Ultragenyx Pharmaceutical Inc (RARE) 2025 Q3 法說會逐字稿

Good afternoon and welcome to the Ultragenyx third quarter 2025 financial results conference call.

下午好，歡迎參加 Ultragenyx 2025 年第三季財務業績電話會議。

(Operator Instructions) It is not my pleasure to turn the call to Joshua Higa, Vice President of Investor Relations.

（接線生指示）很抱歉將電話轉接給投資者關係副總裁 Joshua Higa。

Thank you. We have issued a press release detailing our financial results, which you can find on our website at ultragenyx.com. Joining me on this call are Emil Kakkis, Chief Executive Officer and President; Erik Harris, Chief Commercial Officer; Howard Horn, Chief Financial Officer; and Eric Crombez, Chief Medical Officer. I'd like to remind everyone that during today's call, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties, and our actual results may differ materially.

謝謝。我們已發布新聞稿，詳細介紹了我們的財務業績，您可以在我們的網站 ultragenyx.com 上找到新聞稿。與我一起參加此次電話會議的有：執行長兼總裁 Emil Kakkis；首席商務官 Erik Harris；財務長 Howard Horn；以及首席醫療官 Eric Crombez。我想提醒大家，在今天的電話會議中，我們將發表一些前瞻性聲明。這些聲明存在一定的風險和不確定性，我們的實際結果可能與此有重大差異。

Please refer to the risk factors discussed in our latest SEC filings. I'll now turn the call over to Emil.

請參閱我們最新提交給美國證券交易委員會（SEC）的文件中討論的風險因素。現在我將把電話轉給艾米爾。

Thanks, Josh, and good afternoon, everyone. Today, Ultragenyx is on the cusp of significant evolution and growth. We have four commercial products that have delivered consistent and substantial double-digit annual revenue growth over many years. We have two submissions in progress for programs that are poised to address significant medical need for patients with ultra-rare diseases. We also have multiple late-stage clinical program with transformative commercial potential that are approaching pivotal data readouts.

謝謝你，喬希，大家下午好。如今，Ultragenyx 正處於重大變革和發展的關鍵時期。我們有四款商業產品，多年來一直保持著兩位數的年收入持續成長。我們正在提交兩項計劃，旨在解決患有罕見疾病患者的重大醫療需求。我們還有多項具有變革性商業潛力的後期臨床計畫即將獲得關鍵數據。

We at a defining moment for the company, and I'm pleased to report that our team is ready to maximize the opportunities ahead. We announced earlier today that we took an important step to strengthen our financial position, receiving $400 million of nondilutive capital from OMERS through the cap sale of a portion of our Crysvita royalties. Importantly, we were able to defer the start of payments under this financing until January 2028. These funds and this timing bolster our balance sheet as we approach pivotal data readouts for our most significant commercial opportunities in ostogenis imperfecta and Angan syndrome. Importantly, we'll continue to focus on managing our cash burn and prioritizing our investments.

公司正處於一個關鍵時刻，我很高興地報告，我們的團隊已經做好準備，最大限度地把握未來的機會。今天早些時候，我們宣布，我們採取了一項重要措施來加強我們的財務狀況，透過出售我們部分 Crysvita 特許權使用費，從 OMERS 獲得了 4 億美元的非稀釋性資本。重要的是，我們能夠將此次融資的付款開始時間推遲到 2028 年 1 月。這些資金和時機增強了我們的資產負債表，因為我們即將獲得在成骨不全症和安根症候群方面最重要的商業機會的關鍵數據。重要的是，我們將繼續專注於控制現金消耗並優先考慮投資事項。

Shifting to clinical. We continue to see exciting momentum across our late-stage programs, beginning with GTX-102, our investigational antisense alginate for Angeman syndrome. In July, we announced the pivotal 48-week is PAR study completed enrollment with 129 patients and is expected to read out data in the second half of 2026. Last week, we announced the first patient at a dose in the Phase II/III AURORA study which evaluates GTX-102 in additional ages and genotypes. This study, along with a fully enrolled Phase III SPARC study will generate data across the spectrum of genotypes and ages.

轉向臨床。我們看到後期計畫持續取得令人振奮的進展，首先是 GTX-102，我們正在研究用於治療安格曼症候群的反義藻酸鹽。7 月，我們宣布關鍵的 48 週 is PAR 研究已完成招募 129 名患者，預計將於 2026 年下半年公佈數據。上週，我們宣布了 AURORA II/III 期研究中的首例接受特定劑量治療的患者，該研究旨在評估 GTX-102 在其他年齡和基因型中的療效。這項研究，以及已全面招募受試者的 III 期 SPARC 研究，將產生涵蓋各種基因型和年齡的數據。

Turning to UX 143 for the treatment of osteogenesis in Perfecta, the conduct of the Phase III Orbit and COSMIC study continues to go well. We hear stories from investigators who have patients in the open-label Phase II about how well their patients are doing, the improvement in their bone density and the profound effect this drug is having on their lives. Data from the Phase III studies are on track to read out around the end of the year, which to us means December or January. As we move into the final analysis, we remain confident citruzumab as a mechanism of action its ability to make more bone in the place that need more strength, which should reduce fractures. If successful, this will lead to a transformational treatment for pediatric and adult patients with osteogenesis imperfecta.

Perfecta 使用 UX 143 治療骨生成，III 期 Orbit 和 COSMIC 研究的進行進展順利。我們從參與開放標籤 II 期臨床試驗的研究人員那裡了解到，他們的患者病情控制得很好，骨密度有所改善，而且這種藥物對他們的生活產生了深遠的影響。III 期研究的數據預計將於年底左右公佈，對我們來說，這意味著 12 月或 1 月。進入最終分析階段，我們仍然相信 citruzumab 的作用機制是能夠在需要更多強度的地方產生更多骨骼，從而減少骨折。如果成功，這將為成骨不全症的兒童和成人患者帶來變革性的治療方法。

For our existing approved products, our global commercial organization continues to deliver meaningful revenue and cash flow every year. This year, they are on track to deliver total revenue between $640 million and $670 million, which would be 14% to 20% growth from last year. Crysvita is the largest product in the portfolio, and we expect revenue to continue growing in the US, Canada, Latin America and Turkey as more and more patients initiate this important medicine. To Jovi, AKSA, Mepsevvi also meaningfully contribute to our financial base and provide a steady diversified source of revenue is also expected to grow over time. I'll now turn the call over to Erik Harris to share more details on his team's efforts last quarter.

對於我們現有的已獲批准產品，我們的全球商業組織每年都能持續帶來可觀的收入和現金流。今年，他們的總收入預計將達到 6.4 億美元至 6.7 億美元，比去年增長 14% 至 20%。Crysvita 是產品組合中最大的產品，我們預計隨著越來越多的患者開始使用這種重要的藥物，美國、加拿大、拉丁美洲和土耳其的收入將繼續增長。Jovi、AKSA、Mepsevvi 也為我們的財務基礎做出了有意義的貢獻，並提供了穩定多元化的收入來源，預計隨著時間的推移，這些收入來源也將成長。現在我將把電話交給埃里克·哈里斯，讓他分享更多關於他球隊上個季度表現的細節。

Thank you, Emil, and good afternoon, everyone. As Emil mentioned, the commercial organization is continuing to successfully launch four products across the globe. Starting with Crysvita in Latin America. In the third quarter, our team generated another 50 new start forms that led to approximately 50 more patients on reimbursed therapy. We now have approximately 875 patients on commercial product in the region as the team continues to meet the growing demand for this important product.

謝謝你，艾米爾，大家下午好。正如埃米爾所提到的那樣，該商業機構正在全球範圍內繼續成功推出四款產品。首先是拉丁美洲的 Crysvita。第三季度，我們的團隊又產生了 50 份新的啟動表格，使大約 50 名患者獲得了報銷治療。目前該地區約有 875 名患者正在使用該產品，團隊將繼續滿足對這種重要產品日益增長的需求。

Health care providers continually share positive feedback on how well their patients feel when on Crysvita, and this has led to an increasing number of doctors writing prescriptions for more than one patient. I'll now shift to Crysvita in the United States and Canada, where our partner, Kyowa Kirin, has been leading commercialization since the transition in April 2023. While the third quarter 2025 royalty revenue was impacted by expected seasonality and we also know that there has been continued underlying growth in new start forms and new patients on reimbursed therapy. We expect strong fourth quarter revenue growth consistent with prior quarters. Moving on to AJOVY in the United States.

醫療保健提供者不斷分享患者服用 Crysvita 後感覺良好的正面回饋，這導致越來越多的醫生為不只一位患者開立處方。我現在將轉至 Crysvita 在美國和加拿大的業務，自 2023 年 4 月過渡以來，我們的合作夥伴 Kyowa Kirin 一直負責該地區的商業化工作。儘管 2025 年第三季特許權使用費收入受到預期季節性因素的影響，但我們也知道，新啟動形式和接受報銷治療的新患者數量一直在持續增長。我們預計第四季度營收將保持強勁成長，與前幾季保持一致。接下來是美國的 AJOVY。

Growth of new start forms in the third quarter continued to steadily increase, consistent with patterns we have seen in prior quarters. Since launching this product in 2020, our team has generated approximately 700 new start forms leading to approximately 625 patients on reimbursed therapy. The split between pediatric and adult patients continues to be approximately 65% tees and 35% adults. The number of new prescribers also continues to grow with a total of approximately 275 unique prescribers at the end of the third quarter. For DAJOBI across the EMEA region, we are approaching 300 patients treated under named patient sales across the region.

第三季新開辦企業數量的成長持續穩定上升，與我們前幾季看到的趨勢一致。自 2020 年推出該產品以來，我們的團隊已產生約 700 份新的啟動表格，使約 625 名患者獲得了報銷治療。兒童患者和成人患者的比例仍然約為 65% 的兒童患者和 35% 的成人患者。新增處方醫生的數量也持續成長，截至第三季末，共有約 275 位不同的處方醫生。在整個 EMEA 地區，DAJOBI 已為近 300 名患者提供指定患者銷售服務。

We continue to be pleased with this demand, especially since we are not actively marketing the therapy and simply responding to named patient requests. The majority of demand has been in France, but we also see increasing interest from patients and families in other EMEA countries, including Kuwait, Saudi Arabia and Greece. In closing, I'll make a few brief comments on Kesa, which we began commercializing in our territories outside of the US with formal reimbursement approvals in just the last couple of years. In the EMEA region, we now have patients on reimbursed therapy from nearly all of the major countries, and we have added approximately 120 patients since the beginning of the year.

我們對這種需求感到滿意，尤其是在我們並沒有積極推廣這種療法，而只是回應指定患者的需求的情況下。大部分需求來自法國，但我們也看到其他歐洲、中東和非洲國家（包括科威特、沙烏地阿拉伯和希臘）的患者和家屬對此越來越感興趣。最後，我想就 Kesa 做幾點簡要評論。在過去的幾年裡，我們開始在美國以外的地區對 Kesa 進行商業化推廣，並獲得了正式的報銷批准。在歐洲、中東和非洲地區，我們現在有來自幾乎所有主要國家的患者接受報銷治療，並且自年初以來，我們新增了約 120 名患者。

In total, there are approximately 310 patients across 17 countries who are receiving FTeZA. I want to recognize the tireless efforts from my European team as they continue to successfully navigate the country-by-country pricing negotiations and respond to any patient treatment requests across the whole EMEA region. As I have mentioned in the previous earnings calls, we continue to expect some quarter-to-quarter variability in revenue, but we remain confident in the growing underlying demand of all of our products around the world. With that, I'll turn the call to Howard to share more details on our financial results and guidance.

目前，共有來自 17 個國家的約 310 名患者正在接受 FTeZA 治療。我要表揚我的歐洲團隊的不懈努力，他們繼續成功地進行各國定價談判，並回應整個 EMEA 地區的任何病患治療請求。正如我在先前的財報電話會議上提到的，我們預計收入仍會存在一些季度間的波動，但我們仍然對我們所有產品在全球範圍內不斷增長的潛在需求充滿信心。接下來，我會把電話交給霍華德，讓他分享更多關於我們財務表現和展望的細節。

Thank you, Eric, and good afternoon, everyone. Before I go through our financials and guidance, I want to touch on the financing we announced earlier today. Additional details are in the press release and 8-K, but the essence is that we received $400 million through the sale of an additional 25% of our royalty interest on the future sales of Crysvita in the United States and Canada. Payments to OMERS will start in January 2028 and are capped, just like our prior royalty financing agreement with OMERS. We were fortunate to have many financing tools at our disposal and monetizing another strip of or Crysvita royalty with OMERS proved to be the best option.

謝謝你，埃里克，大家下午好。在詳細介紹我們的財務狀況和業績展望之前，我想先談談我們今天早些時候宣布的融資事宜。更多詳情請參閱新聞稿和 8-K 文件，但重點是，我們透過出售 Crysvita 在美國和加拿大未來銷售的額外 25% 的特許權使用費權益，獲得了 4 億美元。向 OMERS 的付款將於 2028 年 1 月開始，並設有上限，就像我們之前與 OMERS 達成的特許權使用費融資協議一樣。我們很幸運擁有許多融資工具，而將另一條 Crysvita 特許權使用費透過 OMERS 變現被證明是最佳選擇。

We went through a competitive process and OMERS provided an attractive cost of capital and a beneficial payment holiday in a cap transaction. These terms helped us minimize the impact on our P&L and maximize liquidity. Importantly, Crysvita has proven to be a unique and highly valuable asset, one that we expect will continue delivering meaningful value after the cap on this agreement is hit and the royalty stream has returned to Ultragenyx. Adding $400 million to our balance sheet will help us deliver on our expected launches, setting us up for our next stage of growth and on our path to profitability in 2027. We will also continue to maintain our financial discipline, leveraging our existing infrastructure to launch UX 111 and DTX401, if they are approved, and remain focused over the next year on delivering Phase III results for UX143 and GTX-102.

我們經過了激烈的競爭，OMERS 在一筆資本上限交易中提供了極具吸引力的資本成本和有利的付款假期。這些條款幫助我們最大限度地減少了對損益表的影響，並最大限度地提高了流動性。重要的是，Crysvita 已被證明是一項獨特且極具價值的資產，我們預計，即使該協議的上限已達到，特許權使用費流已回歸 Ultragenyx，它仍將繼續帶來有意義的價值。在我們的資產負債表上增加 4 億美元將有助於我們實現預期的產品發布，為我們下一階段的成長做好準備，並為我們 2027 年實現盈利奠定基礎。我們將繼續保持財務紀律，利用我們現有的基礎設施推出 UX 111 和 DTX401（如果獲得批准），並在未來一年繼續專注於交付 UX143 和 GTX-102 的 III 期試驗結果。

Now turning to the financials for the quarter. I'll start with total revenue. In the third quarter of 2025, we reported $160 million, representing 15% growth over the quarter of 2024 and 18% growth for the first nine months of 2025 over the first nine months of 2014. Crysvita contributed $112 million in the third quarter and $57 million from North America, $47 million from Latin America and Turkey and $8 million from Europe. The Jovy contributed $24 million is with its expected steady growth trajectory.

現在來看本季的財務數據。我先從總收入說起。2025 年第三季度，我們報告營收為 1.6 億美元，比 2024 年第三季成長 15%，比 2025 年前九個月成長 18%。Crysvita 第三季貢獻了 1.12 億美元，其中 5,700 萬美元來自北美，4,700 萬美元來自拉丁美洲和土耳其，800 萬美元來自歐洲。Jovy 貢獻了 2400 萬美元，並有望保持穩定成長。

(inaudible) 17milion as demand continues to build following the launch in territories outside of the United States. And Mepsevii contributed $7 million as we continue to treat in this ultra-rare indication. Total operating expenses for the quarter were $331 million, which included R&Ds of $216 million and investments in prelaunch inventory manufacturing, expenses of $87 million and cost of sales of $28 million. Operating expenses also included noncash stock-based compensation of (inaudible) million. For the net loss was $180 million or $1.81 per share.

（聽不清楚）隨著在美國以外地區推出後需求持續成長，銷量已達 1,700 萬。Mepsevii 為我們繼續治療這種極為罕見的疾病貢獻了 700 萬美元。本季總營運支出為 3.31 億美元，其中包括研發支出 2.16 億美元，上市前庫存製造投資支出 8,700 萬美元，以及銷售成本 2,800 萬美元。營運費用還包括（聽不清楚）百萬的非現金股票補償。淨虧損為 1.8 億美元，即每股虧損 1.81 美元。

As of September 30, we had $447 million in cash, cash equivalents and securities, which has been further strengthened by the $400 million readthrough the Crysvita royalty than we announced today. For the three months ended September 30, 2025, net cash used in operations was $91 million. In total, for the nine months ended September 30, 2020, it was $366 million. We do expect 2025 net cash used in operations to increase compared to 2024, and we also reaffirm our path to full year GAAP profitability in 2027. Shifting to revenue guidance for 2025, we are reaffirming the guidance we previously added.

截至 9 月 30 日，我們擁有 4.47 億美元的現金、現金等價物和證券，加上今天宣布的 Crysvita 特許權使用費的 4 億美元，我們的現金儲備進一步增加。截至 2025 年 9 月 30 日止三個月，經營活動使用的淨現金為 9,100 萬美元。截至 2020 年 9 月 30 日的九個月內，總計為 3.66 億美元。我們預計 2025 年經營活動中使用的淨現金將比 2024 年有所增加，我們也重申了我們在 2027 年實現全年 GAAP 盈利的目標。關於 2025 年的收入預期，我們重申先前發布的預期。

Total revenue is expected to be between $640 million and $670 million, which represents 14% to 20% growth over 2012. Crysvita revenue is expected to be to be between $460 million and $480 million, which includes all regions in all forms of revenue to Ultragenyx. This range represents 12% to 17% over 2024. The JoVE revenue is expected to be between $100 million, which represents 2% to 14% growth over 2024. With that, I'll turn the call to Eric Crombez, who will provide dates on the clinical programs.

預計總收入將在 6.4 億美元至 6.7 億美元之間，比 2012 年增長 14% 至 20%。Crysvita 的收入預計在 4.6 億美元至 4.8 億美元之間，其中包括 Ultragenyx 所有地區的所有形式的收入。這一範圍代表到 2024 年增長 12% 至 17%。JoVE 的營收預計將在 1 億美元之間，這意味著到 2024 年將成長 2% 至 14%。接下來，我將把電話轉給埃里克·克羅姆貝茲，他將提供臨床項目的日期。

Thank you, Howard, and good afternoon, everyone. I'll touch on UX 111 for the treatment of MPS IIIA and DTX401 for the treatment of glycogen storage disease type Ia. Starting with UX 111, we have had constructive formal and informal interactions with the FDA since receiving a complete response letter in July. We have also reviewed the additional longer-term data that the FDA requested, and we continue to see a durable treatment effect based on multiple biomarkers related to MPS IIIA with further separation in multiple clinical endpoints from natural history while maintaining an acceptable safety profile. The FDA interactions and internal progress we have made to address the observation give us confidence in a BLA resubmission in early 2026, followed by an FDA review of up to six months.

謝謝你，霍華德，大家下午好。我將簡要介紹用於治療 MPS IIIA 的 UX 111 和用於治療 Ia 型糖原貯積症的 DTX401。從 UX 111 開始，自 7 月收到 FDA 的完整回覆函以來，我們與 FDA 進行了建設性的正式和非正式互動。我們也審查了 FDA 要求的額外長期數據，我們繼續看到基於與 MPS IIIA 相關的多個生物標記的持久治療效果，在多個臨床終點上與自然病程進一步分離，同時保持可接受的安全性。我們與 FDA 的互動以及我們在內部為解決這一問題所取得的進展，使我們有信心在 2026 年初重新提交 BLA，隨後 FDA 將進行長達六個月的審查。

Shifting to DTX401 and in September at the International Congress of inborn errors of metabolism in Japan, we presented final 96-week results from the pivotal Gluco Gen study. These results show durable, clinically meaningful and statistically significant improvement in corn starch reduction while maintaining good glucose control. At week 96, study patients originally treated with DTX401 had been on study for nearly two years and patients originally randomized placebo had 48 weeks of treatment with DTX401 after crossover to study drug. At week 96, patients saw a 61% reduction in daily cornstarch intake across both the DTX401 and placebo to DTX401 crossover groups. This also corresponded to a mean decrease in the number of daily doses of cornstarch with the DTX401 group reducing by almost two doses at week 96.

隨後我們轉向 DTX401，並在 9 月於日本舉行的國際先天性代謝缺陷大會上，公佈了關鍵性 Gluco Gen 研究的最終 96 週結果。這些結果表明，在保持良好血糖控制的同時，玉米澱粉減少量得到了持久、臨床意義和統計意義的改善。到第 96 週時，最初接受 DTX401 治療的研究患者已經接受了近兩年的研究，而最初隨機分配到安慰劑組的患者在交叉接受研究藥物治療後，已經接受了 48 週的 DTX401 治療。在第 96 週，DTX401 組和安慰劑組到 DTX401 交叉組的患者每日玉米澱粉攝取量均減少了 61%。這也與玉米澱粉每日劑量平均減少相對應，DTX401 組在第 96 週減少了近兩劑。

The placebo to DTX401 crossover group on average, dropped to 1.6 daily doses by week 96. The improved glucose control and reduction in dependence on corn starch is particularly important overnight with the increased risk of hypoglycemia while patients are sleeping and less able to detect symptoms. Reducing overnight corn search doses also helps to alleviate the burden of meeting to wait to take cornstarch and the real risk of misdoses. At week 96, 67% of patients were able to eliminate at least one nighttime dose of cornstarch. The DTX401 group saw a 70% reduction of nighttime corn starts when compared to baseline and the crossover group saw a similar mean reduction of 75% compared to week 48.

安慰劑組與 DTX401 交叉組的平均每日劑量在第 96 週降至 1.6 劑。改善血糖控制和減少對玉米澱粉的依賴在夜間尤其重要，因為患者在睡眠時低血糖的風險增加，而且難以察覺症狀。減少夜間玉米澱粉的服用量也有助於減輕等待玉米澱粉的負擔，並降低服用錯誤劑量的風險。到第 96 週時，67% 的患者能夠停止服用至少一種夜間劑量的玉米澱粉。與基線相比，DTX401 組的夜間玉米發作次數減少了 70%，而交叉組與第 48 週相比，平均減少了 75%。

These clinical results were also supported by improvement in patients' impressions of their disease as measured by a global impression of change scale or PGIC and patient interviews. And the DTX401 group, 10 of 12 and or 83% of patients felt that the disease management was improved 96 weeks after receiving DTX401. For the placebo to DTX401 crossover group 18 of 19 or 95% of patients had improved disease management just 48 weeks after receiving DTX401. What is most important is that patients were able to reduce their dependence on day and nighttime cornstarch, feeling better while doing so, all while maintaining good glycemic control. This is why we believe this could be a transformative and life-changing treatment for these patients.

這些臨床結果也得到了患者對自身疾病印象的改善的支持，這種改善是透過總體變化印象量表（PGIC）和患者訪談來衡量的。在 DTX401 組中，12 名患者中有 10 名（即 83%）在接受 DTX401 治療 96 週後感覺病情有所改善。在安慰劑與 DTX401 交叉組中，19 名患者中有 18 名（即 95%）在接受 DTX401 治療 48 週後病情得到改善。最重要的是，患者能夠減少對日夜玉米澱粉的依賴，同時感覺更好，並且保持良好的血糖控制。因此，我們相信這可能會為這些患者帶來變革性的、改變生命的治療。

In August, the FDA granted us the ability to begin a rolling submission of our BLA which is underway and going well. The complete application will include the 96-week clinical data and the CMC updates that are in process based on the UX 111 feedback. We expect to complete the DTX401 rolling submission next month. I'll now turn the call back to Emil to provide some closing remarks.

8 月，FDA 批准我們開始滾動提交生物製品許可申請 (BLA)，目前申請正在進行中，進展順利。完整的申請將包括 96 週的臨床數據以及根據 UX 111 回饋正在進行的 CMC 更新。我們預計下個月完成DTX401滾動提交。現在我將把電話轉回給艾米爾，讓他做些總結發言。

Thank you, Eric. I'll quickly recap the milestones and catalysts as we head toward the end of the year. For US 143 in osteogenesis in Perfecta, the last patients in both the Orbit and COSMIC studies have had their final visits and we are on track to share top line data from these studies in December or January. For GTX-102 in Angelman syndrome, we continue treating patients in the 48-week ASPIRE study and continued enrollment in the support of AURORA study. For DTX401 and GSDIa, the rolling BLA submission continues, and we are on track to complete this filing in December.

謝謝你，埃里克。接近年底，我將快速回顧今年的里程碑事件和關鍵因素。對於 Perfecta 的 US 143 骨生成治療，Orbit 和 COSMIC 研究中的最後一名患者已經完成了最後一次就診，我們預計在 12 月或 1 月分享這些研究的主要數據。對於 Angelman 症候群的 GTX-102，我們繼續在為期 48 週的 ASPIRE 研究中治療患者，並繼續招募患者以支持 AURORA 研究。對於 DTX401 和 GSDIa，滾動式 BLA 提交仍在繼續，我們預計在 12 月完成此提交。

Lastly, UX 111 in Sanfilippo syndrome we are responding to the observation to note of the sale and expect to resubmit the BLA early in 2026. We are well positioned to deliver transformative therapies for rare disease patients while generating meaningful long-term shareholder value. We have a growing base of global revenue, a strong balance sheet and focus to execute on our top priorities. We look forward to sharing with citruzumab data and reading out the GTX-102 Phase III data in the second half of 2026.

最後，針對 Sanfilippo 症候群中的 UX 111，我們正在回應有關銷售的觀察，並預計將於 2026 年初重新提交 BLA。我們擁有得天獨厚的優勢，能夠為罕見疾病患者提供變革性療法，同時創造有意義的長期股東價值。我們擁有不斷成長的全球收入基礎、穩健的資產負債表，並專注於執行我們的首要任務。我們期待在 2026 年下半年與大家分享 citruzumab 的數據，並公佈 GTX-102 III 期數據。

With that, let's move on to your questions. Operator, please provide the Q&A instructions.

那麼，接下來我們來回答您的問題。操作員，請提供問答說明。

Thank you and at this time we'll conduct our question-and-answer session. (Operator Instructions)

謝謝，現在我們將進行問答環節。（操作說明）

Gina Wang, Barclays.

吉娜·王，巴克萊銀行。

Thank you for taking my questions. I know you will have very important data update Orbit and Cosmo, you said around year-end. 2025. So maybe if you can walk us through the logic there. Like should we actually more likely expecting the data will be at the JPMorgan giving the so close to holiday time. And also when you share the data, I assume it will be both cosmic and Orbit data.

謝謝您回答我的問題。我知道Orbit和Cosmo會有非常重要的資料更新，你說過大概會在年底前後發布。2025年。所以，或許您可以為我們解釋一下其中的邏輯。鑑於假期臨近，我們是否更有可能預期摩根大通會公佈相關數據？另外，當你分享數據時，我假設數據既包括宇宙數據也包括軌道數據。

And then if you can also talk about the different scenario, how would you take to the next level.

然後，如果你還能談談不同的情況，你會如何將其提升到下一個階段？

Great. Well, first, I'll say that we -- it's going to include Cassic and Orbit, both together. So both will cap together we're saying December or January because we're doing the cleaning process and the finishing of the day base locking analysis, and we don't have the precise timing we're providing some variability there because of the process is not defined, but we will expect to report on both either in December or in January.

偉大的。首先，我要說的是，它將包括 Cassic 和 Orbit，兩者將共同參與。因此，我們說這兩個數據將在 12 月或 1 月同時達到峰值，因為我們正在進行清理工作和完成每日基準鎖定分析，我們沒有確切的時間安排，由於流程尚未定義，因此存在一定的可變性，但我們預計將在 12 月或 1 月報告這兩項數據。

Good. Let's move on to the next question.

好的。我們來看下一個問題。

Maury Raycroft, Jefferies

莫里‧雷克羅夫特，傑富瑞

Thanks for taking my question. Maybe just following up on Gena's question for OI. Well, I guess to start off, -- can you comment on what you're seeing in the open-label extension from the Phase I? And you provided some anecdotal perspective there, but can you provide more quantitative perspective? And just anything additional on how we should think about the range of effect sizes on fracture reduction? And what would be needed to succeed for the final analysis?

謝謝您回答我的問題。或許只是想跟進一下 Gena 關於 OI 的問題。嗯，我想先問一下——您能否談談您在第一階段開放標籤擴展研究中觀察到的情況？您在那裡提供了一些軼事的觀點，但您能否提供更多量化的觀點？關於我們該如何看待骨折減少效果大小的範圍，還有什麼補充嗎？那麼，要最終取得成功，需要具備哪些條件呢？

Okay. Well, we haven't put out another cut of the Phase II data. So I can't give you any more quantitation. I think what we've been observing the trial is consistent with what we've put out before and we decided to focus our work on the Phase III. So we don't have any more quantitative data, but we're comfortable with what you've seen on Phase 2 is consistent as we move forward.

好的。我們還沒有發布第二階段數據的另一個版本。所以我無法提供更多量化數據。我認為我們觀察到的試驗結果與我們先前發表的結果一致，因此我們決定將工作重點放在 III 期臨床試驗上。所以我們現在沒有更多定量數據了，但我們相信，隨著我們繼續前進，您在第二階段看到的情況將保持一致。

Now with regard to what we expect in Phase II we've said that anywhere between 40% and 70% reduction in fractures in that range is a very good fracture reduction level. And I don't think that the exact percentage within that range matters as much is how patients feel and how they're functioning. And from the Phase II study, it's pretty clear that the way patients are functioning is quite important in terms of their ability to take on exercises to walk better get out of wheelchairs or using walkers, et cetera. So we think anywhere in that range, and I think most KOLs have suggested something better than 40%. We've seen 67% in the Phase II study.

至於我們對第二階段的預期，我們說過，骨折減少 40% 到 70% 都是非常好的骨折減少程度。我認為，這個範圍內的具體百分比並不重要，重要的是患者的感受和他們的功能狀況。從 II 期研究中可以很清楚地看出，患者的功能狀況對於他們能否進行運動以更好地行走、擺脫輪椅或使用助行器等至關重要。所以我們認為任何在這個範圍內都是如此，而且我認為大多數 KOL 都建議高於 40%。我們在二期臨床試驗中看到了 67% 的成功率。

I think anywhere in that range is, I think, would be a clinically meaningful change for these patients. But the effect on their overall function, I think, will ultimately be even more important in how the product launches. And I would tie that back to XLH because the XLH, the RIC score change didn't really change people's views. It shows the drug worked, but how patients felt on the drug that drove the adoption of that drug. So we're speaking from experience there on what we expect.

我認為在這個範圍內的任何變化，對於這些患者來說，都將是具有臨床意義的變化。但我認為，最終對產品整體功能的影響，在產品發布方式上將更為重要。我會把這和 XLH 聯繫起來，因為 XLH 的 RIC 分數變化並沒有真正改變人們的看法。這表明該藥物有效，但真正推動該藥物普及的是患者對藥物的感受。所以，我們是根據經驗來談談我們的預期。

But everything we've seen in Phase II says that this drug has a potential for it to be transformative in changing not only the fracture rate, but how patients feel and how they function on a day-to-day basis.

但我們在二期臨床試驗中看到的一切都表明，這種藥物有潛力帶來變革，不僅可以改變骨折率，還可以改變患者的感受和日常生活。

Yigal Makomovitz, Citi.

Yigal Makomovitz，花旗集團。

Hi, thank you very much. Could you just clarify with regard to the UX 111 and the 401 submission? I thought the idea was to sort out the CMC-related questions on UX 101 first. and then get that submitted and then do 401. But now it seems like you're going to do 401 and then 111. And you mentioned something about an observation.

您好，非常感謝。您能否就 UX 111 和 401 提交進行澄清一下？我原以為應該先解決UX 101中與CMC相關的問題，然後再提交，再做401。但現在看來，你好像要先跑 401 號公路，再跑 111 號公路。你也提到了關於觀察的事情。

So maybe that's the reason. But -- or is there another reason, please?

所以，也許這就是原因。但是——或者有其他原因嗎？

Thank you.

謝謝。

Well, the filings were always very close to each other. I mean, they were always within a month of each other. So what we -- there are some aspects of the program involved the inspection facility that need to be uncommon to both, but there were certain things that were specific to one Eleven in our Type A meeting, FDA made some combination, but it did require us to have full reports. And some of those for take -- took a little bit more time, which is why 111 is now following 401, but there's no real change, just the exact timing of when the final reports for things could be put together that are needed for each. 401 doesn't have some of those things because it is the new filing.

嗯，這些文件提交的時間總是非常接近。我的意思是，他們的時間總是相隔不到一個月。所以，我們——該計劃的某些方面涉及檢查設施，這些方面需要對雙方都不一樣，但有些事情是專門針對我們A類會議中的十一點的，FDA做了一些組合，但它確實要求我們提交完整的報告。有些事項需要更多時間，所以111表格現在跟在401表格後面，但實際上並沒有變化，只是最終報告的提交時間有所不同。 401表格沒有包含某些內容，因為它是一個全新的申報系統。

And so we felt we can get the things that aren't common done in time and kept 401 on track to file this next month. So it's a slight change, but I don't think it's a fundamental change. It's just what we have to get done and when.

因此，我們覺得我們可以及時完成那些不常見的事情，並確保 401 計劃下個月按計劃提交。所以這只是一個小小的變化，但我認為這不是一個根本性的改變。這只是我們必須完成的事情以及完成時間的問題。

Okay. And then if I could just do one follow-up. So on the first OMERS transaction back in 2022, OMERS transaction back in 2022 I guess how much of that is -- how close are you to the cap of the $1.45 billion. If you could comment on that aspect of it.

好的。然後，如果我能再做一次後續跟進就好了。所以，在 2022 年的第一筆 OMERS 交易中，我猜 OMERS 交易在 2022 年進行了多少——你離 14.5 億美元的上限還有多遠？如果您能就這方面發表一下看法就太好了。

Well, I'll let Howard go through it, but we sent, we at that time we sold 30% and we had a cap, and now we're selling a little bit of extension of that plus another piece, but, the cap ultimately is going to cover both pieces but maybe Howard you can explain it simply for them.

好吧，我請霍華德來解釋一下。當時我們賣出了 30% 的產品，並且設定了銷售上限。現在我們又增加了一些產品，但最終銷售上限將涵蓋這兩件產品。霍華德，也許你可以簡單地向他們解釋一下。

Yeah, Yigal, thank you for the question. We can't actually tell you how we're tracking to the cap, but I think what Amel said was important that the prior deal with Omer, the 2020 agreement with the 30% that has its own cap, once it's hit, it will then flow into this new deal, and together that piece plus the additional 25 that we announced today will together have its own cap of 1.55 times the $400 million that we raised. There's actually a really helpful page in our corporate deck that's either on our website or we will be there soon that that describes this.

是的，伊加爾，謝謝你的提問。我們目前還無法告訴大家我們距離上限還有多遠，但我認為 Amel 所說的很重要，即之前與 Omer 達成的 2020 年協議（該協議規定了 30% 的股份上限），一旦達到上限，就會併入這項新協議，而這部分加上我們今天宣布的額外 25%，其上限將是我們籌集的 45 億美元的 1.5 億美元的 1.5 倍。實際上，我們公司資料庫中有一個非常有用的頁面對此進行了描述，該頁面要么已經發佈在我們的網站上，要么很快就會發布。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Hi guys, good evening. Thanks for taking my questions. Just to stay on the point of the OMERS topic, that $400 million that you announced today, how far does that go in helping to address any concerns investors might have about the potential for financing needs coming up in 2026, especially as it relates to September when your priority vouchers would need to be renewed. If you could give some color on that. And then secondly, on the scenarios of Orbit and COSMIC, how are you thinking about if one of the studies is positive and the other is not. So let's say that that Orbit is positive and COSMIC is not and vice versa. How would that impact you think your chances of getting approved in OI . Thanks.

大家好，晚上好。謝謝您回答我的問題。回到 OMERS 的話題，您今天宣布的 4 億美元，這筆資金在多大程度上能夠幫助解決投資者可能對 2026 年潛在融資需求的擔憂，尤其是在 9 月份您的優先券需要續期的時候。如果你能詳細解釋一下就好了。其次，關於 Orbit 和 COSMIC 這兩個項目，如果其中一項研究結果是陽性而另一項研究結果是陰性，您對此有何看法？假設軌道為正，宇宙為負，反之亦然。你認為這會對你獲得OI批准的幾率產生什麼影響？謝謝。

Well, let me answer the Orbit Cote first, then I'll let Howard talk about the OMERS transaction, peering the cash runway, story. With regard to Orbia COSMIC, we think both studies have our power to succeed. So we're expecting both to succeed. If on the outside chance that one doesn't and one does, I think that we'll have enough data to help support the full range of the indication Remember, Orbit is against placebo and its older kids. COSMIC is younger kids and against the control.

好吧，先讓我回答 Orbit Cote 的問題，然後讓 Howard 來談談 OMERS 交易、現金儲備情況等等。關於 Orbia COSMIC，我們認為這兩項研究都有我們成功的能力。所以我們預期兩者都會成功。如果萬一其中一個沒有，而另一個有，我認為我們將有足夠的數據來支持該適應症的全部範圍。記住，Orbit 反對安慰劑及其年齡較大的孩子。COSMIC面向的是年輕一代，他們反對控制。

If we show good bone marrow density improvements in the younger kids, but versus maybe the p-values in hit for -- versus the phosphates, for example, but we show that the effect is still happening. I think we can manage that in terms of getting the age indication by showing the treatment effect is occurring and then safety is good down in the young ages. If the COSMIC study is smaller, but one advantage of it is that it's a narrower population because there are young patients only of two to seven rather than including adults. So even though it's smaller, it also is a narrower population. So it could also achieve with the narrow population, maybe there's less ratio, it could come out positive and show a good effect if Orbit turned out to be -- have too much variation and was missing slightly.

如果我們證明年輕兒童的骨髓密度有良好的改善，但與磷酸鹽相比，p 值可能較低，但我們發現這種效果仍在發生。我認為我們可以透過證明治療效果正在發生，並且年輕患者的安全性良好，來達到年齡指標的目的。COSMIC 研究的樣本量較小，但它的一個優點是樣本人群範圍較窄，因為研究對象僅限於 2 至 7 歲的年輕患者，而不是成年人。所以，雖然它面積較小，但人口密度也較低。所以，即使人口數量較少，比例也可能較低，如果 Orbit 的結果證明其變異性過大且略有缺失，那麼它也可能產生積極的結果並顯示出良好的效果。

But we can then show that the older patients are seeing the same effect we saw before. So I think if we get one or the other study positive, we'll be able to work forward and how we solve the issue of the age range and the indication. I don't expect there to be a difference in how the drug works. I think both studies should show a substantial bone marrow density benefit improvement and should show improvement in fractures. So we're confident in the program, but I think we can make it work with either combination of results.

但我們隨後可以證明，老年患者也出現了我們先前觀察到的相同效果。所以我覺得，如果我們能得到其中一項研究的陽性結果，我們就可以繼續推進，解決年齡範圍和適應症的問題。我不認為藥物的作用方式會有什麼不同。我認為這兩項研究都應該顯示骨髓密度有顯著改善，且骨折情況也有所改善。所以我們對這個方案很有信心，但我認為無論結果如何，我們都能讓它奏效。

Now I'll let Howard talk about the OMERS deal and cash runway question.

現在我讓霍華德來談談OMERS交易和現金儲備問題。

Yes. So I guess maybe I'll couch this in the term -- in terms of our pathway to profitability in there are a number of assumptions that go into that. First of all, the recent changes in timing are all factored into what I'm about to say. But on the revenue front, we expect to have continued double-digit growth from our current products and some contributions from launches. On the expense side, we will continue to manage expenses, but we will incorporate some select investments to to maximize our launches as we talked about today with prelaunch inventory build.

是的。所以我想我可能會用這樣一種說法來表達——就我們實現盈利的途徑而言，其中涉及許多假設。首先，我接下來要說的內容都考慮到了最近時間安排上的變化。但在營收方面，我們預期現有產品將持續維持兩位數成長，新產品上市也將帶來一些貢獻。在支出方面，我們將繼續控制支出，但我們將進行一些選擇性投資，以最大限度地提高我們的產品上市效果，就像我們今天討論的預售庫存建設一樣。

And then on the financial side, we do incorporate monetization of three PRVs. So from UX111, DTX401 and and UX 143. We've talked about in the past, if one of those wasn't to come to pass, that we think that the aggregate value of the others would get us to the same cash point. And of course, today's financing that we announced bolsters the balance sheet. But in aggregate, we think that all of those levers will put us on our path to profitability in '27.

在財務方面，我們確實納入了三個 PRV 的貨幣化。因此，來自 UX111、DTX401 和 UX 143。我們過去曾討論過，如果其中一項未能實現，我們認為其他幾項的總價值也能讓我們達到同樣的現金水準。當然，我們今天宣布的融資計畫也增強了資產負債表。但總的來說，我們認為所有這些措施將使我們在 2027 年走上獲利之路。

Maxwell Skor, Morgan Stanley.

麥克斯韋‧斯科爾，摩根士丹利。

Great, thank you very much for taking my question. So based on your KOL interactions, how do physicians think about potentially initiating cetuzumab, for example, prioritizing younger patients versus those with more advanced disease some checks we've done indicated earlier use in younger patients, but just wondering your thoughts and feedback from the community. I think it which demonstrate the strong fracture effect across the age range.

太好了，非常感謝您回答我的問題。根據您與關鍵意見領袖的交流，醫師們是如何考慮啟動西妥珠單抗治療的呢？例如，是優先考慮年輕患者還是病情較嚴重的患者？我們進行的一些檢查表明，年輕患者可能更早使用西妥珠單抗，但我想聽聽您和社區的意見和回饋。我認為這證明了骨折對各個年齡層的影響都非常顯著。

Thank you.

謝謝。

So I think that it's very likely the earliest adopt with the patient with the most severe disease. And I think for many of that will be the type 3 and type 4 patients, we'd expect a higher fraction of those patients to get treated and many of them are affected at a younger age. But really, at any age of their type 3s and 4s they have a more severe phenotype within type 1 population there may be a range of spectrum. There's a significant fraction, maybe half or more that have enough fractures to be really a detriment and for which even if they're not having fractures there, a change in behavior, their avoidance of activities or the sedentary activities are a problem that they would still want to get treated. So I think the area where most calls would wonder about is on the milder type 1 patients, but a lot of these patients are not even diagnosed very efficiently.

所以我認為，最有可能的是，最早採用這種方法的是病情最嚴重的患者。我認為其中許多是 3 型和 4 型患者，我們預計這些患者中接受治療的比例會更高，而且他們中的許多人在較年輕的時候就會受到影響。但實際上，在任何年齡段，3 型和 4 型患者的表型都比第 1 型患者更嚴重，1 型患者可能存在一個譜系範圍。相當一部分人，可能一半甚至更多，骨折的程度足以造成真正的損害，即使他們沒有骨折，行為的改變，例如迴避活動或久坐不動的活動，也是一個問題，他們仍然希望得到治療。所以我認為大多數來電者都會對病情較輕的 1 型糖尿病患者感到疑惑，但許多這類患者甚至沒有得到有效的診斷。

So we do think that it could shift younger, but I would say from our experience in Crysvita, we see growing and growing use in adult patients because even in OI, there are substantial effect. They may have less fractures, but they still have phone dysfunction that is hurting their ability to enjoy life as well. So I think it will be used across the spectrum, but I would expect younger and more severe patients to get more immediate access compared to others.

所以我們認為它可能會更年輕化，但根據我們在 Crysvita 方面的經驗，我們看到成年患者的使用量越來越大，因為即使在成骨不全症中，它也具有顯著的效果。他們的骨折可能較少，但他們的手機功能仍然受損，這也影響了他們享受生活的能力。所以我認為它將被廣泛應用，但我預計年輕患者和病情較重的患者會比其他患者更快地獲得治療。

Jack Allen, Baird.

傑克艾倫，貝爾德。

Great, thanks so much for taking the questions. Congrats to the team on the progress over the course of the quarter. Two quick ones from me. The first of which was on R&D, Howard, I apologize, but I think your remarks are a little choppy for those on the line at the top of the call. I was hoping you could dive in a little bit more on the third quarter R&D and you referred to as some prelaunch manufacturing spend there. How should we think about that in the quarter and then the run rate moving forward on R&D?

太好了，非常感謝您回答這些問題。祝賀團隊在本季取得的進展。我這裡快速回答兩個問題。第一個問題是關於研發的，霍華德，很抱歉，但我認為你剛才的發言對於電話會議開始時在線的聽眾來說有點斷斷續續。我希望您能更深入地探討一下第三季的研發情況，您提到了其中的一些上市前製造支出。我們該如何看待本季的研發投入以及未來的研發運行速度？

And then just briefly on osteogenesis and Perfecta, I was wondering how you guys are thinking about the commercial opportunity there as compared to maybe XLH and your prelaunch efforts and I guess, analysis of that market.

然後簡單談談骨生成和 Perfecta，我想知道你們是如何看待它的商業機會的，與 XLH 相比，以及你們的上市前努力和市場分析。

Okay. Thank you. I'll touch on the commercial, excuse me, if that's right. Actually, Howard, why don't you do the R&D first?

好的。謝謝。恕我冒昧，我先簡單談談廣告的事。霍華德，其實你為什麼不先做研發呢？

Yes, Jack, you got it. My point that I was trying to make there is in the quarter, the $216 million for R&D expense, -- it came up a little bit. I mean, I guess it was a diversion from our trend, and I wanted to explain that, that was related to investments in prelaunch inventory and getting ready for these launches. So that's the point I was trying to call out. And apologies if the line had garbled, Emil, over to you on OI.

是的，傑克，你明白了。我當時想表達的觀點是，本季研發支出為 2.16 億美元——這個數字略有上升。我的意思是，我想這偏離了我們的發展趨勢，我想解釋一下，這與預售庫存的投資以及為這些產品上市做準備有關。這就是我一直想強調的重點。如果剛才的通話斷斷續續，請見諒，艾米爾，接下來就交給你了。

Yes. So in -- when you look at the population and our view of the OI population is that there is probably 50% to 100% larger than XLH based on our discussion with KOLs. We see a lot of patients and have a big sample size. We think of pricing is probably similar to our Crysvita program. So we'd expect that the OI opportunity is larger than our XLH program.

是的。所以——當你觀察人口數量，根據我們與KOL的討論，我們對OI人群的看法是，OI人群的數量可能比XLH人群大50%到100%。我們接診了很多患者，樣本數很大。我們認為定價可能與我們的 Crysvita 專案類似。因此，我們預計 OI 項目的機會比我們的 XLH 項目更大。

Okay. Thank you.

好的。謝謝。

Joseph Schwartz, Leerink Partners.

Joseph Schwartz，Leerink Partners。

Hey guys. This is Will on for Joe. Congrats on the progress this quarter. I just have one question on the Angolan program. considering there are multiple ASOs in development here, we might be in an environment in a few years where there are multiple approved options. While it's difficult to envision how the competitive landscape might shake out, can you help us understand how the patients, parents and caregivers for this disease may be making their treatment decisions.

嘿，大家好。我是威爾，替喬報道。恭喜你本季的進展。關於安哥拉項目，我只有一個問題。考慮到目前有多個安哥拉國家安全組織（ASO）正在開發中，幾年後我們可能會面臨多個已獲批准的方案的情況。雖然很難想像競爭格局最終會如何發展，但您能否幫助我們了解這種疾病的患者、家長和照護者是如何做出治療決定的？

Is this something purely driven by the overall data? Or are there other attributes such as dosing schedule, specific endpoints, safety, et cetera, that are driving these decisions? Thank you.

這是完全由整體數據驅動的嗎？或者，還有其他因素，例如給藥方案、特定終點、安全性等，正在影響這些決策？謝謝。

An interesting question. Of course, there's a lot of unknowns and what will actually play out. In our mind, right now, our ASO is the most potent and has shown the best long-term data. I think in the end, the data will speak to parents as to what is important. With regard to how they make decisions, we've certainly talked to a lot of parents and understand what their views are of patients.

一個有趣的問題。當然，還有很多未知因素，最終結果如何還不得而知。我們認為，目前我們的 ASO 是最有效的，並且已經展現出最好的長期數據。我認為最終，數據會告訴家長們什麼才是最重要的。至於他們如何做決定，我們當然與許多家長交談過，了解他們對病人的看法。

I would say to you, there's no interest in knowing what the primary versus secondary endpoint or other point. They want to know how their kids are doing, and it's broader than picking one thing, we will have all the endpoints. And I think the endpoints across the different programs are broad enough and cover enough of the same domains for parent to be able to tell. With regard to the schedule, I think that both programs in the long term are ending up in at least the program are both in the Q3 kind of scheduling down the road. I think it's going to be more about -- I don't think the schedule itself is going to matter or if there's a load or not.

我想告訴你，我們並不關心主要終點與次要終點或其他點是什麼。他們想知道孩子們的近況如何，而且這個問題的範圍很廣，不能只專注在某一方面，我們需要了解所有方面。我認為不同項目的終點足夠寬泛，涵蓋了足夠多的相同領域，家長能夠分辨出來。關於日程安排，我認為從長遠來看，這兩個項目最終至少都會安排在第三季進行。我認為更重要的是——我認為日程安排本身或是否有工作量都無關緊要。

I don't think that's going to really alter it to be more about potency. The other thing I think will import is our patient support programs and how we help patients with treatments and Ultrex, we have, I think, one of the best support programs to ensure that people can get access to drug, and they maintain access even when they change insurance and other things. So we'll help support patients to achieve their access goals and getting treated. So at the end of the day, I think the potency and safety will matter will be the most important thing. But if there's multiple products out there, it's how we handle the administration and support for our patients will have a big impact on what works.

我不認為這會真正改變它，讓它更注重效力。我認為另一件值得關注的事情是我們的患者支持計劃，以及我們如何幫助患者接受治療和使用 Ultrex 藥物。我認為我們擁有最好的支持計劃之一，以確保人們能夠獲得藥物，即使他們更換保險或其他情況，也能繼續獲得藥物。因此，我們將幫助患者實現就醫目標並獲得治療。所以歸根究底，我認為效力和安全性才是最重要的。但是，如果市面上有多種產品，那麼我們如何處理管理和支援患者將對哪些產品有效產生重大影響。

And the last thing I'll point out is that we rolled our Phase III and moving along very quickly, and I feel we will have the potential to be out ahead of other ASOs, but let's see which one is best. And I think patients will probably opt for the best one when the trial has all been.

最後我想指出的是，我們已經啟動了第三階段，並且進展非常迅速，我覺得我們有潛力領先於其他應用商店營運商，但讓我們看看誰才是最優秀的。我認為，當所有試驗結束後，患者可能會選擇最好的那一個。

Great. Thanks so much.

偉大的。非常感謝。

Anupam Rama, JPMorgan.

Anupam Rama，摩根大通。

This is Jorge on for Anupam. Maybe just one from us. for GTX-102 following up on Angelin. -- realize here that the Evora supportive study has only just started enrolling. But -- how should we think about the enrollment curve for that trial relative to what you observed with the pivotal Piral? Thank you.

這是Jorge替Anupam報道。或許我們只會發表一篇關於 GTX-102 的文章，作為對 Angelin 的後續研究。 ——請注意，Evora 的支持性研究才剛開始招募受試者。但是—我們應該如何看待該試驗的入組曲線與您在關鍵性試驗 Piral 中觀察到的情況之間的關係呢？謝謝。

Thank you. The AURORA trial, we actually expect to enroll pretty quickly. There's a lot of patients lined up for it. We haven't set a precise time line for enrollment, but we were impressed with the speed of rolling into a sham-controlled trial. This trial is actually open label.

謝謝。AURORA試驗，我們預計很快就能完成招募。有很多病人排隊等著做這個手術。我們沒有設定具體的招募時間表，但我們對迅速進行安慰劑對照試驗感到印象深刻。這項試驗其實是開放標籤試驗。

I think that I'm expecting competition to get enrolled in the trial. And so we expect it to go up pretty quickly. I think it's going to be an important study that for open up our understanding of treatment safety and efficacy, both in a wider array of genotypes. So we do think it will go quickly, but we haven't set right now a time line specifically for it.

我認為應該會有競爭對手參與試驗。因此，我們預計它會很快上漲。我認為這將是一項重要的研究，它有助於我們了解治療的安全性和有效性，尤其是在更廣泛的基因型方面。所以我們認為進展會很快，但目前還沒有具體設定時間表。

Yaron Werber, TD Securities.

Yaron Werber，TD Securities。

Congratulations on a great quarter. This is Stephen on for your own -- just one on OI. How are you thinking about the length of a course of treatment for setrusumab. We've heard different KOLs say different things about exploring bisphosphonates in combination or in cycles. -- with setrusumab just based on the relative effects because setrusumab might build more bone mass, whereas bisphosphonates have a more freezing effect.

恭喜你們本季業績出色。這是 Stephen 的自薦帖子——僅此一個 OI。您認為塞曲單抗的療程需要多長時間？我們聽到不同的意見領袖對探索雙磷酸鹽聯合用藥或週期性用藥發表了不同的看法——尤其是與賽曲單抗聯合用藥，這僅僅是基於相對療效，因為賽曲單抗可能增加骨量，而雙磷酸鹽則具有更強的骨凍結作用。

Do you expect the majority or all patients to be on setrusumab continuously. And then secondly, whether there's any concern about bone pain from folks switching off of bisphosphonates that you've heard of anecdotally? Thanks.

您預計大多數或所有患者都需要持續接受賽曲單抗治療嗎？其次，您是否聽過有人在停用雙磷酸鹽後出現骨痛的案例？謝謝。

Yes. Well, I'll give you my more personal opinions, and I think this phosphates are going to become obsolete. I think they don't create good bone. They hold bone density that exists. But I think the anticatapproach is enabling normal bone metabolism, bone creation and bone absorption but better balanced.

是的。好吧，我來說說我個人的看法，我認為這些磷酸鹽將會被淘汰。我認為它們不能造就好的骨骼。它們保持著原有的骨密度。但我認為抗氧化療法能夠促進正常的骨骼代謝、骨骼生成和骨吸收，並且達到更好的平衡。

And I think in the long run, the paradigm of building bone with anti-sclerostin and then capturing or locking it in with boysphosponates, which has been established in the osteoporosis world will not be the right answer for OI. And we have patients now on a couple of years, and we are confident that chronic therapy is actually necessary in order to maintain the gains in bone they have achieved and to keep bone healthy. I think the FDA even has its own concerns about this phosphates because of longer bisphosphatase seems to result in more fracture as a problem because of the altered structure. So we're trying to break through the paradigm of one year of anti-sclerostin and then bisphosphonate lock-in. I think that model is for a different disease state and a different time.

而且我認為從長遠來看，用抗硬骨蛋白構建骨骼，然後用磷酸二酯捕獲或鎖定骨骼的範式（這種範式已在骨質疏鬆症領域確立）對於成骨不全症來說並不是正確的答案。我們現在有一些患者已經接受了幾年的治療，我們確信，為了保持他們所取得的骨骼改善效果並保持骨骼健康，長期治療實際上是必要的。我認為美國食品藥物管理局（FDA）也對這種磷酸鹽表示擔憂，因為較長的雙磷酸酶似乎會導致結構改變，造成更多的斷裂問題。所以我們正在努力打破一年抗硬骨素治療然後鎖定雙磷酸鹽治療的模式。我認為那個模型是針對不同的疾病狀態和不同的時期設計的。

And I think everything we're seeing says this is a chronic treatment. And that by maintaining antesgrostin treatment, what you're really doing is dialing up the balance between bone production and bone resorption to the proper place in a disease that drives that dial normally down toward resorption and a way for bone production. And that dial needs to stay where it needs to stay in order to keep patients with a steady state of high-quality bone without using bone poison to prevent breakdown of bone as a strategy. So in my view, cetuzumab in the future and bisphosphonates should probably come obsolete for OI.

我認為我們看到的一切表明，這是一種慢性治療。透過維持抗骨吸收治療，你實際上是在將骨骼生成和骨骼吸收之間的平衡調整到適當的位置，以應對這種疾病，這種疾病通常會使這種平衡向骨骼吸收方向傾斜，從而促進骨骼生成。為了讓患者保持高品質的骨骼穩定狀態，而無需使用骨毒物來防止骨骼分解，這個調節旋鈕必須保持在它應該在的位置。因此，我認為，未來西妥珠單抗和雙磷酸鹽可能會被淘汰，不再用於治療成骨不全症。

Salveen Richter, Goldman Sachs.

薩爾文·里克特，高盛。

This is Lydia on for Salveen. Maybe just another on OI. Could you just speak to any statistical work or study design changes you've made post the second interim analysis? Thanks so much.

這裡是莉迪亞，為您帶來薩爾文的報導。或許只是另一篇關於骨關節炎的文章。能否請您談談在第二次中期分析之後，您在統計工作或研究設計方面所做的任何更改？非常感謝。

Well, I don't believe we made any. But Eric, I don't know if you cruise, if you wanted to have any thoughts. I don't think there were any -- I'm not familiar with any changes at all.

嗯，我想我們沒有做出來。但是艾瑞克，我不知道你是否喜歡郵輪旅行，也不知道你有沒有什麼想法。我認為沒有任何變化——我對任何變化都一無所知。

No, the statistical plan remains in place. We, did take the opportunity, to really verify our assumptions, verify our statistical plan, and all of our modeling and rework really told us the plan we had in place is the right plan and really giving us a lot of confidence going into the final day to read out.

不，統計方案仍然有效。我們藉此機會真正驗證了我們的假設，驗證了我們的統計計劃，我們所有的建模和重新工作都告訴我們，我們制定的計劃是正確的計劃，這讓我們在最後一天公佈結果時充滿信心。

So much.

太多了。

Mehdi Goudarzi, Truist Securities.

Mehdi Goudarzi，Truist Securities。

Hi, good afternoon and thanks for taking our questions. This is Mehdi for June. Following previous questions on OI, given Conecs superiority studies in younger narrow population, what are the scenarios if it misses and even if or seats, what are the impacts on adoption of the drug?

您好，下午好，感謝您回答我們的問題。這是六月的Mehdi。繼先前關於 OI 的問題之後，鑑於 Conecs 在年輕小群體中的優越性研究，如果它未能成功，即使成功，對該藥物的採用會產生什麼影響？

Yes. Well, the trial -- thank you. So the point is that COSMIC is head-to-head against bisphosphonates and it has to be superior First of all, I don't think bisphosphonates were -- and those patients had to be -- they were on diphosphate before they started. So we're crossing over onto our drug. I believe the biposy benefit, which is only about 20% is relatively modest.

是的。好的，審判——謝謝。所以重點是，COSMIC 與雙磷酸鹽直接競爭，而且它必須更勝一籌。首先，我認為雙磷酸鹽並不優越——而那些患者必須優越——他們在開始使用 COSMIC 之前就已經在使用二磷酸鹽。所以我們現在要開始服用這種藥物了。我認為生物製劑帶來的效益只有大約 20%，相對來說比較有限。

So we actually are not concerned about it. But the question is the trial being smaller for whatever reason misses, what does it do? We'll still have the safety and nominal density data from that population, which I think would be supportive for allowing a label that includes that age group even if we can't be superior to phosphate. Particularly, remember, in the US, there is no requirement to be superior to another treatment for approval. The treatment that what it would have an effect on adoption, I actually don't think it would.

所以我們其實不擔心。但問題是，如果因為某些原因導致試驗規模縮小，會造成什麼影響？我們仍然會擁有來自該人群的安全性和標稱密度數據，我認為這將支持允許標籤包含該年齡組，即使我們不能優於磷酸鹽。尤其需要記住的是，在美國，批准新療法並不要求它優於其他療法。至於這種治療方法是否會對領養產生影響，我其實不認為會有影響。

I think people will see what's happening. I think the little kids have terrible bone density problems. And I think seeing the big picture across the age group, I think, will drive adoption on all age groups. So I appreciate the question, but I do think that at this time, I don't think we'll have a major impact either way.

我認為人們會明白發生了什麼事。我認為這些小孩子骨密度問題很嚴重。我認為，從整體上看清各個年齡層的情況，將會推動所有年齡層的採用。我很感謝你的提問，但我認為目前來看，無論哪種情況，都不會產生重大影響。

Thank you.

謝謝。

Raj Selvaraju, H.C. Wainright.

拉塞爾瓦拉朱 (Raj Selvaraju)，H.C.溫賴特。

Hey, this is.

嘿，這是。

This is Mitchell on for Ram. I wanted to ask about if you could just talk us through how the Crysvita transaction came to be. And if there's a threshold at which you view a mature product is better used for monetization for capital recycling into the pipeline versus the recurring income from the product?

這是拉姆隊的米切爾。我想請您詳細介紹一下 Crysvita 交易的來龍去脈。如果存在一個門檻，當產品成熟到一定程度時，將其用於資本變現以重新投入研發流程，而不是用於獲取產品的經常性收入，那麼這種情況下，哪種方式更合適呢？

I'll start and then let Howard talk. I mean, we, we're always looking for the most efficient cost of capital and in this case, the valuation people place on the Crusfida royalty was excellent and we did well that way, but I think in general we'd want to try to keep Our revenue streams and not do this, but I think we're just this critical moment here. But for us with three potentially four products launching in the next couple of years, we're going to be in a very different place very soon, and we won't need to be talking about this. But maybe Howard, you can touch on how the Chris transaction came together.

我先開始，然後讓霍華德發言。我的意思是，我們一直在尋找最有效的資本成本，就此而言，人們對 Crusfida 特許權使用費的估值非常高，我們在這方面做得很好，但我認為總的來說，我們應該努力保持我們的收入來源，而不是這樣做，但我認為我們現在正處於一個關鍵時刻。但對我們來說，未來幾年可能會推出三到四款產品，我們很快就會處境截然不同，屆時我們就無需再討論這個問題了。不過霍華德，或許你可以談談克里斯的交易是如何促成的。

Yes. We evaluated a number of different things. This was a competitive process ultimately where we we're looking -- what we were looking for were meaningful proceeds at the lowest cost of capital to minimize the P&L impact of interest expense, while also maximizing our cash preservation, the payment holiday helps with that in these other terms help with it. But as Emil mentioned, we thought that we could take some future-dated revenues and pull them into today to bolster our balance sheet to make sure we had what we needed to launch up to four programs in the near future and to put us on our growth path that we expect.

是的。我們評估了許多不同的面向。這是一個競爭激烈的過程，最終我們尋求的是以最低的資本成本獲得有意義的收益，從而最大限度地減少利息支出對損益表的影響，同時最大限度地保留現金，而付款假期在其他方面有助於實現這一點。但正如埃米爾所提到的那樣，我們認為我們可以將一些未來收入提前到今天，以增強我們的資產負債表，確保我們有足夠的資金在不久的將來啟動多達四個項目，並使我們走上我們預期的增長道路。

Great. Thank you.

偉大的。謝謝。

Laura Chico, Wedbush.

勞拉·奇科，韋德布希。

Hi, good afternoon. This is Thomas on for Laura Chico. Perhaps one question for Seminole and Wilsons. Can you discuss what you will need to see from the fourth cohort to have confidence in advancing the testing or dose into ratio studies?

您好，下午好。這是托馬斯替勞拉·奇科報道。或許可以問塞米諾爾人和威爾遜人一個問題。您能否談談您需要從第四組受試者中看到什麼，才能有信心推進測試或劑量比例研究？

Thank you.

謝謝。

Yeah, thank you. So I'll touch on it and Eric, I don't know if we need to add a little bit more. But I think if you can do a gene therapy, you want to see a substantial effect in the majority of patients, right? We want to see something that's compelling. And what we're doing right now is increasing the dose to try to help enhance the fraction of patients that see that kind of effect. We're excited about what we're seeing and where there's some data being presented soon.

是啊，謝謝。所以我會簡單提一下，艾瑞克，我不知道我們是否需要再補充一些內容。但我認為，如果能進行基因治療，你肯定希望看到對大多數患者產生顯著效果，對吧？我們想看到一些引人入勝的東西。我們現在正在做的就是增加劑量，以期提高看到這種效果的患者比例。我們對目前所看到的情況感到興奮，並且很快就會公佈一些數據。

But Eric, maybe you can talk about what you want to look for in the data for Wilson as we make that decision to go to Phase II.

但是艾瑞克，或許你可以談談你希望從威爾森的數據中尋找什麼，以便我們決定是否要進入第二階段。

Yes. No, and I think it's important to stress that, first and foremost, we are looking for the majority of patients to come off of current standard of care, which is key laters and zinc. And Emil mentioned increasing dose, we also are changing our immunomodulation program. So we think that those changes will be at least additive, if not synergistic with improving or really maximizing the efficacy we see with this gene therapy. So saw great results that we've presented externally so far, and we were close to that mark.

是的。不，我認為必須強調的是，首先，我們希望大多數患者能夠停止目前的標準治療，即服用關鍵的拉特羅和鋅。艾米爾提到要增加劑量，我們也正在改變免疫調節的方案。因此我們認為，這些改變至少會起到疊加作用，甚至可能產生協同效應，從而提高或真正最大限度地發揮這種基因療法的療效。因此，我們看到了迄今為止對外展示的出色成果，而且我們離目標很近了。

We did think it was worth taking this extra time to do this cohort to try to get the majority off of patients. And what's nice with Wilson and looking at copper is you have a lot of different ways to measure copper. So I think we will be able to make a clear decision there.

我們認為，花額外的時間來完成這組研究，以盡量減少患者數量，是值得的。威爾遜銅材的優點在於，它提供了許多不同的銅材測量方法。所以我認為我們能夠在那裡做出明確的決定。

Thank you again that's a great question.

再次感謝，這是一個很好的問題。

Luca Issi, RBC Capital Markets.

伊西 (Luca Issi)，加拿大皇家銀行資本市場部。

Hi team. This is Shelby on for Luca. Can you just remind us how we should think about loss of exclusivity for setrusumab. This has obviously been a long journey for this molecule, given it was originally developed by Novartis, the Mereo and Sinanyou guys. So I believe some of the initial IP actually expires at the end of the decade in 2028. Is that the foundational IP, so a biosimilar can in theory come soon after that?

大家好。這是謝爾比替盧卡發言。您能否提醒我們一下，我們該如何看待賽曲單抗失去獨佔權的問題？顯然，對於這種分子來說，這是一段漫長的旅程，因為它最初是由諾華公司、Mereo 和 Sinanyou 公司開發的。所以我認為，部分初始智慧財產權其實會在十年末的 2028 年到期。這是基礎智慧財產權嗎？理論上，生物相似藥可以很快問世？

Or do you have additional IP that can maybe push out the loss of exclusivity to a later time point? Any color there, much appreciated. Thanks.

或者，您是否擁有其他智慧財產權，可以將獨家銷售權的喪失推遲到以後的時間點？任何顏色都可以，非常感謝。謝謝。

I think we've always looked at the whole exclusivity story as being really important. I think we have, of course, orphan designation, which would give us certain protection, which is well passed in 2030. So I'd start with that. So that's the first part of the story. Second thing, even if there are -- if there were no patents, the truth is that biologics like that rarely change.

我認為我們一直都非常重視獨家性這個問題。我認為我們當然有孤兒認定，這將給我們一定的保護，這項認定已於 2030 年通過。所以我建議從這裡開始。故事的第一部分就到這裡。第二點，即使有專利——如果沒有專利，事實是像這樣的生物製劑很少會改變。

And the follow-on mileage may occur, but I think that it would be different from what typical loss exclusivity. I don't think I can go through all the details of the patents that protect us now for the program. There are also additional things we are putting together related to our discoveries how to treat, how to do chronic treatment and other things. So our -- we feel pretty good about where we're at right now. But you're right, Malkihas been around a while, and it was being developed for OI.

後續里程可能會增加，但我認為這與典型的損失專屬權有所不同。我覺得我無法詳細介紹目前保護我們該專案的各項專利的全部細節。此外，我們也正在整理一些與我們的發現相關的資料，例如如何治療、如何進行慢性治療等等。所以——我們對目前的狀況感覺相當不錯。但你說得對，Malki 已經存在一段時間了，它是為 OI 開發的。

I mean osteoporosis in the past. But I think a combination of brexclusivity and our expectation to have some IP protecting it should put us in a good place to take this program forward.

我指的是我以前得過的骨質疏鬆症。但我認為，英國獨家經營權以及我們希望獲得一些智慧財產權保護的預期，應該能讓我們處於推進該計畫的有利位置。

Sami Corwin, William Blair.

薩米·科溫，威廉·布萊爾。

Good afternoon. Congrats on the progress and thanks for taking my questions. I was curious if you could walk us through, again, the rescue arm in orbit and how that's factored into the statistical analysis plan. And then as you got conversations with neurologists, how are they kind of viewing the utility of the Bailey four cognition versus Baily four communication. Thank you.

午安.恭喜你取得進展，謝謝你回答我的問題。我想請您再次為我們詳細介紹軌道上的救援臂，以及它是如何納入統計分析計劃的。然後，當你與神經科醫生交談時，他們是如何看待 Bailey 四項認知與 Bailey 四項溝通的實用性的。謝謝。

So the rescue arm -- the point of the rec arm is that if a patient was having a lot of fractures and a lot of PIs are worried if they come in the trial of the visas have a lot of fractures. -- they're sort of stuck in the trial, they have to withdraw the kid was doing badly. So we'd offer them that they could rescue if they have a large number of fractures seeing certain or fractures. But they do have to be in the trial at least one year. And then after that, they could rescue.

所以，救援組——救援組的意義在於，如果一個病人骨折很多，很多主要研究者擔心，如果他們參加簽證試驗，就會有很多骨折——他們就有點被困在試驗中了，他們不得不退出，因為孩子的情況很糟糕。因此，我們會向他們提供一些方法，如果他們發現大量骨折或某些骨折，他們可以進行搶救。但他們必須至少參加一年的審判。然後，他們就可以進行救援了。

The idea then is that with a one-year sample time in a higher number of fractures, we will have had enough time to assess their AFR, right, and determine their analyze fracture rate, right? If you have a lot fracture, then a one-year time frame is enough to make that the estimate of the AFR. So if a patient goes into the rescue arm, we include all the time that they've been on drug as included in their analysis and estimate their AFR from the time -- the sampling time. Does that make sense to you? So because we're doing an analyzed fracture rate reduction, we just need a sample time that's adequate estimate of their true fracture.

那麼，我們的想法是，透過一年的樣本時間，對更多骨折病例進行分析，我們將有足夠的時間來評估它們的 AFR，對吧，並確定它們的分析骨折率，對吧？如果骨折很多，那麼一年的時間就足以估算出 AFR。因此，如果患者進入搶救組，我們將他們服用藥物的所有時間都納入分析，並根據採樣時間估算他們的 AFR。你覺得這樣說得通嗎？因為我們要做的是分析性斷裂率降低，所以我們只需要一個樣本時間，就能充分估計它們的真實斷裂情況。

So that's the way it's working. But it was a necessary part of doing the trial and because doctors couldn't keep patients off this phosphonate indefinitely and have a tremendous amount of problems. And rather than having withdraw, it'd be better to find a way to keep them in the trial and cross them over. So thank you for that question. The next question was on the utility of daily four versus cognition versus communication.

事情就是這樣運作的。但這是進行試驗的必要環節，因為醫生不能讓病人無限期地停止服用這種膦酸鹽，而且這樣做會帶來很多問題。與其讓他們退出試驗，不如想辦法讓他們繼續參與試驗並進行交叉試驗。謝謝你的提問。下一個問題是關於每日四項技能與認知和溝通的效用。

I will say to you, honestly, it doesn't matter what the primary endpoint is because I've never talked to parents in how they don't ask me what the primary endpoint of trials are they -- you might talk about what you're measuring, but they are never going to depend on primary or secondary to make decisions. They want to look at all the whole story. And that is what we're going to provide the whole story. We will have a receptive and express communication in our program. We'll have answers for that and we compare them and the idea of what you position first is it's more of a regulatory thing has, I think, limited value and at least in rare I know in other big market disease is the primary endpoint and its exact crafting turns that into a big deal, but in rare, I have not seen it happen.

說實話，主要終點是什麼並不重要，因為我從未與家長談過，他們從來不會問我試驗的主要終點是什麼——你可能會談論你在測量什麼，但他們永遠不會依靠主要終點或次要終點來做決定。他們想了解事情的全貌。這就是我們將要講述的全部故事。我們的課程將著重於開放和積極的溝通。我們會找到答案，並進行比較。我認為，你首先提出的定位更多的是一種監管問題，其價值有限，至少在極少數情況下，我知道在其他大型市場中，疾病是主要終點，而精確的製定會將其變成一件大事，但在極少數情況下，我還沒有看到這種情況發生。

It's not really mattered because people will look at all the data and incorporate it. Our plan then is to focus on the daily four condition, we saw the best effect. It's a fundamental brain function issue. But we're also looking at the rest of the communication and other end points. One, through the multi-mine responder index and then through individual secondary and tertiary endpoints.

其實這並不重要，因為人們會查看所有數據並將其納入考慮。因此，我們的計劃是專注於每天的四個條件，我們發現效果最好。這是大腦基本功能的問題。但我們也在關注其他溝通環節和其他終點。首先，透過多礦響應者指數，然後通過個體二級和三級終點。

So we'll be able to speak to all the issues, all the end points and be able to provide comparisons between the products as well. So I think that's why I'm not as concerned about what people chose is primary. And we have to do that for regulatory purposes. But in the real world, I never went to my doctor and said, my primary end point is this, my secondary is this and what can you do for me? And no one ever speaks that way.

這樣我們就能討論所有問題、所有最終結果，還能比較產品。所以我覺得這就是為什麼我不太在乎人們選擇什麼才是最重要的。出於監管目的，我們必須這樣做。但在現實世界中，我從來沒有去找過我的醫生，說：“我的主要終點是這個，我的次要終點是這個，你能為我做些什麼？”從來沒有人那樣說話。

So I'm really comfortable with what we have. We're covering every domain, and I think I feel good about the type of data we've seen so far in our expansion study patients, making me confident that we're going to see China of changes in communication and cognition and sleep and behaviors and fine motor and expressive that will be, I think, an amazing future for Angelman patients, frankly, because who could have thought we could change a kid with severe developmental way and actually start causing the brains to develop. I think it's a miraculous situation. We're really proud to be part of it.

所以我對我們目前的情況非常滿意。我們正在涵蓋所有領域，我對目前為止在擴展研究患者中看到的數據感到滿意，這讓我相信我們將會看到患者在溝通、認知、睡眠、行為、精細運動和表達方面發生改變，坦白說，我認為這將是安格曼綜合徵患者一個令人驚嘆的未來，因為誰能想到我們能夠改變一個嚴重發育障礙的孩子，並真正開始促進其大腦發育呢？我認為這是一個奇蹟般的局面。我們非常榮幸能參與其中。

Great, appreciate all the color.

太棒了，很喜歡這些色彩。

Gavin Clark-Gartner, Evercore ISI.

Gavin Clark-Gartner，Evercore ISI。

Hey guys, thanks for taking the question. Just wanted to ask on the ongoing ASPIRE ANGEL study. Is there any commentary you can make on the variability you're seeing any of the blinded data, any of the baseline characteristics, really just anything that gives you confidence in the ongoing study?Thanks.

各位，謝謝你們回答這個問題。我想問一下關於正在進行的 ASPIRE ANGEL 研究的情況。您能否就您觀察到的任何盲法資料、任何基線特徵的變異性發表一些評論？或任何能讓您對正在進行的研究充滿信心的資訊？謝謝。

Well, the study is going well, and we're confident. We normally do not talk about data on a trial when it's ongoing. I don't know, Eric, if there's any high-level color you can provide and the patient population. I believe they're very similar to the expansion patients we've already reported on.

研究進展順利，我們很有信心。我們通常不會在試驗進行期間討論試驗數據。埃里克，我不知道你是否能提供一些關於患者群體的高級資訊。我認為他們與我們之前報道過的擴張型患者非常相似。

Yes. No, exactly. And I think that's important. We don't bring on tested things into Phase III. And really carrying over our learnings and understanding from Phase II.

是的。沒錯，正是如此。我認為這很重要。我們不會將經過驗證的產品引入第三階段。真正地將我們從第二階段所獲得的經驗和理解運用到下一階段。

So same entry criteria, same endpoint, same patient population and again, looking in Aspire for patients with full deletion. So those are patients really expressing no protein, very consistent phenotype and the most severe end of that spectrum. So we do anticipate very consistent results to what we saw in Phase II.

因此，入選標準、終點、患者群體均相同，並且再次在 Aspire 中尋找完全基因刪除的患者。所以這些患者確實沒有表現任何蛋白質，表型非常一致，屬於疾病譜中最嚴重的一端。因此，我們預期結果將與二期臨床試驗中觀察到的結果非常一致。

Great thanks.

非常感謝。

There are no further questions at this time. So I'll hand the floor back to Joshua Higa for closing remarks.

目前沒有其他問題了。那麼，我將把發言權交還給 Joshua Higa，讓他做總結發言。

Thank you. This concludes today's call. If there are additional questions, please contact us by phone or at ir@ultragenyx.com. Thank you for joining us.

謝謝。今天的電話會議到此結束。如有其他疑問，請致電或發送郵件至ir@ultragenyx.com與我們聯繫。感謝您的參與。

Thank you. All parties may now disconnect.

謝謝。所有參與者現在可以斷開連接。