bluebird bio Inc (BLUE) 2023 Q4 法說會逐字稿

Good day, and thank you for standing by, welcome to the bluebird bio fourth quarter and 2023 annual results conference call. (Operator Instructions)

美好的一天，感謝您的支持，歡迎參加藍鳥生物第四季和 2023 年度業績電話會議。（操作員說明）

Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Courtney O'Leary, Investor Relations, please go ahead.

請注意，今天的會議正在錄製中。現在我想將會議交給今天的第一位發言人，投資者關係部的考特尼·奧利裡 (Courtney O'Leary)，請繼續。

Good morning, everyone, and thank you for joining our fourth quarter and 2023 annual results call today. My name is Courtney O'Leary, Director of Investor Relations at bluebird bio.

大家早安，感謝您今天參加我們的第四季和 2023 年年度業績電話會議。我叫 Courtney O'Leary，藍鳥生物公司投資者關係總監。

Before I begin, let me review our safe harbor statements. 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.

在開始之前，讓我回顧一下我們的安全港聲明。今天的討論包含 1995 年《私人證券訴訟改革法案》規定的前瞻性陳述，包括對我們未來財務表現和財務狀況的預期。

In addition to statements of the company's plans, expectations or intentions regarding regulatory progress, commercialization plans and business operations. 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.

除了公司關於監管進展、商業化計劃和業務運營的計劃、期望或意圖的聲明外。此類陳述基於目前的預期和假設，這些預期和假設受到風險和不確定性的影響，並涉及許多可能導致實際結果與預測結果有重大差異的風險因素。

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.

這些風險的描述包含在我們向 SEC 提交的文件中，這些文件可在我們網站 www.bluebirdbio.com 的投資者關係部分找到。

On today's call, Andrew Obenshain, bluebird bio CEO, will provide a general corporate update, and then Tom Klima, Chief Commercial and Operating Officer, will discuss progress on the commercial launches of LYFGENIA, ZYNTEGLO and SKYSONA. And finally, Chris Krawtschuk, Chief Financial Officer, will provide a financial update before opening the call up for Q&A.

在今天的電話會議上，bluebird Bio 執行長 Andrew Obenshain 將提供公司整體最新情況，然後商務與營運長 Tom Klima 將討論 LYFGENIA、ZYNTEGLO 和 SKYSONA 的商業發布進度。最後，財務長 Chris Krawtschuk 將在開始問答之前提供財務最新資訊。

With that, I will turn it over to Andrew.

這樣，我就把它交給安德魯。

Thanks Courtney. And thank you, everyone, for joining our call this morning to provide an update of our fourth quarter 2023 annual results, discuss our strategic outlook and planned milestones for 2024.

謝謝考特尼。感謝大家今天早上加入我們的電話會議，提供我們 2023 年第四季度年度業績的最新信息，討論我們的戰略前景和 2024 年計劃的里程碑。

Earlier this morning, we put out an 8-K announcing that we will be restating financial information for 2022 and for the first three quarters of 2023, that we've submitted an extension on our 10-K filing we now anticipate filing the 10-K inclusive of that restatement no later than April 16. Importantly, the restatement does not impact our cash position or revenue. Chris will discuss this in greater detail later in the call.

今天早些時候，我們發布了8-K 聲明，宣布我們將重述2022 年和2023 年前三個季度的財務信息，我們已經提交了10-K 備案的延期，我們現在預計將提交10- K 備案。K 不遲於 4 月 16 日包括該重述。重要的是，重述不會影響我們的現金狀況或收入。克里斯將在稍後的電話會議中更詳細地討論這一點。

2023 was a year of significant progress for bluebird. We established ourselves as a commercial gene therapy leader with a validated commercial strategy that brought both ZYNTEGLO and SKYSONA to patients across the US.

2023 年是藍鳥取得重大進展的一年。我們透過經過驗證的商業策略確立了自己作為商業基因治療領導者的地位，將 ZYNTEGLO 和 SKYSONA 帶給美國各地的患者。

Our recent commercial progress for LYFGENIA builds on that foundation, with the only -- with the FDA approval of LYFGENIA for sickle cell disease last December, bluebird is currently the only commercial gene therapy company with three FDA approved products.

我們最近 LYFGENIA 的商業進展建立在這一基礎上，去年 12 月 FDA 批准 LYFGENIA 用於治療鐮狀細胞疾病，bluebird 是目前唯一一家擁有三種 FDA 批准產品的商業基因治療公司。

Since then, our commercial team has hit the ground running to position ourselves for a strong LYFGENIA launch. We have talked before about the benefits of our significant commercial head start with [tagline with syntego] and today we are seeing the fruits of that labor translate into real momentum for LYFGENIA.

從那時起，我們的商業團隊就開始行動起來，為 LYFGENIA 的強勢推出做好準備。我們之前已經討論過 [與 syntego 的標語] 取得顯著商業領先優勢的好處，今天我們看到這種勞動成果轉化為 LYFGENIA 的真正動力。

We have activated 62 qualified treatment centers and assigned our first outcome space agreement for Medicaid, extending access to LYFGENIA to this critical patient population. In 2024 is off to a fast start with nine patient starts already this year. Tom will dive deeper into our commercial progress momentarily.

我們已經啟動了 62 個合格的治療中心，並為醫療補助分配了我們的第一個結果空間協議，將 LYFGENIA 的使用範圍擴大到了這個關鍵患者群體。2024 年將迎來快速開局，今年已有 9 名患者開始接受治療。湯姆將立即深入了解我們的商業進展。

Last week, we also announced that we encountered -- we entered into a five year term loan with Hercules Capital for up to $175 million. This transaction provided bluebird with an infusion of capital, there's expect to extend our cash runway beyond the next 24-months.

上週，我們也宣布與 Hercules Capital 簽訂了一筆高達 1.75 億美元的五年貸款。此次交易為藍鳥公司注入了資金，預計我們的現金跑道將延長至未來 24 個月以上。

Last August on our Q2 earnings call, we said at a five year vision for bluebird as a stand-alone commercial gene therapy company, we outlined our near-term path to profitability and our expected additional growth and scale in the next five years. This funding forward that vision to capitalize on the multibillion-dollar opportunity in front of us in the US.

去年8 月，在第二季財報電話會議上，我們在藍鳥作為一家獨立的商業基因治療公司的五年願景中表示，我們概述了我們的近期盈利路徑以及​​未來五年的預期額外增長和規模。這筆資金推進了這個願景，即利用美國擺在我們面前的數十億美元的機會。

I will now hand the call over to Tom to highlight the significant progress happening in our commercial launches.

我現在將把電話轉交給湯姆，強調我們的商業發布所取得的重大進展。

Thanks, Andrew, and good morning everyone. As Andrew noted, 2023 was a pivotal year for bluebird, which we built our commercial foundation was ZYNTEGLO in beta-thalassemia and SKYSONA for cerebral adrenoleukodystrophy.

謝謝安德魯，大家早安。正如 Andrew 所指出的那樣，2023 年對藍鳥來說是關鍵的一年，我們為治療 β 地中海貧血的 ZYNTEGLO 和治療腦腎上腺腦白質營養不良的 SKYSONA 建立了商業基礎。

Today, we're capitalizing on the head start to accelerate the launch of LYFEGNIA for sickle cell disease. As a reminder, our launches are focused on three core elements for success. First, establishing a robust network of qualified treatment centers or QTCs. These are transplant centers with significant experience in cell and gene therapy. As Andrew mentioned today, we have 62 activated QTCs unparalleled compared to others in the field.

今天，我們利用領先優勢，加速推出治療鐮狀細胞疾病的 LYFEGNIA。提醒一下，我們的發布重點在於成功的三個核心要素。首先，建立一個強大的合格治療中心或 QTC 網路。這些移植中心在細胞和基因治療方面擁有豐富的經驗。正如安德魯今天提到的，我們有 62 個啟動的 QTC，與該領域的其他公司相比是無與倫比的。

Second, ensuring the value of our therapies are recognized in the patients have timely equitable access. In a moment, I'll dive deeper into our progress on access and reimbursement. And lastly, optimizing the patient and provider experience, gene therapy is a high-touch business where transparency, collaboration and understand the needs of patients, families and providers is paramount.

其次，確保我們的療法的價值得到患者的認可，能夠及時、公平地獲得治療。稍後，我將更深入地探討我們在准入和報銷方面的進展。最後，為了優化患者和提供者的體驗，基因療法是一項高接觸性業務，其中透明度、協作和了解患者、家庭和提供者的需求至關重要。

Our deep understanding of the gene therapy process. Our dedicated focus and our experience over the last 18-months allow us to be a strong partner to our activated QTCs as we help them bring life-changing therapies for their patients.

我們對基因治療過程的深刻理解。我們的專注和過去 18 個月的經驗使我們能夠成為激活的 QTC 的強大合作夥伴，幫助他們為患者帶來改變生活的療法。

Three months into the LYFEGNIA launch, patient demand is strong. I'm very excited to share today that we expect our first patient start will be scheduled imminently, and we are extremely encouraged by the number of enrollments and patients preparing for treatment for multiple treatment centers across our QTC network. We anticipate starts for LYFEGNIA to grow quarter over quarter with the majority occurring in the second half of the year as momentum builds, we anticipate that the first revenues for LYFEGNIA will be reported in Q3.

LYFEGNIA 推出三個月後，患者需求強勁。我今天非常高興地告訴大家，我們預計第一例患者的治療將很快安排，我們對 QTC 網路中多個治療中心的入組人數和準備接受治療的患者數量感到非常鼓舞。我們預計 LYFEGNIA 將開始逐季度成長，隨著勢頭的增強，大部分發生在下半年，我們預計 LYFEGNIA 的第一筆營收將在第三季報告。

Moving to ZYNTEGLO, we continue to see strong linear growth with seven patient starts since the beginning of 2024. In addition, to the 20 patient starts completed ZYNTEGLO 2023. Additionally, we've completed 2 patient starts for SKYSONA since the beginning of 2024. In addition to the 6 patient starts completed for SKYSONA last year.

轉向 ZYNTEGLO，自 2024 年初以來，我們繼續看到強勁的線性成長，有 7 名患者開始治療。此外，20 名患者開始完成 ZYNTEGLO 2023。此外，自 2024 年初以來，我們已經完成了 2 例 SKYSONA 患者啟動。除了去年為 SKYSONA 完成的 6 名患者啟動。

And as a reminder, patient starts, which is when cell collection occurs, remains the key commercial metric to watch in the early stages of our launches as this is the value-creating moment for the company with revenue being recognized when the patient has a few -- infused. For modeling purposes, you can expect that patients are infused one to two quarters following cell collection. And in our experience, once a patient goes through the cell collection, they continue on treatment journey. To date, every patient who has started the process has either completed the process or remains in the process.

提醒一下，患者啟動（即細胞採集發生的時間）仍然是我們推出早期階段需要關注的關鍵商業指標，因為這是公司創造價值的時刻，當患者有一些細胞時，收入就會得到確認。 ——注入。出於建模目的，您可以預期患者會在細胞採集後一到兩個季度接受輸注。根據我們的經驗，一旦患者完成細胞採集，他們就會繼續治療之旅。迄今為止，每位開始該過程的患者要么已完成該過程，要么仍在該過程中。

Going forward we plan to provide quarterly updates on patient starts for each of our therapies as we work towards the 85 to 105 patient starts we guided to in 2024.

展望未來，我們計劃每季提供每種療法的患者啟動情況更新，我們將努力實現 2024 年指導的 85 至 105 名患者啟動。

Turning to access and reimbursement, gene therapies are one time transformative treatments and bring tremendous value to the healthcare system into patients for years, bluebird has led the way in articulating the value of gene therapies to payers and charting paths to access for patients.

談到獲取和報銷，基因療法是革命性的治療方法，多年來為患者的醫療保健系統帶來了巨大的價值，藍鳥在向付款人闡明基因療法的價值並為患者制定獲取途徑方面發揮了帶頭作用。

We continue to see timely access was ZYNTEGLO and SKYSONA was zero ultimate denials for either therapy across both Medicaid and commercial payers. Payers are recognizing the value of these therapies and the high burden of disease.

我們繼續看到 ZYNTEGLO 和 SKYSONA 的及時訪問對於醫療補助和商業付款人的任何一種治療都是零最終拒絕。付款人正在認識到這些療法的價值和疾病的沉重負擔。

And today we're seeing the same early success with LYFEGNIA, where our goal is timely, equitable access for patients and our approach is working we have designed outcomes-based agreements there you need to LYFEGNIA offering payers, meaningful risk sharing tied to VOE related hospitalizations with patients typically followed for three years.

今天，我們看到LYFEGNIA 取得了同樣的早期成功，我們的目標是及時、公平地為患者提供服務，我們的方法正在發揮作用，我們設計了基於結果的協議，您需要LYFEGNIA 為付款人提供與VOE相關的有意義的風險分擔患者住院通常持續三年。

In addition to a commercial offering, we've designed an offering specifically for Medicaid that addresses the need for predictability and operational ease that is essential for states grappling with resource constraints. Earlier this month, we announced that bluebird signed its first outcomes-based agreement for LYFEGNIA with Michigan's Medicaid program demonstrated support from government payers for these types of innovative arrangements.

除了商業產品之外，我們還專門為醫療補助設計了一種產品，可滿足可預測性和操作簡便性的需求，這對於應對資源限制的各州至關重要。本月早些時候，我們宣布藍鳥與密西根州醫療補助計劃簽署了第一份基於結果的 LYFEGNIA 協議，這表明政府付款人對此類創新安排的支持。

We've also signed a total of four commercial outcomes-based agreements for LYFEGNIA covering more than 200 million lives. In three short months, we've already seen close to 90% of coverage policies covered LYFEGNIA at parity, including policies from major national insurers such as Aetna, Anthem, and Cigna.

我們還為 LYFEGNIA 簽署了總共四項基於商業成果的協議，覆蓋超過 2 億人的生命。在短短三個月內，我們已經看到近 90% 的保單均等承保 LYFEGNIA，其中包括 Aetna、Anthem 和 Cigna 等主要國家保險公司的保單。

We continue to be focused on access for Medicaid patients in 2024 and discussions are ongoing with more than 15 Medicaid agencies, representing 80% of individuals sickle cell disease in the US. We are also actively engaged with CMMI on its cell and gene therapy access demonstration that is slated to begin in 2025, which could serve as a bandwidth extender for states who do not have the ability to implement outcomes-based agreements on their own.

我們繼續關注 2024 年醫療補助患者的獲得情況，並且正在與超過 15 個醫療補助機構進行討論，這些機構代表了美國鐮狀細胞疾病患者的 80%。我們也積極與 CMMI 合作進行細胞和基因治療准入示範，該示範計畫將於 2025 年開始，這可以為那些沒有能力自行實施基於結果的協議的州提供頻寬擴展器。

Moving to our QTC network, one of the most significant advantages of our commercial head start has been our ability to build our synergistic QTC network, we now have 62 activated centers, the largest network of qualified treatment centers for hemoglobinopathies, 49 of which are already ready to receive refers for LYFGENIA today.

轉向我們的 QTC 網絡，我們商業領先的最顯著優勢之一是我們有能力建立協同 QTC 網絡，我們現在擁有 62 個激活中心，這是最大的合格血紅蛋白病治療中心網絡，其中 49 個已經在今天準備好接收LYFGENIA 的推薦。

This means that approximately 95% of people living with sickle cell disease are within 200 miles or less of a bluebird QTC. We anticipate additional QTC expansion across our portfolio in 2024. We also recently signed agreements with QTCs and geographies with important proximity to sickle cell patients, where we are meeting patients where they are in Georgia, across Florida and throughout the New York metropolitan area.

這意味著大約 95% 的鐮狀細胞疾病患者位於藍鳥 QTC 200 英里或更短的範圍內。我們預計 2024 年我們的投資組合將進一步擴大 QTC。我們最近也與 QTC 和與鐮狀細胞患者關係密切的地區簽署了協議，我們正在與喬治亞州、佛羅裡達州和整個紐約大都會區的患者會面。

Additionally, five centers have also been activated to administer SKYSONA for patients with CALD. We were able to quickly activate our LYFGENIA QTC due to both learned experience of setting up these centers for ZYNTEGLO and the strong relationships we have built with these centers throughout 2023.

此外，五個中心也已啟動，為 CALD 患者提供 SKYSONA 治療。由於為 ZYNTEGLO 建立這些中心的經驗以及我們在 2023 年與這些中心建立的牢固關係，我們能夠快速啟動 LYFGENIA QTC。

From onboarding through infusion, our QTCs are comfortable with our process and have grown to expect the transparency and the partnership that bluebird brings to the table. To recap, ZYNTEGLO and SKYSONA launches continue to progress as planned, and we anticipate strong linear growth from -- ZYNTEGLO in 2024.

從入職到注入，我們的 QTC 對我們的流程感到滿意，並且越來越期待藍鳥帶來的透明度和合作夥伴關係。回顧一下，ZYNTEGLO 和 SKYSONA 的推出繼續按計劃進行，我們預計 ZYNTEGLO 將於 2024 年實現強勁的線性成長。

We've made incredible early progress in our LYFEGNIA launch building at our validated commercial [platform] we are seeing clear demand from patients and physicians, payers are recognizing the value of LYFEGNIA and providing access and our QTC network is fully ready to help patients start their journey with the curative therapy.

我們在LYFEGNIA 的發布中取得了令人難以置信的早期進展，在我們經過驗證的商業[平台]上構建，我們看到患者和醫生的明確需求，付款人正在認識到LYFEGNIA 的價值並提供訪問權限，我們的QTC 網路已完全準備好幫助患者啟動他們的治療之旅。

And now I'd like to turn the call over to Chris.

現在我想把電話轉給克里斯。

Thanks, Tom and good morning, everyone. Before discussing the details of the restatement and the filing extension we announced this morning, I want to highlight the financial results, we reported in our press release.

謝謝，湯姆，大家早安。在討論我們今天早上宣布的重述和申請延期的細節之前，我想強調一下我們在新聞稿中報告的財務表現。

In the fourth quarter, we reported $7.8 million in total revenue, primarily driven from product revenue from ZYNTEGLO and SKYSONA. As a reminder, we recognize revenue upon infusion of the drug product. Additional drug product for several patients were delivered at the end of December and infused in January.

第四季度，我們報告的總收入為 780 萬美元，主要來自 ZYNTEGLO 和 SKYSONA 的產品收入。提醒一下，我們在註射藥品時確認收入。幾位患者的額外藥品於 12 月底交付，並於 1 月輸注。

So this revenue we recognized in the first quarter of 2024. For the full year 2023, we reported $29.5 million in net revenue was $16.7 million of revenue attributable to ZYNTEGLO and $12.4 million of revenue attributable to SKYSONA. With cumulative gross-to-net discounts across the portfolio of two products of approximately 19%, in 2024, we anticipate gross-to-net discounts in the range of 20% to 25%, with fluctuations based on product and payer mix as well as utilization of our outcomes-based agreements.

所以我們在 2024 年第一季確認了這筆收入。對於 2023 年全年，我們報告的淨收入為 2950 萬美元，其中 ZYNTEGLO 貢獻的收入為 1670 萬美元，SKYSONA 貢獻的收入為 1240 萬美元。兩種產品組合的累積毛淨折扣約為 19%，我們預計到 2024 年，毛淨折扣將在 20% 至 25% 範圍內，波動也會根據產品和付款人組合而變化作為對我們基於結果的協議的利用。

Going forward bluebird plans to provide revenue by product on a quarterly basis and as Tom shared earlier, we expect the first LYFEGNIA patient infusion and revenue recognition in the third quarter of 2024. We ended the year with cash and cash equivalents, marketable securities, and restricted cash of approximately $275 million, which includes $53 million of restricted cash.

展望未來，藍鳥計劃按季度提供按產品劃分的收入，正如 Tom 早些時候分享的那樣，我們預計將於 2024 年第三季度進行首次 LYFEGNIA 患者輸液和收入確認。截至年底，我們的現金和現金等價物、有價證券和限制性現金約為 2.75 億美元，其中包括 5,300 萬美元的限制性現金。

We're very pleased to announce that we entered into the five year term loan with Hercules Capital for $175 million. This financing provides an infusion of non-dilutive capital for bluebird, helping fuel the launch of LYFEGNIA and deliver on our mission as a company. The loan provides for up to $175 million in the aggregate and it's available in four tranches. The first tranche in the amount of $75 million was drawn on closing.

我們非常高興地宣布，我們與 Hercules Capital 簽訂了 1.75 億美元的五年期貸款。此次融資為藍鳥注入了非稀釋性資本，有助於推動 LYFEGNIA 的推出並實現我們作為一家公司的使命。該貸款總額高達 1.75 億美元，分四期提供。第一筆金額為 7500 萬美元的資金在交易結束時提取。

We may draw additional two tranches over the next 18-months in aggregate of an amount up to $50 million and this is subject to the achievement of commercial milestones tied to LYFEGNIA patient starts and gross profit.

我們可能會在未來 18 個月內額外提取兩筆款項，總額高達 5000 萬美元，這取決於與 LYFEGNIA 患者啟動和毛利相關的商業里程碑的實現。

The fourth tranche of up to $50 million may be available at the sole discretion of Hercules. Importantly, and to reiterate Andrew's comments, based on our launch estimates in our current business plans and assuming the first three launches are executed. The transaction is expected to extend our cash runway beyond the next 24-months and puts us in a durable capital position as we approach profitability.

Hercules 可自行決定提供高達 5000 萬美元的第四筆資金。重要的是，重申安德魯的評論，基於我們當前業務計劃中的發布估計並假設前三項發布已執行。這筆交易預計將把我們的現金跑道延長至未來 24 個月以上，並在我們接近盈利時使我們處於持久的資本狀況。

Lastly, this morning, we announced we restate financial information for the full year of 2022, and for the first three quarters of both 2022 and 2023. The restatement relates to the application of our accounting policies for contracts with our contract manufacturing organizations and suppliers, which did not consistently combined lease and non-lease components and was discovered by our internal finance team during the preparation of our annual financial statements.

最後，今天早上，我們宣布重述 2022 年全年以及 2022 年和 2023 年前三個季度的財務資訊。此次重述涉及我們與合約製造組織和供應商簽訂的合約的會計政策的應用，這些政策並未一致地將租賃和非租賃部分合併起來，這是我們的內部財務團隊在編制年度財務報表時發現的。

For 2022, we estimate the understatement of lease assets and lease liabilities of approximately $100 million to $200 million for the full year as well as an estimated understatement of lease assets and liabilities of approximately $30 million to $125 million for the first three quarters of 2022 and 2023.

對於 2022 年，我們估計全年租賃資產和租賃負債低估約 1 億至 2 億美元，2022 年前三個季度租賃資產和負債估計低估約 3000 萬至 1.25 億美元， 2023 年。

While still working through the exact details, the lease will be reclassified as finance leases as a result, and we anticipate the increase of non-cash interest expense on our P&L. The restatement is not expected to have any impact on our cash position or revenue, in consideration of the time, we will take to complete the restatement, we have filed for an extension of our 10-K, and we anticipate that our 2023 10-K, inclusive of the restated periods will be filed April 16.

雖然仍在研究具體細節，但租賃將因此重新分類為融資租賃，我們預計損益表中的非現金利息費用將會增加。考慮到我們完成重述所需的時間，預計重述不會對我們的現金狀況或收入產生任何影響，我們已申請延長 10-K，並且我們預計 2023 年 10-K K，包括重述期間，將於4 月16 日提交。

And with that, let me turn it back over to Andrew.

接下來，讓我把它轉回給安德魯。

Thank you, Chris. And to summarize bluebird is deploying a validated commercial gene therapy strategy with three FDA approved therapies taking place in 2024, and delivering on our promise to patients and their families. We expect 2024 to be a transformative year for our company and we look forward to providing more updates in upcoming quarters as our commercial launch of our LYFEGNIA progresses.

謝謝你，克里斯。總而言之，藍鳥正在部署經過驗證的商業基因治療策略，並於 2024 年實施 FDA 批准的三種療法，並兌現我們對患者及其家人的承諾。我們預計 2024 年將是我們公司變革的一年，隨著 LYFEGNIA 商業發布的進展，我們期待在未來幾季提供更多更新。

And with that, I'd like to open it up for questions. Operator?

說到這裡，我想開放提問。操作員？

(Operator Instructions) Jason Gerberry, Bank of America.

（操作員指示）Jason Gerberry，美國銀行。

Hey, guys thanks for taking my question. I was wondering maybe if you can just speak to in the fourth quarter, the quarterly step-down in revenue and what you're seeing there to what extent that maybe speaks to sort of the conversion dynamics of the starts to an actual revenue recognition event? And then can you comment at all just as a follow-up, just directionally the flow of new starts first half versus second half in your outlook for the full year? Thanks.

嘿，夥計們，謝謝你回答我的問題。我想知道您是否可以談談第四季度收入的季度下降以及您在那裡看到的情況，這可能在多大程度上說明了實際收入確認事件開始的轉換動態？然後，您能否作為後續行動，在您對全年的展望中直接評論上半年和下半年的新開工量？謝謝。

Yeah, good morning, Jason, thanks for the questions.

是的，早上好，傑森，謝謝你的提問。

I might actually, Tom just talk a little bit about the patient dynamics and how they're coming in and the flow both for the fourth quarter was and ZYNTEGLO and then for the first and the second half of this year with LYFGENIA go ahead Tom?

事實上，湯姆可能會簡單談談患者動態以及他們如何進入，第四季度的流程是 ZYNTEGLO，然後是今年上半年和下半年的 LYFGENIA 繼續湯姆嗎？

Yeah, good morning, Jason, thanks for the question. So we saw strong demand in building demand over the course of the year last year for both for ZYNTEGLO and then as we expected, we started 6 patients for SKYSONA.

是的，早上好，傑森，謝謝你的提問。因此，去年我們看到 ZYNTEGLO 的需求強勁，然後正如我們預期的那樣，我們為 SKYSONA 開始了 6 名患者的治療。

With ZYNTEGLO, we actually collected a number of patients at the end of the year, that elected to be treated after the start of the new year. So although the collections were on track in Q4, many of those patients went on to be infused in Q1.

透過 ZYNTEGLO，我們實際上在年底收集了一些患者，他們選擇在新年開始後接受治療。因此，儘管第四季度的收集工作已步入正軌，但其中許多患者在第一季繼續接受輸注。

So that was the reason you saw a little bit of a dip in Q4, but we remain very positive on patient demand for us in ZYNTEGLO. We also are seeing just very strong demand force for LYFGENIA. We expect the linear build over the course of this year with the vast majority of the LYFGENIA starts happening in the second half of the year.

這就是第四季度略有下降的原因，但我們對 ZYNTEGLO 的患者需求仍然非常樂觀。我們也看到對 LYFGENIA 的需求非常強勁。我們預計今年的線性建設將在下半年開始，絕大多數 LYFGENIA 都會開始。

And Jason, just to reiterate, we said on [earlier too], we had some drug products that were delivered to the QTCs in Q4. But actually, we're not using those infusions will happen in Q1 and we recognize there and I would also say the quarter to date where we've had our best strongest quarter to date on starts nine total.

Jason，重申一下，我們[也早些時候]說過，我們有一些藥品已在第四季度交付給 QTC。但實際上，我們不會在第一季使用這些注入，我們認識到這一點，我還想說，迄今為止，我們在總共九個季度中擁有迄今為止最好的最強季度。

Got it thanks.

知道了謝謝。

(Operator Instructions) Danielle Brill, Raymond James.

（操作員說明）Danielle Brill、Raymond James。

Hey, guys, good morning thanks so much for the question. I guess as a follow-up to Jason, do you still have LYFEGNIA to make up over 50% of the total volume this year. And then I know you said that the first patient start imminent, but I believe in the past you communicated that multiple patients would start in 1Q? Just curious with -- getting those patients started? Thank you.

嘿，夥計們，早上好，非常感謝您的提問。我猜身為Jason的後續，今年還有LYFEGNIA占到總量的50%以上嗎？然後我知道您說第一個患者即將開始，但我相信您過去曾傳達過多個患者將在第一季開始？只是好奇──讓這些病人開始嗎？謝謝。

I'd ask Tom to answer that Tom?

我會請湯姆回答這個問題 湯姆？

Yeah, so again, we're excited about the momentum in the demand we're seeing with LYFEGNIA, we do expect roughly half or more of the volume to come from LYFEGNIA, obviously, it's a much larger patient population and we should see a lot of the starts, starting to pick up in the second half of the year as we build momentum.

是的，所以，我們對 LYFEGNIA 的需求勢頭感到興奮，我們確實預計大約一半或更多的數量將來自 LYFEGNIA，顯然，這是一個更大的患者群體，我們應該看到隨著我們建立勢頭，很多事情都開始了，下半年開始加速。

We did say that we would have a patient started in Q1, we believe that we'll have our first patient started very soon imminently. We've seen, again, very strong demand and what we see so far as a number of patients who have enrolled in the process and who are going through the process of getting ready for treatment across a number of different QTCs.

我們確實說過，我們將在第一季開始讓一名患者開始治療，我們相信我們很快就會讓第一個患者開始治療。我們再次看到了非常強勁的需求，到目前為止，我們看到許多患者已經參與了這個過程，並且正在經歷多個不同 QTC 的治療準備過程。

And keep in mind that if you look at just refer you to the package insert for LYFEGNIA. It takes about two months on average for patients to be medically ready as they have to wash out there hydroxyurea or disease modifying therapy, they might be on for at least two months. They have to also go through two rounds of transfusions one month each. So it just takes patients a little longer to get ready for therapy.

請記住，如果您查看，請參閱 LYFEGNIA 的包裝說明書。患者平均需要大約兩個月的時間才能做好醫療準備，因為他們必須接受羥基脲或疾病修飾治療，他們可能需要至少兩個月的時間。他們還必須每個月接受兩輪輸血。因此，患者只需要更長的時間來準備治療。

Got it thanks so much.

明白了，非常感謝。

(Operator Instructions) Jack Allen, Baird.

（操作員說明）Jack Allen、Baird。

Thanks for taking the question. I wanted to ask about your manufacturing capacity and how you think about [potential] influx patients in the quarters and potentially second half as well.

感謝您提出問題。我想詢問你們的製造能力以及你們如何看待本季和下半年的[潛在]湧入患者。

Can you provide some color, it relates to what capacity you have and how could you meet demand as it comes in different kind of waves as we think about the second half being really the build here as it relate to LYFEGNIA?

您能否提供一些顏色，它與您擁有的能力以及如何滿足不同類型的需求有關，因為我們認為下半年實際上是這裡的構建，因為它與 LYFEGNIA 相關？

And so and good morning, Jack. I'll take that one. So the first of all, I think important to understand is that the supply change for ZYNTEGLO, SKYSONA one supply chain and as a side supply chain LYFEGNIA. So the two don't impede upon each other. And the way we've designed it and obviously that we've designed our capacity for LYFEGNIA to be larger than our capacity for ZYNTEGLO, SKYSONA anticipation of a larger demand there.

那麼早安，傑克。我會接受那個。因此，首先，我認為重要的是要了解 ZYNTEGLO、SKYSONA 單一供應鏈以及作為側供應鏈 LYFEGNIA 的供應變化。所以兩者互不妨礙。我們的設計方式很明顯，我們為 LYFEGNIA 設計的產能大於 ZYNTEGLO 的產能，SKYSONA 預計那裡會有更大的需求。

And we do on both sides, both a factor and the drug product. We do anticipate that we have the volume or the capacity to meet the initial launch expectations. Our and what we also have in place is plans to expand that capacity as we see demand coming in. So we do anticipate that we do have capacity for this year and the launch phase of all our products.

我們在兩個方面都做，包括因素和藥物。我們確實預計我們有足夠的數量或能力來滿足最初的發布預期。我們也計劃在看到需求增加時擴大產能。因此，我們確實預期今年和所有產品的推出階段我們確實有產能。

Well, thanks.

非常感謝。

(Operator Instructions) Gena Wang, Barclays.

（操作員指示）Gena Wang，巴克萊銀行。

Thank you for taking my questions. I wanted to know that now you have a little bit early real-world experience, what is your expected from start to finish for LYFEGNIA?

感謝您回答我的問題。我想知道，現在你已經有了一些早期的現實世界經驗，你對 LYFEGNIA 從頭到尾的期望是什麼？

Good morning, Gena Tom go ahead.

早安，吉娜·湯姆，繼續。

Yeah, good morning, Gena. So we what we're saying is that obviously from so collection to infusion is a one to two quarters. The biggest part of that time is just the manufacturing time and range in the package insert is between 70 and 105 days plus two weeks. So that's the vast majority of time and then we obviously ship it back to QTC and then it's up to the QTC, when they infuse it. So we're saying for modeling purposes one to two quarters.

是的，早上好，吉娜。所以我們要說的是，顯然從收集到注入需要一到兩個季度。其中最大的部分就是生產時間，包裝說明書中的範圍為 70 至 105 天加兩週。所以這是絕大多數時間，然後我們顯然會將其運回 QTC，然後由 QTC 決定何時注入它。因此，出於建模目的，我們說的是一到兩個季度。

Thank you.

謝謝。

(Operator Instructions) Eric Joseph, JP Morgan.

（操作員指令）Eric Joseph，摩根大通。

Hi, good morning thanks for taking the question. I guess just if we're looking back at 2023, can you just -- provide a little more color on how many of the 24, I think total sell collections contributed to revenue generation and whether there, yeah, explicitly how many patients actually contributed to revenue recognition? And then how average time to treatment between collection and treatment has trended? What avenues do anticipate there being to sort of improve conversion rates going forward? Thanks.

你好，早安，謝謝你提出問題。我想，如果我們回顧 2023 年，您能否提供更多信息，說明 24 個系列中，我認為總銷售系列中有多少對創收做出了貢獻，以及是否明確有多少患者實際做出了貢獻收入確認？那麼採集和治療之間的平均治療時間趨勢如何？預計未來有哪些途徑可以提高轉換率？謝謝。

So Eric, good morning. So it's 26 collections in 2023. Every single patient that has gone through the process is still in the process of either been infused or had the drug product delivered or where the product is in process all still in the process.

埃里克，早安。所以到 2023 年會有 26 個系列。每位經歷過此過程的患者仍然處於輸注或交付藥品的過程中，或者產品正在加工的地方仍然處於加工過程中。

And we haven't actually given numbers of confusions, so I'm not going directly, but we have said, we have we infuse a number in 2023. We have some products that we've delivered in Q4 but not refuse you'll see that revenue in Q1 and I guess that those patients will be infused early this year.

我們實際上並沒有給出混亂的數字，所以我不會直接給出，但我們已經說過，我們在 2023 年註入了一個數字。我們在第四季度交付了一些產品，但不會拒絕，您將在第一季看到收入，我猜這些患者將在今年年初接受注射。

In general, you'll see that the time from collection to infusion is one to two quarters there will be some outliers there just as a hospital's chooses, refuse late or something else happened. But in general, it's one to two quarters as we get more collections and as we get more data, we'll be able to narrow that number down for you and give you kind of a more precise number. But still we're still dealing with relatively small numbers.

一般來說，你會看到從採集到輸液的時間是一到兩個季度，會有一些異常值，就像醫院的選擇、遲到拒絕或其他情況一樣。但總的來說，隨著我們收集更多的藏品和更多的數據，這個時間是一到兩個季度，我們將能夠為您縮小這個數字，並為您提供更精確的數字。但我們仍然在處理相對較小的數字。

Okay -- to remain in process, I guess is there a -- I guess, a bracket timeframe? I guess how long can a patient kind of be in process as it is or ultimately have a 9, 12-month window.

好的 - 為了繼續進行，我想是否有一個 - 我想，一個括號時間框架？我猜病人可以接受多長時間的治療，或者最終有 9、12 個月的窗口期。

So there's really no end date for that being the process except to the expiration of the drug product is just about a year, right once you manufactured it that the drug product will expire after a year a little bit longer. So that would be the in process. We don't anticipate we're going that far.

所以這個過程實際上沒有結束日期，除了藥品的有效期只有大約一年，一旦你生產出來，藥品將在一年後過期。這就是正在進行中的情況。我們預計我們不會走那麼遠。

But again, remember this is an election that the patient mix to get treated. So very often, they will schedule that around life events, et cetera, that's why it's somewhat unpredictable once we deliver the product back to the hospital when they will get them to use.

但再次請記住，這是患者混合接受治療的選擇。很多時候，他們會圍繞著生活事件​​等安排這一點，這就是為什麼一旦我們將產品送回醫院，他們何時使用它們，就有點難以預測。

Okay thanks for taking the question.

好的，謝謝您提出問題。

(Operator Instructions) Mani Foroohar, Leerink Partners.

（操作員說明）Mani Foroohar，Leerink Partners。

Thanks, guys. On a pivot a little bit into thinking about broader market dynamics. You've obviously talked about finding patient demand volume demand out there for LYFEGNIA, you said that's going to be perhaps half or more of the 85 or 105 patients.

多謝你們。稍微思考一下更廣泛的市場動態。您顯然談到了尋找 LYFEGNIA 的患者需求量，您說這可能是 85 或 105 名患者中的一半或更多。

Can you give us a little bit of sense of how deep that backlog is, how much clarity you have into it. I know you can't give us a numerical guidance number of patients currently, but can you give us some can you put some color around exactly what that backlog of identify of any potential of LYFEGNIA patients looks like? And I guess the separate follow-up, can you give us a sense of exactly what demand metrics and other data was available to Hercules as part of your engagement with them prior to their transaction with them? Just trying to extend their due diligence process as well?

您能否讓我們了解一下積壓的程度以及您對此的了解程度。我知道您目前無法向我們提供患者的指導數字，但您能否給我們一些指導，您能否對任何潛在 LYFEGNIA 患者的積壓識別情況進行一些說明？我想單獨的後續行動，您能否讓我們了解 Hercules 可以使用哪些需求指標和其他數據，作為您在與他們進行交易之前與他們接觸的一部分？只是想延長他們的盡職調查過程嗎？

Yeah. So I shall pass it to Thomas to talk about the backlog or the interest in LYFEGNIA and Chris, I'll talk about just what we provided Hercules, go ahead, Tom.

是的。因此，我將把它傳遞給托馬斯，討論積壓的工作或對 LYFEGNIA 和克里斯的興趣，我將討論我們為赫拉克勒斯提供的內容，繼續吧，湯姆。

Yeah, good morning Mani, keep in mind that if you look back a year, people were asking questions around, could we get to our goal of 40 to 50 QTCs, which was a factor in making sure that patients had access to therapy.

是的，早安，Mani，請記住，如果你回顧一年，人們會問一些問題，我們能否實現 40 到 50 個 QTC 的目標，這是確保患者獲得治療的一個因素。

People are also asking questions around reimbursement and then lastly, people were asking about patient demand. And now we have 62 qualified treatment centers up and running. We've seen reimbursement happen we have positive coverage policy so far, we LYFEGNIA so that box has been checked and now you're looking at patient demand and we've seen historically in market research that over 70% of patients who have more severe sickle cell disease have said they would seek a gene therapy if recommended by their physician.

人們也詢問有關報銷的問題，最後，人們詢問患者的需求。現在我們有62個合格的治療中心正在運作。我們已經看到了報銷的發生，到目前為止，我們有積極的承保政策，我們LYFEGNIA 所以這個框已經被選中，現在你正在考慮患者的需求，我們在市場研究中看到歷史上超過70% 的患者患有更嚴重的疾病鐮狀細胞疾病患者表示，如果醫生建議，他們將尋求基因療法。

And now we're seeing that play out in real life. We have multiple enrollments already just in the few months after approval across multiple QTCs, we wouldn't expect a huge bolus because patients, as Andrew mentioned, can treat get treated for their schedules that also I think QTCs are going to want to treat a handful of patients first before they go through their list of patients.

現在我們正在現實生活中看到這種情況的發生。在多個QTC 獲得批准後的幾個月內，我們已經進行了多次註冊，我們預計不會有大量的推注，因為正如安德魯提到的，患者可以按照他們的時間表接受治療，我也認為QTC 會想要治療在檢查患者名單之前，首先要檢查少數患者。

But anecdotally, we've heard of long wait lists at QTCs of patients who have sickle cell disease that are looking to be treated. So we're again, I can't overemphasize how excited we are about the early demand that we're seeing.

但有趣的是，我們聽說 QTC 等待治療的鐮狀細胞疾病患者名單很長。所以我們再次，我不能過度強調我們對所看到的早期需求有多興奮。

Chris could you comment on (inaudible) provided Hercules?

克里斯，你能評論一下（聽不清楚）提供的赫拉克勒斯嗎？

Thanks to the question. With respect to what Hercules receive. So Hercules receive customary information as it relates to projections, not just 2024, but beyond that and the confidence that having a third party come in and scrutinize our projection should provide confidence to the marketplace on the achievability of those considering they entered into the arrangement for the $175 million finance.

感謝提問。關於赫拉克勒斯收到的東西。因此，Hercules 會收到與預測相關的常規訊息，不僅是2024 年，而且還包括其他預測，並且有信心讓第三方介入並審查我們的預測，這應該為市場提供信心，讓市場相信那些考慮參與該安排的人的可實現性。1.75 億 美元的融資。

What I would say though, is that the patient start guidance that you saw there for LYFEGNIA should not be viewed as consensus, right? That's viewed as progress. So that milestone associated with that not consensus. We provided our guidance, which is the 85 to 105 starts.

但我想說的是，您在 LYFEGNIA 看到的患者開始指南不應被視為共識，對嗎？這被視為進步。因此，與此相關的里程碑並非共識。我們提供了我們的指導，即 85 到 105 開始。

Okay that's helpful, guys. Thanks guys.

好的，這很有幫助，夥計們。多謝你們。

(Operator Instructions) Jeff Hung, Morgan Stanley.

（操作員指令）Jeff Hung，摩根士丹利。

Thanks for taking my questions, for LYFEGNIA with 49 QTCs already receiving referrals, what proportion of these sites might have their first patient cell collections in the first half of the year. What are the gating factors that might result in different timelines, particularly for the 35 sites that were online at the beginning of year? And then I have a follow-up.

感謝您提出我的問題，對於 LYFEGNIA 來說，已經有 49 個 QTC 接受轉診，這些站點中有多少比例可能會在今年上半年收集第一批患者細胞。哪些限制因素可能會導致不同的時間表，特別是對於年初上線的 35 個網站？然後我有一個後續行動。

Go ahead Tom.

湯姆，繼續吧。

Yeah, sure we haven't really given specific guidance for QTC, but needless to say, a lot of QTCs were coming on board late last year in anticipation for LYFEGNIA launch and approval. So we would expect most of our QTC seems to be pretty excited about getting patients started on with LYFEGNIA.

是的，當然我們還沒有真正為 QTC 提供具體指導，但不用說，去年年底，許多 QTC 都在等待 LYFEGNIA 的推出和批准。因此，我們預計我們的大多數 QTC 似乎對讓患者開始使用 LYFEGNIA 感到非常興奮。

In most cases, they are waiting for patients to come in for their regular appointments. And in some cases, they know if they have a waiting list, stay for a patient that wanted to drive a gene therapy through a clinical trial, then those patients might go faster. So we have really the dynamic will play out, but we're excited about the early enrollments that we've seen and across multiple QTCs not one or two QTCs, and we're excited about the excitement for gene therapy.

在大多數情況下，他們正在等待患者前來進行常規預約。在某些情況下，他們知道如果他們有一個等候名單，留下來等待那些想要透過臨床試驗推動基因治療的患者，那麼這些患者可能會走得更快。因此，我們確實有動力發揮作用，但我們對我們所看到的早期註冊和跨多個 QTC 而不是一兩個 QTC 感到興奮，我們對基因治療的興奮感到興奮。

Okay, thanks. And then for the third tranche of the term loan facility, but what would you need to see in patient starts by the end of the year? To be on track to reach the $30 million gross profit milestone by the end of the first half of '25, thanks.

好的謝謝。然後是定期貸款便利的第三部分，但到年底您需要在耐心啟動中看到什麼？到 25 年上半年末，我們預計將達到 3000 萬美元的毛利里程碑，謝謝。

Go ahead, Chris.

繼續吧，克里斯。

So -- we haven't commented on that, we commented on was the exact metric associated with that, but we're not going to comment on the patient start number. Remember, our patient start guidance that we provided in the second tranche was the $35 million by September, the $55 million by the end of the year for LYFEGNIA. And then there's a gross profit metric also. And then the third tranche, but we're not going to provide that level of detail associated with the number of equivalent patient starts to get to the gross profit.

因此，我們沒有對此發表評論，我們評論的是與之相關的確切指標，但我們不會評論患者的起始編號。請記住，我們在第二批中提供的患者啟動指導是到 9 月為 LYFEGNIA 提供 3500 萬美元，到年底為 5500 萬美元。然後還有一個毛利指標。然後是第三部分，但我們不會提供與開始獲得毛利的同等患者數量相關的詳細資訊。

Sorry, Jeff you were asking about the first tranche, you said a third tranche of thinking that the second?

抱歉，傑夫，你問的是第一批，你說的是第三批，第二批呢？

Yeah, I was talking about the third tranche, yeah.

是的，我正在談論第三部分，是的。

So the first tranche of $50 million second tranche is $25 million, which is that it's keyed off of either the that $35 million of the $55 million us starts by the end of the year. And then there's a third tranche, $25 million that is that is keyed off a different metric, really just dropping the gross profit.

因此，第一筆 5000 萬美元的第二筆金額為 2500 萬美元，也就是說，它將從今年年底啟動的 5500 萬美元中的 3500 萬美元中扣除。然後是第三部分，即 2500 萬美元，這是根據不同的指標確定的，實際上只是降低了毛利。

Just to be clear, the first tranche was the $75 million. The second tranche is the $25 million and $25 million is attributable to LYFEGNIA patient starts as I said $35 million by September, $55 million by December 31. And then the third tranche is associated with gross profit.

需要明確的是，第一筆金額為 7500 萬美元。第二部分是 2500 萬美元，其中 2500 萬美元歸屬於 LYFEGNIA 患者的啟動資金，正如我所說的，到 9 月將支付 3500 萬美元，到 12 月 31 日將支付 5500 萬美元。第三部分與毛利相關。

Right.

正確的。

And then of course, as (inaudible), the fourth tranches that $50 million, that's at the discretion of Hercules?

當然，（聽不清楚）第四部分的 5000 萬美元是由赫拉克勒斯自行決定的嗎？

Yes, thank you.

是的，謝謝。

Yeah, you said that you wouldn't comment on the number of patient starts for the $30 million gross profit?

是啊，你說過你不會對3000萬美元毛利的患者啟動數量發表評論嗎？

Yeah okay thank you.

是的，好的，謝謝。

That's correct, that's correct.

沒錯，沒錯。

(Operator Instructions) Salveen Richter, Goldman Sachs.

（操作員指令）Salveen Richter，高盛。

Good morning thanks for taking my question. I'm just in line with the trajectory that you're seeing right now and the understanding of -- the various onboarding dynamics, reimbursement dynamics? How are you thinking about the peak opportunity here for the drug? And just maybe an update on ex-US commercialization. Thank you.

早安，謝謝您提出我的問題。我只是符合你現在看到的軌跡和理解——各種入職動態、報銷動態？您如何看待該藥物的高峰機會？也許只是美國以外商業化的最新情況。謝謝。

Yeah, so Salveen you got I was a little hard to hear, but I think you asked what the peak opportunity is for the drug?

是的，Salveen 你說的我有點難以聽清，但我想你問過這種藥物的最佳機會是什麼？

Yes and ex-US commercialization outlook.

是的，還有美國以外的商業化前景。

Actually okay got it so muted. So if we do see is a multi-billion dollar opportunity at peak in the US alone ex-US, we do think there's a very attractive opportunity there as well. There's a right now we as a company are focused exclusively on the US. If we go ex-US, we most certainly do that with a partner. We are watching very closely to the reimbursement dynamics of gene therapy in Europe as well, such that's kind of it key dynamic they'll determine the opportunity there.

其實還好，這麼安靜。因此，如果我們確實看到僅在美國（美國除外）的高峰期就有數十億美元的機會，我們確實認為那裡也存在非常有吸引力的機會。目前，我們作為一家公司只專注於美國。如果我們走出美國，我們肯定會與合作夥伴一起這樣做。我們也密切關注歐洲基因治療的報銷動態，這是他們決定在那裡機會的關鍵動態。

Thank you.

謝謝。

(Operator Instructions) Sami Corwin, William Blair.

（操作員說明）Sami Corwin、William Blair。

Hi there thanks for taking my questions. I was curious if you could speak a little more as to the cost of good near gross margins and how you expect them to change as your launches across the portfolio continue? And then can you provide any granularity in terms of your assumptions for the LYFEGNIA launch this year and the percentage of patients you expect to be covered for -- covered by Medicaid versus private insurers?

您好，感謝您回答我的問題。我很好奇您是否能多談談近毛利率的成本，以及隨著您繼續推出整個投資組合，您預計它們會如何變化？然後，您能否詳細說明您對今年推出 LYFEGNIA 的假設，以及您期望承保的患者比例（醫療補助與私人保險公司承保的患者比例）？

Yeah, Sami good morning, so let me have Thomas assist the second part first, and then I'll go to Chris Thomas, that percentage on LYFEGNIA on Medicaid.

是的，薩米早上好，所以讓我先讓托馬斯協助第二部分，然後我會去找克里斯·托馬斯，講講 LYFEGNIA 在醫療補助上的百分比。

Just to give you the stats again, about 50% of patients or people living with sickle cell disease are covered by Medicaid, about 45% are covered by commercial insurance and then a small portion of Medicare. It's hard to predict too early patients will be, but we would expect over time that the payer mix will play out like we've seen historically.

再次向您提供統計數據，大約 50% 的鐮狀細胞疾病患者或患有鐮狀細胞疾病的人享受醫療補助，大約 45% 享受商業保險，然後是一小部分醫療保險。很難過早點預測患者的情況，但我們預計隨著時間的推移，付款人組合將像我們歷史上看到的那樣發揮作用。

Chris?

克里斯？

I am just covering on the cost of sales and maybe I'll answer it a slightly different way, which I think is what you're intending is gross margin. So the gross margin for the company will improve as we scale. And we've said that we would get to a 70% gross margin. And as we scale the company not only with filling the capacity with infusions and then continuing to kind of scale the capacity in a gated fashion over time as needed. And the gross margin will continue to improve to achieve that 70% that we discussed.

我只是在討論銷售成本，也許我會以稍微不同的方式回答這個問題，我認為這就是您想要的毛利率。因此，隨著我們規模的擴大，公司的毛利率將會提高。我們說過我們的毛利率將達到 70%。當我們擴大公司規模時，不僅要透過注入來填充產能，然後根據需要繼續以封閉的方式擴大產能。毛利率將繼續提高，達到我們討論的 70%。

Great thanks.

萬分感謝。

(Operator Instructions) Yanan Zhu, Wells Fargo.

（操作員說明）Yanan Zhu，富國銀行。

Hi thanks for taking our questions. So just curious, when you say multiple patient enrolled for LYFEGNIA does enrollment imply approval of inference and the time from enrollment to cell collection is the main gating factor those washout period and also the -- pre transfusions, if not, what might be the gating factor you see. Also as a quick follow-up if you can talk about the 19% gross-to-net to date, is that different significantly between than ZYNTEGLO and SKYSONA?

您好，感謝您回答我們的問題。所以只是好奇，當你說多名患者登記參加LYFEGNIA 時，登記是否意味著推論的批准，從登記到細胞收集的時間是主要的門控因素，這些沖洗期以及- 輸血前，如果不是，門控可能是什麼你看到的因素。另外，作為一個快速跟進，如果您能談談迄今為止 19% 的毛淨比，ZYNTEGLO 和 SKYSONA 之間是否存在顯著差異？

And any expectation for the gross to net for LYFEGNIA to be very different from that 19% number? Thanks.

LYFEGNIA 的毛淨值是否會與 19% 的數字有很大不同？謝謝。

Thanks for the questions Tom, why don't you address the enrollments and then we'll have Chris address that gross-to-net question.

感謝湯姆提出的問題，為什麼你不解決註冊問題，然後我們將讓克里斯解決這個總淨值問題。

Yeah again, we're very excited about the multiple enrollments across multiple QTCs, I think is an indicator of strong demand. The road to yes, as we call it is multifaceted in the two big components there are, obviously, as you mentioned, making sure that they're covered by their insurance and that's taking approximately what it was ZYNTEGLO we're saying on average about two.

是的，我們對多個 QTC 的多次註冊感到非常興奮，我認為這是需求強勁的指標。正如我們所說，通往「是」的道路是多方面的，其中有兩個主要組成部分，顯然，正如您所提到的，確保他們得到保險的承保，這大約相當於我們所說的ZYNTEGLO平均水平二。

And then second part of being ready is being medically ready and this is a little bit different with LYFEGNI than it was for ZYNTEGLO with LYFEGNI there's a washout period of their other medications. For example, hydroxyurea has to be discontinued for at least two months before they start therapy, and they're also supposed to go for transfusions at least two transfusions one month apart.

準備的第二部分是醫學上的準備，這與 LYFEGNI 和 ZYNTEGLO 有點不同，LYFEGNI 有一個其他藥物的沖洗期。例如，在開始治療之前，必須停用羥基脲至少兩個月，並且還應該至少間隔一個月進行兩次輸血。

So once they're enrolled and once they're going through the process, if they're not already doing transfusions, if they're already doing transfusions and they're not on one of the medications that needs to be discontinuing that can go a lot faster.

因此，一旦他們登記並完成整個過程，如果他們尚未進行輸血，如果他們已經進行輸血並且他們沒有服用需要停止的藥物之一，則可以繼續快很多。

So I'm a little hesitant to give you an average right now because it's just going to depend on the patients and we provided enrollments today. Enrollments is an early indicator of patient demand. The thing to watch going forward is number of patient starts that continues to be the value creating moment for the company.

所以我現在有點猶豫是否要給你一個平均值，因為這取決於患者，而且我們今天提供了登記情況。註冊人數是患者需求的早期指標。未來值得關注的是患者開始數量，這仍然是公司創造價值的時刻。

And Chris, want to comment on.

克里斯想發表評論。

So the 19% that we discussed between the combined two products just characteristically the difference between ZYNTEGLO and SKYSONA. ZYNTEGLO has an outcomes-based agreements, SKYSONA does not. And then what to expect on a go forward basis as LYFEGNIA comes into the fray is a higher increase Medicaid population associated with LYFEGNIA. And that's where you saw that we provided guidance to 20% to 25% associated with the combined gross to net population of all three products.

因此，我們討論的兩個產品組合之間的 19% 正是 ZYNTEGLO 和 SKYSONA 之間的典型差異。ZYNTEGLO 有基於結果的協議，而 SKYSONA 沒有。隨著 LYFEGNIA 加入競爭，未來預計與 LYFEGNIA 相關的醫療補助人口將有更高的成長。您可以看到，我們提供了與所有三種產品的總人口與淨人口總和相關的 20% 至 25% 的指導。

Got it thanks.

知道了謝謝。

(Operator Instructions) Luca Issi, RBC Capital Markets.

（操作員指令）Luca Issi，RBC 資本市場。

Hi, this is Reena for Luca Issi. Thanks for taking my question. I just wanted to ask during the last approval call after not receiving the PRV you mentioned that you're engaged in discussion with the agency and attempt to achieve a potentially positive outcome, like ultimately meaning receiving a PRV, just wondering if there was any update on that?

大家好，我是盧卡·伊西的瑞娜。感謝您提出我的問題。我只是想在上次未收到 PRV 的批准電話中詢問您提到您正在與該機構進行討論並試圖實現潛在的積極結果，例如最終意味著收到 PRV，只是想知道是否有任何更新關於那個？

Yeah thanks for the question, we have submitted a request for reconsideration and we have discussions with the agency we're not going to elaborate on ongoing discussion with the agency now, but we believe we have a clear and compelling rationale for why LYFEGNIA, to be a word of PRV will provide an update when we conclude our discussions.

是的，謝謝你的問題，我們已經提交了重新考慮的請求，並且我們與該機構進行了討論，我們現在不打算詳細說明與該機構正在進行的討論，但我們相信我們有一個明確且令人信服的理由來說明為什麼LYFEGNIA當我們結束討論時，PRV 的一句話將提供更新。

Thanks for taking my questions.

感謝您回答我的問題。

Thank you and this will now conclude today's question and answer session. I'll now turn the call back over to Andrew Obenshain, for closing remarks.

謝謝大家，今天的問答環節到此結束。現在我將把電話轉回給安德魯·奧本沙恩，讓他作結束語。

Great thank you, everyone for joining our call this morning and for your questions. Our management team is available for a follow-up call today and please reach out to Courtney, if you would like to connect thank you very much.

非常感謝大家今天早上加入我們的電話會議並提出問題。我們的管理團隊今天可以接聽後續電話，如果您想聯繫，請聯繫 Courtney，非常感謝。

This concludes today's conference call and thank you for your participation you may now disconnect everyone, have a wonderful day.

今天的電話會議到此結束，感謝您的參與，您現在可以與大家斷開連接，祝您有美好的一天。