Clearside Biomedical Inc (CLSD) 2023 Q1 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Clearside Biomedical quarter 2023 financial results and corporate update call. (Operator Instructions) Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker today, Jenny Kobin, Clearside Investor Relations.

美好的一天，感謝您的支持。歡迎參加 Clearside Biomedical 2023 年季度財務業績和公司更新電話會議。 （操作員指示）請注意，今天的會議正在錄製中。我現在想把會議交給今天的發言人，Clearside 投資者關係部的珍妮·科賓 (Jenny Kobin)。

Good morning, 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 and about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. 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, 2022, and our other SEC filings available on our website.

大家早上好，感謝您今天加入我們的電話會議。在開始之前，我想提醒您，在今天的電話會議中，我們將做出某些前瞻性聲明。我們在本次電話會議上發表的有關公司未來預期、計劃和前景的各種言論均構成符合 1995 年《私人證券訴訟改革法案》的前瞻性陳述。實際結果可能與這些前瞻性陳述所表明的結果存在重大差異由於各種重要因素，包括我們截至 2022 年 12 月 31 日的 10-K 表格年度報告的風險因素部分中討論的因素，以及我們網站上提供的其他 SEC 文件。

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截至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，但我們特別聲明不承擔任何這樣做的義務，即使我們的觀點發生變化。

On today's call, we have George Lasezkay, our Chief Executive Officer; and Charles Deignan, our Chief Financial Officer. After our formal remarks, we will open the call for your questions.

出席今天的電話會議的有我們的首席執行官 George Lasezkay；以及我們的首席財務官 Charles Deignan。在我們正式發言後，我們將開始電話詢問您的問題。

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

我現在想把電話轉給喬治。

Thank you, Jenny. We delivered a productive start to 2023 as we execute on our near-term plan to advance our lead asset, CLS-AX, an investigational proprietary suspension of axitinib for suprachoroidal injection. Axitinib is a highly potent tyrosine kinase inhibitor that achieves pan-VEGF blockade, directly inhibiting VEGF receptors 1, 2, and 3 with high potency and specificity.

謝謝你，珍妮。我們在 2023 年實現了富有成效的開端，因為我們正在執行近期計劃，以推進我們的主導資產 CLS-AX，CLS-AX 是一種用於脈絡膜上註射的阿西替尼專有研究懸浮液。阿西替尼是一種高效酪氨酸激酶抑製劑，可實現泛 VEGF 阻斷，直接抑制 VEGF 受體 1、2 和 3，具有高效力和特異性。

We believe this broad VEGF blockade may have advantages over existing therapies for retinal diseases by acting at a different level of the angiogenesis cascade. Suprachoroidal injection of our proprietary CLS-AX suspension delivers axitinib directly to the site of disease and has demonstrated signs of biological effect and the potential for extended duration of therapy in our Phase 1/2a OASIS clinical trial in wet AMD.

我們相信，通過作用於血管生成級聯的不同水平，這種廣泛的 VEGF 阻斷可能比現有的視網膜疾病療法具有優勢。脈絡膜上註射我們專有的 CLS-AX 懸浮液，將阿西替尼直接輸送到疾病部位，並在我們針對濕性 AMD 的 1/2a 期 OASIS 臨床試驗中證明了生物效應的跡象和延長治療持續時間的潛力。

Results from the OASIS trial and extension study were presented last month at the ARVO Annual Meeting by Dr. Dennis Marcus. The trial consisted of four cohorts with single-escalating doses of CLS-AX administered to participants who were then followed for three months.

Dennis Marcus 博士上個月在 ARVO 年會上公佈了 OASIS 試驗和擴展研究的結果。該試驗由四個隊列組成，向參與者施用單次遞增劑量的 CLS-AX，然後對參與者進行三個月的隨訪。

All participants enrolled in OASIS were heavily anti-VEGF treatment experienced with active disease at screening, which was confirmed by an independent reading center. The three-month trial was followed by an additional three-month extension study in a higher-dose cohort for a total of six months follow up for those OASIS participants who elected to continue.

所有參加 OASIS 的參與者在篩選時均接受過嚴格的抗 VEGF 治療，並患有活動性疾病，這一點得到了獨立閱讀中心的證實。為期三個月的試驗之後，又在高劑量隊列中進行了為期三個月的擴展研究，對選擇繼續的 OASIS 參與者進行了總共六個月的隨訪。

CLS-AX was administered by our proprietary SCS Microinjector. It demonstrated an excellent safety and tolerability profile at all doses and in all cohorts. There were no adverse effects, no dose-limiting toxicities, no sign of inflammation. And because we inject behind the retina, we didn't have any instances of vitreous floaters or dispersion of drug into the vitreous.

CLS-AX 由我們專有的 SCS 顯微注射器管理。它在所有劑量和所有隊列中都表現出出色的安全性和耐受性。沒有副作用，沒有劑量限制性毒性，沒有炎症跡象。由於我們在視網膜後面注射，因此沒有出現任何玻璃體漂浮物或藥物分散到玻璃體中的情況。

We anticipated this favorable safety profile, as axitinib is a well-characterized small molecule with much less propensity for ocular inflammation as compared to the administration of biological agents or viral-based gene therapy. In terms of outcomes, the OASIS extension study demonstrated that two-thirds of wet AMD patients in the two higher-dose cohorts were able to go at least six months without additional treatment. Participants experienced a 77% to 85% reduction in treatment burden as measured by the number of anti-VEGF treatments they received during the six months compared to the six-month period prior to entering the OASIS trial.

我們預期這種有利的安全性，因為阿西替尼是一種特徵良好的小分子，與生物製劑或基於病毒的基因治療相比，其引起眼部炎症的可能性要小得多。就結果而言，OASIS 擴展研究表明，兩個高劑量組中三分之二的濕性 AMD 患者能夠在至少六個月內無需額外治療。與進入 OASIS 試驗前的 6 個月相比，根據這 6 個月內接受的抗 VEGF 治療次數衡量，參與者的治療負擔減少了 77% 至 85%。

Also, we observed anatomic signs of biological effect and reported stable mean best-corrected visual acuity, or BCVA, and stable mean central subfield thickness, or CST, in the extension study participants in the two higher-dose cohorts. These promising results are supportive of the potential safety, potency, and pan-VEGF blockade effect of CLS-AX delivered via our SCS Microinjector into the suprachoroidal space.

此外，我們觀察了生物效應的解剖學跡象，並報告了兩個較高劑量組的擴展研究參與者的穩定平均最佳矯正視力（BCVA）和穩定的平均中心子視野厚度（CST）。這些有希望的結果支持了 CLS-AX 通過我們的 SCS 顯微注射器輸送到脈絡膜上腔的潛在安全性、效力和泛 VEGF 阻斷作用。

We're excited to further explore the potential of CLS-AX in ODYSSEY, our planned randomized, double-masked, multi-center Phase 2b clinical trial in participants with wet AMD. Our primary goals for ODYSSEY are to demonstrate improved duration and reduced treatment burden for the CLS-AX arm while maintaining visual acuity. We expect that the results of this trial will provide the necessary data to properly inform the design of a Phase 3 program for CLS-AX in wet AMD.

我們很高興能在 ODYSSEY 中進一步探索 CLS-AX 的潛力，ODYSSEY 是我們計劃在濕性 AMD 參與者中進行的隨機、雙盲、多中心 2b 期臨床試驗。我們 ODYSSEY 的主要目標是證明 CLS-AX 臂的持續時間更長，治療負擔減輕，同時保持視力。我們預計該試驗的結果將提供必要的數據，以便為濕 AMD 中 CLS-AX 的第 3 階段項目的設計提供正確的信息。

We believe CLS-AX has the potential to be the twice-a-year maintenance drug for wet AMD, which, if demonstrated, would compare favorably to on-label maintenance dosing for the currently approved anti-VEGF drugs. LUCENTIS, on label, is 12 times a year; EYLEA, 2 milligrams, is six times a year; and VABYSMO is up to six times per year.

我們相信 CLS-AX 有潛力成為濕性 AMD 的一年兩次維持藥物，如果得到證實，將優於目前批准的抗 VEGF 藥物的標籤維持劑量。 LUCENTIS，標籤上顯示，每年 12 次； EYLEA，2毫克，一年六次； VABYSMO 每年多達六次。

We believe the ODYSSEY trial is balanced to meet its objectives effectively and efficiently with topline results expected in Q3 2024. The ODYSSEY trial will compare CLS-AX against the current standard of care, EYLEA or aflibercept. In essence, we are comparing CLS-AX maintenance versus aflibercept maintenance with the goal of demonstrating similar visual acuity outcomes with a lower treatment burden for the CLS-AX arm.

我們相信 ODYSSEY 試驗是平衡的，可以有效且高效地實現其目標，預計在 2024 年第三季度獲得主要結果。ODYSSEY 試驗將 CLS-AX 與當前的護理標準、EYLEA 或阿柏西普進行比較。本質上，我們正​​在比較 CLS-AX 維持治療與阿柏西普維持治療，目的是證明 CLS-AX 組具有相似的視力結果和較低的治療負擔。

We plan to enroll a total of 60 treatment-experienced patients with wet AMD. Patients will be randomized -- or participants will be randomized, 2:1. 40 participants will receive CLS-AX administered by suprachoroidal injection via the Clearside SCS Microinjector, and 20 participants in the comparator arm will receive intravitreal aflibercept.

我們計劃總共招募 60 名有治療經驗的濕性 AMD 患者。患者將被隨機分配——或者參與者將被隨機分配，比例為 2:1。 40 名參與者將通過 Clearside SCS 顯微注射器進行脈絡膜上註射來接受 CLS-AX，比較組中的 20 名參與者將接受玻璃體內阿柏西普治療。

The trial will include participants diagnosed with wet AMD within 36 months of their screening visit and with a history of responding to anti-VEGF treatments for the disease. Participants will have reading center confirmation of persistent active disease.

該試驗將包括在篩選訪問後 36 個月內診斷出患有濕性 AMD 且具有抗 VEGF 治療反應史的參與者。參與者將得到閱讀中心對持續活動性疾病的確認。

The primary outcome measures for this trial are the mean change in BCVA over 36 weeks as well as the assessment of safety and tolerability of CLS-AX. The secondary outcome measures are: treatment burden, as measured by total injections over trial duration; other changes in visual function and ocular anatomy, such as CST; and the need for supplemental treatment.

該試驗的主要結果指標是 36 週內 BCVA 的平均變化以及 CLS-AX 的安全性和耐受性評估。次要結果指標是： 治療負擔，通過試驗期間的總注射量來衡量；視覺功能和眼部解剖結構的其他變化，例如 CST；以及補充治療的需要。

Participants in both arms will receive three monthly loading doses of aflibercept at 2 milligrams. At the second loading-dose visit, defined as the baseline visit, participants in the CLS-AX arm will also receive 1 milligram of CLS-AX by suprachoroidal injection. Participants in the comparator arm will also receive a sham suprachoroidal injection to ensure masking of the trial.

雙臂參與者將接受三個月負荷劑量的阿柏西普 2 毫克。在第二次負荷劑量訪視（定義為基線訪視）時，CLS-AX 組的參與者還將通過脈絡膜上註射接受 1 毫克 CLS-AX。比較組的參與者還將接受假脈絡膜上註射，以確保試驗的掩蔽。

Participants in the CLS-AX arm will then receive another CLS-AX dose at week 24 unless they require supplemental treatment prior to that visit. Therefore, participants in the CLS-AX arm will receive at least two doses of CLS-AX during the trial, which will provide valuable multi-dose safety information or an end-of-Phase 2 meeting with the FDA and the design of a Phase 3 trial.

CLS-AX 組的參與者將在第 24 週接受另一劑 CLS-AX 劑量，除非他們在該訪視之前需要補充治療。因此，CLS-AX 組的參與者將在試驗期間至少接受兩劑 CLS-AX，這將提供有價值的多劑量安全信息或與 FDA 舉行的第 2 階段結束會議以及第 1 階段的設計3 審判。

In the comparator arm, participants will receive additional aflibercept injections every eight weeks until week 36, unless they require supplemental treatment prior to the scheduled every-eighth-week aflibercept dose. Disease activity assessments will be conducted in both arms at week 12 and then every four weeks through week 32. This will determine if there is a need for supplemental treatment based on the occurrence of any one of the following four criteria compared to baseline: BCVA reduction of greater than 10 letters, an increase in the central subfield thickness of greater than 100 microns, BCVA reduction of greater than five letters and an increase of CST of greater than 75 microns, or the presence of a new or worsening vision-threatening hemorrhage due to wet AMD.

在比較組中，參與者將每八週接受一次額外的阿柏西普注射，直到第 36 週，除非他們在預定的每八週一次阿柏西普劑量之前需要補充治療。將在第 12 週對雙臂進行疾病活動評估，然後在第 32 週每四周進行一次。這將根據與基線相比出現以下四個標準中的任何一項來確定是否需要補充治療： BCVA 降低超過 10 個字母，中央子區域厚度增加超過 100 微米，BCVA 減少超過 5 個字母，CST 增加超過 75 微米，或者由於以下原因出現新的或惡化的危及視力的出血濕AMD。

The detailed trial design slides are available on our website in the corporate presentation. We believe this trial design makes sense for two key reasons. First, we are enrolling treatment-experienced participants with a history of responding to standard anti-VEGF treatments. We believe this will minimize recruitment of anti-VEGF sub- and non-responders and may provide a larger population of participants to facilitate our trial enrollment efforts.

詳細的試驗設計幻燈片可在我們網站的公司演示文稿中找到。我們相信這種試驗設計是有意義的，有兩個關鍵原因。首先，我們正在招募有治療經驗且對標準抗 VEGF 治療有反應史的參與者。我們相信，這將最大限度地減少抗 VEGF 亞反應和無反應的招募，並可能提供更多的參與者，以促進我們的試驗招募工作。

Second, this trial is more closely aligned with the recent FDA draft guidance for wet AMD drug development by utilizing aflibercept as a comparator, BCVA as the primary outcome measure, and utilizing a 36-week duration. Together, this will help us most effectively and efficiently prepare for a Phase 3 program in wet AMD.

其次，該試驗使用阿柏西普作為比較劑，BCVA作為主要結果指標，並採用 36 週的持續時間，與最近 FDA 濕性 AMD 藥物開髮指南草案更加一致。總之，這將幫助我們最有效和高效地準備濕 AMD 的第 3 階段計劃。

Our clinical operation team has been working hard to get ODYSSEY up and running this quarter. I am pleased to announce today that the study will open for enrollment in the next few weeks, and we expect to enroll our first patient shortly thereafter. We are targeting a total of 30 US-based clinical trial sites and expect topline data from the trial in the third quarter of next year.

我們的臨床運營團隊一直在努力讓 ODYSSEY 在本季度啟動並運行。我今天很高興地宣布，該研究將在未來幾週內開放招募，我們預計此後不久將招募第一位患者。我們的目標是美國總共 30 個臨床試驗地點，預計明年第三季度將獲得試驗的主要數據。

Moving on to XIPERE. At ARVO, Dr. Peter Chang presented survey data regarding the use of our SCS Microinjector from retina and uveitis specialists who have completed at least 10 suprachoroidal injections of XIPERE. The findings from the survey of early adopters of XIPERE suggest suprachoroidal injection was easy to learn, and patient improvements in vision and macular edema aligned with the findings in clinical registration trial.

轉向 XIPERE。在 ARVO 上，Peter Chang 博士介紹了視網膜和葡萄膜炎專家使用我們的 SCS 顯微注射器的調查數據，這些專家已經完成了至少 10 次 XIPERE 脈絡膜上腔注射。對 XIPERE 早期採用者的調查結果表明，脈絡膜上註射很容易學習，患者視力和黃斑水腫的改善與臨床註冊試驗的結果一致。

This broadening use of our suprachoroidal delivery product platform is encouraging as multiple clinical trials advance, both with us and our development and commercialization partners. Our US and Canadian commercial partner for XIPERE, Bausch & Lomb, continues to expand outreach with XIPERE product education and SCS injection awareness and training to healthcare providers.

隨著我們以及我們的開發和商業化合作夥伴的多項臨床試驗的進展，我們的脈絡膜上遞送產品平台的廣泛使用令人鼓舞。我們在美國和加拿大的 XIPERE 商業合作夥伴 Bausch & Lomb 繼續通過 XIPERE 產品教育和 SCS 注射意識以及對醫療保健提供者的培訓來擴大影響範圍。

A significant number of physicians have been trained, to date, in the proper use of our SCS Microinjector. Bausch has also filed for XIPERE regulatory approval in Canada, so we're looking forward to market expansion and an additional territory.

迄今為止，已有大量醫生接受過如何正確使用我們的 SCS 顯微注射器的培訓。 Bausch 還在加拿大申請了 XIPERE 監管批准，因此我們期待著市場擴張和新的領域。

Our Asia-Pacific commercial partner for XIPERE, Arctic Vision, is currently enrolling a confirmatory Phase 3 trial in macular edema associated with uveitis and has completed a Phase 1 clinical trial for the treatment of diabetic macular edema. Data from the DME trial is expected to be made public in the near future.

我們的 XIPERE 亞太商業合作夥伴 Arctic Vision 目前正在開展一項針對葡萄膜炎相關黃斑水腫的驗證性 3 期試驗，並已完成治療糖尿病性黃斑水腫的 1 期臨床試驗。 DME 試驗的數據預計將在不久的將來公佈。

Let me now provide a brief update on our SCS Microinjector partner programs. Last week, REGENXBIO announced that they had completed enrollment in the expansion cohorts of Phase 2 AAVIATE and ALTITUDE clinical trials. These trials are utilizing suprachoroidal delivery of RGX-314 in patients with wet AMD and diabetic retinopathy.

現在讓我簡要介紹一下我們的 SCS 顯微注射器合作夥伴計劃。上週，REGENXBIO 宣布他們已完成 2 期 AAVIATE 和 ALTITUDE 臨床試驗擴展隊列的入組。這些試驗利用脈絡膜上腔遞送 RGX-314 治療濕性 AMD 和糖尿病視網膜病變患者。

REGENXBIO expects to report additional interim trial data from both trials, including initial data from the most recent cohorts in the second half of 2023. REGENXBIO also announced that IND sponsorship has now been transferred to AbbVie for continued clinical development of the two suprachoroidal gene therapy clinical programs using Clearside's SCS Microinjector. AbbVie is a widely recognized global leader in eye care. And in the future. RGX-314 will be referred to as ABBV-RGX-314.

REGENXBIO 預計將報告這兩項試驗的額外中期試驗數據，包括 2023 年下半年最新隊列的初始數據。REGENXBIO 還宣布 IND 贊助現已轉移給艾伯維，用於兩項脈絡膜上基因治療臨床的持續臨床開發使用 Clearside 的 SCS 微注射器進行程序。艾伯維 (AbbVie) 是公認的眼保健領域全球領導者。以及未來。 RGX-314 將被稱為 ABBV-RGX-314。

Our oncology partner, Aura Biosciences, is utilizing our SCS Microinjector to deliver their viral-like (sic - virus-like) drug conjugate, bel-sar, for the treatment of choroidal melanoma. Based on promising data presented earlier this year, Aura announced final plans for its global Phase 3 trial utilizing the suprachoroidal route of administration. They expect to begin dosing for the trial in the first half of this year.

我們的腫瘤學合作夥伴 Aura Biosciences 正在利用我們的 SCS 微注射器來輸送其病毒樣（原文如此，病毒樣）藥物綴合物 Bel-sar，用於治療脈絡膜黑色素瘤。基於今年早些時候提供的有希望的數據，Aura 宣布了利用脈絡膜上給藥途徑進行全球 3 期試驗的最終計劃。他們預計將在今年上半年開始試驗劑量。

With that summary of our programs, I'll now turn the call over to our CFO, Charlie Deignan, for a financial update. Charlie?

有了我們計劃的摘要，我現在將把電話轉給我們的首席財務官 Charlie Deignan，以獲取最新的財務信息。查理？

Thanks, George, and good morning, everyone. Our financial results for the quarter were published earlier in our press release and are available on our website. Therefore, I will just provide a summary of our financial status.

謝謝喬治，大家早上好。我們本季度的財務業績已在我們的新聞稿中發布，並可在我們的網站上查看。因此，我將僅提供我們財務狀況的摘要。

As George mentioned, we are making excellent progress in advancing CLS-AX. And we continue to prudently manage our cash balance as we move forward with our programs.

正如 George 提到的，我們在推進 CLS-AX 方面取得了巨大進展。在推進我們的計劃時，我們將繼續謹慎管理我們的現金餘額。

As of March 31, 2023, our cash and cash equivalents totaled approximately $41.4 million. Based on our current outlook, we expect to have sufficient resources to fund our planned operations into the second quarter of 2024. We fully intend to fund the ODYSSEY study, and we'll be exploring the best available options.

截至 2023 年 3 月 31 日，我們的現金和現金等價物總額約為 4140 萬美元。根據我們目前的前景，我們預計將有足夠的資源來資助我們到 2024 年第二季度的計劃運營。我們完全打算為 ODYSSEY 研究提供資金，並且我們將探索最佳的可用選擇。

On a financial housekeeping note, our current shelf registration is expiring. So we plan to file a new shelf registration statement in addition to our 10-Q.

在財務管理方面，我們當前的貨架註冊即將到期。因此，除了 10-Q 之外，我們還計劃提交一份新的貨架登記聲明。

In the coming months, we will be participating in several investor conferences, including the JMP Life Sciences Conference next week and the Wedbush PacGrow Healthcare Conference in August. We look forward to these interactions, and we'll keep you updated on our progress.

在接下來的幾個月中，我們將參加多個投資者會議，包括下週的 JMP 生命科學會議和 8 月的 Wedbush PacGrow 醫療保健會議。我們期待這些互動，並將隨時向您通報我們的進展情況。

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

現在我將把電話轉回給喬治，讓他發表結束語。

Thanks, Charlie. I'd like to wrap up with a few final comments.

謝謝，查理。我想以一些最後的評論作為結束語。

During the first quarter, we enhanced our scientific advisory board composed of industry-leading retinal physicians to obtain expert medical and scientific input for our clinical and preclinical research pipeline. Dr. Tom Ciulla now serves as the Chair of our SAB.

在第一季度，我們加強了由行業領先的視網膜醫生組成的科學顧問委員會，為我們的臨床和臨床前研究管道獲取專家的醫療和科學投入。 Tom Ciulla 博士現任 SAB 主席。

And we have also appointed two well-known retinal physicians as new members of our SAB: Drs. Arshad Khanani and Lejla Vajzovic. The entire scientific advisory board has been instrumental in providing input into our Phase 2b clinical trial design, and we appreciate their ongoing guidance on all of our development programs.

我們還任命了兩位著名的視網膜醫生作為我們SAB的新成員：Drs.阿沙德·卡納尼和萊吉拉·瓦佐維奇。整個科學顧問委員會在為我們的 2b 期臨床試驗設計提供意見方面發揮了重要作用，我們感謝他們對我們所有開發項目的持續指導。

We look forward to the initiation of our ODYSSEY trial this quarter. We believe that the number of participants, the duration, and the outcome measures of the study will provide necessary clinical data to inform the CLS-AX Phase 3 program design.

我們期待本季度啟動 ODYSSEY 試驗。我們相信，該研究的參與者數量、持續時間和結果測量將為 CLS-AX 3 期項目設計提供必要的臨床數據。

As we continue advancing CLS-AX, we are excited about the potential for a potent, well-tolerated tyrosine kinase inhibitor in a multibillion-dollar wet AMD market. While we are intently focused on advancing CLS-AX, we've also been very active intellectually, behind the scenes, on our science and SCS delivery. A research team is experimenting with more advanced injection designs as well as other small molecule candidates that can be delivered into the suprachoroidal space to target a number of retinal diseases.

隨著我們繼續推進 CLS-AX，我們對一種有效、耐受性良好的酪氨酸激酶抑製劑在價值數十億美元的濕性 AMD 市場中的潛力感到興奮。雖然我們專注於推進 CLS-AX，但我們在幕後也非常積極地致力於我們的科學和 SCS 交付。一個研究小組正在試驗更先進的注射設計以及其他小分子候選物，這些小分子候選物可以被輸送到脈絡膜上腔以治療多種視網膜疾病。

In the ophthalmic medical community, there's increasing acceptance for treating serious retinal diseases through the delivery of therapeutics behind the visual field into the suprachoroidal space. We believe this creates significant value for our proprietary SCS Microinjector platform that provides a safe, in-office, repeatable, non-surgical procedure to reach the back of the eye.

在眼科醫學界，通過將治療藥物從視野後面輸送到脈絡膜上腔來治療嚴重的視網膜疾病越來越被接受。我們相信，這為我們專有的 SCS 顯微注射器平台創造了巨大的價值，該平台提供了一種安全、辦公室內、可重複、非手術的手術來到達眼睛後部。

We are well positioned to evaluate new collaboration opportunities along with tracking progress by our current partners. Our industry continues to generate exciting advancements, and we're pleased to be a player in that development of promising new retinal therapies. We look forward to providing updates as we move forward.

我們有能力評估新的合作機會並跟踪現有合作夥伴的進展。我們的行業不斷取得令人興奮的進步，我們很高興成為有前景的新型視網膜療法開發的參與者。我們期待著在前進的過程中提供更新。

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

我現在想請接線員打開提問電話。

Thank you. At this time we will conduct a question-and-answer session. (Operator Instructions) Serge Belanger, Needham.

謝謝。這時我們將進行問答環節。 （操作員說明）Serge Belanger，Needham。

Hi. Good morning. A couple of question for us.

你好。早上好。有幾個問題要問我們。

Morning, Serge.

早上好，塞爾日。

I guess this -- good morning. First one -- in the past, you've mentioned that the ODYSSEY trial was not powered for superiority or non-inferiority. So how should we think about a successful outcome for this trial?

我想是這樣——早上好。第一個——過去，您提到 ODYSSEY 試驗並不是為了優越性或非劣效性。那麼我們應該如何看待這次試驗的成功結果呢？

And secondly, looking back at the OASIS trial, I think in one of the cohorts, there were some issues in how physicians were assessing the retreatment criteria. I'm just curious how you plan to minimize that as an issue for the ODYSSEY trial. Thank you.

其次，回顧 OASIS 試驗，我認為在其中一個隊列中，醫生評估再治療標準的方式存在一些問題。我只是好奇你打算如何最大程度地減少 ODYSSEY 試驗中的問題。謝謝。

Okay. Thanks for the question, Serge. On the first question, you're correct with this study is not powered to be a non-inferiority study or a superiority study, per se. What we're doing is we're trying to -- a successful trial for us would be to show a lower treatment burden, as I mentioned, by looking at the number of injections over the trial period with maintaining stable visual acuity.

好的。謝謝你的提問，塞爾吉。關於第一個問題，您的觀點是正確的，這項研究本身並不能成為一項非劣效性研究或優效性研究。我們正在做的是，我們正在努力——正如我提到的，通過觀察試驗期間的注射次數並保持穩定的視力，對我們來說，一次成功的試驗將顯示出較低的治療負擔。

What we're doing here is we're really looking for means in percentages that give us an estimation of how we would go into Phase 3 on a fixed dosing schedule. So we don't need to do this in Phase 2. And this is not that uncommon -- is to go into Phase 2 and not power it in such a way to be a non-inferiority trial.

我們在這裡所做的實際上是尋找百分比的方法，讓我們能夠估計如何按照固定的給藥方案進入第三階段。所以我們不需要在第二階段這樣做。這並不罕見——進入第二階段而不是以非劣效性試驗的方式為其提供動力。

What we're trying to do is basically find our best estimate of what the fixed dosing schedule would be to go into a non-inferiority trial in Phase 3. So we're not doing it. We're setting up or gathering the data in order for us to properly design and power a Phase 3 program in wet AMD. So this is what we're going to do in Odyssey is gain that estimation of what we need to do in order to design the proper Phase 3 trial.

我們想做的基本上是找到對進入第三階段非劣效性試驗的固定給藥方案的最佳估計。所以我們沒有這樣做。我們正在設置或收集數據，以便我們能夠正確設計和支持濕 AMD 的第 3 階段項目。因此，我們在《奧德賽》中要做的就是估計我們需要做什麼，以便設計適當的第三階段試驗。

Also, we're trying to gauge where we're going to end up in terms of FDA -- the final FDA guidance on trial design in wet AMD. As you know, the FDA produced the draft guidance, and there's a comment period, I believe, that ends this month. And so we'll see where the final guidelines come out. So we're also being very cognizant of the possibility for some changes in that guideline.

此外，我們正在嘗試評估 FDA 的最終結果——FDA 關於濕性 AMD 試驗設計的最終指南。如您所知，FDA 制定了指南草案，並且有一個意見徵詢期，我相信該期將於本月結束。所以我們將看看最終的指導方針會出現在哪裡。因此，我們也非常清楚該指南有可能發生一些變化。

So that's the way we set up our trial for us, if we can see a successful outcome would be for us, as I said, a lower treatment burden. And we would be very happy if we see the vast majority, if not all the patients, going at least four to six months on their duration of the loading-in period versus aflibercept being dosed every eight weeks.

這就是我們為我們安排試驗的方式，如果我們能看到成功的結果，正如我所說，對我們來說，治療負擔就會減輕。如果我們看到絕大多數（如果不是全部）患者在加載期持續至少四到六個月，而不是每八週服用一次阿柏西普，我們會非常高興。

There was a second part to your question. I'm sorry, I've forgotten it now. So --

你的問題還有第二部分。對不起，我現在已經忘記了。所以 -

No problem. It was about the assessment for retreatment. I think there were some issues with the interpretation of that in OASIS. I'm just curious how you (multiple speakers) to minimize them.

沒問題。這是關於再治療的評估。我認為 OASIS 對此的解釋存在一些問題。我只是好奇你們（多個發言者）如何將它們最小化。

Oh, right. Right. We've taken a number of steps to try to decrease those variations from protocol in the protocol. We've enhanced the training. We've enhanced the on-site supervision. We have a computer program that directs the physicians as to what to do exactly. That would be the measurements in office had been done in a more stringent way.

啊對。正確的。我們採取了許多步驟來嘗試減少協議中的這些變化。我們加強了培訓。加強現場監管。我們有一個計算機程序可以指導醫生具體做什麼。那就是辦公室的測量以更嚴格的方式進行。

So we've been very cognizant of some of those off-protocol rescues. And as you recall in the OASIS data, there's protocol rescues. When they were assessed by the independent reading center, most of them should not have been treated. So they should not have been rescued.

因此，我們非常了解其中一些非協議救援。正如您在 OASIS 數據中所記得的那樣，有協議救援。當獨立閱讀中心對他們進行評估時，他們中的大多數人不應該接受治療。所以他們不應該獲救。

So we've been very cognizant of that and set up a very rigid protocol to try to eliminate that. I'm not sure we can eliminate all of that, but we've done our best to try to minimize it, if not eliminate it.

因此，我們非常清楚這一點，並製定了一個非常嚴格的協議來試圖消除這種情況。我不確定我們能否消除所有這些，但我們已盡最大努力將其最小化（如果不能消除的話）。

Thank you.

謝謝。

Annabel Samimy, Stifel.

安娜貝爾·薩米米，斯蒂菲爾。

Hi. Thanks for taking my questions.

你好。感謝您回答我的問題。

Hi, Annabel.

嗨，安娜貝爾。

Good progress -- how are you?

進展順利——你好嗎？

Good.

好的。

I had a couple of questions. One is just going back to the Phase 2 design, as you're talking about having not designed it for superiority or non-inferiority. I guess, the FDA is not going to be looking at lower treatment burden as a natural endpoint in Phase 2, correct -- or in Phase 3. That's never going to be one of their endpoints.

我有幾個問題。一是回到第二階段的設計，因為你所說的設計並不是為了優越性或非劣效性。我想，FDA 不會將降低治療負擔作為第二階段的自然終點，正確的——或者第三階段。這永遠不會成為他們的終點之一。

It's always going to be [b city], safety, and duration. So just -- I want to make sure we're clear that we know what the -- that the endpoints haven't necessarily changed as we go into Phase 3, but you're just looking right now at treatment burden.

永遠是[b城市]、安全性和持續時間。所以，我想確保我們清楚，我們知道，當我們進入第三階段時，終點不一定會改變，但你現在只是關注治療負擔。

We're looking at maintaining a stable visual acuity, and we're doing a treatment burden. And the reason for it -- you're right about what the draft guidelines say. We're very -- we understand that. He was very clear that -- Dr. Chambers and the group were very clear in saying that the treatment burden cannot be a primary endpoint. We understand that.

我們正在尋求保持穩定的視力，並且我們正在承擔治療負擔。其原因是——你對指南草案的說法是正確的。我們非常理解這一點。他非常明確地表示，錢伯斯博士和團隊非常明確地表示，治療負擔不能成為主要終點。我們明白這一點。

But for our Phase 2 trial, we're looking at treatment burden. And we're looking at duration, as I said, to set up the best design possible to go into Phase 3 with a fixed dosing schedule of CLS-AX. And obviously, going to Phase 3, unless the draft guidelines change with their final version, treatment burden would not be a primary endpoint in and of itself in a Phase 3 trial. And the FDA's made that pretty clear.

但對於我們的第二階段試驗，我們正在考慮治療負擔。正如我所說，我們正在考慮持續時間，以建立可能進入第 3 階段的最佳設計，並採用 CLS-AX 的固定給藥方案。顯然，進入第三階段，除非指南草案隨最終版本發生變化，否則治療負擔本身不會成為第三階段試驗的主要終點。 FDA 已經說得很清楚了。

It's very clear they're focused on safety. And it's very clear they are focused on vision. So we understand that. But this is more to give us the kind of information to see, do we have twice-a-year product here? Can we dose it in such a way in Phase 3 to give us the optimal chance of success in Phase 3, doing it according -- in a non-inferiority trial in Phase 3?

很明顯他們非常注重安全。很明顯，他們專注於願景。所以我們理解這一點。但這更多是為了給我們提供一些信息，讓我們看看，我們這裡有一年兩次的產品嗎？我們能否在第 3 階段以這種方式進行劑量，以便在第 3 階段獲得最佳成功機會，並按照第 3 階段的非劣效性試驗進行？

Okay. Got it. And just on the draft guidelines, I guess, what are some of the potential changes that you might possibly be facing to these guidelines? I mean, are they contemplating, potentially, a different standard of care with VABYSMO? Or is there something else that they're contemplating that -- from what you understand is being, I guess, [cost rented] as different ideas of new guideline requirements?

好的。知道了。就指南草案而言，我想，您可能會面臨這些指南的一些潛在變化？我的意思是，他們是否正在考慮使用 VABYSMO 提供不同的護理標準？或者他們是否正在考慮其他事情 - 根據您的理解，我猜，[租賃成本] 作為新指南要求的不同想法？

I don't have any insight into what the FDA might be considering. This is their first shot across the bow. I expect that there will be comments coming in from many corners of the industry to either seek clarification or suggest possible changes to this. I would think it's possible over time that they may add something like VABYSMO as an acceptable or even -- VABYSMO, in particular, find that acceptable as a comparator.

我不知道 FDA 可能會考慮什麼。這是他們第一次射箭。我預計行業各個角落都會提出意見，尋求澄清或建議對此進行可能的改變。我認為隨著時間的推移，他們可能會添加像 VABYSMO 這樣的東西作為可接受的，甚至 - VABYSMO，特別是，發現作為比較器是可以接受的。

But I don't think they're clear now that that's not their position. That could change over the next year or two. But as far as what they plan, I think this is their plan. They're going to let the industry comment on it.

但我認為他們現在還不清楚這不是他們的立場。這種情況可能會在未來一兩年內發生變化。但就他們的計劃而言，我認為這就是他們的計劃。他們將讓業界對此發表評論。

I'm not sure where it's going to come out. I think there are some things about the comparator arm that were a little unclear to some of us in the industry and either require clarification or change. But we'll see. We've had some conversations with the agency, as I'm sure all the other companies have, and we think we understand it well enough for, at least, the ODYSSEY trial, what we need to do there.

我不確定它會在哪裡出現。我認為關於比較器臂的一些事情對於我們業內的一些人來說有點不清楚，需要澄清或改變。但我們會看到。我們已經與該機構進行了一些對話，我相信所有其他公司也進行過一些對話，並且我們認為我們至少對於 ODYSSEY 試驗以及我們需要在那裡做的事情有足夠的了解。

Got it. And then if I could ask one last question. I know that ODYSSEY is not going to include treatment-experienced patients only. But I think -- I understand that you're going to try to minimize the sub-responders. Can you just help us understand why you might want to minimize that population? And if you do have sub-responders, are you going to be doing these different analyses within the trial to -- I don't know -- to separate them out or identify different responses based on their stages of disease?

知道了。然後我可以問最後一個問題嗎？我知道 ODYSSEY 不會只包括有治療經驗的患者。但我認為 - 我理解您將嘗試盡量減少次響應者。您能否幫助我們理解為什麼您可能希望最大程度地減少該人群？如果你確實有亞反應者，你是否會在試驗中進行這些不同的分析——我不知道——將他們分開或根據他們的疾病階段識別不同的反應？

Well, what we're really trying -- we're trying to get -- based on the conversations we had with our KOLs and our scientific advisory board, we're trying to get the largest, most relevant population to them that we can enroll in here. And if you remember the OASIS trial, they were treatment experienced, but they were heavily treatment experienced.

嗯，我們真正想要做的——我們想要得到的——基於我們與 KOL 和科學顧問委員會的對話，我們正在努力為他們爭取最大、最相關的人群。在這裡註冊。如果你還記得 OASIS 試驗，他們經歷過治療，而且經歷過大量治療。

These are people that were referred to as anti-VEGF addicts. They were being treated much more frequently than even the label indication for the anti-VEGF that they were on. We're not looking for that group. We're looking for a group that has shown a positive response to anti-VEGFs, but is not in the category of their needing aflibercept every four to six weeks instead of every eight months -- or eight weeks.

這些人被稱為抗 VEGF 成癮者。他們接受的治療頻率甚至比他們所服用的抗 VEGF 藥物的標籤指示要頻繁得多。我們不是在尋找那個團體。我們正在尋找對抗 VEGF 藥物表現出積極反應的群體，但不屬於他們需要每四到六周而不是每八個月或八週服用阿柏西普的範疇。

We're not looking for the really difficult-to-control patients, but we're not looking for patients that are naive either. So we're taking patients that have had some treatment response, some treatment history, and seeing what we can do when we compare ourselves to aflibercept.

我們不是在尋找真正難以控制的患者，但我們也不是在尋找天真的患者。因此，我們正在招募有一些治療反應、一些治療史的患者，看看當我們將自己與阿柏西普進行比較時我們能做些什麼。

We're trying to get a more -- we're trying to keep a fairly homogeneous group of patients, not trying to get a lot of sub-responders and then we have to go in and do a lot of analysis. We are just trying to take this group that we think is the most relevant group, certainly, in the opinion of our KOL.

我們試圖獲得更多的——我們試圖保留一組相當同質的患者，而不是試圖獲得大量的亞反應者，然後我們必須深入進行大量分析。我們只是試圖選取我們認為最相關的群體，當然，在我們的 KOL 看來。

Okay. That makes sense. Thank you.

好的。這就說得通了。謝謝。

Jonathan Wolleben, JMP.

喬納森·沃萊本，JMP。

Hi. This is Catherine Okoukoni on for Jon. I also have a question about what non-inferiority margins you want to [sit] in terms of BCVA. I know in ODYSSEY, you guys have said, it's not powered non-inferiority. But what would be the goal?

你好。我是喬恩的凱瑟琳·奧庫科尼。我還有一個問題，關於 BCVA 方面您希望[坐]多少非劣效性邊際。我知道在《奧德賽》中，你們說過，這不是動力非劣性。但目標是什麼？

You mean, in terms of -- I'm not sure I quite understand the question. What --

你的意思是，我不確定我是否完全理解這個問題。什麼 -

As far as -- I guess, what are your --

至於——我猜，你是什麼——

Looking at the two groups?

看看兩組？

Yeah. Between the EYLEA arm and then your treatment arm. What would be the margin that you guys would be looking for?

是的。在 EYLEA 手臂和您的治療手臂之間。你們想要的利潤是多少？

I think we have to be within about four letters -- four or five letters, plus or minus. I think it's comparable. We're just looking for a stable comparable BCVA. It's certainly going to have to be clinically acceptable, that's for sure. But we think between the two groups, as long as within a couple letters of the two groups will be fine.

我認為我們必須在大約四個字母之內——四個或五個字母，加上或減去。我認為是有可比性的。我們只是在尋找穩定的可比 BCVA。它肯定必須是臨床可接受的，這是肯定的。但我們認為在這兩個組之間，只要兩個組的幾個字母之內就可以了。

Great. And I just have one follow-up question to that. As far as the reduction in treatment burden versus longer duration, which of these two is more meaningful of the two measures?

偉大的。我只有一個後續問題。就減少治療負擔與延長治療時間而言，這兩項措施中哪一項更有意義？

Well, I think they're related. If I can have 80% of my CLS-AX patients go six months, I've got a very clear treatment burden reduction. So I think the duration is related directly to treatment burden. I mean, if you look at that period of time, you're going to get three aflibercept injections to one CLS-AX injection.

嗯，我認為它們是相關的。如果我能讓 80% 的 CLS-AX 患者接受六個月的治療，我的治療負擔就會得到非常明顯的減輕。所以我認為持續時間與治療負擔直接相關。我的意思是，如果你看看那段時間，你會得到 3 次阿柏西普注射和 1 次 CLS-AX 注射。

So that duration feeds directly into treatment burden reduction. It's more convenient for the patient, for the caregivers, and on a reimbursement basis. So it's better all around. And there's a many of us that are trying to have this extended duration of therapy.

因此，持續時間直接有助於減輕治療負擔。這對患者、護理人員來說都更方便，而且是在報銷的基礎上。所以一切都更好了。我們很多人都在嘗試延長治療時間。

It's better all around for patients, and for payers, and for caregivers that you can maintain stable visual acuity and not have to be injected every four to eight weeks. So I think the two are directly related.

對於患者、付款人和護理人員來說，如果您可以保持穩定的視力，而不必每四到八週注射一次，那麼這對患者、付款人和護理人員來說都是更好的選擇。所以我認為這兩者是直接相關的。

What would be a meaningful result as far as the measure goes in terms of time and then in terms of the duration between treatments?

就時間和治療之間的持續時間而言，什麼是有意義的結果？

Right now, we're looking at -- we're hoping that all of our patients go at least four -- and the vast majority go -- to six months in terms of duration. I mean, if you look at what's now in the market, VABYSMO says, for example, it can be up to four months. But we know that over half of their patients need to be retreated before three months.

現在，我們正在考慮 - 我們希望所有患者的持續時間至少為四個月 - 並且絕大多數為 - 六個月。我的意思是，如果你看看現在市場上的情況，VABYSMO 說，例如，它可能需要長達四個月的時間。但我們知道，他們一半以上的患者需要在三個月前接受治療。

High-dose EYLEA is being up for approval, and they're asking for approval between three and four months after quadrupling the dose. So we think there's a lot of room for improvement and excitement by physicians if we can be over four weeks up to five and six weeks.

高劑量 EYLEA 正在等待批准，他們要求在劑量增加四倍後三到四個月內獲得批准。因此，我們認為，如果我們能夠延長四個星期到五到六週的時間，那麼醫生還有很大的改進空間和令人興奮的地方。

Really, our target is trying to have it twice a year or every sixth month. Sorry. Excuse me, I said weeks -- every -- we'll go four months to six months. Our target really, our hope, is that we have a twice-a-year product.

實際上，我們的目標是嘗試每年兩次或每六個月一次。對不起。對不起，我說的是幾週——每隔幾週——我們會持續四個月到六個月。我們真正的目標，我們的希望，是我們有一個每年兩次的產品。

Thank you so much.

太感謝了。

Thank you. Andreas Argyrides, Wedbush.

謝謝。安德烈亞斯·阿吉里德斯，韋德布什。

Hi, Andreas.

嗨，安德烈亞斯。

Hey, George. Good morning, guys. And thanks for taking my questions here. So just maybe a follow-up to some that have been asked in a different way here. So thinking about -- or heading into ODYSSEY here, what is the bar for efficacy in terms of percentage of injection, frequency reduction, and percent of patients rescue free, given some of the data that you've seen with the competitors? And then, if you could provide updates on ongoing business development discussions regarding the use of the suprachoroidal injector -- thanks.

嘿，喬治。早上好傢伙。感謝您在這裡提出我的問題。因此，也許只是對這里以不同方式提出的一些問題的後續行動。因此，考慮一下——或者在這裡進入 ODYSSEY，根據您在競爭對手中看到的一些數據，注射百分比、頻率減少和患者免費搶救百分比方面的功效標準是什麼？然後，如果您能提供有關脈絡膜上註射器使用的正在進行的業務開發討論的最新信息，謝謝。

Well, I think, I basically have been answering that in some of the previous questions. We're hoping that a significant percentage of our patients in the ODYSSEY trial go five to six months after the injection without rescue. So we're looking for, basically, the lowest degree of rescue possible in the CLS-AX group. I mean, it's also possible even in the comparator group of aflibercept that they're going to need treatment in between their every-eight-week doses.

嗯，我想，我基本上已經在之前的一些問題中回答了這個問題。我們希望 ODYSSEY 試驗中很大一部分患者在註射後五到六個月內都沒有得到救助。所以我們基本上是在 CLS-AX 組中尋找盡可能最低程度的救援。我的意思是，即使在阿柏西普的比較組中，他們也有可能在每八週的劑量之間需要接受治療。

So we're looking at that and we're very -- we think that we're going to get the vast majority of our patients go without need for supplemental therapy at least four, and, hopefully, the vast majority go five or six months. So that's really all I can tell you.

所以我們正在研究這個問題，我們非常認為我們將使絕大多數患者不需要至少四種補充治療，並且希望絕大多數患者能夠接受五到六次補充治療幾個月。這就是我能告訴你的全部。

I don't -- other groups that have done this have had to have rescue. Other groups that are studying, certainly, the tyrosine kinase inhibitors have had patients that are enrolled in their study that, arguably, may not have required any treatment, which may make their data look a little bit better.

我不這麼認為——其他做過這種事的團體也不得不接受救援。當然，其他正在研究酪氨酸激酶抑製劑的小組也有一些患者參加了他們的研究，可以說，這些患者可能不需要任何治療，這可能會讓他們的數據看起來好一點。

We, again, are going -- making sure that what we do when we enroll our patients in our studies, like we did in OASIS and like we intend to do in ODYSSEY, is make sure that patients that are being enrolled have active disease. All of them need to have active disease, so we know that patients require medicine.

我們再次強調，當我們將患者納入研究時，就像我們在 OASIS 中所做的那樣以及我們打算在 ODYSSEY 中所做的那樣，確保所招募的患者患有活動性疾病。他們都需要患有活動性疾病，所以我們知道患者需要藥物。

We do not want to enroll anybody in our trial, and we're trying very hard to prevent this, that may never need treatment over the trial duration period. I mean, there's a significant literature that supports people within that have been diagnosed but have inactive disease, or they're completely dry on diagnosis and may not require any treatment for six months and just watch while waiting.

我們不想讓任何人參加我們的試驗，我們正在努力防止這種情況發生，在試驗期間可能永遠不需要治療。我的意思是，有大量文獻支持那些已被診斷但患有非活動性疾病的人，或者他們完全沒有診斷，可能在六個月內不需要任何治療，只是在等待時觀察。

So we want to eliminate that. We want to know if we have something that really works. And so we want to put it -- we want to put our drug in patients that we know, to the best of our ability, will require treatment. And so, hopefully, in our arm, there's very few, if any, need for supplemental treatment and that the vast majority of the patients go forward to six months after receiving their initial dose of CLS-AX.

所以我們想消除這種情況。我們想知道我們是否有真正有效的東西。所以我們想說——我們希望盡我們最大的能力將我們的藥物用於我們知道需要治療的患者身上。因此，希望在我們的手臂中，幾乎不需要補充治療（如果有的話），並且絕大多數患者在接受初始劑量的 CLS-AX 後可以繼續治療六個月。

On the BD front, we continue to have active discussions with a number of companies that are interested in accessing the suprachoroidal technology that we have. We're the only technology that's been used in the clinic. We got six trials ongoing now around the world with several different partners, including our own trial. We have clinical trials in China. We have clinical trials here in the US.

在 BD 方面，我們繼續與許多有興趣使用我們擁有的脈絡膜上技術的公司進行積極討論。我們是唯一在診所使用的技術。我們現在正在世界各地與幾個不同的合作夥伴進行六項試驗，其中包括我們自己的試驗。我們在中國有臨床試驗。我們在美國進行臨床試驗。

Aura is going to be doing their clinical trials here and overseas with our suprachoroidal microinjector. And so people know if we're clearly the leader in administering drugs in the suprachoroidal space. And people know that if they want to get there and they want to get there in a proven way, in a reliable way, in a safe way, they should be talking to us

Aura 將使用我們的脈絡膜上顯微注射器在國內外進行臨床試驗。因此人們知道我們是否明顯是脈絡膜上腔給藥的領導者。人們知道，如果他們想要實現這一目標，並且希望以經過驗證的方式、可靠的方式、安全的方式實現這一目標，他們應該與我們交談

And so we have those ongoing conversations, but we're not ready to announce anything on the partnering front at this time.

因此，我們正在進行這些對話，但目前我們還沒有準備好宣布任何有關合作的信息。

Okay, great. Thanks for all the updates, and we'll follow up later. Thanks.

好的，太好了。感謝您的所有更新，我們稍後會跟進。謝謝。

Sure. Yeah, no problem.

當然。是的，沒問題。

Thank you. Yi Chen, H.C. Wainwright & Co. Yi? Yi, are you able to speak?

謝謝。陳毅, H.C.溫賴特公司易？伊，你能說話嗎？

Hello. (multiple speakers) me?

你好。 （多個發言者）我？

Yes. Hello, Yi.

是的。你好，易。

Hi. Sorry. Thank you for taking my question. My first question is, could you give us some additional color on the XIPERE launch? And how should we project the license revenue going forward?

你好。對不起。感謝您回答我的問題。我的第一個問題是，您能給我們一些關於 XIPERE 發布的額外信息嗎？我們應該如何預測未來的許可收入？

All right, Yi. Please repeat.

好吧，伊。請重複。

I was asking that, could you give us some additional color on the XIPERE commercial performance? And how should project the license revenue going forward?

我想問一下，您能給我們一些關於XIPERE商業表演的補充嗎？未來的許可收入應該如何預測？

Okay. Charlie, do you want to take that question?

好的。查理，你想回答這個問題嗎？

Sure. Yeah. So from XIPERE, as we all know, Bausch & Lomb has launched that product. They've been very active, training more than 1,000 retinal specialists in the US to use XIPERE. We've heard it had positive feedback, but Bausch has -- we're not allowed to step ahead of them and talk about their sales. And when they're ready to, they will report on it. So I can't give you any insight into Bausch's sales, B&L sales.

當然。是的。所以從XIPERE來看，眾所周知，博士倫推出了該產品。他們非常積極，在美國培訓了 1,000 多名視網膜專家使用 XIPERE。我們聽說它得到了積極的反饋，但 Bausch 卻——我們不被允許領先於他們談論他們的銷售情況。當他們準備好時，他們將對此進行報告。因此，我無法向您提供任何有關 Bausch 銷售、B&L 銷售的信息。

And then from partnering estimates, we don't give out revenue forecast. But there are some licensing milestones, nothing major, coming up, I would assume, as some of our partners move into different phases in their clinical study. Sorry, but we don't give a forecast on our partners in milestones, regulatory milestones.

然後從合作夥伴的估計來看，我們沒有給出收入預測。但我認為，隨著我們的一些合作夥伴進入臨床研究的不同階段，將會出現一些許可里程碑，但沒什麼大不了的。抱歉，我們不會對合作夥伴的里程碑、監管里程碑做出預測。

Thank you. My second question is, given the trial design of the ODYSSEY trial and your [comments] on treatment-naive patients, do you think, in real world practice, long-lasting wet AMD treatment will ever be used on treatment-naive patients?

謝謝。我的第二個問題是，考慮到 ODYSSEY 試驗的試驗設計以及您對初治患者的[評論]，您認為在現實世界的實踐中，長期濕性 AMD 治療是否會用於初治患者？

On treatment-naive? I think with sufficient -- that's why we're going to the group that we're going to first other than treatment naive. But I do think that, eventually, as more data is obtained on ours and other products, I do think that its more extended duration treatment will become more of the norm. Obviously, physicians will work based on data. But as that data is accumulated, I think they will.

未經治療？我認為，這就是為什麼我們首先要加入的小組，而不是單純的治療。但我確實認為，最終，隨著我們的產品和其他產品獲得更多數據，我確實認為其更長持續時間的治療將變得更加規範。顯然，醫生將根據數據開展工作。但隨著數據的積累，我認為它們會的。

Now, there's a difference between saying, they'll use extended duration and will they extend the duration of patient visits to the physician's office? I think that -- I can't really comment on what physician practices would be. But in our estimation, and I think in others' estimation, it's not really going to change significantly, the number of times per year a physician wants to see a patient.

現在，說他們會使用延長的持續時間和他們會延長患者就診醫生辦公室的持續時間之間存在區別嗎？我認為——我無法真正評論醫生的做法。但根據我們的估計，我認為根據其他人的估計，醫生每年想要看病人的次數並不會真正發生重大變化。

But I think it would -- with extended duration, as it gets more -- as more is developed, I think it could make a small difference. For example, if patients with wet AMD are being seen monthly, they may go to being seen every other month. And then they may not need to be injected on every visit.

但我認為，隨著持續時間的延長，隨著它變得越來越多，隨著更多的開發，我認為它可能會產生小小的影響。例如，如果濕性 AMD 患者每月就診一次，他們可能會每隔一個月就診一次。然後可能不需要每次就診時都注射。

But if you're being seen every month and demonstrating stable BCVA and the degree of fluid is holding reasonably stable, maybe they're injected every other visit. So they're being injected four times a year. But only seeing -- and seeing the doctor six times a year, but being injected three times a year or two times a year.

但如果您每個月都來就診，並且表現出穩定的 BCVA 並且液體含量保持相當穩定，則可能每隔一次就診時都會注射一次。所以他們每年註射四次。但只是每年看醫生六次，但每年註射三次或兩次。

So I do think it will eventually change the practice. In our conversations with KOLs, they're very excited about seeing durations longer than two months. You can see from the uptake of VABYSMO right now, where it has the opportunity to go to every four months, but not the guarantee. Because, again, like I said earlier, over half their patients needed to be retreated by three months.

所以我確實認為這最終會改變這種做法。在我們與 KOL 的對話中，他們對於看到持續時間超過兩個月感到非常興奮。從現在VABYSMO的使用情況可以看出，它有機會每四個月去一次，但不能保證。因為，正如我之前所說，他們一半以上的患者需要在三個月內接受治療。

There has been a tremendous uptake in VABYSMO with that small incremental gain. So I think if you are able to show, with very solid data, that you can dose somebody and maintain stable visual acuity and keep the fluid in the retina under control for four to six months with solid data, I think that will change the treatment paradigm eventually in the physician's office.

VABYSMO 獲得了巨大的認可，但增量卻很小。所以我認為，如果你能夠用非常可靠的數據表明，你可以給某人服用藥物並保持穩定的視力，並用可靠的數據將視網膜中的液體控制在四到六個月內，我認為這將改變治療方法範式最終出現在醫生的辦公室。

Thank you.

謝謝。

Thank you. I would now like to turn it back to Dr. Lasezkay for closing remarks.

謝謝。現在我想請 Lasezkay 博士做總結髮言。

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

我要感謝大家今天早上加入我們的電話會議。我們感謝您對 Clearside 的持續關注，我們期待向您通報我們的最新進展。接線員，您現在可以斷開連接了。謝謝。