Solid Biosciences Inc (SLDB) 2022 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Solid Biosciences Strategic Business Update and Financial Results Conference Call. (Operator Instructions)

女士們先生們，感謝你們的耐心等待，並歡迎參加 Solid Biosciences 策略業務更新和財務業績電話會議。 （操作員說明）

I would now like to hand the conference over to Caitlin Lowie, Vice President of Communications and Investor Relations at Solid Biosciences. Ms. Lowie, you may begin.

我現在想將會議交給 Solid Biosciences 傳播和投資者關係副總裁 Caitlin Lowie。洛伊女士，您可以開始了。

Good morning. Thank you, operator. Before we get started, I would like to remind everyone that during today's conference call, we may make forward-looking statements, including statements about the company's financial results, financial guidance, future business strategies and operations and product development and regulatory progress, including statements about the company's IGNITE DMD clinical trial. Actual results could differ materially from those discussed in these forward-looking statements due to a number of important factors, including uncertainty inherent in the clinical development and regulatory process. The extent and duration of the impact of the COVID-19 pandemic and other risks described in the Risk Factors section of our most recently filed annual report on Form 10-K and other periodic reports filed with the SEC. We undertake no obligation to update any forward-looking statements after the date of this call.

早安.謝謝你，接線生。在開始之前，我想提醒大家，在今天的電話會議中，我們可能會做出前瞻性陳述，包括有關公司財務業績、財務指引、未來業務策略和營運以及產品開發和監管進展的陳述，包括有關公司財務表現、財務指引、未來業務策略和營運以及產品開發和監管進展的陳述。關於該公司的 IGNITE DMD 臨床試驗。由於許多重要因素，包括臨床開發和監管過程中固有的不確定性，實際結果可能與這些前瞻性陳述中討論的結果有重大差異。我們最近提交的 10-K 表年度報告和向 SEC 提交的其他定期報告的風險因素部分描述了 COVID-19 大流行的影響程度和持續時間以及其他風險。我們不承擔在本次電話會議之後更新任何前瞻性陳述的義務。

With me on today's call are Ilan Ganot, Co-Founder, President and Chief Executive Officer of Solid Biosciences; Dr. Joel Schneider, our Chief Operating Officer; Dr. Carl Morris, our Chief Scientific Officer; and Dr. Roxana Donisa Dreghici, Senior Vice President and Head of Clinical Development.

參加今天電話會議的有 Solid Biosciences 聯合創辦人、總裁兼執行長 Ilan Ganot； Joel Schneider 博士，我們的營運長； Carl Morris 博士，我們的首席科學官；以及資深副總裁兼臨床開發主管 Roxana Donisa Dreghici 博士。

During today's call; we will share details of the strategic update the company announced this morning. We'll begin with opening remarks from Ilan, followed by Joel, who will share details of an intended change we'll be making to the manufacturing approach for SGT-001. Carl will then review new preclinical data related to SGT-003. Finally, Ilan will provide an overview of the organizational strategy that aligns behind these 2 programs before opening the call to questions.

在今天的電話會議中；我們將分享公司今天早上宣布的策略更新的詳細資訊。首先由 Ilan 致開幕詞，然後由 Joel 致辭，他將分享我們將對 SGT-001 製造方法進行的預期更改的詳細信息。 Carl 隨後將檢視與 SGT-003 相關的新臨床前數據。最後，在開始提問之前，Ilan 將概述這兩個項目背後的組織策略。

Before I turn the call over to Ilan, I want to acknowledge that our first quarter financial results have been reported and can also be found on our Form 10-Q, which was filed with the SEC this morning.

在我將電話轉給 Ilan 之前，我想確認我們第一季的財務業績已經報告，並且也可以在我們今天早上向 SEC 提交的 10-Q 表格中找到。

For opening remarks, I'd like to turn the call over to Solid's CEO, Ilan Ganot. Ilan?

作為開場白，我想將電話轉給 Solid 的執行長 Ilan Ganot。伊蘭？

Thank you, Caitlin, and thanks to all of you for joining us this morning. Solid's ongoing focus in Duchenne has produced 2 potential therapies for this devastating disease. And today, we will outline our strategy to continue development of our lead program, SGT-001, and for the potential benefit of SGT-003's novel capsid to deliver our differentiated microdystrophin. This is all supported by a cash position of approximately $180 million at the end of the first quarter of 2022.

謝謝凱特琳，也謝謝大家今天早上加入我們。 Solid 對 Duchenne 的持續關注已經為這種毀滅性的疾病產生了兩種潛在的療法。今天，我們將概述我們的策略，以繼續開發我們的主導項目 SGT-001，並利用 SGT-003 的新型衣殼的潛在優勢來提供我們的差異化微肌營養不良蛋白。這一切都得到了 2022 年第一季末約 1.8 億美元現金狀況的支持。

The Board and Solid's leadership team remain committed to the progress of both programs, and I'll now summarize our path forward.

董事會和 Solid 的領導團隊仍然致力於這兩個專案的進展，現在我將總結我們前進的道路。

First, following a thorough assessment of currently available alternatives for the manufacturing the SGT-001, where they decide a process that we believe will produce high-quality drug products while narrowing the organization's focus to a single production platform and streamlining our operating structure to a more efficient model. Joel will discuss our refined strategy to advance SGT-001 into late-stage clinical development with transient transfection-based manufacturing.

首先，在對目前可用的SGT-001 製造替代方案進行全面評估後，他們決定採用一種我們認為能夠生產高品質藥品的工藝，同時將組織的重點縮小到單一生產平台，並將我們的營運結構簡化為更有效率的模型。 Joel 將討論我們透過基於瞬時轉染的製造將 SGT-001 推進到後期臨床開發的改進策略。

We believe this transition has minimal impact to our time lines for further development through to the potential BLA filing and improve our potential to make a difference for those living with Duchenne.

我們相信這項轉變對我們進一步開發直至潛在的 BLA 備案的時間線影響極小，並提高了我們為杜興氏症患者帶來改變的潛力。

Second, our next-generation capsid used in SGT-003 has the potential to offer significant advantages for Duchenne gene therapy as well as for the broader gene therapy field for muscle disorders. We will continue to advance towards an IND submission early 2023 and further derisk this program and the novel capsid. We expect the clinical proof of concept for SGT-003 in 2023 will provide further support of our next-generation capsid platform.

其次，我們在 SGT-003 中使用的下一代衣殼有可能為 Duchenne 基因治療以及更廣泛的肌肉疾病基因治療領域提供顯著的優勢。我們將繼續推進 2023 年初提交 IND 的工作，並進一步消除該計劃和新型衣殼的風險。我們預計 2023 年 SGT-003 的臨床概念驗證將為我們的下一代衣殼平台提供進一步支援。

As a result of the focused approach on these programs and Solid's cash runway through Q2 2024, the company will be able to progress through important clinical milestones for both gene therapy programs.

由於對這些項目採取重點關注的方法以及 Solid 到 2024 年第二季的現金跑道，該公司將能夠在這兩個基因治療項目上取得重要的臨床里程碑。

I will now hand it over to Joel to go through our SGT-001 update in more detail.

現在我將把它交給 Joel 來更詳細地介紹我們的 SGT-001 更新。

Thanks, Ilan. In March, we released an interim analysis, a functional and durability data from the first 3 patients dosed in the high-dose cohort 2 years after treatment with SGT-001 as part of the IGNITE DMD Phase I/II study. Across all measures, including motor function, pulmonary function and patient-reported outcome measures, patients are showing consistent durable improvements after dosing compared to expected declines in untreated patients.

謝謝，伊蘭。今年3 月，我們發布了一項中期分析，這是IGNITE DMD I/II 期研究的一部分，在使用SGT-001 治療2 年後，在高劑量隊列中接受給藥的前3 名患者的功能和耐久性數據。在所有指標中，包括運動功能、肺功能和患者報告的結果指標，與未經治療的患者的預期下降相比，患者在給藥後表現出一致的持久改善。

We also shared that patients recently dosed in the high-dose cohort demonstrated microdystrophin expression and localization at 90 days within the range of earlier patients in the high-dose cohort at the same period of time.

我們還分享到，最近在高劑量隊列中接受給藥的患者在 90 天時表現出微抗肌營養不良蛋白的表達和定位，在同一時間段高劑量隊列中早期患者的範圍內。

And finally, all IGNITE DMD patients continue to do well with no long-term safety events.

最後，所有 IGNITE DMD 患者均表現良好，沒有發生長期安全事件。

These data are important as they continue to support the potential that Solid's nNOS-containing microdystrophin is providing durable benefits to patients and warrants further clinical development. We are now focusing on finalizing late-stage clinical and regulatory strategies, supported by a commercial scale manufacturing process.

這些數據非常重要，因為它們繼續支持 Solid 的含有 nNOS 的微肌營養不良蛋白為患者提供持久益處的潛力，並保證進一步的臨床開發。我們現在專注於最終確定後期臨床和監管策略，並得到商業規模製造流程的支持。

As part of our platform development efforts, we undertook a comprehensive analysis comparing transient and HSV-based manufacturing processes across a number of factors. We collected multiple data sets from different scales of manufacturing to help us compare the processes and to assess how they would scale for production.

作為我們平台開發工作的一部分，我們對瞬態和基於 HSV 的製造流程進行了全面分析，並比較了多個因素。我們從不同規模的製造中收集了多個數據集，以幫助我們比較流程並評估它們如何擴大生產規模。

Overall, our analysis concluded that by developing SGT-001 and SGT-003 using transient production platforms, we believe we can achieve a high-quality and highly potent product demonstrating high levels of microdystrophin expression in both our in vitro and in vivo expression assays. We can improve our consistency in product supply yields and have access to a broader supply chain which is reflective of the adoption of this more commonly utilized manufacturing platform.

總的來說，我們的分析得出的結論是，透過使用瞬時生產平台開發SGT-001 和SGT-003，我們相信我們可以獲得高品質和高效的產品，在我們的體外和體內表達測定中顯示出高水平的微肌營養不良蛋白表現。我們可以提高產品供應產量的一致性，並獲得更廣泛的供應鏈，這反映了採用這種更常用的製造平台。

The turnkey commercially scaled solution will allow us to ease our sole reliance on internal development and manufacturing operations. Organizationally, transitioning SGT-001 to a transient-based process will bring Solid under a single manufacturing methodology, allowing us to streamline our operations.

交鑰匙商業規模解決方案將使我們能夠減輕對內部開發和製造業務的唯一依賴。在組織上，將 SGT-001 過渡到基於瞬態的流程將使 Solid 處於單一製造方法之下，使我們能夠簡化營運。

Now I will walk through the next 12 months for SGT-001 as we look to resume dosing in the first half of 2023.

現在，我將回顧 SGT-001 的未來 12 個月，因為我們希望在 2023 年上半年恢復給藥。

Importantly, activities to transition to the new manufacturing process have already begun, with products expected to be available in early 2023, aligning well with our regulatory and clinical activities to support dosing patients.

重要的是，過渡到新製造流程的活動已經開始，產品預計將於 2023 年初上市，這與我們支持患者用藥的監管和臨床活動保持一致。

The transition to the new manufacturing process was a natural opportunity for us to pause and consider how to proceed with clinical development. As part of our strategy, we have decided to conclude enrollment in IGNITE DMD and moving forward, patients will be dosed using material from the new process, and we have already begun conversations with the FDA to determine the design of a future clinical study.

向新製造流程的過渡對我們來說是一個自然的機會，可以停下來考慮如何繼續進行臨床開發。作為我們策略的一部分，我們決定完成 IGNITE DMD 的入組，並展望未來，患者將使用新製程中的材料進行給藥，我們已經開始與 FDA 對話，以確定未來臨床研究的設計。

In addition, we will be initiating a natural history study that will support future clinical activities, both for SGT-001 and SGT-003, helping us establish the risk benefit of our programs.

此外，我們將啟動一項自然史研究，以支持 SGT-001 和 SGT-003 未來的臨床活動，幫助我們確定專案的風險效益。

There are a number of milestones over the next 12 months that we aim to communicate such as updates on our discussions with the FDA and additional data coming out of IGNITE DMD, including 1-year biopsy and functional analysis of all patients dosing the program as well as 3-year follow-up on functional data from patients 4 to 6.

我們計劃在未來 12 個月內傳達許多里程碑，例如我們與 FDA 討論的最新情況以及 IGNITE DMD 提供的其他數據，包括對所有服用該計劃的患者進行的 1 年活檢和功能分析對4 至6 號患者的功能數據進行3 年追蹤。

Now, I will turn the call over to Carl. Carl?

現在，我將把電話轉給卡爾。卡爾？

Thanks, Joel, and good morning, everyone. I'm pleased to be able to share new data coming out of our novel capsid library development program.

謝謝喬爾，大家早安。我很高興能夠分享我們新穎的衣殼庫開發計畫的新數據。

Let me briefly review our SGT-003 program. This program utilizes a novel, rationally-designed capsid that has demonstrated improved muscle tropism compared to AAV9 and packages Solid's differentiated nNOS binding domain-containing microdystrophin.

讓我簡單回顧一下我們的 SGT-003 計畫。該程序利用了一種新穎的、合理設計的衣殼，與 AAV9 相比，該衣殼具有更好的肌肉向性，並包裝了 Solid 的差異化 nNOS 結合域，其中含有微肌營養不良蛋白。

This microdystrophin is the same that is used in SGT-001. And as Joel shared earlier, it has been shared to deliver durable and promising benefits to patients in the IGNITE DMD study.

這種微抗肌營養不良蛋白與 SGT-001 中使用的相同。正如 Joel 之前分享的那樣，它的分享是為了在 IGNITE DMD 研究中為患者帶來持久且有希望的益處。

Over the last couple of years, we have shared a variety of data on SGT-003 and as summarized on this slide. After observing promising data in mouse and human Duchenne muscle cells. As shown on the left, we compare by distribution and microdystrophin expression in dystrophic mice of the novel capsid versus AAV9.

在過去幾年中，我們分享了有關 SGT-003 的各種數據，如本投影片中所總結的。在小鼠和人類杜氏肌肉細胞中觀察到有希望的數據後。如左圖所示，我們比較了新型衣殼與 AAV9 的營養不良小鼠的分佈和微肌營養不良蛋白表現。

Improved muscle tropism was observed within novel capsid that also resulted in (inaudible) significant reduction in circulating creatine kinase levels for AAV9 as shown in the center of the slide.

在新型衣殼中觀察到肌肉向性得到改善，這也導致（聽不清楚）AAV9 循環肌酸激酶水平顯著降低，如幻燈片中心所示。

Additionally, we ran an in vivo study in wild-type mice to determine if we would see similar changes in the level of expression as seen in the MDX mice.

此外，我們在野生型小鼠中進行了一項體內研究，以確定我們是否會看到與 MDX 小鼠中相似的表達量變化。

For this study, we used reporter CMV luciferase construct. As you can see on the right-hand side of this page, we did observe increased expression in the wild type mice as well. And when analyzed, we found more target expression to the muscles with lower biodistribution and expression in the liver when compared to AAV9.

在本研究中，我們使用了 CMV 螢光素酶報告基因構築體。正如您在本頁右側看到的，我們也確實觀察到野生型小鼠的表達增加。在分析時，我們發現與 AAV9 相比，肌肉中的標靶表達更多，生物分佈更低，肝臟中的表達更低。

After the promising results seen in human cells and the mouse studies, we wanted to flavor test the translatability of the increased muscle tropism in nonhuman primates as well as have an exploratory look at safety in larger animals.

在人類細胞和小鼠研究中看到有希望的結果後，我們想要對非人類靈長類動物中增加的肌肉向性的可翻譯性進行風味測試，並探索性地研究大型動物的安全性。

So earlier this year, we initiated the study using CMV luciferase (inaudible) and dosed 8 cynomolgus monkeys. 4 of them, 2 male and 2 female, were dosed with reported construct using AAV9 while the other 4 were dosed with novel capsid being used in SGT-003.

因此，今年早些時候，我們啟動了使用 CMV 螢光素酶（聽不清楚）的研究，並對 8 隻食蟹猴進行了給藥。其中 4 名（2 名男性和 2 名女性）接受了報告的使用 AAV9 的構建體，而另外 4 名則接受了 SGT-003 中使用的新型衣殼。

Our goal for the novel capsid program has been to see at least twofold improvement compared to AAV9 in biodistribution to skeletal and cardiac muscle. What we are highlighting here today is an increase in biodistribution greater than the goal of twofold improvement for both skeletal and cardiac tissue.

我們對新型衣殼計畫的目標是在骨骼和心肌的生物分佈方面與 AAV9 相比至少提高兩倍。我們今天在這裡強調的是生物分佈的增加大於骨骼和心臟組織雙重改善的目標。

We also see a promising twofold reduction in biodistribution to the liver.

我們也看到肝臟的生物分佈有望倍增。

On the next slide, we similarly observed an increase in the luciferase expression as measured using the activity assay in both skeletal muscle and cardiac muscle with greater than tenfold improvements seen in both tissues. And consistent with the biodistribution results, we see decreased expression in the liver with the novel capsid.

在下一張投影片上，我們同樣觀察到骨骼肌和心肌中螢光素酶表現的增加，在這兩種組織中都觀察到了超過十倍的改善。與生物分佈結果一致，我們發現新型衣殼在肝臟中的表現減少。

So overall, these results suggest we may be able to reduce the dose while maintaining expression when compared to AAV9. As we look to next steps for the program, we will continue R&D efforts on both the novel capsid and SGT-003 program for Duchenne using learnings and the promising clinical data from the SGT-001 program.

因此，總的來說，這些結果表明，與 AAV9 相比，我們或許能夠在減少劑量的同時保持表達。當我們展望該計劃的下一步時，我們將利用 SGT-001 計劃的經驗和有前景的臨床數據，繼續為 Duchenne 進行新型衣殼和 SGT-003 計劃的研發工作。

For SGT-003, we are working closely with our manufacturing partner to have product (inaudible) patient dosing. We are looking to engage with the FDA later this year regarding an IND submission we planned for early 2023. We are very optimistic about the potential that SGT-003 holds for patients. The preclinical data continues to suggest that we may be able to improve expression at a lower dose, therefore, reducing viral loads. We will continue to develop this next-generation capsid to the Duchenne patients with the SGT-003 program as well as potentially engage with companies developing gene therapies and other muscle-related disorders.

對於 SGT-003，我們正在與製造合作夥伴密切合作，為患者提供產品（聽不清楚）劑量。我們計劃在今年稍後與 FDA 就計劃於 2023 年初提交 IND 事宜進行接觸。我們對 SGT-003 對患者的潛力非常樂觀。臨床前數據繼續表明，我們也許能夠以較低劑量改善表達，從而減少病毒量。我們將繼續透過 SGT-003 計畫為 Duchenne 患者開發這種新一代衣殼，並可能與開發基因療法和其他肌肉相關疾病的公司合作。

With that, I will hand it back to Ilan.

說完，我就把它還給伊蘭了。

Thank you, Carl, and thanks, Joel. We have a lot of work ahead of us, but we have focused our operations to support these 2 programs, which utilize a single manufacturing approach. That has allowed us to streamline our organization structure and reduce our headcount by approximately 35%, which enables us to extend our run rate into Q2 of 2024 and achieve important clinical milestones.

謝謝你，卡爾，謝謝你，喬爾。我們還有很多工作要做，但我們的營運重點是支持這兩個利用單一製造方法的項目。這使我們能夠簡化組織結構並將員工人數減少約 35%，使我們能夠將運作率延長至 2024 年第二季並實現重要的臨床里程碑。

And over the next 12 months, we will be sharing further data from long-term patient follow-ups an update on our regulatory interactions for both SGT-001 and SGT-003 and potential updates on SGT-001 CMC and clinical plans as well as SGT-003 IND filing, clinical trial and dosing plans.

在接下來的 12 個月中，我們將分享來自長期患者追蹤的更多數據、SGT-001 和 SGT-003 監管相互作用的更新以及 SGT-001 CMC 和臨床計劃的潛在更新以及SGT-003 IND 備案、臨床試驗及給藥計劃。

I also want to mention that as you may have seen in this morning's press release, Joel will be leaving Solid. He has accepted an opportunity to become a CEO of an early-stage privately held gene therapy company. Joel will be staying on through the end of May.

我還想提一下，正如您在今天早上的新聞稿中看到的那樣，Joel 將離開 Solid。他接受了成為早期私人基因治療公司執行長的機會。喬爾將留任至五月底。

Before we open for questions, I want to take a moment to say thank you. First, I want to say thank you to all of some employees for their tireless efforts to bring our treatments to patients. To those who were unfortunately impacted by the strategic reorganization we announced today, I hope you know that your work has made a meaningful contribution to improving the lives of patients living with Duchenne. And for that, I'm deeply grateful.

在我們開始提問之前，我想花點時間向大家表達感謝。首先，我想對所有員工表示感謝，感謝他們為將我們的治療帶給患者所做的不懈努力。對於那些不幸受到我們今天宣布的策略重組影響的人，我希望你們知道你們的工作為改善杜興氏症患者的生活做出了有意義的貢獻。為此，我深表感激。

I also want to thank Joel for 8 years of service and commitment to service. Joel has been instrumental in building the company, the teams and the treatments that are being developed at Solid. I'm now speaking on behalf of everyone at Solid, when I thank Joel for his leadership, partnership and friendship and wish him success with this new chapter.

我還要感謝 Joel 8 年的服務和對服務的承諾。 Joel 在公司建立、團隊以及 Solid 正在開發的治療方法方面發揮了重要作用。我現在代表 Solid 的每個人發言，感謝 Joel 的領導、合作和友誼，並祝福他在新的篇章中取得成功。

Finally, I would like to extend a special thank you to the patients, families and physicians involved in IGNITE DMD, thanks to whom we are now in a position to move to the next phases of development.

最後，我要特別感謝參與 IGNITE DMD 的患者、家屬和醫生，感謝他們，我們現在能夠進入下一階段的發展。

Thank you, again, for dialing in. We'll take some questions now.

再次感謝您撥通電話。我們現在將回答一些問題。

(Operator Instructions)

（操作員說明）

We'll take our first question from Gena Wang of Barclays.

我們將回答巴克萊銀行的 Gena Wang 提出的第一個問題。

Joel, congrats on your next journey, and we will certainly miss you. So I have 2 sets of questions. Maybe the first one is regarding the SGT-003, so you did show luciferase reporter gene data. Did you test the microdystrophin transgene in the new capsid? And based on the current data, what would be your initial thoughts regarding the Phase I dose range? Like will you be able to go down to the E12 range?

喬爾，祝賀你的下一次旅程，我們一定會想念你的。所以我有 2 組問題。也許第一個是關於 SGT-003 的，所以你確實顯示了螢光素酶報告基因數據。您是否在新衣殼中測試了微抗肌營養不良蛋白轉基因？根據目前數據，您對第一階段劑量範圍的初步想法是什麼？例如你能降到E12範圍嗎？

My second question -- second set of questions is regarding the SGT-001. So now with the new trends in transaction-based outsourced manufacturing process. So do you need to do additional CMC or comparability study before you move forward to a pivotal study?

我的第二個問題——第二組問題是關於 SGT-001 的。因此，現在出現了基於交易的外包製造流程的新趨勢。那麼，在進行關鍵研究之前，您是否需要進行額外的 CMC 或可比性研究？

Great questions, Gena. I'll have Carl take on the -003 and Joel will respond to the -001.

很好的問題，吉娜。我將讓 Carl 處理 -003，而 Joel 將回應 -001。

Yes. Thanks, Gena. It would be great to get down to E12, but I don't think that's possible. We are looking at doing it. We need -- still need to do a dose selection study. And so we hope to get drop the dose and so maybe get down by at least twofold. And that is what the goal of the program was always was to get a twofold difference versus AAV9. And so it appears that we've done that both in mice and monkeys.

是的。謝謝，吉娜。如果能降到 E12 就太好了，但我認為這是不可能的。我們正在考慮這樣做。我們仍需要進行劑量選擇研究。所以我們希望減少劑量，也許至少減少兩倍。該計劃的目標始終是獲得與 AAV9 相比的兩倍差異。看來我們在老鼠和猴子身上都做到了這一點。

The second part of your question was around luciferase and first microdystrophin. We didn't dose nonhuman primates with microdystrophin. We dosed them with luciferase but we did do mice and compared the luciferase and the microdystrophin. As luciferase has a little bit higher signal, but the microdystrophin in the mice was about threefold while the luciferase mice was tenfold. So we think we're sort of in the right ballpark for the microdystrophin as well.

你問題的第二部分是關於螢光素酶和第一個微肌營養不良蛋白。我們沒有給非人靈長類動物注射微肌營養不良蛋白。我們給它們注射了螢光素酶，但我們確實對小鼠進行了實驗，並比較了螢光素酶和微肌營養不良蛋白。由於螢光素酶的訊號稍高一些，但小鼠體內的微抗肌肉營養不良蛋白約為螢光素酶小鼠的三倍，而螢光素酶小鼠則為十倍。所以我們認為我們對於微抗肌營養不良蛋白也處於正確的範圍內。

Going into wild-type animals that already have dystrophin, it's a bit problematic trying to administer the microdystrophin and evaluate levels, but this is good. We did it in wild-type mice as well with luciferase and it showed quite promising results there as well. So as a platform, we think this is sort of a really good first step for us.

對於已經含有肌肉營養不良蛋白的野生型動物，嘗試施用微肌營養不良蛋白並評估其水平有點問題，但這很好。我們也在野生型小鼠中使用螢光素酶進行了實驗，結果也顯示出非常有希望的結果。因此，作為一個平台，我們認為這對我們來說是非常好的第一步。

I would just add, Gena, that we had a bunch of internal bars that we needed to cross to get excited about -003, and we crossed them and we are excited and we're taking it into the clinic. And we think there's a lot more potential outside of Duchenne, too. And hopefully, very soon, we will see them in patients and see how good it really is.

我想補充一點，Gena，我們有一堆內部條，我們需要跨越它們才能對 -003 感到興奮，我們跨越了它們，我們很興奮，我們正在把它帶入診所。我們認為杜興之外也有更大的潛力。希望很快我們就能在病人身上看到它們，看看它到底有多好。

Joel, do you want to cover the one?

喬爾，你想報道這個嗎？

Sure. Thanks, Gena, for the question. On comparability, of course, we have a lot of experience in demonstrating comparability between different manufacturing methods. In fact, we just recently accomplished that when we transitioned to our second-generation based HSV manufacturing approach. We've already begun to engage with regulators about the path towards dosing of patients with new process, and believe that the comparability will need to be demonstrated but that can be accomplished through analytical methods and perhaps some in vivo dosing to demonstrate comparability overall.

當然。謝謝吉娜提出的問題。當然，在可比性方面，我們在展示不同製造方法之間的可比性方面擁有豐富的經驗。事實上，我們最近剛剛實現了這一目標，當時我們過渡到基於第二代的 HSV 製造方法。我們已經開始與監管機構就新製程對患者的給藥途徑進行接觸，並認為需要證明可比性，但這可以透過分析方法以及也許一些體內給藥來證明總體可比性來實現。

But obviously, a lot of experience internally with how to demonstrate that comparability and feel confident that we can have a seamless transition between manufacturing methodologies.

但顯然，我們內部在如何證明這種可比性方面擁有豐富的經驗，並對我們能夠在製造方法之間實現無縫過渡充滿信心。

Maybe I'll add to this too that in the process of switching. We did a lot of analytical work. And so we are pretty confident that the new materials will qualify as good, if not better.

也許我也會在切換過程中加入這一點。我們做了很多分析工作。因此，我們非常有信心新材料即使不是更好，也同樣好。

Your next question comes from Joseph Schwartz with SVB Securities.

您的下一個問題來自 SVB 證券公司的 Joseph Schwartz。

And I'd like to also add my best wishes to Joel and his next endeavors. It sounds like you are satisfied that you understand how to best administer SGT-001 in a safe and effective manner now that you've wrapped up IGNITE. So I was wondering if you could summarize what the key features of the risk mitigation protocol are for ensuring that patients who receive SGT-001 can tolerate it optimally.

我還想向喬爾和他接下來的努力致以最美好的祝愿。聽起來您對了解如何以安全有效的方式最好地管理 SGT-001 感到滿意，因為您已經完成了 IGNITE。因此，我想知道您是否可以總結一下風險緩解方案的主要特徵是什麼，以確保接受 SGT-001 的患者能夠最佳地耐受。

Joe, thank you for the question. Obviously, we completed enrollment. We have not wrapped up the study because we continue to monitor patients out to 5 years at least from dosing and with those 9 and have a number of other patients in the study. But I'll have Roxana jump in a little bit on risk benefit and how we feel about moving forward in those things.

喬，謝謝你的提問。顯然，我們已經完成了註冊。我們尚未結束這項研究，因為我們將繼續對患者進行至少 5 年的監測，其中包括這 9 名患者，以及研究中的其他一些患者。但我會讓 Roxana 談談風險收益以及我們對推動這些事情的看法。

Thank you, Ilan. Yes, very good question. Thank you. We feel very confident in the risk-benefit profile of SGT-001 based on the 9 dose subjects to-date. Our 2-year results show that the patients are experiencing a sustained benefit across all the functional outcomes in terms of motor function, pulmonary and patient-reported outcomes.

謝謝你，伊蘭。是的，非常好的問題。謝謝。根據迄今為止的 9 位劑量受試者，我們對 SGT-001 的風險效益狀況非常有信心。我們的 2 年結果表明，患者在運動功能、肺部和患者報告的結果方面的所有功能結果方面都獲得了持續的益處。

In terms of the risk mitigation strategy, we feel very confident that this is the right way forward. We are thinking about finalizing that risk mitigation strategy for the new material, so not maybe everything is going to say in place as it is right now. But as you know with previous updates, we've shared that we've optimized our eculizumab regimen, and we've definitely optimized our follow-up of the patients previous to infusion and after the infusion in the first couple of weeks to very close monitoring. So we're, of course, assessing that, once again, to make sure that everything is still applicable for the new material.

就風險緩解策略而言，我們非常有信心這是正確的前進方向。我們正在考慮最終確定新材料的風險緩解策略，所以也許並不是所有的事情都會像現在這樣到位。但正如您在先前的更新中所知，我們已經分享了我們已經優化了依庫麗單抗治療方案，並且我們肯定已經優化了輸注前和輸注後前幾週患者的隨訪，以非常接近監控。因此，我們當然會再次評估這一點，以確保所有內容仍然適用於新材料。

Okay. And then what are the next steps for SGT-001 and when do you expect to get back in the clinic and what types of patients will you be focusing on enrolling in the next in the next study for -- 001? And have you scheduled an end of Phase II meeting with the FDA yet? Are you thinking about undertaking a Phase 3 at this juncture? Can you help us understand your strategy there?

好的。那麼 SGT-001 的下一步是什麼？您預計什麼時候回到診所？您將重點關注哪些類型的患者參加下一個 001 的研究？您是否已安排與 FDA 舉行第二階段會議？您是否正在考慮在此時進行第三階段？您能幫助我們了解您的策略嗎？

Sure, Joe. I'll take this. It's a quick one. We've already started engaging with the regulators around the switch. We intend to have material ready to those patients with SGT-001 early in 2023, and all the aspects of the clinical trial design as well as the number of patients, (inaudible) inclusion are being finalized.

當然，喬。我要這個。這是一個很快的。我們已經開始與有關交換機的監管機構進行接觸。我們打算在 2023 年初為 SGT-001 患者準備好材料，臨床試驗設計的所有方面以及患者數量、（聽不清楚）納入都正在最終確定。

Your next question comes Maury Raycroft with Jefferies.

你的下一個問題來自傑弗里斯的莫里·雷克羅夫特。

For the new process besides the scaling and the streamlined process and transient transfection, are there any other fundamental changes we should be aware of?

對於新流程，除了規模化、流程簡化和瞬時轉染之外，還有哪些我們應該注意的根本性變化？

Thanks, Maury. I'll take this one. One key aspect this solution that we've identified for late-stage development of -001 is that it's already at a -- what we would consider a Phase III appropriate and commercial scale. We've done extensive work internally on scaling agency process. And as we performed our comprehensive analysis between our internal process and external options, we did seek a process that was already sufficiently optimized for late-stage clinical entry and ultimately commercialization. And so we're excited to be able to access that.

謝謝，莫里。我要這個。我們為-001後期開發確定的此解決方案的一個關鍵方面是，它已經達到了我們認為的第三階段適當的商業規模。我們在內部就擴展代理流程進行了大量工作。當我們對內部流程和外部選項進行全面分析時，我們確實尋求了一種已經針對後期臨床進入和最終商業化進行了充分優化的流程。因此，我們很高興能夠訪問它。

A couple of other key aspects of this is that, of course, transient production is a very widely adopted manufacturing platform. And we think that this will enable us to have broader access to a much wider net of supply chain efforts or supply chain networks. It will also allow us to, we think, overall, improve our manufacturability of clinical supply. And so really, fundamentally, it's the streamlining of our manufacturing (technical difficulty) unified behind a single platform for both gene therapy programs.

當然，這方面的其他幾個關鍵方面是，瞬時生產是一種非常廣泛採用的製造平台。我們認為，這將使我們能夠更廣泛地接觸更廣泛的供應鏈工作或供應鏈網路。我們認為，總體而言，它還將使我們能夠提高臨床供應的可製造性。因此，實際上，從根本上來說，這是我們的製造（技術難度）的簡化，統一在兩個基因治療項目的單一平台後面。

Got it. That's helpful. And then just wondering if you can clarify what you mean by a new outsource process. I guess are there going to be new manufacturing collaborations on the horizon? And how much of a contribution does Forge Biologics have in the new process?

知道了。這很有幫助。然後只是想知道您是否可以澄清新的外包流程的含義。我想即將出現新的製造合作嗎？ Forge Biologics 在新製程有何貢獻？

So we're really excited about the work that Forge is doing for us on SGT-003, but simply for diversification purposes as well as the opportunity to work with a commercially scaled process, we are building a new relationship with a new vendor for the production of SGT-001 at those scales.

因此，我們對 Forge 在 SGT-003 上為我們所做的工作感到非常興奮，但僅僅是為了多樣化的目的以及與商業規模流程合作的機會，我們正在與新供應商建立新的關係以這些規模生產SGT-001。

On the aspect of -- sorry, actually, I'm blanking on the first part of the question.

抱歉，實際上，我對問題的第一部分空白。

Just -- I mean, you basically answered it. Just -- additional.

只是——我的意思是，你基本上已經回答了。只是——額外的。

Yes, the differentiator there for us is that the HSV process is something that we've worked on extensively internally for the last for 6 or 7 years, we are excited to be leveraging external expertise and capabilities to rapidly integrate their expertise into our own around transient production. And so it's really a notion of recognizing the incredible work that our internal teams have done to scale and optimize the HSV process, but recognizing that we can now relieve some of those bandwidth constraints by working with external parties, leveraging their proprietary manufacturing platforms, and really focus on bringing our therapy to patients.

是的，對我們來說，與眾不同之處在於HSV 流程是我們在過去6 到7 年裡在內部廣泛開展的工作，我們很高興能夠利用外部專業知識和能力，將他們的專業知識快速整合到我們自己的周圍瞬時生產。因此，這實際上是認識到我們的內部團隊在擴展和優化HSV 流程方面所做的令人難以置信的工作，但認識到我們現在可以透過與外部各方合作、利用他們專有的製造平台來緩解一些頻寬限制，並且真正專注於將我們的治療帶給患者。

(Operator Instructions)

（操作員說明）

Your next question is from Allison Bratzel with Piper Sandler.

您的下一個問題來自 Allison Bratzel 和 Piper Sandler。

So first, just a couple of clarifications for me on IGNITE DMD. And apologies if you've covered these, I just want to make sure I'm clear. I guess how many total patients were -- did end up being dosed at IGNITE DMD? I think we know 9 were dosed as of November. So just confirming that that's the total number of patients dosed.

首先，我需要對 IGNITE DMD 進行一些澄清。如果您已經涵蓋了這些內容，我深表歉意，我只是想確保我說清楚了。我猜總共有多少患者 - 最終在 IGNITE DMD 接受了注射？我想我們知道截至 11 月已有 9 人被注射。因此，只需確認這就是接受給藥的患者總數。

And then could you also clarify the cadence for data updates from those patients? I think the prior guidance was to disclose 12-month functional data from patient (inaudible) by year-end '22. So I just want to make sure we should still be looking for that.

然後能否澄清一下這些患者數據更新的節奏？我認為之前的指導是在 22 年底前披露患者的 12 個月功能數據（聽不清楚）。所以我只是想確保我們仍然應該尋找它。

And then just lastly for me, a clarification on -- just on the cash runway. I think the guidance is that you'll have a runway through Q2 '24 through important clinical milestones. Could you just kind of outline the important clinical milestones we should be expecting between now and Q2 '24? And just what does that new cash run rate guidance assume for the start of pivotal work?

最後對我來說，關於現金跑道的澄清。我認為指導意見是，您將在 2024 年第二季實現重要的臨床里程碑。您能否概述一下從現在到 24 年第二季我們應該期待的重要臨床里程碑？新的現金運行率指導對於關鍵工作的開始有何假設？

Let me try to wrap it all up in a quick answer. With these 9 patients, we were always going to adopt couple more. And with this switch, we decided to stop enrollment, evaluate the data and move to transfection starting early next year. We obviously continue to monitor all the patients that have been dosed. And yes, we will continue to provide additional clinical and biomarker data as it comes in during this year and probably in the future. We are very excited about the durability of the data that we're seeing. We have biopsies out 2 years that are stable or actually increasing, and we have functional outcomes, especially looking at some of the physical measurements, respiratory measurement. There's some pretty interesting observations there, but we continue to monitor and evaluate and measure and report. The runway will get us for the next 2 years, and a lot of clinical milestones on both programs.

讓我嘗試用一個快速的答案來概括這一切。有了這 9 名患者，我們總是打算收養更多的患者。透過這項轉變，我們決定停止招募，評估數據並從明年初開始轉向轉染。顯然，我們會繼續監測所有已服藥的患者。是的，我們將繼續提供今年以及未來可能出現的更多臨床和生物標記數據。我們對所看到的數據的持久性感到非常興奮。我們進行了兩年的活檢，結果穩定或實際上在增加，我們得到了功能結果，特別是一些身體測量、呼吸測量。那裡有一些非常有趣的觀察結果，但我們將繼續監測、評估、衡量和報告。這條跑道將幫助我們在未來兩年內實現這兩個計畫的許多臨床里程碑。

Our next question comes from Anupam Rama with JPMorgan.

我們的下一個問題來自摩根大通的 Anupam Rama。

I have maybe just a broader strategic question in terms of you started dosing for -001 in 2023 and theoretically, your IND going for -003 early next year, and maybe you start dosing patients soon too. Like why not just prioritize one and maybe extend the cash way a little bit longer?

我可能有一個更廣泛的策略問題，即您在2023 年開始為-001 給藥，理論上，您的IND 將於明年初開始為-003 給藥，也許您也很快就會開始為患者給予藥。例如為什麼不優先考慮一項，或許可以延長現金發放時間？

Good question, Anup, I mean I wouldn't be surprised if it came up internally, too. We're not in the business of shooting down things that work. We think -001 has got great data that supports continued development. I can tell you as somebody with some first-hand experience of this disease. I would love to see that -- touch more patients if possible.

好問題，阿納普，我的意思是，如果這個問題也出現在內部，我不會感到驚訝。我們的職責不是否定那些有效的東西。我們認為-001 已經獲得了支持持續開發的大量數據。作為一個對這種疾病有一些第一手經驗的人，我可以告訴你。我很樂意看到這一點——如果可能的話，接觸更多的病人。

If -003 active in patients does show the same effect that we've seen in mice, that we've seen in monkeys now, certainly the expression levels and the biodistribution levels of the vector, then that's a great finding. It's a really exciting moment for not just Solid, but I think science and muscle diseases. And at that point, we can make different decisions than we do today. Right now, we are confident that both these programs deserve a day in the sun.

如果-003在患者體內的活性確實表現出我們在小鼠中看到的相同效果，我們現在在猴子中看到的效果，當然是載體的表達水平和生物分佈水平，那麼這是一個偉大的發現。這不僅對 Solid 來說是一個非常令人興奮的時刻，而且我認為對於科學和肌肉疾病也是如此。到那時，我們可以做出與今天不同的決定。現在，我們相信這兩個項目都值得大放異彩。

And with that, we conclude our Q&A session and today's call. All parties may now disconnect. Thank you, and have a great day.

我們的問答環節和今天的電話會議到此結束。所有各方現在都可以斷開連接。謝謝您，祝您有美好的一天。