Belite Bio, Inc (BLTE) 2025 Q4 法說會逐字稿

Ladies and gentlemen, thank you for joining us, and welcome to the Belite Bio fourth quarter and fiscal year-end 2025 earnings call. (Operator Instructions) I will now hand the conference over to Sophie Hunt. Please go ahead.

女士們、先生們，感謝各位的到來，歡迎參加 Belite Bio 2025 財年第四季及全年財報電話會議。（操作說明）現在我將把會議交給索菲·亨特。請繼續。

Good afternoon, everyone. Thank you for joining us. On the call today are Dr. Tom Lin, Chairman and CEO of Belite Bio; Dr. Hendrik Scholl, Chief Medical Officer; Dr. Nathan Mata, Chief Scientific Officer; and Hao-Yuan Chaung, Belite Bio's Chief Financial Officer.

大家下午好。感謝您的參與。今天參加電話會議的有：Belite Bio 董事長兼執行長 Tom Lin 博士；首席醫療官 Hendrik Scholl 博士；首席科學官 Nathan Mata 博士；以及 Belite Bio 財務長 Hao-Yuan Chaung。

Before we begin, let me point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. We encourage you to consult the risk factors discussed in our SEC filings for additional detail. Additionally, today, we will be discussing certain non-GAAP financial measures.

在開始之前，我想指出，我們將做出一些基於我們當前預期和信念的前瞻性陳述。這些聲明存在一定的風險和不確定性，實際結果可能與聲明內容有重大差異。我們建議您查閱我們在提交給美國證券交易委員會的文件中討論的風險因素，以了解更多詳情。此外，今天我們也將討論一些非GAAP財務指標。

Reconciliations to the most directly comparable GAAP measures are provided in the press release issued earlier today. And now I'll turn the call over to Hao. Hao?

今天稍早發布的新聞稿中提供了與最直接可比較的 GAAP 指標的調整表。現在我把電話交給郝。郝？

Thank you for joining today's call to discuss our fourth quarter and full year 2025 financial results. 2025 was a year of significant progress for us as we achieved several key milestones. We look forward to a truly transformative year as we position Tinlarebant to potentially become the first ever approved therapy for people living with Stargardt disease.

感謝您參加今天的電話會議，共同探討我們2025年第四季及全年的財務表現。 2025年是我們取得重大進展的一年，我們實現了多個關鍵里程碑。我們期待著充滿變革的一年，因為我們正在努力使 Tinlarebant 有可能成為首個獲批用於治療 Stargardt 病的療法。

The devastating eye disease that usually begins in childhood or young adulthood and leads to progressive vision loss and the legal blindness in almost all cases. Today, I'll provide a recap of our 2025 achievement key milestone for 2026 and financial results.

這種毀滅性的眼疾通常始於兒童期或青年期，會導致進行性視力喪失，幾乎在所有病例中都會導致法定盲。今天，我將回顧我們 2025 年的成就，並介紹 2026 年的關鍵里程碑和財務表現。

Starting with 2025 achievement, of course, the most significant achievement was the announcement of our top line results for the Phase III [Tinlarebant] trial in December. We're very excited to share that the trial maps primary efficacy endpoint demonstrating statistically significance and clinically meaningful 36% reduction in the growth rate of upper lesion, measured by definitely decreased autofluorescence, by (inaudible) and imaging compared with placebo.

當然，從 2025 年的成就來看，最重要的成就是我們在 12 月公佈了 III 期 [Tinlarebant] 試驗的主要結果。我們非常激動地宣布，該試驗的主要療效終點顯示，與安慰劑相比，上部病變的生長速度在統計學上顯著降低，臨床上也具有重要意義，降低了 36%，這是通過（聽不清）和成像方式測量的，自發螢光明顯降低所致。

This result position us well for engagement with the regulatory authorities as we see a path to commercialization in Stargardt disease. In the DRAGON II study, we reached the target number of 60 subject in January. As of February 27, we had enrolled 72 subject, a subject we had passed the screening before the registration closed can still be at (inaudible) trial. We expect the final number of subjects enrolled to be between 72% and 75%. We also completed enrollment in the Phase III PHOENIX trial in GA with (inaudible) subjects.

這一結果使我們在與監管機構接觸方面處於有利地位，因為我們看到了 Stargardt 病商業化的道路。在 DRAGON II 研究中，我們在 1 月達到了 60 名受試者的目標人數。截至 2 月 27 日，我們已招募了 72 名受試者，在註冊截止前通過篩選的受試者仍可能參與（聽不清楚）試驗。我們預計最終入選的受試者人數將在 72% 到 75% 之間。我們也完成了在喬治亞州進行的 III 期 PHOENIX 試驗的受試者招募工作，受試者人數為（聽不清楚）人。

Finally, we completed a $402 million public offering with overallotment fully exercised by the underwriter in Q4. Importantly, the net proceeds went from this along with other raises comparing the year to us extremely well to support commercialization preparation for Stargardt disease, development and expansion of pipelines and general corporate purposes. Now moving to 2026.

最後，我們在第四季完成了 4.02 億美元的公開發行，超額配售權全部由承銷商行使。重要的是，此次融資以及其他融資所得淨收益，與去年同期相比，用於支持 Stargardt 病的商業化準備、產品線開發和擴展以及一般公司用途，表現非常出色。現在展望2026年。

As I said, this will be a transformative year for Belite. The top priority in our plan NDA submission to the FDA in the second quarter of 2026. And with our NDA submission planning, have also kicked off our commercialization profession work for Stargardt disease.

正如我所說，這將是貝利特公司具有變革意義的一年。我們計劃的首要任務是在 2026 年第二季向 FDA 提交 NDA 申請。隨著我們 NDA 提交計畫的推進，我們也開始了針對 Stargardt 病的商業化專業工作。

I'm pleased to share that we have hired all of the key leadership positions and now in the process of building our organization in sales, market access, medical affairs, marketing, regulatory and operations, et cetera. It's a busy but exciting time for us, and we look forward to sharing more as we progress with our launch preparation works.

我很高興地宣布，我們已經聘請了所有關鍵領導職位的人員，現在正在組建我們的銷售、市場准入、醫學事務、行銷、監管和營運等組織。對我們來說，這是一個忙碌而又令人興奮的時期，隨著我們發布準備工作的推進，我們期待與大家分享更多資訊。

Last but not least, I'll now close with the financial recap. For the fourth quarter, R&D expenses were $14.6 million compared to $7.3 million in Q4 2024. The increase was primarily due to the first expenses related to the DRAGON II trial.

最後，我將以財務回顧作為結尾。第四季研發費用為 1,460 萬美元，而 2024 年第四季為 730 萬美元。成長的主要原因是與 DRAGON II 試驗相關的首批費用。

Second, we received a lower Australian R&D tax incentive in Q4, 2025 as such incentive was received in Q3 2025 versus last year it was received in Q4 2024. And third, API manufacturing expenses. On a non-GAAP basis, which excludes share-based compensation expenses, R&D expenses for the fourth quarter was $12.2 million compared to $5.7 million for the same period in 2024.

其次，我們在 2025 年第四季獲得的澳洲研發稅收優惠較低，因為該優惠是在 2025 年第三季獲得的，而去年是在 2024 年第四季獲得的。第三，原料藥生產成本。以非GAAP準則（不含股權激勵費用）計算，第四季的研發費用為1220萬美元，而2024年同期為570萬美元。

We believe this non-GAAP basis provides a better picture of our operating expenses since our share-based compensation expenses is heavily driven by achieving the volume milestone and the volatility of our own stock price and a comparable company stock price using the valuation. SG&A expenses were $13.5 million compared to $4.2 million in Q4 2024.

我們認為，這種非GAAP準則能更好地反映我們的營運費用，因為我們的股份支付費用很大程度上取決於銷售里程碑的實現以及我們自身股價和可比公司股價的波動性（使用估值方法）。銷售、一般及行政費用為 1,350 萬美元，而 2024 年第四季為 420 萬美元。

The increase was primarily due to increase in share-based compensation expenses and professional service fees. As we achieved development milestones and started to prepare for commercialization and value. On a non-GAAP basis, SG&A expenses for the fourth quarter was $4.2 million compared to $1.5 billion in Q4 2024.

成長的主要原因是股權激勵支出和專業服務費的增加。隨著我們取得開發里程碑，並開始為商業化和價值創造做準備。以非GAAP準則計算，第四季的銷售、一般及行政費用為420萬美元，而2024年第四季為15億美元。

Overall, the fourth quarter, we reported a net loss of $25.3 million compared to $10.1 million in Q4 2024. On a non-GAAP basis, we reported a net loss of $13.6 million for the fourth quarter compared to $5.9 million for Q4 2024.

總體而言，第四季我們報告淨虧損 2,530 萬美元，而 2024 年第四季淨虧損為 1,010 萬美元。以非GAAP準則計算，我們報告第四季淨虧損1,360萬美元，而2024年第四季淨虧損為590萬美元。

For the full year, R&D expenses were $45.4 million compared to $29.9 million for the full year 2024. The full year increase was primarily due to first expenses related to PHOENIX trial; second, share-based compensation expenses; and third, API manufacturing expenses, partially offset by the royalty payment recognized in 2024.

全年研發支出為 4,540 萬美元，而 2024 年全年研發支出為 2,990 萬美元。全年成長主要歸因於：第一，與 PHOENIX 試驗相關的支出；第二，股份支付費用；第三，API 生產費用，部分被 2024 年確認的特許權使用費抵消。

On a non-GAAP basis, excluding share-based compensation expenses, the R&D expanses were -- for the full year was $36.2 million compared to $26.2 million for the same period in 2024. SG&A expenses were $38.9 million compared to $10.1 million in 2024.

以非GAAP準則計算，不包括股份支付費用，全年研發支出為3,620萬美元，而2024年同期為2,620萬美元。銷售、一般及行政費用為 3,890 萬美元，而 2024 年為 1,010 萬美元。

The increase was primarily due to increase in share-based compensation expenses and professional service fee. As we achieved (inaudible) milestone and started to prepare for filing and commercialization. On a non-GAAP basis, SG&A expenses were -- for the full year were $9.1 million compared to $4.8 million in 2024.

成長的主要原因是股權激勵費用和專業服務費的增加。當我們達到（聽不清楚）里程碑並開始準備提交申請和商業化時。以非GAAP準則計算，全年銷售、一般及行政費用為910萬美元，而2024年為480萬美元。

For the full year, we reported a net loss of $77.6 million compared to a net loss of $36.1 million in 2024. On a non-GAAP basis, net loss was $38.7 million compared to a non-GAAP net loss of $27.2 million in 2024. Moving to the balance sheet. As I said, we had a successful year of fund raising through underwritten of the offering to registered direct offering and a significant pipe. We're very grateful to our shareholders for their strong support.

全年淨虧損為 7,760 萬美元，而 2024 年淨虧損為 3,610 萬美元。以非GAAP準則計算，淨虧損為3,870萬美元，而2024年非GAAP淨虧損為2,720萬美元。接下來查看資產負債表。正如我所說，我們透過承銷發行、註冊直接發行和大量管道融資，成功籌集了資金。我們非常感謝股東們的大力支持。

As a result, we closed the year with $772.6 million in cash, cash equivalent, US treasury bills and notes as compared with $145.2 million at the end of 2024. Our balance sheet remains strong, and we are well positioned to deliver our near and long-term objectives, including the commercial launch for Stargardt disease.

因此，到年底，我們持有現金、現金等價物、美國國庫券和票據共 7.726 億美元，而 2024 年底這一數字為 1.452 億美元。我們的資產負債表仍然強勁，我們完全有能力實現近期和長期目標，包括 Stargardt 病的商業化上市。

With that, I'll turn the call back to the operator for Q&A.

這樣，我就把電話轉回接線生進行問答環節。

(Operator Instructions) Judah Frommer, Morgan Stanley.

（操作說明）猶大‧弗羅默，摩根士丹利。

Hi guys, thanks for the update. Just a couple of questions for us. I guess on the NDA submission, are you still thinking about that being a rolling submission? And what role would DRAGON II play within that submission process. I would -- maybe in the US and other geographies as well.

大家好，感謝你們的更新。我們還有幾個問題想問一下。關於保密協議的提交，您仍然打算採用滾動提交的方式嗎？那麼，《龍之二號》在這申報過程中將扮演什麼角色？我會的——或許在美國和其他地區也是如此。

And then I guess just given the cash balance that you've amassed here, can you help us with the uses of cash between getting through the remaining Stargardt trials, getting through GA and commercialization and anything else we should be thinking about?

那麼，鑑於您目前累積的現金餘額，您能否協助我們規劃在完成剩餘的 Stargardt 試驗、完成 GA 和商業化以及我們應該考慮的其他事項之間如何使用這些現金？

Okay. I'll answer the first question regarding the NDA. So it will be a rolling submission. We are on track for the NDA submission in Q2. We're expecting the CSR to finalize this month. And once that's finalized, we are ready to submit pretty soon.

好的。我先回答關於保密協議的第一個問題。所以會採取滾動提交的方式。我們正按計劃在第二季提交保密協議。我們預計企業社會責任報告將於本月最終定稿。一旦最終確定下來，我們很快就可以提交了。

What's the next? DRAGON II, Yes. So the DRAGON II will be for Japan only because of the Japanese authorities would like to see the data of Japanese patients. So that's strictly for the Japan. And the commercialization and the budget, I think it was the other question, I'll refer that to Hao. Hao?

接下來是什麼？DRAGON II，是的。因此，DRAGON II 將只在日本使用，因為日本當局希望看到日本患者的數據。所以這僅限於日本。至於商業化和預算，我想那是另一個問題，我會請郝先生回答。郝？

Yeah, so for the next three years, we expect the existing pipeline, including the NDA submission, all of those, what we call that like R&D kind of related activity will cost us about $150 million. And for the commercialization itself for the next three years is probably somewhere between $200 million to $250 million.

是的，所以未來三年，我們預計現有的研發管線，包括新藥申請，所有這些我們稱之為研發相關活動，將花費我們約 1.5 億美元。而未來三年的商業化本身可能需要 2 億至 2.5 億美元。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Good afternoon, thanks for taking my question. Can you just give us a little bit of guidance on how we should be thinking about pricing given the profile of the drug and given the undermet need, we'd be curious to maybe get a sense of a range of what would be appropriate to be considering here? And then can you just remind us what are the key gating items left before you submit the NDA in the second quarter?

下午好，謝謝您回答我的問題。鑑於該藥物的特性以及尚未滿足的需求，您能否就我們應該如何考慮定價提供一些指導？我們很想知道這裡應該考慮的合適價格範圍是什麼？那麼，您能否提醒我們一下，在第二季提交保密協議之前，還有哪些關鍵的審批事項需要完成？

Hao, do you want to take this one as well?

郝，你也想拿這個嗎？

Sure. Well, for the pricing, apparently, it's still early for us to set a price. But I think we have been seeing that the average rare disease for price in the US, being somewhere about $350,000. And we do think it's fair to say that we expect ourselves can be doing better than that, but still early to really set a price.

當然。至於定價方面，現在顯然還為時過早。但我認為我們已經看到，在美國，罕見疾病的平均治療費用約為 35 萬美元。我們認為，我們期望自己能做得更好，但現在真正定個價格還為時過早。

Okay. And then on --

好的。然後…--

Yes, what was the other question?

對，另一個問題是什麼？

Yes, what are the gating factors left before you submit for approval in 2Q?

是的，在第二季提交審批之前，還有哪些關鍵因素需要克服？

I guess we have everything ready. So we're just waiting for the clinical study report. So as we speak, we are on track.

我想我們已經準備好了。所以我們現在就等著臨床研究報告出來了。所以就目前而言，我們一切都很順利。

Timur Ivannikov, Cantor.

蒂穆爾·伊万尼科夫，康托爾。

Thank you. This is Timur for Steve Seedhouse. So our question is about the timing of your potential launch. So assuming you have an NDA filing in the second quarter, do you have initial expectations on the launch timing?

謝謝。我是蒂穆爾，代表史蒂夫·西德豪斯。所以我們的問題是關於您潛在的產品發佈時間。假設您在第二季提交了新藥申請，您對產品上市時間有何初步預期？

And then I think you were talking about maybe 25 field reps. But how quickly after the approval, do you think you can launch? And how do you assess the difficulty of this launch maybe to other rare diseases or other retinal disease? Thank you.

然後我想你當時說的可能是 25 個現場代表。但你認為獲得批准後多久可以啟動？那麼，您該如何評估這項研究成果對其他罕見疾病或其他視網膜疾病的影響難度？謝謝。

Hao, do you want to take this one as well?

郝，你也想拿這個嗎？

Sure, sure. Well, so we expect we probably will launch by Q1 2027. The sales team, as you said, we expect that we have probably a team more focused on genetic testing, which will be one of the key factors to get the patient confirmed. The second team will be more about about the brand. So total somewhere like 25% to 30% we think is a fair assumption at launch potentially.

當然，當然。嗯，所以我們預計大概會在 2027 年第一季推出。正如您所說，我們預期銷售團隊中可能會有一個團隊更專注於基因檢測，這將是確診患者的關鍵因素之一。第二支團隊將更專注於品牌建立。因此，我們認為在發佈時，總佔比可能在 25% 到 30% 左右是一個合理的假設。

After two years of launch, you may expand that team further as you want to get to every quarter in the US. Yeah, so I think being able to launch by Q1 2027 is our goal. And to your question about the challenges, we think compared with other disease, given there is no treatment for Stargardt disease, this should be a fairly straightforward drug.

經過兩年的發展，隨著您計劃將業務拓展到美國的每個季度，您可以進一步擴大團隊規模。是的，所以我認為我們的目標是在 2027 年第一季推出產品。至於你提出的挑戰問題，我們認為與其他疾病相比，鑑於目前尚無治療 Stargardt 病的方法，這應該是一種相當簡單的藥物。

The difficulty will really be getting patients, getting the physicians be aware of this treatment is available. And then shorten the target takes for people to get the generic testing down and get the insurance coverage. I think that as will be the few execution kind of a task that we will be focused on. But I wouldn't see those are like challenges for us.

真正的困難在於如何吸引患者，以及如何讓醫生意識到這種治療方法的存在。然後縮短人們完成通用測試並獲得保險覆蓋所需的時間。我認為這將是我們重點關注的少數幾個執行類任務之一。但我認為這些對我們來說都不算是挑戰。

So how -- maybe we could get Hendrik to also add more color to this question, given that he is prescribing himself. He looks after the stock-up patients, and he knows the whole clinical landscape very well. So Hendrik, do you want to add anything? Any details?

那麼，我們該如何做呢？或許我們可以讓亨德里克也為這個問題補充一些細節，畢竟他是在為自己開處方。他負責照顧住院病人，對整個臨床狀況非常了解。亨德里克，你還有什麼要補充的嗎？有任何細節嗎？

Yeah. Thank you, Timur, but I would like to confirm what Hao just said and pointed out. It's a fact that many patients are lined up in large databases. Many of Stargardt patients because it included testing to make the diagnosis. All being seen in large centers, including large academic centers.

是的。謝謝你，蒂穆爾，但我想確認一下郝剛才所說和指出的內容。很多病人的資訊都儲存在大型資料庫中，這是不爭的事實。許多 Stargardt 患者都接受了診斷測試。所有這些都在大型中心，包括大型學術中心出現。

And such centers typically have database of patients where they also include the genotype of these patients. So these patients, therefore, are immediately available because they are known to the centers and patients can be contacted by treating physicians if the patient [didn't go] herself would not seek chemical care immediately. So I believe because this is a monogenic disease, there's an extra opportunity to get to patients very quickly.

此類中心通常擁有患者資料庫，其中也包括這些患者的基因型。因此，這些患者可以立即獲得治療，因為中心已經掌握了他們的訊息，如果患者本人沒有立即尋求藥物治療，治療醫生也可以聯繫到他們。所以我認為，因為這是一種單基因疾病，所以我們有更多機會迅速接觸到患者。

Marc Goodman, Leerink.

馬克古德曼，Leerink。

Yeah. Sorry about the confusion. Can you talk about your filing plans OUS? And then secondly, what are your latest thoughts on the timing of an interim look for the GA work you're doing? Thanks.

是的。很抱歉造成了誤會。您能談談您在海外的報稅計劃嗎？其次，您對目前正在進行的 GA 工作進行中期評估的時間安排有什麼最新想法？謝謝。

Thanks, Mark. So you're saying that the timing of ex-US NDA emissions or for the US?

謝謝你，馬克。所以你的意思是，美國以外地區 NDA 排放的時間安排，還是針對美國而言？

Yeah, yeah, OUS. Exactly, ex-US

是的，是的，OUS。沒錯，前美國

Okay. So the -- we want to set the priority of the FDA on US we want to put all resources to make sure that we are successful with the NDA in the US. So everything outside of the US will build on to that. And this requires discussions with the regulatory authorities in different regions to see what type of timing that we're expecting, or they're expecting. So this will be an update which regions they will prioritize after the US.

好的。所以——我們希望將美國FDA的優先權放在我們身上，我們希望投入所有資源，確保我們在美國的新藥申請成功。因此，美國以外的一切都將以此為基礎。這就需要與不同地區的監管機構進行討論，以了解我們預期的時間安排，或他們預期的時間安排。所以這次更新將說明他們在美利堅合眾國之後會優先考慮哪些地區。

So we are in constant communications with the EMA, the PMDA and other authorities as well. So we want to keep the US -- keep all the bandwidth on the US FDA, given that we expect there's going to be a lot of questions. So we don't want to dilute our resources at this point by spreading it to -- spread out and the submission -- submitting it on too many regions. Does that answers your question?

因此，我們與EMA、PMDA以及其他相關機構保持密切的溝通。所以我們希望把所有精力都集中在美國食品藥物管理局（FDA）身上，因為我們預計會有很多問題需要解答。所以，我們目前不想因為將資源分散到太多地區而分散資源。這樣回答了你的問題嗎？

Correct.

正確的。

What was the other one?

另一個是什麼？

The interim look for the geographic atrophy. Just curious what your latest thoughts are?

暫時尋找地理萎縮的跡象。只是好奇你最近在想些什麼？

Yes. So right now, we are probably expecting that would be somewhere second half of the year. We haven't actually looked at it yet because we are prioritizing everything on launching Tinlarebant for Stargardt. So we will have a further update for that, probably the next quarter.

是的。所以目前來看，我們預計大概會在今年下半年。我們還沒有真正研究過這個問題，因為我們正在全力以赴地為 Stargardt 推出 Tinlarebant。所以我們會就此發布進一步的更新訊息，可能要等到下個季度。

Yi Chen, H.C. Wainwright.

易晨，H.C. Wainwright。

Hi. This is Eduardo on for you. Just following up on the geographic atrophy trial. Do you have any idea of what level of lesion growth inhibition you're targeting to consider that trial as success in that broad population.

你好。這裡是愛德華多為您報道。跟進一下地理萎縮試驗的結果。您是否清楚，為了將該試驗在如此廣泛的人群中視為成功，您希望達到怎樣的病灶生長抑制水平？

And then also if you had any comments on capital allocation for the LBS009, and how you prioritize that, and when you expect to maybe move into a Phase I study and if you have any details on the specific liver indication as a primary lead.

另外，如果您對 LBS009 的資金分配、優先順序有任何意見，以及您預計何時進入 I 期研究，以及您是否有任何關於以肝臟疾病為主要治療靶點的具體細節，請告知。

So I'll get Hendrik to answer on the GA 1. I'll start with the 009. Right now, there's no plans for 009 yet. So again, we're prioritizing everything on the demand and be a successful launch in the US first, all the others were all and will prioritize after that. Hendrik?

所以我會讓 Hendrik 回答 GA 1 的問題。我先從009開始。目前還沒有009的計畫。所以，我們再次強調，我們將一切以市場需求為先，首先在美國成功推出產品，其他所有地區都將在此之後優先考慮。亨德里克？

And I'm happy -- yeah, I'm very happy to take the question on what's the threshold that would make treatment of GA success with our oral compound. When you think about OAKS, DERBY and GALE 2, the injectable, so [ABCF4-] way, they found efficacy signals of 13%, 21% and 14% in their registration trials. And given that these are injectable that need to be injected essentially monthly for the rest of the life of patients affected by GA.

我很高興——是的，我非常樂意回答這個問題：用我們的口服化合物治療 GA 的成功閾值是多少？當你想到 OAKS、DERBY 和 GALE 2 注射時，他們發現註冊試驗中療效訊號分別為 13%、21% 和 14%。而且這些藥物是注射劑，患有 GA 的患者基本上需要終生每月注射一次。

We feel that if we reach that threshold, then it is already a success. Having said that, I mean, we are more ambitious given what we found in Stargardt disease, 36%, we feel that that reaching 13%, 21%, 14% so roughly what something between 15% and 20% could absolutely be possible, and we would like to go beyond that.

我們認為，如果我們達到那個門檻，就已經算是成功了。話雖如此，我的意思是，鑑於我們在 Stargardt 病中發現的 36% 的發病率，我們更有雄心壯志，我們認為達到 13%、21%、14%，也就是大約 15% 到 20% 之間是完全有可能的，而且我們希望超越這個目標。

But again, since our compound is an oral compound, if we reach the same threshold, we will be the standard of care because it will be a very hot cell for patients to tell them to come in for injections every month if there is an oral treatment available.

但是，由於我們的化合物是口服化合物，如果我們達到相同的閾值，我們將成為標準療法，因為如果有一種口服療法可用，卻要讓患者每月來注射，這對他們來說將是一件非常棘手的事情。

Boris Peaker, Titan.

鮑里斯·皮克，泰坦。

Great, thank you very much for taking the question. Congrats on the progress. Just maybe we'll start with Stargardt. Do you anticipate the label to become a broad Stargardt label for all patients? Or would you think potentially be restricted to patients ages maybe 12 to 20, similar to the pivotal study.

太好了，非常感謝您回答這個問題。恭喜你取得進展。或許我們可以從史塔加特開始。您是否預期該標籤會成為適用於所有患者的通用 Stargardt 標籤？或者您認為可能僅限於 12 至 20 歲的患者，類似於關鍵性研究。

I'll refer this to Nathan and of course, Hendrik to add more details as well. Nathan?

我會把這件事轉交給 Nathan，當然還有 Hendrik，讓他們補充更多細節。內森？

Nathan, here, the CSO. So we've had that discussion with FDA, and we've made the argument that basically it's the same disease, whether it's affecting children or adults, and they concurred. There's no evidence to suggest that these patient populations would be any different.

我是首席安全官內森。所以我們已經和FDA討論過這個問題，我們提出論點，無論影響的是兒童還是成人，基本上都是同一種疾病，他們也同意了。沒有證據顯示這些患者群體的情況會有任何不同。

Of course, Hendrik notes from the ProgStar data that the lesion growth profiles are not dramatically different between children and adults. So yeah, we'll be pressing for the full label from -- for subjects 12 and older because, again, it's the same disease, same genetic sort of dysfunction that leads to the dysfunction of the same protein.

當然，亨德里克從 ProgStar 數據中指出，兒童和成人的病變生長並沒有顯著差異。所以，我們會爭取為 12 歲及以上的受試者提供完整的標籤，因為，再說一遍，這是同一種疾病，同一種基因功能障礙導致同一種蛋白質的功能障礙。

So again, spectrum of the same disease across different populations.

所以，同一種疾病在不同族群的表現譜繫再次顯現。

Got it. And other just to follow up on -- go ahead. Sorry.

知道了。還有其他需要跟進的問題——請繼續。對不起。

No, I just wanted to add that. It's all about the generalizability of the data, right? And there has really been such an easy case to convince the regulator, this is the same disease. And we included adult subjects 18 to 20 years, but we also included adolescents as you know, right? But if there is a patient effect at a 22, 28, 32 with violating mutations in ABCA4, why would that be considered a different disease?

不，我只是想補充一點。關鍵在於數據的普遍適用性，對吧？而且，要說服監管機構，這其實很容易，因為這是同一種疾病。我們納入了 18 至 20 歲的成年受試者，但我們也納入了青少年，如你所知，對吧？但是，如果 ABCA4 基因發生突變，導致 22、28、32 位患者出現不良反應，為什麼會認為這是一種不同的疾病呢？

Why would somebody believe there would be no efficacy if you treat later because -- and Nathan pointed it out, the proxy study has shown that the progression rates amongst different age groups, 12 to 18, 18 to 50 and beyond 50 were essentially similar.

為什麼有人會認為晚些治療就沒有療效呢？正如內森指出的那樣，代理研究表明，不同年齡組（12 至 18 歲、18 至 50 歲和 50 歲以上）的疾病進展率基本上相似。

Got it. And just another follow-up on Stargardt. I understand your initial emphasis is obviously going to be on the US market. But I'm just curious for the ex-US opportunity, how important is visual acuity, I guess, for approval and potentially for just reimbursement and justifying pricing?

知道了。還有關於斯塔加特的後續報導。我知道你們最初的重點顯然會放在美國市場。但我很好奇，對於美國以外的市場，視力敏銳度對於核准、報銷以及定價的合理性有多重要？

Hendrik, do you want to take this as well?

亨德里克，你也想拿這個嗎？

Certainly. I mean, to be clear, visual acuity is important for every regulator, right? It's just how realistic is it that any given trial in Stargardt disease would find a visual acuity efficacy signal, right? When you look at the proxy data, and an average visual acuity loss of 0.55 letters per year, but life expectancy of 60 to 80 years after the first diagnosis, that means that it's simply impossible even if you even have a treatment that arrest the progression to find an efficacy signal when vitality is the primary outcome measure.

當然。我的意思是，說清楚點，視力對每個監管人員都很重要，對吧？問題是，在斯塔加特氏症的任何一項試驗中，發現視力療效訊號的可能性究竟有多大？當你查看代理數據時，會發現平均每年視力下降 0.55 個字母，但首次診斷後的預期壽命為 60 至 80 年，這意味著即使你有一種可以阻止病情進展的治療方法，當活力是主要結果指標時，也根本不可能找到療效信號。

If arrest progression and the progression is 1.1 letters in two years, that would be the difference that you would target, but everybody knows that there's a 15-letter threshold set by the FDA to be clinically meaningful, and the intersection variability of visual acuity measurements in a population of market deterioration patients, such as Stargardt is 8 letters.

如果病情進展停止，兩年內進展為 1.1 個字母，那麼這就是你要達到的目標差異，但大家都知道，FDA 設定的臨床意義閾值為 15 個字母，而像 Stargardt 這樣的市場惡化患者群體中視力測量值的交叉變異性為 8 個字母。

So meaning that visual acuity is an outcome measure is an unrealistic target. But DDAF, which is our primary endpoint has been shown in cross-sectional correlations in the ProgStar study to be highly significantly correlated with visual acuity loss. It just means that you have to trade for a while until eventually you will see a visual acuity benefit.

因此，將視力作為結果指標是不切實際的。但 ProgStar 研究的橫斷面相關性分析表明，作為我們主要終點的 DDAF 與視力喪失高度顯著相關。這意味著你需要進行一段時間的交易，最終才能看到視力的好處。

(Operator Instructions) Bruce Jackson, Benchmark.

（操作說明）布魯斯傑克遜，基準。

Hi good afternoon. So in terms of the commercialization strategy in the United States, you've chosen to go direct, have you given any thought to what your international commercialization strategy might look like?

您好，下午好。所以，就美國的商業化策略而言，你們選擇了直接進入市場，那麼你們有沒有考慮過國際商業化策略會是什麼樣的呢？

Yes, of course. So right now, we are -- we're very flexible that we do have [Moridational] pharmaceutical companies wanting to partner more license. Right now, that's still open. But we believe right now, we -- at least our regulatory submission pathway is pretty straightforward for all regulatory authorities.

是的當然。所以目前，我們非常靈活，確實有一些[Moridational]製藥公司希望與我們合作，獲得更多許可。目前，這個職位仍然開放。但我們相信，至少就目前而言，我們的監管申報途徑對於所有監管機構來說都相當直接明了。

So we believe we can add more value, at least starting from the FDA once we get the approval, we'll see how it goes in other regions, but we believe that we have a very straightforward approval path for all other regions as well. So it depends on what kind of reasonable deals or deals that we think is a good partnership after the FDA after we get FDA approval.

所以我們相信我們可以增加更多價值，至少從 FDA 批准開始，我們會看看在其他地區的情況如何，但我們相信我們在所有其他地區都有一條非常直接的審批途徑。所以，這取決於在獲得 FDA 批准後，我們認為什麼樣的交易才是合理的，什麼樣的合作才是好的。

Okay. Great. And then if I could just get a follow-up on the ex-US regulatory strategy. You've got quite a bit going on this year. Do you intend to seek further approvals in Europe and when might those get submitted and that's --

好的。偉大的。然後，如果能得到關於美國前監管策略的後續資訊就更好了。你今年有很多事情要做。您打算在歐洲尋求進一步的審批嗎？如果打算申請，大概什麼時候提交？--

So the FDA being on top of our priority. And then second, I would say the EMA and probably next to it will be Japan as well. And then followed by China and a lot of the regions.

所以，FDA是我們工作的重中之重。其次，我認為是歐洲音樂節（EMA），其次可能是日本。然後是中國和許多其他地區。

Michael Okunewitch, Maxim.

Michael Okunewitch，Maxim。

Thank you for taking my question. Congrats on all the great progress. I guess I'd like to see if you could help me understand just how well understood the true prevalence of Stargardt diseases given there have been no approved therapies. Do you expect that having something available could help build awareness and uncover additional undiagnosed patients?

感謝您回答我的問題。祝賀你們取得的巨大進步。我想請教您，鑑於目前還沒有獲批的療法，人們對 Stargardt 病的真實患病率究竟了解多少？您是否認為提供某些資訊可以幫助提高公眾意識並發現更多未確診的患者？

Hendrik, can I refer this question to you?

亨德里克，我可以把這個問題交給你問嗎？

I'm happy to answer the question. So the answer is absolutely, absolutely. If there is a treatment, and we have seen that about a decade ago, for patients affected by biallelic mutations in RPE65 to be treated with [LUXTONA] the first gene therapy for that condition, absolutely led to a whole wave of patients that have been under-diagnosed before to be diagnosed.

我很樂意回答這個問題。所以答案是絕對的，絕對的。如果有一種治療方法，就像我們大約十年前看到的那樣，對於患有 RPE65 雙等位基因突變的患者，使用 [LUXTONA]（首個針對該疾病的基因療法）進行治療，絕對導致一大批以前未被診斷出的患者得到確診。

And that includes a proper diagnosis clinically and genetic testing. In stage disease, the symptoms are more straightforward with an RPE65. It's a much more diffused disease affecting night vision in the periphery. In Stargardt disease central vision is affected.

這包括臨床上的正確診斷和基因檢測。在疾病的早期階段，RPE65 的症狀更為明顯。這是一種影響範圍更廣、更嚴重的疾病，主要影響週邊眼部的夜視能力。斯塔加特病會影響中心視力。

Patients see clinical care, but we will need a genetic diagnosis in order to treat patients. What is the true prevalence of stage disease in the past for rare diseases. It was very difficult to find out what the actual prevalence is.

患者接受臨床治療，但我們需要基因診斷才能治療患者。過去罕見疾病的分期疾病的真實盛行率是多少？很難找出實際患病率。

It's only known in the (inaudible) study, BlueMountain Eye study, Rotterdam Eye study what the prevalent eye diseases are, but there's new opportunity since about a decade or so to study genetic databases knowing about the mutations in the target gene and the penetration rate.

目前只有（聽不清楚的）研究、BlueMountain Eye 研究和 Rotterdam Eye 研究才知道常見的眼部疾病是什麼，但大約十年前，我們有機會透過研究基因資料庫來了解目標基因的突變和滲透率。

And this allows us to estimate and taking into account the race mix in the United States that we need to consider about 53,000 patients being affected by ABCA4 mutated retinal disease, including Stargardt disease. So I think that it's a realistic number now, which is firmly based on genetic databases that are available for populations of European descent, East Asian descent and African descent.

這使我們可以估計，考慮到美國的種族組成，我們需要考慮大約 53,000 名患者受到 ABCA4 突變視網膜疾病（包括 Stargardt 病）的影響。所以我認為現在這個數字是比較現實的，它是根據歐洲血統、東亞血統和非洲血統人群的基因資料庫可靠地計算出來的。

Nathan, I believe you've published on this a few times. Anything you want to add?

內森，我相信你已經就此主題發表過幾次文章了。您還有什麼要補充的嗎？

No, no. I think Hendrik covered it very nicely. Yes, we did publish a review article recently, capping the prevalence of start disease, looking at it geographically across the world. And you can really look for that paper. It's published under my name and Hendrick's name just recently.

不，不。我覺得亨德里克解釋得非常好。是的，我們最近發表了一篇綜述文章，從地理角度分析了全球範圍內的星狀病患病率。你真的可以去找找那篇論文。它最近以我和亨德里克的名義出版了。

But yes, so 53,000 in the United States and ex US, of course, more than that globally. So -- and again, the genetics really tells us what the prevalence are. That's what the data are based upon in terms of the publication that we recently submitted -- recently got accepted.

是的，美國境內有 53,000 人，當然，美國以外地區還有更多，全球肯定不只這個數字。所以——再一次，遺傳確實能告訴我們患病率是多少。這就是我們最近提交並被接收的論文中所依據的數據。

And then just one more as a follow-up, if you don't mind. I wanted to see, do you expect that there would be any value in looking into patients younger than 12 years old? And are there any plans for this expansion?

如果你不介意的話，再問一個後續問題。我想了解一下，您認為對 12 歲以下的患者進行研究是否有價值？是否有任何擴張計劃？

Yes. Let me just take that real quick. So we do have an approved pediatric investigational plan with WEMA, which we plan to initiate in April of this year. So that's coming up very soon. That is a two year study. I'm looking at safety and efficacy in children 3 to 11 years of age.

是的。讓我快速看一下。因此，我們與 WEMA 達成了一項已獲批准的兒科研究計劃，我們計劃於今年 4 月啟動該計劃。所以這件事很快就會發生了。這是一項為期兩年的研究。我正在研究該藥物對 3 至 11 歲兒童的安全性和有效性。

So we'll have to wait to see what the safety and efficacy data look like at the end of the 2-year study. But certainly, we do have plans to establish safety and efficacy in patients younger than 12?

所以，我們只能等到兩年的研究結束時，才能看到安全性和有效性數據的情況。但我們確實有計劃來確定對 12 歲以下患者的安全性和有效性？

And Hendrik, I believe that you answered the same question as well as one of the medical conferences just a month ago.

亨德里克，我相信你一個月前在一次醫學會議上也回答過同樣的問題。

Yeah, indeed. And we feel that although in DRAGON patients already had a significantly lost vision on average, we feel that patients before losing significant vision will strongly benefit from Tinlarebant treatment. And that would typically be relatively young patients. So we feel that we absolutely must expand into the pediatric population. And as Nathan pointed out, it will be based on our findings in our pediatric study that we will start in the second quarter of this year.

沒錯，確實如此。我們認為，儘管 DRAGON 患者的平均視力已經嚴重受損，但我們認為，視力尚未嚴重受損的患者將從 Tinlarebant 治療中獲益匪淺。而且這些患者通常比較年輕。因此，我們認為我們絕對必須將業務拓展到兒科領域。正如內森指出的那樣，這將基於我們今年第二季度開始的兒科研究的發現。

There are no further questions at this time. This concludes today's call. Thank you for attending. You may now disconnect.

目前沒有其他問題了。今天的電話會議到此結束。謝謝各位的出席。您現在可以斷開連線了。