Regenxbio Inc (RGNX) 2024 Q3 法說會逐字稿

Welcome, everyone, to the Q3 2024 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 2024 年第三季 REGENXBIO 收益電話會議。（操作員指示）請注意，今天的會議正在錄音。此時。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 third quarter ended September 30, 2024. The press release is available on our website at www.regenxbio.com. Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans.

下午好，感謝您今天加入我們。今天下午早些時候，REGENXBIO 發布了截至 2024 年 9 月 30 日第三季的財務和營運表現。新聞稿可在我們的網站 www.regenxbio.com 上查閱。今天的電話會議將包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。

The forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasts and can be identified by words such as expect plan will may anticipate, believe, should, intend, and other words of similar meaning.

前瞻性陳述受風險和不確定性的影響，可能導致實際結果與預測不同，並可以透過​​預期、計劃、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。

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, 2023, and comparable risk factors sections of REGENXBIO's quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission and available on the SEC's website.

此類前瞻性陳述並非對未來績效的保證，並涉及一定的風險和不確定性。這些風險在 REGENXBIO 截至 2023 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 表季度報告中的可比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, November 6, 2024. And we take 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均截至本次電話會議召開之日，即 2024 年 11 月 6 日。而且，我們不承擔因新資訊、未來事件或其他情況而更新在本次電話會議中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形式財務資訊都是初步的，並不報告專案財務狀況或公司經營成果。實際結果可能存在重大差異。

I will now turn the call over to Curren Simpson, President and CEO of REGENXBIO.

現在我將電話轉給 REGENXBIO 總裁兼執行長 Curren Simpson。

Thank you, Patrick, and thank you, everyone, for joining us today. On the call with me today are Mitchell Chan, our newly appointed Chief Financial Officer; and Dr. Steve Pakola, our Chief Medical Officer. I will begin by recapping our business highlights and key upcoming milestones. Steve will then provide an update on our clinical programs before passing to Mitch, who will review our financial results for the quarter. I'll then provide some closing remarks and open the call for Q&A.

謝謝帕特里克，也謝謝大家今天的參與。今天與我一起通話的還有我們新任命的財務長 Mitchell Chan；以及我們的首席醫療官 Steve Pakola 博士。我將首先回顧我們的業務亮點和即將到來的關鍵里程碑。然後，史蒂夫將提供有關我們臨床項目的最新情況，然後轉交給米奇，米奇將審查我們本季度的財務結果。然後我將做一些結束語並開始問答環節。

This is a very exciting time for REGENXBIO as we continue to generate positive clinical data and prepare to commercialize multiple potential first and best in class gene therapies. We've had another productive quarter and have several important milestones expected before year-end. These include the first functional data from our Duchenne program, which is expected in the coming weeks.

對於 REGENXBIO 來說，這是一個非常令人興奮的時刻，因為我們將繼續產生積極的臨床數據並準備將多種潛在的首創和一流的基因療法商業化。我們度過了又一個富有成效的季度，預計年底前將實現幾個重要的里程碑。其中包括我們杜氏肌肉營養不良症計畫的首批功能數據，預計將在未來幾週內發布。

We're also very excited to have initiated the BLA filing in MPS 2, also known as Hunter syndrome and for the end-of-Phase 2 meeting coming up later this month for RGX-314 in diabetic retinopathy, which we'll refer to as DR.

我們也非常高興地啟動了 MPS 2（又稱亨特氏症候群）的 BLA 申請，並且將於本月稍後召開 RGX-314 治療糖尿病視網膜病變（我們稱之為 DR）的 2 期結束會議。

Recall that this meeting was accelerated from first quarter 2025 to fourth quarter 2024 by AbbVie, our partner for the retinal franchise. You'll hear more from Steve about the great progress being made in [314], including continued progress in DR and Wet AMD.

回想一下，我們的視網膜特許經營夥伴 AbbVie 將這次會議從 2025 年第一季提前到了 2024 年第四季。您將會從史蒂夫那裡了解更多有關 [314] 所取得的巨大進展，包括在 DR 和濕性 AMD 方面的持續進展。

Diving into our programs, I'll start with RGX-202, our next-generation potential best-in-class gene therapy for Duchenne. We expect to initiate the pivotal phase of the ongoing AFFINITY DUCHENNE study imminently. Once that has begun, RGX-202 will be the only next generation gene therapy in Phase 3 study for this devastating disease.

深入研究我們的項目，我將從 RGX-202 開始，這是我們針對杜氏肌肉營養不良症的下一代潛在最佳基因療法。我們期望即將啟動正在進行的 AFFINITY DUCHENNE 研究的關鍵階段。一旦開始，RGX-202 將成為這種毀滅性疾病的 III 期研究中唯一的下一代基因療法。

We've had productive discussions with the FDA as we have advanced RGX-202 to pivotal phase and have confirmed that the accelerated approval pathway remains open to us. RGX-202 continues to demonstrate the potential to drive increased benefit to patients compared to available therapies, and our clinical data to date are checking all the boxes to demonstrate this differentiation. Thus far, we have seen a favorable safety profile, no SAEs and consistent robust microdystrophin expression.

在將 RGX-202 推進至關鍵階段的過程中，我們與 FDA 進行了富有成效的討論，並確認加速審批途徑仍然對我們開放。與現有療法相比，RGX-202 繼續展現出為患者帶來更多益處的潛力，而我們迄今為止的臨床數據已完全證實了這種差異化。到目前為止，我們已經看到了良好的安全性，沒有SAE和一致強勁的微肌營養不良蛋白表現。

The last box to check is functional outcomes, which, as I mentioned, we will begin sharing this month. Earlier this year, we shared encouraging early functional observations from clinic and caregiver videos. We're excited to share the first functional results, which will include data on some of these patients from dose level 1 and 2 at later, more meaningful time points very soon.

最後要檢查的是功能結果，正如我所提到的，我們將在本月開始分享。今年早些時候，我們分享了來自診所和護理人員影片的令人鼓舞的早期功能觀察。我們很高興能夠分享第一批功能性結果，其中將包括部分患者在劑量水平 1 和 2 下的後續更有意義的時間點的數據。

Another key element of differentiation, we believe, is the fact that we are commercial ready when it comes to manufacturing RGX-202 today, which can be a key driver of an effective commercial launch. Our manufacturing uses a modern suspension-based bioreactor process that is highly productive. Needless to say, we are very excited about RGX-202 as a potential best-in-class gene therapy in Duchenne and continue to aggressively accelerate development to potentially be second to market.

我們認為，差異化的另一個關鍵因素是，我們在目前生產 RGX-202 方面已經做好了商業化的準備，這可能是有效商業發布的關鍵驅動因素。我們的生產採用現代懸浮生物反應器工藝，生產效率極高。毋庸置疑，我們對 RGX-202 作為杜氏肌肉營養不良症領域潛在的最佳基因療法感到非常興奮，並將繼續積極加速開發，以期成為市場上第二個這樣的療法。

Let's now pivot to RGX-121, the program furthest in development. RGX-121 is on track to be the first gene therapy and one-time treatment for MPS 2, or Hunter Syndrome. Today, as we announced, the first module of a rolling BLA for RGX-121 was submitted as planned in Q3 2024, and we expect to complete filing the BLA in the first quarter of 2025.

現在讓我們來討論一下 RGX-121，這是開發最深入的專案。RGX-121 有望成為首個針對 MPS 2（即亨特氏症候群）的基因療法和一次性治療方法。今天，正如我們宣布的那樣，RGX-121 滾動 BLA 的第一個模組已按計劃於 2024 年第三季度提交，我們預計將在 2025 年第一季完成提交 BLA。

Like Duchenne, MPS 2 occurs in boys and is a progressive devastating disorder. Also like Duchenne, we are pursuing a BLA under the accelerated approval pathway and would receive a PRV upon regulatory approval. The initiation of our BLA marks a major milestone for patients for whom there is currently no cure and no treatments to address the significant neurocognitive decline.

與杜氏肌肉營養不良症類似，MPS 2 也發生在男孩身上，是一種進行性毀滅性疾病。此外，與杜氏肌肉營養不良症一樣，我們正在加速審批途徑下尋求 BLA，並將在獲得監管部門批准後獲得 PRV。我們的 BLA 的啟動對那些目前無法治癒且沒有治療方法來解決嚴重神經認知能力下降的患者來說是一個重要的里程碑。

It also marks a major milestone for REGENXBIO as RGX-121 represents both our first potential commercial product and an opportunity to build commercial infrastructure that will benefit our other programs, those in line for commercialization. Lastly, I will make a few comments on 314, the late-stage retinal franchise we are developing with our partner, AbbVie.

這也標誌著 REGENXBIO 的一個重要里程碑，因為 RGX-121 既代表了我們的第一個潛在商業產品，也代表了建立商業基礎設施的機會，這將使我們的其他專案（即將商業化的專案）受益。最後，我將對我們與合作夥伴 AbbVie 共同開發的後期視網膜特許經營權 314 發表一些評論。

As you'll hear from Steve, we continue making great strides across multiple indications. The recent positive news from our fellow eye study offer an opportunity to expand the addressable patient population for 314 in wet AMD, where the majority of patients eventually develop bilateral disease.

正如您將從史蒂夫那裡聽到的那樣，我們繼續在多個適應症方面取得長足進步。我們眼科研究的最新積極消息為擴大 314 例濕性 AMD 患者群體提供了機會，大多數患者最終都會發展為雙側疾病。

And the data and progress we are making in DR, another large commercial opportunity is highly encouraging. In DR, we expect to initiate a global pivotal trial in the first half of 2025. We are excited that we will soon have both programs, wet AMD and DR in Phase 3 studies. We look forward to continuing to work with AbbVie to tap the potential of 314 to prevent vision loss for millions worldwide.

我們在 DR 領域取得的數據和進展，另一個巨大的商業機會，非常令人鼓舞。在 DR 方面，我們預計在 2025 年上半年啟動一項全球關鍵試驗。我們很高興很快將同時進行濕性 AMD 和 DR 兩個專案的第 3 階段研究。我們期待繼續與 AbbVie 合作，挖掘 314 的潛力，防止全球數百萬人喪失視力。

In summary, we are making excellent progress and look forward to sharing several important catalysts in the coming weeks, and continue to see clinical results supporting the immense potential of these novel programs. With that, I would like now to turn the call over to Steve for an update on our clinical programs. Steve?

總而言之，我們正在取得顯著進展，並期待在未來幾週分享幾個重要的催化劑，並繼續看到支持這些新計畫巨大潛力的臨床結果。說完這些，我現在想將電話轉給史蒂夫，讓他介紹我們的臨床計畫的最新進展。史蒂夫？

Thank you, Curran. I'll start with RGX-202, a potential one-time gene therapy for the treatment of Duchenne. Today, we announced exciting progress in the Phase 1/2 AFFINITY DUCHENNE trial. This is a multicenter dose escalation and dose expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time dose of RGX-202 in patients with Duchenne aged 1 to 11.

謝謝你，Curran。我首先要介紹的是 RGX-202，它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。今天，我們宣布了第 1/2 期 AFFINITY DUCHENNE 試驗的令人興奮。這是一項多中心劑量遞增和劑量擴展臨床研究，旨在評估RGX-202一次性劑量對1至11歲杜氏肌肉營養不良症患者的安全性、耐受性和臨床療效。

As we approach pivotal phase, I'm pleased to share that we have dosed the last patient in the expansion cohort of dose level 2, which is the pivotal dose level. On the continued strength of our data, we expanded the AFFINITY DUCHENNE trial to include a new cohort of patients aged 1 to 3 years.

當我們接近關鍵階段時，我很高興地告訴大家，我們已經對劑量水平 2 的擴展隊列中的最後一名患者進行了給藥，這是關鍵劑量水平。基於我們數據的持續強化，我們擴大了 AFFINITY DUCHENNE 試驗，將新一批 1 至 3 歲患者納入其中。

And today, we announced that the first patient has been dosed in this cohort. The 1 to 3 age group represents a significant portion of the prevalent population, yet this group has no access to approved or investigational gene therapy.

今天，我們宣布該組第一位患者已接受治療。1 至 3 歲年齡組佔總人口的很大一部分，但這群體無法獲得已批准或正在研究的基因治療。

In the US, REGENXBIO is the only company recruiting patients under four years old. We look forward to initiating the pivotal study and sharing the first functional data from this program in the coming weeks. Now on to updates from our retina franchise, RGX-314, which is being developed in collaboration with AbbVie to treat Wet AMD and DR via subretinal and suprachoroidal routes of administration.

在美國，REGENXBIO是唯一招募四歲以下患者的公司。我們期待在未來幾週內啟動這項關鍵研究並分享該計劃的首批功能數據。現在介紹我們的視網膜特許經營權 RGX-314 的最新進展，該產品正在與 AbbVie 合作開發，透過視網膜下和脈絡膜上腔給藥途徑治療濕性 AMD 和 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 if not treated appropriately. It is a leading cause of blindness in working age adults. As we've shared with our partner, AbbVie, we have accelerated the end-of-Phase 2 meeting with the FDA to this quarter.

我將從 314 開始介紹 DR，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，如果不及時治療，會導致視力喪失，最終導致失明。它是工作年齡成年人失明的主要原因。正如我們與合作夥伴 AbbVie 分享的那樣，我們已將與 FDA 的第二階段結束會議提前至本季。

We look forward to completing this meeting and sharing our proposed pivotal trial program soon. As you may recall, we previously expanded the broad multi-indication global potential of 314 by initiating a new cohort in the ALTITUDE trial for patients with diabetic macular edema or DME, a vision-threatening complication of diabetic eye disease that impacts more than 30 million patients worldwide.

我們期待著盡快完成這次會議並分享我們提出的關鍵試驗方案。您可能還記得，我們​​之前曾在 ALTITUDE 試驗中啟動了針對糖尿病性黃斑水腫 (DME) 患者的新隊列，從而擴大了 314 種廣泛的多適應症全球潛力，DME 是一種威脅視力的糖尿病眼病併發症，影響著全球超過 3000 萬患者。

314 is already well positioned to potentially become the standard of care to treat diabetic retinopathy. Broadening the ALTITUDE trial to include patients with DME further expands the global potential to benefit more patients.

314 已經有望成為治療糖尿病視網膜病變的標準治療方法。將 ALTITUDE 試驗擴大到包括 DME 患者，進一步擴大了全球惠及更多患者的潛力。

In Wet AMD, we are evaluating 314 via two different routes of delivery, subretinal and suprachoroidal. Within subretinal, we have two ongoing pivotal trials, ATMOSPHERE and ASCENT, in North America, Europe and Japan. These trials continue to progress well and global regulatory submissions remain planned for the first half of 2026.

對於濕性 AMD，我們透過兩種不同的給藥途徑（視網膜下和脈絡膜上腔）對 314 進行評估。在視網膜下，我們在北美、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，全球監管提交仍計劃於 2026 年上半年進行。

We recently announced exciting news from our Phase 2 fellow eye study of subretinal 314 in patients with bilateral Wet AMD. This study is the first of its kind, evaluating a potential one-time gene therapy as a treatment for patients with bilateral disease.

我們最近宣布了一項令人興奮的消息，該消息來自我們針對雙側濕性 AMD 患者進行視網膜下 314 治療的 2 期眼科研究。這項研究是同類研究中的首例，評估了一次性基因療法對雙側疾病患者的潛在治療效果。

The positive data demonstrated 314 at the same dose being evaluated in the pivotal program was well tolerated with no cases of intraocular inflammation. We also see continued impressive efficacy, including a 97% reduction in treatment burden at nine months.

正面的數據顯示，在關鍵項目中評估的相同劑量的 314 耐受性良好，沒有出現眼內發炎病例。我們也看到了持續令人印象深刻的療效，包括九個月時治療負擔減少了 97%。

100% of patients needed zero or one supplemental injections, and 78% of patients were completely injection-free while demonstrating sustained vision stability and disease control. Notably, these positive results were seen in difficult to treat patients with high treatment burden prior to 314.

100% 的患者不需要或只需要一次補充注射，78% 的患者完全無需注射，同時保持視力穩定和疾病控制。值得注意的是，這些正面成果是在314之前在難以治療且治療負擔高的患者身上見到的。

The fellow eye study supports plans for a label inclusive of bilateral use, representing a meaningful option for the significant number of patients with Wet AMD in both eyes. Overall, we continue to be encouraged by the progress on our retinal programs.

這項眼科研究支持制定包含雙眼使用的標籤計劃，這對大量雙眼患有濕性 AMD 的患者來說是一個有意義的選擇。總體而言，我們的視網膜計畫所取得的進展繼續令我們感到鼓舞。

I'd like to particularly highlight the safety profile observed, including in our suprachoroidal programs. We are confident in advancing the pivotal phase because of this safety profile, particularly in the setting of short course seven-week prophylactic steroid eye drops, a significantly shorter regimen than those used in other gene therapy trials.

我想特別強調觀察到的安全性概況，包括在我們的脈絡膜上腔計畫中。由於這種安全性，我們對推進關鍵階段充滿信心，特別是在短期七週預防性類固醇眼藥水的環境下，這比其他基因治療試驗中使用的方案要短得多。

In more than 180 patients treated in office, we're seeing a differentiated safety profile, representing a meaningful potential treatment option for patients and physicians. Finally, on RGX-121 being developed for the treatment of MPS 2. Earlier this year, we announced that the CAMPSIITE pivotal trial met its primary endpoint with high statistical significance.

在接受治療的 180 多名患者中，我們看到了差異化的安全性概況，這為患者和醫生提供了有意義的潛在治療選擇。最後，RGX-121 正在開發用於治療 MPS 2。今年早些時候，我們宣布 CAMPSIITE 關鍵試驗達到了主要終點，且具有高度的統計意義。

Patients treated with RGX-121 achieved decreased CSF levels of heparan sulfate D2S6, a key biomarker of brain disease activity to below maximum attenuated disease levels. Our BLA uses the accelerated approval pathway and is based on D2S6 as a surrogate endpoint reasonably likely to predict clinical benefit.

接受 RGX-121 治療的患者腦脊髓液中的硫酸肝素 D2S6（腦疾病活動性的關鍵生物標記）水準降低至低於最大減毒疾病水準。我們的 BLA 採用加速審批途徑，並以 D2S6 作為合理預測臨床益處的替代終點。

We also previously reported that 80% of patients who received the pivotal dose discontinued enzyme replacement therapy or remained treatment naive. This is a meaningful update for patients and families whose only option today is weekly enzyme replacement therapy that does not address the neurocognitive decline of this disease.

我們之前也報告過，80%接受關鍵劑量的患者停止了酵素替代療法或仍未接受治療。對於患者和家屬來說，這是一個很有意義的更新，因為他們目前唯一的選擇是每週進行一次酵素替代療法，但這種療法無法解決這種疾病的神經認知能力下降問題。

RGX-121 is well positioned to be the first gene therapy and one-time treatment for Hunter syndrome that can directly address neurocognitive decline.

RGX-121 有望成為首個能夠直接解決神經認知能力下降問題的亨特氏症候群基因療法和一次性治療方法。

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

總而言之，我們在所有專案的數據更新和試驗進展方面繼續取得重大進展。最後，我要感謝參與和支持所有這些試驗的患者、家屬、臨床醫生和患者權益代表。

And with that, I'll turn the call over to 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 September 30, 2024, with cash, cash equivalents and marketable securities of $279 million compared to $314 million as of December 31, 2023. The decrease was primarily driven by cash used to fund operating activities during the nine months ended September 30, 2024, partially offset by $131 million in net proceeds received from an upsized public offering of common stock and prefunded warrants completed in March 2024.

謝謝你，史蒂夫。REGENXBIO 於 2024 年 9 月 30 日結束本季度，現金、現金等價物和有價證券為 2.79 億美元，而截至 2023 年 12 月 31 日為 3.14 億美元。下降的主要原因是截至 2024 年 9 月 30 日的九個月內用於資助經營活動的現金，部分被 2024 年 3 月完成的普通股擴大公開發行和預付認股權證所獲得的 1.31 億美元淨收益所抵消。

R&D expenses were $54 million for the third quarter of 2024 compared to $58 million for the third quarter of 2023. The decrease was primarily due to decreases in headcount and preclinical activities. REGENXBIO expects its cash balance, cash equivalents and marketable securities of $279 million as of September 30, 2024, to fund its operation into 2026.

2024 年第三季的研發費用為 5,400 萬美元，而 2023 年第三季的研發費用為 5,800 萬美元。下降主要是由於員工數量和臨床前活動的減少。REGENXBIO 預計截至 2024 年 9 月 30 日的現金餘額、現金等價物和有價證券為 2.79 億美元，可為其 2026 年的營運提供資金。

This cash runway guidance is based on the company's current operational plans and excludes the impact of any payment that may be received from AbbVie upon the achievement of development or commercial milestones under our RGX-314 collaboration.

此現金運行指引是基於公司目前的營運計劃，不包括我們在 RGX-314 合作下實現開發或商業里程碑後可能從 AbbVie 收到的任何付款的影響。

Additionally, our runway guidance excludes the potential monetization of a Priority Review Voucher that may be received for RGX-121.

此外，我們的運作指導不包括 RGX-121 可能收到的優先審查券的潛在貨幣化。

With that, I'll turn the call back to Curren.

說完這些，我會把電話轉回給 Curren。

Thanks, Mitch. As you heard, we are making significant progress advancing each of our late-stage programs in multiple large commercial opportunities and are heading into year-end with strong momentum and multiple de-risking events.

謝謝，米奇。正如您所聽到的，我們在多個大型商業機會的各個後期項目中都取得了重大進展，並且正以強勁的發展勢頭和多項降低風險的事件迎接年底的到來。

To recap, in Q4 of this year, we plan on initiating a pivotal trial for RGX-202 under an accelerated approval pathway and look forward to sharing both the trial design and our first functional data. Also in Q4 of this year, we will complete our end-of-Phase 2 meeting with the FDA for 314 in DR. This will pave the way for initiation of the first global pivotal trial in the first half of 2025 and trigger milestones in our collaboration with AbbVie.

總結一下，今年第四季度，我們計劃按照加速審批途徑啟動 RGX-202 的關鍵試驗，並期待分享試驗設計和我們的第一批功能數據。此外，今年第四季度，我們將與 FDA 完成 DR 314 的 II 期結束會議。這將為 2025 年上半年啟動首個全球關鍵試驗鋪平道路，並標誌著我們與 AbbVie 的合作邁上里程碑。

Finally, we will continue the progress of the rolling BLA submission for RGX-121 and expect to complete the submission in Q1 2025. If approved, this would become the first approved gene therapy for treatment of Hunter syndrome, a very meaningful development for the patients and families living with this devastating disorder, and would receive a PRV upon regulatory approval.

最後，我們將繼續推進 RGX-121 的滾動 BLA 提交，並預計在 2025 年第一季完成提交。如果獲得批准，這將成為首個獲批的治療亨特氏症候群的基因療法，這對於患有這種毀滅性疾病的患者及其家庭來說是一個非常有意義的進展，並且將在監管部門批准後獲得 PRV。

It has been a turning point year for us. As we look toward the next 12 months and beyond, we see a company that is positioned to deliver on multiple late-stage opportunities. The groundbreaking science that underlies our programs is demonstrating differentiation against standard of care and available treatments.

對我們來說這是轉捩點的一年。展望未來 12 個月及以後，我們看到一家公司已準備好抓住多個後期機會。我們計畫所依賴的突破性科學正在展示與標準護理和現有治療方法的差異。

Each of our programs 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 we look forward to continued momentum in achieving the important milestones in the last quarter of this year and beyond.

我們的每個項目都代表一次性治療，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。我們期待繼續保持良好勢頭，在今年最後一個季度及以後實現重要的里程碑。

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

最後，感謝大家今天的寶貴時間。我將把電話轉交給提問者。操作員？

(Operator Instructions)

（操作員指令）

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

Hi, it's Tony on for Gena. Quick questions on DMD. For the age one-year-old to three-year-old cohort, are there any concerns there on durability given the patients are still young and may be growing additional muscle tissue? And then if you all do receive biomarker accelerated approval, would multiple time points be needed for a biopsy versus just one-time point at three months? And then also for the data at year-end, how should we think about the magnitude of functional change?

大家好，我是 Tony，代替 Gena。關於 DMD 的快速問題。對於一歲至三歲的兒童群體，考慮到患者還很年輕並且可能正在長出額外的肌肉組織，是否存在耐用性方面的擔憂？那麼，如果你們都獲得了生物標記加速批准，那麼活檢是否需要多個時間點，而不是僅僅在三個月時進行一次？那麼對於年末的數據，我們該如何考慮功能變化的幅度呢？

Hi, Tony, Steve here. Thanks for the questions. So I'll start with your question about the one and three-year- olds. Yes, it is a topic that comes up in the field of how young can you go in terms of the issue of replicating cells. We're actually quite excited about the opportunity here when we think of [AAV8], our vector, because we have a proxy for considering the potential dilution effect of dividing cells and durability because we know AAV8 for liver-directed hemophilia treatment, we actually have durability now out beyond 12 years for a lot of these kids where we see very sustained activity.

嗨，東尼，我是史蒂夫。感謝您的提問。因此，我首先要回答關於一歲和三歲兒童的問題。是的，這是一個在細胞複製問題上可以達到多年輕這個領域出現的主題。當我們想到我們的載體 [AAV8] 時，我們實際上對這裡的機會感到非常興奮，因為我們有一個代理來考慮分裂細胞的潛在稀釋效應和耐用性，因為我們知道 AAV8 用於肝臟定向血友病治療，實際上我們現在可以將這種治療的耐用性超過 12 年，對於許多孩子來說，我們看到了非常持久的活性。

And of course, liver cells divide. So that gives us a lot of confidence here as well. And certainly, there's a major unmet need here because there are no gene therapies currently available for this age group.

當然，肝細胞會分裂。這也給了我們很大的信心。當然，這裡存在著巨大的未滿足需求，因為目前沒有針對該年齡層的基因療法。

Hi, Tony, to your other question around biomarker, we don't have any requests for additional biomarker data beyond what's included in the protocol. So I wouldn't expect anything additional to be requested there. And I think to answer your question about magnitude of effect, certainly, there are benchmarks for what people consider magnitude effect to be adequate for consideration for approval, including the benchmarks we can pull from even Peter Marks assessment of Elevidys.

你好，東尼，關於你關於生物標誌物的另一個問題，除了協議中包含的內容之外，我們沒有要求任何額外的生物標記數據。因此我並不期望那裡會有任何額外的要求。我認為，要回答您關於效應量級的問題，當然，人們認為效應量級足以考慮批准，存在一些基準，包括我們可以從彼得·馬克斯 (Peter Marks) 對 Elevidys 的評估中得出的基準。

And so I think that sets a good precedent for our data that will be coming shortly and how we're thinking about the program. And I think just to reiterate, we're super excited by the biomarker data that we've got in terms of the levels of microdystrophin we're seeing, especially in the eight and older patient population that upfront looks considerably higher than other programs. So thanks for your question.

因此我認為這為我們即將發布的數據以及我們如何思考該計劃樹立了一個良好的先例。我想重申的是，我們對所獲得的生物標記數據感到非常興奮，就我們所看到的微肌營養不良蛋白水平而言，特別是在八歲及以上的患者群體中，其前期水平看起來比其他項目要高得多。感謝您的提問。

Got it. Thanks so much.

知道了。非常感謝。

Vikram Purohit, Morgan Stanley.

摩根士丹利的維克拉姆·普羅希特（Vikram Purohit）。

Hi, everyone. This is Gospel on for Vikram. We have one question on RGX-202. Could you recap for us your latest view on how best to gauge the functional data we are expecting later this month? Thank you.

大家好。這對維克拉姆來說就是福音。我們對 RGX-202 有一個問題。您能否為我們概括一下您對如何最好地評估我們本月稍後預期的功能數據的最新看法？謝謝。

Hi, Gospel, thanks for the question. We're very excited to soon be able to present our functional data. This is something we've been looking forward to. I think we come with the benefit of a lot of precedent and a lot of learnings in the space where we get to look at the totality of the data.

你好，Gospel，謝謝你的提問。我們非常高興很快就能展示我們的功能數據。這是我們一直期盼的事。我認為，我們在查看全部數據方面受益匪淺，並且積累了大量經驗。

So a lot of the usual suspects that you'll be aware of, certainly the timed function tests such as 10-meter walk or run or time to stand, which are measures that we know are valid, clinically meaningful. We'll also look at NSAA, which historically has been looked at.

因此，您會注意到許多常見的測試，當然還有計時功能測試，例如 10 公尺步行或跑步或站立時間，這些測試我們知道是有效的，具有臨床意義。我們也將研究歷史上曾被關注的 NSAA。

And we have the opportunity as well to look at caregiver-reported outcomes. So it's really a unique chance for us to look at a lot of different ways to see how these boys are doing to really assess clinical benefit.

我們也有機會了解護理人員報告的結果。所以，這對我們來說確實是一個獨特的機會，讓我們能夠透過多種不同的方式了解這些男孩的表現，從而真正評估臨床益處。

And Gospel, I would also point to our ability to look at external controls as we think about individual patient data. We can mine pretty substantial databases to look at what the natural history is and expect to include that as part of our analysis. But thanks for the question.

而且，Gospel，我還要指出，當我們考慮個別患者數據時，我們有能力查看外部控制。我們可以挖掘相當豐富的資料庫來了解自然史，並將其作為我們分析的一部分。但感謝您的提問。

Thank you very much.

非常感謝。

Mani Foroohar, Leerink Partners

Leerink Partners 的 Mani Foroohar

Thanks for taking my question. I guess a little more detailed question. So when you think about the data we're going to see from this initial group of patients, is it reasonable to expect that their experience and follow-up and data will be rolled into a larger pool of data collectively for a pivotal data set? Or will a future pivotal data set include being patients recruited in the future, not including these first handful of patients? And I have a quick follow-up.

感謝您回答我的問題。我想這是一個更詳細的問題。因此，當您考慮我們將從這組初始患者中看到的數據時，是否可以合理地預期他們的經驗和後續行動以及數據將被匯總到更大的數據庫以形成關鍵數據集？或者未來的關鍵數據集是否包括未來招募的患者，而不包括這第一批患者？我還有一個快速的跟進。

Thanks for the question, Mani. Yes, we certainly do expect to use data that is being accumulated in our Phase 1/2 study, particularly for patients that were dosed at dose level 2. I'd say most of the functional assessments that we're doing for those patients will be the same as what we're doing in pivotal.

謝謝你的提問，Mani。是的，我們確實希望使用我們在第 1/2 階段研究中累積的數據，特別是針對以劑量水平 2 給藥的患者。我想說，我們對這些患者進行的大部分功能評估與我們在關鍵部位所做的評估相同。

And I think one area I would point out that we're really excited about in terms of transitioning from Phase 1/2 to pivotal is that the process and product quality will be the same through Phase 1/2 development and pivotal development.

我想指出的一點是，在從第 1/2 階段過渡到關鍵階段方面，我們真正感到興奮的一點是，在第 1/2 階段開發和關鍵開發過程中，流程和產品品質將保持不變。

And so if you think back to the [Adcom] for Sarepta, they made a major process change in the middle of their pivotal program. And you could see comparisons of Process A and Process B. We won't have any of that. And I think that will work well in terms of including those patients in our safety database because the product profile is the same throughout the study.

如果你回想一下 Sarepta 的 [Adcom]，你會發現他們在關鍵專案的中期進行了一次重大的流程變更。您可以看到過程 A 和過程 B 的比較。我認為將這些患者納入我們的安全資料庫會很有效，因為整個研究過程中產品概況是相同的。

So we do intend to leverage them as part of that, and that will obviously help us with recruitment, and we will talk further very near term about the details of the pivotal study. I'll turn it over to Steve to comment as well.

因此，我們確實打算利用它們作為其中的一部分，這顯然將有助於我們的招募，我們將在近期進一步討論關鍵研究的細節。我也會將其轉交給史蒂夫進行評論。

Yeah. I just wanted to elaborate on one aspect that further supports the ability to use the patients already dosed in Phase 1/2 is the primary endpoint for accelerated approval is microdystrophin. So it makes perfect sense that the data that we have, particularly with dose level 2, that it's quite natural that we'd be able to use that data in addition to the patients we enroll in the future in the pivotal.

是的。我只是想詳細闡述一個方面，進一步支持使用已在 1/2 期服藥的患者的能力，這是加速批准的主要終點，即微肌營養不良蛋白。因此，我們擁有的數據（尤其是劑量等級 2 的數據）非常合理，很自然地，我們可以將這些數據用於未來在關鍵研究中招募的患者。

That's helpful. I'm going to hop over to ophthalmology for a follow-up if that's okay. You guys have disclosed some detail, including a fairly chunky one-time sizable milestone for achievement of first patient dosed in a pivotal suprachoroidal delivery treatment of DR.

這很有幫助。如果可以的話我將去眼科進行追蹤。你們已經揭露了一些細節，包括一個相當大的一次性里程碑，即在關鍵的脈絡膜上腔給藥治療 DR 中實現首位患者給藥。

Can you walk us through on what time line we might see milestones following your end-of-Phase 2 meeting and how those would be recognized, i.e., how they would flow through the financial statements, when they show up on the balance sheet versus income statement, et cetera, just to clear that up for our own modeling?

您能否向我們介紹第二階段會議結束後我們可能看到的里程碑時間線，以及如何確認這些里程碑，即它們將如何在財務報表中流動，何時出現在資產負債表而不是損益表上，等等，只是為了為我們自己的建模澄清這一點？

Sure, Mani. I'll turn that question over to Mitch.

當然，瑪尼。我將把這個問題轉交給米奇。

Yes. So for modeling purposes, the potential milestone payment could actually show up in the balance sheet. That's where you can actually account for that. And for the P&L, this will be recognized as a one-time non-recurring for obvious reasons, one-time payment there. Hopefully, that helps from that standpoint, Mani.

是的。因此，出於建模目的，潛在的里程碑付款實際上可能會出現在資產負債表中。那您實際上就可以解釋這一點。對於損益表，由於顯而易見的原因，這將被確認為一次性非經常性支出，一次性付款。希望從這個角度來說這能有所幫助，Mani。

So the recognition will be all be recognized in the same quarter as received or is this something that will be recognized ratably over time?

那麼，所有認可都將在收到的同一季度得到認可，還是會隨著時間推移而按比例認可？

No, it's going to be upon receivable.

不，這是應收帳款。

Okay. Thanks guys. I'll hop off. I know you got a lot of analysts waiting in line.

好的。謝謝大家。我就跳下去。我知道有很多分析師在排隊等候。

Annabel Samimy, Stifel.

安娜貝爾·薩米 (Annabel Samimy)，Stifel。

Hi, this is Jack on for Annabel. Thanks for taking our question. So for 202, I believe you've mentioned previously that you might were considering imposing a minimum threshold of microdystrophin expression on your cells in the pivotal trial, even though that might not be something that the agency would necessarily require.

大家好，我是傑克，為您介紹安娜貝爾。感謝您回答我們的問題。因此對於 202，我相信您之前提到過，您可能正在考慮在關鍵試驗中對您的細胞施加微肌營養不良蛋白表達的最低閾值，即使這可能不是該機構必然要求的。

I think the number was something maybe like 10% expression for approval. Is that something that you still feel confident in doing and have you ever discussed that with the FDA?

我認為這個數字可能相當於 10% 的讚同率。您對此仍有信心嗎？

As Curran highlighted, we're going to be coming out with details of our pivotal design in the future in the very near future. What I can say now is that concept of a 10% threshold is something that in the field has roughly been considered something to think about as what would relate potentially to a clinically meaningful amount.

正如 Curran 所強調的，我們將在不久的將來公佈我們關鍵設計的細節。我現在可以說的是，10% 閾值的概念在該領域大致被認為是需要思考的東西，因為它可能與具有臨床意義的量相關。

Fortunately, we're seeing microdystrophin levels that are much higher than that level. So that really gives us a lot of flexibility when we think of designing a study and powering a study. So we look forward to giving more details on that in the coming weeks.

幸運的是，我們看到的微肌營養不良蛋白水平遠高於該水平。因此，當我們考慮設計一項研究並進行研究時，這確實給了我們很大的靈活性。因此，我們期待在未來幾週提供更多詳細資訊。

Got it. And then if I may just ask one more. One of the biggest pushbacks that we hear from investors is not necessarily around 202 microdystrophin expression or safety, but rather just that we have a pretty small sample size to work with at the moment.

知道了。然後我可以再問一個問題。我們從投資者那裡聽到的最大阻力之一不一定是關於 202 微肌營養不良蛋白的表達或安全性，而是我們目前可用的樣本量相當小。

So how meaningful do you think the functional data, the upcoming functional data will be in kind of defining that profile given it's only from a couple of patients or in other words, how well might it translate into a more general population?

那麼，您認為功能數據，即將獲得的功能數據在定義該概況方面有多大意義，考慮到它僅來自幾個患者，或者換句話說，它在多大程度上可以轉化為更普遍的人群？

I think, Jack, that's a good question. And we do have a relatively limited data set. But I think what we're looking for primarily in this data set is conviction that a pivotal trial is highly likely to succeed and that we have a demonstration of efficacy.

傑克，我認為這是一個好問題。但我們的數據集確實相對有限。但我認為，我們在這個資料集中主要尋找的是確信一項關鍵試驗很有可能成功，並且我們已經證明了其功效。

And I think that I would sort of reiterate that the fact that we have a differentiated product, we're almost threefold higher in microdystrophin levels than other programs for patients at a similar age. All of those factors I think will come together even with limited functional data to, I think, especially in the patient community, bring a really strong interest in the program and allow us to enroll quickly.

我想重申的是，我們擁有差異化的產品，我們的微肌營養不良蛋白水平幾乎是同齡患者其他項目的三倍。我認為，即使功能數據有限，所有這些因素都會結合在一起，尤其是在患者群體中，引起人們對該計劃的濃厚興趣，並使我們能夠快速招募。

And so we're really excited about where we are, and I think we're eagerly anticipating being able to share our results just in a few weeks around the functional data.

因此，我們對目前的狀況感到非常興奮，我認為我們熱切期待能夠在幾週內分享有關功能數據的成果。

Great, looking forward to it. Thanks guys.

太棒了，很期待。謝謝大家。

Alec Stranahan, Bank of America

美國銀行亞歷克·斯特拉納漢

Hi, Matthew on for Alec. Thanks for taking our questions. Two quick ones from us. For DMD, are you concerned at all about the durability of impact, especially going into younger patients? And are you at all thinking about redosing? And then for wet AMD, can you provide some color on how you think about the Eylea biosimilars from Amgen and potential market impact?

嗨，馬修代替亞歷克。感謝您回答我們的問題。我們快速說兩句話。對於 DMD，您是否擔心影響的持久性，尤其是對於年輕患者而言？您是否考慮過重新服用？然後對於濕性 AMD，您能否介紹一下您對安進的 Eylea 生物相似藥及其潛在市場影響的看法？

Thanks for the question. So the durability aspect in the younger patients was something we touched on earlier in the call that we have evidence, particularly with our serotype that there is not a dilution of effect over time and that you have good durability even in organs where you have dividing cells.

謝謝你的提問。因此，我們在電話會議早些時候提到了年輕患者的耐久性方面，我們有證據，特別是對於我們的血清型，其效果不會隨著時間的推移而減弱，並且即使在具有分裂細胞的器官中也具有良好的耐久性。

So that's one of the aspects that made us excited to go after this unmet need age group of one to three. So excited that we announced today the dosing of the first patient in that cohort. Redosing, that's something that the field, I think is going to be evaluating over time right now, our focus is on first time treatment with one-time gene therapy for the very large patient population that's out there that isn't going to be able to get treatment for some time even with available treatment options.

所以這是讓我們興奮地去滿足這未滿足需求的 1 至 3 歲年齡組的一個面向。我們今天非常興奮地宣布了該組第一位患者的用藥情況。重複用藥，我認為這個領域現在需要隨著時間的推移進行評估，我們的重點是首次使用一次性基因療法治療非常龐大的患者群體，即使有可用的治療方案，他們在一段時間內也無法得到治療。

We expect to have good durability, as I just mentioned. But certainly, there's the opportunity for us to explore ways that we could go after redosing. Lastly, on Wet AMD, so we're very excited in our pivotal programs with subretinal in collaboration with AbbVie and also in collaboration with AbbVie, the suprachoroidal advancement where, as just discussed, we have diabetic retinopathy that we look forward to finishing our end-of-Phase 2 meeting and being able to advance into pivotal development there. What was the other, if I could ask what was the other aspect about the Wet AMD program?

正如我剛才提到的，我們希望具有良好的耐用性。但可以肯定的是，我們有機會探索重新給藥後可以採取的方法。最後，關於濕性 AMD，我們對與 AbbVie 合作的視網膜下關鍵項目感到非常興奮，同時也對與 AbbVie 合作的脈絡膜上腔進展感到興奮，正如剛才討論的那樣，我們患有糖尿病視網膜病變，我們期待著完成第 2 階段結束會議，並能夠在那裡推進關鍵開發。另外一點是什麼，如果我可以問一下 Wet AMD 計劃的另一個方面是什麼？

Yes. Just how you're thinking about Eylea biosimilars from?

是的。您對於 Eylea 生物相似藥有何看法？

Yeah. So the biosimilar aspect has been something that's been around over time, and we're starting to see more biosimilars come in. We're actually seeing no impact of biosimilars on, for example, some of the branded longer durability products.

是的。生物相似藥已經存在一段時間了，我們也開始看到越來越多的生物相似藥的出現。我們實際上並沒有看到生物相似藥對某些品牌的較長保質期產品產生影響。

So if you think of incremental benefits in terms of durability of high dose Eylea or faricimab, we're not seeing those impacted, which really shows the value proposition that clinicians and patients are seeing. And so we would expect no impact for an even bigger paradigm shift of a one-time treatment that would not only decrease injection burden, but potentially even prevent the need for injection.

因此，如果您考慮高劑量 Eylea 或 faricimab 的持久性方面的增量效益，我們不會看到這些影響，這確實表明了臨床醫生和患者所看到的價值主張。因此，我們預計一次性治療的更大範式轉移不會產生影響，這種治療不僅可以減輕注射負擔，甚至可能避免注射的需要。

Luca Issi, RBC Capital Markets

Luca Issi，加拿大皇家銀行資本市場

Great. Thanks so much for taking my question and congrats on the progress. Maybe, Steve, bigger picture, what was your reaction to the Phase 3 data presented by Pfizer a few weeks back at world? It looks to me that they show pretty impressive evidence of expression there, but still, there was no functional benefit whatsoever there.

偉大的。非常感謝您回答我的問題，並祝賀您的進展。也許，史蒂夫，從更大的角度來看，您對輝瑞幾週前在世界會議上公佈的第三階段數據有何反應？在我看來，它們在那裡表現出了相當令人印象深刻的表達證據，但仍然沒有任何功能上的好處。

So is there a scenario where the FDA here changes the kind of regulatory standard going forward in light of that data and maybe decide to put a little more emphasis on function versus expression here? Again, any thoughts there, much appreciated.

那麼是否存在這樣的情況：FDA 根據這些數據改變未來的監管標準，並決定更加重視功能而不是表達？再次，非常感謝您的任何想法。

And then maybe, Mitch, I believe this is your first time that you're joining the earnings call. Can you just maybe talk about why you decided to join the team as you were doing diligence on REGENXBIO, what do you find particularly attractive about it? Thanks so much.

那麼也許，米奇，我相信這是你第一次參加財報電話會議。您能否談談為什麼在對 REGENXBIO 進行盡職調查時決定加入團隊，您認為它特別有吸引力的地方是什麼？非常感謝。

Thanks, Luca. I'll take the first part before we hand it over to Mitch. So the Pfizer results. So as you mentioned, there's microdystrophin expression, but not a clear signal of efficacy from their trial. As far as we're concerned, this actually is exactly why we right from the beginning of our program focused on designing the best construct that we could.

謝謝，盧卡。在將其交給米奇之前，我將先處理第一部分。輝瑞公司的結果也是如此。正如您所說，有微肌營養不良蛋白的表達，但是試驗中沒有明確的療效訊號。就我們而言，這實際上正是為什麼我們從專案一開始就專注於設計最好的結構。

And part of what that means is reconstituting as closely as we can the native dystrophin molecule in terms of the key functional elements. So that's a key reason why we and our team took the time to develop a second generation construct that, for example, includes the important C terminal domain elements and some other improvements. So really, the overarching aspect is not all constructs are created equal.

這意味著我們要盡可能重建天然肌肉營養不良蛋白分子的關鍵功能元素。這就是我們和我們的團隊花時間開發第二代構造的關鍵原因，例如，其中包括重要的 C 端域元素和一些其他改進。因此，實際上，總體而言，並非所有結構都是平等的。

So the farther you are away from a native dystrophin, the less confidence that you can have that you're going to translate expression into clinical benefit. And the FDA acknowledged that as well in the Adcom for Elevidys, for example, where they raised the importance of CapEx terminal domain elements and the fact that those being absent in some constructs takes away the confidence in terms of the reasonably likely to predict bar.

因此，您距離天然的肌肉營養不良蛋白越遠，您將其表達轉化為臨床益處的信心就越小。例如，FDA 在 Elevidys 的 Adcom 上也承認了這一點，他們提出了 CapEx 終端域元素的重要性，而這些元素在某些結構中缺少的事實會降低對合理預測標準的信心。

So for those reasons, we think the differentiation that we have with our product and how close we are in terms of the key elements preserves our reasonably likely to predict benefit aspect for our program. And certainly, we've seen no change in our discussions with the FDA as recently as our end-of-Phase 2 meeting. So we're aligned on how to proceed with the pivotal program.

因此，基於這些原因，我們認為我們的產品的差異化以及我們在關鍵要素方面的接近程度保留了我們合理地預測計劃收益的可能性。當然，就在最近第二階段結束的會議上，我們與 FDA 的討論沒有任何變化。因此，我們對如何推進這項關鍵計劃的看法是一致的。

And Luca, this is Curran. I guess I would add one thing to Steve's comment -- I mean, if you look at the accelerated approval for Elevidys, they utilized this functional data in that assessment. So it won't surprise us at all that FDA would want to see maybe not as a primary endpoint, but supportive data on the functional side.

盧卡，這是柯倫。我想我要對史蒂夫的評論補充一點——我的意思是，如果你看看 Elevidys 的加速批准，他們在評估中使用了這個功能數據。因此，FDA 也許希望看到的不是主要終點，而是功能上的支持數據，根本不會讓我們感到驚訝。

So we're well prepared to address those questions at the time of filing for accelerated approval, and we're planning for that eventuality. And obviously, I think for we see good uptake now in the market. I think in general, what we are looking for is that with functional data being demonstrated that a lot of patients are going to be interested in our program and certainly around the differentiation aspect given the levels of microdystrophin we are showing. I will turn it over to Mitch.

因此，我們在申請加速批准時已做好充分準備來解決這些問題，並且正在為這種可能性做準備。顯然，我認為我們現在看到市場表現良好。我認為總的來說，我們正在尋找的是，透過證明功能數據，許多患者會對我們的計劃感興趣，考慮到我們所展示的微肌營養不良蛋白的水平，肯定會在分化方面感興趣。我將把它交給米奇。

Yes. Thanks Luca, for the question as well, too. And I must say, I have been here for almost two months. And one of the major reasons why I joined is really the scientific excellence at the company. And during my brief time here, that has translated to be very much true.

是的。我也感謝 Luca 提出這個問題。我必須說，我來這裡已經快兩個月了。我加入的一個主要原因是該公司的科學卓越性。在我在這裡的短暫停留期間，事實證明這一說法完全正確。

And I think the other aspect is over the next, let's call it, 18 months to 24 months, there are potentially several BLAs that could happen at our company. And entering this commercial phase is actually very exciting to say the least.

我認為另一個方面是，在接下來的 18 個月到 24 個月內，我們公司可能會發生幾項 BLA。進入這個商業階段實際上至少可以說是非常令人興奮的。

And these aren't just simple BLAs. These are great opportunities to deliver great medicines to patients. So, these are potential best in class, if not even blockbuster opportunities for this company. So, with that, I would say the value proposition is too great to pass and hence, is why I am here, and I am surrounded by great teammates here, which could actually deliver and execute towards these pivotal moments at the company.

這些不僅僅是簡單的 BLA。這些都是向患者提供優質藥物的絕佳機會。因此，對於該公司來說，這些都是潛在的同類最佳甚至是轟動的機會。因此，我想說，價值主張太好了，不容錯過，這也是我在這裡的原因，我身邊都是很棒的隊友，他們實際上可以在公司實現和執行這些關鍵時刻。

Got it. Thanks so much.

知道了。非常感謝。

Paul Choi, Goldman Sachs.

高盛的保羅·崔（Paul Choi）。

Hi. Thanks. Good afternoon and thank you for taking our questions. I want to switch gears maybe to RGX-121. And I want to see what your latest thoughts are on a potential Adcom following the filing. And then secondly, what are the latest, I guess a bit of feedback you are hearing relative to the [Denali] asset and maybe just how doctors and the physician community are thinking about potentially sequencing these drugs? Thank you very much.

你好。謝謝。下午好，感謝您回答我們的提問。我可能想換到 RGX-121。我想了解一下您對提交文件後潛在的 Adcom 的最新想法。其次，我想您聽到的有關 [Denali] 資產的最新反饋是什麼？非常感謝。

Thanks Paul. Thanks for joining the call. I think on the first question, we are preparing as if there will be an Adcom. That's something that normally you are not notified by FDA until the filing is accepted and they map out their plan for review.

謝謝保羅。感謝您加入通話。我認為關於第一個問題，我們正在為舉辦 Adcom 做準備。通常情況下，FDA 會在申請被接受並制定審查計劃之前，才會通知您。

But on our end, we are certainly planning that an Adcom could be required, but we have no information to say that it's required at this point. I think to your second question, I think there is a huge difference between our approach and Denali's.

但就我們而言，我們確實計劃可能需要 Adcom，但目前我們還沒有資訊表明這是必需的。對於你的第二個問題，我認為我們的方法和 Denali 的方法有很大不同。

I think our approach is extremely inviting for patients, meaning a one-time gene therapy that doesn't require a patient to go in for a weekly IV would be incredibly valuable, and that's how we are thinking about the program.

我認為我們的方法對患者來說極具吸引力，這意味著一次性的基因療法不需要患者每週進行一次靜脈注射，這將非常有價值，這就是我們對該計劃的看法。

In addition, the data that we released early in the year that showed that the majority of patients that were on enzyme replacement therapy before they went on to study haven't had to go back on to it. So, there is more benefit if you think of it that way than even the initial product profile that we had developed.

此外，我們今年年初發布的數據顯示，大多數在研究前接受過酵素替代療法的患者不需要重新接受該療法。所以，如果你這樣想的話，它帶來的好處甚至比我們最初開發的產品配置還要多。

So, we feel like we are in a really strong position with the MPS community as we get closer and closer to a potential commercial approval and feel like we will be able to position our product as a first choice for patients based on the data that we have in hand.

因此，隨著我們越來越接近獲得潛在的商業批准，我們覺得我們在 MPS 社群中處於非常有利的地位，並且我們覺得根據我們掌握的數據，我們將能夠將我們的產品定位為患者的首選。

Great. Thank you.

偉大的。謝謝。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

Hi guys. Thanks for taking our questions. This is Charlie on for Brian. So, yes, I just wanted to revisit the youngest cohort of DMD patients. Just knowing that in general, they are not diagnosed until they are about four years old to five years old, are you having any issues identifying these patients relative to the older cohorts? And do you think there are any efforts there you could make for the potential future market in terms of moving that average age of diagnosis up? Thanks.

嗨，大家好。感謝您回答我們的問題。這是 Charlie 代替 Brian 上場。所以，是的，我只是想重新探訪最年輕的 DMD 患者群體。只是知道一般來說，他們直到四到五歲左右才會被診斷出來，相對於年齡較大的群體，您在識別這些患者方面是否存在任何問題？您認為在提高平均診斷年齡方面，您可以為未來的潛在市場做出什麼努力嗎？謝謝。

Thanks. I'll turn that over to Steve.

謝謝。我將把這個交給史蒂夫。

Thanks Charlie, for the questions. So, I think one aspect is although that's traditionally been the time point of diagnosis, we are seeing newborn screening pick up. And I think we are going to progressively, over the next few years, see more and more states take on newborn screening.

謝謝查理的提問。因此，我認為一方面是，儘管這傳統上是診斷的時間點，但我們看到新生兒篩檢正在興起。我認為，在接下來的幾年裡，我們將逐步看到越來越多的州進行新生兒篩檢。

So, that's going to move things earlier. We announced today that we actually dosed our first patient in that age group. So, that gives you early anecdotal, albeit sense that these patients are there. And we feel confident we are going to be able to find these patients with the investigators that we have.

因此，這將使事情進展得更早。我們今天宣布，我們實際上已經為該年齡組的第一位患者進行了給藥。因此，這可以給你早期的軼事，儘管感覺這些病人就在那裡。我們有信心，我們能夠透過現有的研究人員找到這些患者。

And we think once these patients are found and the families consider the options, just like in the other age groups, the opportunity to consider a second generation potential best-in-class product that has the differentiating aspects that we have been describing is going to be really a compelling opportunity for a lot of these families.

我們認為，一旦找到這些患者，他們的家人就會考慮各種選擇，就像在其他年齡組一樣，考慮具有我們所描述的差異化方面的第二代潛在最佳產品的機會對很多家庭來說真的是一個引人注目的機會。

And certainly, that's one of the reasons we want to get functional data out there as well. Not only does it inform us and the community, but it actually plays an important part in the considerations of the actual families when they are seeing our investigators.

當然，這也是我們希望取得功能資料的原因之一。它不僅向我們和社區提供信息，而且實際上在實際家庭見到我們的調查員時的考慮中發揮著重要作用。

Great. Thank you so much.

偉大的。太感謝了。

Daniil Gataulin, Chardan

丹尼爾·加陶林，Chardan

Hey guys. Thank you for taking the question and congrats on the progress. I have a couple of questions. One on 202 program, I saw in your press release that you got an approval or authorization to start clinical trial in Canada, which you plan on doing in the first half.

嘿，大家好。感謝您回答這個問題，並祝賀您的進展。我有幾個問題。關於202計劃，我在你們的新聞稿中看到，你們獲得了在加拿大啟動臨床試驗的批准或授權，你們計劃在上半年進行臨床試驗。

Can you share some of the details of that trial and whether the data from that trial will be part of the pivotal data package? And then a question on 314, given recent data from the bilateral study, what are your plans for the fellow eye study for suprachoroidal program for Wet AMD and DR? Thank you.

您能否分享該試驗的一些細節，以及該試驗的數據是否會成為關鍵資料包的一部分？然後關於 314 的一個問題，鑑於雙側研究的最新數據，您對針對濕性 AMD 和 DR 的脈絡膜上腔計劃的眼科研究有何計劃？謝謝。

Thanks Daniil. So, we are excited that we have expanded for inclusion with Canada in the program. So, we are going to be able to open up multiple sites there. And we will give more details when we give the overall details on the design, but we had no issues getting approval in Canada, which I think supports the quality that we see with our product and the overall design of our plan and consistency with feedback that we have heard from the FDA.

謝謝丹尼爾。因此，我們很高興將加拿大納入該計劃。因此，我們將能夠在那裡開設多個站點。當我們提供有關設計的整體細節時，我們將提供更多細節，但我們在加拿大獲得批准沒有遇到任何問題，我認為這支持了我們產品的品質和我們計劃的整體設計以及與我們從 FDA 聽到的反饋的一致性。

So, similar to what we discussed before, any of the data that we see in the program from whatever region is going to be relevant both for the pivotal endpoint for accelerated approval, microdystrophin, but also the functional data that Curran mentioned would also be looked at, but not really be the primary focus for the initial approval.

因此，與我們之前討論的類似，我們在項目中看到的來自任何地區的任何數據都將與加速批准的關鍵終點微肌營養不良蛋白相關，而且 Curran 提到的功能數據也會被審查，但實際上並不是初步批准的主要關注點。

314, the bilateral study, we started with the subretinal program as far as evaluating bilateral treatment since we had a lot more exposures, a lot more data. So, it made sense to have the first step be looking at bilateral dosing with that route of administration.

314，這項雙側研究，我們從視網膜下注射計畫開始，就雙側治療進行評估，因為我們有更多的曝光和更多的數據。因此，第一步研究採用此給藥途徑的雙側給藥是有意義的。

Since, we are advancing rapidly along with AbbVie, the DR into pivotal, it's a great question you are raising that we will want to also evaluate bilateral treatment with suprachoroidal. So, we will be planning that. We haven't announced any specific details yet, but certainly, it makes sense that that's what we would want to do.

由於我們正與 AbbVie 一起快速推進 DR 進入關鍵階段，您提出的這個問題非常好，我們也希望評估脈絡膜上腔的雙側治療。所以，我們將進行計劃。我們還沒有公佈任何具體細節，但可以肯定的是，這是我們想要做的。

We are excited at that opportunity because we have seen excellent safety and certainly not the type of immune response that's been seen with, for example, intravitreal or non-localized delivery of gene therapy, where if you have significant inflammation in a first eye, the immune response seen there, if there is any spillover to the systemic circulation, then you would wonder, will that affect the safety and efficacy in the fellow eye.

我們對這樣的機會感到興奮，因為我們看到了極好的安全性，而且肯定不是那種在玻璃體內或非局部基因治療中所見到的免疫反應，如果你的第一隻眼睛有嚴重的炎症，那裡出現的免疫反應，如果有任何溢出到全身循環，那麼你會想知道，這是否會影響對側眼睛的安全性和有效性。

So, that's why we are excited that subretinal with the compartmentalized delivery, we didn't expect to see any issues in fellow eye and we haven't. And suprachoroidal also because it's a compartmentalized delivery where we are not seeing significant immune-mediated responses in the first eye, that also gives us confidence that we will be able to dose in the fellow eye.

所以，這就是為什麼我們對視網膜下分區給藥感到興奮，我們沒有想到會在另一隻眼中看到任何問題，我們也沒有看到。而脈絡膜上腔注射也是一種區間輸送方式，我們在第一隻眼中沒有看到明顯的免疫介導反應，這也讓我們有信心在另一隻眼中註射藥物。

Yi Chen, H.C. Wainwright & Company

陳懿，H.C.溫賴特公司

Hi. Thank you for taking my question. With respect to the pivotal program in diabetic retinopathy, can you comment on whether you plan to enroll a lot of patients without symptoms? And if so, what would you measure as the primary efficacy endpoint? Thank you.

你好。感謝您回答我的問題。關於糖尿病視網膜病變的關鍵項目，您能否評論是否計劃招募大量沒有症狀的患者？如果是的話，您會將什麼作為主要療效終點進行測量？謝謝。

Sorry. It was a little bit difficult to hear you. Could was just referring to the 202 pivotal plan?

對不起。聽清楚您的聲音有點困難。這難道只是指 202 關鍵計畫嗎？

No for 314 for the diabetic retinopathy pivotal program, do you expect to enroll a lot of patients without symptoms? And if so, what would you measure as the primary efficacy endpoint?

否，對於糖尿病視網膜病變關鍵項目 314，您是否預期會招募大量無症狀患者？如果是的話，您會將什麼作為主要療效終點進行測量？

Okay. So, I think this, correct me if I am wrong, but this would relate to the diabetic retinopathy indication in our pivotal program. It's an excellent point in that. In diabetic retinopathy, these patients are often asymptomatic until they develop the blinding complications like diabetic macular edema and proliferative diabetic retinopathy.

好的。所以，我是這樣認為的，如果我錯了請糾正我，但這與我們關鍵項目中的糖尿病視網膜病變指徵有關。這是非常好的觀點。在糖尿病視網膜病變中，這些患者通常無症狀，直到出現糖尿病黃斑水腫和增生性糖尿病視網膜病變等致盲併發症。

But yet they are at significant risk of developing these conditions. So, what's needed is a treatment that could prevent patients from ever developing these blinding complications. And the existing therapies, repeated injections are just not sustainable because patients are asymptomatic.

但他們罹患這些疾病的風險卻相當大。因此，我們需要一種能夠防止患者出現這些嚴重併發症的治療方法。現有的療法，重複注射是不可持續的，因為患者沒有症狀。

So, clinicians and patients are choosing to not be treated because the treatment burden is just too much. So, the whole reason or one of the significant reasons we and AbbVie see this as such a major opportunity is it's a one time in office treatment.

因此，臨床醫生和患者選擇不接受治療，因為治療負擔太重。因此，我們和 AbbVie 將此視為重大機會的全部原因或重要原因之一是，這是一種一次性的辦公室治療。

So, that really does allow this to be a compelling case for the clinician and their patients that one time in office treatment can help prevent them from developing the symptoms and the need for repeated treatment. So yes, we would include asymptomatic patients. We would then monitor for actual measures of whether their severity of their diabetic retinopathy is getting worse.

所以，這確實為臨床醫生及其患者提供了一個令人信服的案例，即門診治療可以幫助他們防止症狀並避免重複治療。所以是的，我們會包括無症狀患者。然後，我們將監測實際指標，以了解他們的糖尿病視網膜病變的嚴重程度是否正在惡化。

And also, we can look at those hard outcome measures of vision threatening complications, where we saw already in our Phase 2 study close to a 90% reduction in vision threatening complications of DME and PDR. So, that's what has us and the community so excited about being able to move forward with the end-of-Phase 2 meeting and then into pivotal development next year.

此外，我們還可以看看那些威脅視力的併發症的硬性結果指標，我們在第 2 階段的研究中已經看到，DME 和 PDR 的威脅視力的併發症減少了近 90%。因此，這就是我們和社區如此興奮的原因，我們可以推進第二階段結束的會議，並進入明年的關鍵發展階段。

Thank you. Got it. Thank you.

謝謝。知道了。謝謝。

Thank you. I would now like to turn the call back over to Curran Simpson, President and CEO, for closing remarks.

謝謝。現在，我想將電話轉回給總裁兼執行長 Curran Simpson，請他致最後一次演講。

Okay. I would like to thank everybody for joining us for the call. We have a lot of really important and exciting milestones to report through the rest of the year, and really excited to reach out to you as each of those are realized, and have a great evening. Look forward to following up with several of you. Thank you.

好的。我要感謝大家參加這次電話會議。我們在今年剩餘的時間裡有很多非常重要和令人興奮的里程碑要報告，並且非常高興在每個里程碑實現時與您聯繫，祝您度過一個愉快的夜晚。期待與你們中的一些人進行跟進。謝謝。

This concludes today's conference call. Thank you for your participation. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。