Clearside Biomedical Inc (CLSD) 2024 Q4 法說會逐字稿

Greetings, and welcome to the Clearside Biomedical fourth quarter 2024 financial results and corporate update call. At this time, all participants are in a listen-only mode and a question-and-answer session will follow the formal presentation (Operator Instructions) Please note, this conference is being recorded.

您好，歡迎您參加 Clearside Biomedical 2024 年第四季財務業績和公司最新情況電話會議。此時，所有參與者都處於只聽模式，正式演示後將進行問答環節（操作員指示）請注意，本次會議正在錄音。

I will now turn the conference over to your host, Jenny Kobin of Investor Relations. Ma'am, the floor is yours.

現在我將會議交給主持人、投資者關係部的珍妮‧科賓 (Jenny Kobin)。女士，請您發言。

Good afternoon, everyone, and thank you for joining us on the call today. Before we begin, I would like to remind you that during today's call, we will be making certain forward-looking statements, various remarks that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995.

大家下午好，感謝大家今天參加我們的電話會議。在我們開始之前，我想提醒您，在今天的電話會議中，我們將做出某些前瞻性陳述，我們在電話會議中對公司未來預期、計劃和前景所做的各種評論均構成《1995 年私人證券訴訟改革法案》所指的前瞻性陳述。

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our annual Report on Form 10-K for the year ended December 31, 2024, and our other SEC filings available on our website.

由於各種重要因素，實際結果可能與這些前瞻性陳述所示的結果有重大差異，包括我們截至 2024 年 12 月 31 日的年度 10-K 表報告的風險因素部分以及我們網站上提供的其他 SEC 文件中討論的因素。

In addition, any forward-looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our views change.

此外，任何前瞻性陳述均代表我們截至今天的觀點，不應被視為代表我們在任何後續日期的觀點。雖然我們可能選擇在未來更新這些前瞻性陳述，但我們明確表示不承擔任何這樣做的義務，即使我們的觀點改變。

On today's call, we have George Lasezkay, our Chief Executive Officer, Dr. Victor Chong, our Chief Medical Officer and Head of Research and Development, and Charlie Deignan, our Chief Financial Officer.

參加今天電話會議的有我們的執行長 George Lasezkay、我們的首席醫療官兼研發主管 Victor Chong 博士，以及我們的財務長 Charlie Deignan。

We also have accompanying slides that are available on Clearside's website in the Events and Presentations section. After our formal remarks, we will open the call for your questions.

我們也提供隨附的幻燈片，可在 Clearside 網站的「活動和簡報」部分找到。正式發言結束後，我們將開始回答大家的提問。

I would now like to turn the call over to George.

現在我想把電話轉給喬治。

Thank you, Jenny, and good afternoon, everyone. Clearside is the proven leader in the delivery of drugs and drug candidates to the suprachoroidal space. Our SCS Microinjector provides safe and reliable delivery with over 15,000 suprachoroidal injections performed to date.

謝謝你，珍妮，大家下午好。Clearside 是向脈絡膜上腔輸送藥物和候選藥物領域公認的領導者。我們的 SCS 微注射器提供安全可靠的輸送，迄今已進行超過 15,000 次脈絡膜上腔注射。

We continue to have increasing interest among retinal specialists and leading pharmaceutical companies in applying our innovative delivery platform to treating serious retinal diseases. We are pleased to announce that the positive results from our ODYSSEY Phase 2b wet AMD clinical trial led to a successful end of Phase 2 meeting with the FDA regarding the planned Phase 3 activities for CLS-AX.

視網膜專家和領先的製藥公司對應用我們的創新交付平台治療嚴重視網膜疾病的興趣日益濃厚。我們很高興地宣布，ODYSSEY 2b 期濕性 AMD 臨床試驗的積極成果促成了與 FDA 就 CLS-AX 計劃的 3 期活動舉行的 2 期會議圓滿結束。

Based on our interactions with the FDA, we are aligned on a pivotal Phase 3 program that we believe is positioned for success and maximizes the commercial potential for CLS-AX and wet AMD. Victor will elaborate on these plans shortly.

根據我們與 FDA 的互動，我們一致同意開展一項關鍵的 3 期計劃，我們相信該計劃將取得成功，並能最大限度地發揮 CLS-AX 和濕性 AMD 的商業潛力。維克多將很快詳細說明這些計劃。

Our commercial and development partners have made excellent progress over the last several months as they continue to validate the broad applicability of suprachoroidal delivery in several indications.

我們的商業和開發合作夥伴在過去幾個月中取得了出色的進展，他們繼續驗證脈絡膜上腔給藥在多種適應症中的廣泛適用性。

Across our partners, suprachoroidal treatments being developed for delivery by our SCS Microinjector are now approved in two Asian territories under regulatory review in China and involved in two ongoing or planned Phase 3 trials.

在我們的合作夥伴中，由我們的 SCS 微注射器進行的脈絡膜上腔治療現已在兩個亞洲地區獲得批准，並在中國接受監管審查，並涉及兩項正在進行或計劃中的 3 期試驗。

Our partner, Arctic Vision, achieved several regulatory milestones in the Asia-Pacific region with ARCATUS, or XIPERE, for the treatment of Uveitic Macular Edema. This year, they announced that a new drug application is currently under regulatory review in China and that the product was approved in Australia and Singapore.

我們的合作夥伴極目生物憑藉 ARCATUS 或 XIPERE 在亞太地區取得了多項監管里程碑，用於治療葡萄膜炎黃斑水腫。今年，他們宣布一項新藥申請目前正在中國接受監管審查，並且該產品已在澳洲和新加坡獲得批准。

Importantly, Arctic Vision also entered into a commercial collaboration with Santen Pharmaceuticals for the marketing and distribution rights to ARCATUS in China.

重要的是，極目生物也與參天製藥達成商業合作，獲得 ARCATUS 在中國的營銷和分銷權。

In addition, REGENXBIO in collaboration with AbbVie announced in January that a global Phase 3 Clinical Program in diabetic retinopathy for their gene therapy candidate, RGX-314, now referred to as SURIVEC is planned to start later this year using our SCS Microinjector. In addition, their Phase 2 ALTITUDE suprachoroidal trial is currently enrolling a cohort of patients with center-involved diabetic Macular Edema and their Phase 3 AVH suprachoroidal trial is enrolling a cohort in wet AMD at dose level four.

此外，REGENXBIO 與 AbbVie 於 1 月合作宣布，計劃於今年稍後使用我們的 SCS 微注射器啟動針對糖尿病視網膜病變的全球 3 期臨床計劃，該計劃針對的是其候選基因治療藥物 RGX-314（現稱為 SURIVEC）。此外，他們的 2 期 ALTITUDE 脈絡膜上腔試驗目前正在招募一群中心型糖尿病性黃斑水腫患者，而他們的 3 期 AVH 脈絡膜上腔試驗正在招募一批劑量水平為四的濕性 AMD 患者。

Our oncology partner, Aura Biosciences, is enrolling its global suprachoroidal Phase 3 trial of Bel-sar for the first-line treatment of patients with choroidal melanom delivered using our SCS Microinjector.

我們的腫瘤學合作夥伴 Aura Biosciences 正在招募 Bel-sar 的全球脈絡膜上腔 3 期試驗，以使用我們的 SCS 微注射器對脈絡膜黑色素瘤患者進行一線治療。

Aura has also initiated a Phase 2 trial in Metastases to the Choroid. And finally, our partner BioCryst recently highlighted plans to initiate clinical testing in 2025 of avoralstat, its plasma kallikrein inhibitor using suprachoroidal administration for the potential treatment of DME.

Aura 也啟動了脈絡膜轉移瘤的第 2 期試驗。最後，我們的合作夥伴 BioCryst 最近強調了在 2025 年開始對其血漿激肽釋放酶抑制劑 avoralstat 進行臨床試驗的計劃，該藥物透過脈絡膜上腔給藥用於治療 DME。

With that, I would now like to turn over the call to our Chief Medical Officer and Head of Research and Development, Dr. Victor Chong, to outline the Phase 3 plans for CLS-AX and other opportunities with

現在，我想將電話轉交給我們的首席醫療官兼研發主管 Victor Chong 博士，概述 CLS-AX 的第三階段計劃以及其他機會

Our suprachoroidal pipeline. Victor?

我們的脈絡膜上腔管道。勝利者？

Thank you, George, and good afternoon, everyone. As George described, we are excited about the result of ODYSSEY that supports CLS-AX as a Phase 3 ready asset for the treatment of wet AMD. Today, I would like to share several slides outlining the Phase 3 plans that we believe will position CLS-AX as a leading maintenance treatment for wet AMD if the results are positive.

謝謝你，喬治，大家下午好。正如喬治所描述的，我們對 ODYSSEY 的結果感到非常興奮，它支持 CLS-AX 作為治療濕性 AMD 的 3 期就緒資產。今天，我想分享幾張投影片，概述第三階段計劃，我們相信，如果結果是正面的，CLS-AX 將成為濕性 AMD 的領先維持治療方法。

To begin, I will highlight two subgroup analysis from ODYSSEY that helped inform the current Phase 3 trial design. Some of these data were presented at Angiogenesis at Retina Society last month, which provide an opportunity for us to continue to gather KOL feedback. The first analysis provided the basis for the targeted patient population and supports enrolling treatment naive patients in Phase 3 trial.

首先，我將重點介紹 ODYSSEY 的兩個亞組分析，它們為目前的 3 期試驗設計提供了參考。其中一些數據已於上個月在視網膜學會血管生成會議上展示，這為我們繼續收集 KOL 回饋提供了機會。第一次分析為目標患者群體提供了基礎，並支持在 3 期試驗中招募未接受過治療的患者。

On this graph, we showed the participant solely redosed the CLS-AX at week 24, meaning that they did not receive any additional interventional treatment before or after the second mandatory CLS-AX dose at week 24.

在此圖表中，我們顯示參與者僅在第 24 週重新服用了 CLS-AX，這意味著他們在第 24 週第二次強制服用 CLS-AX 之前或之後沒有接受任何額外的介入治療。

As you can see, the subgroup analysis shows even more stable BCVA and CST in this participant to week 36. And we believe that by targeting treatment naive patient in the Phase 3 trial, there may be an even greater percentage of patients reaching six months without the need for any intervention.

如您所見，亞組分析顯示，截至第 36 週，該參與者的 BCVA 和 CST 更加穩定。我們相信，透過在第 3 階段試驗中針對未接受過治療的患者，可能會有更大比例的患者在不需要任何干預的情況下達到六個月的治療效果。

On the next slide, a second subgroup analysis support the plan to Phase 3 redesign that exclude the participant with non-disease related changes in visual acuity prior to randomization. This chart exclude the data at which the visit where the patient vision have a change of 10 or more lesser from their previous visit, but did not have a corresponding change in CST of at least 25 microns. What they mean is that the patient did not see as well that day on the eye chart, but without significant OCT changes.

在下一張投影片中，第二個亞組分析支援第 3 階段重新設計計劃，該計劃排除隨機分組前視力發生非疾病相關變化的參與者。此圖表不包括患者視力與上次就診相比變化 10 或更多，但 CST 沒有發生至少 25 微米相應變化的數據。他們的意思是，病人當天的視力表顯示視力不太好，但沒有明顯的 OCT 變化。

This tell us the BCVA change on that day may not be disease related. It may just be that the patient did not perform the test well on that day. In running this analysis, we again saw compelling BCVA result. In the Phase 3 trial, by excluding patients who have a 10 letter change just prior to randomization, we may reduce BCVA variability unrelated to wet AMD activities.

這告訴我們當天的BCVA變化可能與疾病無關。有可能只是病人當天的檢查沒有做好。在運行此分析時，我們再次看到了令人信服的 BCVA 結果。在第 3 期試驗中，排除隨機分組前有 10 個字母變化的患者，我們可以減少與濕性 AMD 活動無關的 BCVA 變異性。

Now I'd like to walk you through the Phase 3 plans and trial design discussed and agreed with the FDA at our recent end of Phase 2 meeting. The plan we presented to the FDA is for two pivotal non-inferiority trial.

現在我想向您介紹我們最近在第 2 階段會議結束時與 FDA 討論並同意的第 3 階段計劃和試驗設計。我們向 FDA 提交的計劃是進行兩項關鍵的非劣效性試驗。

The trial design is similar to the most recent Phase 3 trial in wet AMD that lead to the approval of EYLEA high dose and VABYSMO. The design applies the redosing criteria generally utilized in real world clinical practice which will feature the ability to flexibly dose CLS-AX.

該試驗設計與最近的濕性 AMD 3 期試驗相似，該試驗促使 EYLEA 高劑量和 VABYSMO 獲得批准。該設計採用了現實世界臨床實踐中普遍使用的重複給藥標準，具有靈活調整 CLS-AX 劑量的能力。

And we believe the ability to redose with CLS-AX versus rescuing patient with anti-VEGF product is an important differentiator compared to other TKI programs currently in development.

我們相信，與目前正在開發的其​​他 TKI 項目相比，使用 CLS-AX 重新給藥的能力與使用抗 VEGF 產品搶救患者的能力是一個重要的區別因素。

Slide 9 shows the current plan that Phase 3 program designed to potentially reduce regulatory risk and maximize the commercial opportunity for CLS-AX in wet AMD. I will walk through this key design aspect.

幻燈片 9 展示了第 3 階段計劃的當前計劃，該計劃旨在潛在地降低監管風險並最大限度地提高 CLS-AX 在濕性 AMD 領域的商業機會。我將介紹這個關鍵的設計方面。

As I mentioned previously, the plan is to enroll treatment naive patients which we believe can potentially expand the commercial value of CLS-AX with a broader patient population. From a statistical perspective, we know it is important to reduce variability in a non-inferiority study.

正如我之前提到的，該計劃旨在招募未接受過治療的患者，我們相信這可以擴大 CLS-AX 在更廣泛的患者群體中的商業價值。從統計學角度來看，我們知道減少非劣效性研究中的變異性非常重要。

The plan is optimized outside the population. We know from previous studies, patients with poor vision and or thicker retinas have high variability in the outcome.

該計劃針對人群之外進行了最佳化。我們從先前的研究中了解到，視力較差或視網膜較厚的患者的治療結果差異很大。

Therefore, at screening, participants will be required to have a BCVA reading between 20-80 to 20 over 32. In addition, the CST reading on the OCT must be less than 500 microns. These components are designed to minimize enrollment of highly variable patients to potentially increase the probability of success of the trial.

因此，在篩選時，參與者的 BCVA 讀數需要介於 20-80 到 20/32 之間。此外，OCT 上的 CST 讀數必須小於 500 微米。這些組件旨在最大限度地減少高度可變患者的入組，以潛在地增加試驗成功的可能性。

Between the third and the fourth injection of Aflibercept, we do not normally see a change of vision or anatomy. Therefore, the plan is to exclude participants who had more than a 10 letter change or a CST increase of more than 100 microns from their previous visit.

在第三和第四次注射阿柏西普之間，我們通常看不到視力或解剖結構的變化。因此，計劃排除與上次訪問相比變化超過 10 個字母或 CST 增加超過 100 微米的參與者。

This criteria were strongly recommended by KOLs on our Scientific Advisory Board and are designed to increase the probability of success by further reducing variability.

此標準得到了我們科學顧問委員會的關鍵意見領袖的強烈推薦，旨在透過進一步降低可變性來提高成功的可能性。

On day one, participants will then be randomized one-to-one to CLS-AX 1 milligram or Aflibercept 2 milligram. Participants in the Aflibercept arm will receive treatment every eight weeks per standard dosing label up to the primary endpoint at week 52. In a CLS-AX arm, in week 12, 16, and 20, participants will undergo an assessment for disease activity to determine the personalized treatment interval or PTI.

第一天，參與者將以一對一隨機分配服用 CLS-AX 1 毫克或阿柏西普 2 毫克。阿柏西普組的參與者將依照標準劑量標籤每八週接受一次治療，直到第 52 週達到主要終點。在 CLS-AX 組中，第 12、16 和 20 週，參與者將接受疾病活動評估，以確定個人化治療間隔或 PTI。

Based on the PTI, participants will be assigned to a treatment regimen of every 12, 16, or 20 weeks. The plan is to employ in-office OCT biomarker that will be determined using an AI tool to improve consistency in assessing the need for re-dosing. For those patients who did not meet the criteria at week 20, they will be assigned to a treatment regimen of every 24 weeks.

根據 PTI，參與者將被分配到每 12、16 或 20 週的治療方案。該計劃將採用辦公室內 OCT 生物標記物，並使用人工智慧工具進行確定，以提高評估重新給藥需求的一致性。對於第 20 週未達到標準的患者，他們將被分配到每 24 週一次的治療方案。

Once a dosing interval is established for each participant during the PTI period, the participant will stay at that interval until the primary endpoint at week 52. This is the fixed dosing period. For example, if the participant met the PTI criteria at week 16, they will be given CLS-AX every 16 weeks in a fixed dosing period.

一旦在 PTI 期間為每位參與者確定了給藥間隔，參與者將保持該間隔直到第 52 週的主要終點。這是固定的給藥期。例如，如果參與者在第 16 週符合 PTI 標準，則他們將在固定給藥期內每 16 週接受一次 CLS-AX 治療。

After the primary endpoint is reached, the trial will continue for another year as a safety follow-up period to produce the data required by the FDA for a new drug application. In a CLS-AX arm, the fixed dosing interval will end. The participant will then continue and be treated with variable dosing according to anatomical sign based on the PTI criteria.

達到主要終點後，試驗將持續一年作為安全追蹤期，以產生 FDA 對新藥申請所需的數據。在 CLS-AX 組中，固定給藥間隔將結束。然後，參​​與者將繼續接受治療，並根據 PTI 標準的解剖體徵接受不同劑量的治療。

In the Aflibercept arm, patient will cross over to receive CLS-AX every 16 weeks, which will provide additional safety and efficacy data in an anti-VEGF treatment experienced patient population. It will also provide experience in moving patient from Aflibercept to CLS-AX as a maintenance therapy.

在阿柏西普組中，患者將每 16 週接受一次 CLS-AX 治療，這將為接受過抗 VEGF 治療的患者群體提供額外的安全性和有效性數據。它還將為患者從阿柏西普轉向 CLS-AX 作為維持治療提供經驗。

Wet AMD is a chronic disease requiring numerous injections to maintain vision and stabilize the disease. We are targeting CLS-AX as a maintenance treatment, which accounts for the majority of the wet AMD treatment market.

濕性 AMD 是一種慢性疾病，需要多次注射才能維持視力並穩定病情。我們將 CLS-AX 作為維持治療的目標，它佔據了濕性 AMD 治療市場的大部分份額。

We know from clinical experience that patients require differing frequency of treatment to achieve stable vision. We are the only TKI in development with multi-dosing data from our Phase 2b trial, and the only TKI in development with the ability to re-dose before six months.

我們從臨床經驗中了解到，患者需要不同頻率的治療才能獲得穩定的視力。我們是唯一一款擁有 2b 期試驗的多劑量數據且正在開發的 TKI，也是唯一一款能夠在六個月前重新給藥的正在開發的 TKI。

Therefore, we expect minimal to no anti-VEGF rescue in Phase 3, which could reduce our regulatory risk and prove to be a clear and important differentiator. All in, we believe this important feature of the Phase 3 trial supports a strong regulatory and commercial strategy for the success of CLS-AX.

因此，我們預計第 3 階段的抗 VEGF 救援將很少甚至不需要，這可以降低我們的監管風險，並被證明是一個明顯而重要的區別因素。總而言之，我們相信，第三階段試驗的這一重要特點為 CLS-AX 的成功提供了強而有力的監管和商業策略支援。

On Slide 17, we have laid out the competitive landscape related to dosing flexibility in the wet AMD market. The initially approved anti-VEGF drugs to treat wet AMD work well, but have lower durability and less flexibility in dosing regimen.

在第 17 張投影片上，我們展示了濕 AMD 市場中與劑量彈性相關的競爭格局。最初核准用於治療濕性AMD的抗VEGF藥物效果良好，但持久性較差，給藥方案靈活性較差。

The next generation have moderate durability and a more flexible dosing regimen. We have heard from numerous physicians that the dosing flexibility of one to four months was important to them. In contrast, the protocol for other TKI currently in development only allow for dosing at 24 weeks’ interval, and participants will need to be rescued if they cannot go that long.

下一代具有中等的耐用性和更靈活的給藥方案。我們從許多醫生那裡聽說，一到四個月的劑量彈性對他們來說很重要。相較之下，目前正在開發的其​​他 TKI 方案僅允許以 24 週的間隔給藥，如果參與者無法堅持那麼長時間，則需要進行救援。

With durability up to six months and flexible dosing regimen, we believe CLS-AX will have a potential versatile and commercially appealing label and would be well-positioned to compete in the WET-AMD market, which represents over $12 billion in annual sales.

由於其長達六個月的耐用性和靈活的給藥方案，我們相信 CLS-AX 將擁有潛在的多功能和商業吸引力的標籤，並將在年銷售額超過 120 億美元的 WET-AMD 市場中佔據有利競爭地位。

Before I turn the call to Charlie, I want to take a minute to review our pipeline opportunities. We continue to be excited about the broad potential of suprachoroidal delivery with SCS Microinjector.

在將電話轉給查理之前，我想花一點時間來回顧我們的頻道機會。我們繼續對 SCS 微注射器在脈絡膜上腔給藥方面的巨大潛力感到興奮。

Internally, I see a great potential opportunity beyond wet AMD, where delivering of small molecules via the suprachoroidal space could make a tremendous impact in the treatment of retinal disease.

從內部來看，我看到了濕性 AMD 以外的巨大潛在機會，透過脈絡膜上腔輸送小分子可以對視網膜疾病的治療產生巨大影響。

Our research team is currently evaluating two approaches with certain specific small molecules for in-vivo models for the potential suprachoroidal treatment of geographic atrophy.

我們的研究團隊目前正在評估兩種方法，利用某些特定的小分子在體內模型上對地圖樣萎縮進行潛在的脈絡膜上腔治療。

Our team is doing the necessary work to potentially advancing one or both of these candidates toward an investigational new drug application.

我們的團隊正在進行必要的工作，以潛在地推動其中一個或兩個候選藥物進入新藥研究申請階段。

In GA, we are currently evaluating two methods of action that could potentially be used as an add-on to complement-based therapy. Administered suprachoroidally, this small molecule suspension can treat both sides of the Bruch's membrane, including the retina, RPE, and the Choroid. And with suprachoroidal administration of the agents, we expect to achieve higher concentration of drug in the Choroid.

在 GA 中，我們目前正在評估兩種可能作為補體療法附加療法的作用方法。這種小分子懸浮液透過脈絡膜上腔給藥，可以治療布魯赫膜的兩側，包括視網膜、RPE 和脈絡膜。透過脈絡膜上腔給藥，我們期望在脈絡膜中實現更高的藥物濃度。

As a result, we believe this molecule will improve Choroidal perfusion to improve retinal function directly and slow progression. And modulating for the inflammatory cell can reduce the root cause of complement activation.

因此，我們相信這種分子將改善脈絡膜灌注，從而直接改善視網膜功能並減緩進展。而針對發炎細胞的調節可以減少補體活化的根本原因。

With that, I will turn the call over to our CFO, Charlie Deignan, to provide a financial update.

說完這些，我將把電話轉給我們的財務長 Charlie Deignan，以提供財務更新。

Thank you, Victor, and good afternoon, everyone. Our financial results for the fourth quarter and year-ended 2024 were published earlier in our press release and are available on our website. Therefore, I will just provide a summary of our financial status on today's call.

謝謝你，維克多，大家下午好。我們第四季和 2024 年全年的財務業績已在先前的新聞稿中公佈，並可在我們的網站上查閱。因此，我只會在今天的電話會議上提供我們財務狀況的摘要。

As of December 31st, 2024, our cash and cash equivalents totaled approximately $20 million. We believe we have sufficient resources to fund our planned operations into the fourth quarter of 2025.

截至 2024 年 12 月 31 日，我們的現金及現金等價物總額約為 2,000 萬美元。我們相信，我們有足夠的資源來資助我們計劃在 2025 年第四季的營運。

We are actively pursuing options to fund the CLS-AX Phase 3 program, including potentially partnering with one or more third parties. We look forward to participating in the Needham Virtual Healthcare Conference and the JonesTrading Conference next month.

我們正在積極尋求資助 CLS-AX 第三階段計畫的方案，包括可能與一個或多個第三方合作。我們期待參加下個月的尼德姆虛擬醫療保健會議和瓊斯交易會議。

I will now turn the call back to George for his closing remarks.

現在我將把電話轉回給喬治，請他作最後發言。

Thank you, Charlie. We remain focused on our small molecule suprachoroidal pipeline led by CLS-AX for the treatment of wet AMD. We have seen increasing interest among retinal specialists and leading pharmaceutical companies in applying the suprachoroidal delivery approach to treat serious retinal diseases.

謝謝你，查理。我們仍然專注於以 CLS-AX 為主導的用於治療濕性 AMD 的小分子脈絡膜上腔藥物管線。我們看到視網膜專家和領先的製藥公司對應用脈絡膜上腔給藥方法治療嚴重視網膜疾病的興趣日益濃厚。

Our broad formulation, development, and regulatory expertise in the delivery of agents to the suprachoroidal space makes us well positioned in the overall treatment landscape for retinal diseases. We are grateful for the hard work and dedication of our Clearside team and the ongoing support from our stakeholders as we continue to advance our suprachoroidal delivery pipeline.

我們在向脈絡膜上腔輸送藥物方面擁有豐富的配方、開發和監管專業知識，這使我們在視網膜疾病的整體治療領域佔據有利地位。我們感謝 Clearside 團隊的辛勤工作和奉獻精神，以及利害關係人在我們繼續推進脈絡膜上腔輸送管道過程中給予的持續支持。

I would now like to ask the operator to open the call up for questions.

現在我想請接線生打開電話回答問題。

(Operator Instructions) Jon Wolleben with Citizens.

（操作員指示）Jon Wolleben 與公民在一起。

Hey, good afternoon, and thanks for taking the questions. The subpopulation and the amendments you're making to the planned Phase 3, I'm wondering if you could give any context about how you think that might improve the results from what you saw in Phase 2?

嘿，下午好，感謝您回答問題。對於計劃中的第 3 階段的亞群和所做的修改，我想知道您是否可以提供一些背景信息，說明您認為這些修改可能會如何改善第 2 階段的結果？

Victor, are you there?

維克多，你在嗎？

Sure. Can you hear me?

當然。你聽得到我嗎？

Yes, I can.

是的，我可以。

Yeah, So can you so I think that in the Planned Phase 3 that we tried to exclude the patient with higher rare disease. I think the one to think about is on the Phase 2, we're deliberately selecting the patients who are very difficult to treat, and we believe that moving to a more general population, we would have better results.

是的，所以你可以，所以我認為在計劃的第 3 階段我們試圖排除患有較高罕見疾病的患者。我認為需要考慮的是在第二階段，我們特意選擇了那些很難治療的患者，我們相信，如果將其應用於更廣泛的人群，我們會取得更好的結果。

One of the subgroup analysis, the first one that we mentioned, said those who actually doesn't need any extra treatment, and so one of the concerns was that could be undertreated, but in fact they were not they were actually doing extremely well.

我們提到的第一個亞組分析表明，那些實際上不需要任何額外治療的人，因此人們擔心的問題之一是他們可能治療不足，但事實上他們的情況非常好。

So we believe that when we move to the general population, that segment that only need every six months’ injection would be actually higher. I don't know whether that is what you are referring to, because the second subgroup analysis changed the population slightly in a different way.

因此，我們相信，當我們轉向普通人群時，每六個月只需注射一次的那部分人群實際上會更高。我不知道這是否是您所指的，因為第二個亞組分析以不同的方式稍微改變了人口。

It's sort of helpful. I'm wondering, you know, maybe it's a difficult question to answer, but maybe moving on to two other ones. How long do you think it could take to enroll how long do you think it would take to enroll the treatment-naive population?

這有點幫助。我想知道，也許這是一個很難回答的問題，但也許我們可以轉到另外兩個問題。您認為招募未接受過治療的人需要多長時間？

And then last one for me, did FDA say you need a certain number of patients in each of these treatment intervals to have a sufficient size to show efficacy and safety? Or will it be purely on the individual assessment of the response as well?

然後對我來說最後一個問題，FDA 是否說過需要在每個治療間隔內有一定數量的患者才能達到足夠的規模來證明療效和安全性？或者這也純粹取決於個人對反應的評估？

Yeah, I think the first question first is how long do we expect it to enroll? And usually this kind of trial will be around 12 months or slightly under 12 months. And indeed that we see the recent trial in other Phase 3 doing pretty well. So we were expecting that would be probably just under 12 months.

是的，我認為第一個問題是我們預計它需要多長時間才能入學？通常這種試驗期約為 12 個月或略短於 12 個月。我們確實看到最近其他第 3 階段的試驗進展相當順利。因此我們預計這可能只需要不到 12 個月的時間。

In terms of the agency, that this is the type of analysis very, very similar to what the two recent approvals with EYLEA high dosing and faricimab.

就該機構而言，這種分析類型與最近批准的 EYLEA 高劑量和 faricimab 非常非常相似。

So we do not expect that they would be separating the adverse event rate in different group on different frequency. And it's really the drug as overall. And it's just a similar expectation that we're using the drug when we get to market would be on different interval. So we'll not expect that.

因此，我們不希望他們將不良事件發生率以不同的頻率分為不同的組別。總的來說，它確實是一種藥物。這只是我們對藥物使用的類似預期，當我們將藥物推向市場時，其時間間隔會有所不同。所以我們不會期待這一點。

I think the agency was quite clear that it would be considered as one arm. So the whole event assessment will be merged together. And I think that's a very similar modality that they use for EYLEA high dosing and VABYSMO.

我認為該機構非常清楚，它將被視為一個部門。所以整個活動的評估將會合併在一起。我認為這與他們用於 EYLEA 高劑量和 VABYSMO 的方式非常相似。

Okay, got it. All right. Thanks for taking the questions.

好的，明白了。好的。感謝您回答這些問題。

Serge Belanger with Needham.

Serge Belanger 和 Needham。

Hi, good afternoon. I guess my first question now that the Phase 3 trial plan has been finalized, can you give us an estimate of the overall cost of such a program? And I guess, is it feasible, you know, we're talking about 900 patients total here for Clearside to run such a large program? Thanks.

嗨，下午好。我想我的第一個問題是，現在第三階段試驗計劃已經最終確定，您能否給我們估算一下該計劃的總體成本？我想，對於 Clearside 來說，運行如此大型的專案是否可行，您知道嗎？我們討論的是總共 900 位患者。謝謝。

So I'll answer the second part and let Charlie answer the first part. And yes, we would, using a global CRO. And so we believe that it's something that we would be able to manage.

因此我來回答第二部分，讓查理回答第一部分。是的，我們會使用全球 CRO。因此我們相信這是我們能夠解決的事情。

And although it's a relatively large trial, but at the same time that wet AMD trial is read to be straightforward from both the end point and the investigation meters. And I'll let Charlie answer the first part about the cost.

雖然這是一項相對較大的試驗，但同時，從終點和調查指標來看，濕性 AMD 試驗都很簡單直接。我請查理回答有關成本的第一部分。

Yeah, and Serge, I'll also just remind you, you know, back, we ran two Phase 3 concurrent RVO studies years ago. So, you know, we know how to run Phase 3 trials here. In terms of cost, you know, we're not giving specifics on the cost, but, you know, I think, you know, some of the other Phase 3, I think I've seen, you know, they're around $55 million, $60 million for each study. But, you know, we haven't given out an estimate for our numbers for our trials.

是的，Serge，我還要提醒你，你知道，幾年前我們進行了兩項 3 期並發 RVO 研究。所以，您知道，我們知道如何在這裡進行第三階段試驗。在成本方面，您知道，我們沒有給出具體的成本信息，但是，您知道，我認為，其他一些第三階段的研究，我認為我已經看到，每項研究的成本大約為 5500 萬美元到 6000 萬美元。但是，你知道，我們還沒有給出試驗人數的估計。

Okay, thanks. And I guess one for Victor, I'm just curious, and as you set up the design of the Phase 3, whether you considered emulating one of your potential competitor in running a superiority trial? And why what were the pros and cons and why you decided to go forward with two non-inferiority studies? Thanks.

好的，謝謝。我想 Victor 也有一個問題，我只是好奇，當您設計第三階段時，您是否考慮過模仿您的一個潛在競爭對手來進行優效性試驗？為什麼其優點和缺點是什麼，以及為什麼您決定繼續進行兩項非劣效性研究？謝謝。

The two non-inferiority studies was true and tested, and the agency have reflected that multiple times. And this is a lot more risky if the two trials is not the same. And I can't comment on a competitor why they decided to do something different, and that is their decision.

這兩項非劣效性研究是真實的、經過檢驗的，該機構已多次反映這一點。如果兩次試驗不一樣，風險就會更大。我無法評論競爭對手為什麼決定做不同的事情，這是他們的決定。

And I think from our point of view and also our interaction with the agency, the two non-inferiority trials is proven and tested in virtually, if not every single retinal drug was approved based on the two non-inferiority trials, other than obviously the first one, Lucentis was a superior trial.

我認為，從我們的觀點以及我們與該機構的互動來看，這兩項非劣效性試驗實際上已經得到證明和測試，如果不是每一種視網膜藥物都是基於這兩項非劣效性試驗獲得批准的，那麼除了顯然是第一個試驗之外，Lucentis 是一項更優的試驗。

Thank you.

謝謝。

Debanjana Chatterjee with JonesTrading.

Debanjana Chatterjee 與 JonesTrading 合作。

Hi, thanks for taking my question. I was wondering if you could provide any additional color on the, you know, your financing strategies for the Phase 2 I'm sorry, Phase 3, and how should we think about the timeline of the study initiation? I know you were planning initiation in the second half. Is that still the plan?

你好，謝謝你回答我的問題。我想知道您是否可以提供有關第二階段（對不起，是第三階段）融資策略的更多詳細信息，以及我們應該如何考慮研究啟動的時間表？我知道你計劃在下半場開始。這還是計劃嗎？

Well, want me to take this?

那麼，想讓我拿這個嗎？

Yes, go ahead, Charlie. That's fine.

是的，繼續吧，查理。沒關係。

Yeah, so we're still, in terms of the study, we're gearing up to continue to be ready to start the study in the second half of the year. Obviously, you know, we need to fund the clinical part of the study. You know, as we said, we're pursuing all our options to get the study funded, including potentially partnering with one or more third parties.

是的，就研究而言，我們仍在做好準備，準備在下半年繼續開始研究。顯然，你知道，我們需要資助研究的臨床部分。你知道，正如我們所說，我們正在尋求一切方法來獲得研究資金，包括可能與一個或多個第三方合作。

So that's about all the information I can give you at this point. As soon as we have some clarity, we'll let everybody know. That's all we can say right now.

這就是我現在能給你的所有資訊。一旦我們有了明確的答案，我們就會告知大家。這就是我們現在能說的全部。

Thanks for that. I have a quick follow-up. So if I understood correctly, the sham in the study, is it being administered monthly? And I was just curious as to the design of why would you choose that instead of like every two weeks? Is that to kind of merge it with the PTI phase?

謝謝。我有一個快速的後續行動。如果我理解正確的話，研究中的假實驗是按月進行的嗎？我只是好奇為什麼你們選擇這樣設計而不是每兩週一次？這是將其與 PTI 階段合併嗎？

So the way that we want to do the study is in every single visit, the patient will be given an assessment. And then after the assessment, then they will have a procedure.

因此，我們希望進行研究的方式是在每次就診時對患者進行評估。評估結束後，他們會有一個程序。

So that would be how that we agree with the agency of masking the study so that the patient will not know which arm they would be in.

這就是我們與機構達成的掩蓋研究的方式，讓病人不會知道他們屬於哪一組。

So from a patient perspective, they will have an assessment, and then they will then have a procedure. And the procedure could be a suprachoroidal injection, could be a sham, and could be a Aflibercept injection. And again, that is depending on the PTI that I mentioned earlier, or if they have met the rescue criteria.

因此，從患者的角度來看，他們將接受評估，然後接受治療。這個過程可能是脈絡膜上腔注射，可能是假注射，也可能是阿柏西普注射。再次強調，這取決於我之前提到的 PTI，或者他們是否符合救援標準。

So throughout the study, that there will be a patient that has a Aflibercept injection. Sometimes it could be just in the beginning, only just in the beginning for the AX arm. And then the patient would have the injection in the Aflibercept arm.

因此在整個研究過程中，都會有一位患者接受阿柏西普注射。有時，這可能才剛開始，對於 AX 部門來說，這只是開始。然後患者將接受阿柏西普治療組的注射。

So we have discussed that in detail with the agency, and the agency felt that would be an adequate masking or blind in the way that some other targeted areas use. So that's how we think that was the right thing to do. I'm not sure about the two weeks that you mentioned, but this is going to be done every month, every visit. And other than some visits, there will be no procedure needed.

因此，我們與該機構詳細討論了這個問題，該機構認為這將是其他一些目標區域所使用的適當的掩蔽或盲區。所以我們認為這是正確的做法。我不確定您提到的兩週，但每個月、每次造訪都會這樣做。除了一些訪問外，不需要任何手續。

Okay. Thank you so much.

好的。太感謝了。

Yi Chen with H.C. Wainwright.

陳逸與 H.C. Wainwright 在一起。

Thank you for taking my questions. My first question is, what are the potential factors that could contribute to a BCVA change over 10 letter, so the CST change?

感謝您回答我的問題。我的第一個問題是，哪些潛在因素可能導致 BCVA 變化超過 10 個字母，從而導致 CST 變化？

Yes. So what we have known in the clinic, in fact, that a lot of clinicians don't even believe the vision in the clinic, because it's just that it's such a high variability. BCVA is slightly more reliable. And in fact, at the agency also always talk about this 15 letter, it's only 15 letter is real.

是的。因此，我們在臨床上了解到，事實上，許多臨床醫生甚至不相信臨床上的觀點，因為它的變化性太高了。BCVA 稍微可靠一些。事實上，代理商也總是談論這 15 個字母，但只有 15 個字母是真實的。

And so I think that the understanding that, you know, a lot of our patients are pretty elderly, and then you could have in a bad day that they couldn't really see better that day or the test, they just couldn't deal with it. And that is something that we know in routine clinical practice.

所以我認為，我們的許多病人年紀都很大，如果哪天病情不好，他們就無法看清楚當天的狀況，也無法進行檢查，他們無法應付。這是我們在日常臨床實踐中了解到的事情。

In a clinical trial, there's some of these data points affecting our data. So what we have done in the support analysis that I show is that, you know, the OCT and last thing we have not changed at all. And normally that, you know, if your vision got worse, your OCT will get worse or vice versa.

在臨床試驗中，其中一些數據點會影響我們的數據。因此，我在支援分析中展示的就是，您知道，OCT 和最後一件事我們根本沒有改變。通常情況下，如果您的視力變差，您的 OCT 也會變差，反之亦然。

And the 25 micron is just a kind of a way to think that, well, you have not given a 25-micron change, which is a very small change. And then your vision might not be reliable. And so we just think that this was the cohort analysis. So we took that out. But just that, not the whole patient, obviously, that would take out a lot of data points.

而 25 微米只是一種思考方式，嗯，你沒有給出 25 微米的變化，這是一個非常小的變化。那麼你的視力可能就不可靠了。因此我們認為這只是群組分析。所以我們把它拿出來了。但顯然，僅此而已，而不是整個病人，這會損失很多數據點。

But just that one data point. And then as you can see on the chart, that make it, that result even better. Although all our research is already good anyway. But this is just making it even better, explaining that sometimes that some patients just don't do it well, you know, could be a problem. So translating to our Phase 3 design. Now, obviously, we can't do this in a real study because it's a post analysis to understand.

但僅此一個數據點。然後，正如您在圖表上看到的，結果會更好。儘管我們的研究已經很好了。但這只是讓情況變得更好，解釋說有時候有些病人做得不好，你知道，這可能是一個問題。因此轉化為我們的第三階段設計。現在，顯然，我們無法在真正的研究中做到這一點，因為這需要事後分析才能理解。

And what we decided that, you know, as I mentioned in the call, between the third and the fourth injections, and again, we have a lot of historic data that during those two visits, the vision doesn't change normally.

正如我在電話中提到的那樣，我們決定，在第三次和第四次注射之間，我們再次有大量的歷史數據表明，在這兩次注射期間，視力不會發生正常變化。

So again, if they did change, that means that that patient is unreliable patient. And so we believe that by removing those patients before randomization will help us to reducing the variability.

所以，如果他們確實改變了，那就意味著該患者是不可靠的患者。因此，我們相信，在隨機分組之前移除這些患者將有助於我們減少變異性。

Okay, and by implementing these criteria before randomization, do you expect to have any negative impact on enrollment speed or future market adoption when the CLS-AX eventually reaches the market?

好的，透過在隨機化之前實施這些標準，您是否預期當 CLS-AX 最終進入市場時，會對註冊速度或未來的市場採用產生任何負面影響？

Yeah, so I don't think that it would affect the label in a meaningful way. And again, obviously, that is something that we can't really discuss in detail now. We have seen that in other approved products that they have particular inclusion exclusion criteria, but then the label is still the same as wet AMD (inaudible) AMD.

是的，所以我不認為這會對標籤產生重大影響。顯然，我們現在無法詳細討論這個問題。我們已經看到，在其他核准產品中，它們有特定的納入排除標準，但標籤仍然與濕性 AMD（聽不清楚）AMD 相同。

We discussed with the agency and the agency didn't really raise any concern on the way that we want to do the study. And in fact, that, you know, I think that reducing variability to truly show whether drug work or not, you know, are scientifically justified.

我們與該機構進行了討論，但該機構並沒有對我們進行研究的方式表示任何擔憂。事實上，我認為減少變異性來真正表明藥物是否有效是科學合理的。

So I think from that point of view, the label discussion is too early to talk about it, but we believe from past experience, that should not be a key problem.

所以我認為從這個角度來看，標籤討論還為時過早，但根據我們過去的經驗，這不應該是一個關鍵問題。

In terms of, you know, the recruitment and other things, you know, we actually did some analysis on a data set that I have access to during my academic time. The number of patients that would get rejected, you know, between the third and the fourth injection should be less than 10%.

就招募和其他方面而言，我們實際上對我在學術期間可以存取的資料集進行了一些分析。您知道，第三次和第四次注射之間被拒絕的患者數量應該少於 10%。

And so it won't be a major impact, but we believe that 10% can create a lot of variability. And so by removing them would give us a better, more consistent result. And again, the agency agreed to that.

所以它不會產生重大影響，但我們相信 10% 會產生很大的變化。因此，刪除它們會為我們帶來更好、更一致的結果。該機構再次同意了這一點。

Okay. Thank you very much.

好的。非常感謝。

Andreas Argyrides with Oppenheimer.

Andreas Argyrides 與 Oppenheimer。

Hi, thanks for taking our questions. This is Eka on for Andreas. Can you talk about the powering assumption in the Phase 3 trial? And also, if you would share, do you have any insights on how payers think about reimbursement for a potential three to six-month flexible dosing label for CLS-AX compared to competitors? Thank you.

您好，感謝您回答我們的問題。這是 Eka 為 Andreas 表演的。能談談第三階段試驗中的動力假設嗎？另外，如果您願意分享的話，與競爭對手相比，您對付款人如何看待 CLS-AX 潛在的三至六個月靈活劑量標籤的報銷有什麼見解嗎？謝謝。

So I go to second question first. You might be a little bit easier question, but I think the first question is probably quite technical. And the second part is like we have some payer research and the payer research have support our assessment, how that we can potentially put a commercial value to it.

所以我先回答第二個問題。您的問題可能比較簡單，但我認為第一個問題可能相當技術性。第二部分是我們進行了一些付款人研究，這些研究支持我們的評估，我們如何賦予它商業價值。

And I think that a simplistic way to think about it is that some of our competitors would do something different to us potentially. So on the other hand, from our point of view, is we have a flexible dosing. So we believe that we're quite likely to model from the flexible dosing drugs such as idea high dose.

我認為，一個簡單的想法是，我們的一些競爭對手可能會採取與我們不同的行動。因此，另一方面，從我們的角度來看，我們的劑量是靈活的。因此，我們相信，我們很有可能從靈活劑量的藥物（例如理想高劑量）中進行建模。

And then, you know, one way to think about it is that because we have a small molecule and the device is made by our own device. And so a cost of good would be very low and it would be actually lower than the biologic. So, again, that we can be potentially pricing it very competitively. So I think that is something that for further down the road that we have explored on the payer research and what would be the best way to get into the market.

然後，你知道，一種思考方式是，因為我們有一個小分子，而且該設備是由我們自己的設備製造的。因此，產品成本會非常低，實際上比生物製劑還低。因此，我們可以再次給出非常有競爭力的定價。因此，我認為，這是我們在付款人研究方面進一步探索的問題，也是進入市場的最佳方式。

And then the first question is really a standard Phase 3, the kind of the assumption that we took some of the assumptions that are very similar to VABYSMO, we were changing to potential around a 14 letter variability.

然後第一個問題實際上是一個標準的第三階段，我們採取的一些假設與 VABYSMO 非常相似，我們正在將其更改為大約 14 個字母的可變性。

And we believe that our variability is probably a little bit lower. However, that, you know, we were looking at a very similar to VABYSMO type of number. And we use the 4.5 letter margin as suggested by the agency. And then to get to the 90%, as you would expect on the Phase 3 study.

我們相信我們的變異性可能會低一點。然而，您知道，我們正在查看一個與 VABYSMO 類型的數字非常相似的數字。我們按照機構的建議使用了 4.5 個字母的邊距。然後達到 90%，正如您在第三階段研究中所預期的那樣。

Thank you.

謝謝。

Daniil Gataulin with Chardan.

丹尼爾·加陶林 (Daniil Gataulin) 和 Chardan。

Hey, guys, thank you for taking the question. Victor, I have one for you. Can you please elaborate on redosing criteria, which, as I understand, relies on OCT biomarkers and how these interplay with the rescue criteria of the BCVA loss and the fluid gain? And also, where does the physician's discretion come in in redosing decision? Because I think that's always a big variability factor. Thank you.

嘿，夥計們，謝謝你們回答這個問題。維克多，我有一個給你。您能否詳細說明重新給藥標準（據我了解，該標準依賴於 OCT 生物標記）以及這些標準如何與 BCVA 損失和液體增加的救援標準相互作用？此外，醫師在重新給藥決定上有何判斷力？因為我認為這始終是一個很大的可變因素。謝謝。

Yeah, thank you for that question. And allow me to spend time to explain that. So, redosing and rescue is two different things in our position. So, redosing is similar to what we have seen with EYLEA high dose and VABYSMO. They have a certain criteria. And the two companies have different criteria. And I'm not going to go into detail of their criteria. But, again, neither of those are really used in clinical practice. And we have spent quite a lot of time talking to a lot of KOL, including myself, that we consider that just the thickness is not really that reliable.

是的，謝謝你的提問。請允許我花點時間來解釋這一點。因此，從我們的角度來看，重新給藥和救援是兩碼事。因此，重新服用的情況與我們在 EYLEA 高劑量和 VABYSMO 中看到的情況類似。他們有一定的標準。而且兩家公司的標準也不同。我不會詳細談論他們的標準。但是，這兩種方法在臨床實踐中都沒有實際應用。我們花了很多時間與包括我在內的許多KOL交談，我們認為僅僅厚度並不是那麼可靠。

And, in fact, that something what we call intraretinal fluid, means the fluid is actually inside the retina. So, subretinal fluid, which is the fluid just underneath the retina, so not in the retina. And, again, over the years, we learned that intraretinal fluid, you know, the fluid that is inside the retina, they cause more damage, and as one would expect it, and also cause more visual loss.

事實上，我們所說的視網膜內液是指液體實際上位於視網膜內部。視網膜下液是視網膜正下方的液體，不在視網膜內。而且，多年來，我們再次了解到視網膜內液，即視網膜內部的液體，會造成更大的損害，正如人們所預料的那樣，也會導致更嚴重的視力喪失。

And so, a subretinal fluid, in fact, is actually not as much harm and some debate that even some subretinal fluid is good for you. So, what we have decided is that because now that we can really map out not just the thickness, but we can actually map out the intraretinal fluid and subretinal fluid. And then the exact criteria we have not openly shared yet, but we can share if that is, if we have intraretinal fluid returning, that would be used to redosing the patient earlier.

因此，視網膜下液實際上並沒有那麼大的危害，甚至有人爭辯說，一些視網膜下液對人體有益。因此，我們決定這樣做，因為現在我們不僅可以繪製出厚度，還可以繪製出視網膜內液和視網膜下液。我們還沒有公開分享具體的標準，但如果視網膜內液體回流，我們可以分享，這將用於更早重新給患者註射藥物。

And both subretinal fluid, we will allow a little bit more. So, but that is similar to, as I mentioned, EYLEA high dose and VABYSMO, they, you know, have vision criteria, and they have so-called CST increased criteria. But we're just doing it a little bit more scientific, a little more technical. So, I think that is what we would plan to do, and that's what we're referring to. And luckily that we now have AI tools that can do that.

對於視網膜下液，我們會允許多一點。所以，但這與我提到的 EYLEA 高劑量和 VABYSMO 類似，它們有視力標準，並且有所謂的 CST 增加標準。但我們只是做得更科學一些，更有技術。所以，我認為這就是我們計劃要做的，這也是我們所指的。幸運的是，我們現在有了可以做到這一點的人工智慧工具。

The second part about rescue is, again, just EYLEA high dose and VABYSMO, they were very, very rare that they have rescue. And in fact, that, you know, we have agreed with the agency, the criteria for rescue. And that is different. That is something that, you know, the patients are losing vision, and as well as anatomy is getting worse.

關於救援的第二部分是，再次強調，只有高劑量的 EYLEA 和 VABYSMO 才能進行救援，這種情況非常非常罕見。事實上，您知道，我們已經與該機構就救援標準達成了一致。那是不同的。你知道，患者的視力正在下降，而且身體狀況也越來越差。

And again, this is something that we have agreed with the agency. That is very different, and even different probably in some of our competitive trials. So, obviously, as you said, a physician can always so-called rescue a patient when they wanted to. We can't control that.

再次強調，這是我們與該機構達成的協議。這是非常不同的，甚至可能與我們的一些競爭性試驗有所不同。因此，顯然，正如您所說，醫生在需要時總是可以所謂的拯救病人。我們無法控制這一點。

And on the other hand, what we believe is similar to EYLEA high dose and VABYSMO, and in fact, if anything, our redosing criteria are tighter, in other words, easier. And so we believe that, you know, because of that, we will have no rescue. Very similar to VABYSMO and EYLEA high dose.

另一方面，我們認為這與 EYLEA 高劑量和 VABYSMO 類似，事實上，如果有的話，我們的重新給藥標準更嚴格，換句話說，更容易。因此我們相信，正因為如此，我們將無法獲救。與 VABYSMO 和 EYLEA 高劑量非常相似。

And again, obviously, that is what we believe. And we believe that that design is particularly useful. It's because that has been proven by other drugs already. And so by doing that and by eliminating rescue, we believe that we can also reduce our regulatory risk and improve our possibility of success.

顯然，這正是我們所相信的。我們相信這種設計特別有用。這是因為其他藥物已經證明了這一點。因此，透過這樣做並取消救助，我們相信我們還可以降低監管風險並提高成功的可能性。

Thank you. As we have no further questions in the queue at this time, I would like to hand the call back over to Mr. Lasezkay, for any closing remarks.

謝謝。由於我們目前沒有其他問題，我想將電話交還給 Lasezkay 先生，請他做最後發言。

I want to thank everyone for joining us on the call this afternoon. We greatly appreciate your continued interest in our company, Clearside, and we look forward to updating you on our progress. Operator, you may now disconnect the call.

我要感謝大家今天下午參加我們的電話會議。我們非常感謝您對我們公司 Clearside 的持續關注，我們期待向您通報我們的進展。接線員，您現在可以掛斷電話了。

Thank you, sir. Ladies and gentlemen, this does conclude today's call. You may disconnect your lines at this time and have a wonderful day. We thank you for your participation.

謝謝您，先生。女士們、先生們，今天的電話會議到此結束。此時您可以斷開線路並享受美好的一天。我們感謝您的參與。