bluebird bio Inc (BLUE) 2022 Q4 法說會逐字稿

Good morning, ladies and gentlemen, thank you standing by. Welcome to the bluebird's bio Fourth Quarter and Full Year 2022 Earnings Conference Call. (Operator Instructions) Please note that today's conference may be recorded.

早上好，女士們，先生們，謝謝你們的支持。歡迎來到藍鳥生物第四季度和 2022 年全年收益電話會議。 （操作員說明）請注意，今天的會議可能會被錄製。

I will now hand the conference over to your speaker host, Courtney O'Leary of Investor Relations. Please go ahead.

我現在將把會議交給您的演講主持人，投資者關係部的 Courtney O'Leary。請繼續。

Good morning, everyone, and thank you for joining today's call. I'm Courtney O'Leary, Investor Relations of bluebird bio.

大家早上好，感謝您參加今天的電話會議。我是 bluebird bio 投資者關係部的 Courtney O'Leary。

Before we begin, let me review our safe harbor statement.

在我們開始之前，讓我回顧一下我們的安全港聲明。

Today's discussion contains statements that are forward-looking under the Private Securities Litigation Reform Act of 1995, including expectations regarding our future financial results and financial position, in addition to statements of the company's plans, expectations or intentions regarding regulatory progress and commercialization plans.

今天的討論包含根據 1995 年《私人證券訴訟改革法案》作出的前瞻性陳述，包括對我們未來財務業績和財務狀況的預期，以及公司關於監管進展和商業化計劃的計劃、預期或意圖的陳述。

Such statements are based on current expectations and assumptions that are subject to risks and uncertainties and involve a number of risk factors that could cause actual results to differ materially from projected results. A description of these risks is contained in our filings with the SEC, which are available on the Investor Relations section of our website, www.bluebirdbio.com.

此類陳述基於當前的預期和假設，這些預期和假設存在風險和不確定性，並涉及許多可能導致實際結果與預期結果存在重大差異的風險因素。這些風險的描述包含在我們提交給美國證券交易委員會的文件中，這些文件可在我們網站 www.bluebirdbio.com 的投資者關係部分找到。

Today's agenda is as follows: Andrew Obenshain, our CEO, is going to provide some brief opening remarks and discuss our lovo-cel BLA submission. Then Tom Klima, Chief Commercial and Operating Officer, will highlight positive momentum from our ZYNTEGLO and SKYSONA commercial launches. And finally, Chris Krawtschuk, our Chief Financial Officer, will provide some color on our finances before opening the call up for Q&A, where the team will be joined by Rich Colvin, Chief Medical Officer.

今天的議程如下：我們的首席執行官 Andrew Obenshain 將提供一些簡短的開場白並討論我們提交的 lovo-cel BLA。然後，首席商務和運營官 Tom Klima 將重點介紹我們的 ZYNTEGLO 和 SKYSONA 商業發布帶來的積極勢頭。最後，我們的首席財務官 Chris Krawtschuk 將在開始問答之前提供一些關於我們財務的顏色，首席醫療官 Rich Colvin 將加入該團隊。

With that, I will turn the call over to Andrew.

有了這個，我會把電話轉給安德魯。

Thanks, Courtney, and thank you, everyone, on the line for joining the call this morning. bluebird's vision and mission are stronger than ever. Built on a strong foundation of research and clinical development, today, bluebird is making gene therapy a reality for patients and families in the real world. And I'm immensely proud of the efforts of our entire company as we continue to lead the way for the gene therapy field, proving the commercial model for ex vivo gene therapy with ZYNTEGLO and SKYSONA, and continue to make meaningful progress towards bringing gene therapies to patients and their families with sickle cell disease in the U.S.

謝謝 Courtney，也謝謝大家今天早上在線加入電話會議。 bluebird 的願景和使命比以往任何時候都更加強大。基於強大的研究和臨床開發基礎，今天，bluebird 正在使基因治療成為現實世界中患者和家庭的現實。我為我們整個公司的努力感到無比自豪，因為我們繼續引領基因治療領域，證明了 ZYNTEGLO 和 SKYSONA 體外基因治療的商業模式，並繼續在基因治療方面取得有意義的進展美國鐮狀細胞病患者及其家屬

As Courtney mentioned, Tom and Chris will share updates today on our commercial progress and our financial position. But to start, I will focus my comments on the lovo-cel regulatory path. As noted in our press release this morning, we continue to progress our lovo-cel BLA, but speaking plainly, we will likely miss the Q1 2023 submission goal. Our file is completely written and ready for submission, but we are awaiting feedback from the FDA on CMC.

正如 Courtney 提到的，Tom 和 Chris 今天將分享我們的商業進展和財務狀況的最新消息。但首先，我將把我的評論集中在 lovo-cel 監管路徑上。正如我們今天早上的新聞稿中指出的那樣，我們繼續推進我們的 lovo-cel BLA，但坦率地說，我們很可能會錯過 2023 年第一季度的提交目標。我們的文件已完整編寫並準備提交，但我們正在等待 FDA 對 CMC 的反饋。

To provide context, I will give a time line of our recent interactions with the FDA. In December, we completed drug products comparability analysis and provide the FDA with a snapshot of comparability data.

為了提供背景信息，我將給出我們最近與 FDA 互動的時間表。 12 月，我們完成了藥品可比性分析，並向 FDA 提供了可比性數據的快照。

In February, we received feedback and questions from the FDA and request that these responses be provided prior to the submission of the BLA. Our team did incredible work and pulled forward the full CMC module, along with additional information and provided them with the agency in the first week of March.

2 月，我們收到了 FDA 的反饋和問題，並要求在提交 BLA 之前提供這些答复。我們的團隊做了令人難以置信的工作，推出了完整的 CMC 模塊以及其他信息，並在 3 月的第一周向該機構提供了這些信息。

We believe that this complete data package supports comparability and addresses the questions asked. Now while there's no set time line for the FDA to respond, the agency has conveyed its commitment to a timely response, and we believe that this could ultimately set the stage for a smooth review. We anticipate feedback from the FDA within a matter of weeks, and we'll move quickly to expedite our BLA pending the resolution of the comparability questions. And I will reiterate the file is otherwise complete and ready for submission.

我們相信這個完整的數據包支持可比性並解決了提出的問題。現在，雖然 FDA 沒有設定回應的時間表，但該機構已表達了及時回應的承諾，我們相信這最終可以為順利審查奠定基礎。我們預計將在幾週內收到 FDA 的反饋，我們將迅速採取行動加快我們的 BLA，等待可比性問題的解決。我會重申該文件在其他方面是完整的，可以提交了。

We are grateful to the FDA for the ongoing open dialogue and appreciate the importance of ensuring the agency understands the full content of our analyses. To take a step back, I'd like to remind everyone of the depth of preparation that has gone into both the manufacturing and the clinical development of lovo-cel and the work that will be reflecting the BLA.

我們感謝 FDA 正在進行的公開對話，並認識到確保該機構了解我們分析的全部內容的重要性。退一步說，我想提醒大家注意 lovo-cel 的製造和臨床開發以及將反映 BLA 的工作的深度準備。

First, manufacturing. CMC modules are the largest sections in any gene therapy BLA. With that in mind, bluebird has an active and collaborative dialogue with the FDA on comparability over the past several years. We've also incorporated learnings from SKYSONA and ZYNTEGLO into our BLA for lovo-cel.

第一，製造業。 CMC 模塊是任何基因治療 BLA 中最大的部分。考慮到這一點，藍鳥在過去幾年中與 FDA 就可比性進行了積極和協作的對話。我們還將 SKYSONA 和 ZYNTEGLO 的經驗融入到我們的 lovo-cel BLA 中。

Now as a reminder for those newer to the bluebird story, through the course of clinical development for lovo-cel, we made improvements in the manufacturing of our lentiviral vector and of our lovo-cel drug product, including changing manufacturing processes, manufacturing facilities and testing sites. This included changing from an adherence to a suspension process to ensure that we would meet the patient demand at launch with a robust, scalable and commercially compliant process for the 20,000 patients we believe may be eligible for gene therapy.

現在提醒那些剛接觸 bluebird 故事的人，通過 lovo-cel 的臨床開發過程，我們改進了慢病毒載體和 lovo-cel 藥物產品的製造，包括改變製造工藝、製造設施和測試站點。這包括從依從性轉變為暫停過程，以確保我們能夠在啟動時為我們認為可能有資格接受基因治療的 20,000 名患者提供一個穩健、可擴展且符合商業標準的過程來滿足患者的需求。

Now some of these changes occurred following the completion of our HGB-206 study, which forms the primary evidence base for safety and efficacy to support the BLA. Therefore, the industry required that we demonstrate vector and drug products comparability, where we collect and analyze all the manufacturing data generated from our commercial processes in our commercial facilities and compare them to the manufacturing data generated from our clinical trials in our clinical facilities.

現在，其中一些變化是在我們的 HGB-206 研究完成後發生的，該研究構成了支持 BLA 的安全性和有效性的主要證據基礎。因此，行業要求我們證明載體和藥物產品的可比性，我們收集和分析在我們的商業設施中從我們的商業過程中生成的所有製造數據，並將它們與我們在臨床設施中的臨床試驗中生成的製造數據進行比較。

These analysis were completed at the end of last year. We remain extremely confident in the quality of our overall BLA submission package. And as part of that, we may move to our impressive clinical data. Our clinical data reflects the most robust data available with the longest follow-up across any gene therapy program for sickle cell disease, and it includes more than 50 patients treated and multiple patients followed for more than 6 years. The strength of this package has been reinforced by positive interactions with the FDA.

這些分析是在去年底完成的。我們對整體 BLA 提交包的質量充滿信心。作為其中的一部分，我們可能會轉向我們令人印象深刻的臨床數據。我們的臨床數據反映了所有鐮狀細胞病基因治療計劃中最可靠的數據和最長的隨訪時間，其中包括 50 多名接受治療的患者和多名隨訪超過 6 年的患者。與 FDA 的積極互動加強了該包裝的優勢。

The BLA submission will be based on efficacy results from 36 patients in the HGB-206 Group C cohort and will include a median of 32 months of follow-up and more than 4.5 years of follow-up for some patients. We anticipate that the BLA submission will also include efficacy results from 2 patients with 18 months of follow-up in the HGB-210 study.

BLA 提交將基於 HGB-206 C 組隊列中 36 名患者的療效結果，並將包括中位隨訪 32 個月和部分患者超過 4.5 年的隨訪。我們預計提交的 BLA 還將包括 2 名在 HGB-210 研究中隨訪 18 個月的患者的療效結果。

We plan to request priority review for patients 12 and older with the history of vaso-occlusive events. Importantly, at this time, we are not forecasting any change to our commercial plans for lovo-cel and are continuing to anticipate an early 2024 launch. And we are really looking forward with -- to delivering on the promise of gene therapy for sickle cell patients who have been waiting for therapies like this.

我們計劃要求對 12 歲及以上有血管閉塞事件史的患者進行優先審查。重要的是，目前我們預測 lovo-cel 的商業計劃不會有任何變化，並繼續預計 2024 年初推出。我們真的很期待——為一直在等待這種治療的鐮狀細胞患者實現基因治療的承諾。

As Tom will discuss, the foundation that we are building today to bring ZYNTEGLO to patients will directly translate into our ability to bring lovo-cel to patients. We have the same treating positions, the same QTC network and the same payer relationships. Bluebird has over a year head start launching a gene therapy in inherited hemoglobin disorders versus any other gene therapy program.

正如湯姆將要討論的那樣，我們今天為將 ZYNTEGLO 帶給患者而建立的基礎將直接轉化為我們將 lovo-cel 帶給患者的能力。我們擁有相同的治療職位、相同的 QTC 網絡和相同的付款人關係。與任何其他基因治療計劃相比，Bluebird 已經領先一年多時間推出遺傳性血紅蛋白疾病的基因治療。

And with that, I will turn it over to Tom to highlight how our launches are progressing.

有了這個，我將把它交給湯姆來強調我們的發布進展情況。

Thanks, Andrew, and good morning, everyone. It's exciting to be here this morning to discuss the strong momentum we've built for our 2 approved gene therapies: ZYNTEGLO and SKYSONA. There's a lot of attention and noise in gene therapy these days, but the reality is that bluebird, we are living it every day and bringing these important, onetime treatments to patients.

謝謝，安德魯，大家早上好。很高興今天早上來到這裡討論我們為我們的 2 種獲批基因療法建立的強勁勢頭：ZYNTEGLO 和 SKYSONA。這些天基因治療引起了很多關注和噪音，但現實是藍鳥，我們每天都在生活，並為患者提供這些重要的一次性治療。

During the recent field visit, I received feedback from health care professionals in our QTCs. They praised bluebird for our continued partnership and for leading the way with our deep expertise and through transparency. They reinforce that our trusted partnership over the years will be an important differentiator.

在最近的實地考察中，我收到了 QTC 醫療保健專業人員的反饋。他們讚揚 bluebird 與我們持續的合作夥伴關係，以及憑藉我們深厚的專業知識和透明度引領潮流。它們強化了我們多年來值得信賴的伙伴關係將成為一個重要的差異化因素。

As a reminder, our commercial strategy is built on 3 key pillars, which are fundamental to success in gene therapy launches. First, patients and their families are at the center of everything we do, and they are the ultimate decision-maker. Our continued engagement over the past decade and our ongoing education about gene therapy, are critical for adoption.

提醒一下，我們的商業戰略建立在 3 個關鍵支柱之上，它們是基因治療成功推出的基礎。首先，患者和他們的家人是我們所做一切的中心，他們是最終的決策者。我們在過去十年中的持續參與以及我們對基因治療的持續教育對於採用至關重要。

Second and unique to ex vivo gene therapies, we're building a network of qualified treatment centers or QTCs where the cell collection and infusion of our therapies takes place. These centers of excellence are both part of our supply chain, but there are also ambassadors for patient care and ultimately for our therapies.

其次，也是離體基因療法的獨特之處，我們正在建立一個合格的治療中心或 QTC 網絡，我們的療法的細胞收集和輸注在這裡進行。這些卓越中心都是我們供應鏈的一部分，但也有患者護理大使，最終也是我們治療的大使。

And finally, access and reimbursement, an area where we have innovated as pricing and securing coverage for a one-time therapy is certainly not the same as pricing of chronic therapy. Importantly, we are seeing success in all 3 areas since launch with momentum continuing to build.

最後，獲取和報銷，這是我們創新的領域，因為一次性治療的定價和保障範圍肯定與慢性治療的定價不同。重要的是，自推出以來，我們在所有 3 個領域都取得了成功，並且勢頭不斷增強。

For ZYNTEGLO, we are seeing significant patient demand and uptake highlighting the tremendous unmet need and interest in gene therapy from patients with beta thalassemia. To date, there have been 5 patient starts or cell collections for patients with beta thalassemia coming from our early Wave 1 QTCs. This momentum will continue to build as we grow our QTC network. And notably, as launch progresses, we are already advancing our plans to expand our manufacturing capacity to meet growing projected demand.

對於 ZYNTEGLO，我們看到患者的大量需求和吸收凸顯了 β 地中海貧血患者對基因治療的巨大未滿足需求和興趣。迄今為止，已有 5 名患者開始或從我們早期的第 1 波 QTC 中收集了 5 名 β 地中海貧血患者的細胞。隨著我們發展 QTC 網絡，這種勢頭將繼續增強。值得注意的是，隨著發布的進行，我們已經在推進擴大製造能力的計劃，以滿足不斷增長的預期需求。

On the reimbursement front, we're pleased to report that things continue to go very well. On average, prior authorization is taking only 2 weeks, a strong indicator that payers recognize the value of ZYNTEGLO in a rare disease with significant unmet medical need. Most important, we continue to see zero ultimate denials.

在報銷方面，我們很高興地報告事情繼續進展順利。平均而言，預先授權僅需 2 週，這是一個強有力的指標，表明付款人認識到 ZYNTEGLO 在醫療需求未得到滿足的罕見疾病中的價值。最重要的是，我們繼續看到零最終拒絕。

Switching to QTCs. We have expanded our QTC network as planned with 12 centers activated to date, representing a mix of both pediatric and adult centers. Approximately 30 additional QTCs are in the onboarding stage or MSA negotiation phase and the company remains on track to scale to between 40 and 50 QTCs by the end of 2023. This progress is because of our preparation and is also a signal of patient interest and enthusiasm among physicians for ex vivo LVV gene therapy.

切換到 QTC。我們已按計劃擴大了我們的 QTC 網絡，迄今為止已激活 12 個中心，包括兒科和成人中心。大約 30 個額外的 QTC 處於入職階段或 MSA 談判階段，公司仍有望在 2023 年底之前將 QTC 規模擴大到 40 到 50 個之間。這一進展是由於我們的準備，也是患者興趣和熱情的信號在體外 LVV 基因治療的醫生中。

Importantly, as Andrew mentioned, the efforts we're making with ZYNTEGLO will directly translate to the potential launch of lovo-cel for sickle cell disease in 3 key ways. First, and very simply, the treating physicians are the same. Second, the bluebird QTC network will be the same. This means that from an operational standpoint, our expectation is that we will reduce the lead time for QTC activation for months to weeks because of the synergies. We're really doing the groundwork now so that we will be ready to begin treating patients shortly after approval.

重要的是，正如安德魯提到的那樣，我們與 ZYNTEGLO 所做的努力將直接轉化為可能以 3 種關鍵方式推出用於治療鐮狀細胞病的 lovo-cel。首先，非常簡單，主治醫生是相同的。第二，bluebird QTC網絡將是相同的。這意味著，從運營的角度來看，我們的期望是，由於協同作用，我們將 QTC 激活的準備時間縮短數月至數週。我們現在確實在做基礎工作，以便我們準備好在批准後不久開始治療患者。

And lastly, with payers, we're already being recognized as leading the way with our approach to value demonstration and innovation with our outcomes-based agreements, and this established credibility will carry forward. We will continue to provide updates on key metrics from the Zynteglo launch, including a number of patient starts as launch progresses. We believe the most important metric for you to keep an eye on is the number of patient starts.

最後，對於付款人，我們已經被公認為通過我們基於結果的協議進行價值展示和創新的方法處於領先地位，這種建立的信譽將繼續下去。我們將繼續提供有關 Zynteglo 發布的關鍵指標的更新，包括隨著發布的進展而啟動的一些患者。我們認為您需要關注的最重要指標是患者開始治療的數量。

For SKYSONA, cell collection has been completed for 2 patients. And on March 16, the first commercial infusion was completed at Boston Children's Hospital. I cannot overstate what an incredible moment this was for this patient and his family for the clinicians and researchers and for the entire ALD community.

對於 SKYSONA，已經完成了 2 名患者的細胞收集。而在 3 月 16 日，第一例商業輸液在波士頓兒童醫院完成。對於這位患者及其家人、臨床醫生和研究人員以及整個 ALD 社區來說，我無法誇大這是多麼令人難以置信的時刻。

CALD is a devastating disease, and this was a milestone celebrated by all those who have advocated, invested and fought for treatment options for many, many years. It is difficult to summarize the passion and the pride we all have in being able to deliver SKYSONA to that young boy and his family.

CALD 是一種毀滅性的疾病，這是一個里程碑，所有多年來倡導、投資和爭取治療方案的人都在慶祝這一里程碑。很難用語言來概括我們能夠將 SKYSONA 帶給那個小男孩和他的家人的熱情和自豪。

In conclusion, I'm extremely proud of the progress and dedication of our team and how we're leading the way as a commercial gene therapy company.

總之，我為我們團隊的進步和奉獻精神以及我們作為一家商業基因治療公司如何引領潮流而感到非常自豪。

With that, I'll turn it over to Chris to talk through the financials.

有了這個，我會把它交給克里斯來討論財務問題。

Thanks, Tom, and good morning, everyone. It's gratifying to be speaking with you publicly as bluebird's CFO for the first time since I joined the company back in November of 2022. We now stand in 2023 in the strongest financial position Bluebird has had, since we emerged as a dedicated gene therapy company in November of 2021. I'm immensely proud of the work our bluebird team has done to get us to this point and over the past few months.

謝謝，湯姆，大家早上好。自從我於 2022 年 11 月加入公司以來，第一次以 bluebird 的首席財務官的身份與您公開交談，我感到很高興。我們現在處於 2023 年 Bluebird 擁有的最強大的財務狀況，因為我們成為一家專注於基因治療的公司2021 年 11 月。我為我們的藍鳥團隊在過去幾個月里為實現這一目標所做的工作感到無比自豪。

During the 5 months beginning November of 2022, we were able to raise $326 million in net proceeds from the sale of our 2 PRVs and our equity offering. These actions extended our cash runway into the fourth quarter of 2024, when including our restricted cash. Retiring our near-term balance sheet risk has been a top priority for bluebird, and I'm pleased we're able to provide financing for over 50% of our market cap with just 17% dilution.

在 2022 年 11 月開始的 5 個月內，我們通過出售 2 個 PRV 和股票發行籌集了 3.26 億美元的淨收益。這些行動將我們的現金跑道延長至 2024 年第四季度，其中包括我們的受限現金。消除我們的短期資產負債表風險一直是藍鳥的首要任務，我很高興我們能夠以僅 17% 的稀釋度為超過 50% 的市值提供融資。

We will continue to remain opportunistic and looking at options to extend that cash runway even further. We remain on track with our full year 2023 cash burn guidance in the range of $270 million to $300 million and continue to prudently deploy capital as we launch our first -- I'm sorry, as we launch our 2 first-in-class gene therapy and prepare when lovo-cel is approved and available for patients.

我們將繼續保持機會主義，並尋找進一步擴大現金跑道的選擇。我們保持 2023 年全年現金消耗指導在 2.7 億美元至 3 億美元之間的軌道，並在我們推出第一個時繼續謹慎部署資本——對不起，我們推出了我們的 2 個一流基因lovo-cel 獲得批准並可供患者使用時進行治療和準備。

As a reminder, it's premature to provide revenue and top line guidance at this point in our launches. The company anticipates its first commercial revenue will report Q1 results in May.

提醒一下，在我們的發布中此時提供收入和收入指導還為時過早。該公司預計其第一筆商業收入將在 5 月份報告第一季度業績。

Lastly, I'll touch briefly on the Silicon Valley Bank and its impact to Bluebird. Following the bank collapse earlier this month, we were pleased to see the FDIC announcement and that the impact appears to be minimal for the industry. For bluebird, we remain in a strong financial position and have diverse banking relationships with controls in place for continuous monitoring of the health of these organizations.

最後，我將簡要介紹一下矽谷銀行及其對 Bluebird 的影響。本月早些時候銀行倒閉後，我們很高興看到 FDIC 的公告，而且對行業的影響似乎微乎其微。對於 bluebird，我們保持強勁的財務狀況，並擁有多樣化的銀行關係，並通過適當的控制措施持續監控這些組織的健康狀況。

However, of note, SVB does hold approximately $43 million in restricted cash for bluebird, primarily related to the collateralized letter of credit in connection with the execution of our sublease for the 50 Binney Street lease in Cambridge, Massachusetts. We continue to work on releasing the restricted cash, and we'll provide updates as and when they become available.

然而，值得注意的是，SVB 確實持有約 4300 萬美元的藍鳥受限現金，主要與我們在馬薩諸塞州劍橋市 50 Binney Street 租約的轉租執行相關的抵押信用證有關。我們將繼續努力釋放受限制的現金，我們將在更新可用時提供更新。

With that, I'll turn it back to Andrew.

有了這個，我會把它轉回給安德魯。

Thanks, Chris, and thanks, Tom, for walking us through those updates. It is a really exciting time at Bluebird. We are in the midst of 2 first-in-class launches, showing up for patients with CALD and with beta thalassemia, and they're so close to bringing our gene therapy to individuals living with sickle cell disease.

謝謝 Chris，也謝謝 Tom 帶領我們完成了這些更新。在 Bluebird，這是一個非常激動人心的時刻。我們正在進行 2 項一流的發布，針對 CALD 和 β 地中海貧血患者，他們非常接近將我們的基因療法帶給患有鐮狀細胞病的人。

And with that, I'd like to invite Richard Colvin to join me, Chris and Tom for questions. Operator?

因此，我想邀請 Richard Colvin 和我、Chris 和 Tom 一起提問。操作員？

(Operator Instructions) And our first question coming from the line of Jack Allen with Baird.

（操作員說明）我們的第一個問題來自 Jack Allen 與 Baird 的對話。

Great. And congratulations on the progress over the course of the quarter. I guess my first question is around the lovo-cel updates.

偉大的。並祝賀本季度取得的進展。我想我的第一個問題是關於 lovo-cel 更新的。

Can you provide some context around the number of patients that were treated with the suspension process?

您能否提供一些有關接受暫停程序治療的患者數量的背景信息？

And then just to clarify, is the FDA asking for additional comparability data? Or is this a discussion of existing data?

然後澄清一下，FDA 是否要求提供額外的可比性數據？或者這是對現有數據的討論？

And then finally, any analogous situations that you point towards as it relates to these comments?

最後，您指出與這些評論相關的任何類似情況？

Jack, thanks for the questions. So on the last one, I can't report to any analogous ones in terms of -- because I think it's the -- there's been a CMC with gene therapy in general, has been something that the FDA has been focused on. There are plenty of other examples of people who have switched manufacturing plants et cetera. But I might go into details of other analogous here. The -- your question regarding the -- sorry, what was your second question. Can you repeat that, Jack -- that was -- you asked...

傑克，謝謝你的提問。所以在最後一個方面，我不能向任何類似的人報告——因為我認為這是——一般來說，有一個基因治療的 CMC，一直是 FDA 一直關注的事情。還有很多其他人更換製造工廠等的例子。但我可能會在這裡詳細介紹其他類似的內容。你的問題是——抱歉，你的第二個問題是什麼。你能重複一遍嗎，傑克——那是——你問過……

The second question was about -- just to clarify, is FDA asking for additional data here? Or is it a discussion of existing data as it relates to responses?

第二個問題是——只是為了澄清一下，FDA 是否要求在這裡提供額外的數據？或者它是對與響應相關的現有數據的討論？

Well, let me just walk through the time line again. We provide a snapshot of our data. So a thinner package of our data to the FDA in January. They came back with questions about that data and request for more information. We provided that in early March for them to review.

好吧，讓我再次回顧一下時間線。我們提供數據的快照。因此，我們在 1 月份向 FDA 提交了一份更薄的數據包。他們回來時對該數據提出了疑問，並要求提供更多信息。我們在 3 月初提供了這些內容供他們審查。

And then the question about -- and we're not getting into details right now on the package about how many suspension patients were versus hearing on the details of that package right now.

然後是關於 - 我們現在沒有詳細說明有多少暫停患者與現在聽到該包裹的細節有關的包裹。

And our next question coming from the line Yaron Werber from Cowen.

我們的下一個問題來自 Cowen 的 Yaron Werber 系列。

This is Brendan on for Yaron. I guess just really quickly, looking ahead to potential lovo-cel launch, what can you kind of tell? I know it's a little bit early here, but really based on your conversations around SKYSONA and ZYNTEGLO now, what do you kind of think -- what can you tell us about how you're thinking about pricing and reimbursement? And maybe how those conversations for the first 2 drugs have kind of guided your thinking over the recent months.

這是 Yaron 的 Brendan。我想真的很快，展望潛在的 lovo-cel 發布，你能說些什麼？我知道現在有點早，但實際上根據你現在圍繞 SKYSONA 和 ZYNTEGLO 的談話，你有什麼想法——你能告訴我們你是如何考慮定價和報銷的嗎？也許最近幾個月關於前兩種藥物的對話在某種程度上指導了您的思考。

Yes, I'd like to hand that over to Tom to respond.

是的，我想把它交給 Tom 來回應。

Yes, thank you for the question. We've been obviously working on the potential price for lovo-cel for quite some time. Clearly, we will take the same data-driven approach to assessing the value of lovo-cel that we took to approach the value of ZYNTEGLO and SKYSONA, taking into consideration, obviously, the positive clinical outcomes, quality of life improvements, health system cost savings and potential societal impact of patients and families.

是的，謝謝你的提問。顯然，我們研究 lovo-cel 的潛在價格已經有一段時間了。顯然，我們將採用與評估 ZYNTEGLO 和 SKYSONA 的價值相同的數據驅動方法來評估 lovo-cel 的價值，顯然，考慮到積極的臨床結果、生活質量的改善、衛生系統成本病人和家庭的儲蓄和潛在的社會影響。

Again, we'll go through the process. It's probably a little bit too early to give you much more detail on that. But we -- I will say that we are already working with payers and talking to them about what an outcomes-based agreement might look like.

同樣，我們將完成整個過程。現在向您提供更多詳細信息可能還為時過早。但我們——我要說的是，我們已經在與付款人合作，並與他們討論基於結果的協議可能是什麼樣子。

Keep in mind that with ZYNTEGLO, the outcomes-based agreement was pretty straightforward. And with a larger population in sickle cell disease, we'll come up with something different that meets the needs of that population.

請記住，對於 ZYNTEGLO，基於結果的協議非常簡單。隨著鐮狀細胞病患者人數的增加，我們將提出一些不同的方法來滿足該人群的需求。

And our next question coming from the line of Jason Gerberry with Bank of America.

我們的下一個問題來自美國銀行的 Jason Gerberry。

Just a follow-up, just one on the regulatory point. So there's no additional CMC work. It's purely just kind of waiting for a response from the FDA at this point. And then one commercial question.

只是一個後續行動，只是一個關於監管點的問題。所以沒有額外的 CMC 工作。這純粹是在等待 FDA 在這一點上的回應。然後是一個商業問題。

Just within the context of sickle cell, how would you envision centers sort of embracing and adopting 2 competing gene therapies if they're presumably rolling out around the same time?

就鐮狀細胞而言，如果它們大概同時推出，您如何設想中心會接受並採用兩種相互競爭的基因療法？

Just kind of curious if that presents anything unique? And if centers might only choose one? Any color in terms of how you're thinking about that process evolving?

只是有點好奇這是否有什麼獨特之處？如果中心只能選擇一個？就您如何看待該過程的演變而言，有任何顏色嗎？

Jason, I'll take the first part of that question, hand the second part over to Tom. So in terms of -- we believe that we've submitted a complete data package at this point. We're confident in what we've put together. It's in the hands of the FDA right now, and we are waiting for their response to make sure that they agree with that. And then I'll hand it over to Tom for the...

Jason，我將回答這個問題的第一部分，將第二部分交給 Tom。因此，就-我們相信我們此時已經提交了完整的數據包。我們對我們所做的一切充滿信心。它現在在 FDA 手中，我們正在等待他們的回應以確保他們同意這一點。然後我會把它交給湯姆...

Yes. Jason, I think it's a good question. We -- I think the first important thing to point out is that we're actively treating patients today in these QTCs for beta thalassemia and we'll have over a year head start. And we believe based on feedback that, that will translate into an advantage for our therapies with the experience and synergies. We don't believe that most centers will be exclusive to one therapy or the other.

是的。傑森，我認為這是個好問題。我們——我認為首先要指出的重要一點是，我們今天正在這些 QTC 中積極治療患者的 β 地中海貧血，我們將有一年多的領先優勢。我們相信，根據反饋，這將通過經驗和協同作用轉化為我們療法的優勢。我們認為大多數中心不會只接受一種療法或另一種療法。

If you look at other markets like the CAR T market, for example, most centers of excellence like we'll like to offer all available -- especially all available innovative therapies. So we wouldn't anticipate centers offering just one of the therapies.

例如，如果你看看其他市場，比如 CAR T 市場，大多數卓越中心都願意提供所有可用的——尤其是所有可用的創新療法。所以我們預計中心不會只提供其中一種療法。

And our next question coming from the line of Yanan Zhu with Wells Fargo.

我們的下一個問題來自 Yanan Zhu 與 Wells Fargo 的對話。

So first on the regulatory process for lovo-cel. I was wondering what questions or what type of questions did FDA raise if you have any additional color on that?

首先是關於 lovo-cel 的監管程序。我想知道如果您對此有任何其他顏色，FDA 會提出什麼問題或什麼類型的問題？

We're not going to get into the details of the questions right now to say. They did ask some questions and ask for some more data that we have -- we believe we've fully responded to those questions and submitted the data that we have. So we submitted, it's really the full CMC package from the BLA that we pulled forward plus additional data. So it's a very robust package that we submitted.

我們現在不打算深入討論問題的細節。他們確實提出了一些問題並要求提供更多我們擁有的數據——我們相信我們已經完全回答了這些問題並提交了我們擁有的數據。所以我們提交了，它實際上是我們從 BLA 中提取的完整 CMC 包以及其他數據。所以這是我們提交的一個非常強大的包。

Got it. Got it. And then on the ZYNTEGLO launch, a couple of questions here. How many patients have verified their benefit or -- rather have gotten prior authorization at this point. And with regard to the 5 patient starts, do you still estimate 70 to 90 days of manufacturing time? And any estimate on when the first infusion for ZYNTEGLO might occur?

知道了。知道了。然後在 ZYNTEGLO 發佈時，這裡有幾個問題。有多少患者已經驗證了他們的利益，或者 - 更確切地說，此時已經獲得了事先授權。關於 5 位患者的啟動，您是否仍估計製造時間為 70 至 90 天？對 ZYNTEGLO 的第一次輸注可能發生的時間有何估計？

So I'm going to pass that over to Tom.

所以我要把它轉交給湯姆。

Yes. We really are pleased with how the launch is going, and we continue to see consistent volume of patients who are initiating benefits verification and moving through to the prior authorization phase. We at launch provided that as a metric because it was really the only thing that we had that was the indicator of demand. We've moved now to focusing on the number of patient starts. So those that have moved through that process and actually started therapy with the cell collection process.

是的。我們對啟動的進展情況感到非常滿意，我們繼續看到越來越多的患者開始進行福利驗證並進入預先授權階段。我們在發佈時將其作為指標提供，因為它確實是我們唯一擁有的需求指標。我們現在已經開始關注患者開始的數量。因此，那些已經完成該過程並實際開始使用細胞收集過程進行治療的人。

So we aren't providing any updates. I will just say that we feel very strong about how things are going, and that number continues to increase and be steady. With regard to the 5 patients, we did report this morning that the 1 patient was infused with SKYSONA at Boston Children's. We reported that one, because that was publicized by Boston Children's, but we're not providing quarter-by-quarter guidance on how many patients are being infused.

所以我們不提供任何更新。我只想說，我們對事情的進展感到非常強烈，而且這個數字繼續增加並保持穩定。關於這5名患者，我們今天早上確實報告說，其中1名患者在波士頓兒童醫院輸注了SKYSONA。我們報告了一個，因為波士頓兒童醫院對此進行了宣傳，但我們沒有提供有關有多少患者接受輸液的季度指南。

Yes. And then, Tom, he asked question about the manufacturing time as well. We still believe that's 70 to 90 days.

是的。然後，湯姆，他也問了關於製造時間的問題。我們仍然相信那是 70 到 90 天。

That's correct. For ZYNTEGLO it's 79 days. And for SKYSONA, it's a little bit less around 55 to 60 days.

這是正確的。對於 ZYNTEGLO，它是 79 天。而對於 SKYSONA，大約需要 55 到 60 天。

I see. Got it. That's helpful. And maybe lastly, the label -- potential label you're working towards with the lovo-cel submission. I think you mentioned this is a patient greater than 12 years of age. But I guess how -- I think is it -- are there 2 patients with this age range, 12 to 18 that's in the package. And in general, how confident you are that you could get a label that go down to that age of 12 years once you submit the lovo-cel NDA -- BLA.

我懂了。知道了。這很有幫助。也許最後，標籤——您正在使用 lovo-cel 提交的潛在標籤。我想你提到這是一個 12 歲以上的病人。但我想——我想是這樣的——包裹中有 2 名年齡在 12 到 18 歲之間的患者。總的來說，一旦你提交了 lovo-cel NDA -- BLA，你就有多大的信心獲得一個適用於 12 歲的標籤。

Yes. So there's more than 2 patients in there. We're not going to get into the actual split of numbers right here, but we are submitting for the 12 and over. We have studied this patient group, there's clinical benefit for this group as well. Rich, do you want to make any more comments to that?

是的。所以那裡有兩個以上的病人。我們不打算在這裡討論實際的數字劃分，但我們提交的是 12 及以上的數字。我們研究了這個患者群體，對這個群體也有臨床益處。 Rich，你想對此發表更多評論嗎？

No. Thanks, Andrew. No. We have just what Andrew said, there have been more than 2 patients, and we have studied them in Study 206 and also in 210.

不，謝謝，安德魯。沒有。正如安德魯所說，我們有超過 2 名患者，我們在研究 206 和 210 中都對他們進行了研究。

Right. Got it. Got it. Yes. So I only got the 210 number. Yes, got it. That's helpful.

正確的。知道了。知道了。是的。所以我只得到了210號碼。是的，明白了。這很有幫助。

And our next question coming from the line of Sami Corwin with William Blair.

我們的下一個問題來自 Sami Corwin 和 William Blair 的對話。

I know previously, you've stated that there are some patients who will initiate benefits verification for ZYNTEGLO or received prior authorization, but will not proceed with treatment. And I guess I was just curious, if you're collecting any data with that regard as to reasons patients are proceeding with treatment.

我之前知道，您曾表示有些患者會啟動 ZYNTEGLO 的福利驗證或獲得事先授權，但不會繼續進行治療。我想我只是好奇，如果你正在收集任何關於患者繼續治療的原因的數據。

And then just a second one on ZYNTEGLO. With your current number of QTCs in place, how many patients are you able to reach with the current QTCs in place? And how many will you be able to reach if you hit your goal 40 to 50 centers by the end of the year?

然後是 ZYNTEGLO 上的第二個。以您當前的 QTC 數量，您可以使用當前的 QTC 接觸到多少患者？如果您在年底前達到 40 到 50 個中心的目標，您能達到多少個？

Go ahead, Tom.

來吧，湯姆。

Yes, great question. So we do collect information on patients who start the -- both the benefits verification and prior authorization part of the process. And should they choose not to go forward with therapy, we do collect and monitor the different reasons why. I won't get into a comprehensive list today, but it could be something as simple as they're finding out that a QTC is going to be in their state soon, so they want to wait until a QTC is closer to where they live or they want to wait for to get through an event in their life like a play or a school graduation or something like that.

是的，很好的問題。因此，我們確實收集了有關開始該流程的福利驗證和事先授權部分的患者的信息。如果他們選擇不繼續治療，我們會收集和監測不同的原因。我今天不會列出一個完整的列表，但這可能很簡單，比如他們發現 QTC 很快就會進入他們所在的州，所以他們想等到 QTC 離他們住的地方更近一些或者他們想等待完成生活中的事件，例如戲劇或學校畢業典禮或類似的事情。

So we aren't seeing a lot of patients completely fall out of the funnel, so to speak, but we're seeing more kind of continuation type of reasons, at least in the early phase. And the second -- what's the second part of your question?

因此，可以這麼說，我們並沒有看到很多患者完全脫離漏斗，但我們看到了更多的延續類型的原因，至少在早期階段是這樣。第二個問題的第二部分是什麼？

How many patients are able to reach with your current QTCs in place and how many you'll be able to reach if you hit your goal of 40 to 50 centers?

您當前的 QTC 能夠覆蓋多少患者？如果您達到 40 到 50 個中心的目標，您將能夠覆蓋多少患者？

Yes. So of the 1,500 patients in the U.S. who have -- QTC -- our initial Wave 1 QTC network we thought we could reach about 50 patients. That was with our first 5 QTCs. We're now at 12 QTCs. And ultimately, our goal is to get to between 40 and 50 QTCs, which would give us access to the roughly 850 patients that we feel fall within our label. So that's the ultimate goal by the end of the year.

是的。因此，在美國擁有 QTC 的 1,500 名患者中，我們認為我們可以覆蓋大約 50 名患者。那是我們的前 5 個 QTC。我們現在有 12 個 QTC。最終，我們的目標是達到 40 到 50 個 QTC，這將使我們能夠接觸到我們認為屬於我們標籤的大約 850 名患者。所以這是年底前的最終目標。

And our next question coming from the line of Mani Foroohar with SVB Securities.

我們的下一個問題來自 SVB 證券公司的 Mani Foroohar。

This is Jenny on for Mani. We were just wondering if you could provide any clarity on differences between beta thal, sickle cell disease and CALD on time between new patient start forms and revenue recognition.

這是珍妮為瑪尼。我們只是想知道您是否可以在新患者開始表格和收入確認之間按時提供任何關於 βthal、鐮狀細胞病和 CALD 之間差異的清晰信息。

And if so, what are the key variables that would drive any differences going forward?

如果是這樣，推動未來差異的關鍵變量是什麼？

Yes, that's -- so let me turn that over to Tom just to talk about the kind of the lovo-cel, the ZYNTEGLO and the SKYSONA manufacturing times just from the time of initiative from the time of a new patient being getting a start form until we can go to the drop back and maybe I'll hand it over to Chris just to talk about revenue recognition.

是的，那是——所以讓我把它轉交給湯姆，談談 lovo-cel 的種類、ZYNTEGLO 和 SKYSONA 的製造時間，從新患者獲得開始表格的倡議時間開始直到我們可以回到回落之前，也許我會把它交給克里斯來談談收入確認。

Yes. So we're intentionally building in a lot of synergies so that we both maximize our current launches but set ourselves up for success for lovo-cel. So the -- a lot of the operational stuff that we're going through now becomes very simple when we get to lovo-cel. So we feel that we will be able to reduce kind of the QTC onboarding time when we get to lovo-cel 2 weeks. .

是的。因此，我們有意建立大量的協同效應，以便我們既能最大限度地發揮當前的發布效果，又能為 lovo-cel 的成功做好準備。因此，當我們使用 lovo-cel 時，我們現在正在經歷的很多操作都變得非常簡單。所以我們覺得當我們到 lovo-cel 2 週時，我們將能夠減少 QTC 的入職時間。 .

The turnaround time from the time we collect cells until the time we are ready to shift those cells back to QTC is between 70 to 90 days on average for ZYNTEGLO and 55 to 60 days for SKYSONA. The majority of that time is based on the testing and the release -- the testing assays and the release that we do after we manufacture. We believe the time for lovo-cel will be roughly the same, but we don't have that finalized yet. So stay tuned for that one.

從我們收集細胞到我們準備好將這些細胞轉移回 QTC 的周轉時間對於 ZYNTEGLO 平均為 70 至 90 天，對於 SKYSONA 為 55 至 60 天。大部分時間是基於測試和發布——我們在製造後進行的測試分析和發布。我們相信 lovo-cel 的時間將大致相同，但我們還沒有最終確定。所以請繼續關注那個。

But operationally, how they enroll for treatment is going to be very much the same with the same treating physicians. So keep in mind, the physicians now are getting their experience so that as we get to sickle cell disease, they already have those experiences and the learnings from the ZYNTEGLO and SKYSONA launch.

但在操作上，他們如何註冊治療將與相同的主治醫生非常相同。所以請記住，醫生們現在正在積累經驗，所以當我們談到鐮狀細胞病時，他們已經有了這些經驗和從 ZYNTEGLO 和 SKYSONA 推出中學到的東西。

And Chris, do you want to talk about revenue?

克里斯，你想談談收入嗎？

Sure. Thanks, Tom. And with respect to revenue recognition, we recognize revenue on bluebird's financial statements in the patients infused.

當然。謝謝，湯姆。關於收入確認，我們在輸液患者中確認藍鳥財務報表的收入。

And our next question coming from the line of Dane Leone from Raymond James.

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

Sorry to rehash it again. But obviously, there's just -- with some of the history of the CMC discussion that the bluebird team has had with the FDA specifically. Can you just kind of break it down really simply why this is not a situation of years past? And from a technical perspective, really, the differences here, what you have to resolve in your communications versus some of the hiccups that you've experienced before that you actually had to take corrective action on before having an accepted filing.

很抱歉再次重複它。但顯然，藍鳥團隊專門與 FDA 進行了一些 CMC 討論的歷史。您能否真正簡單地分解一下為什麼這不是過去幾年的情況？從技術角度來看，真的，這裡的差異，你必須在你的溝通中解決的問題與你之前經歷過的一些問題相比，你實際上必須在接受申請之前採取糾正措施。

Dane, good question. The last couple of years, the entire gene therapy space has gone through a learning period, right? And Bluebird, we -- as innovators, we've always been on the first to experience the pain. And you've seen that over the last couple of years ago.

戴恩，問得好。最近幾年，整個基因治療領域都經歷了一個學習期，對吧？而 Bluebird，我們——作為創新者，我們總是最先體驗痛苦。在過去的幾年裡，你已經看到了這一點。

And both the FDA and the industry, the gene therapy industry have matured in terms of mutual understanding what is required for CMC. And so over the last 2 years, we have been in constant dialogue with the FDA about comparability and how to approach it. And the conversations over the last couple of years have been focused on what we would need to do, the recipe that we need to follow how we do it. The conversation today is of the content of the analysis and what we submitted. So that's the difference.

FDA 和行業，基因治療行業在相互理解 CMC 的要求方面已經成熟。因此，在過去的兩年裡，我們一直在與 FDA 就可比性以及如何處理它進行持續對話。過去幾年的對話一直集中在我們需要做什麼，我們需要遵循的方法。今天的談話是分析的內容和我們提交的內容。這就是區別。

So just to be perfectly clear, and again, sorry to rehash it. There's no suggestion or thought that you would need to run any additional assays or do assay work there's a request for additional information that you have in-house.

因此，為了完全清楚，再次抱歉重複它。沒有任何建議或想法表明您需要運行任何額外的化驗或進行化驗工作，需要提供您內部擁有的其他信息。

So I cannot predict the FDA, okay. As -- but as closer we are to them, one of the things I will never get on conference call is, say is the FDA will not come back and ask for more data. I just can't, right? I think that's -- but we are extremely confident in the package that we put together. Really the entire BLA CMC package plus additional information. We've been working on this for years now, right? We think we've been trying to see around every corner we can. So I think what you're hearing is on the bluebird side, we have a lot of confidence. I cannot speak for the FDA.

所以我無法預測 FDA，好吧。因為——但隨著我們離他們越來越近，我在電話會議上永遠不會得到的一件事是，說 FDA 不會回來要求更多數據。我不能，對吧？我認為那是 - 但我們對我們放在一起的一攬子計劃非常有信心。真的是整個 BLA CMC 包加上附加信息。我們多年來一直致力於此，對吧？我們認為我們一直在嘗試盡可能地查看每個角落。所以我認為你聽到的是藍鳥方面的，我們很有信心。我不能代表 FDA。

And our next question coming from the line of Gena Wang with Barclays.

我們的下一個問題來自 Gena Wang 與巴克萊銀行的合作。

And this is [Shao Jiong] on for Gena. Two questions from us. The first question is about the -- patient infused with ZYNTEGLO. So if I remember correctly, your first patient cell collection for ZYNTEGLO was earlier than SKYSONA. So if you think about the time difference from cell collection to infusion is about 15 to maybe 20, 30 days. Should we assume the first patient have been infused with ZYNTEGLO or any other factors in play about the time line here?

這是 Gena 的[邵炯]。我們有兩個問題。第一個問題是關於——注入 ZYNTEGLO 的患者。因此，如果我沒記錯的話，您為 ZYNTEGLO 收集的第一個患者細胞比 SKYSONA 早。因此，如果您考慮從細胞採集到輸注的時間差大約為 15 到 20、30 天。我們是否應該假設第一位患者已經輸注了 ZYNTEGLO 或任何其他影響時間線的因素？

I'm going to pass that to Tom to respond.

我要把它轉給 Tom 來回應。

Yes. So we don't plan on updating month-by-month or quarter-by-quarter on number of infusions. Keep in mind that the part we can control is the vein-to-vein time or the time from apheresis to the time we ship the cells back. We cannot control the time after QTC gets the cells back when they might infuse that. We did talk about the SKYSONA one because it was made public by Boston Children's Hospital. They actually publicized on it quite a bit and announced it at a meeting. We had committed to being on track to recognize our first infusion commercially in Q1, and we feel happy that we achieved that. But yes, you're right in that the main difference is that the ZYNTEGLO lead time is 70 to 90 days on average and SKYSONA is a little bit shorter. So that's the one variable. And keep in mind that SKYSONA, the boys with SKYSONA progressed rapidly. So there's much more of an urgency to treat with SKYSONA.

是的。因此，我們不打算按月或按季度更新輸液次數。請記住，我們可以控制的部分是靜脈到靜脈時間或從單採血液成分術到我們將細胞運回的時間。我們無法控制 QTC 取回細胞後的時間，他們可能會注入細胞。我們確實談到了 SKYSONA，因為它已被波士頓兒童醫院公開。他們實際上對此進行了很多宣傳，並在會議上宣布了這一點。我們曾承諾在第一季度實現我們的第一次商業輸注，我們很高興我們實現了這一目標。但是，是的，你是對的，主要區別在於 ZYNTEGLO 的平均交貨時間為 70 到 90 天，而 SKYSONA 則稍短一些。所以這是一個變量。請記住，SKYSONA，擁有 SKYSONA 的男孩們進步很快。因此，使用 SKYSONA 治療的緊迫性要大得多。

If I may ask the second question. So my understanding is bluebird will get paid directly from QTC. So how much out of the data price to payment they can get for example, so what did the payer agreed to pay to the QTC for $2.8 million per patient and the QTC want to make some profit out of it, what will be the discount to bluebird? Will discount be the same for all QTCs under the master service agreement?

如果我可以問第二個問題。所以我的理解是 bluebird 將直接從 QTC 獲得報酬。那麼他們可以從支付的數據價格中得到多少，例如，付款人同意以每位患者 280 萬美元的價格向 QTC 支付多少，而 QTC 想從中獲利，折扣是多少藍鳥？主服務協議下所有 QTC 的折扣是否相同？

Tom, go ahead.

湯姆，繼續。

Yes. If I'm understanding your question correctly, bluebird just receives the price of the drug. QTCs through the -- as they go through the prior authorization process or securing the payers' commitment to pay for not only the drug but also the cost of the procedure and then they negotiate a case rate for themselves. So they negotiate usually something around the drug and something around the procedure of the transplant. But that is very private information. QTCs don't share that information with us and payers don't show that information with us. So that's a bit of an unknown to us, but they do that on the side for therapies like this.

是的。如果我沒有正確理解你的問題，bluebird 只會收到藥物的價格。 QTC 通過 - 當他們通過事先授權程序或確保付款人承諾不僅支付藥物而且支付程序費用時，然後他們為自己協商案件費率。因此，他們通常會圍繞藥物和移植程序進行談判。但這是非常私人的信息。 QTC 不會與我們分享該信息，付款人也不會向我們展示該信息。所以這對我們來說有點未知，但他們在進行此類治療時會這樣做。

And our next question coming from the line of Luca Issi from RBC Capital.

我們的下一個問題來自 RBC Capital 的 Luca Issi。

Great. This is Lisa on for Luca. Just a couple on ZYNTEGLO here. Just wondering if you can add some more color on the 5 patients who had cell collections.

偉大的。這是 Luca 的 Lisa。 ZYNTEGLO 上只有幾個。只是想知道您是否可以為 5 名收集細胞的患者添加更多顏色。

Did these collections occur at more than 1 of the 12 QTCs that are currently online? And what is the -- and also as well, if you could add more color on the growing patient demand that you are seeing? Is this coming from a handful of doctors in a localized geography? Or is this coming from more broadly throughout the U.S.?

這些收集是否發生在當前在線的 12 個 QTC 中的 1 個以上？如果您可以為您看到的不斷增長的患者需求添加更多顏色，那是什麼？這是來自本地化地理區域的少數醫生嗎？或者這是否來自更廣泛的美國各地？

Yes. Sure. Good questions. Yes, the patient, we won't get into center by center, but the 5 patients that we reported are coming from multiple centers from our early Wave 1 QTCs. And that's why we're confident as we bring up more QTCs, we continue to see demand in each QTC that we bring on board. So the growing demand is coming from not only the existing QTCs that have already started treating patients. But as we bring on each new QTC, they have patients to be treated. So the answer to that is both.

是的。當然。好問題。是的，患者，我們不會逐個中心進入，但我們報告的 5 名患者來自我們早期第 1 波 QTC 的多個中心。這就是為什麼我們在提出更多 QTC 時充滿信心，我們繼續看到我們帶來的每個 QTC 的需求。因此，不斷增長的需求不僅來自已經開始治療患者的現有 QTC。但是當我們帶來每個新的 QTC 時，他們都有患者需要治療。所以答案是兩者兼而有之。

And keep in mind, our plan was to start with the 5 QTCs and roughly, we thought about 50 patients at launch and then to rapidly grow that to between 40 and 50 QTCs by the end of the year. That also, I think, maximizes our opportunity and sets us up for success with ZYNTEGLO, but also really lays the foundation for lovo-cel and sickle cell disease.

請記住，我們的計劃是從 5 個 QTC 開始，粗略地說，我們在啟動時考慮了 50 名患者，然後到年底迅速將其增加到 40 到 50 個 QTC。我認為，這也最大限度地增加了我們的機會，並為 ZYNTEGLO 的成功奠定了基礎，但也確實為 lovo-cel 和鐮狀細胞病奠定了基礎。

That's helpful. And then just maybe a quick one on sickle cell. Are there plans to expand beyond the 40 to 50 QTC centers planned already for 2023 when sickle cell potentially launches in 2024?

這很有幫助。然後也許只是關於鐮狀細胞的快速一個。當鐮狀細胞可能在 2024 年啟動時，是否有計劃擴展到 2023 年已經計劃的 40 到 50 個 QTC 中心？

Yes, it's a good question. Right now, our goal is to get to between 40 and 50 QTCs this year by the end '23. What we're learning and what we know about patients in both -- with both beta-thalassemia and with sickle cell disease is that some patients are willing to travel, but some patients would prefer to get treated closer to their home.

是的，這是個好問題。現在，我們的目標是今年到 23 年底達到 40 到 50 個 QTC。我們正在了解的以及我們對這兩種疾病的患者的了解——同時患有β-地中海貧血和鐮狀細胞病的是一些患者願意旅行，但一些患者更願意在離家更近的地方接受治療。

Our goal ultimately will be to bring our treatments to patients so that they don't have to travel very far for treatment. But we're not going to say what we're growing to beyond the 40 to 50 right now. It's fair to assume that we'll probably end up with higher than 50, but we're not commenting on how many at this time.

我們的最終目標是將我們的治療方法帶給患者，這樣他們就不必長途跋涉去接受治療。但我們不會說我們現在正在成長到超過 40 到 50 人。可以公平地假設我們最終可能會超過 50 個，但我們目前不評論有多少。

And our next question coming from the line of Salveen Richter with Goldman Sachs.

我們的下一個問題來自高盛的 Salveen Richter。

This is [Anabel] on for Salveen. We have 2 questions. The first one on lovo-cel. In light of this delay, how are you thinking about the competitive positioning of lovo-cel?

這是 Salveen 的 [Anabel]。我們有 2 個問題。第一個在 lovo-cel 上。鑑於這種延遲，您如何看待 lovo-cel 的競爭定位？

And then on ZYNTEGLO, how much overlap do you think there would be between the QTC that you're going to establish this year and then those that would be needed for sickle cell? And then just quickly on the ex U.S. opportunity. When do you think you would be ready to think about that?

然後在 ZYNTEGLO 上，您認為您今年要建立的 QTC 與鐮狀細胞所需的 QTC 之間會有多少重疊？然後迅速抓住前美國的機會。你認為你什麼時候準備好考慮這個問題？

I'll just take the last one first and hand it to Tom. On the ex U.S., we are focused on the U.S. only right now. We got this -- we are getting the therapies launched, getting the therapy to patients in the U.S. It's not on our radar screen for ex U.S. at the moment. Tom, go ahead.

我先拿最後一個，然後交給湯姆。關於前美國，我們現在只關注美國。我們得到了這個——我們正在啟動治療，讓美國的患者接受治療。目前，它不在我們前美國的雷達屏幕上。湯姆，繼續。

Yes, sure. I'm going to start with your QTC question first. Our QTC -- the way we designed our QTC network was to -- the QTCs that have expertise in cell and gene therapy, but also treat both beta thalassemia and sickle cell disease.

是的，當然。我將首先從您的 QTC 問題開始。我們的 QTC——我們設計 QTC 網絡的方式是——QTC 在細胞和基因治療方面具有專業知識，但也治療 β 地中海貧血和鐮狀細胞病。

Over index those that have high populations of beta-thalassemia first, and then we're going to grow to QTCs that have higher concentrations of the patients with sickle cell disease. But the simple answer is we believe that 100% of our network will be both ZYNTEGLO and SKYSONA patients -- I'm sorry, centers.

首先對那些具有高β-地中海貧血人群的指標進行過度索引，然後我們將發展到鐮狀細胞病患者濃度更高的QTC。但簡單的答案是，我們相信我們網絡的 100% 都是 ZYNTEGLO 和 SKYSONA 患者——對不起，中心。

When you think about the competition in your competitive question, I think I said this earlier, but I think the first and foremost thing to point out is that we're already in these treatment centers. And so even with the slight shift in our time line, we believe that we have a competitive advantage by being there first and we'll be there first for over a year. And then as we've done market research over the years, we've seen a slight advantage for lovo-cel. So we feel very confident that the shift in time line is not going to impact either of those things.

當您考慮競爭問題中的競爭時，我想我之前說過，但我認為首先要指出的是我們已經在這些治療中心。因此，即使我們的時間線略有變化，我們相信我們通過率先到達那里而具有競爭優勢，並且我們將率先到達那裡一年多。然後，隨著我們多年來進行的市場調查，我們看到了 lovo-cel 的微小優勢。所以我們非常有信心，時間線的改變不會影響這兩件事。

And our next question coming from the line of Matthew Harrison with Morgan Stanley.

我們的下一個問題來自 Matthew Harrison 與摩根士丹利的對話。

This is (inaudible) on for Matthew. So can you comment on the cadence of the patient starts. So what happens after patient starts, like how long it takes to -- for cell collection? And do you expect all the patient starts to be converted into dosed patients? In other words, should we expect some patients maybe not going into dosing after starts?

這是（聽不清）馬修的。那麼你能評論一下病人開始的節奏嗎？那麼在患者開始後會發生什麼，比如細胞收集需要多長時間？您是否希望所有患者都開始轉變為服用藥物的患者？換句話說，我們是否應該期望一些患者在開始後可能不會進行給藥？

Go ahead, Tom.

來吧，湯姆。

Yes. As far as cadence, just to give you a high-level review, a patient will come in for obviously a consultation as they start the benefits verification and prior authorization process. .

是的。就節奏而言，只是為了給你一個高水平的審查，患者在開始福利驗證和事先授權程序時顯然會進行諮詢。 .

As I noted on the call, the prior authorization process is taking about 2 weeks on average, which is great news the payers recognize the value of ZYNTEGLO and SKYSONA. And then obviously, they'll go through their cell collection and then go back home.

正如我在電話中指出的那樣，事先授權過程平均需要大約 2 週的時間，這是付款人認可 ZYNTEGLO 和 SKYSONA 價值的好消息。然後很明顯，他們將完成他們的細胞收集，然後回家。

This -- as I mentioned, cell collection to when we ship the cells back is between 70 and 90 days and then it's really up to the patient and QTC to decide when they come back in for their infusion and their treatment.

這——正如我提到的，細胞收集到我們將細胞運回的時間在 70 到 90 天之間，然後真正由患者和 QTC 決定他們何時回來進行輸液和治療。

That part is a little bit less clear to us right now, and we will wait until we treat a lot more patients before we kind of give thoughts on how long that might take on average. But the -- your last question was how many patients that -- we're focusing in right now on starts because we believe that once the patient goes through the apheresis process, they're committed to therapy. So we don't anticipate a lot of patients to pull out of therapy or fall out of the funnel once they go through the cell collection. But that's why we're focusing on patient starts.

這部分現在對我們來說有點不太清楚，我們會等到我們治療了更多的病人，然後再考慮平均需要多長時間。但是 - 你的最後一個問題是有多少患者 - 我們現在關注的是開始，因為我們相信一旦患者經歷了血液分離過程，他們就會致力於治療。因此，我們預計不會有很多患者在完成細胞採集後退出治療或掉出漏斗。但這就是我們關注患者開始的原因。

And I'm showing no further questions at this time. I would now like to turn the call back over to Mr. Andrew Obenshain, for any closing remarks.

我現在沒有進一步提問。我現在想將電話轉回給 Andrew Obenshain 先生，聽取任何結束語。

Thank you very much, and thank you, everyone, for joining this morning. I just wanted to reiterate how proud I am of our team in terms of what we've done over the last several years to bring 2 therapies to patients and getting close to 1/3 and completing this BLA and actually pulling the workflow over in a timely manner. So -- and we -- it is a time where bluebird is finally delivering on the mission it had for over a decade. So really, really proud of the team. So thank you, everyone.

非常感謝，也感謝大家今天早上的加入。我只是想重申，我為我們的團隊感到自豪，因為我們在過去幾年中所做的工作為患者帶來了 2 種療法，接近 1/3 並完成了這個 BLA，並實際上將工作流程拉到了一個及時的方式。所以——我們——現在是藍鳥終於完成其十多年來的使命的時候了。所以真的，真的為團隊感到驕傲。所以謝謝大家。

Ladies and gentlemen, that does conclude the conference for today. Thank you for your participation. You may now disconnect.

女士們，先生們，今天的會議到此結束。感謝您的參與。您現在可以斷開連接。