2Seventy Bio Inc (TSVT) 2022 Q2 法說會逐字稿

Hello and welcome to 2seventy bio's second-quarter 2022 financial results conference call. (Operator Instructions). Please be advised that this call is being recorded. I would now like to turn the call over to Jenn Snyder, head of corporate affairs. You may begin.

您好，歡迎來到 2seventy bio 的 2022 年第二季度財務業績電話會議。 （操作員說明）。請注意，此通話正在錄音中。我現在想把電話轉給公司事務主管 Jenn Snyder。你可以開始了。

Thank you, operator. This morning 2seventy bio issued a press release providing a business update in addition to second-quarter 2022 financial results. The press release can be found in the Investors & Media section of the company's website at 2seventybio.com. On the call today are Nick Leschly, Chief Kairos Officer; Chip Baird, Chief Financial Officer; and Steve Bernstein, Chief Medical Officer.

謝謝你，接線員。今天上午 2seventy bio 發布了一份新聞稿，除了 2022 年第二季度的財務業績外，還提供了業務更新。該新聞稿可在公司網站 2seventybio.com 的投資者和媒體部分找到。今天的電話會議是凱羅斯首席官 Nick Leschly； Chip Baird，首席財務官；和首席醫療官史蒂夫伯恩斯坦。

As a reminder, today's discussion will include forward-looking statements related to 2seventy bio's current plans and expectations which are subject to certain risks and uncertainties. These forward-looking statements include statements regarding our strategic plans, timelines and expectations and statements regarding our financial condition, expectations and other future financial results among others.

提醒一下，今天的討論將包括與 2seventy bio 的當前計劃和預期相關的前瞻性陳述，這些計劃和預期受到某些風險和不確定性的影響。這些前瞻性陳述包括關於我們的戰略計劃、時間表和預期的陳述，以及關於我們的財務狀況、預期和其他未來財務結果的陳述。

Actual results may differ materially due to various risks, uncertainties and other factors, including those described in the Risk Factors section of our most recent forms 10-Q, 10-K and other SEC filings. These forward-looking statements represent our views as of this call and should not be relied upon as representing our views as of any subsequent date.

由於各種風險、不確定性和其他因素，包括我們最近的 10-Q、10-K 表格和其他 SEC 文件的風險因素部分中描述的因素，實際結果可能存在重大差異。這些前瞻性陳述代表我們在本次電話會議上的觀點，不應被視為代表我們在任何後續日期的觀點。

You are cautioned not to place any undue reliance on these forward-looking statements and, except as required by law, we undertake no obligation to update or revise any forward-looking statements. At this time I would like to turn the call over to Nick Leschly. Nick?

請注意不要過度依賴這些前瞻性陳述，除非法律要求，我們不承擔更新或修改任何前瞻性陳述的義務。此時，我想將電話轉給 Nick Leschly。缺口？

Thank you, Jenn, and good morning, everyone. Thanks for joining us for an update on the second-quarter 2022 results. Last week 2seventy passed the 270-day milestone since the launch of our company. So, I'll spend a few minutes talking about the recent company highlights, including the fantastic news announced this morning with our partner BMS on the KarMMA-3 study. Then I'll hand it over to Steve and Chip for a bit more on the clinical and financial side of the house. After that we'll be sure to get to your questions.

謝謝你，Jenn，大家早上好。感謝您加入我們以更新 2022 年第二季度的業績。上週 2seventy 走過了我們公司成立以來的 270 天里程碑。因此，我將花幾分鐘時間談談最近的公司亮點，包括今天早上與我們的合作夥伴 BMS 宣布的關於 KarMMA-3 研究的好消息。然後我將把它交給史蒂夫和奇普，以了解更多關於房子的臨床和財務方面的信息。之後，我們一定會回答您的問題。

We're off to a great start for the first half of this year. Our 2seventy team is gelling as we build upon several tracks. Our commercial business is growing with significant demand for ABECMA. We continue to treat as many patients as we can and, as previously stated, we're committed to capacity improvements which we've been able to achieve.

今年上半年我們有了一個良好的開端。我們的 2seventy 團隊在建立多條賽道時正在凝聚。隨著對 ABECMA 的大量需求，我們的商業業務正在增長。我們將繼續盡可能多地治療患者，並且如前所述，我們致力於提高我們已經能夠實現的能力。

We're tracking towards the high-end of our anticipated 2022 revenues for ABECMA sales. And on our clinical side, our pipeline continues to progress with multiple clinical stage programs in both BMHL and AML, as well as an emerging set of programs in solid tumors in collaboration with Regeneron.

我們正在追踪 ABECMA 銷售的預期 2022 年收入的高端。在我們的臨床方面，我們的管道繼續在 BMHL 和 AML 的多個臨床階段項目中取得進展，以及與 Regeneron 合作的一組新興實體腫瘤項目。

Zooming out, the mission of 2seventy is clear and powerful. Existing standards are good, but not good enough. The immunotherapies have opened the door to the immune system, but are also not yet good enough. 2seventy's ability to design next gen cell therapy product solutions, that both integrate novel technologies and also partner us across modalities, is unprecedented and exciting.

縮小，2seventy 的使命清晰而有力。現有的標準很好，但還不夠好。免疫療法為免疫系統打開了大門，但還不夠好。 2seventy 設計下一代細胞治療產品解決方案的能力，既整合了新技術，又與我們合作跨模式，這是前所未有的和令人興奮的。

Perhaps George Yancopoulos from Regeneron recently publicly said that when you are layering and integrating modalities, we are on the trail to the Holy Grail. This is a statement we firmly agree with.

或許 Regeneron 的 George Yancopoulos 最近公開表示，當您對模式進行分層和整合時，我們就在通往聖杯的道路上。這是我們堅決同意的聲明。

On the financial front, we took the time during the earlier part of this year to reshape our operating model and reduce our overhead costs. We continue to evolve to meet the needs of the growing ABECMA opportunity that BMS recently outlined in their earnings call, including exciting top-line growth.

在財務方面，我們在今年早些時候花時間重塑我們的運營模式並降低我們的間接成本。我們繼續發展以滿足 BMS 最近在其財報電話會議中概述的不斷增長的 ABECMA 機會的需求，包括令人興奮的收入增長。

On the cost side, this quarter we saw an increased investment in ABECMA ramp up activities and higher than anticipated vector costs. You will hear more detail from Chip on how this has impacted our near-term guidance. Importantly, we remain confident in our runway into 2025.

在成本方面，本季度我們看到對 ABECMA 活動的投資增加，並且高於預期的載體成本。您將從 Chip 那裡聽到更多關於這如何影響我們近期指導的詳細信息。重要的是，我們對進入 2025 年的跑道充滿信心。

Shifting gears, we are extremely excited to share the great news regarding our earlier line study, Phase 3 study for ABECMA called KarMMA-3, studying patients with two to four prior lines of therapy. After performing at preplanned interim analysis and receiving the recommendation by the Data and Safety Monitoring Board, the study was unblinded and has met its primary endpoint of demonstrating a statistically significant improvement in progression free survival.

換檔，我們非常高興地分享關於我們早期線研究的好消息， ABECMA 的第 3 期研究稱為 KarMMA-3，研究具有兩到四個先前治療線的患者。在進行預先計劃的中期分析並收到數據和安全監測委員會的建議後，該研究是非盲的，並已達到其主要終點，即無進展生存期有統計學意義的改善。

It's hard to overstate our excitement for patients with myeloma and, along with BMS, this news certainly increases our conviction of the potential of ABECMA over the long term. It is both exciting and humbling. With that I'll hand it over to Steve, our Chief Medical Officer, to give a bit more of the exciting news of today and clinical updates this quarter. Steve?

很難誇大我們對骨髓瘤患者的興奮，與 BMS 一起，這一消息無疑增加了我們對 ABECMA 長期潛力的信心。這既令人興奮又令人謙卑。有了這個，我將把它交給我們的首席醫療官史蒂夫，以提供更多今天令人興奮的消息和本季度的臨床更新。史蒂夫?

Thank you, Nick. Good morning, everybody. It is an incredibly exciting day indeed. So, to expand on the updates that Nick shared this morning, 2seventy and BMS issued a press release announcing positive top-line results from a prespecified interim analysis of KarMMA-3, which is a Phase 3 global, randomized, multicenter, open label study that evaluates ABECMA in relapsed and refractory multiple myeloma patients who have had two to four prior lines of therapy.

謝謝你，尼克。大家早上好。這確實是令人難以置信的激動人心的一天。因此，為了擴展 Nick 今天上午分享的更新，2seventy 和 BMS 發布了一份新聞稿，宣布對 KarMMA-3 的預先指定的中期分析取得了積極的頂線結果，這是一項 3 期全球、隨機、多中心、開放標籤研究評估 ABECMA 在已經接受過兩到四線治療的複發性和難治性多發性骨髓瘤患者中的作用。

They must have been refractory to their last regimen, and have been previously exposed to a proteosome inhibitor, an IMiD and Daratumumab, so-called triple exposed. And the outcome of these patients was compared to that of standard combination regimens.

他們一定對他們的最後一個方案無效，並且之前已經暴露於蛋白體抑製劑、IMiD 和 Daratumumab，即所謂的三重暴露。並將這些患者的結果與標準聯合方案的結果進行比較。

This makes ABECMA the first BCMA directed CAR T therapy to demonstrate clinical superiority versus standard regimens in a randomized controlled trial. Indeed these results came ahead of schedule compared to our original timing guidance of data in 2023, and we are so pleased for what these data could mean in terms of potential paths to treat earlier line patients.

這使得 ABECMA 成為第一個 BCMA 定向 CAR T 療法，在隨機對照試驗中證明了與標準方案相比的臨床優勢。事實上，與我們最初對 2023 年數據的時間指導相比，這些結果提前了，我們對這些數據在治療早期患者的潛在途徑方面可能意味著什麼感到非常高興。

The study met the primary endpoint of progression free survival. The safety results were consistent with the well-established and predictable profile demonstrated in the pivotal KarMMa trial. We, along with Bristol-Myers Squibb, expect to present additional data from this study at a medical meeting in the future and discuss these findings with health authorities.

該研究達到了無進展生存的主要終點。安全性結果與關鍵的 KarMMa 試驗中證明的成熟和可預測的概況一致。我們與 Bristol-Myers Squibb 一起，希望在未來的醫學會議上展示這項研究的更多數據，並與衛生當局討論這些發現。

We also presented additional data for ABECMA in June at the 2022 ASCO annual meeting, including the largest data set to date for ABECMA patients treated in the commercial setting by the multiple myeloma cell therapy consortium of academic institutions. The data presented were consistent with what was seen in the pivotal KarMMa study, despite the fact that the overwhelming majority of such patients would not have met the eligibility criteria of KarMMa, reinforcing the efficacy and safety profile of ABECMA.

我們還在 6 月的 2022 年 ASCO 年會上展示了 ABECMA 的其他數據，包括迄今為止由學術機構的多發性骨髓瘤細胞治療聯盟在商業環境中治療的 ABECMA 患者的最大數據集。儘管絕大多數此類患者不符合 KarMMa 的資格標準，但所提供的數據與關鍵的 KarMMa 研究中的結果一致，從而加強了 ABECMA 的療效和安全性。

Looking forward, we expect to share proof of concept data for our KarMMa-2 study in high risk early stage multiple myeloma in 2022 that will further inform our earlier line development plans.

展望未來，我們希望在 2022 年分享我們在高風險早期多發性骨髓瘤中進行的 KarMMa-2 研究的概念驗證數據，這將進一步為我們早期的生產線開發計劃提供信息。

In addition, at ASCO 2022, we presented updates from our portfolio of oncology cell therapies, a trial in progress poster on CRC-403, a Phase 1/2 study of BBT-369 in patients with relapsed refractory B non-Hodgkin's lymphoma, and a trial in progress poster on PLAT-08, a Phase 1 study of SC-DARIC33 in relapsed refractory pediatric and young adult AML presented by Seattle Children's Therapeutics.

此外，在 ASCO 2022 上，我們展示了我們的腫瘤細胞療法組合的更新、CRC-403 的正在進行中的試驗海報、BBT-369 在復發難治性 B 非霍奇金淋巴瘤患者中的 1/2 期研究，以及PLAT-08 正在進行的試驗海報，這是一項 SC-DARIC33 在復發難治性兒科和年輕成人 AML 中的 1 期研究，由西雅圖兒童治療公司提出。

Overall this is a very exciting time for 2seventy as we move many years of efforts into translational stages supported by a significant ongoing ramp-up of our internal drug manufacturing throughput that's needed to drive our overarching strategy of moving rapidly into efficient and exhaustive proof of concept studies into the clinic. Quite a privilege and looking forward to sharing more. Now I'll turn the call over to Chip for a deeper dive on the second-quarter results. Chip?

總體而言，對於 2seventy 來說，這是一個非常激動人心的時刻，因為我們將多年的努力轉入轉化階段，這得益於我們內部藥物生產量的持續顯著提升，這是推動我們快速進入高效和詳盡的概念證明的總體戰略所必需的進入臨床研究。相當榮幸，期待分享更多。現在，我將把電話轉給 Chip，以更深入地了解第二季度的業績。芯片？

Thanks, Steve, and good morning, everyone. During the second quarter, ABECMA generated $72 million in US commercial revenue, up 29% compared to the prior quarter. As a reminder, we share all profits and losses related to ABECMA equally with BMS for the development, manufacturing and commercialization of ABECMA in the US. We continue to see very strong demand for ABECMA and we are pleased with the growth trajectory there.

謝謝，史蒂夫，大家早上好。第二季度， ABECMA 在美國創造了 7200 萬美元的商業收入，比上一季度增長 29%。提醒一下，我們與 BMS 平分與 ABECMA 相關的所有損益，用於 ABECMA 在美國的開發、製造和商業化。我們繼續看到對 ABECMA 的強勁需求，我們對那裡的增長軌跡感到滿意。

We remain on track to achieve the high-end of our 2022 US ABECMA revenue guidance of between $250 million and $300 million. We reported our share of collaboration loss of $4.3 million for the second quarter, which includes our share of gross profit less costs associated with commercialization of ABECMA in the US.

我們仍有望實現 2022 年美國 ABECMA 收入指引的高端，即 2.5 億美元至 3 億美元。我們報告了第二季度我們在合作損失中的份額為 430 萬美元，其中包括我們在毛利中的份額減去與 ABECMA 在美國商業化相關的成本。

Given the strong demand for ABECMA, and our growing belief in the potential for this therapy to play an important role in earlier lines, we've been making significant investments to increase manufacturing capacity across the supply chain.

鑑於對 ABECMA 的強勁需求，以及我們越來越相信這種療法在早期生產線中發揮重要作用的潛力，我們一直在進行重大投資以提高整個供應鏈的製造能力。

In addition to our manufacturing capacity investments, we have experienced costs per vector that were higher than anticipated. This does not affect our 2020 revenue target as we believe we have sufficient vector to achieve that target, and we are continuing to invest in increasing manufacturing capacity in the future. That said, we are partnering closely and supporting BMS in their efforts to lower vector manufacturing costs and continue to increase manufacturing capacity.

除了我們的製造能力投資外，我們還經歷了高於預期的每個載體的成本。這不會影響我們 2020 年的收入目標，因為我們相信我們有足夠的載體來實現該目標，並且我們將在未來繼續投資於提高製造能力。也就是說，我們正在密切合作並支持 BMS 努力降低矢量製造成本並繼續提高製造能力。

Between the capacity investments and the higher vector costs, we are increasing our 2022 guidance for net cash spend to $245 million to $265 million. We continue to forecast cash runway into 2025 based on our current operating plan. This runway is sufficient to achieve important milestones across our business. I'd now like to turn the call back to Nick for closing remarks. Nick?

在產能投資和更高的載體成本之間，我們將 2022 年的淨現金支出指引提高到 2.45 億美元至 2.65 億美元。根據我們目前的運營計劃，我們繼續預測到 2025 年的現金跑道。這條跑道足以實現我們業務的重要里程碑。我現在想把電話轉回給尼克，以便結束髮言。缺口？

Thank you, Chip, and thank you, Steve. As you can see, it has been a very productive and rewarding quarter. Much to be excited about here at 2seventy and I'm grateful to our team who have all demonstrated such tremendous dedication and focus over the past few months, if not the past few years.

謝謝你，奇普，謝謝你，史蒂夫。如您所見，這是一個非常富有成效和收穫頗豐的季度。在 2seventy 非常激動，我很感謝我們的團隊，他們在過去幾個月（如果不是過去幾年）都表現出如此巨大的奉獻精神和專注。

In closing I'll just say that our mission as a company, what drives us every day is the concept of time. It's pretty simple but it's very powerful. Giving the people we serve more time by developing new therapies [at the rough] cancer treatment landscape is what 2seventy was designed to do and what we are all focused on. We look forward to sharing more updates in the coming months as we continue to advance this mission. With that, Kyle -- operator, we're ready for questions.

最後，我只想說，我們作為一家公司的使命，每天驅動我們的是時間的概念。這很簡單，但非常強大。 2seventy 旨在為我們服務的人們提供更多時間，[在粗糙的]癌症治療領域開發新療法，也是我們所有人關注的重點。隨著我們繼續推進這一使命，我們期待在未來幾個月內分享更多更新。有了這個，凱爾——接線員，我們準備好提問了。

(Operator Instructions). Salveen Richter, Goldman Sachs.

（操作員說明）。 Salveen Richter，高盛。

Good morning and thanks for taking our question. This is Elizabeth on for Salveen. Just wondering if you could comment on the powering or how stringent the criteria was to stop at the prespecified interim analysis. And then if there's any comment on CR-8 that you could provide? And then a follow-up on vector supply for 2023 and how to think about that. Thank you.

早上好，感謝您提出我們的問題。這是伊麗莎白在薩爾文。只是想知道您是否可以評論供電或停止在預先指定的中期分析上的標準有多嚴格。然後，如果您對 CR-8 有任何意見可以提供嗎？然後是關於 2023 年矢量供應的後續行動以及如何考慮這一點。謝謝你。

Thank you. Just a heads up here, I'll pass it over to Steve, but, as you can imagine right now, where obviously the data is continuing to be crunched here and will be, as we said in the script, communicated later at a medical meeting. So, I'll pass it over to Steve to share what he can, but just a heads up, it'll be pretty limited. Steve?

謝謝你。只是在這裡提醒一下，我會把它交給史蒂夫，但是，正如你現在可以想像的那樣，顯然數據在這裡繼續被處理，並且正如我們在腳本中所說，稍後會在醫療中心進行交流會議。所以，我會把它交給史蒂夫分享他能做的，但只是提醒一下，它會非常有限。史蒂夫?

Sure. Thanks, Nick, and thanks for your question. It was a prespecified analysis. This was our interim analysis for superiority, and the DSMB recommended that we unblind the study and it was a positive result. In terms of response rates, I can share that the secondary endpoint of overall response rate was met and was statistically significant. But at this time that's all that I can share.

當然。謝謝，尼克，謝謝你的問題。這是預先指定的分析。這是我們對優越性的中期分析，DSMB 建議我們對這項研究進行揭盲，這是一個積極的結果。在響應率方面，我可以分享總體響應率的次要終點得到滿足並且具有統計學意義。但在這個時候，這就是我能分享的全部。

And on the vector supply question, why don't we -- Chip, do you want to take that one?

關於向量供應問題，我們為什麼不——Chip，你想拿那個嗎？

Sure, thanks, Nick. Good question. Yes, we've continued to make step-ups throughout this year in terms of our weekly capacity in terms of patients that we can provide drug product to. We continue to work with the regulators to make additional step-ups and we have plans to make step-ups later this year and in 2023 as well. So, that is a picture that month-to-month, quarter-to-quarter continues to improve. And we should have more to share in terms of our outlook for 2023 as we get closer to the end of this year.

當然，謝謝，尼克。好問題。是的，就我們可以向其提供藥品的患者而言，我們在每週的產能方面一直在不斷提高。我們將繼續與監管機構合作以進行更多升級，我們計劃在今年晚些時候和 2023 年也進行升級。因此，這是一個逐月、逐季度持續改善的情況。隨著我們接近今年年底，我們應該有更多關於 2023 年的展望可以分享。

Awesome. Thanks so much and congrats on the update.

驚人的。非常感謝並祝賀更新。

Daina Graybosch, SEB Securities.

SEB 證券的戴娜·格雷博斯 (Daina Graybosch)。

A couple follow-ups on the previous ones. Can you just remind us the statistical design for KarMMA-3, in particular what triggered the events that triggered this interim? And what were the primary and secondary? And if you will, since you said the OR is secondary, how far down the secondary hierarchy you were able to get?

對之前的一些後續行動。您能否提醒我們 KarMMA-3 的統計設計，特別是什麼觸發了觸發此過渡的事件？什麼是主要和次要的？如果你願意，既然你說 OR 是次要的，那麼你能得到的次要層次結構有多遠？

And then on cost, could you help break down this -- the net cash spend you expect, the $245 million to $265 million, Chip? Can you help us understand how much of that is on discovery on your early clinical programs, and then on ABECMA programs? And then how much is being spent, as you said, on supporting scale up and manufacturing for ABECMA? Thank you.

然後在成本方面，你能幫忙分解一下嗎——你預期的淨現金支出，2.45 億美元到 2.65 億美元，奇普？您能否幫助我們了解其中有多少是在您的早期臨床項目中發現的，然後是 ABECMA 項目中的發現？然後，正如您所說，在支持 ABECMA 的擴大規模和製造方面花費了多少？謝謝你。

So first question here, I'll pass that off again to Steve, but maybe he can go through to top line some of the design questions. But we're not dancing down the chart. The data that we've given so far is what was driven, that was PFS and OR, both of which were statistically significant. So, that's the extent of the data we'll be sharing at this point. But if you zoom out I'm sure Steve has a few comments and then we'll go over to Chip. Steve?

所以這裡的第一個問題，我會再次把它交給史蒂夫，但也許他可以回答一些設計問題。但我們並沒有在圖表上跳舞。到目前為止，我們提供的數據是驅動因素，即 PFS 和 OR，這兩個數據都具有統計學意義。所以，這就是我們此時將要共享的數據的範圍。但是，如果您縮小範圍，我敢肯定史蒂夫有一些評論，然後我們將轉到 Chip。史蒂夫?

Yes, as Nick mentioned, the primary endpoint was PFS and that was the primary endpoint for which the interim analysis statistics were driven. The key secondary endpoints were response rate and, as we mentioned, we can say that both the PFS and the overall response rate was significantly improved. Overall survival is a key secondary endpoint and the follow-up for overall survival remains ongoing. I'm not sure if there were any other, Daina, questions that --.

是的，正如尼克提到的，主要終點是 PFS，這是驅動中期分析統計數據的主要終點。關鍵的次要終點是反應率，正如我們所提到的，我們可以說 PFS 和總體反應率都得到了顯著提高。總生存期是一個關鍵的次要終點，總生存期的隨訪仍在進行中。我不確定是否還有其他問題，戴娜——。

If you could talk about what specifically was the three specified triggers to do the PFS analysis.

如果您能談談執行 PFS 分析的三個指定觸發器具體是什麼。

Yes, I'm honestly not sure how much I could really get into that to be very truthful.

是的，老實說，我不確定我能在多大程度上真正做到這一點。

But it was preplanned, it's preplanned (multiple speakers).

但它是預先計劃好的，它是預先計劃好的（多位發言者）。

Yeah. It was preplanned in terms of events. So, it was an event driven preplanned analysis.

是的。它是根據事件預先計劃好的。因此，這是一個事件驅動的預先計劃分析。

Great and, Chip, do you want to cover off a little bit of the breakdown of the net?

太好了，Chip，你想掩蓋一點網絡故障嗎？

Yes, so -- Daina, it's a good question and there is disclosure in our 10-Q that can give you an even better feel for how the investments across programs meter out. From a development perspective, ide-cel remains our biggest investment with the various KarMMa studies and investments in manufacturing scale up. 369 is the next largest, and DARIC-33 also a clinical stage program. The balance is earlier stage research programs, collaborations with Regeneron and other partners there.

是的，所以--戴娜，這是一個很好的問題，我們的 10-Q 中有披露可以讓您更好地了解跨項目的投資如何計量。從發展的角度來看，ide-cel 仍然是我們最大的投資，因為 KarMMa 的各種研究和對製造規模的投資正在擴大。 369 次之，DARIC-33 也是一個臨床階段項目。平衡是早期階段的研究計劃，與再生元和其他合作夥伴的合作。

On the manufacturing side, I can just comment we've invested both on the drug product side together with BMS in terms of scaling that capacity, and then, as I mentioned, continuing to work on vector supply and increasing scale there.

在製造方面，我可以評論說，我們在擴大產能方面與 BMS 一起在藥品方面進行了投資，然後，正如我所提到的，繼續致力於載體供應並擴大規模。

And one thing I might just add there, one of the things we've been working on, and Chip referenced it in his script -- or we both did -- which was as we spun the company, we continue to make sure we're fit for purpose across the business. And as we level in on that, that's something that's still certainly ongoing and we're making good progress on.

我可能會在其中添加一件事，這是我們一直在做的事情，Chip 在他的腳本中引用了它——或者我們都這樣做了——在我們拆分公司時，我們將繼續確保我們重新適應整個業務的目的。當我們對此有所了解時，這肯定仍在進行中，我們正在取得良好進展。

But we feel pretty good about the team we have for the purpose that we have, that is not just ABECMA but is also very much believing in the future of the technology and approach that we have, and that's what I was referring to a little bit there. So, a pretty aggressive investment in that side as well as research and what we call Horizon S is certainly ongoing in there. But the bigger driver certainly for the burn and the burn increase has to do with ABECMA.

但是我們對我們擁有的團隊感到非常滿意，這不僅僅是 ABECMA，而且非常相信我們所擁有的技術和方法的未來，這就是我所指的一點那裡。因此，在這方面的相當積極的投資以及研究和我們所說的 Horizon S 肯定正在進行中。但燒錢和燒錢增加的更大驅動因素肯定與 ABECMA 有關。

Yaron Werber, Cowen.

亞倫·沃伯，考恩。

Congrats on the data. I know you can't say a lot, but I wanted to just probe a little bit. When you're thinking about second to fourth line, you can have doublet or you really have triplet therapies here. It could be again -- did you expect some patients to get Darzalex again, or are they typically getting another IMiD and sort of another PI?

恭喜數據。我知道你不能說很多，但我只想稍微探討一下。當您考慮二線到四線時，您可以使用雙聯療法，或者您真的有三聯療法。可能會再次出現——您是否期望一些患者再次獲得 Darzalex，或者他們通常會獲得另一個 IMiD 和某種其他 PI？

And if you can, what do you think is a comp in terms of prior data with respect to PFS and ORR? These are obviously triple exposed, so the question is what they were getting at that point.

如果可以的話，您認為在 PFS 和 ORR 方面的先驗數據方面是什麼比較？這些顯然是三重暴露的，所以問題是他們當時得到了什麼。

And then secondly for Chip, we're beginning to see a little bit of a range for you now for the collaboration with Bristol on OpEx. And I know this is going to be, obviously, variable depending on spending and clinical supply, etc. But can you give us some brackets to where you are on -- toward profitability and sustainability? Because it sounds like the clinical spend is now getting a lot more manageable and predictable? You only have essentially one big study and one small study ongoing. Thank you.

其次，對於 Chip，我們現在開始看到與 Bristol 在 OpEx 上的合作的一些範圍。而且我知道這顯然會根據支出和臨床供應等因素而變化。但是您能否給我們一些括號來說明您所處的位置——朝著盈利能力和可持續性發展？因為聽起來臨床支出現在變得更易於管理和可預測？您基本上只有一項大型研究和一項小型研究正在進行中。謝謝你。

Excellent questions on that. So, let me kick that over to Steve because I think those are an important set of questions to make sure we understand the triplet and the expectations thereof. So, Steve, why don't you cover off on that and we'll jump to Chip after?

很好的問題。所以，讓我把它交給史蒂夫，因為我認為這些是一組重要的問題，以確保我們理解三元組及其期望。那麼，史蒂夫，你為什麼不掩飾一下，然後我們會跳到奇普？

Yes, sure. No, that is an excellent question. So, let me reply in two -- make two points in that regard. The first point is that the standard of care arm in the randomization was the choice of five approved combination therapies and the investigators chose which combination therapy that they would use if patients were randomized to that arm and it's a regimen that they could not have had before so that it increases the potential likelihood of benefit.

是的，當然。不，這是一個很好的問題。所以，讓我回答兩點——在這方面提出兩點。第一點是，隨機分組中的護理標準是選擇五種已獲批准的聯合療法，如果患者被隨機分配到該組，研究人員會選擇他們將使用的聯合療法，這是他們以前無法接受的治療方案從而增加受益的潛在可能性。

In terms of your question what, would be expected, I think that is an important question. Because these patients are: one, have been refractory to their last line of therapy, which means that they have progressed within 90 days of their last line of therapy; and second, as you alluded to, they were triple exposed.

關於你的問題，我認為這是一個重要的問題。因為這些患者是： 一，對最後一線治療無效，這意味著他們在最後一線治療後的 90 天內出現了進展；其次，正如你所提到的，它們是三重暴露的。

And if you look in the literature and across the studies, there's not an awful lot of large databases on the outcome of patients who are triple exposed, but the totality of the data suggests that if you fail daratumumab, your overall response and your performance status both were extremely poor.

如果你查看文獻和研究，沒有太多關於三次暴露患者結果的大型數據庫，但總體數據表明，如果你失敗了 daratumumab，你的整體反應和你的表現狀態兩人都非常貧窮。

So, we had some ideas of what this might look like and really built our study upon that. But what we were very encouraged was in this study that ABECMA really had a statistically significant -- what we believe is a clinically significant improvement over the poor response rate and poor performance that is seen in patients who had failed daratumumab.

所以，我們對這可能是什麼樣子有了一些想法，並真正建立了我們的研究。但我們非常鼓舞的是，在這項研究中 ABECMA 確實具有統計學意義——我們認為這是對 daratumumab 失敗患者的不良反應率和不良表現的臨床顯著改善。

Thanks, Yaron. Good questions. Sorry, we forgot to skip over to Chip here. Let him out of jail. Chip?

謝謝，亞龍。好問題。抱歉，我們忘了在這裡跳到 Chip。讓他出獄。芯片？

Thanks for that Nick. Yaron, good question. In terms of how to think about the ABECMA spend, you're right on the noncommercial side, those OpEx related to the clinical studies are in a more predictable range. For the existing studies there we would predict that that glide path continues, although I would refer you to the quote in today's press release saying, I think we are thinking together with BMS about future investments in ABECMA.

謝謝那個尼克。亞龍，好問題。就如何考慮 ABECMA 支出而言，您在非商業方面是正確的，與臨床研究相關的運營支出處於更可預測的範圍內。對於那裡的現有研究，我們預計該下滑路徑將繼續，儘管我想請您參考今天新聞稿中的引述，我認為我們正在與 BMS 一起考慮未來對 ABECMA 的投資。

And you'll hear more from us on that throughout the second half of this year as those plants develop. But these data today I think give us increasing conviction in the long-term role of ABECMA in the treatment of myeloma.

隨著這些植物的發展，你會在今年下半年聽到更多關於這方面的信息。但我認為今天的這些數據讓我們越來越相信 ABECMA 在治療骨髓瘤中的長期作用。

And then on the path to sustained ability, profitability, I think what you're seeing in this quarter's results is increased investment on the manufacturing side. And I think our priority is getting to all of the patients that we can, making those investments to make those ramps in terms of monthly and quarterly capacity. And that is going to have an impact in the short term hearing from us today in terms of that path to profitability.

然後在通往持續能力和盈利能力的道路上，我認為你在本季度的業績中看到的是製造業方面的投資增加。我認為我們的首要任務是盡可能地接觸到所有患者，進行這些投資以提高每月和每季度的產能。這將在短期內對我們今天聽到的關於盈利之路的影響產生影響。

But we think that trade-off is justified given the patients who continue to queue and wait for this therapy. So, longer-term as we head into 2023 and beyond, we think that picture is attractive and it's an attractive commercial business. But in the short-term we're making the right investments to maximize the ABECMA potential.

但我們認為，考慮到繼續排隊等待這種治療的患者，這種權衡是合理的。因此，從長遠來看，隨著我們進入 2023 年及以後，我們認為這幅畫很有吸引力，而且它是一個有吸引力的商業業務。但在短期內，我們正在進行正確的投資，以最大限度地發揮 ABECMA 的潛力。

Thanks, Chip. And Yaron, you and I have talked about this a couple times. But I think as you zoom back out, there are a lot of questions around the myeloma market opportunity for CAR T broadly. And I think that's been dispelled, the interest is there. Then there is where does ABECMA fit relative to [siltasalin], is there room for both, etc., etc. I think that also is becoming quite clear in our opinion saying there is ample room here to service an unfortunately big market opportunity with these patients who are just desperate for help.

謝謝，奇普。 Yaron，你和我已經談過幾次了。但我認為，當你縮小範圍時，關於 CAR T 的骨髓瘤市場機會存在很多問題。我認為這已經被消除了，人們的興趣就在那裡。然後是 ABECMA 相對於 [siltasalin] 適合的位置，兩者都有空間，等等等等。我認為這也變得非常清楚，我們認為這裡有足夠的空間來服務這些不幸的巨大市場機會急需幫助的患者。

And now as we start thinking about earlier lines, I think we have that growing conviction and excitement. So, pretty much on every turn that we've taken we get more excited. But you're absolutely right, it's still bouncy -- a lot less bouncy than it was 6 to 12 months ago, still a little bouncy right now as far as the execution side and being able to level that off.

現在，當我們開始考慮早期的台詞時，我認為我們有越來越多的信念和興奮。因此，幾乎在我們採取的每一個轉彎時，我們都會變得更加興奮。但你是絕對正確的，它仍然是有彈性的 - 比 6 到 12 個月前的彈性要少得多，就執行方面而言，現在仍然有一點彈性，並且能夠將其拉平。

But as we get into 2023 here, we feel a high degree of confidence along with BMS. And that -- we're very pleased with BMS and they are paying attention frankly like -- I couldn't even possibly have imagined a better partner in this regard. And I think they're certainly very committed to the cell therapy space in that regard. So, hopefully, Yaron, that helps.

但是當我們在這裡進入 2023 年時，我們對 BMS 充滿信心。而且——我們對 BMS 非常滿意，他們坦率地關注著——我什至無法想像在這方面有更好的合作夥伴。我認為他們在這方面肯定非常致力於細胞治療領域。所以，希望亞龍，這會有所幫助。

Matthew Harrison, Morgan Stanley.

馬修哈里森，摩根士丹利。

So, maybe just one follow-up question on the KarMMA-3 interim analysis. So, I'm just wondering whether you can comment on -- because you mentioned this is a planned interim analysis. So, I'm just wondering whether you can comment on whether -- how many interim analyses you have planned in total for the PFS.

所以，也許只是關於 KarMMA-3 中期分析的一個後續問題。所以，我只是想知道你是否可以發表評論——因為你提到這是一項計劃中的中期分析。所以，我只是想知道您是否可以評論您是否為 PFS 計劃了總共多少次中期分析。

And then my second question is on the 369 and the DARIC33 program. So, you mentioned that you'll have a data readout for these two programs later this year. So, can you discuss what kind of safety data we could get for this year for these two programs? Thanks.

然後我的第二個問題是關於 369 和 DARIC33 程序的。所以，您提到您將在今年晚些時候為這兩個程序讀取數據。那麼，您能否討論一下我們今年可以獲得這兩個項目的哪些安全數據？謝謝。

Yeah, I'll pass that off to Steve. I don't think we've outlined the specifics of a statistical plan here. But, Steve, do you want to comment on that and then I can take the high level 369 and DARIC question?

是的，我會把它交給史蒂夫。我認為我們沒有在這裡概述統計計劃的細節。但是，史蒂夫，你想對此發表評論，然後我可以回答高級別的 369 和 DARIC 問題嗎？

Yes, I mean this was our first interim analysis for superiority.

是的，我的意思是這是我們對優勢的第一次中期分析。

Yes. So, I'm just wondering whether -- I mean just whether you will have any additional interim analysis or this will be the only one analysis on PFS? I know you'll have other interim analysis on OS.

是的。所以，我只是想知道是否——我的意思是您是否會有任何額外的中期分析，或者這將是唯一一項關於 PFS 的分析？我知道您將對操作系統進行其他中期分析。

Well, we're following for OS and we're planning on presenting all of the data hopefully at a meeting later this year.

好吧，我們正在關注 OS，我們計劃在今年晚些時候的會議上展示所有數據。

(multiple speakers).

（多個揚聲器）。

Just to be clear, if I'm getting you right, though, we met our primary employee, right?

需要明確的是，如果我沒聽錯的話，我們遇到了我們的主要員工，對吧？

So, that's the key bit, primary endpoint was met, it was meant early. And that's something we're excited about just because we were not anticipating this, because you expect the full length of the study. So, we were excited to certainly see that.

所以，這是關鍵，主要終點已經達到，這意味著早期。這正是我們感到興奮的事情，因為我們沒有預料到這一點，因為您期望研究的完整長度。所以，我們很高興看到這一點。

On the 369, DARIC33, that obviously depends on enrollment as we go towards the end of this year and the beginning of next. And I think we've consistently said first half of next year is when you're going to start seeing more substantive data. But in the beginning it's safety, how are we looking at getting into these patients. And then you start seeing how -- hopefully the impact that it has.

在 369、DARIC33 上，這顯然取決於今年年底和明年年初的招生情況。我認為我們一直在說明年上半年是你將開始看到更多實質性數據的時候。但一開始是安全的，我們如何看待這些患者。然後你開始看到 - 希望它產生的影響。

But a lot of this and the timing of this is something we're looking at very much depends on how the dosing and how the safety goes, etc. But beyond that, that should be a rough expectation, end of this year and first half of next, to get good visibility into both those programs.

但是很多這種情況和發生這種情況的時間是我們正在考慮的事情，很大程度上取決於劑量和安全性如何等等。但除此之外，這應該是一個粗略的預期，今年年底和上半年接下來，為了更好地了解這兩個程序。

Okay, thank you.

好的謝謝你。

Operator, next question?

接線員，下一個問題？

There are no further questions at this time. I would now like to turn the conference back to Nick Leschly for closing remarks.

目前沒有其他問題。我現在想把會議轉回給 Nick Leschly 來做閉幕詞。

Just want to thank everybody, and apologies for the quick turnaround on this. So, appreciate you guys making the time and effort to jump on the call with us here. If anyone has additional questions or anything they'd like to dig more into, please follow up with us directly, get in touch with our investor group and we're more than happy to follow up. Thank you, everybody, and have a great day.

只是想感謝大家，並為這方面的快速轉變表示歉意。所以，感謝你們抽出時間和精力與我們通話。如果有人有其他問題或他們想深入研究的任何內容，請直接與我們聯繫，與我們的投資者組聯繫，我們非常樂意跟進。謝謝大家，祝您有美好的一天。

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

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。