Regenxbio Inc (RGNX) 2025 Q3 法說會逐字稿

Welcome everyone to the third quarter 2025 REGENXBIO earnings conference call. (Operator Instructions) Please be advised that today's conference is being recorded at this time. I'd like to turn the conference over to Patrick Christmas, Chief Legal Officer of REGENXBIO. Please go ahead.

歡迎大家參加 REGENXBIO 2025 年第三季財報電話會議。（操作員指示）請注意，今天的會議正在錄音。接下來，我將把會議交給 REGENXBIO 的首席法務官 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 third quarter ended September 30, 2025. The press release is available on our website at www.regenxbio.com.

早安，感謝各位今天收看我們的節目。今天早些時候，REGENXBIO 發布了截至 2025 年 9 月 30 日的第三季財務和營運表現。新聞稿可在我們的網站 www.regenxbio.com 上查閱。

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.

今天的電話會議將包含有關我們財務前景的前瞻性聲明，以及監管和產品開發計劃。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結果不同。可以透過諸如 expect、plan、will、may、anticipate、believe、should、intend 等詞語以及其他類似含義的詞語來識別。

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

任何此類前瞻性陳述均不構成對未來績效的保證，並涉及某些風險和不確定性。這些風險在 REGENXBIO 截至 2024 年 12 月 31 日止年度的 10-K 表格年度報告的風險因素和管理層討論與分析部分中有所描述。

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. Any information we provide on this conference call is provided only as of the date of this call, November 6, 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.

以及 REGENXBIO 向美國證券交易委員會提交的 10-Q 表格季度報告中的類似風險因素部分，這些報告已提交給美國證券交易委員會，並可在 SEC 網站上查閱。我們在本次電話會議中提供的任何資訊僅截至本次電話會議當天（2025 年 11 月 6 日）為止。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中作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，今天的電話會議將被錄音並進行網路直播。此外，任何未經審計或模擬的財務資訊均為初步訊息，並不代表對公司財務狀況或經營績效的預測。實際結果可能與實際情況有重大差異。

I'll now turn the call to Curran Simpson, President and CEO of REGENXBIO. Curran?

現在我將把電話轉給 REGENXBIO 的總裁兼執行長 Curran Simpson。柯倫？

Thank you, Patrick, and thank you everyone for joining us today. I am pleased to share the strong momentum across our late stage pipeline of gene therapies, with the potential to deliver the best outcomes in devastating diseases.

謝謝你，派崔克，也謝謝今天所有到場的各位。我很高興地與大家分享我們後期基因療法研發管線的強勁勢頭，這些療法有望在治療毀滅性疾病方面取得最佳療效。

Our progress is anchored in our leading end-to-end capabilities, including in-house commercial ready manufacturing, and innovative science, all driven by our commitment to bring new medicines to patients in need.

我們的進步源於我們領先的端到端能力，包括內部商業化生產和創新科學，所有這些都源於我們致力於為有需要的患者帶來新藥的承諾。

Today, I am joined by Doctor Steve Pakola, our Chief Medical Officer, to discuss the exciting clinical development across our rare and retinal franchises; and Mitch Chan, our Chief Financial Officer, to provide financial updates.

今天，我邀請到了首席醫療官史蒂夫·帕科拉博士，來討論我們罕見疾病和視網膜疾病領域令人振奮的臨床進展；以及首席財務官米奇·陳，來提供財務方面的最新信息。

Let's dive in and start with RGX-202, our wholly owned program for Duchenne muscular dystrophy. We are very encouraged by our progress in this program and are moving rapidly to deliver a much-needed differentiated treatment to Duchenne patients.

讓我們深入了解一下，首先從我們自主研發的杜氏肌肉營養不良症治療計畫 RGX-202 開始。我們對該計畫的進展感到非常鼓舞，並正在迅速推進，為杜氏肌肉營養不良症患者提供急需的差異化治療。

Our comprehensive therapeutic approach behind RGX-202 includes a novel construct. RGX-202 is the only microdystrophin that includes the CT domain, making it closest to naturally occurring dystrophin.

RGX-202 背後的綜合治療方法包括一種新型結構。RGX-202 是唯一含有 CT 結構域的微型肌肉營養不良蛋白，因此最接近天然存在的肌肉營養不良蛋白。

A novel immune suppression regimen designed to enable high dose delivery and proactively counter issues seen in other AAV programs. And commercial ready manufacturing that is delivering the highest purity levels in Duchenne gene therapies.

一種新型免疫抑制方案，旨在實現高劑量輸送，並主動應對其他 AAV 項目中出現的問題。並且實現了商業化生產，可提供杜氏肌肉營養不良症基因療法中最高的純度水平。

Boys with Duchenne have one chance at gene therapy. That's why we specifically designed RGX-202 with these elements to maximize opportunity for functional benefit. We are very pleased to see that this approach is resulting in the favorable safety and efficacy profile seen in Phase I/II.

患有杜氏肌肉營養不良症的男孩只有一次接受基因治療的機會。正因如此，我們特意在設計 RGX-202 時融入了這些元素，以最大限度地發揮其功能優勢。我們非常高興地看到，這種方法在 I/II 期臨床試驗中取得了良好的安全性和有效性。

We're also very excited to announce that we completed enrollment in the AFFINITY DUCHENNE pivotal trial, putting us on track to share top-line pivotal data in early Q2 2026, and submit a BLA using the accelerated approval pathway in mid-2026.

我們也非常興奮地宣布，我們已完成 AFFINITY DUCHENNE 關鍵性試驗的患者招募，這使我們能夠在 2026 年第二季度初分享主要關鍵性數據，並在 2026 年年中通過加速審批途徑提交生物製品許可申請 (BLA)。

To meet demand from the patient community and support accelerated approval plans, the confirmatory trial is open and continues to enroll patients. As a reminder, we were able to complete enrollment ahead of our original year and guidance, underscoring the community's enthusiasm for RGX-202 and strong need for new treatment options. We have more than enough supply of RGX-202 ready and available for the entire confirmatory study.

為了滿足患者群體的需求並支持加速審批計劃，確認性試驗正在進行中，並繼續招募患者。提醒大家，我們提前完成了原定年份和指導目標的招募工作，這凸顯了社區對 RGX-202 的熱情以及對新治療方案的強烈需求。我們有充足的 RGX-202 可供整個驗證性研究使用。

Delivering on the commercial readiness plans we shared last quarter, we have produced the first batches of RGX-202 intended for commercial supply at our manufacturing innovation center here in Rockville, and expect to imminently complete our PPQ or process performance qualification campaign.

為了落實上個季度公佈的商業準備計劃，我們在位於羅克維爾的製造創新中心生產了第一批用於商業供應的 RGX-202，並預計很快將完成我們的 PPQ 或工藝性能鑑定活動。

There is a significant commercial opportunity for RGX-202 due to our novel construct, immune suppression regimen, and our manufacturing capabilities, including our ability to produce 2,500 doses per year, which make us uniquely prepared for clinical and commercial success. We continue to invest in preparations for a commercial launch in 2027 when the vast majority of the prevalent population will remain available.

由於我們採用了新型結構、免疫抑制方案以及我們的生產能力（包括每年生產 2,500 劑的能力），RGX-202 具有巨大的商業機會，這使我們能夠以獨特的方式獲得臨床和商業上的成功。我們將繼續投資，為 2027 年的商業化上市做準備，屆時絕大多數人口仍將處於活躍狀態。

Now to RGX-121, also known as clemidsogene lanparvovec, the potential first gene therapy and one-time treatment for MPS-II. Our recent FDA interactions regarding the ongoing BLA have been highly productive, and we remain confident in RGX-121 approval by early next year.

現在來談談 RGX-121，也稱為 clemidsogene lanparvovec，它是 MPS-II 的潛在首個基因療法和一次性治療藥物。我們最近與 FDA 就正在進行的 BLA 進行的互動非常富有成效，我們仍然有信心 RGX-121 在明年初獲得批准。

We delivered positive 12 month data to FDA, which Steve will discuss in more detail. And the FDA completed inspections of our clinical sites and in-house manufacturing facility with no observations, a rare and significant achievement.

我們向 FDA 提交了積極的 12 個月數據，史蒂夫將對此進行更詳細的討論。FDA 完成了對我們臨床試驗點和內部生產設施的檢查，沒有發現任何問題，這是一項罕見而意義重大的成就。

These developments have further strengthened our confidence in the ongoing BLA review. With our commercial MPS partner, Nippon Shinyaku, we look forward to the February 8 PDUFA date and delivering the first commercial doses of RGX-121 by early next year.

這些進展進一步增強了我們對正在進行的BLA審查的信心。我們與商業 MPS 合作夥伴日本新藥株式會社 (Nippon Shinyaku) 一起，期待著 2 月 8 日的 PDUFA 日期，並於明年初交付首批 RGX-121 商業劑量。

Let's turn our focus to our retinal disease franchise and our ongoing partnership with AbbVie to develop surabgene lomparvovec or sura-vec for wet AMD and diabetic retinopathy. These programs have the strength of AbbVie's leading clinical and commercial global eye care infrastructure behind them.

讓我們把注意力轉向我們的視網膜疾病產品線，以及我們與艾伯維公司正在進行的合作，以開髮用於治療濕性老年黃斑部病變 (AMD) 和糖尿病視網膜病變的 surabgene lomparvovec 或 sura-vec。這些計畫背後有艾伯維領先的全球眼科臨床和商業基礎設施的支持。

In subretinal wet AMD, we recently announced that the last patient was enrolled in our two global Phase III studies. This is a tremendous accomplishment. Together, ATMOSPHERE and ASCENT represent the largest global gene therapy program ever conducted, with over 1,200 patients enrolled across 200 sites.

在視網膜下濕性老年黃斑部病變（AMD）方面，我們最近宣布，我們兩項全球 III 期研究中的最後一名患者已經入組。這是一項了不起的成就。ATMOSPHERE 和 ASCENT 共同構成了有史以來規模最大的全球基因治療項目，在 200 個地點招募了 1200 多名患者。

If approved, subretinal sura-vec would not only be the first gene therapy for wet AMD, a disease that impacts millions worldwide, but also the first gene therapy for a non-rare indication. We look forward to sharing topline data in the fourth quarter of 2026.

如果獲得批准，視網膜下注射 sura-vec 不僅將成為首個用於治療濕性 AMD（一種影響全球數百萬人的疾病）的基因療法，而且還將成為首個用於治療非罕見疾病的基因療法。我們期待在 2026 年第四季分享主要數據。

As a reminder, we manufacture all clinical and future commercial sura-vec at our facility here in Rockville. Like wet AMD, our diabetic retinopathy program is designed to deliver sura-vec to patients that rely on frequent, lifelong injections to halt degeneration and vision loss, and we look forward to initiating the Phase IIb/III pivotal program.

再次提醒大家，我們所有的臨床用和未來商業用 sura-vec 都是在我們位於羅克維爾的工廠生產的。與濕性 AMD 類似，我們的糖尿病視網膜病變計畫旨在為需要終身頻繁注射以阻止退化和視力喪失的患者提供 sura-vec，我們期待啟動 IIb/III 期關鍵性計畫。

Across our pipeline, these achievements reflect the strength of focused execution and a differentiated approach to developing and delivering best in class therapeutics. With that, I would like to now turn the call over to Steve for more in-depth updates on our clinical programs. Steve?

在我們的產品線中，這些成就體現了我們專注執行的強大實力以及在開發和提供一流療法方面採取的差異化方法。接下來，我想把電話交給史蒂夫，讓他為我們詳細介紹我們的臨床計畫。史蒂夫？

Thank you, Curran. I'll start with the RGX-202 program for the treatment of Duchenne. As Curran mentioned, we are incredibly excited that enrollment has completed in the AFFINITY DUCHENNE pivotal trial. As a reminder, this study is designed to enroll ambulatory patients aged 1 and older, and is the most advanced clinical stage gene therapy program for Duchenne.

謝謝你，柯倫。我將首先介紹用於治療杜氏肌肉營養不良症的 RGX-202 方案。正如柯倫所提到的，我們非常高興 AFFINITY DUCHENNE 關鍵性試驗的招募工作已經完成。提醒大家，本研究旨在招募 1 歲及以上的可獨立行走的患者，是杜氏肌肉營養不良症最先進的臨床階段基因治療計畫。

RGX-202 has demonstrated a highly differentiated safety and efficacy profile with consistent, robust microdystrophin expression in the Phase I/II study. Last month at the International Congress of the World Muscle Society, we presented individual NSAA data on the first four patients who received the pivotal dose.

RGX-202 在 I/II 期研究中表現出高度差異化的安全性和有效性，並具有持續、穩健的微型肌肉營養不良蛋白表達。上個月在世界肌肉協會國際大會上，我們展示了接受關鍵劑量治療的前四名患者的個別 NSAA 數據。

All four patients one year after dosing exceeded expected disease trajectory across multiple methods of assessment. Specifically, each patient exceeded their expected functional outcomes when compared to matched external controls and the well-established CPAP disease progression model.

給藥一年後，所有四名患者的病情進展均超過了預期，並透過多種評估方法證實了這一點。具體來說，與匹配的外部對照組和已建立的 CPAP 疾病進展模型相比，每位患者的功能結果都超出了預期。

These data combined with the June 2025 data showing all patients demonstrated improvement on time function tests, reinforce our belief that 202 is driving meaningful functional benefits for patients with this degenerative disease.

這些數據與 2025 年 6 月的數據相結合，表明所有患者在時間功能測試中均表現出改善，這進一步強化了我們的信念，即 202 正在為患有這種退化性疾病的患者帶來有意義的功能益處。

It's important to note the majority of these patients were 8 years and older at dosing, an age when functional decline is expected, making these results particularly impressive. The Duchenne patient and physician communities continue to recognize the excellent safety profile 202 has demonstrated to date.

值得注意的是，這些患者中的大多數在接受治療時年齡都在 8 歲及以上，而這個年齡層正是功能衰退的時期，因此這些結果尤其令人印象深刻。杜氏肌肉營養不良症患者和醫生群體繼續認可 202 迄今所展現的卓越安全性。

As reported in the Phase I/II study, we have seen no SAEs or adverse events of special interest, including no thrombocytopenia or liver injury. We attribute this to our proactive immune suppression regimen, our novel construct using the NAV AAV8 vector, and our field leading product purity with more than 80% full capsids.

正如 I/II 期研究報告所述，我們沒有發現任何嚴重不良事件或特別值得關注的不良事件，包括血小板減少症或肝損傷。我們認為這歸功於我們積極主動的免疫抑制方案、使用 NAV AAV8 載體的創新構建以及我們行業領先的產品純度（超過 80% 的完整衣殼）。

We are very pleased with how these differentiated elements enable us to deliver 202 at the 2e14 vector genome per kilogram dose. We believe this dose gives patients and families the best shot at efficacy without compromising safety.

我們非常高興這些差異化元素使我們能夠以每公斤劑量 2e14 載體基因組提供 202。我們相信，這種劑量能夠在不影響安全性的前提下，為患者及其家人提供最佳療效。

In the Phase I/II study, this approach has translated into a favorable safety and efficacy profile for patients. With this momentum in our pivotal study and results to date in Phase I/II, we intend to expand the RGX-202 program outside of the US and are actively exploring opportunities to do so, starting in Europe.

在 I/II 期研究中，這種方法已轉化為對患者良好的安全性和有效性。憑藉我們在關鍵研究中取得的進展以及迄今為止在 I/II 期試驗中取得的成果，我們打算將 RGX-202 計畫擴展到美國以外的地區，並正在積極探索這方面的機會，首先從歐洲開始。

Shifting focus to RGX-121, the positive 12 month pivotal data delivered to the FDA and presented at ICIM in September were consistent with the previous findings and demonstrated the long-term potential of RGX-121 to change the course of MPS-II.

將重點轉向 RGX-121，向 FDA 提交並在 9 月 ICIM 上公佈的 12 個月關鍵性積極數據與先前的研究結果一致，並證明了 RGX-121 具有改變 MPS-II 病程的長期潛力。

Further, we saw a continued favorable safety profile and a strong correlation between biomarker level and neurodevelopmental improvement. If approved, RGX-121 would become the first and only gene therapy for MPS-II, and potentially the only one-time treatment option to address the neurodevelopmental decline for this devastating disease.

此外，我們還觀察到良好的安全性，以及生物標記水平與神經發育改善之間的強相關性。如果獲得批准，RGX-121 將成為第一個也是唯一一個用於治療 MPS-II 的基因療法，並且有可能成為解決由這種毀滅性疾病引起的神經發育衰退的唯一一次性治療方案。

The Hunter and MPS communities have been fierce advocates for the need to deliver new treatment options to their children as quickly as possible. We look forward to continuing to advance our BLA and potentially bringing this much needed therapy to boys living with Hunter syndrome in the coming months.

亨特和MPS社區一直強烈倡導盡快為他們的孩子提供新的治療方案。我們期待繼續推進我們的 BLA 項目，並有可能在未來幾個月內將這種急需的療法帶給患有亨特氏症候群的男孩們。

Turning to our retina sura-vec franchise for wet AMD and diabetic retinopathy, or DR. Completing enrollment in our pivotal wet AMD studies is a major milestone in our and AbbVie's continued effort to serve the millions of patients worldwide suffering retinal diseases.

轉向我們的視網膜 Sura-Vec 特許經營，用於治療濕性 AMD 和糖尿病視網膜病變 (DR)。完成我們關鍵性濕性 AMD 研究的入組是我們和艾伯維為全球數百萬視網膜疾病患者持續努力中的一個重要里程碑。

The data from our subretinal wet AMD program have been excellent, with durable outcomes reported through four years. Additionally, in the fellow eye study, sura-vec has demonstrated comparable safety and efficacy when dosed in the second eye. These results, along with patient enthusiasm to return and receive treatment in their second eye, underscore the robust interest we're seeing among patients and physicians.

我們的視網膜下濕性老年黃斑部病變（AMD）治療計畫的數據非常出色，四年來一直保持良好的治療效果。此外，在另一隻眼睛的研究中，當對另一隻眼睛進行給藥時，sura-vec 已顯示出相當的安全性和有效性。這些結果，以及患者對返回接受另一隻眼睛治療的熱情，都凸顯了我們在患者和醫生中看到的濃厚興趣。

Finally, I'll speak to sura-vec for DR using in-office suprachoroidal delivery. We continue to make progress towards initiating a global pivotal program. Site selection is in progress for the Phase IIb/III double mast sham injection controlled trial for patients with non-proliferative DR or NPDR.

最後，我將與 sura-vec 討論使用門診脈絡膜上腔注射治療 DR 的方法。我們在啟動全球關鍵計劃方面持續取得進展。針對非增殖性糖尿病視網膜病變 (NPDR) 患者，IIb/III 期雙側乳房假注射對照試驗的選址工作正在進行中。

In the Phase II ALTITUDE trial, a single in-office injection of sura-vec was well tolerated. In patients with NPDR, sura-vec demonstrated durable, long-term efficacy, including meaningful DRSS improvement and an over 70% reduction in the risk of vision threatening events.

在 II 期 ALTITUDE 試驗中，單次門診注射 sura-vec 耐受性良好。在 NPDR 患者中，sura-vec 顯示出持久的長期療效，包括顯著的 DRSS 改善和超過 70% 的視力威脅事件風險降低。

Finally, I'd like to express my sincere gratitude to all the patients, families, clinicians, site staff, and patient advocacy representatives who have supported all these trials.

最後，我要向所有支持這些試驗的患者、家屬、臨床醫生、現場工作人員和患者權益倡導代表表達我誠摯的謝意。

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

接下來，我將把電話交給米奇，讓他回顧我們的財務指導。米奇？

Thank you, Steve, and good morning everyone. REGENXBIO ended the quarter on September 30, 2025 with cash equivalents, and marketable securities of $302 million compared to $245 million as of December 31, 2024.

謝謝你，史蒂夫，大家早安。REGENXBIO 截至 2025 年 9 月 30 日的季度末，現金等價物和有價證券為 3.02 億美元，而截至 2024 年 12 月 31 日，該等現金等價物和有價證券為 2.45 億美元。

The increase was primarily driven by the $110 million upfront payment from Nippon Shinyaku in the first quarter of 2025, and $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 the cash used to fund operating activities in the first three quarters of 2025.

成長主要得益於 2025 年第一季日本新藥支付的 1.1 億美元預付款，以及 2025 年第二季與 Healthcare Royalty 合作夥伴進行特許權使用費貨幣化獲得的 1.45 億美元淨收益，但部分被 2025 年前三個季度用於營運活動的現金所抵消。

Revenues were $30 million for the quarter ended September 30, 2025, compared to $24 million for the quarter ended September 30, 2024. The increase was primarily due to the development service revenue under the Nippon Shinyaku partnership in the third quarter of 2025.

截至 2025 年 9 月 30 日的季度營收為 3,000 萬美元，而截至 2024 年 9 月 30 日的季度營收為 2,400 萬美元。成長主要歸功於 2025 年第三季與日本新藥合作的開發服務收入。

We expect the September 30 cash balance reported today to fund our operations into early 2027. Note, this cash runaway guidance does not include multiple non-diluted financing opportunities that could further extend our cash runway.

我們預計今天公佈的 9 月 30 日現金餘額足以支持我們的營運到 2027 年初。請注意，此現金流量預測不包括可能進一步延長我們現金流的多項非稀釋性融資機會。

These include the sale of our anticipated priority review voucher for RGX-121, development or sales milestone for our MPS programs, development milestone associated with our diabetic retinopathy program per the AbbVie collaboration, and potential additional funds from the May 2025 Healthcare Royalty's agreement.

這些包括出售我們預期的 RGX-121 優先審評券、我們 MPS 項目的開發或銷售里程碑、根據與艾伯維的合作，我們糖尿病視網膜病變項目的開發里程碑，以及 2025 年 5 月醫療保健特許權使用費協議中可能獲得的額外資金。

Together these non-diluted opportunities could further extend our cash runway well beyond 2027. In all, we find ourselves in a strong financial position as we advance towards multiple product launches.

這些未稀釋的股權機會加在一起，可以進一步延長我們的現金儲備，使其遠遠超過 2027 年。總而言之，隨著我們推動多款產品的上市，我們目前處於穩健的財務狀況。

With that, I turned a call back to Curran to provide final thought.

說完這些，我又給柯倫打了個電話，讓他做最後總結。

Thank you, Mitch. As you've heard today, our strong execution throughout 2025 has positioned us for an exciting and transformational year ahead, including the anticipated approval of RGX-121 by February and top-line readouts in Duchenne and wet AMD, both large indications and large commercial opportunities.

謝謝你，米奇。正如您今天所聽到的，我們在 2025 年的強勁執行力使我們為即將到來的激動人心且具有變革意義的一年做好了準備，其中包括預計在 2 月份獲得 RGX-121 的批准，以及在杜氏肌營養不良症和濕性 AMD 中取得初步成果，這兩項適應症都具有很大的適應症和巨大的商業機會。

Each of these potential best-in-class gene therapies address a significant unmet need for patients and are built upon our 15-year history of pioneering AAV gene therapy, with a commitment to scientific excellence and disciplined execution.

這些潛在的同類最佳基因療法均能滿足患者的重大未滿足需求，並且建立在我們 15 年來在 AAV 基因療法領域開拓創新的歷史之上，秉承著對卓越科學和嚴謹執行的承諾。

I want to thank our REGENXBIO team, partners, and the patients and families who participate in our trials. Your partnership is key to advancing our mission to improve lives through gene therapy.

我要感謝 REGENXBIO 團隊、合作夥伴以及參與我們試驗的患者及其家屬。您的合作對於我們透過基因療法改善人們的生活這項使命至關重要。

With that, I'll turn the call over for questions. Operator?

接下來，我將把通話交給提問者。操作員？

(Operator Instructions) Judah Frommer, Morgan Stanley.

（操作說明）猶大‧弗羅默，摩根士丹利。

Hi, good morning, guys. Thanks for taking the questions, and congrats on the progress here. Maybe first, just on 202, can you help us with when next interactions with FDA will be? And can we get your thoughts on, clearly news coming out of FDA that impacts the DMD community with arguably higher unmet need in DMD.

大家好，早安。感謝您回答這些問題，也恭喜您在這裡的進展。首先，關於 202 號法案，您能否告知我們下次與 FDA 的溝通時間？我們能否聽聽您對 FDA 最新發布的消息有何看法？這些訊息顯然會影響 DMD 患者群體，而 DMD 患者群體中存在著相當高的未滿足醫療需求。

But also just on external controls and other gene therapy programs, how are you thinking about the potential for the accelerated pathway for 202 at this point? Thanks.

但就外部控制和其他基因療法項目而言，您目前如何看待 202 加速途徑的潛力？謝謝。

Thanks, Judah. Yeah, I mean, if you think about the progress next year, we'll have top-line data that we've pointed to in early Q2, and then we've also guided to a mid-2026 BLA submission. So absolutely, we'll have potentially several FDA interactions. Of course, the key one is the pre-BLA meeting.

謝謝你，猶大。是的，我的意思是，如果你考慮明年的進展，我們將在第二季初獲得我們預測的初步數據，然後我們也預計在 2026 年年中提交 BLA 申請。所以，我們一定會與美國食品藥物管理局（FDA）進行多次溝通。當然，最關鍵的是BLA預備會議。

And based on that timing, we haven't got a specific date set for it, but it would happen somewhere around the vicinity of topline data and preparing to file the BLA. I think in general, we are watching carefully other programs going through FDA and the debate around external controls.

根據這個時間安排，我們還沒有確定具體的日期，但大概會在公佈主要數據和準備提交生物製品許可申請（BLA）前後進行。我認為總的來說，我們正在密切關注其他正在接受 FDA 審批的項目以及圍繞外部控制的論點。

We've continued to update our access to some of the same databases, for example, that were used in the Elevidys approval. And I think that when we look at it, one of the things that's striking to me is, especially in our older patients, we're not looking at a marginal stabilization of patient functional outcome, we're looking at a really significant difference from natural history, in which we're matching that patient to say 12, up to 20 patients.

我們一直在更新對一些相同資料庫的存取權限，例如，Elevidys 審批過程中使用的那些資料庫。我認為，當我們審視這個問題時，讓我印象深刻的一點是，尤其是在我們的老年患者中，我們看到的不是患者功能結果的邊緣穩定，而是與自然病程的顯著差異，我們將該患者與 12 到 20 名患者進行匹配。

And so I don't think we're going to be going into FDA with sort of a modest benefit approach. I think what we're seeing in our data is a significant benefit and even improvement in patients that you would expect maybe the best case at their age would be stabilization.

所以我認為我們不會以較保守的效益評估方式去向FDA申請批准。我認為我們從數據中看到的是顯著的益處，甚至患者的病情有所改善，而你可能預期他們這個年齡段最好的結果也只是病情穩定。

So I think that's the strength at which we think we're eligible for accelerated approval, and I won't leave out, to date the safety profile of the program. So you think about benefit to risk ratio, and I think we can provide a significant advantage over the product on the market to date.

所以我認為，這就是我們認為有資格獲得加速批准的優勢所在，而且我也不會忽略該專案迄今為止的安全狀況。所以你要考慮收益與風險比，我認為我們可以提供比目前市場上同類產品更大的優勢。

Great, thanks. And then maybe just a quick one for Mitch. On cash runway, I guess kind of, when you internally probability weight potential for these non-diluted financings that you listed. Can you give us a sense of where those could potentially get you through without kind of bringing in external capital or how you're thinking about the potential for a cash runway, if we do layer in some of those non to live options thank you.

太好了，謝謝。然後也許就給米奇快速來一發。關於現金儲備，我想大概是這樣，當你內部對列出的這些非稀釋性融資的潛力進行機率加權評估時。您能否簡要說明一下，如果不引入外部資本，這些措施可能可以幫助您度過難關？或者，如果您確實考慮加入一些非生存性選項，您是如何看待現金流的？謝謝。

Yeah, absolutely. So if you factor in the non-diluted financing options inclusive of the PRV as an example, and for modeling purposes, if you use the market price, as you're probably well aware of what the prices are for these PRVs, it could significantly get us into well into 2027, if not even early parts of 2028.

是的，絕對的。因此，如果您將包括 PRV 在內的非稀釋融資方案考慮在內，並且為了建模目的，如果您使用市場價格（您可能很清楚這些 PRV 的價格），那麼即使不是到 2028 年初，也可能足以讓我們在 2027 年很長一段時間內實現目標。

But again, this is all contingent on what the market prices of some of these items can go for. Other non-dilutive financing, for example, the milestone associated with the DR, first patient dose, that we already disclosed is $100 million. So that in itself you can factor into the cash runway.

但話說回來，這一切都取決於這些商品的市場價格。其他非稀釋性融資，例如，與 DR 相關的里程碑，即首劑患者用藥，我們已經揭露為 1 億美元。所以這本身就可以納入現金儲備的考量。

Great, thanks.

太好了，謝謝。

Mani Foroohar, Leerink Partners.

Mani Foroohar，Leerink Partners。

Hi, good morning. This is Lili Nsongo on for Mani. Thanks for taking your question. Just a quick question regarding the confirmatory trial for DMD. Maybe could you provide an update in terms of the tempo of enrollment and where do you see enrollment be at the time of filing?

您好，早安。這裡是莉莉‧恩松戈為馬尼報道。感謝您回答我的問題。關於DMD確診試驗，我有個問題想請教一下。您能否提供一下目前的招生進度情況，以及您預計在提交申請時招生人數會達到什麼水平？

Good question. So we've begun enrolling the confirmatory study, actually right at the end of October when we completed the pivotal enrollment, and it's hard to predict at this point where we'll be, let's say mid-2026 at the point of filing, but I would expect us to be substantially through enrollment of the confirmatory study, given that's pre-specified in our protocol is an additional 30 patients.

問得好。因此，我們已經開始招募驗證性研究的受試者，實際上就在 10 月底完成關鍵性招募之後。目前很難預測，比如說，到 2026 年年中提交申請時，我們會達到什麼程度，但我預計我們將基本完成驗證性研究的招募工作，因為我們的方案中預先規定需要額外招募 30 名患者。

So we'll have to monitor that as we go. And we'll definitely give updates throughout the first half of next year regarding progress. Steve, maybe you just want to comment quickly on high-level design for confirmatory.

所以我們需要邊走邊觀察。我們一定會在明年上半年陸續發布有關進展的最新消息。史蒂夫，或許你只是想就確認的高級設計快速發表一下意見。

Sure. So the basic concept is very similar to what we've already done. So we're looking for a broad patient population of ambulatory patients, 1 year old and above, so very broad, and this is really based on the data that we've seen to date.

當然。所以基本概念和我們已經做過的非常相似。因此，我們正在尋找廣泛的門診患者群體，年齡在 1 歲及以上，範圍非常廣泛，這實際上是基於我們迄今為止所看到的數據。

Whereas Curran mentioned, we're seeing very good differentiation, not just on safety, but also in terms of functional benefit for these boys. And that's particularly striking in the older boys and we're seeing results that have never been seen by any program when you look at function in those 8 and older boys.

正如柯倫所說，我們看到了非常好的差異，不僅在安全性方面，而且在對這些男孩的功能性益處方面也是如此。這一點在年齡較大的男孩身上尤其顯著，我們看到，在觀察 8 歲及以上男孩的功能時，所取得的成果是任何其他項目都從未見過的。

And no placebo controls, so that's stayed consistent. And we're looking to enroll an additional 30 patients. And it's key what Curran mentioned, we're just continuing to roll along with all the sites that we've got up and going, that we're enrolling in the pivotal. They're energized.

而且沒有設定安慰劑對照組，所以結果一直保持一致。我們計劃再招募 30 名患者。正如柯倫所提到的，我們正繼續推進所有已經啟動並運行的站點，並讓關鍵人員參與其中。他們精力充沛。

And one of the things we're seeing is with each new update that we give that's showing more and more differentiation, we're getting more and more enthusiasm from the investigators and the patient families that they see. So we're very excited about the pace of enrollment.

我們看到的其中一點是，隨著我們每次更新，產品差異化程度越來越高，研究人員和他們接觸到的患者家屬也越來越熱情。我們對目前的招生速度感到非常興奮。

Thank you.

謝謝。

Gena Wang, Barclays.

吉娜·王，巴克萊銀行。

Thank you for taking my questions. So I would just ask one regarding the regulatory part. I know you have two programs like DMD and MPS too, you need to talk to the FDA. Just wondering, so for the DMD. When will you have a pre-BLA meeting with FDA?

謝謝您回答我的問題。所以我只想問一個關於監管方面的問題。我知道你們也有兩個類似 DMD 和 MPS 的項目，你們需要和 FDA 談談。只是好奇問問，對於DMD來說​​。你們何時會與FDA舉行BLA申請前會議？

And then, also regarding the MPS-II, I know PDUFA is a February 8, any additional meetings set up before approval? Maybe any update color you can have in terms of interacting with the FDA, especially after [Nick Covidon] departure, and any concern regarding prior agreed upon the accelerator approval path.

另外，關於MPS-II，我知道PDUFA的截止日期是2月8日，在批准之前是否還會安排其他會議？或許您能提供一些關於與 FDA 互動方面的最新信息，尤其是在 [Nick Covidon] 離開之後，以及關於之前商定的加速審批途徑的任何疑慮。

Sure. I'll -- hi, Gena, I'll take the second question first, and then circle back to Duchenne. For the Hunter program, we're far along with the BLA review. The PDUFA date was moved to February 8, from the initial date.

當然。我──嗨，吉娜，我先回答第二個問題，然後再回到杜氏肌肉營養不良症的問題上。對於亨特計劃，我們的 BLA 審查工作已經進行到相當深入的階段了。PDUFA 日期從原定日期延至 2 月 8 日。

We expect between now and that decision point to have a late cycle meeting with FDA and that we're getting messages from the project leader to schedule that. So that's moving along as what I would call business usual.

我們預計從現在到做出決定之前，會與 FDA 舉行後期會議，並且我們正在收到專案負責人的消息，安排這次會議。所以一切都在按部就班地進行著，我稱之為正常業務發展。

I think it's important to point out on the Hunter program, we're already past our facility inspection. No observations. Our clinical sites have been inspected as well, with no observations as well. And so some of the things that have held up other programs were de-risked, if you will, in that process.

我認為有必要指出，在亨特計畫中，我們已經通過了設施檢查。未觀察到任何現象。我們的臨床場所也接受了檢查，同樣沒有發現任何問題。因此，在這個過程中，一些阻礙其他專案進展的因素的風險也降低了。

And the other, I think, area that we interact, as we undergo this review is in the information requests that we get from FDA. And I think I would characterize those as well as typical requests, some of which in an encouraging way, are questions related to commercial aspects of a program, specifications, pharmacovigilance.

我認為，我們在進行這項審查的過程中，也會與 FDA 的資訊請求進行互動。我認為這些請求以及一些典型的請求，其中一些令人鼓舞地與項目的商業方面、規格、藥物警戒有關。

So the color of the interactions we're having is positive, and we feel positive about the data we provided for that program. And therefore, our confidence is high that this program, and we think patients support that, has a really, really important place in therapies.

因此，我們之間的互動是積極的，我們對為該項目提供的數據感到滿意。因此，我們非常有信心，這個計畫（我們認為患者也支持這一點）在治療領域具有非常非常重要的地位。

For Duchenne, the pre-BLA meeting will happen between our top-line data which we pointed to early Q2 of 2026 and the filing of the BLA. We haven't got a specific date for it yet, but that somewhere in that time frame is when we would expect to have it.

對於杜氏肌肉營養不良症，BLA 申請前的會議將在我們公佈初步數據（我們預測為 2026 年第二季度初）和提交 BLA 申請之間舉行。我們目前還沒有具體的日期，但預計會在那段時間範圍內完成。

Luca Issi, RBC Capital Markets.

伊西 (Luca Issi)，加拿大皇家銀行資本市場部。

Good morning, team. Thanks for taking our questions. This is Cassie on for Luca. Congrats on the progress this quarter. Maybe a question on your manufacturing capacity, if you can talk about your in-house capacity. The Rockville site is obviously up and running and already produced for its commercial batch.

早安，各位同事。謝謝您回答我們的問題。這是卡西替盧卡上場。恭喜本季的進展。或許可以問一下貴公司的生產能力，如果您能談談貴公司的內部產能就更好了。羅克維爾工廠顯然已經投入運營，並已開始生產商業批次的產品。

So I'm wondering, what is the scale of production volume that the site is designed to deliver today, and what percentage of domestic patients are you planning on capturing with that site? Maybe for both the MPS-II and DMD if you could speak to that. Thank you so much.

所以我想知道，該網站目前設計的生產規模是多少，以及你們計劃透過該網站吸引多少比例的國內患者？如果您能談談MPS-II和DMD的情況，或許可以考慮一下。太感謝了。

Sure, yeah. The manufacturing facility contains a 2,000 liter bioreactor. It's the largest bioreactor that we know of utilized in gene therapy, and we've already scaled the program up to that level. We've been public about being able to produce up to 2,500 doses of RGX-202 per year.

當然，是的。該生產設施包含一個2000公升的生物反應器。這是我們所知的基因療法中使用的最大的生物反應器，我們已經將該計畫擴展到這個規模。我們已經公開表示，我們每年能夠生產多達 2,500 劑 RGX-202。

And I think keeping in mind that just is what we can do on an ongoing basis. We can certainly inventory, which we're doing presently more quantities than that to have a significant number of doses available at launch.

我認為我們應該始終牢記這一點，這才是我們能夠持續做的事情。我們當然可以儲備比這更多的庫存，而且我們目前正在這樣做，以便在疫苗上市時有相當數量的劑量可用。

The Hunter program, being an ultra-rare program, I would characterize -- it uses less than 5% of our overall capacity, so it's not -- we have good yields, good expression, and we have our own internal fill-finish capability, so we can run very efficiently, but it doesn't take up a significant amount of our overall capacity.

Hunter 項目是一個極其罕見的項目，我會這樣描述它——它佔用了我們總產能的不到 5%，所以它不是——我們產量高，表現力好，而且我們擁有自己的內部灌裝和包裝能力，所以我們可以非常高效地運行，但它並沒有佔用我們總產能的很大一部分。

Thanks so much.

非常感謝。

Annabel Samimy, Stifel.

Annabel Samimy，Stifel。

Hi, thanks for taking my question and great progress on all the programs. Just on the issue of using FDA Natural History as a control in DMD. I guess, it's clear that you have both propensity match comparisons and now the CPAP disease progression model.

您好，感謝您回答我的問題，也感謝您在所有專案上取得的巨大進展。僅就使用 FDA 自然史作為 DMD 的對照這一問題而言。我想，很明顯，你們既有傾向性配對比較，現在又有了 CPAP 疾病進展模型。

Is that something designed into AFFINITY perspectively, and could that lend further support? And is it a measurement that's accepted not only in the DMD community, but also considered as a valid metric from FDA. That's the first question.

這是 AFFINITY 設計時就考慮到的視角嗎？這能否提供進一步的支援？而且，這種測量方法不僅在 DMD 群體中被接受，而且也被 FDA 視為有效的指標。這是第一個問題。

Okay, great. Hi, Annabelle. I think that's a great one for Steve to address.

好的，太好了。你好，安娜貝爾。我覺得這個問題很適合由史蒂夫來解答。

Sure. Hi, Annabelle. Great question. I think right off the bat, it's important to recognize each program and indication is different. So, starting with DMD, external natural history matching can be done in different ways and you mentioned a couple of them. That's why we're excited about our data.

當然。你好，安娜貝爾。問得好。我認為首先要認識到的是，每個項目和適應症都是不同的。所以，從 DMD 開始，外在自然史匹配可以透過不同的方式進行，你提到了其中的幾種。這就是我們對數據感到興奮的原因。

We're seeing clear response across the dose range that's very consistent when we look at a traditional external natural history matching by baseline characteristics, and also the CPAP model. There is also the propensity score matching approach that's been accepted by the FDA and that's actually prospectively specified in our protocol as an accepted approach for 202.

我們看到，在整個劑量範圍內都有明顯的反應，當我們觀察傳統的外部自然史匹配基線特徵以及 CPAP 模型時，這種反應非常一致。還有一種傾向評分配對方法，該方法已被 FDA 接受，並且實際上已在我們的方案中預先規定為 202 的可接受方法。

On the 121 program, importantly, we've had numerous interactions with the FDA, of course, and there hasn't been an issue of how we've prospectively looked at our individual data. And the only thing that's been asked for from an efficacy standpoint was what we provided in terms of the encouraging one year data.

重要的是，在 121 計劃中，我們當然與 FDA 進行了多次互動，而且在我們如何前瞻性地審視個人資料方面也沒有出現任何問題。從療效角度來看，唯一被要求提供的就是我們所提供的令人鼓舞的一年期數據。

And since then, we discussed with the FDA was there any other data that would be needed, and the answer was no, that this would allow them to complete their review. So I think this reality of what type of feedback we've gotten from the current regime puts us in a good place for both these indications.

從那時起，我們與 FDA 討論了是否還需要其他數據，答案是否定的，這些數據足以讓他們完成審查。所以我認為，從現任政府得到的回饋類型，讓我們在這兩個方面都處於有利地位。

Okay, great. And I'm going to be different and ask wet AMD question. I guess, can you opine on the recent M&A and licensing activity for gene therapy and wet AMD obviously we had Lily, Fred, Bren and a 4-DMT licensing and of course, your licensing. So does the Street have it wrong on the level of interest from retina specialists? And where's your program rank as far as level of engagement with these retinal specialists?

好的，太好了。我要另闢蹊徑，問一個關於AMD的問題。我想，您能否就最近的基因療法和濕性 AMD 領域的併購和授權活動發表一下看法？顯然，我們看到了 Lily、Fred、Bren 和 4-DMT 的許可，當然還有您自己的許可。那麼，華爾街對視網膜專家的興趣程度判斷有誤嗎？那麼，就與這些視網膜專家的互動程度而言，您的專案排名如何？

Sure. I think, it might be good, Steve, to reflect on what we just heard out of AAO regarding gene therapy in general and specifically our program.

當然。史蒂夫，我認為，我們不妨回顧一下我們剛從美國眼科學會 (AAO) 那裡聽到的關於基因治療（尤其是我們計畫）的資訊。

Sure. So I think there's tremendous excitement about one-time treatment, and the way to do that is gene therapy. And one strong piece of evidence is what we're hearing actually from retina specialists. And this is coming from the past ASRS survey of close to 1,000 retina specialists, where every year, a number of questions are asked of these experts in the field, the actual treating clinicians.

當然。所以我認為大家對一次性治療非常興奮，而實現這一目標的方法就是基因療法。而我們從視網膜專家那裡聽到的，恰恰提供了強而有力的證據。這是來自 ASRS 過去對近 1000 名視網膜專家的調查，每年都會向這些領域的專家，也就是實際的臨床醫生提出一些問題。

An important one is exactly what you're asking, how -- what pipeline approaches are you most interested in, asked to retina specialists across all the different approaches. And half the respondents say gene therapy because of the one-time potential here, that isn't the case for any of the other treatment approaches like TKIs or any other durability approaches.

其中一個重要的問題正是你所問的，即如何——你最感興趣的是哪些治療流程，向所有不同方法的視網膜專家提出這個問題。一半的受訪者表示，基因療法具有一次性療效的潛力，而其他治療方法，如 TKI 或其他任何持久性療法，則不具備這種潛力。

Because no matter how long you extend that durability, you're still going to need injections indefinitely for any of the indications that we're looking at. I think we're seeing that in terms of interest in the field and some of the licensing deals or M&A deals that you mentioned, Annabelle.

因為無論你如何延長藥物的耐久性，對於我們所討論的任何適應症，你仍然需要無限期地進行注射。安娜貝爾，我認為我們已經從人們對該領域的興趣以及你提到的一些許可協議或併購交易中看到了這一點。

And of course, we have a major global partnership with AbbVie, who has quite a lot of experience globally, including quite a reputation when it comes to ophthalmology and experience there. So their continued advancement with our program, including paying $2 of every $3 for the advancements both in diabetic retinopathy and other areas, I think really speaks to the validation of not just gene therapy, but specifically our program with the muscle of AbbVie behind it globally.

當然，我們也與艾伯維公司建立了重要的全球合作夥伴關係，該公司在全球範圍內擁有豐富的經驗，尤其是在眼科領域享有盛譽並擁有豐富的經驗。因此，他們持續推進我們的項目，包括為糖尿病視網膜病變和其他領域的進展支付每 3 美元中的 2 美元，我認為這真正體現了基因療法的有效性，尤其是我們項目在全球艾伯維強大支持下的有效性。

Okay, that's a great color. Thank you.

好的，這個顏色真棒。謝謝。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

Hey guys, this is Matthew on for Alec. Appreciate you taking our questions. Given a recent expectation for a box warning for a competitor product and the removal of the non-ambulatory indication, just curious whether your expectation is for something similar on your label or other AAV gene therapy labels and how you're thinking about long-term development in the non-ambulatory population in general. Thanks.

大家好，我是Matthew，代Alec報道。感謝您回答我們的問題。鑑於最近有報導稱，競爭對手的產品可能會被加上黑框警告，並且取消了非行走適應症，我很好奇您是否也預期您的產品標籤或其他 AAV 基因治療產品標籤上會出現類似的情況，以及您如何看待非行走人群的長期發展。謝謝。

Thanks for the question. I think in terms of expectations, I mean, I think our track record in Phase I/II on safety has been exemplary, and I wouldn't expect a black box warning of that nature, given that we've shown clearly the incidence rate of any sort of liver injury for us is virtually non-existent in terms of the data.

謝謝你的提問。我認為就預期而言，我的意思是，我認為我們在第一/二期臨床試驗中的安全性記錄堪稱典範，鑑於我們已經清楚地表明，就數據而言，任何類型的肝損傷發生率幾乎為零，我不認為會出現那種性質的黑框警告。

Whereas we're seeing, on the label for Elevidys or in their filing that they have upwards of 40% liver injury, in the approved product. So I think we don't expect that. In fact, we expect to leverage safety as part of the accelerated approval pathway that we're pursuing.

而我們在 Elevidys 的標籤或他們的文件中看到，核准產品中肝損傷發生率高達 40%。所以我覺得我們不應該期待這種情況發生。事實上，我們希望利用安全性作為我們正在尋求的加速審批途徑的一部分。

And I think accompanying that is strong conviction that the differentiation of the product with the immune suppression regimen we utilize and the construct and manufacturing purity, put those altogether, I think we have something very different, and very exciting to the patient community today.

我認為，同時，我們堅信，我們採用的免疫抑制方案、產品結構和生產純度等差異化因素，將這些因素綜合起來，使我們擁有了非常獨特的產品，這對於當今的患者群體來說非常令人興奮。

Brian Skorney, Baird.

Brian Skorney，Baird。

Hey, good morning, everyone. I actually like to tack to regulatory questions on the EMA side of things. I know, EMA is granted 121, RMAT designation, but I was just wondering the status of any plans, for it at the EMA, and also any thoughts on the potential sufficiency of the AFFINITY DUCHENNE study for EMA review or what else you think you need to do? There's your FDA confirmatory sufficient for EMA filing? Thanks.

嘿，大家早安。我其實更喜歡就歐洲藥品管理局（EMA）方面的監管問題發表意見。我知道 EMA 已授予 121 號 RMAT 指定，但我只是想知道 EMA 是否有任何相關計劃，以及您對 AFFINITY DUCHENNE 研究是否足以提交 EMA 審查有何看法，或者您認為還需要做些什麼？你們的FDA確認函是否足以提交EMA申請？謝謝。

Yeah, we've had some interactions with EMA regarding RGX-121, and I think that what we're typically seeing there is the requirement for a control arm -- placebo control arm, still seems to be the predominant feedback that we get.

是的，我們已經就 RGX-121 與 EMA 進行了一些溝通，我認為我們通常看到的是需要設定對照組——安慰劑對照組，這似乎仍然是我們得到的主要回饋。

Having said that, there's a significant opportunity in named patient sales that would potentially exist often an accelerated approval. So I think that's something that we are carefully evaluating and could be part of our commercialization approach.

也就是說，指定病患銷售領域存在著巨大的機會，而且往往需要加速審核。所以我認為，這是我們正在認真評估的事情，並且可能成為我們商業化策略的一部分。

Steve, do you want to address the Duchenne question?

史蒂夫，你想談談杜氏肌肉營養不良症的問題嗎？

Sure. Hi, Brian. So based on all the discussions we've had stateside, so to speak, we're very confident on our approach here. Not having had the discussions outside the US, we don't want to project what will be the case.

當然。嗨，布萊恩。因此，根據我們在美國進行的所有討論，我們對我們在這裡採取的方法非常有信心。由於我們沒有在美國以外的地方進行過討論，我們不想預測未來會發生什麼。

Certainly, historically, there has been a need for a placebo control there. We recognize the problems of that as well as with the patient advocacy community. There is increased data that keeps growing with different ways of assessing, function that are becoming accepted in different regulatory regions like the SB95C, just to give one example.

當然，從歷史上看，那裡一直需要安慰劑對照。我們也意識到了這方面的問題，以及病患權益倡議團體的問題。數據不斷增加，評估方法也越來越多樣化，功能也逐漸被不同的監管區域所接受，例如 SB95C，這只是一個例子。

So it's something that's an evolving field, but it's really going to take actual discussion. And we keep coming back to differentiation because it matters. So the functional data, if we continue to see what we're seeing, including, in the older boys, not just stabilization but improvement, we think we're in a stronger position for being able to come up with an approach that would be acceptable ex-US.

所以這是一個不斷發展的領域，但確實需要真正的討論。我們之所以不斷強調差異化，是因為它至關重要。因此，如果我們繼續看到我們所看到的情況，包括年齡較大的男孩不僅病情穩定而且病情有所改善，那麼我們認為我們更有可能找到美國以外地區可以接受的方法。

Great, thank you.

太好了，謝謝。

Sean McCutcheon, Raymond James.

Sean McCutcheon，Raymond James。

Hi guys, thanks for the question. Just one for me on diabetic retinopathy. A competitor was able to get an agreement with the FDA for an ordinal two-step DRSS change, primary endpoint for the pivotal studies in NPDR.

大家好，感謝你們的提問。我只需要一份關於糖尿病視網膜病變的資料。競爭對手與 FDA 達成協議，對 NPDR 的關鍵研究的主要終點進行有序的兩步驟 DRSS 變更。

Can you speak to how that's informing your discussions with AbbVie on your pivotal NPDR program and the ability to adjust that study plan to potentially improve probability of success, relative to a two-step DRSS improvement at one year? Thanks.

您能否談談這是如何影響您與艾伯維就關鍵的 NPDR 項目進行的討論，以及調整該研究計劃以提高成功機率的能力（相對於一年內 DRSS 兩步改善而言）？謝謝。

Sure, I can take that.

當然可以。

It's a great question. Steve, go ahead.

這是一個很好的問題。史蒂夫，你先說。

Sure. Yeah, thanks for the question. Yeah, it -- I think one item off the bat is that the ordinal approach is something people have thought about over time. The prior lead or director of the ophthalmic division had always required a meaningful change in DRSS with meaningful defined as either two-step improvement change or in either direction of worse or improvement.

當然。謝謝你的提問。是的，我認為首先要指出的是，序數方法是人們隨著時間的推移一直在思考的問題。眼科部門的前任負責人或主管一直要求 DRSS 發生有意義的變化，而有意義的變化被定義為兩級改善，或朝著惡化或改善的方向發展。

So the advance of being able to get more information out of each patient's DRSS change by looking in an ordinal way, now with the new regime has come on the table. So it is definitely something we've been looking at, both us and AbbVie and in close collaboration. So I think it gives us more options.

因此，透過按序數方式查看每位患者的 DRSS 變化，從而獲取更多資訊的進步，現在隨著新方案的出台而成為現實。所以這絕對是我們和艾伯維一直密切合作、共同關注的問題。所以我認為這給了我們更多選擇。

Fortunately, what we've seen is, we look good in both respects, two-step improvement, a greater proportion of patients achieving that, and also two-step worsening, a greater proportion of patients, showing that in a placebo controlled setting as well as what you expect without treatment in the real world and other controlled -- negative controlled arms. So we think we're really well positioned to really take advantage of what looks best in our discussions with the FDA.

幸運的是，我們看到，我們在兩方面都表現良好：兩步驟改善，達到這一目標的患者比例更高；兩步惡化，患者比例也更高。這表明，在安慰劑對照環境下，以及在現實世界中不進行治療的情況下，和其他對照（陰性對照）組所預期的情況，都與此相符。因此，我們認為我們已經做好了充分準備，可以充分利用與 FDA 討論中出現的最佳方案。

Thank you.

謝謝。

Daniil Gataulin, Chardan.

丹尼爾·加陶林，查爾丹。

Yes, hi. Good morning, guys. Thank you for taking my question. Quick one on suprachoroidal with AMD. First, can you remind us how many patients you're looking to enroll at those level IV for the study. And now with the subretinal program fully enrolled, do you expect the speed of enrollment for suprachoroidal program to pick up a little bit now, with the shifted focus to the program. Thank you.

是的，你好。各位早安。感謝您回答我的問題。簡單介紹一下伴隨老年性黃斑部病變的脈絡膜上腔出血。首先，您能否提醒我們一下，您希望在研究的 IV 級階段招募多少位病患？現在視網膜下注射治療項目已經全部招滿，隨著重點轉移到脈絡膜上註射治療項目，您是否預計該項目的招收速度會加快一些？謝謝。

Steve, go ahead.

史蒂夫，你先說。

Thanks for the question, Daniil. So SCS, wet AMD is advancing. We're looking to enroll 20 patients in that arm. As you mentioned, we reached the quite significant milestone of completing enrollment in the SR wet AMD pivotal studies, the largest gene therapy program, ever conducted across any indication.

謝謝你的提問，丹尼爾。所以SCS，濕式AMD正在取得進展。我們計劃在該組招募 20 名患者。正如您所提到的，我們達到了一個非常重要的里程碑，完成了 SR 濕性 AMD 關鍵性研究的入組，這是迄今為止針對任何適應症開展的最大規模的基因治療計畫。

It's a great point that now, with that trial completed enrollment, a lot of the overlapping sites can now, focus on the suprachoroidal delivery route. So yes, indeed, we're seeing a pickup in enrollment in that study.

現在，隨著該試驗的招募工作完成，許多重疊的試驗點現在可以專注於脈絡膜上腔給藥途徑，這是一個非常好的結果。所以，是的，我們確實看到研究的參與人數增加。

Got it. And a quick follow-up for subretinal program. Do you expect AbbVie to file in the US and the EU roughly at about the same time?

知道了。以及針對視網膜下病變項目的快速後續追蹤。您預計艾伯維會在美國和歐盟大致同時提交申請嗎？

Yeah. I think that's a safe assumption. We haven't got a specific timeline for the filing mapped out. We're primarily focused on top-line data next year. But we would expect a global filing, and we'll be more specific as we get closer about the interval between US and ex-US filings. But they're recruiting not the basis of the ASCENT study, being recruited in Europe was to enable that to be a smooth process.

是的。我認為這是一個合理的假設。我們還沒有製定具體的提交時間表。明年我們主要關注的是整體數據。但我們預計會提交全球性申報，隨著美國申報和美國境外申報之間的時間間隔臨近，我們會給出更具體的資訊。但他們招募人員並非 ASCENT 研究的基礎，在歐洲招募人員是為了讓這個過程順利進行。

Okay. Got it. Thank you very much, and congrats on all the progress.

好的。知道了。非常感謝，也祝賀你們取得的所有進展。

[Bill Munn], Clear Street.

[比爾·蒙恩]，清晰的街道。

Good morning and thanks. So I just wanted to look again at the functional endpoints on 202 and just ask about the powering around those and whether or not you believe there's a certain threshold or I guess outcome that you need to see as a bar for success to really kind of put together a definitive answer in front of the FDA that kind of can't be denied.

早安，謝謝。所以我只是想再看一下 202 的功能終點，並詢問圍繞這些終點的動力問題，以及您是否認為存在某種閾值或結果，需要將其視為成功的標準，以便在 FDA 面前給出一個無法否認的明確答案。

Steve, do you want to cover that?

史蒂夫，你想報道這件事嗎？

Sure, thanks for the question. So we are seeing a nice response, both in terms of change from baseline with improvement, even in the older boys where you might expect just stabilization or worsening, and with improvement, just stabilization.

當然，謝謝你的提問。所以我們看到了一個不錯的反應，無論是從基線變化來看，都有所改善，即使是年齡較大的男孩，你可能預期他們的情況只會穩定或惡化，但也有所改善，只是病情穩定了而已。

So I think we're in a good position where if we continue to see what we're seeing, and what we report on in early Q2 next year, with not only the primary endpoint for accelerated approval, but also the microdystrophin, I think we're going to be very well set up.

所以我認為我們現在處境很好，如果我們繼續看到我們目前看到的情況，以及我們在明年第二季度初報告的情況，不僅包括加速批准的主要終點，還包括微型肌肉營養不良蛋白，我認為我們將做好非常充分的準備。

And that's based on to your question, looking at the traditional endpoints. So certainly NSAA where marginal effect, if any, depending on the age of the patients has been seen previously, and also the time function tests. So the traditional time to stand, 10 meter walk, run, time to climb, as the traditional ones where there's a lot of data out there and we have the opportunity to look with propensity matching.

這是基於你的問題，從傳統終點的角度來看的。因此，NSAA 的效果（如果有的話）取決於患者的年齡，這一點以前已經觀察到，而且時間功能測試也是如此。所以，傳統的站立時間、步行 10 公尺、跑步時間、攀爬時間，這些都是有很多數據可供參考的傳統測試，我們有機會透過傾向性配對來研究它們。

So how good of a data do we have to see? Again, if we continue to see what we're seeing, we're going to pass that bar because of the differentiation that we're seeing. And some bars you can look at are not only against natural history, but also there's data and published interpretations of the data on minimally important clinical difference that we're surpassing.

那麼，我們所掌握的數據品質如何呢？再說一遍，如果我們繼續看到我們現在所看到的，我們將通過這個標準，因為我們看到了差異化。而有些指標不僅違反自然規律，而且有數據和已發表的解釋表明，我們在最小重要臨床差異方面已經超越了這些指標。

And we can also look by age and by baseline status, what's been seen with approved therapy. And that allows us to feel that we're in a good position to have power based on the data that we're seeing. Again, if we continue to see what we're seeing. The overall package is important as well, so the benefit risk relative to that functional improvement, then we go to the safety where again we're seeing very good differentiation.

我們也可以根據年齡和基線狀態，查看已批准療法的效果。這讓我們覺得，根據我們所看到的數據，我們處於一個能夠掌握權力的有利位置。再說一遍，如果我們繼續看到我們所看到的一切。整體方案也很重要，因此要考慮相對於功能改進的收益風險，然後我們再來看安全性，在這方面我們又看到了非常好的差異。

Okay. And on your suprachoroidal program, where are you on your understanding of how closely that can recapitulate the amount of vector delivery of your subretinal delivery?

好的。關於您的脈絡膜上腔注射方案，您對該方案在多大程度上能夠重現視網膜下注射的載體輸送量有怎樣的了解？

So (inaudible) are you asking if the protein levels match in terms of transgene expression between the two?

所以（聽不清楚）你想問這兩個基因改造表現體系的蛋白質量是否匹配嗎？

Yeah.

是的。

I think because Steve can comment further, but because they're delivered to different compartments of the eye, it's very difficult to do direct comparison. So ultimately what we look at is sustained vision and safety. But Steve, maybe you want to comment further on the differences we see.

我認為史蒂夫可以進一步評論，但由於它們被輸送到眼睛的不同部位，因此很難進行直接比較。所以歸根結底，我們關注的是持續的視野和安全。但是史蒂夫，或許你想就我們看到的這些差異再做進一步的評論。

Sure. So geographically, they're different spaces. They're both close to the target tissue, and they're both in compartmentalized spaces, so that's why we selected them. So that they greatly limit off-target tissue potential side effects, in terms of immunogenicity.

當然。所以從地理位置來看，它們是不同的空間。它們都靠近目標組織，而且都位於分隔的空間內，所以我們選擇了它們。因此，它們大大限制了非目標組織潛在的免疫原性副作用。

That also changes as Curran mentioned, the reality that you really can't compare the apples and oranges. But fortunately, what really matters is what do you see clinically, which shows that you have the transgene product at the target tissue where you need it.

正如柯倫所提到的那樣，情況也會發生變化，因為現實是蘋果和橘子根本無法相提並論。但幸運的是，真正重要的是臨床觀察結果，這表明基因改造產物已到達目標組織中所需的位置。

And that's where the diabetic retinopathy data is so compelling for us in AbbVie that you're seeing what you want to see. And that's why we're advancing with suprachoroidal already and actually accelerated development, so that we can -- we and AbbVie can actually start Phase IIb/III next year.

而這正是艾伯維認為糖尿病視網膜病變數據如此令人信服的原因——你看到的正是你想看到的。這就是為什麼我們已經推進脈絡膜上腔注射療法，並實際上加快了研發速度，以便我們和艾伯維明年能夠真正開始 IIb/III 期臨床試驗。

Got it. Thank you.

知道了。謝謝。

Yi Chen, H.C. Wainwright.

易晨，H.C. Wainwright。

Good morning. Thank you for taking my questions. Could you comment on your current thinking regarding the pricing strategy for RGX-121 versus 202? And also how large a sales team do you think you need for 121 versus 202? Thank you.

早安.謝謝您回答我的問題。您能否談談您目前對RGX-121和RGX-202定價策略的看法？另外，您認為銷售團隊規模在 121 和 202 之間分別需要多大？謝謝。

Yeah. So if you recall earlier in the year, we signed an agreement with NS Pharma for commercialization in the US. And so the pricing decisions will be made by NS Pharma as we move through the approval process, and Mitch can comment.

是的。所以，如果你還記得的話，今年早些時候，我們與 NS Pharma 簽署了在美國進行商業化的協議。因此，定價決定將由 NS Pharma 在審批過程中做出，Mitch 可以對此發表評論。

We certainly will enjoy a nice royalty from sales, but the actual price determination will be made by them. We would eventually make the price decisions since we wholly own the Duchenne asset, and I'd say at this point, it's very preliminary for us to state any sort of thinking on pricing, until we get closer to commercialization.

我們當然會從銷售中獲得一筆可觀的版稅，但實際價格將由他們決定。由於我們完全擁有杜氏肌肉營養不良症的資產，最終價格將由我們決定。我認為，在接近商業化之前，我們現在就定價問題發表任何想法都還為時過早。

Yeah. So as you recall from the NS Pharma partnership, we are eligible to receive meaningful double-digits in sales royalty. So as Curran has mentioned, pricing decisions will be made by NS Pharma at a later time.

是的。正如您從 NS Pharma 的合作關係中了解到的那樣，我們有資格獲得可觀的兩位數銷售分成。正如柯倫所提到的，定價決定將由NS Pharma在稍後做出。

Thank you.

謝謝。

Paul Choi, Goldman Sachs.

Paul Choi，高盛。

Hi, thank you. Good morning, everyone, and thanks for taking the questions. With regard to 202, could you please comment on where you think you might see the potentially greatest demand initially as you start to commercialize in 2027.

您好，謝謝。各位早安，感謝大家回答問題。關於 202，您能否評論一下，當您在 2027 年開始商業化時，您認為最初可能需求最大的領域在哪裡？

Do you think about it in a particular Exxon's Kipper experienced patients or just thinking primarily about newly diagnosed patients? Any color there would be helpful.

您考慮的是埃克森美孚的 Kipper 有經驗的患者，還是主要考慮新確診的患者？任何顏色都會有所幫助。

And then, second on, with regard to your collaboration with AbbVie and 314, how are you thinking about sort of rough timelines for potential Medicare coverage of 314 post-approval? And just sort of what are sort of the block steps they're involved with -- for gene therapy coverage in this particular Medicare population. Thank you very much.

其次，關於您與艾伯維和 314 的合作，您認為 314 獲批後，Medicare 可能涵蓋的大致時間表是什麼？那麼，他們參與的基因療法涵蓋範圍的具體步驟是什麼呢？ （針對特定醫療保險族群）非常感謝。

Yeah, I'll take the first one. I think, obviously, if you look at the inclusion criteria for the study, we're dosing patients 1 and older. So we'll have data at the time of review for potentially a broad label. One thing that we see based upon the public announcements on sales is that the prevalent market really isn't changing in terms of Duchenne.

好的，我要第一個。我認為，很明顯，如果你看一下這項研究的納入標準，我們給 1 歲及以上的患者用藥。因此，在審查時我們將有數據，以便可能做出廣泛的標籤。從公開的銷售公告來看，杜氏肌肉營養不良症的市場現況並沒有真正的變化。

So by 2027, the prevalent market will be something like 14,000 patients. And if you think about eligible for gene therapy, it's probably closer to 3,000 patients when you subtract out non-ambulatory. So at the time of launch, our aim is to have a broad label and really be able to address patients of all ages.

因此，到 2027 年，市場規模將達到約 14,000 名患者。如果考慮符合基因治療條件的患者，減去無法行走的患者，可能接近 3000 人。因此，在上市之初，我們的目標是擁有廣泛的適應症，真正能夠滿足所有年齡層患者的需求。

But to your point, we do expect that over time as the prevalent market diminishes, which could be past 2030, is that at that point we would be in a great position to address the incident market. Most KOLs think early treatment is ultimately the answer for gene therapy. And we'll have the data in hand to support that age group, based on the fact that we're already dosing kids right after diagnosis in some cases.

但正如您所說，我們預計隨著時間的推移，當現有市場萎縮時（可能要到 2030 年以後），我們將處於非常有利的地位來應對突發事件市場。大多數意見領袖認為，早期治療才是基因治療的最終答案。而且，我們將掌握數據來支持該年齡組，因為在某些情況下，我們已經在確診後立即給兒童用藥。

I think on the Medicare coverage for 314, that's a question that I'll differ out a bit. We haven't had those discussions with AbbVie. AbbVie will obviously be leading the significant element of the commercialization. But we do believe broad access for gene therapy is fairly easily achieved. It's just too early in terms of our conversations with AbbVie to be specific there.

關於 314 條款的 Medicare 覆蓋範圍，我認為這個問題我需要稍微解釋一下。我們還沒有和艾伯維公司進行過這些討論。顯然，艾伯維將在商業化這一重要環節中發揮主導作用。但我們相信，基因療法的廣泛普及是比較容易達成的。就我們與艾伯維的對話而言，現在談論具體細節還為時過早。

Okay, thank you.

好的，謝謝。

This does conclude today's question-and-answer session and conference call. Thank you for participating, and you may now disconnect. Have a good day.

今天的問答環節和電話會議到此結束。感謝您的參與，您現在可以斷開連接了。祝你有美好的一天。