in the past year. Today, I'll summarize our 2022 financial performance and then discuss our 2023 guidance.

我們的財務表現反映了過去一年整個業務的重大進展。今天，我將總結我們 2022 年的財務業績，然後討論我們 2023 年的指導。

Total revenues were $528 million in the fourth quarter and $1.96 billion for the full year in 2022, representing year-over-year growth of 23% and 25%, respectively.

2022年第四季總營收為5.28億美元，全年總營收為19.6億美元，分別較去年同期成長23%及25%。

This included record net product sales of $464 million in the fourth quarter and $1.7 billion for the full year, reflecting year-over-year growth of 26% and 23%, respectively. This growth was driven primarily by ADCETRIS and PADCEV as well as contributions from the launch of TIVDAK.

其中包括第四季創紀錄的 4.64 億美元淨產品銷售額和全年 17 億美元的淨產品銷售額，分別較去年同期成長 26% 和 23%。這一成長主要得益於 ADCETRIS 和 PADCEV 以及 TIVDAK 推出的貢獻。

Royalty revenues were $53 million in the fourth quarter and $165 million for the full year in 2022. Full year royalty revenues increased 9% over 2021 driven by strong commercial performance by our partners, notably Takeda with its sales of ADCETRIS and Roche with its sales of Polivy.

2022 年第四季特許權使用費收入為 5,300 萬美元，全年特許權使用費收入為 1.65 億美元。由於合作夥伴強勁的商業表現，全年特許權使用費收入較 2021 年增長 9%，尤其是武田的 ADCETRIS 銷售額和羅氏的 Polivy 銷售額。

Collaboration revenues were $11 million in the fourth quarter and $91 million for the full year in 2022. These included royalties on sales of PADCEV by Astellas in its territory as well as other collaboration revenues, including a new collaboration with Zai Lab in the third quarter.

2022 年第四季合作收入為 1,100 萬美元，全年合作收入為 9,100 萬美元。其中包括安斯泰來在其地區銷售 PADCEV 的特許權使用費以及其他合作收入，包括第三季與再鼎醫藥的新合作。

Cost of sales was $108 million in the fourth quarter and $410 million for the full year in 2022. These include product cost of sales and royalties for each of our 4 brands, profit share amounts owed to our collaboration partners, Astellas and Genmab, as well as noncash amortization of acquired technology costs for TUKYSA.

2022 年第四季銷售成本為 1.08 億美元，全年銷售成本為 4.1 億美元。其中包括我們 4 個品牌各自的產品銷售成本和特許權使用費、欠我們的合作夥伴 Astellas 和 Genmab 的利潤分成金額，以及 TUKYSA 收購技術成本的非現金攤銷。

R&D expenses were $358 million in the fourth quarter and $1.34 billion for the full year in 2022. These reflect continued investment to expand the potential of our approved products and to advance our pipeline programs.

2022 年第四季的研發費用為 3.58 億美元，全年研發費用為 13.4 億美元。這反映了我們持續的投資，以擴大我們已獲批准產品的潛力並推動我們的產品線計劃。

SG&A expenses were $216 million in the fourth quarter and $821 million for the full year in 2022. This was driven by ongoing commercialization efforts in the U.S. and Europe as well as other corporate activities to support our growing business.

2022 年第四季銷售、一般及行政費用為 2.16 億美元，全年為 8.21 億美元。這得益於我們在美國和歐洲持續進行的商業化努力以及為支持我們不斷成長的業務而開展的其他公司活動。

Next, I will turn to our financial outlook. We expect total revenues in 2023 to be in the range of $2.14 billion to $2.24 billion, representing growth of 9% to 14% over 2022.

接下來，我將談談我們的財務前景。我們預計 2023 年總營收將在 21.4 億美元至 22.4 億美元之間，比 2022 年成長 9% 至 14%。

Beginning this year, we are providing product sales guidance at a portfolio level. This reflects the expansion of our commercial portfolio to now 4 approved products, an increasing number of indications and expanding geographies. We will continue to report quarterly results at a brand level.

從今年開始，我們將在產品組合層面提供產品銷售指導。這反映了我們的商業組合擴大到現在 4 種核准產品、越來越多的適應症和不斷擴大的地理範圍。我們將繼續在品牌層級報告季度業績。

With that in mind, looking across the portfolio, we are guiding to product sales of $1.925 billion to $2.0 billion, representing an increase of 13% to 17% over 2022. We expect ADCETRIS growth to be driven by continued use across the 7 indications, most notably in frontline Hodgkin lymphoma, and we expect ADCETRIS to reach blockbuster status in our territories this year for the first time.

考慮到這一點，縱觀整個產品組合，我們預計產品銷售額將達到 19.25 億美元至 20 億美元，比 2022 年增長 13% 至 17%。我們預計 ADCETRIS 的成長將受到 7 種適應症的持續使用所推動，最顯著的是霍奇金淋巴瘤的一線治療，我們預計 ADCETRIS 今年將首次在我們的地區達到重磅藥物地位。

PADCEV is an important and established brand for the company. Our guidance today does not include contributions from the potential U.S. label expansion for PADCEV which has a PDUFA action date of April 21. We expect that ADCETRIS and PADCEV, will remain the largest contributors to our sales in 2023, and we look at the second half of 2022 as a good indicator of how each of our brands will perform going into 2023. As a reminder, first quarter sales are typically the lowest of the quarters with growth seen throughout the year.

PADCEV 是該公司一個重要且成熟的品牌。我們今天的指引不包括 PADCEV 潛在的美國標籤擴展帶來的貢獻，該標籤擴展的 PDUFA 行動日期為 4 月 21 日。我們預計 ADCETRIS 和 PADCEV 仍將是 2023 年我們銷售額的最大貢獻者，我們將 2022 年下半年視為我們每個品牌在 2023 年表現的良好指標。提醒一下，第一季的銷售額通常是全年成長的季度中最低的。

We are excited about the recent label expansion for TUKYSA into metastatic colorectal cancer patients. While the label expansion takes us beyond breast cancer, it represents a relatively modest commercial opportunity. From an overall brand perspective, while we expect contributions from colorectal cancer, we also expect continued headwinds from Enhertu in breast cancer in the near term, and that will impact overall growth in 2023.

我們對 TUKYSA 最近擴展到轉移性大腸直腸癌患者的標籤擴展感到非常興奮。雖然標籤擴展使我們不再局限於乳癌，但它代表著一個相對溫和的商業機會。從整體品牌角度來看，雖然我們預期大腸直腸癌領域將有所貢獻，但我們也預期短期內 Enhertu 在乳癌領域將繼續面臨阻力，這將影響 2023 年的整體成長。

And finally, while we continue our efforts to drive TIVDAK growth in its current indication, which has become an important treatment option for women with advanced cervical cancer, we continue to look for future growth opportunities for TIVDAK through our basket trial efforts in other tissue factor expressing solid tumors, and Roger will provide a development update later.

最後，我們將繼續努力推動 TIVDAK 在當前適應症方面的成長，該適應症已成為晚期子宮頸癌女性的重要治療選擇，同時，我們將繼續透過在其他組織因子表達實體腫瘤中的籃子試驗努力尋找 TIVDAK 未來的成長機會，Roger 稍後將提供開發更新。

Next, we expect royalty revenues to be in the range of $170 million to $185 million primarily reflecting sales of ADCETRIS by Takeda in its territory along with contributions from sales of Polivy by Roche. As a reminder, the Takeda royalty rate tiers reset at the beginning of each year.

接下來，我們預計特許權使用費收入將在 1.7 億美元至 1.85 億美元之間，主要反映武田在其領土內銷售 ADCETRIS 以及羅氏銷售 Polivy 的貢獻。提醒一下，武田的專利費率等級每年年初都會重置。

Finally, we expect collaboration revenues to be in the range of $45 million to $55 million, which includes PADCEV royalties from Astellas as well as amounts earned from our other collaboration partners.

最後，我們預計合作收入將在 4500 萬美元至 5500 萬美元之間，其中包括來自安斯泰來 (Astellas) 的 PADCEV 特許權使用費以及從我們的其他合作夥伴那裡獲得的金額。

R&D expenses are expected to be in the range of $1.425 billion to $1.525 billion. This reflects continued investment in clinical trials to further expand our commercial brands, advance our earlier stage agents and drive our ADC innovation.

研發費用預計在14.25億美元至15.25億美元之間。這反映了我們對臨床試驗的持續投資，以進一步擴大我們的商業品牌、推動我們的早期藥物並推動我們的 ADC 創新。

SG&A expenses are expected to be in the range of $880 million to $930 million focused on commercial execution to drive growth of our approved products and to support our overall growth strategy.

預計銷售、一般及行政費用將在 8.8 億美元至 9.3 億美元之間，重點用於商業執行，以推動我們已批准產品的成長並支持我們的整體成長策略。

Cost of sales is expected to be in the range of $420 million to $470 million. Growth over 2022 will be driven by increased product sales and higher profit share payments to our collaborators.

銷售成本預計在4.2億美元至4.7億美元之間。 2022 年的成長將得益於產品銷售的成長和向合作者支付的更高利潤分成。

Noncash expenses are expected to be in the range of $330 million to $375 million, the majority of which is stock-based compensation. Taken together, our financial guidance reflects our strategy to support the growth of our current approved brands and fund the development of a growing pipeline.

非現金支出預計在 3.3 億美元至 3.75 億美元之間，其中大部分為股票薪酬。總的來說，我們的財務指導反映了我們的策略，即支持當前批准的品牌的成長並為不斷增長的產品線開發提供資金。

Now I'll turn the call over to Roger for an overview of our research and development projects. Roger?

現在我將把電話轉給羅傑，讓他概述我們的研發項目。羅傑？

Thank you, Todd, and good afternoon, everyone.

謝謝你，托德，大家下午好。

I'm happy to share recent clinical development updates for both our approved medicines and our pipeline. I will begin with ADCETRIS, which is the foundation of care in CD30 expressing lymphomas. Since our last call, we have achieved a number of important milestones.

我很高興與大家分享我們已核准的藥物和研發管線的最新臨床開發進度。我將從 ADCETRIS 開始，它是 CD30 表達淋巴瘤的治療基礎。自上次通話以來，我們已取得許多重要的里程碑。

In September, the NCCN guidelines were updated elevating the ADCETRIS combination to a Category 1 preferred treatment option for adults with previously untreated Stage 3 or 4 Hodgkin lymphoma. Based on the impressive overall survival data from the ECHELON-1 trial. These data are currently under review by FDA for potential inclusion in the label.

9 月，NCCN 指南進行了更新，將 ADCETRIS 組合提升為未經治療的 3 期或 4 期霍奇金淋巴瘤成人患者的 1 類首選治療方案。 根據 ECHELON-1 試驗令人印象深刻的整體生存數據。這些數據目前正在接受 FDA 的審查，以確定是否可能納入標籤中。

In November, ADCETRIS was approved by the FDA for pediatric patients 2 years and older with previously untreated high-risk classical Hodgkin lymphoma in combination with standard chemotherapy based on the Children's Oncology Group study. We continue to evaluate other potential indications for ADCETRIS, including DLBCL and solid tumors, the latter of which we expect to report data in the first half of this year.

11 月，根據兒童腫瘤組的研究，FDA 批准 ADCETRIS 與標準化療聯合用於治療 2 歲及以上未曾治療的高風險經典霍奇金淋巴瘤兒科患者。我們將繼續評估 ADCETRIS 的其他潛在適應症，包括 DLBCL 和實體腫瘤，我們預計將在今年上半年報告後者的數據。

Moving on to PADCEV. PADCEV has been granted priority review with a PDUFA date of April 21, 2023, for our supplemental BLA based primarily upon data from Cohort K of the EV-103 trial. As a reminder, this cohort studied the safety and efficacy of PADCEV in combination with KEYTRUDA in frontline cisplatin-ineligible patients with unresectable, locally advanced or metastatic urothelial cancer. At ESMO, we presented data that showed the combination generated in ORR of 64.5%, median cycles of therapy of 11 months and a median duration of response that has not yet been reached.

繼續討論 PADCEV。 PADCEV 已獲得優先審查，PDUFA 日期為 2023 年 4 月 21 日，我們的補充 BLA 主要基於 EV-103 試驗的 K 組數據。提醒一下，該隊列研究了 PADCEV 與 KEYTRUDA 聯合治療無法切除、局部晚期或轉移性尿路上皮癌的一線順鉑不合格患者的安全性和有效性。在 ESMO，我們展示的數據表明，該組合療法的 ORR 為 64.5%，治療週期中位數為 11 個月，而反應持續時間中位數尚未達到。

This week at ASCO GU, analysis evaluating the response of the PADCEV combination across different patient subgroups treated in EV-103 Cohort K will be presented. These data confirm the consistent benefit of PADCEV and KEYTRUDA amongst key patient populations, including those with liver metastases and low levels of PD-L1 expression.

本週在 ASCO GU 上，將展示評估 PADCEV 組合對 EV-103 K 群組中接受治療的不同患者亞群的反應的分析。這些數據證實了 PADCEV 和 KEYTRUDA 在關鍵患者群體（包括肝轉移和 PD-L1 表達量低的患者）中的一致益處。

Of note, we completed global enrollment of EV-302 in November of 2022 and estimate PFS topline data to be available by year's end.

值得注意的是，我們於 2022 年 11 月完成了 EV-302 的全球招募，並預計 PFS 頂線資料將於年底前公佈。

An extension study in China continues to enroll. This is a global study evaluating PADCEV in combination with KEYTRUDA in both cis-ineligible and cis-eligible patients which is a broader frontline population than was enrolled in Cohort K. EV-302 is intended to support submissions around the world, including in Europe and Asia and is the confirmatory trial for a potential U.S. accelerated approval of PADCEV in the EV-103 Cohort K treatment setting.

在中國的延伸研究仍在繼續招生。這是一項全球性研究，評估了 PADCEV 與 KEYTRUDA 聯合治療順式受體不符合條件和符合順式受體條件的患者的效果，該研究的一線人群比 K 隊列中招募的人群更廣泛。 EV-302 旨在支援包括歐洲和亞洲在內的全球範圍內的提交，並且是為美國可能在 EV-103 K 隊列治療環境中加速批准 PADCEV 而進行的確認性試驗。

In muscle invasive bladder cancer, which is a stage earlier than metastatic disease, we continue to advance PADCEV with 2 ongoing global Phase III studies evaluating the combination with KEYTRUDA given perioperatively. In non-muscle invasive bladder cancer, which is the earliest disease stage, we are conducting a Phase I study, EV-104 with PADCEV given as intravesicular therapy. Initial data may be presented later this year.

對於肌肉層浸潤性膀胱癌（比轉移性疾病更早的階段），我們繼續推進 PADCEV，目前正在進行 2 項全球 III 期研究，評估其與圍手術期給藥的 KEYTRUDA 的聯合使用。對於非肌肉層浸潤性膀胱癌（即最早的疾病階段），我們正在進行 I 期研究，以 EV-104 和 PADCEV 作為膀胱內治療。初步數據可能會在今年稍後公佈。

Beyond urothelial cancer, together with Astellas, we are also considering PADCEV's potential in other Nectin-4 expressing solid tumors and will be sharing initial data in the first half of this year.

除了尿路上皮癌之外，我們還與安斯泰來一起研究 PADCEV 在其他表達 Nectin-4 的實體瘤中的潛力，並將在今年上半年分享初步數據。

Continuing with TUKYSA, we recently received accelerated approval in combination with trastuzumab for the treatment of allowed patients with previously treated metastatic colorectal cancer. Importantly, NCCN guidelines have been updated to include TUKYSA as a treatment option for patients with HER2-expressing RAS wild-type metastatic colorectal cancer. Clinical situations outlined in the guidelines include a primary treatment option for patients who received adjuvant FOLFOX or CAPOX within the last 12 months, a first-line treatment option for metastatic disease where patients are ineligible for intensive chemotherapy and second-line and beyond treatment option for patients who progress on any frontline chemotherapy. A Phase III trial has been initiated in frontline metastatic colorectal cancer, which is intended to serve as a confirmatory trial in the United States and support global submissions.

繼續使用 TUKYSA，我們最近獲得了加速批准，與曲妥珠單抗聯合用於治療先前接受過治療的轉移性結直腸癌患者。重要的是，NCCN 指南已更新，將 TUKYSA 納入為 HER2 表達 RAS 野生型轉移性結直腸癌患者的治療選擇。指引概述的臨床情況包括：過去 12 個月內接受過輔助 FOLFOX 或 CAPOX 治療的患者的主要治療選擇、患者不適合接受強化化療的轉移性疾病的一線治療選擇以及在任何一線化療後病情出現進展的患者的二線及以上治療選擇。一線轉移性結直腸癌的 III 期試驗已經啟動，旨在作為美國的確認性試驗並支持全球提交。

Moving to breast cancer. HER2CLIMB-02, our Phase III study of TUKYSA in combination with KADCYLA in metastatic second-line+ patients completed enrollment in June of 2022, and topline data is anticipated in the first half of this year. KADCYLA is an important treatment option for patients with HER2-positive metastatic breast cancer, and if the trial is successful, the combination of TUKYSA plus KADCYLA could provide an alternative late line option, including for patients with brain metastases. Additionally, for TUKYSA, we plan to present data in the first half of this year from our basket trial in combination with trastuzumab in previously treated metastatic solid tumors with HER2 alterations, with a focus on biliary tract cancers.

轉向乳癌。 HER2CLIMB-02 是我們針對轉移性二線+患者進行的 TUKYSA 與 KADCYLA 聯合治療的 III 期研究，該研究於 2022 年 6 月完成入組，預計將於今年上半年獲得頂線數據。 KADCYLA 是 HER2 陽性轉移性乳癌患者的重要治療選擇，如果試驗成功，TUKYSA 與 KADCYLA 的組合可以為包括腦轉移患者在內的患者提供替代的晚期治療選擇。此外，對於 TUKYSA，我們計劃在今年上半年展示我們的籃子試驗數據，該試驗與曲妥珠單抗聯合用於治療先前接受過治療的 HER2 改變的轉移性實體瘤，重點是膽道癌。

I'll turn now to TIVDAK, which is approved in the United States for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The Phase III trial in cervical cancer innovaTV 301 is close to completing global enrollment with the potential for topline data in the second half of this year. This study is intended to serve as the confirmatory trial in the United States and to support global regulatory applications.

現在我來談談 TIVDAK，該藥物已在美國獲準用於治療化療期間或化療後病情進展的複發性或轉移性子宮頸癌患者。子宮頸癌 III 期試驗 innovaTV 301 即將完成全球招募，並有可能在今年下半年獲得頂線數據。這項研究旨在作為美國的確認性試驗並支持全球監管應用。

Beyond cervical cancer, we continue to study the potential for TIVDAK in other malignancies through an ongoing Phase II study, innovaTV 207. Initial data with a modified dosing schedule in head and neck cancer is projected to be presented this year.

除了子宮頸癌之外，我們還透過正在進行的 II 期研究 innovaTV 207 繼續研究 TIVDAK 在其他惡性腫瘤中的潛力。預計今年將公佈針對頭頸癌的修改後給藥方案的初步數據。

Continuing with disitamab vedotin or DV, this HER2-directed ADC is being evaluated as monotherapy and in combination with KEYTRUDA for the treatment of metastatic urothelial cancer in HER2-expressing tumors. We plan to initiate a Phase III trial in frontline metastatic urothelial cancer in combination with KEYTRUDA later this year. Additionally, development activities are underway to evaluate DV as a monotherapy and in combination with TUKYSA or KEYTRUDA in HER2 low metastatic breast cancer and HER2 expressing gastric cancers.

繼續使用 disitamab vedotin 或 DV，這種 HER2 導引 ADC 正在被評估為單一療法以及與 KEYTRUDA 聯合用於治療 HER2 表達腫瘤中的轉移性尿路上皮癌。我們計劃在今年稍後啟動與 KEYTRUDA 聯合治療一線轉移性尿路上皮癌的 III 期試驗。 此外，目前正在進行開發活動，以評估 DV 作為單一療法以及與 TUKYSA 或 KEYTRUDA 聯合治療 HER2 低轉移性乳癌和 HER2 表達胃癌的療效。

Moving to our early-stage pipeline, starting with SGN-B6A a wholly owned vedotin ADC targeting integrin beta-6. We reported Phase I clinical data in November at SITC. In addition to a manageable and tolerable safety profile at the explore dose regimens, the initial antitumor activity observed in heavily pretreated patients with advanced solid tumors appears encouraging and has triggered expansion cohorts in non-small cell lung cancer, head and neck cancer and esophageal cancer. Focusing on the lung cancer subset, we observed a 33% confirmed objective response rate. Updated clinical data, including initial durability of response will be reported later this year.

轉向我們的早期管道，從 SGN-B6A 開始，這是針對整合素 β-6 的全資 vedotin ADC。我們於 11 月在 SITC 報告了 I 期臨床數據。除了在探索劑量方案下可控制且可耐受的安全性外，在接受過大量治療的晚期實體瘤患者中觀察到的初始抗腫瘤活性似乎令人鼓舞，並引發了非小細胞肺癌、頭頸癌和食道癌的擴展隊列。重點關注肺癌亞組，我們觀察到確認的客觀緩解率為 33%。更新後的臨床數據（包括初始反應持久性）將於今年稍後公佈。

Turning now to SGN-B7H4V. This is a novel vedotin ADC targeting the immune checkpoint B7H4 with potential opportunities in breast, ovarian and endometrial cancer. We are making progress in the first-in-human trial and anticipate sharing initial clinical data this year.

現在轉向 SGN-B7H4V。這是一種針對免疫檢查點 B7H4 的新型 vedotin ADC，在乳癌、卵巢癌和子宮內膜癌中具有潛在治療潛力。我們在首次人體試驗中取得了進展，預計今年將分享初步臨床數據。

We continue to advance our IND engine with ADCs and other targeted therapies for cancer. In partnership with Sanofi, we are planning a 2023 IND submission for CEACAM5 targeted ADC with preclinical data supporting the submission to be presented at an upcoming medical meeting.

我們將繼續利用 ADC 和其他針對癌症的標靶療法來推進我們的 IND 引擎。我們與賽諾菲合作，計劃於 2023 年提交針對 CEACAM5 靶向 ADC 的 IND，並在即將舉行的醫學會議上展示支持該提交的臨床前數據。

Further, we are planning additional IND submissions with ADCs utilizing novel drug linkers and payloads. SGN-BB228, a costimulatory bispecific has recently achieved first patient enrolled in a Phase I first-in-human trial initially focused on relapsed or refractory metastatic melanoma. SGN-EGFRRD2, a preclinical bispecific targeting gamma delta T cells and EGFR positive tumor cells is on track for an IND submission in 2023.

此外，我們正計劃提交更多利用新型藥物接頭和有效載荷的 ADC 的 IND 申請。 SGN-BB228 是一種共刺激雙特異性藥物，最近在 I 期首次人體試驗中招募了第一位患者，該試驗最初針對復發或難治性轉移性黑色素瘤。 SGN-EGFRRD2 是一種針對 γδT 細胞和 EGFR 陽性腫瘤細胞的臨床前雙特異性藥物，預計將於 2023 年提交 IND 申請。

Over the course of this year, we look forward to achieving multiple important data and regulatory milestones encompassing our approved portfolio and our pipeline assets. Seagen has now emerged as a company with the expertise, capabilities and passion to discover, develop, manufacture and commercialize transformative medicine that impact lives. We operate from a position of strength as we work to build Seagen into a leading global oncology company.

今年，我們期待在已獲批准的產品組合和管道資產方面取得多個重要的數據和監管里程碑。 Seagen 現已發展成為一家擁有專業知識、能力和熱情的公司，致力於發現、開發、製造和商業化影響生活的變革性藥物。我們憑藉著實力，致力於將 Seagen 打造成為全球領先的腫瘤學公司。

We will now turn to Q&A. And to increase the chances that those participating on today's call have an opportunity to ask questions, we ask that you please limit yourself to 1 question each. Operator?

我們現在進入問答環節。為了增加今天電話會議參與者提問的機會，我們要求每個人只問 1 個問題。操作員？

(Operator Instructions) And our first question today comes from Salveen Richter from Goldman Sachs.

（操作員指示）我們今天的第一個問題來自高盛的 Salveen Richter。

With the non-muscle invasive bladder cancer data set that's reading out for PADCEV in the first half, can you help us, one, understand the mechanistic rationale as we think about the drug working in metastatic bladder and the likelihood of working in this tumor type? And then two, what the bar would be for this to be positive? And then just remind us when the muscle invasive bladder cancer data will be presented?

透過在上半年為 PADCEV 讀取的非肌肉層侵襲性膀胱癌資料集，您能否幫助我們，首先，理解藥物在轉移性膀胱中起作用的機制原理以及在這種腫瘤類型中起作用的可能性？第二，要達到正面的效果，標準是什麼？然後請提醒我們何時會呈現肌肉侵襲性膀胱癌數據？

Salveen, it's David. Thanks for that. It's a great question. As you know, we're pretty excited about the franchise we're building in bladder cancer and the strategy with PADCEV, it's move increasingly to earlier lines of therapy. We're going to further build upon that bladder cancer presence by eventually introducing DV also to bladder cancer but directed to HER2-positive patients. I think you're right to focus on both the muscle and non-muscle invasive bladder cancer because those markets are so much bigger than where our current approval is.

薩爾文，我是大衛。謝謝。這是一個很好的問題。如您所知，我們對在膀胱癌領域建立的特許經營權以及 PADCEV 的策略感到非常興奮，它正在逐漸轉向早期治療。我們將進一步鞏固膀胱癌的應用，最終將 DV 引入膀胱癌，但針對 HER2 陽性患者。我認為你關注肌肉侵襲性膀胱癌和非肌肉侵襲性膀胱癌是正確的，因為這些市場比我們目前的批准範圍要大得多。

Roger, I think it would be best if you could share some insights on that program.

羅傑，我認為如果你能分享一些關於該計劃的見解就最好了。

Sure, David. No problem. Thank you. So Salveen, it's a great question. And frankly speaking, the profile, the potential profile of PADCEV given into the bladder could be an excellent one for the following reasons.

當然，大衛。沒問題。謝謝。所以 Salveen，這是一個很好的問題。坦白說，由於以下原因，將 PADCEV 注入膀胱後，其潛在性能可能會非常好。

Firstly, Nectin-4 is expressed stably across all of the disease states. So we have as much Nectin-4 expression in this very early superficial bladder cancer, a patient population as we would have in metastatic disease. Secondly, when we instill PADCEV in its current formulation into the bladder, we do this both preclinically and of course, we'll share some data clinically when we are able but we had no preclinical systemic exposure. So the profile, the tolerability and safety profile of PADCEV may look a little bit more favorable potentially than with systemic administration.

首先，Nectin-4 在所有疾病狀態下都穩定表現。因此，我們在這種非常早期的淺表性膀胱癌患者群體中發現的 Nectin-4 表達水平與轉移性疾病患者群體中的一樣高。其次，當我們將 PADCEV 以其當前配方注入膀胱時，我們會在臨床前進行此操作，當然，我們會在有能力時分享一些臨床數據，但我們沒有進行臨床前全身暴露。因此，PADCEV 的概況、耐受性和安全性可能比全身給藥更有利。

Secondly, we showed in an orthotopic bladder cancer model that we could, in fact, by giving PADCEV into the bladder sort of in direct contact with the tumor impact and have an antitumor effect. So I think we're optimistic. We're excited actually about the opportunity. And obviously, we'll be sharing that information such as we have later in the year.

其次，我們在原位膀胱癌模型中表明，事實上，我們可以透過將 PADCEV 注入膀胱，直接接觸腫瘤，產生抗腫瘤作用。所以我認為我們很樂觀。我們確實對這個機會感到非常興奮。顯然，我們將在今年晚些時候分享這些資訊。

We are starting in the place where almost everyone does begin, which is with a BCG unresponsive population. So these are folks who failed standard therapy.

我們從幾乎每個人都會遇到的起點開始，也就是 BCG 無反應族群。這些人是未能接受標準治療的人。

In terms of what could a registration path look like? What could the hurdle look like? I think that has already been defined for that population, and there is some FDA guidance with regard to what type of endpoints, things like complete response rates with CIS type disease. But we're still in the exploratory phase. But we do see -- we can see a path forward for the BCG unresponsive and frankly, for a broader population as well as there are other drugs that are being developed in this space.

註冊路徑是什麼樣的？這個障礙是什麼樣的？我認為這已經針對該人群進行了定義，並且 FDA 針對終點類型（例如 CIS 類型疾病的完全緩解率）提供了一些指導。但我們仍處於探索階段。但我們確實看到——我們可以看到 BCG 的無反應性以及針對更廣泛人群的前進道路，並且還有其他藥物正在該領域開發。

Our next question comes from Matthew Harrison from Morgan Stanley.

我們的下一個問題來自摩根士丹利的馬修哈里森。

I was just wondering, I know obviously, guidance doesn't include the potential impact from Cohort K, but I was wondering if you could just provide maybe some broader commentary on how you think about the ramp if you are to receive accelerated approval in that setting? And any factors that you think could influence the trajectory in the second half of this year?

我只是想知道，我知道，指導顯然不包括來自 Cohort K 的潛在影響，但我想知道您是否可以提供一些更廣泛的評論，說明如果您要在這種情況下獲得加速批准，您對坡道的看法？您認為哪些因素可能會影響今年下半年的發展軌跡？

Matthew, thanks for mentioning that our guidance does not include Cohort K for 2023. I just want to say the review is going well. And I think once we have the guidance and we see the label, we will be able to update people. And it's likely to be pretty meaningful in terms of incremental sales during the course of the year. .

馬修，感謝您提到我們的指導不包括 2023 年的 K 組。我只想說審查進展順利。我認為，一旦我們有了指導，看到了標籤，我們就能向人們更新資訊。這對於全年的增量銷售來說可能意義重大。 。

I think I'm going to turn it over to Chip now. If you can give any color on uptake without going into too much specifics, because I think we're going to hold a lot of that until we see the final label.

我想我現在要把它交給 Chip。如果您可以給出任何有關吸收的顏色而不需要講太多細節，因為我認為我們會保留很多內容直到我們看到最終的標籤。

Yes, sure. Thanks, David. So I would have just a couple of comments. We have an established presence in this marketplace in the second-line setting, PADCEV is now the standard of care. So we have good insight into this space and have the capability of continuing to grow the brand into the frontline setting. The market itself is substantially larger than the current label that we have. In fact, it would probably be the largest commercial label that we would have -- similar label we would have to date. And if you look at it by the numbers, it's about 20,000 patients with about 18,000 of those drug treated and about half of those, which are cisplatin-ineligible. And so this is a real meaningful opportunity for the teams.

是的，當然。謝謝，大衛。所以我只想發表幾點評論。我們已經在二線市場中佔據了主導地位，PADCEV 現在是治療標準。因此，我們對這個領域有著深入的了解，並且有能力繼續將品牌發展到前線環境。市場本身比我們目前擁有的標籤大得多。事實上，這可能是我們迄今為止擁有的最大的商用品牌——類似的品牌。如果從數字上看，大約有 20,000 名患者，其中約 18,000 名接受藥物治療，而其中約有一半不適合使用順鉑。所以這對球隊來說是一個真正有意義的機會。

Our next question comes from Jessica Fye from JPMorgan.

下一個問題來自摩根大通的傑西卡費伊 (Jessica Fye)。

For PADCEV, can you talk about how much growth you see remaining in the U.S. in the existing approved indications, recognize that you're obviously embedding growth for the product this year, but I guess I'm talking about ultimately how close are you to fully penetrating the late line opportunity?

對於 PADCEV，您能否談談您認為在現有批准的適應症中美國還有多少增長空間，您是否認識到您今年顯然正在為該產品嵌入增長，但我想我最終談論的是您距離完全滲透後期機會還有多遠？

Thanks, Jess. So the brand will continue to grow in the existing indications, albeit at a slower rate. The big opportunities are going to be moving up into earlier lines of therapy.

謝謝，傑西。因此，儘管速度較慢，但該品牌仍將在現有領域繼續成長。最大的機會在於進入更早期的治療方法。

Our next question comes from Jay Olson from Oppenheimer.

我們的下一個問題來自奧本海默公司的傑伊·奧爾森。

Maybe I'll shift gears over to HER2-positive breast cancer. Can you just talk about your latest thoughts on the competitive landscape especially with regards to Enhertu. And also, how do you expect EV to differentiate from HER2 as well? And then also maybe any perspective on TUKYSA in terms of the competitive landscape?

也許我會轉向 HER2 陽性乳癌。您能否談談您對競爭格局的最新看法，尤其是關於 Enhertu 的看法。此外，您認為 EV 與 HER2 有何不同？那麼從競爭格局的角度來看，您對 TUKYSA 有何看法？

Jay, it's David. So I'll give some introductory color, and I'm going to ask Roger and Chip to add to that. Clearly, the breast center market is pretty dynamic right now. The introduction of Enhertu, which is a very good drug, has shaken things up a bit. People seem to get durable responses on that medicine, and it causes drug developers to think carefully about how they would bring additional or perhaps even still better drugs into that marketplace. .

傑伊，我是大衛。因此我將給出一些介紹性的內容，然後我會請 Roger 和 Chip 來補充。顯然，乳腺中心市場目前非常活躍。 Enhertu 是一種非常好的藥物，它的推出讓情況發生了一些變化。人們似乎對該藥物的反應持久，這促使藥物開發人員仔細思考如何將更多甚至更好的藥物推向市場。 。

In the case of DV, my initial thinking and Roger will add some more is that there's an opportunity to come in behind Enhertu largely because we have a different payload and a very good drug. And as you know, breast cancer patients will go through multiple lines of therapy during the course of their treatment.

就 DV 而言，我最初的想法（Roger 會補充一些）是，我們有機會超越 Enhertu，主要是因為我們有不同的有效載荷和非常好的藥物。眾所周知，乳癌患者在治療過程中會接受多種治療。

In the case of TUKYSA, where we're differentiated as a small molecule with really good data and benefit in patients with brain metastases, our strategy there is to as you know, combine TUKYSA with other drugs. We have a trial underway which we'll report out in the not-too-distant future, combining TUKYSA with KADCYLA. KADCYLA that will then expand, perhaps roughly double the size of the patient population that would be eligible for TUKYSA KADCYLA containing regimen. If you think of TUKYSA as currently a brain mets drug KADCYLA being used really for visceral mets and now a doctor use a combination to treat that entire set of patients. But that gives you just some color. It's one of the more difficult markets to forecast at the moment, but we can chat some more about that.

就 TUKYSA 而言，我們將其區分為一種小分子，擁有非常好的數據，並且對腦轉移患者有益，我們的策略是將 TUKYSA 與其他藥物結合。我們正在進行一項試驗，將 TUKYSA 與 KADCYLA 結合起來，並在不久的將來發布報告。 KADCYLA 的治療範圍將會擴大，可能使符合 TUKYSA KADCYLA 治療方案的患者人數增加一倍左右。如果您認為 TUKYSA 目前是一種腦轉移藥物，那麼 KADCYLA 實際上被用於治療內臟轉移，現在醫生使用這種組合來治療所有患者。但這只是給你一些顏色。這是目前最難預測的市場之一，但我們可以就此進一步討論。

Roger, do you want to add anything about -- from a clinical standpoint?

羅傑，從臨床角度來說，你還有什麼要補充的嗎？

I would just add, David, I think, again, agreeing with your statements Enhertu is a great drug. It's making a difference. It's actually defined a population in breast cancer that is sort of previously not defined, which is a HER2-low population. And we are excited about DV and having that defined population ahead of us, we see an opportunity. Once patients have gone to a sort of chemotherapy-based type of therapy, I don't think we see any difficulty with physicians and patients accepting that they could go from one ADC to another, as you point out, there are different payloads, and we have a different antibody. Ours is not trastuzumab. It's a proprietary antibody directed against HER2.

我只想補充一點，大衛，我再次同意你的說法，Enhertu 是一種很棒的藥物。這正在產生影響。它實際上定義了乳癌中以前未定義的一個群體，即 HER2 低群體。我們對 DV 感到非常興奮，並且擁有如此明確的人口群體，我們看到了機會。一旦患者接受了某種基於化療的治療，我認為醫生和患者不會有任何困難接受他們從一種 ADC 轉換到另一種 ADC，正如您所指出的，有不同的有效載荷，而且我們有不同的抗體。我們的不是曲妥珠單抗。它是一種針對 HER2 的專有抗體。

So we're still working on those development plans. And I would also point out that -- and we believe it pretty strongly. One of the hallmarks perhaps of a vedotin-based ADC is in the context of an immunotherapy like a PD-1 inhibitor, we believe we may potentially have a leg up, where that combination, as you can see with our PADCEV, KEYTRUDA data really has an impactful outcome. And so any development plans we think about for DV, we think about the possibility of combining with a PD-1 inhibitor. And as you mentioned, we have tucatinib as well. And so combining those assets are also in our plans.

所以我們仍在製定這些開發計劃。我還要指出的是──我們非常堅信這一點。基於維多汀的 ADC 的一個標誌可能是在 PD-1 抑制劑等免疫療法的背景下，我們相信我們可能具有優勢，正如您從我們的 PADCEV、KEYTRUDA 數據中看到的那樣，這種組合確實會產生有影響力的結果。因此，我們在考慮 DV 的任何開發計劃時，都會考慮與 PD-1 抑制劑結合的可能性。正如您所提到的，我們也有圖卡替尼。因此，合併這些資產也在我們的計劃中。

Our next question comes from Stephen Willey from Stifel.

我們的下一個問題來自 Stifel 的 Stephen Willey。

I guess just on B6A. I know that you're talking to an update in the first half of this year. I think you're kind of emphasizing durability of responses that have been observed to date. But should we expect any additional dose expansion data along with that update? And to what extent does the dose that you've selected for dose expansion in head and neck inform the dosing schedule that you want to take forward into lung?

我猜只是在 B6A 上。我知道您正在談論今年上半年的更新。我認為您是在強調迄今為止觀察到的反應的持久性。但是我們是否應該期待隨著該更新而出現任何額外的劑量擴展數據？您所選擇的用於頭部和頸部劑量擴展的劑量在多大程度上影響了您想要進入肺部的給藥計劃？

Okay. So Stephen, let me start, and then I'll ask Roger to follow up and more specifically answer your question. Let me just say we have a lot of experience in this company with the ADCs. So when we see early data across different dosing cohorts in the disease, we have a pretty good read. It's not full proof, but a pretty good read on where our product is likely to go. And let me just say, B6A is shaping up to become a transformative asset for this company. We're very excited about it. There will be data cuts later this year, which we'll be sharing.

好的。那麼，史蒂芬，讓我先開始，然後我會請羅傑跟進並更具體地回答你的問題。我只想說，我們公司在 ADC 方面擁有豐富的經驗。因此，當我們看到該疾病不同劑量組的早期數據時，我們會有很好的解釋。雖然這不是完整的證據，但可以很好地表明我們的產品可能會走向何方。我只想說，B6A 正在成為這家公司的轉型資產。我們對此感到非常興奮。今年稍後將會出現數據削減，我們將會分享。

Roger. Any more thoughts?

羅傑。還有其他想法嗎？

So it's a great question. And obviously, I think we'll hold the details until we get to present. But what I would say in general is that we will land on one dosing schedule regardless of the disease. So the cross information or the flow of information from one expansion cohort to the other is a coordinated event in terms of us trying to land on what we consider to be an optimized dosing schedule. And as David said, we look forward to sharing durability data and there's potential for further data cuts in the year as well.

這是一個很好的問題。顯然，我認為我們會保留細節，直到我們真正實現它。但總的來說，無論什麼疾病，我們都會採用一種給藥方案。因此，就我們試圖找到我們認為的優化給藥時間表而言，交叉資訊或從一個擴展隊列到另一個擴展隊列的資訊流是一個協調事件。正如大衛所說，我們期待分享耐用性數據，今年也有可能進一步削減數據。

Our next question comes from Geoff Meacham from Bank of America.

下一個問題來自美國銀行的 Geoff Meacham。

This is Hao calling in for Geoff. So I think my question is related to ADCETRIS. So again, a very strong quarter. I think you cited about price, COVID and penetration momentum there. Just wanted to get a sense about how you see in 2023? Do you see that sort of trend to continue in 2023?

我是郝，正在為傑夫打電話。所以我認為我的問題與 ADCETRIS 有關。所以，這又是一個非常強勁的季度。我認為您提到了價格、COVID 和滲透勢頭。只是想了解一下您對 2023 年的看法？您認為這種趨勢會在 2023 年持續下去嗎？

It's David. Let me just say, in Todd's commentary, we mentioned that this product will become a blockbuster in our territories, which is the U.S. and Canada. Typically, when brands start to accelerate because of new labels and new guidelines, they maintain that acceleration for a period of time. So our thinking about '23 will be another strong year for the brand.

是戴維。我只想說，在托德的評論中，我們提到這款產品將在我們的領土，即美國和加拿大，成為轟動之作。通常，當品牌因為新標籤和新指南而開始加速發展時，它們會在一段時間內保持這種加速發展。因此我們認為 2023 年將是該品牌另一個強勁的一年。

Our next question comes from Gregory Renza from RBC Capital Markets.

下一個問題來自加拿大皇家銀行資本市場的 Gregory Renza。

Great. Congrats on the quarter and the progress so far. David and team, just maybe a question and a request for your renewed thoughts on really the path to profitability. Just curious as you have prioritized certainly the pipeline programs doubling down on the commercial portfolio, how you think about the investments that you're committing to and just that ramp there as it relates to looking at these early programs that you believe have a high probability or a better probability of success as it pertains to looking at profitability?

偉大的。恭喜本季以及迄今為止的進展。大衛和團隊，也許只是一個問題和一個請求，請你們重新思考真正的獲利之路。我很好奇，既然您已經優先考慮了管道項目，並且加倍投入商業投資組合，那麼您如何看待您所承諾的投資，以及在考慮盈利能力時，您認為這些早期項目的成功概率高還是高？

Yes. So I'll start and then Todd will follow up. I mean the short answer is in the JPMorgan meeting, Healthcare conference meeting and in this call, we're highlighting 3 global or near globally owned assets, each of which can be a blockbuster. And just to put that into context for you, non-small cell lung cancer for B6A is a market that's, call it, 6x the size in terms of epi than the first line PADCEV bladder canister market. So we're talking about really tremendous opportunities for our company.

是的。所以我先開始，然後托德會跟進。我的意思是，簡短的回答是在摩根大通會議、醫療保健會議和本次電話會議上，我們重點介紹了 3 種全球或接近全球擁有的資產，每一種都可能成為重磅炸彈。為了讓您更了解情況，B6A 非小細胞肺癌市場規模是第一線 PADCEV 膀胱罐市場的 6 倍。所以，我們談論的是我們公司面臨的真正巨大的機會。

So the way I think about these things is our first priority is to invest adequately in terms of having the breadth of pivotal trials necessary to capture those huge upsides. Obviously, we're very thoughtful about how we spend our cash. Balance sheet is strong. And when we do get to profitability, I would suspect it's not going to be eating out minor profits but would be profits that really matter, they would become substantial.

因此，我認為我們的首要任務是進行充分的投資，進行廣泛且必要的關鍵試驗，以獲得巨大的優勢。顯然，我們對如何花錢非常謹慎。資產負債表強勁。當我們真正獲利時，我認為它不會蠶食掉微小的利潤，而是會蠶食掉真正重要的利潤，這些利潤將變得非常可觀。

Anything you'd want to add?

您還有什麼要補充的嗎？

Yes. Maybe just one thing. Thanks, Greg, for the question. If you, this is first all a question that we've gotten for a long time, and it's a good question is one we steer out. I think our strategy continues to be investing in our portfolio and our platforms to bring more meaningful drugs to patients in need. And I think if you just look at last year's print, we -- our revenues were up about 25% for the quarter and the year. When you look at the '23 guide, even excluding Cohort K, we're up about 15%, and this brings our total revenues to $2.25 billion just about. So I think that's an illustration of how successful we think the strategy has been.

是的。或許只是一件事。謝謝格雷格提出的問題。如果您願意，這首先是我們長期以來一直遇到的一個問題，這是一個好問題，也是我們要解決的問題。我認為我們的策略是繼續投資我們的產品組合和平台，為有需要的患者提供更多有意義的藥物。我認為，如果你看去年的業績，我們本季和全年的營收成長了約 25%。當您查看 23 年指南時，即使不包括 K 組，我們也成長了約 15%，這使我們的總收入達到 22.5 億美元。所以我認為這說明了我們認為該戰略是多麼成功。

With that in mind, we've got an amazingly broad and deep pipeline to continue investing in. You heard a little bit on the call today about programs like B6A and DV and B7H4. These are drugs that address meaningful solid tumor populations and they're assets that for all intents and purposes are wholly owned by Seagen. So we think those are the types of assets that make a lot of sense for us to invest in and invest in heavily to really continue to drive the growth and the success that we've had today.

考慮到這一點，我們有一個非常廣泛和深入的管道可以繼續投資。您在今天的電話會議上聽到了一些關於 B6A、DV 和 B7H4 等項目的資訊。這些藥物針對的是重要的實體腫瘤群體，而這些資產實際上完全由 Seagen 所有。因此，我們認為這些類型的資產對我們來說非常有意義，值得我們大力投資，以真正繼續推動我們今天的成長和成功。

I think just to add to that in another way, I think what Todd just told you was we could get profitable pretty soon if we wanted to, but we would be cutting off our future, which is much more exciting than where we are today.

我想從另一個角度補充一點，我認為托德剛才告訴你的是，如果我們願意的話，我們很快就能盈利，但我們會切斷我們的未來，而我們的未來比我們現在的狀況要令人興奮得多。

Agreed.

同意。

Our next question comes from Michael Schmidt from Guggenheim Securities.

我們的下一個問題來自古根漢證券公司的邁克爾施密特。

This is Yige on for Michael. One question on PADCEV. You previously reported medium treatment duration of 11 cycles for PADCEV KEYTRUDA combo in Cohort K. Is that a good modeling assumption for PADCEV duration in first-line cisplatin-ineligible patients in clinical practice post approval as we are nearing the PDUFA date in April? And how could this number still change with longer follow-up as there were still roughly 1/3 of the patients still on treatment by the last data cutoff?

這是 Yige 為 Michael 表演的。關於 PADCEV 的一個問題。您之前報告過，K 組 PADCEV KEYTRUDA 組合的中位數治療持續時間為 11 個週期。由於我們即將在 4 月接近 PDUFA 日期，這是否是批准後臨床實踐中對一線順鉑不合格患者的 PADCEV 持續時間的良好建模假設？截至上次數據截止時，仍有約 1/3 的患者仍在接受治療，那麼，隨著追蹤時間的延長，這個數字怎麼還會改變呢？

Yes. So we are very excited about this upcoming FDA decision with the April PDUFA date. I'm going to ask Chip to try to give you a little bit of thinking about how long we think patients might be on therapy. One thing I would say to you is that they will be on therapy longer in the frontline setting and in the second-line setting in part because these patients are generally healthier, in part because the dose density is probably a little bit less and all told patients should do better when this drug is combined with KEYTRUDA, given the synergies that we see between vedotin and anti-PD1.

是的。因此，我們對 FDA 即將於 4 月做出的​​ PDUFA 決定感到非常興奮。我將請 Chip 嘗試讓您思考我們認為患者可能需要接受多長時間的治療。我想告訴你的是，他們將在一線治療和二線治療中接受更長時間的治療，部分原因是這些患者通常更健康，部分原因是劑量密度可能稍微低一些，並且考慮到我們在 vedotin 和抗 PD1 之間看到的協同作用，當這種藥物與 KEYTRUDA 結合使用時，患者的情況應該會更好。

Chip, any more thinking you'd want to add?

Chip，您還有什麼要補充的嗎？

Yes. Sure, David. I think it's just important to note we don't have a label yet. So certain details on this could change. But our general thinking with regard to the clinical trial experience we have is that we would expect to see a longer duration than what we do in second line. The duration in frontline, we think is going to be somewhere closer to 7 months.

是的。當然，大衛。我認為需要注意的是，我們還沒有標籤。因此，這方面的某些細節可能會改變。但根據我們的臨床試驗經驗，我們總體的想法是，我們預計其持續時間會比二線試驗更長。我們認為，在前線的服役時間將接近 7 個月。

As David mentioned, it's a little bit less of a dose dense regimen on a monthly basis, and the patients are also generally speaking, a little bit fitter. So we think that's kind of what we're looking towards.

正如大衛所提到的，這種治療方案每月的劑量密度會稍微低一些，而且患者的健康狀況總體上也會更好一些。所以我們認為這就是我們所期待的。

Our next question comes from Andy Hsieh from William Blair.

下一個問題來自 William Blair 的 Andy Hsieh。

David, congrats. Great to hear from you. So I am just curious about the biology and underlying clinical characteristics of first-line cisplatin-eligible patients versus, let's say, second or third line as you enrolled in the EV-301 study or the initial accelerated approval. I'm just curious, is it beyond the realm of possibility to receive a broad label as the FDA reviews the PADCEV in frontline UC?

大衛，恭喜。很高興收到你的來信。因此，我只是好奇，當您參加 EV-301 研究或初始加速批准時，一線順鉑治療患者的生物學和潛在臨床特徵與二線或三線患者的生物學和潛在臨床特徵相比如何。我只是好奇，當 FDA 審查前線 UC 中的 PADCEV 時，獲得廣泛的標籤是否是不可能的？

So I'm going to put this one to Roger.

所以我要把這個交給羅傑。

Let me just say -- you gave me a nice opening there -- compliment. Let me just say that I'm really happy to be at Seagen. I'm about 3 months in right now, I'm even more bullish on the future of this company, and you heard some of that in the call. We have strong in-line growth. B6A shaping up to be a transformative asset, leading position in bladder cancer. And although we haven't been asked, Chip, we have a discovery team that's getting ready to file this year IND with the campto payload. This company is really on the move.

我只想說——你給了我一個很好的開場——讚美。我只想說我真的很高興來到 Seagen。現在大約已經過了 3 個月，我對這家公司的未來更加看好，您在電話會議中也聽到了一些。我們擁有強勁的線上成長。 B6A 有望成為一種轉化資產，在膀胱癌治療中佔據領先地位。儘管我們沒有被要求，Chip，但我們有一個發現團隊，正準備在今年提交帶有 campto 有效載荷的 IND。這家公司確實在不斷發展。

Now for your specific question, Roger, what do you think? .

現在回答你的具體問題，羅傑，你怎麼看？ 。

Andy, thanks. It's an interesting question. I think our view is essentially, we get -- we hope we get what we ask for. As David said, the review is going well. The population is well defined as cisplatin-eligible based on characteristics of things like renal dysfunction and hearing loss. And we have right behind it, EV-302, which we've signaled we may -- we'll have topline data sometime in this year towards the end of the year perhaps.

安迪，謝謝。這是一個有趣的問題。我認為我們的觀點本質上是，我們得到——我們希望得到我們所要求的。正如大衛所說，審查進展順利。根據腎功能障礙和聽力損失等特徵，明確將族群定義為適合使用順鉑治療。緊隨其後的是 EV-302，我們已經表示我們可能會在今年年底左右獲得主要數據。

So I think although it would be fantastic, I think it would be very unlikely. My personal view is if we're successful, the likely outcome is the label will reflect the population we studied, which is cisplatin-eligible patients.

所以我認為，儘管這很棒，但可能性很小。我個人的觀點是，如果我們成功了，那麼可能的結果是標籤將反映我們研究的人群，即適合順鉑治療的患者。

Our next question comes from Joe Catanzaro from Piper Sandler.

我們的下一個問題來自 Piper Sandler 的 Joe Catanzaro。

Congrats on the progress. So Roger, you just mentioned EV-302. With enrollment now complete, I was wondering if you had any visibility into the extent of avelumab maintenance usage in the control arm and how you think about how that may impact the potential performance of the control arm in that study.

恭喜你取得進展。羅傑，你剛才提到了 EV-302。現在招募已經完成，我想知道您是否了解對照組中 Avelumab 維持使用的情況，以及您認為這可能會如何影響該研究中對照組的潛在表現。

Roger?

羅傑？

Yes, sure. Thanks, Joe, for the question. So just to give you a little bit of history, if you recall, avelumab went through its approval process as we were rolling out EV-302. And it is obviously part of the care of patients with frontline disease provided they have either a response, complete response, partial response or have disease control -- meaningful disease control. And so the population that actually gets avelumab is relatively restricted compared to the population that we're looking at on EV-302. Nonetheless, they will be used. I can't share with you what that level will be. It is a global trial. So EV-302 has been conducted around the world. And if physicians on the control arm consider that avelumab should be used well then that likely will happen. So I can say there is avelumab use, I just can't give you any more detail as to how much.

是的，當然。謝謝喬提出這個問題。因此，我為大家介紹一下歷史，如果您還記得的話，avelumab 在我們推出 EV-302 時經歷了審批流程。顯然，這是對第一線疾病患者護理的一部分，前提是他們有反應、完全反應、部分反應或疾病得到控制——有意義的疾病控制。因此，與我們關注的 EV-302 族群相比，實際接受 Avelumab 治療的族群相對受限。儘管如此，它們還是會被使用。我無法告訴你們這個水平會是怎樣。這是一次全球性的試驗。因此EV-302已在世界各地開展。如果對照組的醫生認為應該很好地使用 avelumab，那麼這種情況就很可能會發生。所以我可以說阿維魯單抗是有用的，但我無法告訴你更多關於其用量的細節。

With regard to the outcome, I mean, obviously, the trial itself will demonstrate in the end what the value in terms of things like overall survival and progression-free survival is with PADCEV and KEYTRUDA. I would remind you, we have done -- although there are single-arm experiments, we have done 2 experiments through the form of Cohort code A and Cohort K in a population of cisplatin-eligible patients that are generally perhaps not as well as an older than cisplatin-eligible patients. And the survival curves we've generated from there give us optimism and confidence that if we repeat that type of outcome in the context of a broad global trial, which includes all of these different populations and a degree of avelumab use I mean, again, we have -- we're optimistic. We're excited about the combination. Until the trial reads out, I can't tell you what the results will be. But I think we have a good shot at the positive outcome.

關於結果，我的意思是，顯然，試驗本身最終將證明 PADCEV 和 KEYTRUDA 在整體存活率和無惡化存活率等方面的價值。我要提醒你，我們已經做過了——儘管有單臂實驗，但我們已經通過隊列代碼 A 和隊列 K 的形式在順鉑適用患者群體中進行了兩項實驗，這些患者通常可能不如順鉑適用患者年齡大。我們從中得到的生存曲線給了我們樂觀和信心，如果我們在廣泛的全球試驗中重複這種結果，其中包括所有這些不同的人群和一定程度的阿維魯單抗的使用，我的意思是，我們再次感到樂觀。我們對這一結合感到非常興奮。在審判結果公佈之前，我無法告訴你結果會如何。但我認為我們很有可能會取得正面成果。

Our next question comes from Andrew Berens from SVB Securities.

我們的下一個問題來自 SVB 證券的 Andrew Berens。

Congrats on the quarter. I know you're not able to promote first line for PADCEV until you get a label but I'm just wondering if you're already seeing some usage following the presentation of the data set. Some of our doc checks suggest that they're already using it in the first line already. And then I just was wondering if you could -- you mentioned developing some novel ADC technologies. Wondering if you could let us peek under the covers and see you and give us an idea of what you're looking at?

恭喜本季取得佳績。我知道在獲得標籤之前您無法推廣 PADCEV 的第一行，但我只是想知道您是否已經在展示資料集後看到了一些用法。我們的一些文件檢查表明他們已經在第一行使用它了。然後我只是想知道您是否可以——您提到開發一些新穎的 ADC 技術。想知道您是否可以讓我們透過被子偷看您，並告訴我們您在看什麼？

So first of all, I'll just ask Chip any sense of whether or not PADCEV maybe already used in the first-line bladder cancer setting?

因此首先，我只想問 Chip，PADCEV 是否已經用於第一線膀胱癌治療？

Yes. So that would be organic. We don't promote to that, obviously. But there's been a little bit, but not much. It's minimal right now.

是的。所以這是有機的。顯然，我們不會提倡這一點。但有一點，但不是很多。目前還很少。

And then you asked for -- to hear a little bit more about our discovery efforts. At JPMorgan, we talked about multiple waves of therapies and technologies. And we were, I would say, purposely superficial so as to not give too much away, I indicated in one of my answers already earlier today that we are filing our first campto-based payload INDs. So that's certainly one area will be coming in the very near term.

然後你要求──多了解一些我們的發現工作。在摩根大通，我們討論了多波療法和技術。我想說，我們故意說得膚淺，以免透露太多信息，我今天早些時候在一個回答中已經指出，我們正在提交第一份基於 Campto 的有效載荷 IND。所以這肯定是近期內將會出現的一個領域。

We have a number of other proprietary targets that we think will be particularly suitable for our current vedotin technology. And then I'll go a little further and just say we are now working on what we believe could be better makers as well as payloads that are quite different from anything you've seen so far. There's quite an expertise into our discovery group. Roger, as you know, recently became Head of R&D and we're working to prioritize where we focus. There's actually many, many opportunities, and we're going through the process of now choosing the assets, which we will heavy up on the resources to get them into the clinic.

我們還有許多其他專有目標，我們認為這些目標特別適合我們目前的 vedotin 技術。然後我會進一步說，我們現在正在研究我們認為可以更好的製造器以及與您迄今為止看到的任何東西都截然不同的有效載荷。我們的發現團隊擁有相當多的專業知識。如您所知，羅傑最近成為研發主管，我們正在努力確定重點關注的領域。實際上有很多很多的機會，我們現在正在經歷選擇資產的過程，我們將投入大量資源將它們引入診所。

I think we have time for one, maybe one more question.

我想我們還有時間再問一個問題。

Our next question comes from Dane Leone from Raymond James.

我們的下一個問題來自 Raymond James 的 Dane Leone。

Congratulations on the update. One for me, if you will. With regards to the readout that we could expect of HER2CLIMB-02. It's interesting. It's obviously a larger study, well-controlled to signal of the benefit of tucatinib with trastuzumab (inaudible) . And the question that I think a lot of people have is what are the actual expectations statistically that your team put in place to tease out a PFS signal in this study. And is your expectation that that PFS benefit would come primarily from tucatinib's ability to address brain mets and progression on intracranial disease. Or is your team ultimately looking for a bigger PFS hurdle more broadly from the synergy of the 2 agents?

恭喜更新。如果你願意的話，給我一個。關於我們可以預期的 HER2CLIMB-02 讀數。這很有趣。這顯然是一項更大規模、控制良好的研究，可以顯示出圖卡替尼與曲妥珠單抗的益處（聽不清楚）。我認為很多人都有疑問，從統計學角度來看，您的團隊對本研究中梳理 PFS 訊號的實際期望是什麼。您是否預期 PFS 益處主要來自於 Tucatinib 解決腦轉移和顱內疾病進展的能力。或者您的團隊最終是否希望從兩種藥物的協同作用中尋求更廣泛的 PFS 障礙？

Roger, do you want to start on that one?

羅傑，你想從這個開始嗎？

That's an interesting question. Just to remind you sort of set the scene view on HER2CLIMB-02, it has the same essential design elements as HER2CLIMB. And importantly, for this population, obviously, KADCYLA is a well-known drug that is used in second line and plus and as David said, focusing on metastatic disease. But as we did with HER2CLIMB, the eligibility criteria allow patients with brain mets, either controlled or active. And so we expect to have a meaningful number of patients with brain metastases in HER2CLIMB, obviously, as we did -- in HER2CLIMB-02 as we did in HER2CLIMB.

這是一個有趣的問題。只是為了提醒您在 HER2CLIMB-02 上設定場景視圖，它具有與 HER2CLIMB 相同的基本設計元素。重要的是，對於這個人群來說，顯然 KADCYLA 是一種眾所周知的藥物，用於二線及以上治療，正如 David 所說，專注於治療轉移性疾病。但正如我們對 HER2CLIMB 所做的那樣，資格標準允許患有腦轉移的患者，無論是受控的還是活躍的。因此，我們預期 HER2CLIMB 中會有大量腦轉移患者，顯然，就像我們在 HER2CLIMB-02 中所做的那樣，就像我們在 HER2CLIMB 中所做的那樣。

With regard to assumptions around treatment effect, just to remind you again of the design, this is a simple add-on design. So this is the addition of tucatinib to KADCYLA and so any benefits of tucatinib accrues, I think, will be pretty evident. I can't share with you specific assumptions. But we are looking for all of the above. If you mentioned, are we looking for treatment effects in a broad population? Yes. Are we looking for meaningful treatment effects in a subset of patients with brain metastases? The answer is yes. And I think we see the potential for tucatinib instead of being an all decision for physicians, if a trial is positive and the results are meaningful, physicians will and patients be able to make the decision if KADCYLA is part of the treatment plan to add tucatinib to the combination.

關於治療效果的假設，只是再次提醒您設計，這是一個簡單的附加設計。因此，這是將 Tucatinib 添加到 KADCYLA 中，因此我認為 Tucatinib 帶來的任何好處都將非常明顯。我無法與你分享具體的假設。但我們正在尋找以上所有的東西。如果您提到，我們是否在尋求廣泛人群的治療效果？是的。我們是否正在尋找針對腦轉移患者亞群的有意義的治療效果？答案是肯定的。我認為我們看到了圖卡替尼的潛力，而不需要由醫生來決定，如果試驗是積極的，結果有意義，醫生和患者將能夠決定是否將 KADCYLA 作為治療計劃的一部分，將圖卡替尼添加到組合中。

Great. So thanks, Roger.

偉大的。所以謝謝你，羅傑。

Let me just conclude by saying this is going to be a very exciting year for us. Many data and regulatory milestones. I'm thrilled to be here, and I thank you for all the attention you're paying to our company. With that, we'll close the call.

最後，我想說，對我們來說，這將會是個非常令人興奮的一年。許多數據和監管里程碑。我很高興來到這裡，感謝大家對我們公司的關注。就這樣，我們就結束通話了。

Ladies and gentlemen, with that, we'll conclude today's conference call and presentation. We do thank you for joining. You may now disconnect your lines.

女士們、先生們，今天的電話會議和演講就到此結束。我們非常感謝您的加入。現在您可以斷開線路了。