Regenxbio Inc (RGNX) 2025 Q2 法說會逐字稿

Welcome everyone to the second-quarter 2025 the REGENXBIO earnings conference call. (Operator Instructions) Please note, slide reference during this call are available in the webcast and at the events page of REGENXBIO website.

歡迎大家參加2025年第二季REGENXBIO收益電話會議。（操作員指示）請注意，本次通話期間的投影片參考可在網路廣播和 REGENXBIO 網站的活動頁面上找到。

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

現在，我想將會議交給 Regenxbio 首席法律官 Patrick Christmas。請繼續。

Good morning and thank you for joining us today. Earlier this morning, Regenxbio released financial and operating results for the second quarter ended June 30, 2025. The press release is available on our website at www.regenxbio.com. Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans.

早安，感謝您今天加入我們。今天早些時候，Regenxbio 發布了截至 2025 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 上查閱。今天的電話會議將包含關於我們財務前景以及監管和產品開發計劃的前瞻性聲明。

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.

這些前瞻性陳述受風險和不確定性的影響，可能導致實際結果與預測不同，並可以透過​​諸如預期、計劃、將、可能、預期、相信、應該、打算等詞語和其他類似含義的詞語來識別。

Any such forward-looking statements are not guarantees of future performance and involves certain risks and uncertainties. These risks are described in the risk factors in the management's discussion and analysis section of Regenxbio annual report on Form 10-K for the full year ended December 31, 2024. And comparable risk factor 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.

任何此類前瞻性陳述都不能保證未來的表現，並涉及一定的風險和不確定性。這些風險在 Regenxbio 截至 2024 年 12 月 31 日的全年 10-K 表年度報告的管理層討論與分析部分的風險因素中進行了描述。以及 Regenxbio 10-Q 表季度報告中的可比較風險因素部分，這些報告已提交給美國證券交易委員會，並可在美國證券交易委員會的網站上查閱。

Any information we provide on this conference call is provided only as of the date of this call, August 7, 2025, 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召開之日 2025 年 8 月 7 日，我們不承擔因新資訊、未來事件或其他原因而更新我們在本次電話會議上可能做出的任何前瞻性陳述的義務。

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，今天的通話將被錄音並進行網路直播。此外，任何可能提供的未經審計或備考財務資訊都是初步的，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'll now turn the call to Curran Simpson, President and CEO of Regenxbio. Curran?

現在我將電話轉給 Regenxbio 總裁兼執行長 Curran Simpson。柯倫？

Thank you, Patrick, and thank you everyone for joining us. I hope that you're having a great summer. Today I'm pleased to be joined by Dr. Steve Pakola, our Chief Medical Officer, and Mitchell Chan, our Chief Financial Officer, to review the exceptional progress being made by the REGENXBIO team as we prepare for our first commercial approval this year and multiple potential near-term product launches.

謝謝你，派崔克，也謝謝大家加入我們。我希望你度過一個愉快的夏天。今天，我很高興與我們的首席醫療官 Steve Pakola 博士和首席財務官 Mitchell Chan 一起回顧 REGENXBIO 團隊在為今年的首次商業批准和多個潛在的近期產品發布做準備時所取得的卓越進展。

Before we begin, I'd like to acknowledge the Duchenne community and the recent events they have faced. We understand these have been incredibly challenging and uncertain times and express our deepest sympathies to the families experiencing loss.

在我們開始之前，我想感謝杜氏肌肉營養不良症社群以及他們最近所面臨的事件。我們理解這是一個極具挑戰性和不確定性的時期，我們向遭受損失的家庭表示最深切的同情。

These recent events have only reinforced our strong commitment to deliver RGX 202 as a potential best in class gene therapy for Duchenne. We believe that RGX-202 has the potential to safely provide strong functional benefit and durability, offering hope for better lives.

這些最近發生的事件只會加強我們的堅定承諾，即將 RGX 202 作為杜氏肌肉營養不良症的最佳基因療法。我們相信 RGX-202 具有安全地提供強大的功能優勢和耐用性的潛力，為更美好的生活帶來希望。

With positive and growing interest from the patient community and physicians, I am very pleased to share that we are accelerating our guidance for RGX-202. We now expect to complete enrollment in the ongoing pivotal study this October. Our ability to move this timeline up from end of year further solidifies RGX-202's position as the potential next gene therapy to market for Duchenne.

隨著患者群體和醫生的積極和日益增長的興趣，我很高興地告訴大家，我們正在加快對 RGX-202 的指導。我們預計今年十月將完成正在進行的關鍵研究的招募。我們能夠將這一時間表從年底提前，進一步鞏固了 RGX-202 作為杜氏肌肉營養不良症的潛在下一個基因療法的地位。

The community is clearly in need of additional options. We continue to actively enroll and open new sites in the Affinity DUCHENNE Pivotal trial. With plans to roll directly into a confirmatory study to support our accelerated approval. Additionally, we are in the unique position of having drug supply in hand for our pivotal and confirmatory trials.

社區顯然需要更多選擇。我們將繼續積極招募 Affinity DUCHENNE Pivotal 試驗人員並開設新站點。計劃直接進行確認性研究以支持我們的加速批准。此外，我們擁有獨特的優勢，可以為我們的關鍵試驗和確認性試驗提供藥品供應。

We remain on track to report topline data in early 2026. Submit a BLA in mid-2026. And potentially be on the market by 2027 when the vast majority of the DMD population is expected to remain untreated. From the beginning of this program, we implemented a differentiated therapeutic approach. We pioneered a proactive immune suppression regimen to drive improved safety outcomes and reduce the potential risk of known liver issues found in other programs.

我們仍有望在 2026 年初報告營收數據。於 2026 年中期提交 BLA。預計到 2027 年，該藥物將有可能上市，但屆時預計絕大多數 DMD 患者仍未接受治療。從這個計畫開始，我們就實施了差異化的治療方法。我們率先採用了主動免疫抑制方案，以改善安全結果並降低其他項目中發現的已知肝臟問題的潛在風險。

Our Phase 1, 2 data to date supports that our approach is effective. RGX-202 also has consistent industry leading purity levels in DUCHENNE. With over 80% full capsid content in our product. This is important because higher purity leads to less total vector load delivered to patients, and they contribute to the positive safety profile we've seen to date.

我們迄今為止的第 1、2 階段數據支持我們的方法是有效的。RGX-202 在杜氏硬度計中也具有業界領先的純度水準。我們的產品中完整衣殼含量超過 80%。這很重要，因為純度越高，輸送給患者的總載體負荷就越少，而且有助於我們迄今為止看到的積極的安全性。

We believe our in-house manufacturing capabilities are a highly strategic asset and gives us a unique ability to serve the large Duchenne market available at launch. We are pleased to announce we are initiating commercial manufacturing this fall at our manufacturing innovation center here in Rockville, Maryland.

我們相信，我們的內部製造能力是一項高度策略性的資產，並使我們擁有獨特的能力來服務上市時龐大的杜氏肌肉營養不良症市場。我們很高興地宣布，我們將於今年秋天在位於馬裡蘭州羅克維爾的製造創新中心啟動商業化生產。

This GMP facility can produce up to 2,500 doses of RGX-202 per year. With our strong momentum and it's the only investigational gene therapy enrolling in a Phase 3 study in North America. RGX 202 is well positioned to be next to market and a potential best in class gene therapy for Duchenne.

該 GMP 設施每年可生產多達 2,500 劑 RGX-202。憑藉我們強勁的發展勢頭，這是北美唯一參與第三階段研究的基因療法。RGX 202 已做好充分準備進入市場，並有望成為杜氏肌肉營養不良症的最佳基因療法。

Let's turn our focus to our retinal disease franchise. In partnership with AbbVie, we continue to advance ADBV RGX-314. Also known as serab gene Lumparvovec or cerovec. As the potential one-time gene therapy for chronic retinal conditions.

讓我們把焦點轉向視網膜疾病領域。我們與 AbbVie 合作，繼續推進 ADBV RGX-314。也稱為 serab 基因 Lumparvovec 或 cerovec。作為慢性視網膜疾病的潛在一次性基因治療方法。

I'm very pleased that earlier this morning, we announced an update to our agreement with AbbVie to advance cerovec into pivotal phase for diabetic retinopathy.

我很高興今天早上我們宣布了與 AbbVie 的協議更新，將 cerovec 推進到治療糖尿病視網膜病變的關鍵階段。

Based on positive two year data from the Phase 2 altitude trial, we will initiate a Phase 2B/3 trial. The cost of the study will be covered by the accompanying milestones, including the $100 million we receive upon the first patient dose in the Phase 2B portion of the trial. Steven Mitch will share more about the data and financials shortly.

根據第 2 階段高原試驗兩年來的積極數據，我們將啟動第 2B/3 階段試驗。研究費用將由隨附的里程碑付款支付，其中包括我們在試驗第 2B 階段的第一位患者接受劑量治療時收到的 1 億美元。史蒂文·米奇 (Steven Mitch) 很快就會分享更多有關數據和財務的資訊。

But let me reiterate our excitement about this program, which gives us another pivotal program in chronic eye care with our partner AbbVie. Both wet AMD and Dr represent large multi-billion dollar commercial opportunities. And we believe cerovec has the potential to preserve vision, prevent disease progression, and serve as a meaningful alternative to today's standard of care.

但讓我重申我們對這個計畫的興奮之情，它為我們與合作夥伴 AbbVie 提供了另一個慢性眼科護理的關鍵計畫。濕性AMD和Dr都代表著數十億美元的巨大商業機會。我們相信 cerovec 具有保護視力、防止病情進展的潛力，並成為當今護理標準的有意義的替代方案。

Last but not least, the FDA accepted our BLA for RGX-121, now known as clomidzogine Lemparvovec for the treatment of MPS 2 or Hunter syndrome. This BLA was accepted under the accelerated approval pathway with the targeteddufa date of November 9. Pre-BLA activities are progressing well. We have completed the mid-cycle review meeting and our first PLI and BMO inspections with the FDA successfully with no observations.

最後但同樣重要的一點是，FDA 接受了我們對 RGX-121 的 BLA，現在稱為氯米佐嗪 Lemparvovec，用於治療 MPS 2 或亨特綜合徵。該 BLA 已根據加速審批途徑獲得批准，預計批准日期為 11 月 9 日。BLA 前期活動進展順利。我們已成功完成了中期審查會議以及與 FDA 的第一次 PLI 和 BMO 檢查，沒有任何發現。

These are exciting achievements and a testament to the exceptional quality of our people, process, and science. If approved, RGX-121 will be Regenxbio's first approved gene therapy. Commercial preparations with our partner Nippon Shinyaku are progressing well. Products intended for launch has already been produced, and we are committed with our partner to bringing this potentially transformative treatment to patients in early 2026.

這些都是令人興奮的成就，證明了我們的人員、流程和科學的卓越品質。如果獲得批准，RGX-121 將成為 Regenxbio 首個核准的基因療法。我們與合作夥伴日本新藥株式會社的商業準備工作進展順利。計劃推出的產品已經生產出來，我們與合作夥伴致力於在 2026 年初為患者帶來這種具有變革意義的治療方法。

These accomplishments demonstrate our seamless and focused execution against our strategy to bring potentially transformative gene therapies to patients. We remain excited for, and well positioned to deliver on opportunities ahead of us.

這些成就證明了我們無縫且專注地執行了我們的策略，為患者帶來具有變革性的基因療法。我們仍然對眼前的機會感到興奮，並已做好準備去抓住它。

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

說到這裡，我現在想把電話轉給史蒂夫，讓他介紹我們的臨床計畫的最新情況。史蒂夫。

Thank you, Curren. Today, we're excited to share updates across our multiple pivotal programs. I'll start with our retina franchise, cerovec, which is being developed in collaboration with AbbVie to treat wet AMD and diabetic retinopathy, or DR.

謝謝你，Curren。今天，我們很高興與大家分享我們多個關鍵項目的最新進展。我首先介紹我們的視網膜特許經營權 cerovec，該產品正在與 AbbVie 合作開發，用於治療濕性 AMD 和糖尿病視網膜病變（DR）。

First, I'll address CEROVEC for DR being evaluated in the Phase 2 altitude trial using in-office super coroidal delivery. I'm pleased to highlight the data supporting our advancement to pivotal stage. The data slides are available in the webcast and on the events page of our website, and you can follow along as I discussed.

首先，我將介紹在第 2 階段高原試驗中使用辦公室內超級冠狀動脈輸送技術評估的 DR 用 CEROVEC。我很高興強調支持我們進入關鍵階段的數據。數據幻燈片可以在網路廣播和我們網站的活動頁面上找到，您可以按照我的討論進行操作。

As outlined on slide 3, DR impacts more than 20 million people globally, and these patients are at increased risk of developing vision threatening complications.

如投影片 3 所述，DR 影響著全球超過 2,000 萬人，這些患者罹患威脅視力的併發症的風險較高。

Moving to slide 4, a one-time in-office conjection of CEROVEC has the potential to provide long-lasting improvement to disease severity and reduce the risk of vision-threatening events or DTEs. Using one-time in-office super corrodial delivery is convenient for the working age population impacted by DR.

轉到幻燈片 4，一次性在辦公室注射 CEROVEC 有可能長期改善疾病嚴重程度並降低視力威脅事件或 DTE 的風險。使用一次性診室超級腐蝕劑遞送對於受到 DR 影響的工作年齡人口來說十分方便。

Also, this route of administration allows targeted delivery into a compartmentalized space to limit exposure to the vitreous and anterior segment.

此外，這種給藥途徑可以將藥物標靶輸送到分隔空間，以限制玻璃體和前段的暴露。

Slides 5 and 6, show the altitude trial design, and baseline characteristics of participants with non-proliferative diabetic retinopathy or NPDR.

幻燈片 5 和 6 展示了高原試驗設計以及非增生性糖尿病視網膜病變或 NPDR 患者的基線特徵。

Moving to safety data on slide 7, CEROVEC was well tolerated at all dose levels. Further illustrated on slide 8, we are very pleased to share that at two years in dose level 3, with short course prophylactic topical steroids, there were zero cases of intraocular inflammation.

轉到幻燈片 7 上的安全數據，CEROVEC 在所有劑量水平下均具有良好的耐受性。如幻燈片 8 進一步說明的那樣，我們很高興地告訴大家，在劑量水平 3 的兩年內，使用短期預防性局部類固醇，沒有出現任何眼內發炎病例。

Moving to efficacy on slide 9, starting with the one year results. As expected in the untreated control group, patients generally get worse, with 41% experiencing at least two-step worsening in their diabetic retinopathy severity score or DRSF. In stark contrast, NPDR patients treated with dose levels 2 and 3 are generally improving.

轉到第 9 張投影片上的功效，從一年的結果開始。正如未接受治療的對照組所預期的那樣，患者的病情普遍惡化，其中 41％ 患者的糖尿病視網膜病變嚴重程度評分或 DRSF 至少惡化了兩級。與此形成鮮明對比的是，接受劑量 2 和 3 治療的 NPDR 患者的病情普遍有所改善。

And now on slide 10, for the first time, we share two year results. CEROVEC demonstrated a dose-dependent increased rate of meaningful DRSS improvement, with 50% of dose level 3 patients achieving at least a two-step improvement without need for any supplemental treatment. A rate 6 times that of historical control.

現在在第 10 張投影片上，我們第一次分享了兩年的成果。CEROVEC 顯示出劑量依賴性增加的有意義的 DRSS 改善率，50% 的劑量水平 3 患者無需任何補充治療即可實現至少兩步改善。這速度是歷史控制速度的6倍。

Slide 11 further illustrates the durable efficacy seen over time at dose level 3 out to two years. Importantly, these imaging results are translating into benefit in terms of decreased risk of vision threatening events.

投影片 11 進一步說明了在劑量水準 3 下隨時間推移觀察到的長達兩年的持久療效。重要的是，這些影像結果轉化為降低視力威脅事件風險的益處。

On slide 12, Theraact treated NPDR patients at a dose-dependent reduction in VTEs, with dose level 3 achieving at least a 70% reduction in VTEs compared to historical control.

在第 12 張投影片上，Theraact 以劑量依賴性方式減少 VTE 來治療 NPDR 患者，與歷史對照組相比，劑量水準 3 可使 VTE 減少至少 70%。

In summary, on slide 13, a single in-office injection of CEROVEC was well tolerated and demonstrated durable long-term efficacy, including meaningful DRSS improvement and significant reduction in the risk of vision threatening events.

總而言之，在第 13 張投影片上，單次辦公室注射 CEROVEC 耐受性良好，並表現出持久的長期療效，包括有意義的 DRSS 改善和視力威脅事件風險的顯著降低。

Based on these compelling results, in an agreement with AbbVie, we are initiating a global pivotal program. The initial pivotal trial will be a two-part Phase 2b3 double mast placebo-controlled superiority trial, including 2 dose arms of errava. The primary endpoint will be proportion of patients with at least a two-step improvement on DRSS at one year.

基於這些令人信服的結果，我們與 AbbVie 達成協議，啟動一項全球關鍵計畫。初步關鍵試驗將是一項由兩部分組成的 2b3 期雙重安慰劑對照優效性試驗，包括 2 個劑量組的 errava。主要終點是一年內 DRSS 至少有兩步驟改善的患者比例。

This pivotal trial will have two sequential parts. The first part will be the dose selection phase that includes dose level 3 and dose level 4 arms from altitude to allow interim evaluation of safety and efficacy, to then select the dose or doses to carry forward into enrollment of part 2 of the pivotal protocol. Site selection is already in progress, and we look forward to sharing more on this program as we progress.

此次關鍵審判將分為兩個連續的部分。第一部分將是劑量選擇階段，包括高海拔劑量水平 3 和劑量水平 4 組，以便對安全性和有效性進行中期評估，然後選擇劑量或劑量進行關鍵方案第 2 部分的招募。選址工作已在進行中，我們期待在進展過程中分享更多有關該計劃的資訊。

In Wet AMD, we are evaluating CEROVEC via two different delivery forms, subretinal and suprachoroidal. Within sub-retinol, we have two ongoing pivotal trials, atmosphere and ascent in the US, Europe, and Japan. These trials continue to progress well with enrollment nearing completion. Overall, we remain encouraged by the ongoing progress with CEROVEC, especially the safety profile observed in our scorroidal programs.

對於濕性 AMD，我們透過兩種不同的傳遞形式（視網膜下和脈絡膜上腔）評估 CEROVEC。在亞視黃醇領域，我們在美國、歐洲和日本進行了兩項關鍵試驗，分別是氛圍試驗和上升試驗。這些試驗持續進展順利，招募工作已接近完成。總體而言，我們對 CEROVEC 的持續進展感到鼓舞，尤其是在我們的 scorroidal 專案中觀察到的安全性。

This is particularly notable in the setting of short course prophylactic steroid eye drops, a significantly shorter regimen than those used in other gene therapy trials.

這在短期預防性類固醇眼藥水的環境中尤其明顯，其療程比其他基因治療試驗中使用的療程短得多。

Moving to RGX-202. A potential best in class one-time gene therapy for the treatment of Duchenne. RGX 202 is the only microdistrophin construct to include the C-terminal domain, making it the closest to naturally occurring dystrophin. The CT domain has been shown to prolong microdystrophin activity and preserve muscle health by protecting it against contraction-induced damage.

移至 RGX-202。一種潛在的用於治療杜氏肌肉營養不良症的最佳一次性基因療法。RGX 202 是唯一包含 C 端結構域的微肌營養不良蛋白構建體，使其最接近天然存在的肌營養不良蛋白。CT 結構域已被證明可以延長微肌營養不良蛋白的活性，並透過保護肌肉免受收縮引起的損傷來維持肌肉健康。

This pre-clinical research was recently published in ASGCT's peer reviewed journal. This construct, combined with the highest purity levels in the field and a proactive immune suppression regimen are translating into the clinic with better functional outcomes and favorable safety profile, including in older boys.

這項臨床前研究最近發表在 ASGCT 的同行評審期刊。這種結構與該領域最高的純度水平和積極的免疫抑制方案相結合，正在轉化為臨床，具有更好的功能結果和良好的安全性，包括對年齡較大的男孩。

In June, we presented new positive Phase 1 2 interim data for 202 at the pivotal dose. Showing meaningful functional improvements compared to expected disease trajectory. Notably, at 12 months, all patients demonstrated improvement on time function tests compared to baseline, with time to stand, 10 meter walk, run, and time to climb results exceeding the minimally important difference.

6 月份，我們公佈了 202 關鍵劑量的新的積極第 1 2 階段中期數據。與預期的疾病軌跡相比，顯示出有意義的功能改善。值得注意的是，在 12 個月時，所有患者的時間功能測試均與基線相比有所改善，站立時間、10 公尺步行、跑步和爬坡時間結果均超過了最小重要差異。

The majority of patients were eight years and older at dosing, an age when functional decline would typically be expected. 202 also continue to be well tolerated with no SAEs or adverse events of special interest.

大多數患者在服藥時年齡在 8 歲及以上，這個年齡通常會出現功能衰退。 202 也繼續具有良好的耐受性，沒有出現 SAE 或特別值得關注的不良事件。

Even at our higher dose level, we have seen no thrombocytopenia and no evidence or signs of liver injury in any patient, including as assessed by liver function testing.

即使在較高劑量水平下，我們也沒有看到任何患者出現血小板減少症，也沒有出現肝損傷的證據或體徵，包括透過肝功能測試評估的結果。

To build on what Curran shared earlier, the differentiated therapeutic approach for 202 includes a proactive short course immune suppression regimen that was developed from the outset of this program in collaboration with the patient community and leading Duchenne physicians. We pioneered this approach for improved safety outcomes.

基於 Curran 先前分享的內容，202 的差異化治療方法包括主動的短期免疫抑制方案，該方案是從該計劃一開始就與患者社區和領先的杜氏肌肉營養不良症醫生合作開發的。我們率先採用這種方法來改善安全結果。

We're very pleased with how this patient-focused approach, along with our differentiated product, is translating into a favorable safety profile observed to date. We expect the complete enrollment of the 30 patients in the AFFINITY DUCHENNE pivotal trial to support accelerated approval by October of this year, and we will continue to enroll after that for a confirmatory trial.

我們非常高興看到這種以患者為中心的方法以及我們的差異化產品轉化為迄今為止觀察到的良好安全狀況。我們預計，AFFINITY DUCHENNE 關鍵試驗的 30 名患者將在今年 10 月前全部入組，以支持加速批准，之後我們將繼續入組以進行確認性試驗。

Now on to RGX-121. It's such an incredibly exciting time for Regenxbio and the Hunter syndrome community, with the ongoing progress for RGX-121 BLA. 121 represents a potentially transformative one-time treatment for patients with Hunter's syndrome.

現在開始討論 RGX-121。對於 Regenxbio 和亨特綜合徵社區來說，這是一個令人難以置信的激動人心的時刻，RGX-121 BLA 正在不斷取得進展。 121 代表著對亨特氏症患者俱有潛在變革性的一次性治療方法。

We look forward to an anticipated FDA decision in November. Overall, we're making significant progress across all our late stage programs. I'd like to express my sincere gratitude to all the patients, families, clinicians, site staff, and patient advocacy representatives who have supported these trials.

我們期待 FDA 十一月份做出決定。總體而言，我們在所有後期專案上都取得了重大進展。我要向所有支持這些試驗的病人、家屬、臨床醫生、現場工作人員和病人權益代表表示誠摯的感謝。

With that, I'll turn the call over to Mitch to review our financial guidance. Mitch.

說完這些，我將把電話轉給米奇來審查我們的財務指導。米奇。

Thank you, Steve, and good morning everyone.

謝謝你，史蒂夫，大家早安。

REGENXBIO ended the quarter on June 30, 2025 with cash equivalent, and marketable securities of $364 million compared to $245 million as of December 31, 2024. The increase was primarily driven by the $110 million upfront payment from the Dipan Shinyaku in the first quarter of 2025 and the $145 million in net proceeds received from the royalty monetization with healthcare royalty partners in the second quarter of 2025 and was partially offset by cash used to fund operating activities in the first half of 2025.

REGENXBIO 於 2025 年 6 月 30 日結束本季度，現金等價物和有價證券為 3.64 億美元，截至 2024 年 12 月 31 日為 2.45 億美元。這一增長主要得益於 2025 年第一季 Dipan Shinyaku 支付的 1.1 億美元預付款以及 2025 年第二季度與醫療保健特許權使用費合作夥伴進行特許權使用費貨幣化所獲得的 1.45 億美元淨收益，但被 2025 年上半年用於資助經營活動的現金部分抵消。

R&D expenses were $60 million for the quarter ended June 30, 2025, compared to $49 million for the quarter ended June 30, 2024. The increase was primarily attributed to manufacturing-related expenses and other clinical supply costs and clinical trial expenses for CEROVEC and RGX-202 pivotal trials.

截至 2025 年 6 月 30 日的季度研發費用為 6,000 萬美元，而截至 2024 年 6 月 30 日的季度研發費用為 4,900 萬美元。成長主要歸因於製造相關費用和其他臨床供應成本以及 CEROVEC 和 RGX-202 關鍵試驗的臨床試驗費用。

Turning to the specifics around CEROVEC announcement today, Steve went through the very encouraging data we continue to generate in DR and a new Phase 2 3 study that both AbbVie and REGENXBIO believe will be designed to strengthen the body of evidence for CEROVEC in DR and maximize the probability of success in a planned global Phase 3 program.

談到今天 CEROVEC 公告的具體內容，史蒂夫介紹了我們在 DR 中繼續生成的非常令人鼓舞的數據以及一項新的 2 期 3 期研究，AbbVie 和 REGENXBIO 都認為這項研究旨在加強 CEROVEC 在 DR 中的證據，並最大限度地提高計劃中的全球 3 期計劃的成功概率。

Under the terms of the amended agreement, we are effectively being paid in advance half of the $200 million dollar milestone that would have been earned upon dosing of the pivotal trial. We will now be paid $100 million upon first patient dose in the phase 2B3 trial and receive the next $100 million upon dosing of the first patient in the second Phase 3 trial. This brings in $100 million upon first subject dose and more than covered the cost of the phase 2b trial.

根據修訂後的協議條款，我們實際上將提前獲得關鍵試驗給藥後應獲得的 2 億美元里程碑款項的一半。現在，我們將在 2B3 期試驗中為第一位患者用藥時獲得 1 億美元的報酬，並在第二期 3 期試驗中為第一位患者用藥時獲得下 1 億美元的報酬。這項研究為首例受試者註射帶來了 1 億美元的收入，足以支付 2b 期試驗的費用。

Additionally, the amendment reflects AbbVie continued investment in the CEROVEC program and their independent pursuit of the Phase 3 achieved trial to further support the global commercial opportunity. We expect the June 30 cash balance reported today to fund our operation into early 2027 and enables us to accelerate towards multiple product launches.

此外，該修訂反映了 AbbVie 對 CEROVEC 計劃的持續投資及其對第 3 階段試驗的獨立追求，以進一步支持全球商業機會。我們預計今天報告的 6 月 30 日現金餘額將為我們到 2027 年初的營運提供資金，並使我們能夠加速推出多種產品。

Please note this cash runway guidance does not include multiple non-diluted financing opportunities that could further extend our cash runways significantly beyond 2027.

請注意，此現金跑道指引不包括多項非稀釋融資機會，這些機會可能會在 2027 年以後進一步延長我們的現金跑道。

These include development or sales milestone for RGX-121, the sale of our anticipated priority review voucher for RGX-121, development milestones associated with AbbVie's collaboration, including those in diabetic retinopathy program, as well as the potential additional funds from the May 2025 healthcare royalty agreement.

這些包括 RGX-121 的開發或銷售里程碑、我們預期的 RGX-121 優先審查憑證的銷售、與 AbbVie 合作相關的開發里程碑（包括糖尿病視網膜病變計劃中的里程碑），以及 2025 年 5 月醫療保健特許權使用費協議帶來的潛在額外資金。

With that, I would turn the call back to Curran to provide final thoughts.

有了這些，我會把電話轉回給 Curran，讓他提供最終的想法。

Thank you, Mitch. Today's exciting updates make it clear that we are executing at a high level across all aspects of our business. Bringing us one step closer to becoming a commercial company. Our strategy is clear and focused with our leading in-house and end capabilities. We are rapidly advancing multiple late stage programs.

謝謝你，米奇。今天令人興奮的更新清楚地表明，我們在業務的各個方面都表現得非常出色。使我們距離成為一家商業公司更近了一步。我們的策略清晰，重點突出，擁有領先的內部和終端能力。我們正在快速推進多個後期專案。

These potential first or best in class gene therapies represent the opportunity to address significant unmet need for patients with rare and retinal diseases. We have our first potential FDA approval on the horizon this year.

這些潛在的首創或同類最佳基因療法為解決罕見疾病和視網膜疾病患者的重大未滿足需求提供了機會。我們今年即將獲得第一個 FDA 批准。

Most importantly, we maintain a strong financial position and have multiple avenues for non-dilutive financing to support the continued development and potential commercialization of our products.

最重要的是，我們保持強大的財務狀況，並擁有多種非稀釋性融資管道，以支持我們產品的持續開發和潛在商業化。

I want to thank our REGENXBIO team for their dedication, our physician partners for their collaboration, and the patients and families who participate in our trials. Your contributions are essential to our mission of improving lives through the curative potential of gene therapy.

我要感謝 REGENXBIO 團隊的奉獻精神、我們的醫生合作夥伴的合作以及參與我們試驗的患者和家屬。您的貢獻對於我們透過基因療法的治療潛力改善生活的使命至關重要。

With that, thanks for your time today. I'll turn the question to call over for questions, operator.

感謝您今天抽出時間。我將把問題轉交給接線員來回答問題。

Thank you. We will now begin a question and answer session. (Operator instructions)

謝謝。我們現在開始問答環節。（操作員指示）

Judah Frommer, Morgan Stanley.

猶大‧弗洛默，摩根士丹利。

Yeah. Hi, guys. Thanks for taking the questions and congrats on all the progress updates here. Maybe one on DMD and then another on DR. I guess with DMD, anything you can share regarding reaction from the DMD community, maybe more specifically about the conditioning or prophylaxis regimen that you have in 202?

是的。嗨，大家好。感謝您回答這些問題，並祝賀這裡所有的進度更新。也許一個在 DMD 上，另一個在 DR 上。我想問一下，關於 DMD，您能分享 DMD 社群的反應嗎，更具體地說，關於您在 202 年所採取的調理或預防方案？

It seems like the community is probably a little more attuned to sirolimus specifically after that patient death in Brazil. So anything you can share about how the community is feeling about that regimen. And then switching to Dr, I guess, any thoughts on what’s happening in dose level three between year one and year two to see that improvement in DRSS?

似乎整個社會對雷帕黴素的關注度有所提高，尤其是在巴西那位患者死亡之後。那麼可以分享一下社區對療法的感受嗎？然後轉到醫生，我想，對於第一年和第二年之間劑量水平三發生的情況，有什麼想法可以觀察到 DRSS 的改善嗎？

And more generally, can you share with us kind of how the discussions with AbbVie went in changing the plan for, the pivotal design here to go through the 2b and then the three, any change in level of excitement from them or is it more just kind of proving out the dose level? Thank you.

更一般地說，您能否與我們分享一下與 AbbVie 的討論如何改變計劃，這裡的關鍵設計是如何通過 2b 和 3，他們的興奮程度有任何變化嗎？或者這只是為了證明劑量水平？謝謝。

Sure, thanks for the questions. I think on 202, I would characterize the interest at the patient community as kind of at an all-time high for our type of program. I think certainly the proactive immune suppression regimen that we’ve been talking about since the beginning has even greater appeal in this way that people think about safety and high dose AAV treatments.

當然，謝謝你的提問。我認為在 202 上，病患群體對我們這類計畫的興趣達到了前所未有的高度。我認為，我們從一開始就討論的主動免疫抑制方案無疑具有更大的吸引力，因為人們會考慮安全性和高劑量的 AAV 治療。

And I think we are seeing that in our interest in the study itself and we’re doing things like conducting webinars With Cure Duchenne to maybe more broadly get the word out about the program and obviously as related to enrollment, we’re expanding sites pretty dramatically this year.

我認為，我們對這項研究本身很感興趣，我們正在做一些事情，例如與「治愈杜氏肌肉營養不良症」組織一起舉辦網路研討會，以便更廣泛地宣傳該計劃，顯然，就招生而言，我們今年將大幅擴展研究地點。

I think at a base level, the interest in gene therapy is still very strong in the patient community and I think the interest in our program in particular has risen dramatically. And I think the interest in our program in particular has risen dramatically.

我認為從根本上來說，患者群體對基因治療的興趣仍然非常強烈，而且我認為對我們的計畫的興趣尤其急劇上升。我認為人們對我們項目的興趣尤其顯著地上升了。

The one thing I would say is that I think the patients initially the immune suppression regimen was portrayed as onerous and potentially not commercially viable. We’re finding that the patients actually love the level of monitoring and surveillance that we’re doing as it related to the study because I think it brings them comfort that hopefully none of these events that are controllable will occur.

我想說的是，我認為患者最初的免疫抑制方案被描述為繁重的並且可能不具有商業可行性。我們發現，患者實際上喜歡我們在研究中進行的監測和監測級別，因為我認為這給他們帶來了安慰，希望這些可控的事件都不會發生。

I think I’ll ask Steve to characterize the DR data, if that’s okay.

如果可以的話，我想我會請史蒂夫來描述 DR 數據。

Sure, thanks for the questions Judah. So, as you pointed to the improved efficacy that we’ve seen over time, how do we look at that data? I think the overarching aspect is you certainly want durability to really confirm that you have the sustained anti VEGF activity. And I think if you’re having disease modification, then you even have that opportunity to see continuing improvement even after a single administration.

當然，感謝 Judah 提出的問題。那麼，正如您所指出的，我們隨著時間的推移看到了療效的提高，我們如何看待這些數據？我認為最重要的一點是你肯定希望持久性能真正證實你具有持續的抗 VEGF 活性。我認為，如果您正在進行疾病改良，即使經過一次治療，您也有機會看到病情持續改善。

And I think that’s the part that is so compelling, particularly for this indication that you can have a single injection that has durable benefit both in terms of DRSS imaging improvement, but also very key preventing those vision threatening complications. So, I really think that we would have been excited with stability across the two dose levels.

我認為這是十分引人注目的部分，特別是對於這種適應症，只需一次注射即可在 DRSS 成像改善方面帶來持久的益處，而且對於預防那些威脅視力的併發症也是非常關鍵的。所以，我真的認為我們會對兩種劑量水平的穩定性感到興奮。

But to actually see this improvement at dose level 3 at two years has really given both us and AbbVie the excitement to pivot in a positive way to really make sure we don’t leave any efficacy on the table. You know, it’s worth noting this data came in first half of this year. So, we were rolling along, planning to move ahead, given that we’d already met the target product profile.

但實際上看到劑量水平 3 在兩年內出現這種改善，確實讓我們和 AbbVie 都感到興奮，並決定以積極的方式轉變，真正確保我們不會忽視任何療效。你知道，值得注意的是這些數據是今年上半年的數據。因此，我們繼續前進，並計劃繼續前進，因為我們已經達到了目標產品形象。

But now we’ve got this amazing opportunity, and it’s not only the efficacy side, but it’s key that we’re seeing excellent safety without intraocular inflammation with a relatively short topical steroid regimen. So, we have the flexibility to potentially not leave efficacy on the table because of our safety that we’ve seen with our compartmentalized delivery. So, that’s really how both we and AbbVie are looking at this as a tremendous opportunity.

但現在我們有了這個絕佳的機會，這不僅是在療效方面，而且關鍵是我們看到，透過相對較短的局部類固醇治療方案，它具有極佳的安全性，而且不會引起眼內發炎。因此，由於我們在分區配送中看到了安全性，因此我們可以靈活地不放棄療效。所以，我們和 AbbVie 都將此視為一個巨大的機會。

Gina Wang, Barclays.

巴克萊銀行的吉娜·王 (Gina Wang)。

Thank you. Maybe I just follow, Steve, your comments. Is that the reason you wanted to adding dose level 4 for the pivotal study phase 2b to evaluate, you know, the potential further improvement with a higher dose and giving a good safety? And, also, for the pivotal study, are you thinking about one year, or would that be two year study?

謝謝。史蒂夫，也許我只是關注你的評論。這就是您想要在關鍵研究階段 2b 中添加劑量水平 4 的原因嗎，以評估更高劑量是否可能進一步改善並提供良好的安全性？另外，對於關鍵研究，您考慮的是一年還是兩年的研究？

Related question is, what is the reason to amend agreement? And then if, Mitch, you can share with us how much cost will be for the running the Phase 2b study? And then quickly on BMD, just wondering if you have any recent interaction with the FDA since Nicole Verdun departure, so as well, Prasad departure, any concerns regarding the pivotal path that was agreed on by the prior administration?

相關問題是，修改協議的理由是什麼？那麼，米奇，您能否與我們分享第 2b 階段研究需要多少成本？然後快速談談 BMD，只是想知道自從 Nicole Verdun 離職以來，您是否與 FDA 有過任何互動，還有 Prasad 離職，對於前政府同意的關鍵路徑有任何擔憂嗎？

Thanks Gina, I’ll start and maybe work my way backwards to the questions. I think on FDA, we’re certainly having a lot of interaction with FDA as it relates to the hunter program now. I don’t think there’s a new facility inspection, the PLI that we mentioned that has come in with no observations, we’re super proud of that and I think that that not only plays well for our chances of approval on 121 but our future chances of approval on the Duchenne program and of course 314.

謝謝吉娜，我會開始，然後可能再反過來回答問題。我認為在 FDA 方面，我們現在肯定與 FDA 就獵人計劃進行了很多互動。我認為沒有新的設施檢查，我們提到的 PLI 沒有發現任何觀察結果，我們對此感到非常自豪，我認為這不僅對我們獲得 121 批准的機會有很大幫助，而且對我們未來獲得杜氏肌肉營養不良症計劃和 314 批准的機會也有很大幫助。

So we’re really pleased with the FDA interactions that we’re having and we haven’t seen any shift more broadly on say clinical trial design, to date on any other programs. So I would say right now it’s still what we’ve been saying, which is consistent interactions with FDA as expected in the late stage reviews that we’re encountering.

因此，我們對與 FDA 的互動感到非常滿意，到目前為止，我們還沒有看到任何其他項目在臨床試驗設計方面出現任何更廣泛的轉變。所以我想說，現在我們仍然在說，正如我們所預期的，在後期審查中與 FDA 保持一致的互動。

Steve, I’ll ask you to maybe comment on the question on, actually before I do, I think Mitchell characterized the milestone amendment change, but there’s actually a mechanical aspect to that, that in the original contract, a Phase 2B wasn’t really ever contemplated. So we were actually pleased to see AbbVie basically update that amendment to recognize the 2B and initiate part of that full milestone as part of that, that was something that I felt helped us in terms of cash runway being able to be paid at the initiation of the 2B rather than how it was originally written as first patient in a pivotal, even though we see the 2B as being intimately combined as a pivotal.

史蒂夫，我想請你對這個問題發表評論，實際上在我發表評論之前，我認為米切爾描述了里程碑修正案的變化，但實際上有一個機械方面，即在原始合約中，第 2B 階段從未真正被考慮過。因此，我們很高興看到 AbbVie 基本上更新了該修正案，以承認 2B 並啟動該完整里程碑的一部分，我認為這在現金流方面對我們有幫助，能夠在 2B 啟動時支付，而不是像最初寫的那樣作為關鍵的第一位病人，即使我們認為 2B 與關鍵緊密結合。

Steve, did you want to comment on this question regarding DR for DL4?

史蒂夫，你想對有關 DL4 的 DR 的問題發表評論嗎？

So the first part of your DR question, why DL4? Certainly, it’s both efficacy and safety, the fact that we saw the improvement in DL3 and that data coming in at two years in the first half of this year. The other piece of the equation is safety.

那麼你的 DR 問題的第一部分是，為什麼是 DL4？當然，它既有效又安全，事實上，我們看到了 DL3 的改善，而數據在今年上半年已經出來兩年了。等式的另一個部分是安全性。

And as you know, we have our altitude DME arm with DL4, as well as our AV8 wet AMD dose level 4 arm. So, in the first half of this year, we got to take advantage of interim follow-up on these patients, including those earlier months after dosing, which really gives you the read on the key time period as far as safety and tolerability.

如您所知，我們有一個帶有 DL4 的高海拔 DME 臂，以及 AV8 濕性 AMD 劑量等級 4 臂。因此，在今年上半年，我們必須對這些患者進行中期隨訪，包括服藥後的最初幾個月，這確實可以讓您了解安全性和耐受性的關鍵時間段。

So, in short, we’re seeing what we want to see in terms of efficacy in the DR study, as well as what we see across dose level 3 and 4. So, we’re going up because we can. And I think it makes sense that you really don’t want to leave efficacy on the table. And it’s worth evaluating in a dose selection phase.

所以，簡而言之，我們在 DR 研究中看到了我們想要看到的療效，以及我們在劑量等級 3 和 4 中看到的結果。所以，我們繼續前進，因為我們能夠做到。我認為你確實不想放棄功效，這是有道理的。並且值得在劑量選擇階段進行評估。

When you think of how massive this DR opportunity is, particularly for a one time in office treatment, we in AbbVie felt this was a great opportunity where we can look at two separate doses to really risk mitigate leaving anything on the table. And as you know as well, it’s not uncommon in retina pivotal trials where relatively speaking, they’re not too large that you can often take two doses into pivotal. So, we’re really trying to keep open our options given the results that we’ve seen.

當您想到這個 DR 機會有多麼巨大時，特別是對於一次性辦公室治療，我們 AbbVie 認為這是一個很好的機會，我們可以研究兩種不同的劑量，以真正降低風險，避免留下任何東西。而且您也知道，這在視網膜關鍵試驗中並不罕見，相對而言，它們的規模不是太大，您通常可以服用兩劑進入關鍵階段。因此，根據我們所看到的結果，我們確實在努力保持開放的選擇。

I think, I’m Michelle, have you found I missed that, Steve, on the one or two year, endpoint,

我想，我是米歇爾，你有沒有發現我錯過了，史蒂夫，在一兩年的終點，

And we also have the benefit of a lot of regulatory history with the FDA, including our prior end of Phase 2 meeting, where we know that this DRSS endpoint is accepted for adequate and well controlled trials. And we know accepted at the one year time point. So, makes sense for us to take advantage of that opportunity. So, the primary endpoint is at one year.

我們也受惠於 FDA 的大量監管歷史，包括我們先前結束的第 2 階段會議，我們知道這個 DRSS 終點已被接受用於充分且控制良好的試驗。我們知道在一年的時間點上它被接受了。因此，我們利用這個機會是有意義的。因此，主要終點是一年。

Sorry for interrupting Steve. Mitch, did you want to comment again on the milestone structure?

抱歉打擾了史蒂夫。米奇，你想再評論一下里程碑結構嗎？

Yeah, absolutely. And it’s a great question. I would say the $200 million remains intact. I think as Curran mentioned, the amendment was made because the Phase 2 b was not contemplated earlier. So in total, the $200 million is basically split into two, $100 million and $100 million. And the first $100 million will more than cover this clinical trial for the Phase 2b. We don’t want to go into specifics in terms of the costs, but I will reiterate that the $100 million will more than cover the study costs. Thanks for your question.

是的，絕對是如此。這是一個很好的問題。我想說這 2 億美元仍然保持不變。我認為正如 Curran 所提到的，做出這項修改是因為之前沒有考慮到第 2 階段 b。所以總的來說，這 2 億美元基本上被分成了兩個部分，1 億美元和 1 億美元。首筆 1 億美元足以支付 2b 期臨床試驗的費用。我們不想談論具體的費用，但我要重申的是，1 億美元足以支付研究費用。謝謝你的提問。

Mani Faroohar, Leerink Partners.

Mani Faroohar，Leerink Partners。

Hey guys, you have Ryan on for Mani. Thanks for taking our question and congrats on the update. So I know it’s early days, still enrolling the pivotal, but as you guys look to a DMD launch playing out, I’m kind of just curious how you see the dynamics of the broader prevalent patient population versus those ineligible for existing therapies right now.

嘿夥計們，Ryan 代替 Mani。感謝您回答我們的問題，並祝賀更新。所以我知道現在還為時過早，仍在招募關鍵患者，但隨著你們期待 DMD 的推出，我只是有點好奇你們如何看待更廣泛的普遍患者群體與目前不符合現有療法的患者群體的動態。

Like do you see the first part of launch really being tailored to one more than the other or is this just going to be a pretty broad launch across the board?

例如，您是否認為發布的第一部分實際上是針對某一特定目的而定制的，還是這只是一次全面的、相當廣泛的發布？

And then maybe just one on Wet AMD. Can you just talk about whether the subretinal launch is a means to the suprachoroidal or whether you see a durable albeit smaller market for this type of approach? Thanks.

然後也許只有一個關於 Wet AMD 的資訊。您能否談談視網膜下發射是否是脈絡膜上腔注射的手段，或者您認為這種方法雖然市場規模較小但具有持久性？謝謝。

I can start with the second question. I think we see it in subretinal as an entity on its own. Now, if down the road, a suprachoroidal Wet AMD approach for CEROVEC has the same product profile in the clinic as what we’re seeing in sub retinal, you could argue that the in office procedure would be preferable but I think there will always be as well certain geographies that are very amenable to the sub retinal administration.

我可以從第二個問題開始。我認為我們在視網膜下將其視為一個獨立的實體。現在，如果將來 CEROVEC 的脈絡膜上腔濕性 AMD 方法在臨床上具有與我們在視網膜下看到的相同的產品特性，您可能會認為辦公室內程序會更可取，但我認為總會有某些地區非常適合視網膜下給藥。

We’re seeing really robust recruitment for example in Europe on our sub retinal study. So I think that both are very viable and I think the sub retinal product profile and clinical data we’re seeing can sustain itself, time will tell.

例如，在歐洲，我們在視網膜下研究中看到了非常強勁的招募勢頭。所以我認為兩者都非常可行，而且我認為我們所看到的視網膜下產品概況和臨床數據可以維持下去，時間會證明一切。

I think on the approach to the commercial market for Duchenne, if you look at our study design, we’re recruiting one and older. So we see the opportunity here for a broad label and we see the opportunity with a differentiated product that we’re seeing strong functional benefit and also a very favorable safety profile. We see opportunity to take a dominant position in the market based on our initial data.

我認為，在杜氏肌肉營養不良症的商業市場方法上，如果你看看我們的研究設計，你會發現我們正在招募一歲及以上的患者。因此，我們看到了廣泛標籤的機會，也看到了差異化產品的機會，我們看到了強大的功能優勢以及非常有利的安全性。根據我們的初步數據，我們看到了在市場上佔據主導地位的機會。

Right now we’re not exploring the non-ambulatory aspect of Duchenne and that’s something we’re still contemplating, although you could make the thesis that our immune suppression regimen would be incredibly favorable for that patient population. Our focus is 100% on the ambulatory study that we’re running now and a broad label as the outcome.

目前，我們還沒有探索杜氏肌肉營養不良症的非行走方面，這是我們仍在考慮的事情，儘管你可以認為我們的免疫抑制方案對該患者群體非常有利。我們的重點是目前正在進行的門診研究以及作為結果的廣泛標籤。

Elle Mary, UBS.

艾莉瑪麗，瑞銀。

Thanks for taking my question. Just a follow-up on the last question. Just curious how you’re thinking about a potential strategy in non-ambulatory patients given your preconditioning regimen, and curious if you’ve had any discussions with the FDA on that in the past, and any color you can share in terms of how they might be thinking about non ambulatory safety.

感謝您回答我的問題。這只是對最後一個問題的後續回答。我只是好奇，考慮到您的預處理方案，您是如何考慮針對非臥床患者的潛在策略的，並且好奇您之前是否與 FDA 就此進行過討論，您能否分享一下他們如何看待非臥床安全性。

And then just second, as we think about the subretinal Phase 3, which will be a major catalyst when that comes up, can you elaborate a little bit on what you think would be sort of competitive or clinically meaningful, particularly as we look towards some of those secondary endpoints?

其次，當我們考慮視網膜下第 3 階段時，它將成為主要的催化劑，您能否詳細說明您認為什麼會具有競爭力或臨床意義，特別是當我們著眼於一些次要終點時？

Sure, I think on the question around non ambulatory, we have not one aspect I would point out for our ambulatory ongoing pivotal study, we pointed to completion in October, we do have a broader set of mutations allowed in the inclusion criteria than other studies, so we are taking, as I said, a broad approach to the labels, not just age but also mutation status.

當然，我認為關於非臥床患者的問題，對於我們正在進行的臥床關鍵研究，我沒有一個方面要指出，我們指出在 10 月份完成，我們在納入標準中允許的突變範圍比其他研究更廣泛，所以正如我所說的，我們對標籤採取了廣泛的方法，不僅是年齡，還有突變狀態。

I think in non-ambulatory, there’s still a lot to learn from some of the recent events that we’ve all heard about, and I think we’re taking a cautious approach to that right now. We have not had detailed discussions with the FDA around a non-ambulatory study design, but that is something we plan to.

我認為，在非行走方面，我們仍然可以從最近發生的一些我們都聽說過的事件中學到很多東西，而且我認為我們現在對此採取了謹慎的態度。我們尚未與 FDA 就非門診研究設計進行詳細討論，但這是我們計劃要做的。

But I think that’s going to be related with expansion of our safety database in our existing program. We want that to be a prerequisite to exploring non ambulatory that we establish early on a good safety profile in the ambulatory population.

但我認為這與我們現有程式中的安全資料庫的擴展有關。我們希望這成為探索非步行患者的先決條件，即儘早為步行患者建立良好的安全狀況。

I’ll ask Steve to comment on the subretinal question for secondaries.

我會請史蒂夫對次級視網膜下問題發表評論。

I think as you mentioned, it’s a very significant milestone coming up, the completion of our two pivotal trials for subretinal treatment of Wet AMD. You know, as far as what we’re looking for and what we think will fill a significant unmet need in the space, the two aspects are of course the primary endpoint where safety has to be maintained and we need to show non inferiority on VA both from a regulatory standpoint, but also from a commercial standpoint.

我認為正如您所說，這是一個非常重要的里程碑，我們完成了兩項針對濕性 AMD 視網膜下治療的關鍵試驗。您知道，就我們所尋找的以及我們認為將填補該領域未滿足的重大需求而言，這兩個方面當然是必須保持安全性的主要終點，我們需要從監管的角度和商業的角度證明 VA 的非劣效性。

You raise an important point on the secondary endpoints, particularly the injection burden. Because with a one-time injection that’s certainly one of the key value propositions here where we know that patients are not getting the injections in the real world and are continuing to lose vision.

您提出了關於次要終點的一個重要觀點，特別是注射負擔。因為一次性注射無疑是這裡的關鍵價值主張之一，我們知道患者在現實世界中不會接受注射並且會繼續喪失視力。

So, how do you quantify that? Well, it roughly hasn’t changed over time where what we hear from clinicians in a lot of discussions that we’ve had over the years, it’s been pretty stable that we’d like to see at least a 50% reduction in injection burden. And to be able to achieve that with a one-time injection, while maintaining vision in a controlled study where the control arm is getting very prescribed on label treatment.

那麼，您如何量化這一點？嗯，它大致沒有隨著時間的推移而改變，多年來我們在許多討論中從臨床醫生那裡聽到的是，它是相當穩定的，我們希望看到注射負擔至少減少 50%。並且能夠透過一次性注射實現這一目標，同時在對照研究中保持視力，其中對照組在標籤治療上得到嚴格規定。

We believe that not only will lead to lower injection burden and treatment burden for patients in the real world, but because they have that sustained anti VEGF activity, it also will be a benefit provision maintenance, which really makes the total package of the value proposition quite compelling.

我們相信，這不僅會降低現實世界中患者的注射負擔和治療負擔，而且由於它們具有持續的抗 VEGF 活性，也將是一種福利提供維持，這確實使整個價值主張非常引人注目。

Luca Issi, RBC

盧卡·伊西（RBC）

Good morning. Thanks for taking our questions. This is Lisa on for Luca. Maybe just on diabetic retinopathy. Just wondering if you can walk us through the potential path to approval here. Can the Phase 2b3 be used as a registrational study alone, or will an additional two Phase 3 studies be required for approval?

早安.感謝您回答我們的問題。這是 Lisa 為 Luca 表演的。也許只是關於糖尿病視網膜病變。只是想知道您是否可以向我們介紹獲得批准的潛在途徑。2b3 期研究可以單獨用作註冊研究嗎，還是需要另外兩項 3 期研究才能獲得批准？

And maybe just on the efficacy here for DR, it looks like 50% of patients did not require further treatment, but just wondering if you can comment on the 50% that did. Did they go back to a regular cadence of anti VEGF injections, or did they need only periodic supplemental injections?

也許僅就 DR 的療效而言，看起來 50% 的患者不需要進一步治療，但我只是想問您是否可以對需要進一步治療的 50% 患者發表評論。他們是否恢復了定期注射抗 VEGF 藥物，還是只需要定期補充注射？

And just last one on subretinal for Wet AMD on the pivotal study, can you comment on the state of enrollment, has this trial been fully enrolled, and if so, when did enrollment close?

最後，關於視網膜下注射治療濕性 AMD 的關鍵研究，您能否評論一下招募情況？這項試驗是否已經全部招募完畢？如果是，招募何時結束？

Thanks for the questions. I can start with the last one around subretinal enrollment. We’re seeing really robust enrollment and I think we’re in a situation where completion of enrollment is essentially imminent, but we will certainly update when those studies are both fully enrolled looking forward to that. But we feel really good about enrollment and as I mentioned earlier, maybe unexpectedly, really strong trend in enrollment in Europe, which AbbVie is conducting those sites.

感謝您的提問。我可以從最後一個關於視網膜下登記的問題開始。我們看到入學人數非常龐大，我認為我們即將完成入學申請，但我們一定會在這些研究全部入學後更新資訊。但我們對招生情況感到非常滿意，正如我之前提到的，也許出乎意料的是，AbbVie 正在歐洲開展這些計畫的招生趨勢非常強勁。

So stay tuned, and that’s why we continue to guide to top line data in 2026 based on optimism around completing enrollment for those studies.

所以請繼續關注，這就是為什麼我們基於對完成這些研究的招生的樂觀態度，繼續指導 2026 年的頂線數據。

I’ll ask Steve to comment on the DR data.

我會請史蒂夫對 DR 數據進行評論。

Yeah, so the first part of your question, Lisa, on the potential path to regulatory approval. So, we believe there is the requirement traditionally needed of course, of two adequate and well controlled studies. So, that’s our plan. Notably, the Phase 2b3 study that will be starting would be intended to be one of those two studies. So, I think that’s encouraging. That’s why we say we’re starting our pivotal program.

是的，麗莎，你問題的第一部分是關於獲得監管部門批准的潛在途徑。因此，我們認為當然需要進行兩項充分且控制良好的研究。這就是我們的計劃。值得注意的是，即將開始的 2b3 期研究將是這兩項研究之一。所以，我認為這是令人鼓舞的。這就是我們說我們正在啟動關鍵計劃的原因。

In terms of the data from the two year results that we showed on DL3, 50% of the patients had at least two step improvement without needing supplemental injections. That doesn’t mean that the other 50% of patients needed supplemental injections. It actually was a minority of patients who wound up getting any intravitreal injections. And we felt it was important to really lay out how each of these DL3 patients did over one year and two years, so you can see that evolution.

就我們在 DL3 上展示的兩年結果數據而言，50% 的患者至少有兩步驟改善，而無需補充注射。這並不意味著其他 50% 的患者需要補充注射。實際上，只有少數患者最終接受了玻璃體內注射。我們認為，真正闡述這些 DL3 患者在一年和兩年內的表現非常重要，這樣您才能看到他們的變化。

And I refer you to slide 11, so you can see those details. But again, it was only a minority of patients that wound up getting any injections. And those 50% where we saw at least two step improvement without any injection is really the key take home message.

請您參閱第 11 張投影片，以便您可以看到這些細節。但同樣，只有少數患者最終接受了注射。而我們看到的 50% 的患者在沒有任何注射的情況下至少有兩步的改善，這才是真正關鍵的一點。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

Just a couple from us. First on 202, I guess, given everything that's happened the past two months with Sarepta. What is your current view on the market dynamic at launch. And any updated sort of percent breakdown of the prevalent pool at that point would be helpful. And then, I appreciate the differences between 202 and Levida, as well as the emerging safety profile for 202.

距離我們只有幾對。考慮到過去兩個月 Sarepta 發生的一切，我想首先是 202。您目前對產品發佈時的市場動態有何看法？此時，任何關於流行池的百分比細分的更新都會有所幫助。然後，我了解了 202 和 Levida 之間的差異，以及 202 新興的安全性。

But do you expect, a class effect for liver injury could be applied to the label given they are both AV gene therapies. And then lastly, on 314, -- I guess, how should we view, the two pivotal studies versus the phase 3 chief study that ABBY is planning to launch? Do you think data from the first two sub-retinal studies will be sufficient to file with achieve more for being leveraged for commercialization, with the physicians, and any color that would be helpful. Thank you.

但是，您是否預料到，鑑於它們都是 AV 基因療法，可以將肝損傷的類效應應用於標籤。最後，關於 314，我想，我們應該如何看待這兩個關鍵研究與 ABBY 計劃啟動的第三階段主要研究？您是否認為前兩項視網膜下研究的數據足以提交文件，以便為商業化、與醫生以及任何有幫助的顏色提供更多利用？謝謝。

Sure, thanks for the question. The last one is fairly straightforward. The subretinal pivotal studies atmosphere and ascent, will be sufficient for filing an approval. And the study that we mentioned today is really a post marketing approach to judge the efficacy of the product in against real world outcomes. So they're very separate and the two pivotal's that we're running which are highly powered as a result of some sample size increases we made, we feel will be very adequate for filing.

當然，謝謝你的提問。最後一個相當簡單。視網膜下關鍵研究的氣氛和上升，將足以獲得批准。我們今天提到的研究實際上是一種上市後方法，用於根據現實世界的結果來判斷產品的功效。因此，它們是非常獨立的，並且由於我們增加了一些樣本量，我們正在運行的兩個關鍵數據具有很高的功率，我們認為這對於歸檔來說非常適合。

And I think in terms of the market dynamic at launch, for, back to your question on 202, we certainly see a really significant level of the prevalent population still being available to us. Based on some of the interruptions in launch, maybe greater than 90% of what we initially estimated of the prevalent population. So that that will lead us to potentially at launch itself.

我認為，就發佈時的市場動態而言，回到您關於 202 的問題，我們確實看到很大一部分流行人群仍然可以為我們提供服務。根據發射過程中的一些中斷情況，可能會超過我們最初估計的流行人口的 90%。因此，這將使我們在發佈時就有可能實現這一目標。

Ensuring that we have adequate quantities of drug available for launch, which is readily possible given that we have in-house manufacturing, we have really highly productive process. And we can stockpile at launch a significant number of doses. So our intention is to be able to be in a position to take on a significant portion of the market.

確保我們有足夠數量的藥物可供上市，這很容易實現，因為我們有內部製造，我們擁有非常有效率的流程。我們可以在發射時儲存大量劑量。因此，我們的目標是能夠佔據相當大的市場份額。

At launch, and I think, where we're positioned, in terms of timeline and our differentiated product profile, really makes this a potential blockbuster opportunity. On the question around, enabling.

在發佈時，我認為，就時間表和差異化產品配置而言，我們所處的位置確實使其成為一個潛在的轟動機會。關於周圍問題，啟用。

The injury --

受傷--

Yes, Steve, I was going to defer that to you.

是的，史蒂夫，我本來打算把這件事交給你處理。

Okay. Great. So, Alec, yeah, you referred to, the existing therapy. And the liver injury components and liver failure components in the label. And how that could, potentially lead to any kind of class, effect considerations. I think each program has to be looked at in its own right, and I think that's why the points Curran has made about the clear differentiation that we have in terms of product purity, with a much higher full to empty capsidd ratio that's industry leading.

好的。偉大的。那麼，亞歷克，是的，你提到了現有的治療方法。以及標籤中的肝損傷成分和肝衰竭成分。以及這如何可能導致任何類型的類別和效果考慮。我認為每個項目都必須根據其自身情況來看待，我認為這就是 Curran 所指出的我們在產品純度方面有明顯差異的原因，我們的滿衣殼與空衣殼的比例要高得多，在業界處於領先地位。

And of course, our proactive immune modulation approach. And the existing therapy has per label up to 40% rate of liver injury. And I think we're seeing Our differentiated approach translate in the clinic to a clear differentiation in terms of risk of liver injury, where we, in our phase 12 studies, see 0 of 13 patients with any signs or symptoms of liver injury, including on LFT assessment. So, This gives us a lot of confidence in terms of how we can show differentiation on safety overall, but also in terms of potential risks to the liver.

當然，還有我們的主動免疫調節方法。而現有的治療方法每份標籤上的肝損傷發生率高達40%。我認為，我們看到我們的差異化治療方法在臨床上轉化為對肝損傷風險的明確區分，在我們的第 12 階段研究中，我們發現 13 名患者中 0 名出現肝損傷的任何體徵或症狀，包括 LFT 評估。因此，這讓我們對如何在整體安全性方面表現出差異化以及對肝臟的潛在風險方面充滿信心。

Jack Padovano, Stifel.

傑克·帕多瓦諾（Jack Padovano），Stifel。

Hi team, this is Jack on for Annabel. Thanks for taking our questions. So on the rationale for the phase 2B with 314, I know you mentioned that you don't want to leave FX on the table, which makes sense. So the two-step improvement for dose level, two seemed equivalent to, dose level 1 at year one, Or sorry, -- I think I may have gotten that mixed up for dose level 3 equivalent to dose level 2 at year one.

大家好，我是傑克，為安娜貝爾 (Annabel) 服務。感謝您回答我們的問題。因此，關於 314 階段 2B 的理由，我知道您提到您不想將 FX 留在談判桌上，這是有道理的。因此劑量水平的兩步改進，第二步似乎相當於第一年的劑量水平 1，或者抱歉，我認為我可能把它混淆了，劑量水平 3 相當於第一年的劑量水平 2。

And the real differentiation only emerges at year two. What was the decision to include dose level 4 here partially driven because you feel like you need to improve efficacy even further to sufficiently convince FDA with just the year one data, kind of essentially asking if that 21%, 22% efficacy is sufficient for approval already and you just think you can do even better.

而真正的差異要到第二年才會顯現。您決定在這裡納入劑量等級 4，部分原因是什麼？因為您覺得需要進一步提高療效，才能僅憑第一年的數據就足以說服 FDA，這本質上是在問 21%、22% 的療效是否足以獲得批准，而您認為可以做得更好。

I think it's the latter. I think we feel dose level 4 has the opportunity to do better. But on its own, the dose level 3 results we feel are sort of the anchor dose that met our product profile and would be, I think, received well in a review. Steve, do you want to comment a little bit on just the power of the signal that we're seeing?

我認為是後者。我認為我們認為劑量 4 有機會做得更好。但就其本身而言，我們認為劑量水平 3 的結果是一種符合我們產品特性的錨定劑量，我認為，在審查中會受到好評。史蒂夫，你想就我們看到的訊號強度發表一點評論嗎？

Sure. So Jack, you point to the equivalence in terms of two-step improvement at one year. The key consideration is the effect size we're seeing there meets our target product profile, and the reason it meets that is we know that that's an acceptable endpoint and an acceptable effect size from a benefit risk standpoint when you take into account this being a single injection.

當然。所以傑克，你指出了一年內兩步驟改進的等效性。關鍵的考慮因素是，我們看到的效果大小符合我們的目標產品概況，而它符合這一概況的原因是，我們知道，當你考慮到這是一次注射時，從效益風險的角度來看，這是一個可接受的終點和一個可接受的效果大小。

And the ability to decrease treatment burden when you look at that overall benefit risk consideration. The other key aspect is what the clinicians care most about is the effect on imaging translating into actual benefits for patients in in terms of not only decrease injection burden, but actually preventing patients from developing the blinding complications.

當您考慮整體利益風險時，可以減輕治療負擔。另一個關鍵方面是臨床醫生最關心的，即成像效果能否轉化為患者的實際利益，不僅可以減少注射負擔，而且實際上可以防止患者出現致盲併發症。

So we that's why we feel comfortable with the one-year results where we've seen that translate into a meaningful reduction in those important events. And we see that held up to a very significant, clinically meaningful level at the two-year time point. So that's why we and AbbVie, feel very comfortable with the one year. Endpoint and we know we're going to continue to get to your data and long-term data to give even more confidence to the clinical community.

因此，我們對一年的結果感到滿意，因為我們已經看到這些重要事件的顯著減少。我們發現，在兩年的時間點上，這個水準達到了非常顯著的、具有臨床意義的水準。這就是為什麼我們和 AbbVie 對這一年感到非常滿意。終點，我們知道我們將繼續獲得您的數據和長期數據，以給予臨床界更多的信心。

Brian Skorney, Robert W. Baird

布萊恩·斯科尼、羅伯特·W·貝爾德

Thank you for taking my question. Also I wanted to just, push to get a little more granularity on the DR 2B versus 2B3 versus 3 study design on the 2b3, is this a 2B portion where you get some interim data? From a small sample size and then roll into a phase 3 portion or is is sort of the whole thing running blinded before full readout?

感謝您回答我的問題。另外，我只是想進一步了解 DR 2B 與 2B3 與 2b3 的 3 個研究設計，這是您獲取一些中期數據的 2B 部分嗎？從小樣本開始，然後進入第 3 階段，還是在完整讀數之前對整個過程進行盲測？

I'm trying to get a feel for the cadence where this is going to be one readout and then you would start the second pivotal phase 3, or there's an earlier 2V portion readout that leads to. The start of the phase 3 portion of the 23 and then at some time later at the start of the second phase 3 portion. And in terms of the control arm, is it going to be sham or open label and have you potentially thought about an active control in any of these studies just looking at the event rates, you have in DL 3, it wouldn't be out of the question to even potentially show benefit of over IEA particularly, if events are compliance driven though.

我試著了解節奏，這將是一個讀數，然後你將開始第二個關鍵階段 3，或有一個較早的 2V 部分讀數。23 的第三階段部分開始，然後在稍後的某個時間點開始第二階段第三部分。就對照組而言，它是假治療還是開放標籤治療，您是否考慮過在這些研究中設置主動控制，只看事件發生率，在 DL 3 中，如果事件是由合規性驅動的，那麼甚至有可能顯示出優於 IEA 的優勢。

Thanks for the question, Brian. I think at a high level I can comment that the way the 2b is designed is to efficiently as efficiently as possible move through different phases. So it's structured that the 2b has an interim readout in which it rolls into a phase 3. And the concept and, -- the plan with AbbVie is that would also trigger immediately starting the second pivotal so that we could go as quickly as possible.

謝謝你的提問，布萊恩。我認為從高層次來說，我可以評論 2b 的設計方式是為了盡可能有效率地完成不同的階段。因此，其結構是 2b 有一個臨時讀數，然後進入第 3 階段。而 AbbVie 的計畫和理念是，這也將立即觸發第二個關鍵階段，讓我們能夠盡快採取行動。

I'll let Steve comment on the other details you asked about.

我會讓史蒂夫評論您詢問的其他細節。

Yes, I think that the key is really that the phase 2B3 study, we are going to roll over into the part two of that study, and it's all under one protocol. So yes, the part one informs that. Now, we do plan to take advantage of interim looks at that data to really help inform by assessing the ongoing safety and efficacy of the ability to then advance into part two.

是的，我認為關鍵在於 2B3 階段研究，我們將進入該研究的第二部分，並且一切都遵循一個協議。是的，第一部分已經告知了這一點。現在，我們確實計劃利用對這些數據的中期觀察來真正幫助提供信息，透過評估持續的安全性和有效性，然後進入第二部分。

On your second question, both pivotals, including, part one of the first study, will be double masked. So we really want to get the highest quality from these studies. So we are going to use a sham injection, to get the greatest validity in terms of looking at actual treatment effect. The interesting question about active control for diabetic retinopathy before vision threatening events has occurred is that while other drugs like Ileia, Have treatment of DR on label.

關於您的第二個問題，兩個關鍵數據（包括第一項研究的第一部分）都將雙重遮蔽。所以我們確實希望從這些研究中獲得最高品質的結果。因此，我們將使用假注射，以在觀察實際治療效果方面獲得最大的有效性。關於在發生威脅視力的事件之前對糖尿病視網膜病變進行主動控制的一個有趣問題是，雖然其他藥物如 Ileia，在標籤上都有治療 DR 的標籤。

The reality is this is clearly not standard of care, precisely because of the unsustainable treatment burden of repeated injections indefinitely, because when you stop those repeated injections, patients referred, and you wind up going back to the risk of vision threatening events. So even if we wanted to run a active comparator, it would, frankly, bank enrollment almost impossible because patients don't want to go through that repeated injection. So it basically validates why we feel a onetime injection has so much potential for this massive unmet need.

事實是，這顯然不是標準治療方法，正是因為無限期重複注射會造成難以承受的治療負擔，因為當你停止重複注射時，患者會被轉診，最終又會回到視力威脅事件的風險中。因此，即使我們想運行一個主動比較器，坦白說，銀行登記幾乎是不可能的，因為患者不想經歷反覆注射。因此，這基本上證實了為什麼我們認為一次性注射對於滿足這一巨大的未滿足需求具有如此大的潛力。

And the inclusion, Steve, of the sham control was something we covered in all of the regulatory sessions we had last year. Is that correct?

史蒂夫，我們在去年的所有監管會議上都討論了加入假對照的問題。對嗎？

Yes, that's right. That's always been our plan and we've always had alignment with the FDA on that.

是的，沒錯。這一直是我們的計劃，我們一直與 FDA 保持一致。

Bill Maughan, Clear Street.

比爾‧莫恩 (Bill Maughan)，《清晰街》。

So you've mentioned a few different aspects of 202 that make it differentiated from levies, those being, for example, the full capture ratio, your manufacturing process, and your immune modulation, conditioning regimen. So I just wanted to ask on the immune modulation. And whether or not you think that that is the majority of the differentiation. And if so, if you simply added immune modulation to [levidu], is there a chance that this could become more similar than different in terms of safety?

因此，您提到了 202 的幾個不同方面，這些方面使它與徵稅有所區別，例如，完全捕獲率、製造過程以及免疫調節和調理方案。所以我只是想問免疫調節的問題。不管您是否認為這就是主要的區別。如果是這樣，如果您只是在 [levidu] 中添加免疫調節，那麼在安全性方面，它們是否有可能變得更相似而不是不同？

Thanks for the question. I think in general it's hard to pull those apart from each other. We wouldn't have pre-clinical data where we look at each effect in isolation, but maybe I'll let Steve comment. I do believe from what we're seeing that they all play into effect because our goal is to deliver the maximum dose that's in line with our pre-clinical data to deliver a functional benefit.

謝謝你的提問。我認為總體來說很難將它們區分開來。我們沒有單獨研究每種影響的臨床前數據，但也許我會讓史蒂夫發表評論。我確實相信，從我們所看到的情況來看，它們都會發揮效果，因為我們的目標是提供符合臨床前數據的最大劑量，以提供功能益處。

And that's what drove us really to initially go to the highest purity we could, which is above 80%. But the immune suppression was a separate. A separate thought from our clinical development group, as Steve mentioned, put together, I think that both of them have power in establishing the safety profile that we've seen so far, but I can't comment on whether or not that'll mean depression regimen would perform the same with the ladus. Steve, do you have thoughts on that?

這才是真正促使我們最初追求最高純度（即 80% 以上）的原因。但免疫抑制是另一回事。正如史蒂夫所提到的，我們的臨床開發小組提出了另一個想法，我認為，綜合起來，它們都有能力建立我們迄今為止看到的安全性概況，但我無法評論這是否意味著抑鬱症治療方案對 ladus 的效果相同。史蒂夫，你對此有什麼想法嗎？

Yes, I agree that we think all compo all of these components play a part. It, it's really not. Possible to give any, percentage of breakdown on that, and they probably all interact as well. I think one of the key considerations is because we built this in upfront, because we cared about safety and the overall sense of benefit risks for our product, and realized that that was a key differentiator. We're the only program that actually has safety.

是的，我同意我們認為所有這些組件都發揮了作用。實在，實在不是。有可能給出任何細分百分比，並且它們可能都相互影響。我認為其中一個關鍵的考慮因素是我們預先建立了這一點，因為我們關心產品的安全性和整體利益風險，並意識到這是一個關鍵的區別因素。我們是唯一真正具有安全性的項目。

And efficacy data where we can begin to answer that question in terms of with this constellation of differentiation, are we seeing a favorable safety profile. So as Curren mentioned, we don't know what would happen with the other programs if they added any of our proactive immune modulation, so that that would remain to be seen.

透過功效數據，我們可以開始回答這個問題，根據這種差異化，我們是否看到了良好的安全性。因此，正如 Curren 所提到的，我們不知道如果其他程序添加了我們的任何主動免疫調節，會發生什麼情況，因此這還有待觀察。

Sean McCutcheon, Raymond James.

肖恩麥卡琴、雷蒙德詹姆斯。

Hey guys, thanks for squeezing me in. One on 202. So moving the full enrollment of that pivotal cohort, up to October. Can you speak to the flexibility this may allow you to potentially over-enroll, or to get a head start on the enrollment of the confirmatory study to position yourselves well amid some of the shifting, let's call them perspectives and uncertainty at the FDA. Thanks.

嘿夥計們，謝謝你們邀請我。202 上有一個。因此，將該關鍵群體的全面入學時間提前至 10 月。您能否談談這種靈活性，它可能使您能夠進行超額註冊，或者在確認性研究的註冊方面取得領先，以便在 FDA 的一些變化（我們稱之為觀點和不確定性）中處於有利地位。謝謝。

That's a great question. I think we've pointed out in the release and other venues that we do intend to continue to enroll, once we fully enroll the pivotal program. Our protocol was originally written to enroll approximately 30 patients in the pivotal arm and then an additional 30 patients. In the confirmatory study as well. So we have plenty of room to continue to add patients throughout the year, and we can make amendments along the way.

這是一個很好的問題。我想我們已經在發布會和其他場合指出，一旦我們完全招募關鍵人員，我們確實打算繼續招募。我們的方案最初是為在關鍵組招募約 30 名患者，然後再招募另外 30 名患者。在驗證性研究中也是如此。因此，我們有足夠的空間在全年繼續增加患者，並且我們可以在過程中進行修改。

But I think I would express our main goal is to continue enrollment and expand our safety database. We have all of the drug supply we need and we're making more, as we pointed out, because we think that that will be important and it will address any risk in Sample size discussions, for example, and, that's one of the rationales as well as why we're expanding sites dramatically from where we were only a year ago.

但我認為我們的主要目標是繼續招生並擴大我們的安全資料庫。我們擁有所需的所有藥品供應，並且我們正在生產更多，正如我們所指出的，因為我們認為這很重要，並且可以解決樣本量討論中的任何風險，這是其中一個理由，也是為什麼我們在一年前的基礎上大幅擴展站點的原因。

Daniil Gataulin, Chardan.

丹尼爾·加陶林，Chardan。

I have a couple, first on 202, given the uncertainty in the, DMD gene therapy space, are you considering requesting another meeting, with the FDA, before your pre-BLA meeting to ensure the thinking has not changed too dramatically. Maybe if, you can mention if you can, if you're considering a special protocol assessment for CO2.

我有幾個問題，首先關於 202，鑑於 DMD 基因治療領域的不確定性，您是否考慮在 BLA 前會議之前請求與 FDA 舉行另一次會議，以確保想法沒有發生太大變化。如果您正在考慮對二氧化碳進行特殊協議評估，也許您可以提一下。

And second for 314, with your, supercoidal space microinjector partner, going through the significant restructuring, what is the strategy to ensure that you have access to microinjectors going forward. And are you considering switching to a different microinjector partner?

第二，對於 314，您的超螺旋空間微注射器合作夥伴正在經歷重大重組，您採取了什麼策略來確保您將來能夠使用微注射器。您是否考慮更換其他顯微注射器合作夥伴？

Sure, I can address the, -- excuse me, the last question first. I think we feel confident with continued supply of microinjector regardless of business situation with Clearside, we have significant inventories in hand and also provisions for continuing supply that were part of the original a contract that we've signed. Ao we feel very confident, in our ability to continue to access the devices and are in close contact with clearSight as well to just ensure no issues with continuity.

當然，我可以先回答──對不起，最後一個問題。我認為，無論與 Clearside 的業務狀況如何，我們都對繼續供應微注射器充滿信心，我們手頭上有大量庫存，並且還有繼續供應的條款，這是我們簽署的原始合約的一部分。因此，我們非常有信心，我們有能力繼續存取這些設備，並與 clearSight 保持密切聯繫，以確保連續性不會出現問題。

In terms of the, just trying to pull back to the first question. An FDA meeting sooner than planned. That's something I think we're thinking about. I don't think there's any urgency to do that because right now our primary goal is enrollment and not just the pivotal but the confirmatory study. And as we get further along, I would expect we'll look for a check in with FDA, but I don't think right now we're getting any signals from FDA.

就此而言，只是想回到第一個問題。FDA 會議比計劃提前召開。我認為我們正在考慮這個問題。我認為沒有必要這麼做，因為現在我們的主要目標是招生，不僅是關鍵的研究，而且是確認性研究。隨著我們進一步推進，我希望我們會尋求 FDA 的檢查，但我認為現在我們還沒有收到來自 FDA 的任何訊號。

That make that urgent because we're in constant contact with the review teams both for 121 and for 202. We're not detecting any significant shifts in, what they're looking for in the study or study design. And I think in particular Macery's statements about rare disease development, I think the situation in Duchenne over the last couple of months has only underscored the need for additional therapies to be available.

這使得事情變得緊急，因為我們與 121 和 202 的審查團隊保持密切聯繫。我們沒有發現他們在研究或研究設計中尋找的內容有任何重大轉變。我認為特別是馬塞里關於罕見疾病發展的言論，我認為過去幾個月杜氏肌肉營養不良症的情況更加凸顯了對額外療法的需求。

And for that to be done urgently, and I feel like our data package, if what we did in phase 12 replicates in our pivotal program, will be very compelling for FDA.

為了盡快完成這項工作，我覺得我們的資料包，如果我們在第 12 階段所做的工作在我們的關鍵專案中得到複製，對 FDA 來說將非常有吸引力。

Paul Choi, Goldman Sachs.

高盛的保羅·崔（Paul Choi）。

Congratulations on all the progress. Thanks for taking our questions. I want to maybe, continue, the questions just on the FDA landscape here. And, I guess, -- what your confidence for the DMD program is in the absence of a permanent head of [Siber] just given the, sort of focus on that particular disease state indication.

祝賀你取得的所有進展。感謝您回答我們的問題。我想繼續問一些有關 FDA 概況的問題。而且，我想，在沒有 [Siber] 常任負責人的情況下，您對 DMD 計劃的信心是什麼，只是考慮到對該特定疾病狀態指徵的關注。

And then my second question is, -- I guess as you think about the Medicare changes to the recent RA changes for reimbursement of injectable AAV8, how are you, potentially thinking about pricing for your product there over the longer term given what seems to be continual downward pressure from the Medicare reimbursement side? Thank you very much for taking our questions.

然後我的第二個問題是——我想當您考慮醫療保險對最近 RA 對注射 AAV8 報銷的變化時，考慮到醫療保險報銷方面似乎持續的下行壓力，您如何考慮長期內您的產品定價？非常感謝您回答我們的問題。

Sure, I think on this last question, it's pretty early days. We haven't really had substantive discussions with Avi regarding pricing strategy, but I think as we conclude enrollment of the sub-retinal studies and we look forward to top light data next year, those discussions will increase and we'll be able to talk a bit more about at least how we're thinking about that, but I think early days right now.

當然，我認為對於最後一個問題，現在討論還為時過早。我們還沒有與 Avi 就定價策略進行過實質性的討論，但我認為，隨著我們完成視網膜下研究的招募，並期待明年獲得頂級光數據，這些討論將會增加，我們將能夠至少更多地談論我們對此的看法，但我認為現在還為時過早。

And that's something I would want to comment on, in the absence of discussion with AAV8. But I think in terms of FDA and leadership change, if you think about it, we're enrolling our pivotal study. We've said that we will conclude that in October and then we will continue enrollment for the confirmatory study. We will probably still be enrolling the confirmatory study at the time of our pre-BLA meeting.

在沒有與 AAV8 進行討論的情況下，我想對此發表評論。但我認為，就 FDA 和領導層變動而言，如果你考慮一下，我們正在進行關鍵研究。我們說過，我們將在十月得出結論，然後繼續招募驗證性研究。我們可能仍會在 BLA 前會議期間進行確認性研究。

And so if there's anything that surfaces along the way, we have the opportunity to adjust and either increase enrollment if that's the ask or stand on our data which we think will be extremely strong. And so I don't think there's any near term need to contact leadership at FDA. We have good contact at the review division level and avenues for information requests and going back and forth or meetings type C meetings if we choose other elements of it.

因此，如果在此過程中出現任何問題，我們都有機會進行調整，如果需要，可以增加入學人數，或根據我們認為非常強勁的數據進行調整。因此我認為短期內沒有必要聯繫 FDA 的領導階層。如果我們選擇其他要素，我們可以與審查部門保持良好的聯繫，並有管道提出資訊請求並來回溝通，或召開 C 類會議。

But I do want to reiterate our pivotal protocol was reviewed by the review team that was very similar to the team that reviewed the Levidus. And in detail, and that review team from what we can tell, is largely intact today, even though there have been many changes in leadership of the FDA and I think that's comforting to us and, again, the urgency for additional therapies in Duchenne couldn't be at a higher level in my view, based on what we've seen happen over the last couple of months.

但我確實想重申，我們的關鍵協議已經由審查小組進行了審查，該小組與審查 Levidus 的小組非常相似。詳細地說，據我們所知，儘管 FDA 的領導層發生了許多變化，但審查小組今天基本上保持完整，我認為這讓我們感到欣慰，而且，根據我們在過去幾個月看到的情況，我認為對杜氏肌肉營養不良症進行額外治療的緊迫性已經達到了一個新的高度。

Yi Chen, HC Wainwright.

陳毅，HC溫賴特。

Thank you for taking my question. Could you please, comment on whether the dosing level of Currava for the subretinal delivery for WeMD is much lower than the super-roidal delivery, for what MDDR and DME and whether the dosing difference is associated with the route of delivery to achieve similar ethics.

感謝您回答我的問題。您能否評論一下，對於 WeMD 的視網膜下給藥，Currava 的劑量水平是否比超類固醇給藥低得多，對於 MDDR 和 DME 來說，劑量差異是否與給藥途徑有關，以達到類似的道德標準。

Thanks. Steve, I'll have you comment on that.

謝謝。史蒂夫，我請你對此作出評論。

Thanks for the question, you. So the doses that we're looking at in the sub-retinal pibital studies are lower. These are two separate routes of administration. We've been leaders in the exploration in, suprachoroidal, looking across two different indications. So we knew from the start that different round of administration. And also in the case of diabetic retinopathy, different indication with different VEGF drive, that we had to really look for a dose response anew in that new route of administration.

謝謝你的提問。因此，我們在視網膜下垂體研究中觀察到的劑量較低。這是兩種不同的給藥途徑。我們一直是脈絡膜上腔的探索領域的領導者，研究兩種不同的適應症。所以我們從一開始就知道這是不同輪次的管理。而且在糖尿病視網膜病變的情況下，不同的適應症具有不同的 VEGF 驅動力，我們必須在新的給藥途徑中重新尋找劑量反應。

And so we thoroughly looked at that and also looked at safety with this new route of VEGF administration where, going higher on dose, we knew we had that flexibility. From our pre-clinical data. So here as well, we, we're able to go higher. And so importantly, not only the clear meeting of target product profile with the supraproidal. But also, we wanted to replicate the good parts of sub-retinol.

因此，我們徹底研究了這一點，並研究了這種新的 VEGF 給藥途徑的安全性，透過增加劑量，我們知道我們具有這種靈活性。根據我們的臨床前數據。因此，在這裡，我們也能走得更高。因此，重要的是，不僅目標產品概況與超類產品概況明確相符。但同時，我們也想複製視黃醇的優點。

But not needing a surgical procedures, so to be able to do that in office and early on, -- we chose supraorbital because it preserved the targeted local delivery into the a compartmentalized space, the supraorbital space. And that really increases the belief in safety both within the eye or any systemic effect. So we also have bilateral dosing, with good safety and efficacy results that we've seen in a bilateral study.

但不需要手術，因此能夠在辦公室內儘早進行手術——我們選擇了眶上手術，因為它保留了將藥物輸送到分隔空間（眶上空間）的針對性局部輸送。這確實增強了人們對眼睛或全身影響安全性的信心。因此，我們也進行了雙側給藥，並在雙側研究中看到了良好的安全性和有效性結果。

So all these, this constellation of aspects had us confident to be able to go higher on dose with this new route of administration.

因此，所有這些方面都讓我們有信心透過這種新的給藥途徑提高劑量。

There are no further questions at this time. And this concludes today's conference call. Thank you for joining me now disconnect.

目前沒有其他問題。今天的電話會議到此結束。感謝您現在加入我，斷開連接。