Regenxbio Inc (RGNX) 2024 Q2 法說會逐字稿

Welcome, everyone, to the Q2 2024 Regenxbio earnings conference call. (Operator Instructions)

歡迎大家參加 2024 年第二季 Regenxbio 收益電話會議。（操作員說明）

At this time, I'd like to turn the conference over to Patrick Christmas, Chief Legal Officer of Regenxbio. Please go ahead.

這次，我想將會議交給 Regenxbio 首席法務官 Patrick Christmas。請繼續。

Good afternoon and thank you for joining us today. Earlier this afternoon, Regenxbio released financial and operating results for the second quarter ended June 30, 2024. The press release is available on our website at www.regenxbio.com.

下午好，感謝您今天加入我們。今天下午早些時候，Regenxbio 發布了截至 2024 年 6 月 30 日的第二季財務和營運業績。新聞稿可在我們的網站 www.regenxbio.com 上取得。

Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend, and other words of similar meaning. Any such forward-looking statements are not guarantees of future performance and involve certain risks and uncertainties.

除了監管和產品開發計劃之外，今天的電話會議還將包括有關我們財務前景的前瞻性聲明。這些前瞻性陳述存在風險和不確定性，可能導致實際結果與預測不同，可以透過預期、計劃、將、可能、預期、相信、應該、打算和其他類似詞語來識別。任何此類前瞻性陳述都不是對未來績效的保證，並且涉及某些風險和不確定性。

These risks are described in the risk factors and the management's discussion and analysis sections of Regenxbio's annual report on Form 10-K for the full year ended December 31, 2023 and comparable risk factors sections of Regenxbio's quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission and available on the SEC's website.

這些風險在 Regenxbio 截至 2023 年 12 月 31 日的全年 10-K 表格年度報告的風險因素和管理層討論和分析部分以及 Regenxbio 10-Q 表格季度報告的類似風險因素部分進行了描述，已向美國證券交易委員會備案並可在SEC 網站上取得。

Any information we provide on this conference call is provided only as of the date of this call, August 1, 2024 and we undertake no obligation to update any forward-looking statements we may make on this call on account of new information, future events, or otherwise.

我們在本次電話會議上提供的任何資訊僅截至本次電話會議之日（2024 年 8 月 1 日）提供，我們沒有義務更新我們在本次電話會議上可能因新資訊、未來事件、或其他方式。

Please be advised that today's call is being recorded and webcast. In addition, any unaudited or pro forma financial information that may be provided is preliminary and does not purport to project financial positions or operating results of the company. Actual results may differ materially.

請注意，今天的電話會議正在錄音並進行網路直播。此外，可能提供的任何未經審計或備考財務資訊均為初步信息，並非旨在預測公司的財務狀況或經營業績。實際結果可能存在重大差異。

I would now turn the call over to Curran Simpson, President and CEO of Regenxbio.

我現在將電話轉給 Regenxbio 總裁兼執行長 Curran Simpson。

Thank you, Patrick. Good afternoon, everyone, and thank you for joining us. I'm pleased to be leading today's call, my first one as Regenxbio's Chief Executive Officer.

謝謝你，派崔克。大家下午好，感謝您加入我們。我很高興主持今天的電話會議，這是我作為 Regenxbio 執行長的第一次電話會議。

Today, we'll be sharing a number of exciting positive updates and discuss the momentum happening across our pipeline of differentiated AAV therapeutics. I'll begin with a recap of our business highlights as well as an update of our corporate goals and key milestones that we have achieved.

今天，我們將分享一些令人興奮的正面更新，並討論我們差異化 AAV 療法管道中發生的勢頭。首先，我將回顧我們的業務亮點以及我們的企業目標和我們已實現的關鍵里程碑的最新情況。

Dr. Steve Pakola, our Chief Medical Officer, will provide an update on our clinical programs; and then Vit Vasista, our Chief Financial Officer, will provide an overview of financial results for the second quarter ended June 30, 2024. At the end of the call, we'll open up the line for questions.

我們的首席醫療官 Steve Pakola 博士將提供我們臨床計畫的最新資訊；然後，我們的財務長 Vit Vasista 將概述截至 2024 年 6 月 30 日的第二季財務業績。通話結束時，我們將開通提問專線。

It's been a productive first half of the year for Regenxbio as we make significant progress advancing each of our programs toward pivotal stage clinical trials and future commercialization.

今年上半年對 Regenxbio 來說是富有成效的，因為我們在推動每個專案走向關鍵階段臨床試驗和未來商業化方面取得了重大進展。

Our priority programs are RGX-202 for the treatment of Duchenne; AbbVie RGX-314 program for the treatment of wet AMD and diabetic retinopathy, or DR, being developed in collaboration with AbbVie; and RGX-121 for the treatment of MPS II, or Hunter syndrome.

我們的優先項目是用於治療 Duchenne 的 RGX-202；艾伯維 RGX-314 計畫用於治療濕性 AMD 和糖尿病視網膜病變 (DR)，正在與艾伯維合作開發； RGX-121 用於治療 MPS II 或亨特氏症候群。

Our lead programs, specifically 202 and 314, represent large commercial opportunities where our product candidates are differentiated from current standard of care, can be expedited via accelerated approval due to significant unmet need, and support meaningful value generation soon and for the long-term.

我們的主導項目，特別是202 和314，代表著巨大的商業機會，我們的候選產品與當前的護理標準不同，可以透過加速批准來加速由於未滿足的重大需求，並支持短期和長期有意義的價值創造。

Let me begin with RGX-202, which represents the next generation of microdystrophin gene therapies and is poised to potentially be the second AAV-based product to reach the market.

讓我從 RGX-202 開始，它代表了下一代微肌營養不良蛋白基因療法，並有望成為第二個進入市場的基於 AAV 的產品。

There are a number of exciting developments for RGX-202. Steve will share more details about the positive data reported today, demonstrating consistent, robust microdystrophin expression across treated patients reflecting a broad range of ages, but I first want to highlight the differentiating factors that we believe will make RGX-202 a best-in-class product and the excellent progress we are making to both expedite its development and maximize its commercial potential.

RGX-202 有許多令人興奮的進展。Steve 將分享有關今天報告的積極數據的更多詳細信息，證明在反映廣泛年齡範圍的治療患者中一致、強大的微抗肌營養不良蛋白表達，但我首先想強調我們認為將使RGX-202 成為最佳藥物的差異化因素。

RGX-202 is a differentiated product candidate utilizing an advanced microdystrophin construct with potential for improved functional benefit as shown in our preclinical data. It is the only microdystrophin product that includes the C-terminal domain, a key region of the naturally occurring dystrophin gene, which has been shown in preclinical studies to protect the muscle from contraction-induced stress and improve the ability of the muscle to repair itself.

RGX-202 是一種差異化的候選產品，利用先進的微肌肉營養不良蛋白結構，具有改善功能益處的潛力，如我們的臨床前數據所示。它是唯一包含C 端結構域的微肌營養不良蛋白產品，C 端結構域是天然存在的肌營養不良蛋白基因的關鍵區域，臨床前研究已顯示該結構域可保護肌肉免受收縮引起的壓力並提高肌肉自我修復的能力。

As I mentioned, RGX-202 is demonstrating consistently high levels of microdystrophin expression across patients of all ages. But I want to note that it is in older ambulatory boys where we're seeing the highest levels of microdystrophin expression reported in older ambulatory patients, especially compared to other published data.

正如我所提到的，RGX-202 在所有年齡層的患者中均表現出持續高水平的微肌營養不良蛋白表達。但我想指出的是，在老年門診男孩中，我們發現老年門診患者中微肌營養不良蛋白表達水平最高，特別是與其他已發表的數據相比。

And RGX-202 has been well-tolerated and no SAEs have been reported, which is a significant element of the overall risk-benefit analysis for patients, caregivers and regulatory agencies, and a meaningful differentiator versus other Duchenne gene therapy trials.

RGX-202 耐受性良好，未報告任何 SAE，這是患者、照護者和監管機構總體風險效益分析的重要組成部分，也是與其他 Duchenne 基因治療試驗的有意義的區別。

As I mentioned, our goal is to be the next approved gene therapy in Duchenne, and we are taking all of the necessary steps towards this goal. We recently completed a successful end of Phase 2 meeting with the US FDA and walked away from this meeting confident in our plans to file a BLA using microdystrophin as the primary endpoint for accelerated approval.

正如我所提到的，我們的目標是成為 Duchenne 的下一個批准的基因療法，我們正在採取所有必要的步驟來實現這一目標。我們最近成功結束了與美國 FDA 的第二階段會議，並在結束這次會議時對我們使用微肌營養不良蛋白作為加速批准的主要終點提交 BLA 的計劃充滿信心。

The meeting also involved a discussion of our industry-leading NAVXpress suspension-based, commercial-ready manufacturing process used in this trial. At our in-house manufacturing facility, we have the capacity and yields to produce 2,500 doses of RGX-202 per year.

會議還討論了本次試驗中使用的行業領先的基於 NAVXpress 懸吊的商業化製造流程。在我們的內部製造工廠，我們有能力和產量每年生產 2,500 劑 RGX-202。

Given the differentiating characteristics of RGX-202 and the significant ongoing unmet need in the Duchenne community, plus our manufacturing expertise, we are well-positioned to advance this program towards commercialization.

考慮到 RGX-202 的差異化特徵以及 Duchenne 社區持續未滿足的重大需求，加上我們的製造專業知識，我們有能力推動該項目走向商業化。

Turning to AbbVie RGX-314, our gene therapy being developed in chronic retinal diseases with our partner AbbVie, we have made several advancements across the suprachoroidal trials in diabetic retinopathy and wet AMD.

談到艾伯維 RGX-314，我們與合作夥伴艾伯維正在開發針對慢性視網膜疾病的基因療法，我們在糖尿病視網膜病變和濕性 AMD 的脈絡膜上試驗中取得了一些進展。

First, with regard to the ALTITUDE trial of 314 for the treatment of DR using suprachoroidal delivery, we are accelerating plans for our end of Phase 2 meeting with the FDA. This meeting is now expected to take place in the fourth quarter of this year versus our initial guidance of first-quarter 2025. The new timeline supports the rapid acceleration towards pivotal trials with initiation expected in the first half of 2025.

首先，關於 314 使用脈絡膜上腔給藥治療 DR 的 ALTITUDE 試驗，我們正在加快與 FDA 舉行第二階段會議的計畫。此次會議目前預計將於今年第四季舉行，而我們最初的指導方針是 2025 年第一季。新的時間表支持快速加速關鍵試驗，預計將於 2025 年上半年啟動。

Importantly, Regenxbio will be entitled to a $200 million milestone payment upon successful dosing of the first patient with AbbVie RGX-314 in DR, which again is anticipated in 2025.

重要的是，在第一位 DR 患者成功接受艾伯維 RGX-314 給藥後，Regenxbio 將有權獲得 2 億美元的里程碑付款，預計將在 2025 年完成。

We are also excited to announce that working with our partners at AbbVie, we will be expanding the broad, multi-indication global potential of 314 by initiating a new cohort in the ALTITUDE trial for patients with diabetic macular edema, DME. 314 is well positioned to become the standard of care to treat the progression of diabetic retinopathy.

我們也很高興地宣布，我們將與艾伯維 (AbbVie) 的合作夥伴合作，透過針對糖尿病性黃斑水腫 (DME) 患者啟動 ALTITUDE 試驗的新隊列，擴大 314 廣泛的多適應症全球潛力。 314 有望成為治療糖尿病視網膜病變進展的護理標準。

Broadening the ALTITUDE trial to include patients with DME further expands the global potential of 314. We have also made important progress on our 314 programs for wet AMD as well as in our RGX-121 program for MPS II as we approach potential approval and becoming the first gene therapy for Hunter syndrome.

擴大 ALTITUDE 試驗範圍以納入 DME 患者進一步擴大了 314 的全球潛力。隨著我們即將獲得批准並成為第一個針對亨特氏症候群的基因療法，我們在針對濕性 AMD 的 314 計畫以及針對 MPS II 的 RGX-121 計畫上也取得了重要進展。

We remain on schedule to initiate a rolling BLA filing in the third quarter of 2024. Approval of the planned BLA could result in receipt of a priority review voucher in 2025.

我們仍按計劃在 2024 年第三季啟動滾動 BLA 備案。計劃中的 BLA 獲得批准可能會在 2025 年收到優先審查憑證。

Overall, we are making excellent progress and have provided positive updates across all programs with a number of additional catalysts on track to be shared later this year. We remain excited by our progress as we continue on the strategic plan. We are accelerating the development of our pipeline and expanding their value for shareholders, while bringing potentially life-changing therapies to patients facing great unmet need.

總體而言，我們正在取得出色的進展，並為所有計劃提供了積極的更新，並預計在今年晚些時候分享一些額外的催化劑。在我們繼續實施戰略計劃的過程中，我們對所取得的進展仍然感到興奮。我們正在加快產品管線的開發，擴大其為股東帶來的價值，同時為面臨巨大未滿足需求的患者提供可能改變生活的療法。

With that update, I'd like to now turn the call over to Steve for an update on our clinical programs. Steve?

隨著這項更新，我現在想將電話轉給史蒂夫，以獲取有關我們臨床計畫的最新資訊。史蒂夫？

Thank you, Curran. I'll start with RGX-202, a potential one-time gene therapy for the treatment of Duchenne. Today, we reported new microdystrophin expression data from the two new patients aged 5.8 and 8.5 years, who received RGX-202 at dose level 2, the dose we are advancing to pivotal phase.

謝謝你，庫蘭。我將從 RGX-202 開始，這是一種潛在的一次性基因療法，用於治療杜興氏症。今天，我們報告了兩名分別為5.8 歲和8.5 歲的新患者的新微抗肌營養不良蛋白表達數據，他們接受了2 級劑量的RGX-202，我們正在將這一劑量推進到關鍵階段。

Microdystrophin expression was measured to be 77.2% and 46.5%, respectively, compared to control at three months. As of July 8, 2024, RGX-202 continues to be well tolerated with no serious adverse events. And all patients who reach three-month trial assessments indicate meaningful increases in expression of RGX-202 microdystrophin and reduction from baseline in serum creatinine kinase levels, supporting evidence of clinical improvement.

三個月時，與對照組相比，微抗肌營養不良蛋白表現量分別為 77.2% 和 46.5%。截至 2024 年 7 月 8 日，RGX-202 的耐受性仍然良好，沒有出現嚴重的不良事件。所有達到三個月試驗評估的患者均顯示 RGX-202 微肌營養不良蛋白表達顯著增加，血清肌酸激酶水平較基線降低，支持臨床改善的證據。

We are very excited as today's data adds to the totality of evidence, demonstrating consistent high microdystrophin expression across all treated patients. In addition, early evidence of strength in motor function improvement were observed via trial clinic assessment and home videos shared by caregivers.

我們非常興奮，因為今天的數據增加了證據的整體性，證明所有治療患者的微肌營養不良蛋白一致高表達。此外，透過臨床試驗評估和護理人員分享的家庭影片觀察到運動功能改善強度的早期證據。

On the continued strength of our data, in June, we announced the expansion of the AFFINITY DUCHENNE trial to include a new cohort of patients aged one to three years. This is a cohort of boys where there remains no approved gene therapy products and a cohort that represents a significant portion of the untreatable prevalent population of Duchenne boys. As we ultimately seek a broad label for RGX-202, we will continue to produce data where limited or no data exists to further establish a differentiated product profile that can enhance RGX-202's commercial potential.

憑藉我們數據的持續強勁，我們於 6 月宣布擴大 AFFINITY DUCHENNE 試驗範圍，納入一組新的 1 至 3 歲患者群體。這是一個尚無批准的基因治療產品的男孩隊列，也是代表無法治療的 Duchenne 男孩流行人群的很大一部分的隊列。當我們最終為 RGX-202 尋求廣泛的標籤時，我們將繼續在數據有限或沒有數據的情況下提供數據，以進一步建立差異化的產品概況，從而增強 RGX-202 的商業潛力。

Moving to 314, which is being developed in collaboration with AbbVie to treat wet AMD, DR, and DME via subretinal and suprachoroidal route of administration. I'll start with 314 for DR, being evaluated in the Phase 2 ALTITUDE trial using in-office suprachoroidal delivery. As Curran mentioned, with our partner, AbbVie, we have accelerated our end of Phase 2 meeting with the FDA and believe this puts us in an excellent position to initiate our first pivotal trial in DR.

轉向 314，該藥物正在與艾伯維 (AbbVie) 合作開發，透過視網膜下和脈絡膜上給藥途徑治療濕性 AMD、DR 和 DME。我將從 314 開始進行 DR，在 2 期 ALTITUDE 試驗中使用診室脈絡膜上腔給藥進行評估。正如Curran 所提到的，我們與我們的合作夥伴艾伯維(AbbVie) 一起，加快了與FDA 的第二階段會議的結束速度，並相信這使我們處於有利地位，可以啟動我們的第一個DR關鍵試驗。

Today, we announced that we are now enrolling a new cohort of the ALTITUDE trial to evaluate 314 in patients with center-involved diabetic macular edema, or CIDME. DME is a vision-threatening complication of diabetic eye disease and impacts more than 30 million patients globally.

今天，我們宣布正在招募新的 ALTITUDE 試驗隊列，以評估 314 名患有中心糖尿病性黃斑水腫 (CIDME) 的患者。DME 是糖尿病眼疾的一種威脅視力的併發症，影響著全球超過 3000 萬名患者。

We are also evaluating 314 for the treatment of wet AMD via subretinal delivery in two ongoing pivotal trials, ATMOSPHERE and ASCENT in the US, Europe, and Japan. These trials continue to progress well.

我們也在美國、歐洲和日本進行的兩項正在進行的關鍵試驗 ATMOSPHERE 和 ASCENT 中評估 314 以視網膜下給藥治療濕性 AMD 的效果。這些試驗持續進展順利。

Our long-term follow-up data from the Phase 1/2 subretinal trial out to four years have set the gold standard in clinical development for wet AMD gene therapy. We have also fully enrolled the open-label Fellow Eye study evaluating 314 in patients previously treated with 314 in the other eye. This study is expected to support a label-inclusive of bilateral use, representing a meaningful option for the significant number of patients with wet AMD in both eyes.

我們從 1/2 期視網膜下試驗長達四年的長期追蹤數據為濕性 AMD 基因治療的臨床開發設定了黃金標準。我們也全面納入了開放標籤 Fellow Eye 研究，對先前接受過 314 另一隻眼睛治療的患者進行了 314 評估。這項研究預計將支持包含雙眼使用的標籤，這對於大量雙眼患有濕性 AMD 的患者來說是一個有意義的選擇。

Also in wet AMD, today, we announced 314 was well tolerated at dose level 3 in the AVA trial for wet AMD using the in-office suprachoroidal delivery. In patients who received short-course prophylactic steroid eye drops, there were no drug-related SAEs and no cases of intraocular inflammation, endophthalmitis, vasculitis, retinal artery occlusion, choroidal effusion, or hypotony.

同樣在濕性 AMD 中，今天，我們宣布，在使用診室脈絡膜上腔給藥的濕性 AMD AVA 試驗中，314 在劑量水平 3 下具有良好的耐受性。在接受短程預防性類固醇眼藥水的患者中，沒有出現藥物相關的 SAE，也沒有出現眼內發炎、眼內炎、血管炎、視網膜動脈閉塞、脈絡膜積液或眼壓過低的病例。

We are encouraged by the positive safety profile seen to date, and we plan to enroll a new cohort at dose level 4 as we evaluate dose levels on a path toward pivotal stage. We continue to be encouraged by the progress on our 314 programs, and I'd like to particularly highlight the safety profile observed, including in our suprachoroidal programs.

我們對迄今為止所看到的積極的安全性感到鼓舞，我們計劃在劑量水平 4 上招募一個新的隊列，因為我們評估通往關鍵階段的劑量水平。我們繼續對 314 項目的進展感到鼓舞，我想特別強調觀察到的安全狀況，包括我們的脈絡膜上項目。

We are confident in our plan to advance into new disease states and dose levels because of this safety profile, particularly in the setting of short-course seven-week prophylactic steroid eye drops. In more than 130 patients treated in-office, we're seeing a differentiated safety profile for ocular gene therapies, representing a meaningful potential treatment option for patients and physicians globally.

由於這種安全性，我們對進入新的疾病狀態和劑量水平的計劃充滿信心，特別是在短期七週預防性類固醇眼藥水的情況下。在超過 130 名在診間接受治療的患者中，我們看到了眼部基因療法的差異化安全性，這為全球患者和醫生提供了有意義的潛在治療選擇。

Finally, on RGX-121 being developed for the treatment of MPS II, or Hunter syndrome. In February at the WORLDSymposium, we announced that the CAMPSIITE pivotal trial met its primary endpoint with high statistical significance.

最後，關於正在開發用於治療 MPS II 或亨特綜合症的 RGX-121。在二月的 WORLDSymposium 上，我們宣布 CAMPSIITE 關鍵試驗達到了具有高度統計顯著性的主要終點。

Patients treated with RGX-121 achieved decrease in cerebrospinal fluid, CSF; levels of heparan sulfate, D2S6, a key biomarker of brain disease activity to below maximum attenuated disease levels. We plan to share new data from the CAMPSIITE trial in the second half of this year. We believe RGX-121 is well-positioned to be the first gene therapy and one-time treatment for Hunter syndrome.

使用 RGX-121 治療的患者腦脊髓液、CSF 減少；硫酸乙醯肝素 D2S6（大腦疾病活動的關鍵生物標記）的水平低於最大減毒疾病水平。我們計劃在今年下半年分享 CAMPSIITE 試驗的新數據。我們相信 RGX-121 完全有能力成為亨特綜合症的第一個基因療法和一次性治療方法。

We've completed a successful pre-BLA meeting with the FDA that finalize details of our planned rolling BLA submission. The key takeaways from the meeting included alignment on the use of CSF D2S6 as a key biomarker and surrogate endpoint reasonably likely to predict clinical benefit to support accelerated approval. We also reached alignment on CMC manufacturing requirements and on the confirmatory trial design.

我們已經與 FDA 成功召開了 BLA 前會議，最終確定了我們計劃的滾動 BLA 提交的詳細資訊。會議的主要收穫包括使用 CSF D2S6 作為關鍵生物標記和替代終點，合理地預測臨床獲益，以支持加速批准。我們也就 CMC 製造要求和驗證性試驗設計達成了一致。

To conclude, we continue to make significant progress with data updates and trial progression across all programs in our pipeline. Lastly, I'd like to thank the patients, families, clinicians, and patient advocacy representatives who have been involved in and supported all of these trials.

總而言之，我們在管道中所有項目的數據更新和試驗進展方面繼續取得重大進展。最後，我要感謝參與並支持所有這些試驗的患者、家屬、臨床醫生和患者權益代表。

And with that, I'll turn the call over to Vit to review our financial guidance. Vit?

接下來，我會將電話轉給 Vit，以審查我們的財務指導。維特？

Thank you, Steve. REGENXBIO ended the quarter on June 30, 2024 with cash, cash equivalents, and marketable securities of $327 million compared to $314 million as of December 31, 2023. The increase was primarily attributable to $131 million in net proceeds received from an upsized public offering of common stock and prefunded wanted completed in March 2024, partially offset by cash used to fund operating activities in the first half of 2024.

謝謝你，史蒂夫。截至 2024 年 6 月 30 日，REGENXBIO 的現金、現金等價物及有價證券為 3.27 億美元，截至 2023 年 12 月 31 日為 3.14 億美元。這一增長主要歸因於 2024 年 3 月完成的普通股擴大公開發行和預融資通緝所獲得的 1.31 億美元淨收益，部分被 2024 年上半年用於為營運活動提供資金的現金所抵消。

R&D expenses were $49 million for the second quarter of 2024 compared to $60 million for the second quarter of 2023. The decrease was largely driven by reduced manufacturing and clinical supply costs for AbbVie RGX-314 and RGX-202 and personnel-related costs as a result of reduced headcount. The decrease was partially offset by increases in clinical trial expenses for AbbVie RGX-314 and RGX-202.

2024 年第二季的研發費用為 4,900 萬美元，而 2023 年第二季的研發費用為 6,000 萬美元。這一下降主要是由於艾伯維 RGX-314 和 RGX-202 的製造和臨床供應成本降低以及人員減少導致的人員相關成本所致。這一減少被艾伯維 RGX-314 和 RGX-202 臨床試驗費用的增加部分抵消。

Regenxbio expects its balance in cash, cash equivalents, and marketable securities of $327 million as of June 30, 2024 to fund its operations into 2026. This cash runway guidance is based on the company's current operational plans and excludes the impact of any payments that may be received from AbbVie upon the achievement of development or commercial milestones under AbbVie RGX-314 collaboration, including a potential $200 million milestone for achievement of the first patient dose in the pivotal trial for suprachoroidal delivery for treatment of DR.

Regenxbio 預計，截至 2024 年 6 月 30 日，其現金、現金等價物和有價證券餘額為 3.27 億美元，為其 2026 年的營運提供資金。此現金跑道指導基於公司當前的營運計劃，不包括在艾伯維 RGX-314 合作下實現開發或商業里程碑時可能從艾伯維收到的任何付款的影響，包括為實現脈絡膜上腔給藥治療DR 的關鍵試驗中的首個病患劑量。

Additionally, our runway guidance excludes the potential monetization of our priority review voucher that may be received for RGX-121.

此外，我們的跑道指南不包括 RGX-121 可能收到的優先審查憑證的潛在貨幣化。

With that, I will turn the call back to Curran to provide his first set of final thoughts.

這樣，我將把電話轉回給柯蘭，以提供他的第一組最終想法。

Thanks, Vit. Today was another exciting day for our 202 program with additional positive data. And as we look ahead to the rest of the year, we are encouraged by our discussions with the FDA and are finalizing pivotal plans that will enable us to utilize the accelerated approval pathway to rapidly advance 202 as a potential best-in-class treatment for Duchenne.

謝謝，維特。今天對於我們的 202 計劃來說又是激動人心的一天，有更多積極的數據。當我們展望今年剩餘時間時，我們對與 FDA 的討論感到鼓舞，並正在敲定關鍵計劃，這些計劃將使我們能夠利用加速審批途徑迅速推進 202 作為潛在的同類最佳治療方法杜興。

Additionally, we are pleased to be accelerating the end of Phase 2 meeting for DR in partnership with AbbVie to enable a pivotal start next year. As we close today and reflect on the first half of the year, I'll emphasize that our plans are on track, and we continue to expand value as we make excellent progress in advancing therapies that address significant unmet needs.

此外，我們很高興與艾伯維 (AbbVie) 合作加快結束 DR 第二階段會議，以便在明年實現關鍵的開始。當我們今天結束並回顧今年上半年時，我要強調的是，我們的計劃正在步入正軌，隨著我們在推進解決重大未滿足需求的療法方面取得了巨大進展，我們將繼續擴大價值。

Thanks, everyone, for your time today. I'll turn the call over for questions. Operator?

謝謝大家今天抽出時間。我將轉接電話詢問問題。操作員？

(Operator Instructions) Gena Wang, Barclays.

（操作員指示）Gena Wang，巴克萊銀行。

Thank you. Congrats on the new data regarding the 202 in DMD. So I have two questions, one is a 202. I know you will meet with the FDA, finalize the pivotal study. But do you have a goal of the protein level you wanted to achieve? And do you expect FDA will set some threshold in order for accelerated approval?

謝謝。恭喜 DMD 中關於 202 的新數據。所以我有兩個問題，一個是202。我知道您將與 FDA 會面，完成關鍵研究。但是您有想要達到的蛋白質水平目標嗎？您是否預計 FDA 會設定一些門檻以加速批准？

And another question is regarding the 314, suprachoroidal indication in DR and wet AMD, what's the reason for dose level 4? And will you also inculcation with existing neutralizing antibody?

另一個問題是關於 314、DR 和濕性 AMD 的脈絡膜上腔適應症，劑量水準 4 的原因是什麼？您還會灌輸現有的中和抗體嗎？

Thank you for the question, Gena. In terms of -- can I clarify the first question, a goal for --?

謝謝你的提問，吉納。就——我可以澄清第一個問題，就是目標——？

Protein level.

蛋白質水平。

Protein -- microdystrophin level. We've proposed a threshold with FDA, and that's one of the things that we'll be waiting for the minutes and sort of final agreement in addition to the back and forth that will occur with the pivotal plan that will be submitted.

蛋白質－微肌營養不良蛋白質水平。我們已經向 FDA 提出了一個門檻，這是我們將等待會議記錄和最終協議的事情之一，此外還將在提交的關鍵計劃中進行反覆的討論。

We feel that just in general, thinking about the field and what we've been able to glean from our investigators that a level above 10% is likely to result in functional benefit. I think that will be a discussion that we have going forward. But if you think about our data, to date, every patient that we've published data on is above that threshold.

我們認為，總的來說，考慮到該領域以及我們從研究人員那裡收集到的信息，高於 10% 的水平可能會帶來功能性益處。我認為這將是我們未來的討論。但如果你考慮我們的數據，到目前為止，我們發布的數據中的每位患者都高於該閾值。

I'll field the second question to Steve if that's okay.

如果可以的話，我將向史蒂夫提出第二個問題。

Hi, Gena. Thanks for the questions. So 314 and going to dose level 4 in our Phase 2 studies, why do that? We've certainly met our target product profile in diabetic retinopathy, and that's why we're so excited with the advancement towards pivotal that Curran and I have summarized.

嗨，吉娜。感謝您的提問。那麼 314 並在我們的 2 期研究中採用劑量水平 4，為什麼要這樣做？我們確實已經達到了糖尿病視網膜病變的目標產品概況，這就是為什麼我們對 Curran 和我總結的關鍵進展感到如此興奮。

We've also seen, as I have highlighted, excellent safety. So I think the key consideration is we're going higher in part because we can. We really have the flexibility given the excellent safety that we believe is due to the compartmentalized route into the suprachoroidal space as opposed to less compartmentalized spaces like the intravitreal space and particularly with our product RGX-314.

正如我所強調的，我們也看到了出色的安全性。所以我認為關鍵的考慮因素是我們能夠走得更高，部分原因是我們可以。我們確實具有靈活性，因為我們相信，由於進入脈絡膜上腔的分隔路線而不是玻璃體內空間等分隔較少的空間，特別是我們的產品 RGX-314，因此具有出色的安全性。

So in collaboration with AbbVie, we're doing this. And I think it also fits just general basic drug development, where if you have good safety to really fully characterize a product, it makes sense to continue looking at higher doses, if you can.

因此，我們正在與艾伯維 (AbbVie) 合作來實現這一目標。我認為它也適合一般的基礎藥物開發，如果你有良好的安全性來真正全面地表徵產品，那麼如果可以的話，繼續研究更高的劑量是有意義的。

Thank you.

謝謝。

Vikram Purohit, Morgan Stanley.

維克拉姆‧普羅希特，摩根士丹利。

Great. Thanks for taking our questions. We had two, first on 202. Could you just speak a bit more about the functional assessment data we're going to be getting later this year, what your guidance is to best interpret that to get a sense of differentiation, real-world differentiation, and how that data set might play into discussions with regulators on next steps?

偉大的。感謝您回答我們的問題。我們有兩個，第一個是 202。您能多談談我們今年稍後將獲得的功能評估數據嗎？討論下一步行動？

And then secondly, on 314, for suprachoroidal and wet AMD. Could you talk a bit about how you see that program moving towards a pivotal program and how that pivotal program, potentially for 314 and wet AMD, could overlap with efforts with the subretinal approach? Thanks.

其次，314，用於脈絡膜上腔和濕性 AMD。您能否談談您如何看待該計劃向關鍵計劃的發展，以及該關鍵計劃（可能針對 314 和濕性 AMD）如何與視網膜下方法的努力重疊？謝謝。

Okay. I can take the first question, or Steve, do you want to start with the second one or --?

好的。我可以回答第一個問題，或者史蒂夫，你想從第二個問題開始還是——？

I missed the second one. Could you repeat the second one?

我錯過了第二個。你能重複第二個嗎？

Sure, yeah. It was about 314 suprachoroidal and wet AMD. Just wondering what the path is to a pivotal program there and how you see a potentially pivotal effort 314 and wet AMD overlapping with your efforts with the subretinal program you currently have underway.

當然，是的。約為 314 脈絡膜上腔和濕性 AMD。只是想知道那裡的關鍵計劃的路徑是什麼，以及您如何看待潛在的關鍵工作 314 和濕 AMD 與您目前正在進行的視網膜下計劃的工作重疊。

Sure. So with all the experience we have with wet AMD, we have a pretty good sense of assessing both safety and efficacy, both from our subretinal experience and also the prior cohorts we've done with suprachoroidal.

當然。因此，憑藉我們在濕性 AMD 方面的所有經驗，我們對評估安全性和有效性有很好的認識，這既來自我們的視網膜下經驗，也來自我們先前對脈絡膜上腔進行的隊列研究。

So I think it's the usual endpoints that we think of. We get to take advantage of the totality of evidence on top of, of course, having good safety. So biomarkers like retinal thickness, where we get a very good objective measure, BCBA, and of course, a reduction in treatment burden.

所以我認為這是我們想到的通常的終點。當然，除了良好的安全性之外，我們還可以利用全部證據。因此，像視網膜厚度這樣的生物標記物，我們可以得到非常好的客觀測量值、BCBA，當然還有治療負擔的減輕。

So we'll really look at all of those to see what type of response we get at six months and longer and really compare that to what's been seen, for example, even in our subretinal program, where we want to see good durability and really maintain anatomic control as measured by retinal thickness and BCBA control while dramatically reducing injection burden. And we've often talked about at least 50% of patients not needing any injections and over 50% reduction in injection burden.

因此，我們將真正研究所有這些，看看我們在六個月或更長時間後得到什麼類型的反應，並將其與所看到的進行比較，例如，即使在我們的視網膜下項目中，我們希望看到良好的耐久性和真正的效果。我們經常談論至少 50% 的患者不需要任何注射，注射負擔減少 50% 以上。

And this is Curran. To the first question, in terms of functional data in the fall, just to baseline, we measure microdystrophin at a three-month time point. And then on the functional assays, we measure generally every three months, a month, a number of functional assessments that you've seen historically with other programs.

這是庫蘭。對於第一個問題，就秋季的功能數據而言，就基線而言，我們在三個月的時間點測量微肌營養不良蛋白。然後在功能分析方面，我們通常每三個月、一個月進行一次您在其他程式中見過的一些功能評估。

And in the fall, I would expect to see a significant amount of functional data out to 12 months for the dose level 1 patients. And for some of the early dose level 2 patients, you'll see six- and probably nine-month data for them, things like time to rise and NSA as an example. We haven't finalized exactly what data will come out because it's still emerging, but that's the plan for the fall.

在秋季，我預計會看到 1 級劑量患者 12 個月內的大量功能數據。對於一些早期劑量 2 級的患者，您將看到他們六個月甚至九個月的數據，例如起床時間和 NSA 等。我們還沒有最終確定將發布哪些數據，因為數據仍在不斷湧現，但這就是秋季的計劃。

Vikram, you also had the question of how do we see this in the context of our ongoing pivotal subretinal program for wet AMD when thinking about suprachoroidal. I think it's fair to say that both we and AbbVie really see opportunities in both, and that's why we both are together advancing further evaluation of SCS at DL4 for this while we continue with the pivotal program with subretinal.

Vikram，您也提出了這樣的問題：在我們正在進行的濕性 AMD 關鍵視網膜下計劃的背景下，在考慮脈絡膜上膜時我們如何看待這一點。我認為可以公平地說，我們和艾伯維都確實看到了這兩者的機會，這就是為什麼我們雙方共同推進 DL4 的 SCS 的進一步評估，同時我們繼續視網膜下的關鍵計劃。

Certainly, the opportunity that we see with subretinal given the gold standard in safety and efficacy that we've shown an excellent durability has us very excited about that. There's, of course, the opportunity to expand the optionality by having an in-office procedure. And we look forward to gathering more data in the additional cohort to keep evaluating that option.

當然，考慮到安全性和有效性的黃金標準，我們在視網膜下看到了機會，我們已經表現出出色的耐用性，這讓我們感到非常興奮。當然，有機會透過辦公室內程序來擴大選擇範圍。我們期待在額外的隊列中收集更多數據，以繼續評估該選項。

That’s helpful. Thank you.

這很有幫助。謝謝。

Paul Choi, Goldman Sachs.

保羅‧崔，高盛。

Hi, good afternoon and thanks for taking our questions. My first is, I was wondering if you can maybe just elaborate on interest levels in the patient community and clinical community for 202, a potential pivotal trial later this year or early next year in the wake of the recent elevates label expansion and approval there?

你好，下午好，感謝您回答我們的問題。我的第一個問題是，我想知道您是否可以詳細說明202 患者群體和臨床群體的興趣水平，這是一項可能在今年晚些時候或明年初進行的關鍵試驗，因為最近標籤擴展和批准得到了提升？

And then my second question on 314 is with regard to dose cohort 4 here. I know you specified that there would be prophylactic steroid use here, but could you maybe comment on a view whether there would be potentially reduced need for rescue VEGF use. A competitor recently provided some updated data for their program and I think this came as a bit of a surprise.

然後我關於 314 的第二個問題是關於這裡的劑量組 4。我知道您指定這裡將使用預防性類固醇，但您是否可以評論是否可能減少對救援 VEGF 使用的需求。一位競爭對手最近為他們的程式提供了一些更新的數據，我認為這有點令人驚訝。

So just any thoughts there as to whether dose cohort 4 could potentially either increase the injection-free frequency or reduce the rescue usage as you prosecute that cohort? Thank you.

那麼，在起訴該組時，第 4 組劑量是否可能會增加免注射頻率或減少救援使用，有什麼想法嗎？謝謝。

I can take the first one, and then I'll have Steve address the second question. I think on patient recruitment for 202, we've been able to check in with sites and investigators at meetings like PPMD, and we've seen nothing but really strong interest in the program.

我可以回答第一個問題，然後我會讓史蒂夫解決第二個問題。我認為關於 202 的患者招募，我們已經能夠在 PPMD​​ 等會議上與站點和調查人員進行核實，我們除了看到對該計劃的強烈興趣之外什麼也沒看到。

Many of these centers have up to 100 patients. And just having discussions with the investigators around are people still interested in our study given that there's a product on the market. The resounding answer is yes. There are many patients that are looking at our program and seeing the differentiation that it offers, seeing the safety that's been demonstrated to date.

其中許多中心擁有多達 100 名患者。考慮到市場上有一種產品，只要與周圍的研究人員進行討論，人們仍然對我們的研究感興趣。響亮的答案是肯定的。有許多患者正在關注我們的計劃並看到它提供的差異化，看到迄今為止已被證明的安全性。

And I would say that there's strong interest. And therefore, on our end, strong confidence in our ability to recruit the study. So early days, I feel very confident in our ability to recruit the pivotal program.

我想說的是，人們對此很感興趣。因此，我們對招募這項研究的能力充滿信心。所以在早期，我對我們招募關鍵項目的能力非常有信心。

And I'll turn it over to Steve to address the 314 question.

我會將其交給 Steve 來解決 314 問題。

Sure. So regarding DL4 assessment in these indications, we certainly think there's the opportunity that we could decrease rescue use further than what we've seen while maintaining visual acuity benefit instability and also anatomic control.

當然。因此，關於這些適應症中的 DL4 評估，我們當然認為我們有機會比我們所看到的進一步減少救援使用，同時保持視敏度益處的穩定性和解剖學控制。

As I mentioned to one of the earlier questions, we have the flexibility to do that. You referred to some other data that's come out earlier this year. And I think one always has to look at that issue of can you go up higher on dose and if there's either a concern about additional safety issues, including immune response and inflammation.

正如我在之前的一個問題中提到的，我們可以靈活地做到這一點。您提到了今年早些時候發布的一些其他數據。我認為人們總是必須考慮這樣的問題：是否可以增加劑量以及是否擔心其他安全問題，包括免疫反應和發炎。

And also, if you start to run into the issue of how long a duration of prophylactic steroids can really be tolerated. So that's why we're very excited about our safety profile where we don't need extended prophylactic steroids. So I think the totality of that dose give us the chance to go up higher and see if we can reduce injection burden further.

而且，如果您開始遇到預防性類固醇的持續時間可以真正耐受多長時間的問題。這就是為什麼我們對我們的安全性感到非常興奮，因為我們不需要長期使用預防性類固醇。因此，我認為該劑量的總量使我們有機會提高劑量，看看我們是否可以進一步減少注射負擔。

And just one follow-on, Paul, to the question on recruitment. One of the purposes of the data release we did today was really to show people the differentiated level of microdystrophin in some of the older patients that have been treated. So that's just another piece of information that a patient can use when they're deciding what therapy to have their child treated with. So that was one of the purposes of that release is to help people understand our product a bit more.

保羅，關於招募問題的一個後續。我們今天發布數據的目的之一實際上是向人們展示一些已接受治療的老年患者中微肌營養不良蛋白的差異水平。因此，這只是患者在決定讓孩子接受哪種治療時可以使用的另一個訊息。因此，該版本的目的之一是幫助人們更多地了解我們的產品。

Great. Thanks for taking our questions.

偉大的。感謝您回答我們的問題。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

This is Mary Kate on for Alec today. Thanks for taking our questions. Just one on DMD. Given questions around safety for others in the field, what kind of safety database do you expect you'll be required to collect for approval in terms of size and duration of follow-up? Thank you.

這是瑪麗凱特今天為亞歷克主持的節目。感謝您回答我們的問題。只有一個關於 DMD 的。考慮到該領域其他人的安全問題，您預計需要收集什麼樣的安全資料庫以供批准其規模和後續持續時間？謝謝。

Yeah. That's, I think, something that we're still working on and probably will tie out completely in the pivotal plan that we'll submit to FDA. So we're really not able to comment in terms of various specifics there.

是的。我認為，這是我們仍在努力的事情，並且可能會在我們將提交給 FDA 的關鍵計劃中完全結合起來。所以我們真的無法就那裡的各種細節發表評論。

I think in general, our proposal on sample size is in the 30- to 40-patient region, but that's really a discussion that's ongoing with FDA. But I think the reasons that we feel that's a valid number is, number one, we have a commercial-ready process that we won't make changes to during the -- in terms of product profile during the pivotal studies, and so that should reduce the sample size.

我認為總的來說，我們關於樣本量的建議是在 30 到 40 名患者區域，但這實際上是與 FDA 正在進行的討論。但我認為我們認為這是一個有效數字的原因是，第一，我們有一個商業準備流程，在關鍵研究期間的產品概況方面，我們不會對其進行更改，因此應該減少樣本量。

And second, the initial safety record that we've already demonstrated in the trial to date should be a positive in terms of how FDA might view the program and how they assess what the sample size should be. So we feel like we're in a good position there. And I think that gives us a good feeling that the recruitment will be accelerated into next year.

其次，我們迄今為止在試驗中已經證明的初步安全記錄對於 FDA 如何看待該計劃以及如何評估樣本量應該是正面的。所以我們覺得我們在那裡處於有利地位。我認為這讓我們有一種良好的感覺，招募將加速到明年。

Understood. Thank you.

明白了。謝謝。

Annabel Samimy, Stifel.

安娜貝爾·薩米米，斯蒂菲爾。

Hi, thanks for taking my question. We also have two. First, on DMD. Just bringing back the question of functional data and what you might be looking for. Given the broad age group that you're looking at and maybe the different levels of ambulation, are you giving any consideration to stratifying those patients based on age group and measuring them on different metrics depending on their age and then matching against the natural history for that specific age group? So how much granularity might we see already and maybe what are you possibly baking into Phase 3?

您好，感謝您提出我的問題。我們也有兩個。首先，關於DMD。只是帶回功能數據的問題以及您可能正在尋找的內容。考慮到您正在考慮的廣泛年齡組以及可能不同的行走水平，您是否考慮根據年齡組對這些患者進行分層，並根據他們的年齡使用不同的指標進行測量，然後與自然史進行匹配那個特定的年齡層？那麼我們可能已經看到了多少粒度，也許您可能會在第三階段中烘焙什麼？

And then on 314, I guess I'm trying to understand how you're thinking about this dose level 4 in light of other competitors in the space. Do you feel that the benchmark for you is your subretinal? Is it the benchmark for you or other competitors in the space?

然後在 314 上，我想我正在嘗試了解您根據該領域的其他競爭對手如何看待 4 級劑量。你覺得你的基準是你的視網膜下嗎？它是您或該領域其他競爭對手的基準嗎？

And given, I guess, maybe a little bit of a race in the gene therapy space, is there less urgency to be the first one out there or the one to get it right because the population is large and maybe they're a little bit less desperate than, say, in the genetic rare disease area? Are people looking at this competitive landscape the wrong way? So a little broader question. Thanks.

我想，考慮到基因治療領域可能存在一點競賽，成為第一個出現的人或做對的人的緊迫性是否會降低，因為人口規模很大，也許他們有點小比遺傳罕見疾病領域更不那麼絕望嗎？人們是否以錯誤的方式看待這種競爭格局？這是一個更廣泛的問題。謝謝。

I can start with 202. And I think we think about functional data in sort of two dimensions. As it relates to accelerated approval, our primary driver will be measuring microdystrophin at three months as our primary endpoint.

我可以從202開始。我認為我們從二維角度來思考功能數據。由於它與加速批准有關，我們的主要驅動力將在三個月內測量微肌營養不良蛋白作為我們的主要終點。

But along with that, of course, we're measuring functional data along the way. And initially, what I would expect in the fall is likely a reference of functional data to baseline levels for the specific patient.

當然，除此之外，我們還會一路測量功能數據。最初，我預計秋季可能會提供特定患者基線水平的功能數據參考。

Now, if we think about a confirmatory study, you're absolutely correct that studying natural history and matching patients either by age or by disease progression would be part of that strategy that we're having discussions on. So it's actually -- I would expect to see both sort of views as it relates to functional data.

現在，如果我們考慮一項驗證性研究，你絕對是對的，研究自然史並按年齡或疾病進展來配對患者將是我們正在討論的策略的一部分。所以實際上 - 我希望看到這兩種與功能數據相關的視圖。

I'll turn it over to Steve for the 314 question.

我會將 314 問題轉交給 Steve。

Thanks, Annabel. So as far as benchmarking, as I mentioned, we got a lot of experience, many of us from prior programs as well, but certainly in-house with our subretinal program. Really, the target is pretty similar in terms of what you have to show when we think of suprachoroidal, perhaps slightly a little broader, given the nonsurgical in-office opportunity of suprachoroidal.

謝謝，安娜貝爾。正如我所提到的，就基準測試而言，我們獲得了很多經驗，其中許多人也來自先前的項目，但肯定是在我們的視網膜下項目內部。事實上，當我們想到脈絡膜上腔時，目標與您必須展示的內容非常相似，考慮到脈絡膜上腔的非手術就診機會，可能稍微更廣泛一些。

I think an important context when thinking of different programs is really assessing how much durability has really been shown. So really being able to look out to six months and beyond relative to when the last loading dose may have been given, for example, in indications like wet AMD.

我認為在考慮不同的項目時，一個重要的背景是真正評估真正顯示的耐久性。因此，相對於最後一次負荷劑量的給藥時間，確實能夠專注於六個月甚至更長的時間，例如，在濕性 AMD 等適應症中。

And I think with certain agents that require repeat injection, even though they have greater durability, there's the reality that at some point, you're going to need the reinjection. And if you're looking at a time point, that's too early to see that are you going to start seeing the need for rescue creep up. And that's why we're excited about a gene therapy approach where you have stable, consistent anti-VEGF activity that can allow for really the ultimate goal of having sizable proportion of patients not needing any injections.

我認為對於某些需要重複注射的藥物，即使它們具有更大的耐用性，但現實是在某些時候，您將需要重新註射。如果你看一個時間點，那麼現在判斷你是否會開始看到救援的需要逐漸增加還為時過早。這就是為什麼我們對基因療法感到興奮，這種方法具有穩定、一致的抗 VEGF 活性，可以真正實現讓相當大比例的患者不需要任何注射的最終目標。

So we feel good about this approach, and we know how to look at the safety and efficacy to really know when we're in a position to move forward.

因此，我們對這種方法感覺良好，我們知道如何看待安全性和有效性，以真正了解我們何時能夠繼續前進。

Thank you.

謝謝。

Mani Foroohar, Leerink Partners.

Mani Foroohar，Leerink 合夥人。

Hi, good afternoon. This is CJ Yeh on for Mani. Thanks for taking our question. Could you please comment on your strategy in DMD? Are you targeting younger patients than [structure's] current label since you've announced you've expanded age range to one to three, while structure's youngest age is four? Thanks.

嗨，下午好。這是 Mani 的 CJ Yeh。感謝您提出我們的問題。您能評論一下您在 DMD 方面的策略嗎？自從您宣布將年齡範圍擴大到一到三歲以來，您的目標是否是比[結構]當前標籤更年輕的患者，而結構的最小年齡是四歲？謝謝。

Hi, this is Curran. Yeah, I think it's safe to say we want to build an adequate safety database at a minimum for the patients in ages one to three, but we'll be enrolling across a wide variety of ages in the studies.

嗨，這是庫蘭。是的，我認為可以肯定地說，我們希望至少為一到三歲的患者建立足夠的安全資料庫，但我們將在研究中招募不同年齡的患者。

And we had made the decision to expand and look at this broad age range, including one to three, before any ELEVIDYS label expansion. So we've seen this opportunity. And now, with the results safety that we've seen and the microdystrophin expression we've seen across a wide age range on the upper end, it's great opportunity to look at one to three year olds.

在 ELEVIDYS 品牌擴張之前，我們決定擴大並關注這個廣泛的年齡範圍，包括一到三歲。所以我們看到了這個機會。現在，憑藉我們所看到的結果的安全性以及我們在廣泛年齡範圍內所看到的微抗肌營養不良蛋白的表達，這是觀察一到三歲兒童的絕佳機會。

Perfect. Thanks for your commentary.

完美的。感謝您的評論。

Eliana Merle, UBS.

埃利安娜梅爾，瑞銀。

Hi, this is Eric Moskal calling in for Eliana. Thanks so much for question. My first one is 202. Do you have any in-house data on patients already dosed with 202 beyond the three months to help us better understand durability and what the effects might be over time? And what do you expect to see over time? Do you expect label to be stable for three months or more? Or do they deepen over time? And I have a follow-up.

大家好，我是埃里克·莫斯卡爾 (Eric Moskal) 打電話給埃利安娜 (Eliana)。非常感謝您的提問。我的第一個是202。你們是否有關於已經服用 202 超過三個月的患者的任何內部數據，以幫助我們更好地了解耐久性以及隨著時間的推移可能產生的影響？隨著時間的推移，您期望看到什麼？您期望標籤能夠穩定三個月或更長時間嗎？或者它們會隨著時間的推移而加深嗎？我有一個後續行動。

I'm sorry, are you referring to microdystrophin levels beyond three months or other functional data, for example?

抱歉，您指的是超過三個月的微肌營養不良蛋白水平或其他功能數據嗎？

Microdystrophin, yeah.

微抗肌營養不良蛋白，是的。

Okay. No, we're taking a biopsy prior to treatment and then at three months. We don't have biopsies beyond that time point basically per direction with FDA. However, we'll obviously be measuring durability in terms of functional outcomes in the out periods.

好的。不，我們會在治療前和三個月後進行活檢。基本上按照 FDA 的指示，我們不會在該時間點之後進行活檢。然而，我們顯然會根據過時的功能結果來衡量耐久性。

Yes, we don't have data beyond three months, but I think our preclinical data would suggest really excellent durability. And the construct that includes the C-Terminals has a longer half-life than microdystrophin that's devoid of that. So I would expect both higher levels of microdystrophin and perhaps sustained levels relative to what you've seen in other literature.

是的，我們沒有超過三個月的數據，但我認為我們的臨床前數據表明它具有非常出色的耐用性。包含 C 端的構建體比不含 C 端的微抗肌營養不良蛋白具有更長的半衰期。因此，與您在其他文獻中看到的相比，我預計微抗肌營養不良蛋白的水平會更高，而且可能會保持持續水平。

Got it. And just one quick follow-up. Is there anything that you've been able to identify in terms of patient characteristics that's correlated so far with a higher microdystrophin expression or higher functional assessment?

知道了。只需一個快速跟進。到目前為止，您是否能夠在患者特徵方面識別出與較高的微肌營養不良蛋白表達或較高的功能評估相關的任何內容？

So the usual caveat that there aren't enough patients that really have confidence in terms of predictors, I'd say the biggest learning so far is actually that age is not predicting a lower microdystrophin as you go up on age, which has been a concern that the community has had, whether that might be the case in some data from other programs suggest that that may be an issue, but we've not seen that at all.

因此，通常需要注意的是，沒有足夠的患者對預測因素真正有信心，我想說，迄今為止最大的學習實際上是，隨著年齡的增長，年齡並不能預測微肌營養不良蛋白的降低，這一直是社區擔心，其他項目的某些數據是否會出現這種情況，這表明這可能是一個問題，但我們根本沒有看到這一點。

So I think the striking thing from our data is even in the eight and older, we're seeing very robust microdystrophin levels. Beyond that, we're seeing microdystrophin levels across the patients. So no clear differentiator or predictor in this sample to date.

因此，我認為我們的數據中引人注目的一點是，即使在八歲及以上的兒童中，我們也看到了非常強烈的微肌營養不良蛋白水平。除此之外，我們也看到患者體內的微肌營養不良蛋白水平。因此，迄今為止，該樣本中沒有明確的區分因素或預測因素。

Got it. Thank you.

知道了。謝謝。

Luca Issi, RBC.

盧卡·伊西，加拿大皇家銀行。

Oh, great. Thanks so much for taking my question and congrats on the progress. Maybe, Curran, can you just expand a bit more on your recent end of Phase 2 meeting with the FDA? I appreciate it, you're still waiting for the minutes, but can you confirm that your read is that you can get accelerated approval and expression across all patients with DMD and not only patients that are excluded from the Sarepta label today, either because of age or existing immunity. I think it's an important distinctive. So any color, much appreciated.

哦，太好了。非常感謝您提出我的問題並祝賀我的進展。也許，Curran，您能否進一步介紹一下您最近結束的與 FDA 的第二階段會議？我很感激，您仍在等待會議記錄，但您能否確認您的解讀是，您可以在所有DMD 患者中獲得加速批准和表達，而不僅僅是今天被排除在Sarepta 標籤之外的患者，無論是因為年齡或現有免疫力。我認為這是一個重要的特色。所以任何顏色，非常感謝。

And then maybe still in DMD, how are you thinking about a confirmatory trial? Will we still use North Star as the primary endpoint? Or do you think there are other endpoints that can be more sensitive here? Any color, much appreciate it. Thanks so much.

然後也許還在 DMD，您如何考慮驗證性試驗？我們仍會使用北極星作為主要終點嗎？或者您認為還有其他端點可以更敏感嗎？任何顏色，非常欣賞。非常感謝。

I can work a bit in reverse. We'll use North Star, but we're obviously measuring a number of additional functional indicators that you've seen, as I mentioned earlier, time to rise and some of the timed walks that are associated.

我可以做一些反向工作。我們將使用北極星，但我們顯然正在測量您所看到的許多附加功能指標，正如我之前提到的，起床時間以及一些相關的定時行走。

So I would characterize it as we're measuring everything because there are -- it's still a field where I think the functional assays are evolving and each product is different. And I think we want to be able to capture as much functional data as we can across as many indices as we can.

因此，我將其描述為我們正在測量一切，因為我認為功能分析仍然是一個不斷發展的領域，每種產品都是不同的。我認為我們希望能夠在盡可能多的指數中捕獲盡可能多的功能數據。

Related to accelerated approval, our strategy is to approach this for a broad approval, not a narrow approval for only patients that are ineligible for current therapy. And the basis for that is simply the differentiation of the product.

與加速批准相關，我們的策略是獲得廣泛批准，而不是僅針對不符合當前治療條件的患者進行狹隘批准。其基礎就是產品的差異化。

That's, I think, one of the basic tenets of the accelerated approval is unmet need. And we feel we have a really strong evolving case that addresses unmet need, and our ambition will be to obtain as broader label as possible.

我認為，加速批准的基本原則之一就是滿足未滿足的需求。我們認為我們有一個非常強大的不斷發展的案例來解決未滿足的需求，我們的目標是獲得盡可能廣泛的標籤。

Got it. Thanks so much.

知道了。非常感謝。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

Hey, thanks for taking the question. On the Phase 3 plans for diabetic retinopathy, just trying to gauge your level of confidence in AbbVie's level of confidence in the first-half initiation next year. What are sort of the primary questions that the company is we to get answered by the FDA or the FDA hopes do you think the FDA will need to answer so at the end of Phase 2 meeting to sort of ensure that this Phase 3 gets kicked off?

嘿，謝謝你提出問題。關於糖尿病視網膜病變的第三階段計劃，只是想衡量一下您對艾伯維明年上半年啟動的信心程度。公司需要 FDA 回答的主要問題是什麼，或者 FDA 希望您認為 FDA 需要在第二階段會議結束時回答，以確保啟動第三階段？

And maybe just some color on the DME cohort. And is the consideration -- is there a consideration to pursue these more progressed patients? Or is the thought you're really just to supplement with some data in patients who have progressed on to DME?

也許只是 DME 隊列中的一些顏色。是否有考慮去追尋這些進展較大的患者？或者您只是想補充一些已進展為 DME 的患者的數據？

I'll give a brief comment and then turn it over to Steve. I certainly think we and AbbVie have a really high level of confidence in DR progressing into pivotal next year. And I think that's shown in the acceleration of the end of Phase 2 meeting into this year. We're eager to get this study up and going.

我將給出一個簡短的評論，然後將其轉交給史蒂夫。我當然認為我們和艾伯維對 DR 明年進入關鍵階段充滿信心。我認為第二階段會議加速到今年結束就反映了這一點。我們渴望進行這項研究。

And I think I'll let Steve comment on the details of the pivotal approach, but we feel like there's a very standard approach to developing in diabetic retinopathy established endpoints and precedent. But I'll let Steve comment on the details of what we're thinking and how that study should go.

我想我會讓史蒂夫評論關鍵方法的細節，但我們覺得有一個非常標準的方法來發展糖尿病視網膜病變的既定終點和先例。但我會讓史蒂夫評論我們正在思考的細節以及這項研究應該如何進行。

Yeah. Fortunately, as Curran mentioned, there's a roadmap for diabetic retinopathy that's been laid by repeat injection anti-VEGF that has really allowed us to know what do you expect from a negative control arm if you're not receiving an active agent. And that, of course, really helps us to power studies in combination with the actual proof-of-concept data that we have. We also know a lot about the endpoints that are accepted.

是的。幸運的是，正如 Curran 所提到的，透過重複注射抗 VEGF 藥物製定了治療糖尿病視網膜病變的路線圖，這確實讓我們知道，如果您不接受活性藥物，您對陰性對照組有何期望。當然，這確實有助於我們結合我們擁有的實際概念驗證數據來推動研究。我們也對所接受的端點了解很多。

So we feel very confident that this has really derisked quite a lot from a regulatory standpoint. So it's really assessing some things around the edges and some definitions and the like, frankly, when it comes to the pivotal designs.

因此，我們非常有信心，從監管的角度來看，這確實降低了許多風險。因此，坦白說，當涉及到關鍵設計時，它實際上是在評估一些邊緣事物和一些定義等。

So I think that's one of the aspects that given the positive results that we've seen why we have been able to accelerate and bring this end of Phase 2 meeting into Q4 instead of Q1 next year. And then your --

因此，我認為這是我們所看到的積極成果的一個方面，為什麼我們能夠加速並將第二階段會議的結束推遲到明年第四季而不是第一季。然後你的--

I was just going to ask about the DME cohort.

我只是想問一下 DME 隊列的情況。

Yeah. So we are looking at center-involved DME. Of course, that's the traditional indication. So we don't see a need to go outside the box in terms of the type of patient population that we'd be looking at so that we can really have the context of what others have looked at and what others have seen.

是的。所以我們正在尋找中鋒參與的DME。當然，這是傳統的指示。因此，我們認為沒有必要在我們要研究的患者群體類型方面跳出框框，這樣我們才能真正了解其他人所觀察到的情況和其他人所看到的情況。

So, yeah, it's just a great opportunity. We do know diseases like DME or the complication of DME and wet AMD that there's a little higher VEGF drive than it exists with, say, non-proliferative diabetic retinopathy without DME. So we think we're right around the dose response range where this is going to be very interesting to look at DL4 in this patient population.

所以，是的，這只是一個很好的機會。我們確實知道 DME 等疾病或 DME 和濕性 AMD 的併發症，與沒有 DME 的非增殖性糖尿病視網膜病變相比，VEGF 驅動力略高。因此，我們認為我們正處於劑量反應範圍附近，在這個患者群體中觀察 DL4 將會非常有趣。

Great. Thank you.

偉大的。謝謝。

Daniil Gataulin, Chardan Capital Markets.

丹尼爾·加陶林，查丹資本市場。

Hey, guys. Thank you for taking the question and congrats on your roll. I have a quick question on wet AMD program, this retina delivery. When do you anticipate sharing data from the Fellow Eye study? And as a follow-up to that, how it translates to suprachoroidal injections given those are more likely interact with the immune system. What is your long-term strategy for treating Fellow Eye using suprachoroidal to a degree? Thank you.

嘿，夥計們。感謝您提出問題並祝賀您獲得成功。我有一個關於濕 AMD 計劃的快速問題，即視網膜交付。您預計什麼時候分享 Fellow Eye 研究的數據？作為後續行動，考慮到脈絡膜上註射更有可能與免疫系統相互作用，它如何轉化為脈絡膜上註射。您在一定程度上使用脈絡膜上腔治療同胞眼的長期策略是什麼？謝謝。

I'll turn that one to Steve.

我會把這個轉給史蒂夫。

Hi, Daniil. So as far as when we would have Fellow Eye results, we have the update today that we completed enrollment of the Fellow Eye study. So if you add on up to six months or so from that would give you a rough range of when we traditionally have been comfortable releasing data in this type of indication to really show a stable effect at least.

嗨，丹尼爾。就我們何時獲得 Fellow Eye 結果而言，我們今天收到了更新，我們已完成 Fellow Eye 研究的註冊。因此，如果您再加上六個月左右的時間，您將得到一個粗略的範圍，即我們傳統上一直在這種類型的適應症中舒適地發布數據的時間，以至少真正顯示出穩定的效果。

We were excited to have this study not just from a regulatory standpoint to have that label expansion to allow bilateral disease. But as you referred, the immune response, whether you would have a greater immune response that could affect safety and/or efficacy when you dose the second eye, subretinal, I think, is the most straightforward to feel confident that you won't have an issue dosing the Fellow Eye because of the immune-privileged status of the subretinal space.

我們很高興能夠進行這項研究，而不僅僅是從監管的角度來看，標籤擴展以允許雙側疾病。但正如您所提到的，免疫反應，無論您是否會產生更大的免疫反應，當您對第二隻眼睛（視網膜下）進行給藥時，是否會影響安全性和/或功效，我認為，是最直接的讓您有信心不會有由於視網膜下空間的免疫特權狀態，對對眼的劑量存在問題。

Suprachoroidal, we've seen much less inflammation and no safety issues in terms of inflammation compared to, say, intravitreal administration. So that gives us confidence that suprachoroidal would have that opportunity as well. So we decided to take it one step at a time, first look at subretinal Fellow Eye, but over time, certainly, it would make sense to assess Fellow Eye with suprachoroidal as well.

與玻璃體內注射相比，脈絡膜上註射的發炎要少得多，並且沒有發炎方面的安全問題。因此，這讓我們相信脈絡膜上層也有這樣的機會。因此，我們決定一步一腳印，首先觀察視網膜下的“Fellow Eye”，但隨著時間的推移，當然，用脈絡膜上層評估“Fellow Eye”也是有意義的。

Got it. Thank you very much for taking the question.

知道了。非常感謝您提出問題。

Ladies and gentlemen, there are no questions. That concludes today's call. Thank you, all, for joining. You may now disconnect.

女士們先生們，沒有問題了。今天的電話會議到此結束。謝謝大家的加入。您現在可以斷開連線。