Regenxbio Inc (RGNX) 2025 Q1 法說會逐字稿

Welcome everyone to the first quarter of 2025 Regenxbio earnings conference call. (Operator Instructions) As a reminder, this call may be recorded.

歡迎大家參加2025年第一季Regenxbio收益電話會議。（操作員指示）提醒一下，此通話可能會被錄音。

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 afternoon and thank you for joining us today. Earlier this afternoon, Regenxbio released financial and operating results for the first quarter ended March 31, 2025. The press release is available on our website at www.regenxbio.com.

下午好，感謝您今天加入我們。今天下午早些時候，Regenxbio 發布了截至 2025 年 3 月 31 日的第一季財務和營運業績。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括有關我們的財務前景以及監管和產品開發計劃的前瞻性聲明。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，並可透過預期、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 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, and comparable Risk Factors sections of Regenxbio's quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission, and available on the SEC's website.

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 表年度報告的風險因素和管理層討論與分析部分以及 Regenxbio 10-Q 表季度報告中的類似風險因素部分中有描述，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, May 12, 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 5 月 12 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 report 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，並不報告公司的專案財務狀況或經營成果。實際結果可能存在重大差異。

I will now turn the call over 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 today. We've had an impressive start to the year at Regenxbio and are in store for an exciting remainder of 2025. Today, you will hear about our strong late-stage clinical progress, which sets us up to potentially bring multiple first or best-in-class gene therapies to patients over the coming years. We will also discuss other key elements that we believe position us to successfully transition to commercial stage, including our US-based in-house commercial-ready manufacturing and broad potential to secure non-dilutive funds.

謝謝派崔克，也謝謝大家今天加入我們。Regenxbio 今年取得了令人印象深刻的開局，並有望在 2025 年剩餘時間裡取得令人興奮的成績。今天，您將了解我們強勁的後期臨床進展，這為我們在未來幾年為患者帶來多種首創或一流的基因療法奠定了基礎。我們還將討論我們認為能夠讓我們成功過渡到商業階段的其他關鍵因素，包括我們位於美國的內部商業化製造能力和獲得非稀釋性資金的廣泛潛力。

With me on today's call are Dr. Steve Pakola, our Chief Medical Officer; and Mitch Chan, our Chief Financial Officer. I'll start with a review of recent business highlights, then turn it over to Steven Mitch for clinical and financial updates. Then, I'll have a few closing remarks before opening the call for Q&A.

今天與我一起參加電話會議的還有我們的首席醫療官 Steve Pakola 博士；以及我們的財務長 Mitch Chan。我將首先回顧最近的業務亮點，然後將其交給 Steven Mitch 進行臨床和財務更新。然後，在開始問答環節之前，我將先講幾句結束語。

Starting with our most advanced program, RGX-121 or clemidsogene lanparvovec, the potential first-gene therapy and one-time treatment for MPS II or Hunter syndrome, a devastating disease that affects approximately 2,000 patients worldwide. Any day now, we expect the FDA acceptance of the BLA, which we submitted under the accelerated approval pathway in March 2025. RGX-121 remains on track for potential FDA approval in the second half of this year.

從我們最先進的項目 RGX-121 或 clemidsogene lanparvovec 開始，它是針對 MPS II 或亨特綜合徵的潛在首個基因療法和一次性治療，MPS II 或亨特綜合徵是一種影響全球約 2,000 名患者的毀滅性疾病。我們預計 FDA 隨時都會接受我們於 2025 年 3 月根據加速審批途徑提交的 BLA。RGX-121 預計將在今年下半年獲得 FDA 批准。

Earlier this year, we established a key strategic partnership with Nippon Shinyaku to commercialize our neurodegenerative franchise, including RGX-121 and RGX-111 for severe MPS I, and commercial preparations are progressing well. Together with Nippon, our goal is to deliver RGX-121 to patients beginning in the first half of 2026.

今年早些時候，我們與日本新藥建立了重要的策略合作夥伴關係，以商業化我們的神經退化性疾病特許經營權，包括用於治療嚴重 MPS I 的 RGX-121 和 RGX-111，商業化準備工作進展順利。我們與 Nippon 合作的目標是從 2026 年上半年開始向患者提供 RGX-121。

Accelerating quickly, right behind RGX-121 is RGX-202, our next-generation candidate for Duchenne muscular dystrophy. I am pleased to report that our pivotal study continues advancing rapidly. We have surpassed 50% enrollment for our pivotal data set. We're seeing increased interest and enthusiasm from the patient community about RGX-202 and its differentiated profile. And we remain on track to submit a BLA in mid-2026 and seize our unique second to market or fast follower opportunity in Duchenne.

緊隨 RGX-121 之後的是 RGX-202，這是我們治療杜氏肌肉營養不良症的下一代候選藥物。我很高興地報告，我們的關鍵研究繼續快速進展。我們關鍵資料集的註冊率已超過 50%。我們看到患者群體對 RGX-202 及其差異化特性的興趣和熱情日益增長。我們仍有望在 2026 年中期提交 BLA，並抓住杜氏肌肉失養症領域獨特的第二個上市或快速跟進機會。

Positive input from our growing investigator community supports our belief that RGX-II has the potential to be a preferred and differentiated treatment option. It's important to keep in mind that, one, RGX-202 is the only investigational next-generation DMD gene therapy in pivotal study and the only investigational therapy with both robust microdystrophin and functional data available.

我們不斷成長的研究人員群體的正面意見支持了我們的信念，即 RGX-II 有可能成為一種首選的差異化治療方案。重要的是要記住，首先，RGX-202 是關鍵研究中唯一研究性的下一代 DMD 基因療法，也是唯一具有強大的微肌營養不良蛋白和功能數據的試驗性療法。

Two, RGX-202 has the potential to be approved for patients aged one to three, who currently have no access to gene therapy. And last, DMD represents a large addressable market. With over half of the prevalent DMD population projected to remain untreated as of 2027, the expected year of RGX-202's commercial launch.

二、RGX-202 有可能獲準用於治療目前無法接受基因治療的一至三歲患者。最後，DMD 代表著一個巨大的潛在市場。預計到 2027 年（RGX-202 預計商業化推出的年份），超過一半的 DMD 患者仍未接受治療。

Given our strong and rapid clinical progress, conviction in our differentiated profile, and in recognition of the ongoing unmet need, we will begin producing RGX-202 commercial supply at our manufacturing innovation center here in Rockville, Maryland in the third quarter of this year. With full clinical and planned confirmatory supply already in hand, we will build commercial inventory to be prepared for a smooth launch and meet patient needs immediately upon the potential approval of RGX-202.

鑑於我們強勁而快速的臨床進展、對我們差異化產品的信心以及對持續未滿足的需求的認識，我們將於今年第三季度開始在位於馬裡蘭州羅克維爾的製造創新中心生產 RGX-202 商業供應。在已經獲得完整的臨床和計劃確認供應的情況下，我們將建立商業庫存，為順利推出做好準備，並在 RGX-202 獲得批准後立即滿足患者的需求。

As a reminder, our manufacturing innovation center is a state-of-the-art integrated GMP facility that can produce up to 2,500 doses of RGX-202 annually, enough to treat approximately one fifth of the estimated North American DMD population. All while delivering industry leading purity levels in Duchenne with over 80% for capsids. We look forward to sharing additional Phase 1/2 functional data for RGX-202 in the first half of this year as we aggressively advance towards commercialization.

提醒一下，我們的製造創新中心是一個最先進的綜合 GMP 設施，每年可生產多達 2,500 劑 RGX-202，足以治療北美 DMD 人口估計的約五分之一。同時，杜氏肌肉營養不良症的純度達到行業領先水平，衣殼純度超過 80%。我們積極推動商業化進程，期待今年上半年分享 RGX-202 的更多 1/2 期功能數據。

Moving to our retinal programs, we continue to work closely with our partner AbbVie to progress ABBV-RGX-314 or surabgene lomparvovec. 314 is advancing in two pivotal studies for sub-retinal wet AMD, one Phase 2 study for suprachoroidal wet AMD, and preparations for a pivotal program are underway in diabetic retinopathy or DR using suprachoroidal delivery.

轉向我們的視網膜項目，我們繼續與我們的合作夥伴 AbbVie 密切合作，以推進 ABBV-RGX-314 或 surabgene lomparvovec。 314 正在進行兩項針對視網膜下濕性 AMD 的關鍵研究、一項針對脈絡膜上濕性 AMD 的 2 期研究，並且正在準備透過脈絡膜上腔給藥治療糖尿病視網膜病變或 DR 的關鍵項目。

We remain on track to be the first gene therapy on the market for wet AMD with a product that has demonstrated compelling durability and strong patient interest. Both wet AMD and DR represent large multi-billion-dollar commercial opportunities, and we believe 314 has the potential to preserve vision and serve as a meaningful alternative to today's standard-of-care. In summary, we remain excited for and are well positioned to deliver on the opportunities ahead of us.

我們仍有望成為市場上首個針對濕性 AMD 的基因療法，我們的產品已展現出極強的耐用性和患者的強烈興趣。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 314 有潛力保護視力並成為當今標準治療的有效替代方案。總而言之，我們仍然對未來的機會感到興奮，並且已準備好去抓住它。

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, Curran. I'll start with RGX 202, a potential one-time gene therapy for the treatment of Duchenne. RGX-202 uses the Nav AAV8 vector and it's the only microdystrophin construct to include the C-terminal domain, a key element of naturally occurring dystrophin, critical to protecting muscle from contraction-induced damage. This novel construct combined with the highest purity levels in the field, make 202 a potential best-in-class gene therapy for Duchenne.

謝謝你，Curran。我將從 RGX 202 開始，這是一種用於治療杜氏肌肉營養不良症的潛在一次性基因療法。RGX-202 使用 Nav AAV8 載體，它是唯一包含 C 端結構域的微肌營養不良蛋白構建體，C 端結構域是天然存在的肌營養不良蛋白的關鍵元素，對於保護肌肉免受收縮引起的損傷至關重要。這種新穎的結構與該領域最高的純度水平相結合，使 202 成為杜氏肌肉營養不良症的潛在最佳基因治療方法。

As Curran mentioned, I'm pleased to share that today we announced the pivotal phase of the AFFINITY Duchenne trial is beyond 50% enrolled. Our accumulating Phase 12 results are showing impressive evidence of differentiation on safety, biomarker and functional outcomes. This is driving increased excitement throughout the Duchenne community, giving us further confidence as we move toward our target of completing pivotal enrollment in the second half of this year.

正如 Curran 所提到的，我很高興地告訴大家，今天我們宣布 AFFINITY Duchenne 試驗的關鍵階段的參與率已超過 50%。我們不斷累積的第 12 階段結果顯示出安全性、生物標記和功能結果方面令人印象深刻的差異化證據。這激發了整個杜氏肌肉營養不良症社區的興奮之情，讓我們更有信心朝著今年下半年完成關鍵招生的目標邁進。

This trial is enrolling ambulatory patients aged one and above, generating data where limited results exist for Duchenne therapies. Based on the clinical profile and in partnership with our investigators, we expanded the inclusion criteria to a broader range of exon mutations. Additional trial sites continue opening in the US and Canada, and we are making great strides in our pivotal strategy to enroll across a wider age range with an aim to secure a broad label supported by a clear and robust product profile.

這項試驗招募了一歲及以上的門診患者，以產生杜氏肌肉營養不良症療法結果有限的數據。根據臨床特徵並與我們的研究人員合作，我們將納入標準擴展到更廣泛的外顯子突變。美國和加拿大將繼續開放更多試驗點，我們正在大力推進關鍵策略，以擴大受試者的年齡範圍，從而確保獲得由清晰、強大的產品特性支援的廣泛標籤。

In November, we reported positive safety and efficacy data from the Phase 1/2 study, including positive functional outcomes from the first five participants at 9 and 12 months. These results presented last November showed 202 recipients exceeded external natural history controls and established benchmarks for clinical outcomes.

11 月，我們報告了第 1/2 階段研究的積極安全性和有效性數據，包括前五名參與者在第 9 個月和第 12 個月的積極功能結果。去年 11 月公佈的這些結果顯示，202 名接受者超過了外部自然史控制並為臨床結果建立了基準。

Specifically, we observed functional improvements in all five evaluated patients, including those at dose level 2. Consistent robust expression, transduction and localization of our differentiated 202 microdystrophin in muscle with all participants above 10% expression. We have also seen a favorable safety profile with no serious adverse events or AEs of special interest.

具體來說，我們觀察到所有五名接受評估的患者（包括劑量等級 2 的患者）的功能都有改善。我們的分化型 202 微肌營養不良蛋白在肌肉中表現出一致、強烈的表達、轉導和定位，所有參與者的表達均超過 10%。我們也看到了良好的安全性，沒有嚴重的不良事件或特別值得關注的不良事件。

Building on this data in March at the 2025 MDA Conference, we presented new biomarker data from two patients, including the first data from our cohort of patients under four years of age. This patient aged three at dosing had a microdystrophin expression level of 122% of control. Patients aged one to three represent a significant portion of the prevalent Duchenne population, yet this group has no access to approved gene therapy.

基於 2025 年 3 月 MDA 會議上的這些數據，我們展示了來自兩名患者的新生物標記數據，其中包括來自我們四歲以下患者群體的首批數據。該患者在服藥時年齡為 3 歲，其微肌營養不良蛋白表現量為對照組的 122%。一至三歲的患者佔杜氏肌肉營養不良症患病人群的很大一部分，但這群體無法獲得經批准的基因治療。

Overall, the Phase 1/2 data show consistent microdystrophin expression in all12 patients spanning all age groups, functional improvements and evidence of altering the trajectory of disease,and a favorable safety profile. As the program advances, we expect an increased focus on the dose level 2 cohort, as these patients receive the commercial dose level. We look forward to sharing additional data from the Phase 1/2 study in the first half of this year.

總體而言，1/2 期數據顯示，所有年齡層的 12 名患者均有一致的微肌營養不良蛋白表達、功能改善和改變疾病軌蹟的證據，以及良好的安全性。隨著計畫的進展，我們預計劑量等級 2 組患者將受到更多關注，因為這些患者接受的是商業劑量等級的治療。我們期待在今年上半年分享第 1/2 階段研究的更多數據。

Now, on to our retinal franchise, 314, which is being developed in collaboration with AbbVie to treat wet AMD and diabetic retinopathy or DR. I'll start with 314 for DR being evaluated in the Phase 2 ALTITUDE trial using in-office suprachoroidal delivery. Like wet AMD, DR is a progressive disease that causes vision loss, and ultimately blindness is not treated appropriately.

現在，讓我們來談談我們的視網膜特許經營權 314，該特許經營權正在與 AbbVie 合作開發，用於治療濕性 AMD 和糖尿病視網膜病變或 DR。我將從 314 開始，該 DR 正在第 2 階段 ALTITUDE 試驗中使用辦公室內脈絡膜上腔給藥進行評估。與濕性 AMD 一樣，DR 是一種進行性疾病，會導致視力喪失，並且由於無法適當治療，最終會導致失明。

As we've shared, we've completed our end of Phase 2 meeting with the FDA in the fourth quarter of last year and are actively working with AbbVie on plans for our Phase 3 clinical program that would support global regulatory filings. We look forward to sharing more on that program as preparations progress.

正如我們所分享的，我們已於去年第四季度完成了與 FDA 的第二階段會議，並正在積極與 AbbVie 合作制定支持全球監管備案的第三階段臨床計劃。隨著準備工作的進展，我們期待分享有關該計劃的更多資訊。

In wet AMD, we are evaluating 314 via two different delivery forms, sub-retinal 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. As we've announced in January, enrollment of both pivotal trials is expected to complete this year, and we expect to share topline data in 2026.

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）對 314 進行評估。在亞視黃醇領域，我們在美國、歐洲和日本正在進行兩項關鍵試驗，ATMOSPHERE 和 ASCENT。這些試驗持續進展順利。正如我們在一月份宣布的那樣，這兩項關鍵試驗的招募預計將於今年完成，我們預計將在 2026 年分享頂線數據。

314 is on track to be the first gene therapy on the market for wet AMD. And it's poised to deliver a compelling product profile based on the impressive safety and durability seen in our Phase 1/2A trial. In this trial, 314 achieved meaningful reduction in treatment burden and sustained treatment effect through four years. Overall, we remain encouraged by the ongoing progress with 314.

314 預計將成為市面上首個針對濕性 AMD 的基因療法。並且，根據我們在第 1/2A 階段試驗中所看到的令人印象深刻的安全性和耐用性，它將提供引人注目的產品特性。在本次試驗中，314 實現了治療負擔的顯著減輕，並且在四年內持續維持治療效果。總體而言，我們對 314 的持續進展感到鼓舞。

I'd like to particularly highlight the differentiated safety profile observed in our in-office suprachoroidal program. This is particularly notable in the setting of short course seven-week prophylactic c steroid eye drops, a significantly shorter regimen than those used in other gene therapy trials. This continues to support the potential of 314 as a meaningful treatment option for patients and physicians.

我想特別強調我們在辦公室脈絡膜上腔靜脈計畫中觀察到的差異化安全性。這在為期七週的短期預防性 c 類固醇眼藥水治療中尤其明顯，該治療方案比其他基因治療試驗中使用的治療方案要短得多。這繼續支持了 314 作為患者和醫生有意義的治療選擇的潛力。

Finally, turning to our MPS program. It's an incredibly exciting time for Regenxbio in the Hunter syndrome community with the recent submission of our BLA for RGX-121. This filing is supported by data from a campsite trial, which met its primary pivotal endpoint with high statistical significance.

最後，談談我們的 MPS 計劃。對於亨特症候群社群的 Regenxbio 來說，這是一個無比令人興奮的時刻，我們最近提交了 RGX-121 的 BLA。此項申請得到了露營地試驗數據的支持，該試驗達到了其主要關鍵終點，具有很高的統計意義。

In addition, we previously reported that 80% of pivotal dose patients either discontinued enzyme replacement therapy or remain treatment naive, along with evidence of neurodevelopment improvement sustained through four years post-dosing.

此外，我們先前報告稱，80% 的關鍵劑量患者要么停止酶替代療法，要么保持未接受治療，同時有證據表明，神經發育改善在服藥後四年內持續存在。

121 represents a potential significant advancement, not only improving patient outcomes, but also improving the daily lives of patients and families. As a one-time gene therapy, 121 has the potential to achieve these benefits while also reducing the treatment burden and the significant amount of time families spend getting weekly enzyme replacement therapy. We look forward to an anticipated FDA approval decision in the second half of 2025.

121 代表著潛在的重大進步，不僅可以改善患者的治療效果，還可以改善患者和家人的日常生活。作為一次性基因療法，121 有可能實現這些益處，同時還可以減少治療負擔和家庭每週進行酵素替代療法所花費的大量時間。我們期待 FDA 在 2025 年下半年做出批准決定。

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

總而言之，我們在所有專案的數據更新和試驗進展方面都取得了重大進展。我要感謝所有參與和支持這些試驗的病人、家屬、臨床醫生和病人權益代表。

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. Regenxbio ended the quarter on March 31, 2025, with cash, cash equivalent and marketable securities of $272 million compared to $245 million as of December 31, 2024.

謝謝你，史蒂夫。Regenxbio 於 2025 年 3 月 31 日結束本季度，現金、現金等價物和有價證券為 2.72 億美元，而截至 2024 年 12 月 31 日為 2.45 億美元。

The increase was primarily driven by the $110 million upfront payment received under the Nippon Shinyaku collaboration and was partially offset by cash used to fund the operating activities during the first quarter of 2025.

這一增長主要得益於與日本新藥合作項目收到的 1.1 億美元預付款，但被 2025 年第一季用於資助經營活動的現金部分抵消。

R&D expenses were $53 million for the quarter ended March 31, 2025, compared to $54.8 million for the quarter ended March 31, 2024. The decrease was primarily due to clinical trial expenses for RGX-314 and RGX-202. We expect the balancing cash, cash equivalent and marketable securities of $272 million as of March 31, 2025, to fund our operations into the second half of 2026. This cash runway guidance is based on the company's current operational plans and excludes the impact of any future potential royalty income associated with RGX-121.

截至 2025 年 3 月 31 日的季度，研發費用為 5,300 萬美元，而截至 2024 年 3 月 31 日的季度為 5,480 萬美元。下降的主要原因是 RGX-314 和 RGX-202 的臨床試驗費用。我們預計，截至 2025 年 3 月 31 日的現金、現金等價物和有價證券餘額為 2.72 億美元，將為我們 2026 年下半年的營運提供資金。此現金流指引是基於公司目前的營運計劃，不包括與 RGX-121 相關的任何未來潛在特許權使用費收入的影響。

If we include additional non-dive financing, we expect the cash runway to potentially extend well beyond 2026. For instance, some examples of our non-diluted financing options include development and sales milestone, reversion of our royalty income and the potential sale of our Priority Review Voucher or RGX-121, if approved, which has recently sold for at least $150 million. Collectively, we have many non-dilutive financing optionalities that could extend our cash runway well beyond the second half of 2026.

如果我們納入額外的非潛水融資，我們預計現金流量可能會延長至 2026 年以後。例如，我們的非稀釋融資選擇的一些例子包括開發和銷售里程碑、特許權使用費收入的回歸以及我們的優先審查券或 RGX-121 的潛在出售（如果獲得批准），該券最近以至少 1.5 億美元的價格售出。總的來說，我們擁有許多非稀釋性融資選擇，可以將我們的現金流延長至 2026 年下半年以後。

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

說完，我轉身回撥給 Curran，告訴他最後的想法。

Thanks, Mitch. As you heard today, there's tremendous momentum and strong execution across our pipeline to advance our programs towards key milestones.

謝謝，米奇。正如大家今天所聽到的，我們的整個專案流程都擁有巨大的動力和強大的執行力，可以推動我們的專案朝著關鍵的里程碑邁進。

To recap, we have submitted our first BLA and our partnership with Nippon Shinyaku for our MPS programs is off to a strong start. We look forward to a potential FDA approval of RGX-121 this year. The pivotal study of RGX 202 is moving rapidly, and we believe it remains well positioned to potentially serve as the next and preferred gene therapy in Duchenne.

總而言之，我們已經提交了第一份 BLA，並且我們與 Nippon Shinyaku 在 MPS 專案上的合作取得了良好的開端。我們期待 FDA 今年批准 RGX-121。RGX 202 的關鍵研究正在快速進展，我們相信它仍有可能成為杜氏肌肉營養不良症的下一個首選基因療法。

We are planning for success and we will initiate commercial supply manufacturing in the coming months in anticipation of a 2027 commercial launch. We also plan to share updated functional data in the first half of this year. And with enrollment more than halfway through, we expect to complete enrollment of the pivotal study this year and share topline data in the first half of 2026.

我們正在為成功做準備，並將在未來幾個月啟動商業供應製造，以期在 2027 年實現商業發布。我們也計劃在今年上半年分享更新的功能數據。目前招募工作已過半，我們預計今年將完成關鍵研究的招募工作，並在 2026 年上半年分享主要數據。

Our partnership with AbbVie is advancing towards multiple large global commercial opportunities. We expect to complete enrollment of two global pivotal trials for sub-retinal wet AMD and are working with AbbVie on a pivotal study in diabetic retinopathy in 2025.

我們與 AbbVie 的合作正朝著多個大型全球商業機會邁進。我們預計將完成兩項針對視網膜下濕性 AMD 的全球關鍵試驗的招募，並將與 AbbVie 合作在 2025 年開展一項針對糖尿病視網膜病變的關鍵研究。

As we lead the way in AAV gene therapy, our team is looking forward to presenting at ASGCT this week. Our presentations in New Orleans highlight our in-house and end capabilities and deep translational expertise. Presentations will include pre-clinical research supporting the novel construct of RGX-202, including the C-terminal domain, capsid discovery research and the RGX-202 manufacturing process development enabling industry-leading purity levels in Duchenne gene therapy.

由於我們在 AAV 基因治療方面處於領先地位，我們的團隊期待本週在 ASGCT 上進行展示。我們在新奧爾良的演示突出了我們的內部和終端能力以及深厚的翻譯專業知識。演示內容將包括支持 RGX-202 新型構造的臨床前研究，包括 C 端結構域、衣殼發現研究和 RGX-202 製造工藝開發，從而實現杜氏基因治療的行業領先純度水平。

We are in a very unique position in our industry. Each of our assets represent one-time treatments with the potential to transform the trajectory and management of disease for patients in need of new and better options. And are demonstrating beneficial differentiation against standard-of-care and available treatments. And we have a balance sheet that enables us to better navigate the current macro environment and execute against our near-term and exciting milestones.

我們在業界處於非常獨特的地位。我們的每項資產都代表一次性治療，有可能為需要新的和更好的選擇的患者的疾病軌跡和管理改變。並且顯示出與標準護理和現有治療方法相比的有益差異。我們擁有資產負債表，可以讓我們更好地駕馭當前的宏觀環境，並實現我們近期令人興奮的里程碑。

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

最後，感謝大家今天抽出時間。我將把電話轉交給提問者。操作員？

(Operator Instructions) Mani Foroohar, Leerink Partners.

（操作員指示）Mani Foroohar，Leerink Partners。

Hey, guys. Thanks for taking the call. I've got two quick ones. I think first is around timing for the Hunter BLA. You mentioned this month, you had a couple of people who've reached out around timing, and I admit to doing this math myself, with 60 days marched out from March 13 should be right around now. Is that math too close or we think about it wrong? I think there's a little bit of sensitivity around any hypothetical FDA delay or is it just we're not taking into account federal holidays, and then I have a follow up.

嘿，大家好。謝謝您接聽電話。我有兩個快速的。我認為首先是關於 Hunter BLA 的時間表。您提到這個月，有幾個人就時間問題與您聯繫，我承認我自己也做過計算，從 3 月 13 日開始算起還有 60 天，現在應該差不多了。這個數學計算是否太接近了，或者我們的想法是否錯誤？我認為任何假設的 FDA 延遲都會有點敏感，或者只是我們沒有考慮到聯邦假日，然後我會跟進。

Hi, Mani, thanks for the call and the question. Yeah, we're certainly pointing towards imminent in terms of timing around the BLA acceptance. I think we feel really good about where the review stands. We've been getting regular interactions on a few areas, the information requests that normally come in as part of the review. And also, we do orientation meetings early on regarding the submission and the BLA contents. All of that is pretty much business normal. We haven't gotten any questions that would lead us to believe otherwise. And so I think, you'll expect to hear from us soon about hopefully an acceptance.

你好，Mani，謝謝你的來電和提問。是的，就 BLA 接受的時間而言，我們當然是迫在眉睫的。我認為我們對審查結果感到非常滿意。我們在一些領域一直保持著定期互動，這些資訊請求通常作為審查的一部分提出。此外，我們也會提前召開有關提交和 BLA 內容的指導會議。所有這些都是正常的商業行為。我們還沒有收到任何讓我們產生其他想法的問題。所以我想，您很快就會收到我們的回复，希望您能接受這個邀請。

Great. And moving on to something a little more substantive. Obviously, you and others have watched closely as your competitor Sarepta has had some stumbles both commercially and from a regulatory perspective, and there have been changes at the helm of CBAR, which have driven a lot of debate around the space. I'm not the first or the second or 1,000th to ask that question.

偉大的。接下來討論一些更實質的事情。顯然，您和其他人一直密切關注著您的競爭對手 Sarepta 在商業和監管方面遇到的一些挫折，而且 CBAR 的領導層也發生了變化，這引發了該領域的許多爭論。我不是第一個、第二個或第一千個問這個問題的人。

How do you think about the bar for approvability in DMD on an accelerated basis expectations around biomarkers/biomarker data versus functional data? Like where is that conversation and how it evolved with the additional input of what we've seen from Sarepta as well as any potential changes at the helm of CBAR.

您如何看待 DMD 中對生物標記/生物標記數據與功能數據的加速批准標準？例如那次談話進行到哪裡了，以及隨著我們從 Sarepta 看到的額外輸入以及 CBAR 掌舵者的任何潛在變化，它是如何發展的。

Yeah, thanks. I think, from the very beginning on the program, we've pointed towards accelerated approval pathway. Those were discussions we had with the FDA in our end of Phase 2 meeting which were very positive and productive. Our intention from the beginning has been to provide functional corollary, if you will, to microdystrophin as part of the filing and review process.

是的，謝謝。我認為，從該計劃一開始，我們就已指明了加速審批途徑。這些都是我們在第二階段會議結束時與 FDA 進行的討論，非常積極且富有成效。如果你願意的話，從一開始我們的意圖就是在備案和審查過程中為微肌營養不良蛋白提供功能推論。

And so we feel really good about our data, the strength of the data in terms of safety profile and initial functional data that we provided. We really look forward to additional functional updates first half of this year to continue that story. And I think we've seen nothing but continued and maybe increased opportunity for us given the benefit to risk ratio we think we're developing and the existence of what we think will be a very sizable prevalent market upon potential approval in 2027.

因此，我們對我們的數據感到非常滿意，就安全性概況和我們提供的初始功能數據而言，數據的強度也非常高。我們非常期待今年上半年有更多的功能更新來延續這個故事。我認為，鑑於我們正在開發的收益風險比，以及我們認為在 2027 年獲得批准後將形成一個非常龐大的流行市場，我們看到的機會持續增加。

So I think our conviction and our opportunity only continues to increase as the program evolves. And I think, in terms of how FDA would view that, I think, certainly, Dr. McCarry provided good context on rare disease development and the support for programs like ours where I think we can provide benefit to patients.

因此我認為，隨著計劃的發展，我們的信念和機會只會不斷增加。我認為，就 FDA 如何看待這一點而言，McCarry 博士確實為罕見疾病的發展提供了良好的背景信息，並且為像我們這樣的項目提供了支持，我認為我們可以為患者帶來益處。

Great, thanks for that clarity, guys.

太好了，謝謝大家的澄清。

Thanks.

謝謝。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

Thank you for taking my questions. I will follow Mani's questions. I will also ask a few more. So giving reason a lot of the safety event, so I will ask very specific questions like, do you expect any changes from the FDA regarding requirement of the safety profiles? And also, for your pivotal study, any changes in terms of the enrollment speed and the patient type?

感謝您回答我的問題。我將關注 Mani 的問題。我還會再問幾個。因此，給出許多安全事件的理由，所以我會問非常具體的問題，例如，您是否預計 FDA 對安全性要求會做出任何改變？另外，對於您的關鍵研究，入組速度和患者類型方面有任何變化嗎？

And my second question, lastly, after recent appointment of a new CBAR director, and do you expect any changes on your accelerated approval path that was previously aligned with the FDA?

最後，我的第二個問題是，在最近任命了一位新的 CBAR 主任之後，您是否預計之前與 FDA 保持一致的加速審批路徑會發生任何變化？

I think I'll take the last one. I think it's very early to project any potential changes and accelerated approval, but we certainly don't see any signs of that today. Our program in terms of enrollment is absolutely on track with how we projected it. We feel highly confident that we will enroll the study this year, the pivotal study of n=30. We'll continue to do enrollment throughout the remainder of the year as well to support our confirmatory study as well.

我想我會選擇最後一個。我認為現在預測任何潛在的變化和加速批准還為時過早，但我們今天肯定沒有看到任何跡象。我們的招生計劃完全按照我們預期的方式進行。我們非常有信心今年能夠進行這項涉及 n=30 的關鍵研究。我們也將在今年剩餘時間內繼續進行招生工作，以支持我們的驗證性研究。

And I think from the beginning of the program, I've been pointing towards, during the time of submission and review, having substantial functional data to accompany that. So I think I don't see anything emerging in some of the dialogue that we've heard from FDA that's contrary to that approach, so I think our plan is unaltered at this point regarding that.

我認為從專案一開始，我就一直強調，在提交和審查期間，要有大量的功能數據來配合。因此，我認為，我們從 FDA 聽到的一些對話中沒有看到任何與這種方法相反的內容，所以我認為我們目前的計劃沒有改變。

I do think that the strong functional data we reported in November, coupled with the safety profile to date that we've been able to portray in our earnings and press releases really points towards a potential improvement in benefit to risk for Duchenne patients, and we think that will be something that will be interesting to the review team as we complete our filing next year.

我確實認為，我們在 11 月報告的強勁功能數據，加上迄今為止我們在收益和新聞稿中所描述的安全性概況，確實表明杜氏肌肉營養不良症患者的風險收益可能會有所改善，我們認為這將是審查團隊在明年完成申報時感興趣的事情。

I do think that this points towards our immune suppression regimen, which is, I think, innovative in the sense of proactively addressing known SAE types for Duchenne patients treated with high dose AAV. I think looking at that approach today is directly in line with potentially better outcomes for patients is what we've seen so far in terms of not just the experience during treatment, but then the post-treatment monitoring.

我確實認為這指向了我們的免疫抑制方案，我認為該方案在主動解決已知的使用高劑量 AAV 治療的杜氏肌肉營養不良症患者的 SAE 類型方面具有創新性。我認為，從今天的角度來看，這種方法與患者可能獲得的更好的治療結果直接相關，這不僅是在治療期間的體驗方面，而且在治療後的監測方面也是我們目前所看到的。

And maybe I'll let Steve elaborate a bit on that from the clinical perspective.

也許我會讓史蒂夫從臨床角度詳細說明這一點。

Hi, Gena. Thanks for the question. It is certainly an area of high interest in Duchenne community given the recent death, unfortunately, with the (inaudible) program. I'd say the overarching aspect is that I think you've heard and seen, and we certainly have seen this both the MDA and in our subsequent one on one discussions is this just brightens the spotlight on safety. So I think even before this event, safety is king. And I think that's why a lot of the points that Curran mentioned are only giving greater comfort to our investigators and the patient families that they speak to about the differentiated aspects of our program.

你好，吉娜。謝謝你的提問。鑑於最近該（聽不清楚）計畫不幸發生死亡事件，這無疑是杜氏肌肉營養不良症社群高度關注的領域。我想說，總體而言，我認為你已經聽到和看到了，我們當然已經在 MDA 中看到了這一點，並且在我們隨後的一對一討論中，這只是更加關注安全問題。所以我認為即使在這次事件發生之前，安全就是最重要的。我認為這就是為什麼 Curran 提到的許多觀點只會讓我們的研究人員和他們所談論的有關我們計劃的差異化方面的患者家屬感到更加安心。

So I think this is why we designed the construct that we did. This is why, over the years, we've advanced and we're very proud of our high purity level with the highest full to empty capsid ratio in the field, and also the robust immune modulation regimen that Curran mentioned. So I think those factors are giving us and the community comfort, and that's why we're absolutely on track with our recruitment.

所以我認為這就是我們設計該結構的原因。這就是為什麼多年來我們不斷進步，並為我們的高純度水平和該領域最高的滿空衣殼比率以及 Curran 提到的強大的免疫調節方案感到非常自豪。所以我認為這些因素為我們和社區帶來了安慰，這也是為什麼我們的招募工作完全按照計劃進行。

Thank you.

謝謝。

I think I'd also point to the imminent review and outcome of the hopeful acceptance of the 121 program. I think that'll be sort of an early data point on accelerated approval, as you know the Hunter program is following an accelerated approval pathway. In that case, we had a pre-BLA meeting that was also supportive for that program. So assuming that we conclude with an acceptance of that BLA in the near term, I think that'll be a first data point to support that, that pathway is still viable and an active process in FDA.

我想我還要指出即將進行的審查以及對 121 計劃充滿希望的接受結果。我認為這將是加速審批的早期數據點，正如你所知，亨特計劃正在遵循加速審批途徑。在這種情況下，我們召開了 BLA 前會議，也支持該計劃。因此，假設我們在短期內接受該 BLA，我認為這將是支持這一點的第一個數據點，該途徑仍然可行並且是 FDA 中的活躍過程。

Judah Frommer, Morgan Stanely.

摩根士丹利的 Judah Frommer。

Yeah, hi, guys. Congrats on the progress. Thanks for taking the questions. First, I was hoping we could get a little incremental color on the planning process along with AbbVie for the diabetic retinopathy Phase 3 trial. Any updated thinking on timing or potential impacts, the probability of recognizing that milestone? And then separately, just more broadly on interactions with FDA given how many programs you have that you are interacting with them on? Any changes recently you'd point to or is it sort of business as usual and contact with the same individuals as you'd anticipate? Thank you.

是的，大家好。恭喜你取得進展。感謝您回答這些問題。首先，我希望我們能夠與 AbbVie 一起對糖尿病視網膜病變 3 期試驗的規劃過程獲得一些進展。對於時間安排或潛在影響以及實現這一里程碑的可能性，您有什麼最新的想法嗎？然後單獨談談與 FDA 的更廣泛的互動，考慮到您與 FDA 互動的項目數量？您最近有什麼變化嗎？還是一切如常，如您所料，還是和原來的人保持聯繫？謝謝。

Thanks. Yeah, I think I can probably comment on the second question first, which is we are actually having a pretty significant number of interactions with FDA both on submissions that have already been filed and information requests that are being provided.

謝謝。是的，我想我可以先評論一下第二個問題，那就是我們實際上與 FDA 進行了相當多的互動，包括已經提交的申請和正在提供的資訊請求。

The only way I can really characterize it right now is that it is very much business normal. So without getting into detail on the type -- the details of information requests, none of them are really questioning the broader strategy of the program or the clinical data that was provided. It's more customary questions about the CMC process, etc.

我現在唯一能真正描述它的方式是，這非常正常。因此，無需詳細了解資訊請求的類型和細節，他們都沒有真正質疑該計劃的更廣泛策略或所提供的臨床數據。這是關於 CMC 製程等較常見的問題。

So I think I just would characterize it as business normal. The review teams seem to be quite intact in terms of good continuity with the teams that we met with last year. And like I said, with the Hunter program, we're going to have a very near-term outcome in terms of BLA acceptance, we hope, which will confirm that we're on track for a late fall potential approval.

所以我認為我只是將其描述為正常的商業行為。與我們去年會面的團隊相比，這些審查團隊似乎保持了良好的連續性。正如我所說的，透過 Hunter 計劃，我們希望能夠在 BLA 接受方面取得一個非常短期的成果，這將證實我們預計在秋末獲得潛在批准。

On DR, we are continuing to collect the final feedback that as we pointed to early in the year. AbbVie and we have obtained feedback from US, EU, Japan, regulatory agencies. As you know, in DR, there's choices to be made in terms of end points that have already been established, two steps worsening, two steps improvement. So all of those are being considered as part of developing a final pivotal protocol. And once that's complete, we'll begin site activation, etc. We're still pointing towards first patient dose this year, and we'll be more specific on timing as we get near that event.

關於 DR，我們正在繼續收集年初指出的最終回饋。AbbVie 和我們已經獲得了美國、歐盟、日本監管機構的回饋。如您所知，在 DR 中，需要根據已經確定的終點做出選擇，兩步惡化，兩步改善。因此，所有這些都被視為制定最終關鍵協議的一部分。一旦完成，我們將開始站點啟動等。我們仍然計劃今年為第一批患者提供劑量，隨著事件的臨近，我們將更具體地確定時間。

Ellie Merle, UBS.

瑞銀的艾莉·梅爾（Ellie Merle）。

Hi, guys, this is [Tejas] on for Ellie. I guess just some of the incremental updates we can expect this year in DMD. So you mentioned some additional functional data in one each. Am I correct in assuming that's not at ASGCT? And then is there an arena you'd expect to present that at or should we expect a press release of that data?

大家好，我是 [Tejas]，為 Ellie 主持。我想，這些只是我們今年在 DMD 中可以期待的一些增量更新。所以你在每個中都提到了一些額外的功能數據。我是否可以正確地假設那不在 ASGCT 呢？那麼您是否期望在某個場合展示這些數據，或者我們是否應該期待發布有關這些數據的新聞稿？

And then, you also mentioned starting commercial supply manufacturing later this year. It's supply but is it the same process that you're using in your current trials? And will you be able to provide any color on the CMC process with the FDA or any other meetings you might have on the statistical plan throughout the year? Thank you.

然後，您還提到今年稍後開始商業供應製造。這是供應，但它與您目前試驗中使用的過程相同嗎？您能否提供有關 FDA 的 CMC 流程或全年統計計劃方面的任何其他會議的詳細資訊？謝謝。

Sure. Let me start with the CMC process. So yes, we did point to initiation of commercial production this year. So that's a combined effort, number one. The batches that are produced as part of our first commercial production are also batches that will be submitted as part of the plan mid-2026 BLA. And the process that's being -- will be validated as part of that exercise is the exact same process that's in the clinic today. So no changes anticipated to what patients are being dosed currently in our pivotal program as we move to our commercial process.

當然。讓我先從 CMC 流程開始。是的，我們確實指出今年將開始商業化生產。所以，首先，這是共同的努力。作為我們首次商業生產的一部分而生產的批次也是將作為 2026 年中期 BLA 計劃的一部分提交的批次。作為該練習的一部分，正在驗證的過程與當今臨床中的過程完全相同。因此，隨著我們進入商業化流程，預計我們關鍵項目中目前患者的用藥劑量不會改變。

And as we pointed out, we have a a quite mature CMC approach off our platform, NAVXpress process, which we think FDA will really regard highly. In fact, it's the same process that they've reviewed in other programs and actually toured on site as part of FDA training in the last couple of years. So we feel really strongly that we have a very low risk approach to CMC with a process that produces very high purity capsid, which FDA has been cleared as an expectation. And not any significant changes required to get to commercial in which we can produce 2,500 doses per year.

正如我們所指出的，我們的平台 NAVXpress 流程擁有相當成熟的 CMC 方法，我們認為 FDA 會高度重視它。事實上，這與他們在其他項目中審查過的過程相同，並且在過去幾年中作為 FDA 培訓的一部分進行了現場參觀。因此，我們堅信，我們採用的 CMC 方法風險非常低，能夠生產出純度非常高的衣殼，這一點已獲得 FDA 的批准。並且不需要進行任何重大改變就可以實現商業化，我們每年可以生產 2,500 劑。

Back to the first question. In terms of data, so we expect -- so there's only I think six weeks left in the first half '25. I think you could expect likely a press release around the additional data. And the focus of the data will really be on expanding the dose level 2 patients that were treated in the Phase 1/2 study out to 12 months. So a larger number of patients out that far and showing all the same functional outcomes that we did in November.

回到第一個問題。就數據而言，我們預計——我認為 2025 年上半年只剩下六週了。我認為您可能會期待有關附加數據的新聞稿。數據的重點實際上將放在將第 1/2 階段研究中接受治療的劑量水平 2 患者延長至 12 個月。因此，到目前為止，有大量患者表現出與我們 11 月相同的功能結果。

So just trying to enlarge the data set there and as well update on any biomarker data that may have come in recently. But it really will be focusing on the pivotal level dose and how those patients are doing. And I think just in general the feedback we're getting from sites and from investigators is really positive right now.

因此，只是嘗試擴大那裡的數據集，並更新最近可能出現的任何生物標記數據。但它真正關注的是關鍵劑量水平以及患者的狀況。我認為，總體而言，我們現在從網站和調查人員那裡得到的回饋都非常積極。

Thanks. And just quickly, those pivotal dose patients in the Phase 1/2 will be included in the pivotal data set for filing in mid-26. Correct?

謝謝。很快，1/2 期的關鍵劑量患者將被納入 26 年中期提交的關鍵資料集。正確的？

Yeah, all patients that qualify for the inclusion criteria of the pivotal program would be included in the pivotal. data set.

是的，所有符合關鍵計畫納入標準的患者都將納入關鍵計畫。數據集。

Thanks.

謝謝。

Annabel Samimy, Stifel.

安娜貝爾·薩米 (Annabel Samimy)，Stifel。

Hi, thanks for taking my question. Just to go back to regulatory bodies and changes there, just given the FDA's focus on safety with gene therapy, I guess we've been talking a lot about the rare conditions and how the carrier is very focused on the rare diseases and life-threatening conditions. Does that make it potentially harder for gene therapy and non-life threatening conditions like retinal disease, for example? And are there any issues related to that for the DR indication, any delays there?

你好，謝謝你回答我的問題。回到監管機構及其變化，鑑於 FDA 對基因治療安全性的關注，我想我們已經討論了很多關於罕見疾病以及載體如何關注罕見疾病和危及生命的疾病。這是否會使基因治療和非危及生命的疾病（例如視網膜疾病）變得更加困難？與此相關的 DR 指示是否有任何問題，是否有延遲？

And then, one last question regarding regulatory bodies. RFK Junior just asked the HHS Committee on Genetic Screening, so can you tell us how this might affect not MPS but rather DMD and trying to get into the younger population and whether there are any complications there. Thanks.

然後，最後一個問題是關於監管機構的。RFK Junior 剛剛向 HHS 基因篩檢委員會詢問，您能否告訴我們這會如何影響 DMD 而不是 MPS，並試圖進入年輕人群，以及是否存在任何併發症。謝謝。

Sure, I can take the second one, but I think maybe first, I'll let Steve comment on whether or not we're seeing any change in FDA stance regarding retinal programs, but I think the -- what I would convey before Steve speaks is I think we know that safety in non-rare is an absolute focus. And I think that's probably the incredible promise of the sub-retinal program. The safety profile in the data that we've seen today looks excellent.

當然，我可以回答第二個問題，但我想也許首先，我會讓史蒂夫評論一下我們是否看到 FDA 對視網膜項目的立場有任何變化，但我認為 - 在史蒂夫發言之前我想傳達的是，我認為我們知道非罕見病的安全性是絕對的重點。我認為這可能是視網膜下注射計畫的驚人前景。我們今天看到的數據的安全性看起來非常好。

Maybe I'll let Steve elaborate on that a little bit.

也許我應該讓史蒂夫稍微詳細說明這一點。

Sure. Hi, Annabel. So on retinal, I think another broad aspect is that's not an accelerated approval pathway, so there's not a request for greater flexibility. So fortunately, there, we know the regulatory route and we're already executing on that, for example, in sub-retinal. And we have a plan to do the same in suprachoroidal.

當然。你好，安娜貝爾。因此，關於視網膜，我認為另一個廣泛的方面是，這不是一個加速審批途徑，因此沒有要求更大的靈活性。幸運的是，我們知道監管途徑，我們已經在執行，例如在視網膜下。我們計劃在脈絡膜上腔做同樣的事情。

On the safety side, just as Curran mentioned, we feel very good about the safety package that we'll have for sub-retinol and suprachoroidal. And that's because we've intentionally selected routes of administration for 314 that are compartmentalized, and that decrease the risk of the types of safety findings, specifically inflammation that have really hounded other routes of administration like intravitreal.

在安全性方面，正如 Curran 所提到的，我們對視黃醇下和脈絡膜上腔的安全方案感到非常滿意。這是因為我們有意選擇了 314 的分隔給藥途徑，從而降低了出現安全問題的風險，特別是炎症，而炎症一直困擾著玻璃體內注射等其他給藥途徑。

So we feel very well set up not only in our rare programs, but also in the common retina indications that we're looking at when it comes to safety.

因此，我們不僅在罕見項目方面做得非常好，而且在安全方面，我們在關注的常見視網膜指徵方面也做得非常好。

And, Annabel, to come back to the question on genetic screening, newborn screening, we're working closely with the MPS society and with Duchenne advocacy groups on newborn screening, and their approach largely is at a state level to advance and increase the number of states that provide that. So I think it would be ideal if all entities were working together in concert on that, but that doesn't mean that if one group is not supporting it, the others won't be able to fill that gap and move forward. So we see that as a priority in rare disease and it's something we'll work with the advocacy groups to support.

安娜貝爾，回到基因篩檢、新生兒篩檢的問題上，我們正​​在與 MPS 協會和杜氏肌肉營養不良症倡導團體密切合作，開展新生兒篩檢，他們的方法主要是在州一級推進並增加提供此類服務的州的數量。因此，我認為，如果所有實體都齊心協力，那將是理想的，但這並不意味著，如果一個團體不支持，其他團體就無法填補這一空白並向前邁進。因此，我們認為這是罕見疾病領域的優先事項，我們將與倡導團體合作提供支援。

Okay, and if I can just ask one quick follow-up to be clear on the last question about ASGCT. You will not be presenting functional data there, correct? I understood it to be a DR within the next six weeks. Is my understanding correct?

好的，我可以快速問一個問題來澄清關於 ASGCT 的最後一個問題。您不會在那裡展示功能數據，對嗎？我理解這是未來六週內的一個 DR。我的理解正確嗎？

Yeah, it will not be at ASGCT, so no need to book your flight. We'll definitely likely provide that as a press release in the near term.

是的，它不會在 ASGCT，所以無需預訂航班。我們肯定會在近期以新聞稿的形式發布這一消息。

Okay. Great, thank you.

好的。太好了，謝謝。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

Hey, guys. Thanks for taking our questions. This is Matthew on for Alec. Maybe just double clicking on a previous point. Has there been any change in baseline characteristics, patient age, etc, that you've seen for the DMD trial? And then, maybe second, what's the percentage purity for your preps that you're comfortable with or looking for, sort of, as you're moving forward with manufacturing?

嘿，大家好。感謝您回答我們的問題。這是馬修 (Matthew) 代替亞歷克 (Alec)。也許只需雙擊前一個點即可。在 DMD 試驗中，您是否發現基線特徵、患者年齡等有任何變化？然後，也許第二點，隨著製造的推進，您對製劑的純度百分比是多少，或者您期望的純度百分比是多少？

Yeah, we actually -- that is something that will be shown at ASGCT. We have a presentation on the CMC process that I think we'll get quite a nice level of detail for people to see we're very proud of it. But the purity level for the product is 80% or greater. And I think just as important, consistency between batches, which we've heard others struggle with, is also highly consistent between batches. So that's what we would point to.

是的，實際上我們會在 ASGCT 上展示一些東西。我們有一個關於 CMC 流程的演示，我認為我們會向人們提供相當詳細的信息，讓我們對此感到非常自豪。但產品的純度達80%或更高。我認為同樣重要的是，批次之間的一致性（我們聽說其他人對此感到困擾）也高度一致。這就是我們要指出的。

In terms of I think your question was around enrollment of the pivotal study, we're quite pleased so far with not just the pace of enrollment but the breadth of patient ages that are enrolling in the study to date. So as we look at it today and as we look out towards the remainder of the year, we feel like we will have a very balanced number of patients across the ages to support a broad label when we file.

就我認為您的問題而言，是關於關鍵研究的招募，到目前為止，我們不僅為招募速度感到滿意，而且迄今為止參加研究的患者年齡範圍也令人十分滿意。因此，當我們回顧今天的情況並展望今年剩餘時間時，我們感覺我們將擁有非常均衡的各年齡層患者數量，以支持我們提交的廣泛標籤。

Luca Issi, RBC Capital Markets.

伊西 (Luca Issi)，加拿大皇家銀行資本市場部。

Oh, great. Hi, team. This is Shelby on for Luca, and thanks for taking the question. Maybe on wet AMD sub-retinal. You've shown recently that the fellow eye can be treated safely, confirming that the eye is somewhat immune privileged. Are you planning on filing that data? And is your initial label going to reflect bilateral dosing? Any color there, much appreciated. Thanks.

噢，太好了。大家好。我是謝爾比 (Shelby)，代表盧卡 (Luca) 發言，感謝您回答這個問題。可能是視網膜下濕性 AMD。您最近表明，對側眼睛可以安全治療，證實了該眼睛具有一定的免疫特權。您打算歸檔這些資料嗎？您的初始標籤是否會反映雙側劑量？無論什麼顏色，都非常感激。謝謝。

Hi, Shelby, nice to see you. Steve is part of the Joint Development Committee that plans, sort of, a strategy around the filings, maybe he can comment on that question.

你好，謝爾比，很高興見到你。史蒂夫是聯合發展委員會的成員，該委員會負責制定有關申請的策略，也許他可以對這個問題發表評論。

Sure. Hi, Shelby. Great question. This is actually something that we prospectively addressed even as early as our end of Phase 2 meeting because it's very relevant in wet AMD where most patients do have bilateral disease. So it would be very advantageous if both eyes ultimately could be treated. And we, again, always saw that our [CABR] routes of administration where you would expect less immune response would be more amenable to being able to treat both eyes.

當然。你好，謝爾比。好問題。實際上，早在第二階段會議結束時，我們就已經開始著手解決這個問題，因為它與濕性 AMD 非常相關，因為大多數患者都有雙側疾病。因此，如果雙眼最終都能得到治療，那將是非常有利的。而且，我們再次發現，我們的 [CABR] 給藥途徑預期免疫反應較少，更適合治療雙眼。

And that's why we prospectively addressed this explicitly with the FDA and that's what led to our fellow eye study. And as you mentioned, we're seeing -- that we're in a good position as far as fellow eye. So yes, I confirm that that's certainly our intent, that this is certainly part of any package that would go in that would inform clinicians on being able to treat both eyes.

這就是為什麼我們要向 FDA 明確提出這個問題，並由此開展我們的眼科研究。正如您所提到的，我們看到，就其他人而言，我們處於有利地位。是的，我確認這確實是我們的意圖，這確實是任何可以告知臨床醫生如何治療雙眼的方案的一部分。

Paul Choi, Goldman Sachs.

高盛的保羅·崔（Paul Choi）。

Hi, thank you. Good afternoon and thanks for taking our questions. I want to ask first on RGX-121 at Hunter's with the imminent -- your expectations of an imminent acceptance of your BLA. I just want to see if you're also potentially assuming an ad-com given that this could potentially be the first approved gene therapy for the condition.

你好，謝謝。下午好，感謝您回答我們的問題。我想先就 Hunter 的 RGX-121 詢問您對即將接受 BLA 的預期。我只是想看看您是否也可能假設一個廣告，因為這可能是第一個獲批的針對該病症的基因療法。

And then, second, regarding the RGX-202 Duchenne Phase 1/2 functional data update that you referenced earlier, can you maybe just comment on, again, how many patients we'd expect to follow up for and how current the the data cut might potentially be for that functional update that that's coming up soon? Thank you.

其次，關於您之前提到的 RGX-202 Duchenne 1/2 期功能數據更新，您能否再次評論一下，我們預計會跟進多少名患者，以及即將發布的功能更新的數據截斷可能有多新？謝謝。

Sure, yeah, I can comment on the first question around Adcom. We are planning as if we need an ad-com. From an internal perspective, we have a team working on being ready for that should it be requested. We don't have a final answer from FDA as to whether one is required yet. Initial discussions were hinting towards no. But we're waiting to get confirmation one way or another through the review process, but we will be prepared if one is needed ahead of time.

當然，是的，我可以對 Adcom 的第一個問題發表評論。我們正在計劃，就好像我們需要一個廣告公司一樣。從內部角度來看，我們有一個團隊隨時準備好應對此類請求。我們尚未從 FDA 得到是否需要該標準的最終答案。最初的討論暗示答案是否定的。但我們正在等待透過審查程序以某種方式獲得確認，但如果需要提前確認，我們會做好準備。

For 202, in terms of just coming back to -- Oh, I'm sorry, yeah, about the the next upcoming functional release. So we are planning on enlarging the data set to four possibly five patients dosed at DL2 as part of the functional update. Not all of them may be out to 12 months, but minimally they would be out to nine months and so. That's still something that we're pulling together, QC-ing the data and looking forward to getting out before the first half of the year.

對於 202，就剛剛回顧而言 - 哦，對不起，是的，關於即將發布的下一個功能版本。因此，作為功能更新的一部分，我們計劃將資料集擴大到四名或五名接受 DL2 治療的患者。雖然並非所有的期限都會達到 12 個月，但至少也會達到 9 個月左右。我們仍在匯總這些信息，對數據進行品質控制，並希望在今年上半年之前將其發布。

Okay. Great. Thank you for that.

好的。偉大的。謝謝你。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

Hi, this is Luke on for Brian. Thanks for the question. Sorry if this was already asked, but on the 202 commercial build out, has the team set a goal for the quantity of product that you expect to be available by the time of a potential launch?

大家好，我是盧克，為布萊恩報道。謝謝你的提問。抱歉，如果這個問題已經被問過了，但是在 202 商業建設中，團隊是否設定了您預計在潛在發佈時可用的產品數量目標？

It's a great question. We're actually going through that process of review now as we evaluate our commercial strategy in total. I would just remind you that in the course of one year, we can produce 2,500 doses. And so we'll come to a point as we get closer to a review of the BLA to talk a little bit more about how many doses we would have at launch.

這是一個很好的問題。實際上，我們現在正在進行審查過程，以全面評估我們的商業策略。我只是想提醒大家，一年內我們可以生產 2,500 劑。因此，當我們接近審查 BLA 時，我們會進一步討論我們在推出時會有多少劑量。

We would certainly want to be in a position to quickly address the prevalent market with a significant number of doses. We would estimate the prevalent market could be in the ambulatory side of the market, something in the order of 5,000 to 7,000 patients, and we would want to be prepared to quickly be able to address that market. So we'll get more specific on the number of doses available at launch, but we're in a unique position to be able to build a significant amount of inventory ahead of 2027.

我們當然希望能夠快速地滿足市場上大量劑量的需求。我們估計，主要的市場可能是門診市場，大約有 5,000 到 7,000 名患者，我們希望做好準備，能夠迅速滿足該市場的需求。因此，我們將更具體地說明推出時可用的劑量數量，但我們處於獨特的地位，能夠在 2027 年之前建立大量庫存。

Great, thanks. And just one more quick one on your 314 wet AMD studies, has the availability of PAVBLU impacted enrollment pace at all or are these generally unique groups of patients and indication?

太好了，謝謝。關於您的 314 項濕性 AMD 研究，我再快速問一下，PAVBLU 的可用性是否影響了入組速度，或者這些通常是獨特的患者群體和適應症？

Thanks for that one. I think I'll ask Steve. He's a little closer to that particular question.

謝謝你。我想我會問史蒂夫。他對這個特定問題比較了解。

Yeah. Across different agents that are out there, either on the market or investigational, we over time haven't seen any of that impact or recruitment, so we're at a good clip, so that's why we keep reiterating our guidance. So we're excited to finish enrollment this year, excited to have top-line results next year.

是的。對於市場上現有的或正在研究的不同藥物，我們隨著時間的推移並沒有看到任何影響或招募，所以我們處於良好的狀態，這就是我們不斷重申我們的指導的原因。因此，我們很高興今年能夠完成招生，也很高興明年能取得優異的成績。

Awesome. Thank you.

驚人的。謝謝。

Sean McCutcheon, Raymond James.

肖恩麥卡琴、雷蒙德詹姆斯。

Hey, guys. Thanks for taking the question. Just to build on wet AMD, can you provide some detail on how you're thinking about the suprachoroidal opportunity? Obviously, we're looking forward to the start of the NPDR Phase 3, but I think we're all curious on the dose necessary to move forward in wet AMD. And how you're thinking about that value proposition on the fields of sub-retinal? Thanks.

嘿，大家好。感謝您回答這個問題。僅就濕性 AMD 而言，您能否提供一些有關您如何看待脈絡膜上腔機會的詳細資訊？顯然，我們期待 NPDR 第 3 階段的開始，但我認為我們都對治療濕性 AMD 所需的劑量感到好奇。您如何看待視網膜下領域的價值主張？謝謝。

Hi, I think I'll let Steve answer that question.

嗨，我想我會讓史蒂夫來回答這個問題。

Sure, so this is obviously a massive market. So if you look at the retinal space driven by the anti-VEGF target mechanism and treatments thereof, we're at [18 billion] and continuing to grow. So I think there's a lot of opportunity across the VEGF-driven retinopathies. We and AbbVie are advancing as we were just saying on the sub-retinal global program or wet AMD, so we're obviously excited about sub-retinal delivery for that indication.

當然，這顯然是一個巨大的市場。因此，如果你觀察到由抗 VEGF 標靶機制及其治療所驅動的視網膜空間，你會發現它已經達到了 [180 億]，並且還在繼續增長。所以我認為 VEGF 驅動的視網膜病變有許多治療機會。正如我們剛才所說，我們和 AbbVie 正在推進視網膜下全球計畫或濕性 AMD，因此我們顯然對視網膜下給藥治療該適應症感到興奮。

We do see increased optionality and opportunities with the one-time in office suprachoroidal, and that's why we both are advancing in that space.

我們確實看到了一次性診室脈絡膜上腔靜脈導管的可選性和機會的增加，這就是我們都在該領域取得進展的原因。

I think DR in particular is compelling when you consider the reality that patients with non-proliferative diabetic retinopathy who have not developed the sight-threatening complications, like DME and like proliferative disease, that these patients really are going to need an in-office one-time treatment option that even if you have greater durability agents, if you're going to need repeat injections indefinitely for the rest of your life, that's not going to be a very compelling opportunity. So that's why we and AbbVie are so excited about the opportunity of a one-time in-office treatment to really address that unmet need of DR.

我認為 DR 尤其引人注目，因為考慮到患有非增生性糖尿病視網膜病變且尚未出現危及視力的併發症（如 DME 和增生性疾病）的患者確實需要在診所接受一次性治療，即使您擁有更持久的藥物，但如果您需要在餘生中無限期地重複注射，那麼這不是一個非常引人注目的機會。這就是為什麼我們和 AbbVie 對一次性診所治療的機會如此興奮，以真正解決 DR 的未滿足需求。

Thank you.

謝謝。

(Operator Instructions) Yi Chen, HC Wainwright Company.

(操作員指示) Yi Chen，HC Wainwright 公司。

Hi, there. Good afternoon. This is [Eduardo] on for you. Just a quick question if you had any thoughts on the recent announcement about -- this morning, I think or last night about potential pricing on branded drugs, that you feel like that's going to have a significant impact on your ability to price, your gene therapies across these indications?

你好呀。午安.這是[Eduardo]為您帶來的。只是一個簡單的問題，如果您對最近宣布的問題——我想是今天早上或昨晚關於品牌藥物的潛在定價——有什麼看法，您認為這會對您針對這些適應症的基因療法的定價能力產生重大影響嗎？

Yeah, I think it's early to tell. I think if you look at some of the commentary by John Crowley from BIO or the Alliance for Regenerative Medicine, I think that initially the impact to cell and gene therapy in general might be less than could be for broader branded therapies.

是的，我認為現在下結論還為時過早。我認為，如果你看一下 BIO 或再生醫學聯盟的 John Crowley 的一些評論，我認為最初對細胞和基因療法的影響可能小於對更廣泛的品牌療法的影響。

It's too early to tell, so I think we, from our perspective, there's no immediate impact to anything that we're doing, but certainly something we have to pay attention to and sort of the macro environment as we get closer to an approval.

現在下結論還為時過早，所以我認為，從我們的角度來看，我們正在做的任何事情都不會受到直接影響，但隨著我們越來越接近批准，我們肯定需要關註一些宏觀環境。

Got it. Thanks. That's really helpful.

知道了。謝謝。這真的很有幫助。

Thank you. I'm showing no further questions at this time. This does conclude the questionand-answer session, and you may now disconnect. Everyone, enjoy the rest of your day.

謝謝。我目前沒有其他問題。問答環節到此結束，您現在可以斷開連線了。大家，享受今天剩下的時間。