Carisma Therapeutics Inc (CARM) 2021 Q1 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Sesen Bio Quarter 1 2021 Business Update Call. (Operator Instructions)

美好的一天，感謝您的支持。歡迎參加 Sesen Bio 2021 年第一季業務更新電話會議。 （操作員說明）

I would now like to hand the conference over to your speaker, Ms. Erin Clark, Vice President of the Corporate Strategy and Investor Relations. Please go ahead.

現在我想將會議交給您的發言人，公司策略和投資者關係副總裁艾琳克拉克女士。請繼續。

Thank you, and good morning, everyone. Welcome to our first quarter business update call. On today's call, we will discuss our operating results for the first quarter ended March 31, 2021, as well as an update on the commercial readiness progress to date ahead of our target PDUFA date of August 18, 2021.

謝謝大家，大家早安。歡迎致電我們第一季的業務更新。在今天的電話會議上，我們將討論截至 2021 年 3 月 31 日的第一季的營運業績，以及在 2021 年 8 月 18 日的目標 PDUFA 日期之前迄今為止的商業準備進度的最新資訊。

Joining me on today's call are Dr. Thomas Cannell, President and Chief Executive Officer; Dr. Chad Myskiw, Executive Director of Supply Chain; and Monica Forbes, our Chief Financial Officer.

與我一起參加今天電話會議的還有總裁兼執行長 Thomas Cannell 博士； Chad Myskiw 博士，供應鏈執行董事；和我們的財務長莫妮卡·福布斯。

Earlier this morning, we issued a press release outlining some of the highlights that will be covered on the call today. The press release and the slides to which we will refer are available in the Investors section of the company's website at sesenbio.com. I would like to remind you that today's discussion will include forward-looking statements related to the company's current plans and expectations, which are subject to risks and uncertainties. Actual results may differ materially due to various factors, including those described in Sesen Bio's most recent annual report on Form 10-K, quarterly report on Form 10-Q and other SEC filings. These statements represent Sesen Bio's views as of this call and should not be relied upon as of any future date. Sesen Bio undertakes no obligation to publicly update these forward-looking statements.

今天早些時候，我們發布了一份新聞稿，概述了今天電話會議將討論的一些要點。我們將參考的新聞稿和幻燈片可在公司網站 sesenbio.com 的投資者部分取得。我想提醒您，今天的討論將包括與公司當前計劃和預期相關的前瞻性陳述，這些陳述存在風險和不確定性。實際結果可能因各種因素而存在重大差異，包括 Sesen Bio 最近的 10-K 表年度報告、10-Q 表季度報告和其他 SEC 文件中描述的因素。這些陳述代表 Sesen Bio 截至本次電話會議的觀點，不應在未來任何日期被依賴。 Sesen Bio 不承擔公開更新這些前瞻性聲明的義務。

With that, I will turn the call over to Tom. Tom?

這樣，我就把電話轉給湯姆。湯姆？

Thank you, Erin, and good morning, everyone. Thank you so much for calling in and participating in our business update today.

謝謝你，艾琳，大家早安。非常感謝您今天致電並參與我們的業務更新。

Please turn to Slide 3, which is a summary of the 3 key takeaways for our call today: First, Vicineum has a unique and compelling value proposition, especially when it comes to its potential to improve patient outcomes while reducing overall health care costs; second, we believe we have a clear regulatory path forward with potential approval in the U.S. in August of this year, and in Europe in early 2022; and finally, given the substantial unmet need in bladder cancer and the highly differentiated clinical profile of Vicineum, we project a significant global commercial opportunity.

請參閱投影片 3，它總結了我們今天電話會議的 3 個關鍵要點：首先，Vicineum 擁有獨特且令人信服的價值主張，尤其是在降低整體醫療保健成本的同時改善患者治療效果的潛力方面；其次，我們相信我們有一條明確的監管路徑，可能在今年 8 月在美國獲得批准，並於 2022 年初在歐洲獲得批准；最後，鑑於膀胱癌的大量未滿足需求以及 Vicineum 高度差異化的臨床特徵，我們預計將帶來重大的全球商業機會。

Please turn to Slide 4. If you've been following us for a long time, like many of you have, you know we always start our presentation with the patient journey to make sure we are focused on realizing our mission to save and improve the lives of patients. It is important to understand the unmet medical need in bladder cancer through this lens, not only to understand why there is such a significant patient need for a product like Vicineum, but also to understand why we believe prescribing physicians will prefer Vicineum versus available agents. An important takeaway from this slide is that urologists play a key role, guiding the patient through their journey. Most medical decisions, including treatment choice, will be decided by the patient and their urologist, and we'll talk about why that is important in a few minutes.

請翻到幻燈片4。 。透過這個視角來了解膀胱癌未滿足的醫療需求非常重要，不僅要了解為什麼患者對 Vicineum 這樣的產品有如此巨大的需求，還要了解為什麼我們相信處方醫生會更喜歡 Vicineum 而不是現有藥物。這張投影片的一個重要結論是，泌尿科醫師發揮關鍵作用，引導病患完成整個旅程。大多數醫療決定，包括治療選擇，將由患者及其泌尿科醫生決定，我們將在幾分鐘內討論為什麼這很重要。

Please turn to Slide 5. This shows our anticipated regulatory timeline for our 4 biggest global markets. We continue to make progress across each of these key regions. In the U.S., the team is laser-focused on responding to information requests, site inspections and preparing for the late-cycle meeting with the FDA in July. We continue to be encouraged by what we have found to be an engaging and collaborative review process. As you may recall, the late cycle meeting was originally scheduled in June, but due to delays scheduling site visits outside the U.S. caused by the pandemic, we're now planning for that meeting in mid-July. You can see we remain on track for our target PDUFA date of August 18, and our current plans are to begin promotion to physicians and patients upon potential approval in August, with commercial product supply available in urology clinics by the fourth quarter. Given the market dynamics in this market, we would expect signs of early commercial success by mid-2022.

請參閱投影片 5。我們繼續在這些關鍵領域取得進展。在美國，該團隊專注於回應資訊請求、現場檢查以及為 7 月與 FDA 舉行的後期會議做準備。我們發現這是一個有吸引力的協作審查過程，這讓我們繼續感到鼓舞。您可能還記得，後期週期會議原定於 6 月舉行，但由於疫情導緻美國境外實地考察的安排出現延誤，我們現在計劃在 7 月中旬舉行該會議。您可以看到，我們仍在按計劃實現8 月18 日的目標PDUFA 日期，我們目前的計劃是在8 月份獲得潛在批准後開始向醫生和患者推廣，並在第四季度之前在泌尿外科診所提供商業產品。鑑於該市場的市場動態，我們預計到 2022 年中期就會出現早期商業成功的跡象。

In Europe, we achieved an important milestone with the conditional acceptance of our proprietary brand named Vicineum. In addition, the EMA notified us that the MAA submission was found to be valid and that the review procedure has officially started, with potential approval in early 2022.

在歐洲，我們實現了一個重要的里程碑，我們的專有品牌 Vicineum 獲得有條件接受。此外，EMA 通知我們，MAA 提交的文件被認為是有效的，並且審查程序已正式啟動，可能會在 2022 年初獲得批准。

Next, in China, the IND was approved by the CDE, which triggers a milestone payment from our partner, Qilu Pharmaceutical. It also enables Qilu to conduct a proposed clinical trial to assess the efficacy and safety of Vicineum in patients in China, and we expect the first patient to be dosed in that trial next month.

接下來，在中國，IND 獲得了 CDE 的批准，這觸發了我們的合作夥伴齊魯製藥的里程碑付款。它還使齊魯能夠開展一項擬議的臨床試驗，以評估 Vicineum 對中國患者的療效和安全性，我們預計下個月將在該試驗中對第一位患者進行給藥。

Finally, in the MENA region, we continue to work closely with our partner, Hikma Pharmaceuticals, to submit marketing authorization applications in 2021 in key markets, with the first wave of potential country approvals for Vicineum in the MENA region as early as 2022.

最後，在中東和北非地區，我們繼續與我們的合作夥伴 Hikma Pharmaceuticals 密切合作，並於 2021 年在關鍵市場提交行銷授權申請，最早將於 2022 年在中東和北非地區獲得第一批 Vicineum 潛在國家批准。

Turning to Slide 6. Just a reminder that while our planned trade names in the U.S. and Europe will be spelled slightly differently, they will both be pronounced the same, Vicineum. We would expect most countries outside the U.S. and Europe to utilize 1 of these 2 spellings.

轉向幻燈片 6。我們預計美國和歐洲以外的大多數國家/地區都會使用這兩種拼字中的一種。

Turning to our brand strategy. We believe we are positioned to launch a best-in-class therapeutic that will improve patient outcomes while reducing overall health care costs. Given the differentiated value proposition of Vicineum, we expect that Vicineum will become the market leader in the non-muscle invasive bladder cancer market in late 2022, on a path to realize global peak sales of $1 billion to $3 billion.

轉向我們的品牌策略。我們相信，我們有能力推出一流的治療方法，改善患者的治療效果，同時降低整體醫療成本。鑑於 Vicineum 的差異化價值主張，我們預期 Vicineum 將在 2022 年底成為非肌肉層浸潤性膀胱癌市場的市場領導者，實現全球銷售額高峰 10 億至 30 億美元。

Turning to Slide 7. You can see a high-level view of our customer engagement strategy. First, we have identified about 300 national and regional key opinion leaders, or KOLs, where a very high level of engagement is warranted. For these customers, we will deploy medical science liaisons with the full support of our medical affairs department. We'll also engage some of those KOLs as speakers at a variety of company-sponsored and independent conferences and programs.

轉向投影片 7。首先，我們確定了約 300 名國家和地區關鍵意見領袖 (KOL)，需要高度參與。對於這些客戶，我們將在醫學事務部門的全力支持下部署醫學科學聯絡員。我們也將邀請其中一些 KOL 作為發言人在各種公司贊助的獨立會議和項目上發表演講。

Next, I want to mention our reimbursement support strategy. Vicineum is going to be a buy-and-bill product, and we will be selling directly into the urology clinic. Given this, it is critical that we have the right support to ensure clinics are reimbursed for Vicineum, and that we provide helpful resources to patients as they go through the reimbursement process. Next, from a sales force perspective, there are about 2,000 high-prescribing physicians our sales force will target. We recently announced a partnership with the leading contract sales organization, Syneos Health, who will provide logistical support in hiring and deployment of the sales force. The sales force will include 35 representatives across 4 geographic regions. This will enable reps to see each target on average a couple times a month with a very reasonable investment in terms of operating expense.

接下來我想提一下我們的報銷支援策略。 Vicineum 將成為購買後計費的產品，我們將直接向泌尿科診所銷售。有鑑於此，至關重要的是，我們必須獲得適當的支持，以確保診所獲得 Vicineum 的報銷，並在患者完成報銷流程時為他們提供有用的資源。接下來，從銷售人員的角度來看，我們的銷售人員將瞄準約 2,000 名高處方醫生。我們最近宣布與領先的合約銷售組織 Syneos Health 建立合作夥伴關係，後者將為銷售人員的招募和部署提供後勤支援。銷售隊伍將包括來自 4 個地理區域的 35 名代表。這將使銷售代表能夠平均每月幾次查看每個目標，並在營運費用方面進行非常合理的投資。

Finally, there are also some high-prescribing physicians who are located in more rural locations and are harder to see, but it still makes sense to interact with them virtually. For targets located at these sites, we'll use inside sales reps to efficiently reach these prescribers. Overall, we are confident in our customer engagement strategy. Bladder cancer is a highly concentrated market, and we believe we have developed an approach which will lead to strong product uptake and sustainable growth.

最後，還有一些開處方率較高的醫生，他們位於農村地區，較難見到，但與他們進行虛擬互動仍然有意義。對於位於這些站點的目標，我們將使用內部銷售代表來有效地聯繫這些處方者。總的來說，我們對我們的客戶參與策略充滿信心。膀胱癌是一個高度集中的市場，我們相信我們已經開發出一種方法，將帶來強勁的產品吸收和永續成長。

Please turn to Slide 8, which highlights the results of our market research of Vicineum relative to KEYTRUDA. When we show high prescribers of bladder cancer the profile for Vicineum and for KEYTRUDA, they say that they would choose Vicineum over 80% of the time, because they view Vicineum to have an advantage in terms of safety, ease of integration into their clinical practice, and overall physician interest in using the product. Physicians have a very favorable brand image of KEYTRUDA, and therefore, when physicians choose Vicineum over KEYTRUDA 80% of the time, that strongly positions us for a successful launch.

請參閱投影片 8，其中重點介紹了我們對 Vicineum 相對於 KEYTRUDA 進行的市場研究結果。當我們向膀胱癌的高處方者展示 Vicineum 和 KEYTRUDA 的概況時，他們表示超過 80% 的情況下他們會選擇 Vicineum，因為他們認為 Vicineum 在安全性、易於融入臨床實踐方面具有優勢，以及醫生對使用該產品的整體興趣。醫生對 KEYTRUDA 的品牌形象非常滿意，因此，當醫生在 80% 的情況下選擇 Vicineum 而不是 KEYTRUDA 時，這為我們的成功上市奠定了堅實的基礎。

With that, I'll hand the call over to Chad.

這樣，我就把電話轉給查德。

Thanks, Tom. If everyone can please turn to Slide 9. Given the complexity of manufacturing biologics, we've purpose-built a very reliable and robust supply chain with world-class manufacturing partners. Our current supplier for drug substance is FUJIFILM, and for drug product, Baxter. Both of these CMOs are industry leaders with a long history of manufacturing excellence and a strong regulatory track record with the FDA and other regulatory agencies. To strengthen our existing supply chain, we are currently transferring the Vicineum manufacturing process to Qilu Pharmaceutical, our partner in the Greater China region, to add them as an additional source of drug substance and drug product supply in the future. Qilu has a very large and experienced manufacturing team and already supplies commercial products to the U.S. So we feel very good about bringing them on board.

謝謝，湯姆。如果每個人都可以，請參閱幻燈片 9。我們目前的原料藥供應商是 FUJIFILM，而藥品供應商是 Baxter。這兩家 CMO 都是行業領導者，擁有悠久的卓越製造歷史，並在 FDA 和其他監管機構中擁有良好的監管記錄。為了加強我們現有的供應鏈，我們目前正在將Vicineum的生產流程轉移給我們在大中華地區的合作夥伴齊魯製藥，以將其作為未來原料藥和製劑供應的額外來源。齊魯擁有一支非常龐大且經驗豐富的製造團隊，並且已經向美國供應商業產品，因此我們對引進他們感到非常高興。

For third-party logistics and specialty distribution services, we are working with Cardinal Health in the U.S. Cardinal is one of the most well-respected and capable players in this industry. They have significant expertise in cold chain logistics and deep relationships with the uro-oncology community. So we feel very confident we can leverage the experience of our supply chain partners to support a world-class launch of Vicineum.

對於第三方物流和專業分銷服務，我們正在與美國康德樂 (Cardinal Health) 合作。他們在冷鏈物流方面擁有豐富的專業知識，並與泌尿腫瘤學界有著深厚的關係。因此，我們非常有信心能夠利用供應鏈合作夥伴的經驗來支持 Vicineum 的世界級推出。

Turning to Slide 10, and the manufacturing process for Vicineum, which is produced via e coli fermentation. The general approach of using microbial fermentation to manufacture recombinant proteins was pioneered by Genentech in the 1970s with insulin, and continues to be widely used to manufacture peptides and small proteins such as antibody fragments. This system is very well understood and well characterized. The specific process you see here is the proposed commercial process and was developed by Sesen Bio throughout clinical development and then transferred to FUJIFILM and Baxter. FUJIFILM manufactures the drug substance. So that is all the steps up to and including bulk drug substance formulation. This material is then sent to Baxter for drug product manufacturing, which is just a fill finish, and they will also do the labeling, secondary packaging and sterilization of the product.

轉向幻燈片 10，以及透過大腸桿菌發酵生產的 Vicineum 的製造過程。使用微生物發酵製造重組蛋白的一般方法是基因泰克 (Genentech) 在 20 世紀 70 年代與胰島素一起首創的，並繼續廣泛用於製造勝肽和抗體片段等小蛋白。該系統非常容易理解並且具有良好的特徵。您在這裡看到的具體流程是擬議的商業流程，由 Sesen Bio 在整個臨床開發過程中開發，然後轉移到 FUJIFILM 和 Baxter。富士膠片生產該原料藥。這就是原料藥配方之前的所有步驟（包括原料藥配方）。然後，這些材料被送到百特進行藥品生產，這只是填充完成，他們還將對產品進行貼標、二次包裝和滅菌。

On Slide 11, we've highlighted what we see as some of the key advantages of the manufacturing process for Vicineum in comparison to other biologics and gene therapies. We're using microbial fermentation, a well-understood system that has and continues to be used to manufacture many recombinant proteins. The reliability of this system reduces the risk of manufacturing issues that can lead to supply shortages. And the non-muscle invasive bladder cancer space is very sensitive to supply issues, given the ongoing BCG shortage and manufacturing problems with past products such as VALSTAR. Because microbial processes tend to be shorter and less complex than mammalian systems, and since we do not have any process intermediates or conjugation steps, as you have with antibody drug conjugates, we expect to achieve a competitive cost of goods. Finally, having such strong manufacturing partners leads to a reliable and robust supply chain to support the launch of Vicineum.

在投影片 11 中，我們強調了 Vicineum 製造流程與其他生物製劑和基因療法相比的一些關鍵優勢。我們正在使用微生物發酵，這是一種眾所周知的系統，已經並將繼續用於製造許多重組蛋白。該系統的可靠性降低了可能導致供應短缺的製造問題的風險。鑑於 BCG 持續短缺以及 VALSTAR 等過去產品的製造問題，非肌肉浸潤性膀胱癌領域對供應問題非常敏感。因為微生物過程往往比哺乳動物系統更短、更簡單，而且由於我們沒有任何過程中間體或綴合步驟，就像抗體藥物綴合物一樣，我們希望實現具有競爭力的商品成本。最後，擁有如此強大的製造合作夥伴可以帶來可靠且強大的供應鏈來支持 Vicineum 的推出。

With that, I'll turn the call over to Monica.

這樣，我就把電話轉給莫妮卡。

Thank you, Chad. Please turn to Slide 12 for a few financial highlights. We significantly strengthened our cash position in the first quarter, ending with approximately $110 million in cash and cash equivalents. We also saw a strong increase in stock price and market cap versus year-end 2020. With a strong balance sheet, we believe we are well positioned to continue to build for a successful launch ahead of the potential approval of Vicineum in August of this year.

謝謝你，查德。請參閱投影片 12 以了解一些財務亮點。第一季我們的現金狀況顯著增強，現金和現金等價物約為 1.1 億美元。與 2020 年底相比，我們的股價和市值也出現了強勁增長。

Turning to Slide 13. As we prepare for commercial readiness in the U.S., we continue to manage our balance sheet through stage-gated investments which are focused on our highest priority initiatives, such as supporting the regulatory process in the U.S. and Europe and the commercial launch of Vicineum in the U.S., illustrated by the dark blue bars. We also continue to strategically raise capital to strengthen our cash position as shown on the dark purple bars. I will remind you that given our strong cash position, as of April 1, we shut down our ATM for April and May. We will reactivate the facility no sooner than June and will continue to operate it on a periodic basis, consistent with our historical practice, with the goal of minimizing dilution and decreasing the need to do a large dilutive financing event.

轉向投影片13。商業Vicineum 在美國推出，以深藍色長條表示。我們也繼續策略性地籌集資金，以加強我們的現金狀況，如深紫色條所示。 我要提醒您的是，鑑於我們的現金狀況良好，截至 4 月 1 日，我們在 4 月和 5 月關閉了 ATM。我們將在 6 月之前重新啟動該設施，並將按照我們的歷史慣例繼續定期運營，目標是最大限度地減少稀釋並減少進行大型稀釋性融資活動的需要。

With that, I will turn the call back to Tom. Tom?

這樣，我會將電話轉回給湯姆。湯姆？

Thank you, Monica. So please turn to Slide 14, which is a summary of the 3 key takeaways from our call today. First, Vicineum has a unique and compelling value proposition, especially when it comes to its potential to improve patient outcomes while reducing overall healthcare costs. Second, we believe we have a clear regulatory path forward in both the U.S. and Europe. We continue to work closely with the regulatory agencies as we approach upcoming milestones. Finally, given the substantial unmet need in bladder cancer and the highly differentiated clinical profile of Vicineum, we project a significant global commercial opportunity.

謝謝你，莫妮卡。因此，請參閱投影片 14，它總結了我們今天電話會議的 3 個關鍵要點。首先，Vicineum 擁有獨特且令人信服的價值主張，尤其是在改善患者治療效果同時降低整體醫療成本的潛力方面。其次，我們相信美國和歐洲都有明確的監管路徑。隨著我們接近即將到來的里程碑，我們將繼續與監管機構密切合作。最後，鑑於膀胱癌的大量未滿足需求以及 Vicineum 高度差異化的臨床特徵，我們預計將帶來重大的全球商業機會。

With that, we will open up for questions. Ruby?

至此，我們將開放提問。紅寶石？

(Operator Instructions)

（操作員說明）

Your first question comes from the line of John Newman from Canaccord.

你的第一個問題來自 Canaccord 的 John Newman。

John? You might have us on mute, John.

約翰？你可能會讓我們靜音，約翰。

Hi, can you hear me?

嗨，你聽得到我說話嗎？

Yes, I can hear you.

是的，我聽得到你的聲音。

Tom, sorry about that.

湯姆，對此感到抱歉。

No problem.

沒問題。

Tom, thanks for all the updates. So Tom, I just wondered if you could comment a bit on the design of the Phase III studies that were run for Vicineum. And the reason I'm asking is, whether you would expect full approval or accelerated approval, given that -- when I looked back at the guidance, it seemed to me at least like the design for your studies, I think was consistent with full approval. Obviously, that will be up to the FDA, but just curious if you could comment there.

湯姆，感謝您的所有更新。 Tom，我只是想知道您是否可以對 Vicineum 進行的 III 期研究的設計發表一些評論。我問的原因是，您是否希望獲得全面批准或加速批准，因為當我回顧指南時，在我看來，它至少像您的研究設計，我認為與全面批准是一致的。顯然，這將取決於 FDA，但只是好奇你是否可以在那裡發表評論。

Yes. Thanks, John. It's a great question. Obviously, it's very topical because last week, the FDA had ODAC meetings or advisory committee meetings, discussing the accelerated approval pathway. So you're right. In the February 2018 guidance, the FDA says that for carcinoma in situ, you can conduct a single-arm trial, and that you would be eligible for either full or accelerated approval. And they said, we'll make that call during the review process. We had our first pre-BLA meeting in June 2019, and again, there was a lot of good news there. We had a clear regulatory path forward, and the FDA gave 2 pieces of guidance. They said, we expect that you'll need an Advisory Committee meeting, and we'll expect that you're on an accelerated, not a full approval pathway, which means you'll need a confirmatory trial. So that's how we've been kind of planning things, and that was the guidance we gave at that time. Obviously, we feel like this, as the data come together, it just keeps looking better and better.

是的。謝謝，約翰。這是一個很好的問題。顯然，這是一個非常熱門的話題，因為上週 FDA 召開了 ODAC 會議或諮詢委員會會議，討論了加速審批途徑。所以你是對的。在 2018 年 2 月的指南中，FDA 表示，對於原位癌，您可以進行單臂試驗，並且您將有資格獲得完全或加速批准。他們說，我們將在審查過程中做出決定。我們在 2019 年 6 月舉行了第一次 BLA 前會議，會議再次帶來了許多好消息。我們有明確的監管路徑，FDA 給出了兩個指示。他們說，我們預計您需要召開諮詢委員會會議，我們預計您將採取加速而非完全批准的途徑，這意味著您將需要進行確認性試驗。這就是我們計劃事情的方式，這就是我們當時給予的指導。顯然，我們有這樣的感覺，隨著數據匯集在一起，它看起來越來越好。

And so it was really good news in February of this year when the FDA said, oh, it appears that an ADCOM will not be required and we don't have one scheduled. What they haven't weighed in on yet -- we probably won't learn until right around the PDUFA date, right around August 18 -- is, whether they'll require an accelerated approval, which means a confirmatory trial, which was their previous guidance, or whether they're prepared to give full approval. So still, our guidance is the same based on what the FDA told us during the pre-BLA meeting. Our guidance is that we expect to accelerate approval, and we are ready. We have a protocol written. We're ready for a confirmatory trial, if that's their decision. And that would be great news. That would be a great event for us, is to get that accelerated approval in August. But there is the chance of the upside scenario where we actually get full approval, and so that's something we'll all just be watching for as we approach the PDUFA date.

因此，今年 2 月 FDA 表示，哦，看來不需要 ADCOM，而且我們也沒有安排，這確實是個好消息。他們還沒有權衡的——我們可能要到 PDUFA 日期前後，即 8 月 18 日左右才能得知——是，他們是否需要加速批准，這意味著確認性試驗，這是他們的之前的指導，或者他們是否準備好給予完全批准。 儘管如此，我們的指導仍然基於 FDA 在 BLA 前會議期間告訴我們的內容。我們的指導是，我們預計會加快審批速度，我們已經準備好了。我們已經寫好了協議。如果他們決定的話，我們已經準備好進行確認性試驗。這將是個好消息。對我們來說，這將是一件大事，即在八月獲得加速批准。但也有可能出現積極的情況，即我們實際上獲得了完全批准，因此，隨著 PDUFA 日期的臨近，我們都將密切關注這一情況。

Did you have a follow-up question, John?

約翰，您還有後續問題嗎？

I did, actually. So it's interesting. I'm just wondering, just in your view, what will change in terms of the views on the company once Vicineum hits the market? Just curious as to what investors might learn over time when Vicineum or if Vicineum is approved in the market that could sort of, in your opinion, kind of change your views on the trajectory of Sesen.

事實上，我做到了。所以這很有趣。我只是想知道，在您看來，一旦 Vicineum 上市，人們對公司的看法會發生什麼變化？只是好奇當 Vicineum 或 Vicineum 在市場上獲得批准時，隨著時間的推移，投資者可能會學到什麼，在您看來，這可能會改變您對 Sesen 發展軌蹟的看法。

Yes. It's a good question, and we get that a lot. I will, since this is all about forward-looking statements, remind everyone of Slide 2, especially the risks and uncertainties. But we've guided that we believe, based on the comprehensive Monte Carlo simulation, that there is an 80% probability of Vicineum having peak sales of $1 billion to $3 billion. And you can use whatever PD ratios you want, but if we're right, the company value has the potential to be much higher than our current market cap, right? And so if that happens, John, then I think the market will have learned and really come to understand 3 things.

是的。這是一個很好的問題，我們常常聽到這樣的問題。由於這都是前瞻性陳述，我會提醒大家注意投影片 2，尤其是風險和不確定性。但我們認為，基於全面的蒙特卡羅模擬，Vicineum 有 80% 的可能性實現 10 億至 30 億美元的峰值銷售額。你可以使用任何你想要的 PD 比率，但如果我們是對的，公司價值有可能遠遠高於我們目前的市值，對吧？因此，約翰，如果這種情況發生，那麼我認為市場將會學到並真正理解三件事。

First of all, I'd say, it's the powerful role of the urologists, which I alluded to talking about the patient journey, and then the clear understanding of the 3 key drivers that motivate them, all of which play in the favor, I think, of Vicineum. So first, urologists make decisions based on medical drivers and especially, the benefit-risk profile. They're looking for a product that delivers the best efficacy with the least safety risk, and we believe we're the clear winner versus KEYTRUDA in that regard because we have comparable efficacy and a much better safety profile.

首先，我想說，這是泌尿科醫生的強大作用，我在談論患者旅程時提到了這一點，然後是對激勵他們的 3 個關鍵驅動因素的清晰理解，所有這些都有利於，我想想Vicineum。因此，首先，泌尿科醫師根據醫療驅動因素，特別是利益風險狀況做出決策。他們正在尋找一種能夠提供最佳功效且安全風險最小的產品，我們相信在這方面我們是 KEYTRUDA 的明顯贏家，因為我們具有可比的功效和更好的安全性。

Second of all, urologists make decisions on emotional drivers. It's well understood. They are very loyal and committed to their patient. They do not want to refer to another doctor like medical oncology because they're concerned that other specialties do not adequately understand bladder cancer. And if the urologist chooses Vicineum, they get to keep treating the patient. If they choose KEYTRUDA, someone else probably treats their patient. So we think the emotional drivers are a big factor that the market will come to understand.

其次，泌尿科醫師會根據情緒驅動因素做出決定。這很好理解。他們對病人非常忠誠和忠誠。他們不想轉診腫瘤科等其他醫生，因為他們擔心其他專業無法充分了解膀胱癌。如果泌尿科醫師選擇 Vicineum，他們就可以繼續治療患者。如果他們選擇 KEYTRUDA，其他人可能會治療他們的患者。因此，我們認為情緒驅動因素是市場逐漸理解的重要因素。

And then finally, it's the business drivers. It's important to understand urology clinics make their money through treatment rooms and diagnostic tests. If that urologist chooses Vicineum, their urology clinic gets to keep treating the patient and running diagnostic tests every 3 months, including cytology, cystoscopy, biopsy. And so on the other hand, if they choose KEYTRUDA, the active dynamic medical center, the medical oncology practice, derives that business benefit. And again, to this point, I believe that urologists are always going to do the best thing for the patient, and always make their decision based on medicine first. But if you can choose the best product for the patient, the treatment adoption will be accelerated if that is a more profitable approach for the clinic and the doctor. So I think there is a lot for the market to understand about the urologist and the medical, emotional and business drivers that we think will really shape the treatment of non-muscle invasive bladder cancer.

最後，是業務驅動因素。重要的是要了解泌尿科診所透過治療室和診斷測試賺錢。如果泌尿科醫師選擇 Vicineum，他們的泌尿科診所將繼續治療患者並每 3 個月進行一次診斷測試，包括細胞學、膀胱鏡檢查、活檢。另一方面，如果他們選擇 KEYTRUDA，活躍的動態醫療中心、腫瘤醫學實踐，就會獲得商業利益。再說一遍，到目前為止，我相信泌尿科醫生總是會為患者做最好的事情，並且始終先根據醫學做出決定。但如果你能為病人選擇最好的產品，如果這對診所和醫生來說是一種更有利可圖的方法，那麼治療的採用將會加速。因此，我認為市場對泌尿科醫生以及醫療、情緒和商業驅動因素有很多需要了解的地方，我們認為這些驅動因素將真正影響非肌肉侵襲性膀胱癌的治療。

The second thing, John, I think, is -- and we've talked about this because there's a good backup slide on this, is the virtuous cycle that's created when you have the advocacy of all 3 customer segments: patients, payers and physicians. And this is pretty rare for new product launches to have advocacy from all 3 segments, and here's why that's important. The stronger the advocacy from patients and their families, and the more they ask for a new product, the more likely the doctor is to prescribe that product. That phenomenon has been well documented. The stronger the efficacy of physicians and key opinion leaders, the more likely that payers will add the product to formulary and reimburse the product fully. Remember, it's mostly physicians that sit on these managed care P&T committees. So that physician view really matters. And then the better the reimbursement is from payer, the lower the out-of-pocket cost for patients and the better the patient access to therapy. And I think when all 3 groups are advocating, the stronger the feedback loop is. And that can drive, I think, very strong, early and sustainable uptake. So that's the second phenomenon, I think, is the interplay and the virtuous cycle between the different customer segments, and I think that's fairly unique in our situation.

約翰，我認為第二件事是——我們已經討論過這個問題，因為有一個很好的備用幻燈片，就是當你得到所有3 個客戶群體（病人、付款人和醫生）的倡導時所創建的良性循環。對於新產品的發布來說，得到所有三個細分市場的支持是非常罕見的，這就是為什麼這很重要。患者及其家人的倡議越強烈，他們對新產品的要求越多，醫生就越有可能開出產品。這種現像已有詳細記錄。醫生和關鍵意見領袖的功效越強，付款人就越有可能將產品添加到處方集中並全額報銷產品。請記住，這些管理式醫療 P&T 委員會的成員主要是醫生。所以醫生的觀點確實很重要。然後，付款人的報銷越好，患者的自付費用就越低，患者獲得治療的機會就越大。我認為當所有三個群體都在倡導時，反饋循環就會越強。我認為，這可以推動非常強勁、早期和可持續的採用。我認為，第二個現像是不同客戶群之間的互動和良性循環，我認為這在我們的情況下是相當獨特的。

Finally, I think something that people aren't completely paying attention to yet is just how lucky we are to have KEYTRUDA as our primary competitor. KEYTRUDA is arguably the most important oncology product in the modern era. I mean as you know well, John, they grew 30% last year with sales last year of $14.4 billion. And many -- I haven't seen your projections, but many analysts project it to surpass $20 billion and become the best-selling pharmaceutical product of all time. And I believe it has right now the best brand image of any oncology product. So KEYTRUDA is indicated for 19 types of cancer, and in one of those, NMIBC, we believe we're better than them. We believe we will surpass KEYTRUDA, become the market leader in NMIBC. And I think, as you know, a real strength of our company, I think, is the commercial and marketing expertise. And when you beat the dominant market leader in one single area, it has a transformational effect on your brand image and the value of your company. So from a commercial marketing perspective, it's a very important phenomenon.

最後，我認為人們還沒有完全關注的是我們有 KEYTRUDA 作為我們的主要競爭對手是多麼幸運。 KEYTRUDA 可以說是現代最重要的腫瘤學產品。我的意思是，約翰，你很清楚，他們去年成長了 30%，銷售額達到 144 億美元。我還沒看到你們的預測，但許多分析師預測它的銷售額將超過 200 億美元，成為有史以來最暢銷的醫藥產品。我相信它目前擁有所有腫瘤產品中最好的品牌形象。因此 KEYTRUDA 適用於 19 種癌症，在其中一種癌症 NMIBC 中，我們相信我們比他們更好。我們相信我們將超越KEYTRUDA，成為NMIBC市場的領導者。我認為，如您所知，我們公司的真正優勢是商業和行銷專業知識。當您在某一領域擊敗市場主導者時，會對您的品牌形象和公司價值產生變革性影響。所以從商業行銷的角度來看，這是一個非常重要的現象。

So anyway, we think we've got the best situation for a new product launch, to be positioned against one of the most important oncology products of all time. And I believe by the time we potentially launch our next indication for -- potentially for head and neck cancer, that, that will be a whole different ballgame. So basically, what should investors be watching for? I think, watch the role of urologists and what motivates them, watch the virtuous cycle between physicians, payers and patients, and watch the market share battle between KEYTRUDA and Vicineum. And obviously, after August, we'll structure our presentation so that's easy to follow.

因此，無論如何，我們認為我們已經獲得了新產品發布的最佳時機，可以針對有史以來最重要的腫瘤產品之一進行定位。我相信，當我們可能推出下一個適應症——可能是針對頭頸癌時，那將是一場完全不同的比賽。 那麼基本上，投資人該關注什麼？我認為，觀察泌尿科醫生的角色以及激勵他們的因素，觀察醫生、付款人和患者之間的良性循環，觀察 KEYTRUDA 和 Vicineum 之間的市場份額爭奪戰。顯然，八月之後，我們將建立我們的演示文稿，以便於理解。

Any follow-up on that, John?

約翰，有後續行動嗎？

No, that's great.

不，那太好了。

Your next question comes from the line of Roger Song from Jefferies.

您的下一個問題來自 Jefferies 的 Roger Song。

Great. Maybe just a quick follow-up on John's question earlier. So obviously, if you can get a full approval in August, there will be a real kind of upside. But just tell us a little bit about the logistics, because as far as I know, you -- I think from the last guidance, you may need to start the confirmatory study before the PDUFA date or maybe just to finalize the protocol. Probably, you already get some additional kind of guidance from the FDA, if you need a confirmatory study. And obviously, you're having kind of back and forth with the FDA right now. Just tell us a little bit what should we expect what is going to happen before the approval decision, in terms of the confirmatory study, your site inspection and the late cycle meetings?

偉大的。也許只是對約翰之前的問題的快速跟進。顯然，如果你能在八月獲得完全批准，將會有真正的好處。但請告訴我們一些有關後勤工作的信息，因為據我所知，我認為從上一次指導來看，您可能需要在 PDUFA 日期之前開始驗證性研究，或者只是為了最終確定協議。如果您需要驗證性研究，您可能已經從 FDA 獲得了一些額外的指導。顯然，您現在正在與 FDA 進行反覆的討論。請告訴我們一點，在批准決定之前，我們應該期望在驗證性研究、現場檢查和後期週期會議方面會發生什麼？

Yes. That's a great question. And I think, as I've said before, it's definitely the FDA's preference that you launch your confirmatory trial right around the time of approval. So we had a Type C meeting with the FDA. We agreed on the protocol synopsis and the overall approach. As we've talked about, we plan on targeting the less than adequate BCG population, that's patients that have had only 1 to 6 installations. And so we will be ready to go. We have a team to -- put together a clinical trial oversight team. And as we move through the process, if it seems increasingly likely that it's [exard] approval, we'll be ready in the third quarter to launch a study.

是的。這是一個很好的問題。我認為，正如我之前所說，FDA 絕對傾向於在批准前後立即啟動驗證性試驗。因此我們與 FDA 舉行了 C 類會議。我們就協議概要和總體方法達成了一致。正如我們所討論的，我們計劃針對卡介苗不足的人群，即僅安裝過 1 到 6 次的患者。我們就準備出發吧。我們有一個團隊來組成臨床試驗監督團隊。隨著我們完成整個過程，如果它獲得批准的可能性似乎越來越大，我們將在第三季準備好啟動一項研究。

I will say, even if they don't require a confirmatory trial, it's something I want to do anyway, is to do that clinical trial in the less than adequate BCG population. We have data to suggest that Vicineum is even more effective in that -- in patients that have had less exposure to BCG. It also puts us on a path toward, hopefully someday, first-line therapy, with or without combination therapy, depending on how we design the trial. So even if we don't need the confirmatory trial, we do intend to do a study in that patient population. So that's kind of the thinking right now, Roger. And then what I would say is, if we learn more at the late cycle meeting, which is mid-July, then obviously, we'll disclose that and might even -- we'll come out and make sure that investors know what the update is there.

我會說，即使他們不需要驗證性試驗，無論如何，我想做的就是在卡介苗不足的人群中進行臨床試驗。我們有數據表明，Vicineum 在這方面甚至更有效——對於接觸卡介苗較少的患者。它也讓我們走上了一線治療的道路，希望有一天，可以使用或不使用聯合療法，這取決於我們如何設計試驗。因此，即使我們不需要驗證性試驗，我們也確實打算在該患者群體中進行研究。這就是現在的想法，羅傑。 然後我想說的是，如果我們在 7 月中旬的周期末會議上了解更多信息，那麼顯然，我們會披露這一點，甚至可能 - 我們會出來確保投資者知道什麼更新就在那裡。

Did you have a followup, Roger?

羅傑，你有後續嗎？

Yes, I do have one follow-up. So yes, first of all, thanks for the color. And my next question is related to the financials, understanding your contracting CSO and to do the sales. So just tell us a little bit about what is the level of the ramp-up in terms of the SG&A? And what is the pace? And since you're having kind of $110 million in the bank, and what is the current cash [your Opex your guidance]?

是的，我確實有一個後續行動。所以，是的，首先，感謝你的顏色。我的下一個問題與財務有關，了解您的簽約 CSO 並進行銷售。那麼請告訴我們一些關於 SG&A 方面的成長水準是多少？節奏是怎樣的？既然你在銀行裡有 1.1 億美元，那麼當前的現金是多少 [你的營運支出，你的指導]？

Yes. Yes, that's great. Well, I'll talk -- I'll just talk about the ramp-up the contract sales organization. I'll let Monica speak to kind of what we think the cost is per annum for a contract sales organization of that size. So we've said publicly, it's 35 representatives and up to 10 reimbursement specialists. We are -- we've got the National Sales Director hired as well as the VP of Sales. We're in the process and close to finalizing all the Region Sales Directors, and then we're getting ready to go with the representative interviews and then training. So all of that will happen throughout the spring in getting those representatives to be ready to be out there in August. Same thing with the reimbursement specialists and the concierge call center that we'll set up to support patients through the process.

是的。是的，那太好了。好吧，我會談談——我只會談談合約銷售組織的發展。我會讓莫妮卡談談我們認為這種規模的合約銷售組織的每年成本是多少。所以我們公開說，有 35 位代表，最多 10 位報銷專家。我們已經聘請了全國銷售總監和銷售副總裁。我們正在準備並接近最終確定所有區域銷售總監，然後我們準備進行代表面試和培訓。因此，所有這些都將在整個春季發生，讓這些代表做好八月份的準備。我們將設立報銷專家和禮賓呼叫中心來支持病患完成整個過程。

So we have a lot of experience with Syneos. I've worked with them in the past. This is really their area of expertise as they can find talent, have a very expeditious recruiting process and then train those representatives, and they're going to be ready to go. So that's how we're thinking about the rollout of the contract sales organization.

所以我們在 Syneos 方面擁有豐富的經驗。我過去曾與他們合作過。這確實是他們的專業領域，因為他們可以找到人才，有一個非常迅速的招募流程，然後培訓這些代表，他們就準備好了。這就是我們考慮推出合約銷售組織的方式。

Monica, I'll just let you talk about OpEx in regard to that.

Monica，我將讓您談談與此相關的營運支出。

Sure. Thanks, Tom. Roger, so we haven't guided specifically on what our cash burn will be once we kind of stand up the sales force and build the full commercial team. But we have said with regards to the CSO and the number of representatives that we will hire, we expect roughly $10 million to $15 million on an annual basis for that part of the commercial team. And then I think you also referred to our cash balance. And just with regards to the cash balance of $110 million at the end of the first quarter, we do expect that - again, although we're not guiding on cash burn -- we do expect the $110 million to be sufficient to fund operations through the fourth quarter of this year.

當然。謝謝，湯姆。羅傑，所以我們沒有具體指導一旦我們建立銷售團隊並建立完整的商業團隊，我們的現金消耗將會是多少。但我們已經說過，關於 CSO 和我們將僱用的代表人數，我們預計這部分商業團隊每年大約獲得 1000 萬至 1500 萬美元的費用。然後我想你也提到了我們的現金餘額。僅就第一季末 1.1 億美元的現金餘額而言，我們確實預計，儘管我們沒有對現金消耗進行指導，但我們確實預計 1.1 億美元將足以透過以下方式為營運提供資金：今年第四季。

Your next question comes from the line of Arthur Yu He from H.C. Wainwright.

您的下一個問題來自 H.C. 的 Arthur Yu He。溫賴特。

This is Arthur for RK. I just had a one question regarding the manufacturing part. So as we know there is industry-wide backlog for FDA conduct the on-site inspection. I just wonder -- so these such kind of on-site inspection also required for the approval for Vicineum, and how the communication between you guys and the agents regarding that issue?

這是 RK 的 Arthur。我只是有一個關於製造部分的問題。據我們所知，FDA 進行現場檢查的整個行業都有積壓。我只是想知道，Vicineum 的審批也需要這樣的現場檢查，你們和代理商之間關於這個問題是如何溝通的？

Yes. I'll just answer that at a high level, and then I'll check with Chad to see if he wants to add anything on top of it. So again, as the FDA prepares for the mid -- for the late cycle meeting in mid-July, obviously, they're doing their clinical and their manufacturing site inspections. And as we mentioned, because of the pandemic, which -- again, there was just something in the pink sheets that there's been delays kind of across the board in the FDA getting out. But we do feel confident that they'll have all of those wrapped up in time so that we can have a good, really productive late cycle meeting in July and still on a pathway for potential approval in August of this year. And again, you can imagine the most important of those site inspections would be at FUJI, which is our bulk drug substance manufacturer, and that's where probably 90% of the overall complexity and the work is around manufacturing. And we feel very confident. FUJI was with us when we had the Type B meeting with the FDA in terms of demonstrating analytical comparability, and they're a world-class manufacturer with a real good track record with the FDA and from a regulatory perspective. So we feel good for us about how that's going, recognizing these site inspections have been a real challenge for the agency since the pandemic hit.

是的。我會從高層次回答這個問題，然後我會與查德核實，看看他是否想在此基礎上添加任何內容。同樣，當 FDA 為 7 月中旬的中期會議做準備時，顯然他們正在進行臨床和生產現場檢查。正如我們所提到的，由於大流行，再次強調，粉紅單中的某些內容在 FDA 的發布中出現了全面的延誤。但我們確實有信心，他們會及時完成所有這些工作，以便我們能夠在 7 月份召開一次良好的、真正富有成效的後期週期會議，並仍在為今年 8 月份的潛在批准做好準備。再說一次，您可以想像這些現場檢查中最重要的是在 FUJI，這是我們的原料藥製造商，那裡可能 90% 的整體複雜性和工作都圍繞著製造進行。我們感到非常有信心。當我們與 FDA 舉行 B 類會議以展示分析可比性時，富士與我們在一起，從監管角度來看，他們是一家世界級製造商，在 FDA 中擁有良好的記錄。因此，我們對事情的進展感到滿意，並認識到自大流行爆發以來，這些現場檢查對該機構來說是一個真正的挑戰。

Chad, anything you want to add to that?

查德，你還有什麼要補充的嗎？

No, Tom, I think you answered that very well.

不，湯姆，我認為你回答得很好。

Great. Thanks. RK (sic) [Arthur], did you have another question or a follow-up?

偉大的。謝謝。 RK（原文如此）[Arthur]，您還有其他問題或後續行動嗎？

No, thank you, thank you for the color.

不，謝謝你，謝謝你的顏色。

At this time, there are no further questions on queue. I would now like to hand the conference over to our President and CEO, Dr. Thomas Cannell.

目前，隊列中沒有其他問題。現在我想將會議交給我們的總裁兼執行長托馬斯·坎內爾博士。

Thank you, Ruby, and thank you, everyone, for your good questions today and your interest in Sesen Bio. I'd also like to take this time to thank our employees. We only have roughly 30 employees, and they're just doing herculean work in bringing this product to market and being prepared for manufacturing and supply chain and all the commercial prep that's underway. And so I just want to thank the team for everything they're doing. They're just -- it's just an outstanding effort, and they're working so well. You will be hearing again from us soon. Thank you again to all our investors for your interest, and please stay safe and have a good week.

謝謝 Ruby，也謝謝大家今天提出的好問題以及對 Sesen Bio 的興趣。我還想藉此機會感謝我們的員工。我們只有大約 30 名員工，他們只是在將產品推向市場、為製造和供應鏈以及所有正在進行的商業準備做好準備方面做著艱鉅的工作。所以我只想感謝團隊所做的一切。他們只是——這只是一項傑出的努力，而且他們工作得很好。您很快就會再次收到我們的訊息。再次感謝我們所有投資者的關注，請保持安全並度過愉快的一周。

So with that, that concludes our call for today. Thank you all very much. And Ruby, I'll hand it back to you.

我們今天的呼籲到此結束。非常感謝大家。魯比，我會把它還給你。

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

謝謝。今天的電話會議到此結束。您現在可以斷開連線。