Clearside Biomedical Inc (CLSD) 2023 Q2 法說會逐字稿

Greetings, and welcome to the Clearside Biomedical second-quarter 2023 financial results and corporate update call. (Operator Instructions) Please note this conference is being recorded.

您好，歡迎您參加 Clearside Biomedical 2023 年第二季財務表現及公司更新電話會議。 （操作員說明）請注意，本次會議正在錄製中。

I will now turn the conference over to your host, Jenny Corbin of Investor Relations. You may begin.

現在我將把會議交給東道主投資者關係部門的珍妮·科爾賓 (Jenny Corbin)。你可以開始了。

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中就公司未來預期、計畫和前景發表的各種言論均構成符合 1995 年《私人證券訴訟改革法案》目的的前瞻性陳述。

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, 2022, our quarterly report on Form 10-Q for the quarter ended June 30, 2023, and our other SEC filings available on our website.

由於各種重要因素的影響，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2022 年12 月31 日的年度報告10-K 表格的風險因素部分中討論的因素、我們的季度報告截至 2023 年 6 月 30 日的季度的 10-Q 表，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，即使我們的觀點改變。

On today's call, we have George Lasezkay, our Chief Executive Officer; and Charlie Deignan, our Chief Financial Officer. After our formal remarks, we will open the call for your questions. I would now like to turn the call over to George.

出席今天的電話會議的有我們的執行長 George Lasezkay；以及我們的財務長 Charlie Deignan。在我們正式發言後，我們將開始電話詢問您的問題。我現在想把電話轉給喬治。

Thanks, Jenny. The last six months have demonstrated that Clearside is the clear leader in delivering agents to the suprachoroidal space.

謝謝，珍妮。過去六個月的情況表明，Clearside 在向脈絡膜上腔輸送藥劑方面無疑是領先者。

We have a proprietary suprachoroidal space injection technology that utilizes our patented SCS Microinjector. We're able to deliver small molecules and gene therapy behind the visual field, targeting multiple retinal diseases. We have the first and only FDA-approved SCS product with XIPERE. And we have four external validating SCS delivery collaborations as well as an early-stage internal research and development pipeline.

我們擁有專有的脈絡膜上腔注射技術，該技術利用我們專利的 SCS 顯微注射器。我們能夠在視野後面提供小分子和基因治療，針對多種視網膜疾病。我們擁有第一個也是唯一獲得 FDA 批准的 XIPERE SCS 產品。我們有四個外部驗證 SCS 交付合作以及一個早期的內部研發管道。

Importantly, as we expand our development opportunities, both internally and with our partners, our versatile therapeutic platform continues to grow. Together with our licensing partners, there are now six ongoing SCS trials in five different indications utilizing four potential therapies.

重要的是，隨著我們在內部和與合作夥伴擴大發展機會，我們的多功能治療平台不斷發展。與我們的許可合作夥伴一起，目前正在進行六個 SCS 試驗，針對五種不同的適應症，利用四種潛在的療法。

Clearside's lead internal clinical development program is CLS-AX, our proprietary suspension of axitinib, delivered into the suprachoroidal space. CLS-AX is targeting the multibillion-dollar market for wet AMD. So let me take a moment to talk about the market opportunity and why we believe we can truly make a difference in the lives of the millions of patients suffering from this disorder.

Clearside 的主要內部臨床開發項目是 CLS-AX，這是我們專有的阿西替尼懸浮液，輸送到脈絡膜上腔。 CLS-AX 的目標是數十億美元的濕 AMD 市場。因此，讓我花點時間談談市場機會以及為什麼我們相信我們能夠真正改變數百萬患有這種疾病的患者的生活。

Wet AMD is a crowded arena for the development of new products, mainly due to the large and growing market as a result of the aging population, particularly, in the US. With the higher demand, there's room for new treatments that provide significant improvement over current therapies including reducing the treatment burden for patients and their caregivers.

濕式 AMD 是新產品開發的一個擁擠的舞台，這主要是由於人口老化導致市場規模龐大且不斷增長，特別是在美國。隨著需求的增加，新的治療方法有很大的空間，可以比現有的治療方法提供顯著的改進，包括減輕患者及其照護者的治療負擔。

Based on the label for existing marketed products for wet AMD, Lucentis is recommended to be dosed 12 times a year; Eylea, 2 milligrams, six times a year; and recently approved Vabysmo, up to six times per year. In contrast, we believe that CLS-AX may be up to a twice-a-year treatment for wet AMD.

根據現有濕性 AMD 市售產品的標籤，Lucentis 建議每年服用 12 次； Eylea，2毫克，每年六次；最近批准了 Vabysmo，每年最多六次。相較之下，我們認為 CLS-AX 可能最多可用於治療濕性 AMD 每年兩次。

This matters because it has been well documented that patient compliance is a challenge. And therefore, a treatment option where patients maintain their vision with less frequent dosing may achieve improved patient outcomes. CLS-AX could reduce the onerous treatment burden for patients who currently require frequent dosing and numerous office visits with existing approved drugs.

這很重要，因為有充分證據表明患者的依從性是一個挑戰。因此，患者以較低劑量維持視力的治療選擇可能會改善患者的治療效果。 CLS-AX 可以減輕目前需要頻繁用藥和多次就診使用現有核准藥物的患者的繁重治療負擔。

CLS-AX has the potential to be a better maintenance treatment option based on three main differentiating factors. First, CLS-AX utilizes axitinib, which is the most highly potent tyrosine kinase inhibitor, delivering ten times more potency than other TKIs in preclinical studies.

基於三個主要差異化因素，CLS-AX 有潛力成為更好的維持治療選擇。首先，CLS-AX 利用阿西替尼，這是最有效的酪胺酸激酶抑制劑，在臨床前研究中其效力比其他 TKI 強十倍。

Second, CLS-AX is administered suprachoroidally using our proprietary SCS Microinjector. This delivery mechanism does not require surgery and does not require an implant inserted into the eye. It's delivered by physicians in their office and has proven to be safe and reliable both commercially and in multiple clinical trials. And thirdly, in our OASIS Phase 1/2a clinical trial, we showed that a single administration of CLS-AX demonstrated a favorable safety profile with no signs of inflammation.

其次，CLS-AX 使用我們專有的 SCS 顯微注射器在脈絡膜上給藥。這種輸送機制不需要手術，也不需要將植入物插入眼睛。它由醫生在他們的辦公室提供，並在商業和多項臨床試驗中被證明是安全可靠的。第三，在我們的 OASIS 1/2a 期臨床試驗中，我們顯示單次施用 CLS-AX 表現出良好的安全性，沒有發炎跡象。

In terms of duration in the extension study of OASIS in higher-dose cohorts with a single dose of CLS-AX, two-thirds of the participants did not need supplemental treatment for six months or more. Also, these 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. Importantly, we also observed signs of biological effect with stable mean best corrected visual acuity or BCVA and stable mean central subfield thickness or CST.

就單劑量 CLS-AX 高劑量隊列中 OASIS 擴展研究的持續時間而言，三分之二的參與者在六個月或更長時間內不需要補充治療。此外，與進入 OASIS 試驗前的六個月相比，這些參與者的治療負擔減少了 77% 至 85%，以他們在六個月內接受的抗 VEGF 治療的次數來衡量。重要的是，我們還觀察到了穩定的平均最佳矯正視力（BCVA）和穩定的平均中心子視野厚度（CST）的生物效應跡象。

Encouraged by the promising OASIS results and following the FDA draft guidance for drug development of treatments for wet AMD, last quarter, we initiated ODYSSEY, a randomized double-masked multi-center Phase 2b clinical trial in participants with wet AMD. The overall objective for the trial is to evaluate the safety, efficacy, and duration of CLS-AX treatment in participants with wet AMD.

受到 OASIS 有希望的結果的鼓舞，並遵循 FDA 濕性 AMD 治療藥物開發指南草案，上個季度，我們啟動了 ODYSSEY，這是一項針對濕性 AMD 參與者的隨機雙盲多中心 2b 期臨床試驗。該試驗的總體目標是評估 CLS-AX 治療濕性 AMD 參與者的安全性、有效性和持續時間。

The other arm in the trial is a current standard of care, Eylea or aflibercept. Our goals for the ODYSSEY trial are to demonstrate similar visual acuity outcomes with a lower treatment burden for the CLS-AX arm and to obtain the necessary clinical data to determine a desired CLS-AX fixed dosing regimen for a Phase 3 wet AMD clinical development program.

試驗的另一組是目前的護理標準，Eylea 或 aflibercept。我們 ODYSSEY 試驗的目標是證明 CLS-AX 組的視力結果相似且治療負擔較低，並獲得必要的臨床數據以確定 3 期濕性 AMD 臨床開發計劃所需的 CLS-AX 固定劑量方案。

We are pleased that the trial is off to a solid start and is progressing as planned. Multiple participants have been randomized to receive either CLS-AX or aflibercept. Clinical trial sites have been eager to be part of the trial, and we have nearly all of our planned 30 sites currently open to enroll participants in the trial.

我們很高興試驗已經有了一個良好的開端，並且正在按計劃進行。多位參與者被隨機分配接受 CLS-AX 或阿柏西普治療。臨床試驗中心一直渴望成為試驗的一部分，我們計劃的 30 個試驗中心目前幾乎全部開放，以招募試驗參與者。

As a reminder, ODYSSEY is expected to enroll a total of 60 participants, randomized to either CLS-AX 1 milligram or aflibercept 2 milligrams, with a 2:1 randomization schedule. This means that there is expected to be 40 participants in the CLS-AX arm and 20 participants in the aflibercept arm. The treatment period is a total of 36 weeks.

提醒一下，ODYSSEY 預計將總共招募 60 名參與者，按照 2:1 的隨機方案隨機分配到 CLS-AX 1 毫克或阿柏西普 2 毫克。這意味著 CLS-AX 組預計有 40 名參與者，阿柏西普組預計有 20 名參與者。治療期總共為36週。

In the trial, CLS-AX will be administered by suprachoroidal injection using Clearside SCS Microinjector. And aflibercept will be administered by intravitreal injection.

在試驗中，CLS-AX 將使用 Clearside SCS 顯微注射器透過脈絡膜上註射進行給藥。阿柏西普將透過玻璃體內注射進行給藥。

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

此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。次要結果測量是透過總注射量測量的治療負擔，包括試驗期間補充治療的需要，以及視覺功能和眼部解剖學（例如 CST）的其他變化。

One important component of ODYSSEY is the eligibility criteria. Our inclusion criteria is designed to ensure that participants in our trial have active disease at screening. Eligible participants will be treatment-experienced and will undergo diagnostic imaging after screening visit, followed by masked reading center confirmation of persistent active disease.

ODYSSEY 的重要組成部分之一是資格標準。我們的納入標準旨在確保試驗參與者在篩檢時患有活動性疾病。符合條件的參與者將具有治療經驗，並將在篩選訪問後接受診斷影像，然後由盲讀中心確認持續活動性疾病。

This level of specificity is to ensure that participants are in need of treatment, will likely respond to, and benefit from treatment with anti-VEGF therapy. We believe this will allow the proper assessment of the potential advantages of CLS-AX in patients with wet AMD.

這種程度的特異性是為了確保參與者需要治療、可能對抗 VEGF 療法產生反應並從中受益。我們相信這將有助於正確評估 CLS-AX 在濕性 AMD 患者中的潛在優勢。

We further believe CLS-AX will demonstrate the ability to maintain visual acuity with a longer duration of action in order to reduce the treatment burden for patients with wet AMD. We are confident in our overall trial design and the potential success in ODYSSEY. And we look forward to reporting top-line data in the third quarter of 2024.

我們進一步相信，CLS-AX 將證明能夠在更長的作用時間內維持視力，從而減輕濕性 AMD 患者的治療負擔。我們對整體試驗設計和 ODYSSEY 的潛在成功充滿信心。我們期待在 2024 年第三季報告頂線數據。

Moving on to XIPERE, we continue to receive positive feedback from clinicians regarding the use of XIPERE with patients. Our North American commercial partner for XIPERE, Bausch + Lomb, continues to conduct product education and training sessions for healthcare providers, with more than 1,200 retinal specialists trained to date. These sessions have been well attended and well received.

接下來是 XIPERE，我們繼續收到臨床醫生關於 XIPERE 在患者中使用的正面回饋。我們的 XIPERE 北美商業合作夥伴 Bausch + Lomb 繼續為醫療保健提供者開展產品教育和培訓課程，迄今已培訓了 1,200 多名視網膜專家。這些會議出席人數眾多，並受到好評。

Physicians report that the suprachoroidal injection procedure utilizing the SCS Microinjector is easy to learn, and that XIPERE is highly effective in treating their patients with macular edema associated with uveitis. Looking forward, Bausch + Lomb is focused on increasing engagement with uveitis specialists across the country and working on reimbursement parameters that will make it simpler for physicians to use XIPERE for their patients.

醫生報告說，利用 SCS 顯微注射器進行脈絡膜上腔注射程序很容易學習，且 XIPERE 在治療與葡萄膜炎相關的黃斑水腫患者方面非常有效。展望未來，博士倫致力於加強與全國葡萄膜炎專家的合作，並研究報銷參數，使醫生更容易為患者使用 XIPERE。

Our Asia-Pacific partner, Arctic Vision, continues to move forward in two indications with their development of XIPERE, which they refer to as Arcatus. For the first indication of uveitic macular edema, Arctic Vision is currently enrolling a confirmatory Phase 3 trial in China. If positive, the data will allow Arctic to apply for marketing approval in China.

我們的亞太合作夥伴 Arctic Vision 繼續在 XIPERE 的兩個適應症方面取得進展，他們稱之為 Arcatus。對於葡萄膜炎性黃斑水腫的第一個適應症，Arctic Vision 目前正在中國進行一項驗證性 3 期試驗。如果數據為陽性，北極將能夠申請在中國的營銷許可。

In addition, Arctic recently announced that the Therapeutic Goods Administration of Australia has formally accepted its new drug application for suprachoroidal use of Arcatus for the treatment of uveitic macular edema. The acceptance of the NDA in Australia is an additional validation of the suprachoroidal administration being an innovative recognized form of ophthalmic drug delivery and another step towards the global commercialization of XIPERE.

此外，Arctic近期宣布，澳洲治療產品管理局正式受理其脈絡膜上腔使用Arcatus治療葡萄膜炎性黃斑水腫的新藥申請。澳洲新藥申請的接受是對脈絡膜上腔給藥作為一種創新的公認眼科藥物輸送形式的進一步驗證，也是 XIPERE 全球商業化的又一步。

The second indication of Arctic is diabetic macular edema. Arctic has completed a Phase 1 clinical trial, and we expect them to report the data from the trial later this year. This data could provide helpful insight into the potential for broadening the use of XIPERE in other indications. We're excited about the progress Arctic Vision has made to expand the use of XIPERE, and we look forward to further updates from them.

Arctic的第二個適應症是糖尿病黃斑水腫。 Arctic 已完成一期臨床試驗，我們預計他們將在今年稍後報告試驗數據。這些數據可以幫助深入了解 XIPERE 在其他適應症中擴大使用的潛力。我們對 Arctic Vision 在擴大 XIPERE 的使用方面取得的進展感到興奮，並期待他們的進一步更新。

We also continue to work closely with our partners developing breakthrough technologies to deliver gene therapy and ocular oncology treatment utilizing suprachoroidal delivery with our SCS Microinjector. Earlier this month, Regenxbio announced updates on its ABBV-RGX-314 program for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie.

我們也繼續與合作夥伴密切合作，開發突破性技術，利用我們的 SCS 顯微注射器進行脈絡膜上腔遞送來提供基因治療和眼部腫瘤治療。本月早些時候，Regenxbio 宣布更新與 AbbVie 合作開發的用於治療濕性 AMD 和糖尿病視網膜病變的 ABBV-RGX-314 計畫。

In July, Regenxbio presented interim data from the Phase 2 AAVIATE and ALTITUDE trials, demonstrating suprachoroidal delivery of 314, administered to patients with prophylactic steroid eye drops, resulted in zero cases of intraocular inflammation. Additional data from Regenxbio on both trials is expected over the next six months.

7 月，Regenxbio 公佈了 2 期 AAVIATE 和 ALTITUDE 試驗的中期數據，證明脈絡膜上腔遞送 314 給使用預防性類固醇眼藥水的患者，導致眼內發炎病例為零。 Regenxbio 預計將在未來六個月內提供有關這兩項試驗的更多數據。

Interim efficacy data from the ALTITUDE trial in diabetic retinopathy is planned for American Academy of Ophthalmology meeting in November of 2023. And the interim efficacy data from the AAVIATE trial in wet AMD is expected to be presented at the Hawaiian Eye and Retina meeting in January 2024.

糖尿病視網膜病變的 ALTITUDE 試驗的中期療效數據計劃在 2023 年 11 月的美國眼科學會會議上公佈。濕性 AMD 的 AAVIATE 試驗的中期療效數據預計將在 2024 年 1 月的夏威夷眼和視網膜會議上公佈。

Our oncology partner, Aura Biosciences, announced their progress last week with their drug candidate, bel-sar, for the treatment of choroidal melanoma. Their global Phase 3 clinical trial is expected to dose the first patient in the second half of 2023 and is designed as a superiority trial comparing bel-sar versus sham, with the primary endpoint as time to tumor progression.

我們的腫瘤學合作夥伴 Aura Biosciences 上週宣布了他們的候選藥物 Bel-sar 在治療脈絡膜黑色素瘤的進展。他們的全球 3 期臨床試驗預計將在 2023 年下半年對第一位患者進行給藥，該試驗被設計為比較 Bel-sar 與 Sham 的優效性試驗，主要終點為腫瘤進展時間。

Aura has qualified trial sites globally, with multiple sites ready to enroll patients in the US. In addition, Aura expects to present updated efficacy data in the second half of 2023. The Phase 2 data will include 12 months median follow-up of patients treated with the therapeutic regimen intended to be used in the global Phase 3 trial.

Aura 在全球擁有合格的試驗地點，其中多個地點已準備好在美國招募患者。此外，Aura 預計將在 2023 年下半年提供更新的療效數據。2 期數據將包括接受全球 3 期試驗中使用的治療方案治療的患者的中位隨訪 12 個月。

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

有了我們計劃的摘要，我現在將把電話轉給我們的財務長 Charlie Deignan，以獲取最新的財務資訊。

Thank you, George, and good afternoon, everyone. Our financial results for the second quarter were published earlier in our press release and are available on our website. Therefore, I would just provide a summary of our financial status.

謝謝喬治，大家下午好。我們第二季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，我只想提供我們財務狀況的摘要。

As of June 30, 2023, our cash and cash equivalents totaled approximately $35 million. We continue to prudently manage our cash as we move forward with our programs. And we have worked to fine-tune our budget over the next year. Based on our current outlook, we now expect to have sufficient resources to fund our planned operations into the third quarter of 2024.

截至 2023 年 6 月 30 日，我們的現金及現金等價物總額約為 3,500 萬美元。在推進我們的計劃的同時，我們將繼續謹慎管理我們的現金。我們已經努力調整明年的預算。根據我們目前的前景，我們現在預計將有足夠的資源為我們計劃營運至 2024 年第三季的營運提供資金。

Over the next few months, we look forward to participating in several investor conferences, including the H.C. Wainwright Ophthalmology Conference this Wednesday, the Cantor Global Healthcare Conference in September, and the JonesTrading healthcare summit in October. We look forward to keeping you updated on our progress.

在接下來的幾個月裡，我們期待參加一些投資人會議，包括 H.C.本週三的溫賴特眼科會議、九月的坎托全球醫療保健會議和十月的瓊斯貿易醫療保健高峰會。我們期待向您通報我們的最新進展。

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. In closing, our state-of-the-art suprachoroidal injection technology continues to advance globally. CLS-AX is targeting a large market opportunity in wet AMD with a new mechanism of action utilizing pan-VEGF inhibition and a unique suprachoroidal delivery using our SCS Microinjector.

謝謝，查理。最後，我們最先進的脈絡膜上註射技術在全球範圍內不斷發展。 CLS-AX 瞄準了濕性 AMD 的龐大市場機會，採用了利用泛 VEGF 抑制的新作用機制，以及使用我們的 SCS 微注射器進行獨特的脈絡膜上腔輸送。

We are confident in our Phase 2b ODYSSEY trial design and the potential for CLS-AX to offer patients a therapy that will maintain their vision while reducing the burden of frequent injections. Our current partners are making meaningful progress as well and reporting encouraging clinical data across their respective programs.

我們對 2b 期 ODYSSEY 試驗設計以及 CLS-AX 為患者提供維持視力同時減輕頻繁注射負擔的療法的潛力充滿信心。我們目前的合作夥伴也取得了有意義的進展，並報告了各自專案中令人鼓舞的臨床數據。

We continue to receive positive feedback on our SCS Microinjector and the potential advantages of drug delivery to the suprachoroidal space. We remain very active within the medical community at scientific meetings and in ongoing discussions with key opinion leaders in the treatment of back-of-the-eye diseases.

我們不斷收到有關 SCS 顯微注射器以及將藥物輸送到脈絡膜上腔的潛在優勢的積極回饋。我們在醫學界的科學會議上仍然非常活躍，並與關鍵意見領袖就眼後疾病的治療進行持續的討論。

Clearside has pioneered drug delivery behind the visual field to treat retinal disorders. We will continue to explore opportunities to expand the use of our suprachoroidal injection technology platform.

Clearside 率先在視野後面進行藥物輸送，以治療視網膜疾病。我們將繼續探索擴大脈絡膜上註射技術平台用途的機會。

Now, I'd like the operator to open the call for questions.

現在，我希望接線員開始提問。

(Operator Instructions) Jon Wolleben, JMP Securities.

（操作員指令）Jon Wolleben，JMP 證券。

Hey, thanks for taking the questions and the updates. A couple for me, George. You mentioned almost 30 sites are open now. Wondering if you still feel good about that number, if you think you'll add more, or you have enough. And then also, I think you commented that patients are being dosed. Can you tell us how many have been dosed so far in the study?

嘿，感謝您提出問題和更新。喬治，給我一對。您提到現在有近 30 個站點開放。想知道您是否仍然對這個數字感覺良好，是否認為您會添加更多，或者您已經足夠了。然後，我認為您評論說患者正在服用藥物。您能告訴我們到目前為止，研究中已經注射了多少劑量嗎？

Okay, Jon. Our goal was 30, and we're very close to 30. We feel comfortable with 30. We have a lot of interests. We may enroll a few extra over 30. That's possible. But right now, our goal is 30, and we're just about there. So we're feeling very good with that.

好吧，喬恩。我們的目標是 30 歲，而且我們非常接近 30 歲。我們對 30 歲感到滿意。我們有很多興趣。我們可能會額外招收一些30歲以上的學生。這是可能的。但現在，我們的目標是 30，而且我們快到了。所以我們對此感覺非常好。

In terms of updates, we have reported that we've begun the randomization process. So we've had multiple patients, be randomized between the CLS-AX arm and the aflibercept arm. But at this point in time, we're not giving updates on the actual number of patients in the trial.

在更新方面，我們報告說我們已經開始隨機化過程。因此，我們有多名患者被隨機分配到 CLS-AX 組和阿柏西普組。但目前，我們沒有提供試驗中實際患者人數的最新資訊。

Okay. And then, an interesting nuance in the design for ODYSSEY is the ability to redose CLS-AX depending on when someone hits rescue criteria. Wondering about your modeling about -- how many patients do you think will be redosed with CLS-AX or rescued with Eylea based on the OASIS data? I think this could give us a lot of interesting information we're not going to get from other TKI studies.

好的。然後，ODYSSEY 設計中一個有趣的細微差別是能夠根據某人何時達到救援標準來重新配置 CLS-AX。想知道您的模型 - 根據 OASIS 數據，您認為有多少患者將接受 CLS-AX 重新給藥或使用 Eylea 進行搶救？我認為這可以為我們提供許多我們無法從其他 TKI 研究中獲得的有趣資訊。

Yeah. Listen, we've designed this trial in a way that we think we're going to be -- have a lot of success in getting this to be a four-to-six-month treatment. And I'm very hopeful, and I expect a high degree of success of getting the vast majority of the patients towards six months.

是的。聽著，我們以我們認為將要進行的方式設計了這項試驗——在將其變成四到六個月的治療方面取得了巨大的成功。我非常有希望，我希望絕大多數患者能夠在六個月內獲得成功。

I don't believe -- unless there's deviations from protocol, I would be very surprised if we have any rescues that are less than 12 weeks in the CLS-AX arm. Our expectation is there's -- be very few, if any, early-stage rescues in less than 12 weeks after the first CLS-AX dose, which if you remember, we've got the three loading doses, and we're dosing CLS-AX at the second loading dose of aflibercept.

我不相信——除非有違反協議的情況，否則如果我們在 CLS-AX 組中進行少於 12 週的救援，我會感到非常驚訝。我們的預期是，在第一次CLS-AX 劑量後不到12 週內，即使有的話，早期救援也非常少，如果你還記得的話，我們已經有了三個負荷劑量，而且我們正在服用CLS -阿柏西普第二負荷劑量的 AX。

So we're doing aflibercept on label for both groups in terms of loading. And then we're going -- switching to -- in the aflibercept arm, they're being dosed every two months on label. In the CLS-AX arm, we're going to dose at least every six months with CLS-AX unless supplemental therapy is required earlier. But I really don't anticipate any significant number of patients being rescued before 12 weeks after the initial dose.

因此，我們正在為兩組患者在標籤上進行阿柏西普的負荷量。然後我們將轉向阿柏西普組，按照標籤每兩個月給藥一次。在 CLS-AX 組中，我們將至少每六個月使用 CLS-AX 一次，除非需要更早進行補充治療。但我確實預計在初始劑量後 12 週內不會有大量患者獲救。

Okay.

好的。

I think OASIS really -- the OASIS data really gives us that kind of encouragement. Again, we have to run the trial. We have to do -- carry out the trial according to the protocol. But if we run it according to the protocol and based on what we saw on OASIS, I think there'll be very few.

我認為 OASIS 確實 - OASIS 數據確實給了我們這種鼓勵。同樣，我們必須進行試驗。我們必須做──按照方案進行試驗。但如果我們按照協議並根據我們在 OASIS 上看到的情況來運行它，我認為這樣的人會很少。

Can you talk about the opportunity for treat and extend with CLS-AX versus potentially looking at a treatment-naive population in a subsequent study? And I'll hop back in the queue. Thanks again.

您能否談談使用 CLS-AX 進行治療和擴展的機會與在後續研究中可能觀察未接受治療的人群的機會？我會跳回到隊列中。再次感謝。

Okay. Jon, just real quick. Could you repeat that again? I just missed the last part of that.

好的。喬恩，快點。你能再說一次嗎？我剛剛錯過了最後一部分。

How do you think about the treat-and-extend opportunity like you're studying now, or potentially looking at a treatment-naive population in a subsequent study?

您如何看待治療和延長機會，就像您現在正在研究的那樣，或者在後續研究中可能觀察未接受治療的人？

Well, like I said, that we're going to make sure that everybody in the CLS-AX arm gets a dose at six months if they didn't require one earlier. I think our real hope is that there'll be people that are being treated at six months that, by virtue of looking at BCVA changes and CST changes, really don't require it.

好吧，就像我說的，我們將確保 CLS-AX 組中的每個人在六個月後都獲得一劑疫苗（如果他們不需要提前註射的話）。我認為我們真正的希望是，有些人在六個月後接受治療，透過查看 BCVA 變化和 CST 變化，他們確實不需要它。

So we're looking at a multiple-dose therapy. But we're also going to be looking at the biological indicators, the anatomical indicators, and being able to report out whether it was -- they really met a need. And so what we're trying to do here is we're really trying to determine what the proper fixed dose is to go into Phase 3. Because I believe that we need to go into Phase 3 with a fixed dosing regimen.

所以我們正在研究多劑量療法。但我們也將研究生物指標、解剖學指標，並能夠報告它們是否真的滿足了需求。因此，我們在這裡要做的是，我們真正試圖確定進入第 3 階段的正確固定劑量。因為我相信我們需要以固定劑量方案進入第 3 階段。

Aflibercept has a fixed dosing regimen, but physicians quite often use the treat and extend. I think patients are going to be coming into the office -- they're not going to come into the office twice a year or once a year. They're going to be coming back every couple of months, every other month. And if they come in six months after getting their CLS-AX dose, in practice, if it was approved, and their BCVA is stable, and the CST is stable, I think it'll be just like any other therapy that people feel comfortable doing treat and extend.

阿柏西普有固定的給藥方案，但醫師經常使用治療和延長治療。我認為病人將會來到辦公室——他們不會每年兩次或每年一次。他們每隔幾個月、每隔一個月就會回來一次。如果他們在接受 CLS-AX 劑量後六個月內來，實際上，如果它獲得批准，並且他們的 BCVA 穩定，並且 CST 穩定，我認為這將像人們感到舒適的任何其他療法一樣進行治療和擴展。

I'm not sure if that's completely responsive to your question. But I really look forward to seeing a fixed dosing regimen where we can clearly -- as I mentioned in the opening remarks, I mean, if you look at on label now, and even with Vabysmo, which was just recently approved, that dose is every four months at a maximum. And there's -- a number of people have to be dosed after four loading doses at every two months or three months.

我不確定這是否完全回答了你的問題。但我真的很期待看到一個固定劑量方案，我們可以清楚地看到——正如我在開場白中提到的，我的意思是，如果你現在看一下標籤，即使是最近剛剛批准的Vabysmo，該劑量也是最多每四個月一次。而且，許多人必須每兩個月或三個月注射四次負荷劑量。

I think if we're in the four-to-five-month -- five-to-six-month category, that's a major improvement for patients. And I think even at that point, doctors will still look to treat and extend past that. So we may be going past five, six, seven months in number of patients.

我認為，如果我們處於四到五個月乃至五到六個月的類別，這對患者來說是一個重大改進。我認為即使到了那個時候，醫生仍然會尋求治療並超越這一點。因此，我們的患者數量可能會超過五、六、七個月。

That is helpful, George.

這很有幫助，喬治。

We have to see the data. And we really have to go into Phase 3, I believe, with fixed dosing regimen rather than the way it was done in the past, where there's a kind of a treat and extend, and we'll see how far we go. Our goal is to really set up that fixed dosing regimen.

我們必須看到數據。我相信，我們確實必須進入第三階段，採用固定劑量方案，而不是像過去那樣進行治療和延長，我們將看看我們能走多遠。我們的目標是真正建立固定劑量方案。

Got it. All right. Thanks again.

知道了。好的。再次感謝。

Sure.

當然。

Andreas Argyrides, Wedbush Securities.

安德烈亞斯‧阿吉里德斯 (Andreas Argyrides)，韋德布什證券公司 (Wedbush Securities)。

Hi, Andreas.

嗨，安德烈亞斯。

Good afternoon. This is Caroline, actually, on for Andreas.

午安.實際上，這是卡洛琳，為安德烈亞斯配音。

Hi, Caroline.

嗨，卡洛琳。

Hi.

你好。

Sorry, I can't see anything.

抱歉，我什麼也看不見。

It's okay.

沒關係。

(multiple speakers) Okay.

（多個發言者）好的。

No worries. Thank you for taking our questions; just two from us. Can you discuss your targeted timeline for enrollment in ODYSSEY and how enrollment is progressing? Are you seeing any impact from the availability of Vabysmo? And then second, can you just discuss the powering assumptions for ODYSSEY.

不用擔心。感謝您回答我們的問題；離我們只有兩個人。您能否討論一下 ODYSSEY 註冊的目標時間表以及註冊進度如何？您認為 Vabysmo 的推出有任何影響嗎？其次，您能討論一下《奧德賽》的動力假設嗎？

Okay, sure. The powering assumption, we're not conducting a non-inferiority trial. We're not conducting a superiority trial. So there really isn't a powering assumption in here.

好吧，當然。強而有力的假設是，我們沒有進行非劣效性試驗。我們不是在進行優勢試驗。所以這裡確實沒有一個強而有力的假設。

What we're looking at is aflibercept on label and see what -- over the 36 weeks, how those patients in the aflibercept arm do in terms of keeping a stable BCVA and CST. And then we're going to look at the CLS-AX arm. And what we're trying to do is to see whether the BCVAs and the CSTs are similar between the two groups and what our ideal dosing regimen would be on a fixed basis going into Phase 3.

我們關注的是標籤上的阿柏西普，看看在 36 週內，阿柏西普組的患者在保持穩定的 BCVA 和 CST 方面表現如何。然後我們將看看 CLS-AX 手臂。我們想做的是看看兩組之間的 BCVA 和 CST 是否相似，以及進入第 3 階段時我們理想的固定劑量方案是什麼。

Should it be every four months? Should it be every five months? Should it be every six months? Maybe can we go longer than that, okay? So there's not -- this is not set up as a trial that has sufficient patients to have a powered outcome, as you would think of in a non-inferiority trial in particular.

應該每四個月一次嗎？應該每五個月一次嗎？應該每六個月一次嗎？也許我們可以走得更遠，好嗎？因此，這並不是一項擁有足夠患者的試驗，能夠產生強有力的結果，正如您在非劣效性試驗中所想到的那樣。

So we think that the Phase 2 design here in terms of total patients that are in the treatment arm is very consistent with the way a number of the recent Phase 2 trials have been run. We're not looking to convert this into a Phase 3. We're looking to run a standard Phase 2b trial here, trying to compare in estimation -- on an estimation basis, how well we're doing and where we should go into Phase 3 on a fixed dosing.

因此，我們認為，就治療組中的患者總數而言，這裡的 2 期設計與最近進行的許多 2 期試驗的方式非常一致。我們不打算將其轉化為第 3 階段。我們希望在這裡進行標準的第 2b 階段試驗，嘗試在估計的基礎上比較估計，我們做得如何以及我們應該進入哪裡第三階段固定劑量。

In terms of the enrollment, as I mentioned in the press release and in the opening remarks, we're nearly at the 30 targeted sites that we want. We have all of our previous sites from OASIS are included in ODYSSEY. So we have very -- people that are very experienced with CLS-AX already in. We'll be closing that out soon.

在註冊方面，正如我在新聞稿和開場白中提到的，我們幾乎已經達到了我們想要的 30 個目標網站。我們之前所有來自 OASIS 的網站都包含在 ODYSSEY 中。因此，我們已經擁有對 CLS-AX 非常有經驗的人員。我們很快就會結束這項工作。

And then on enrollment, we're not going to give enrollment updates per se. But what we are not changing is our disclosure regarding when we think top-line data is going to be available. We're still looking at third quarter of next year. And the way we've been able to enroll sites and as we see enrollment of participants going on, we're still very comfortable with Q3 of 2024 in terms of top-line data.

然後在註冊時，我們不會提供註冊更新本身。但我們不會改變的是我們關於何時可以獲得頂線數據的揭露。我們仍在關註明年第三季。從我們註冊網站的方式以及我們看到參與者註冊的情況來看，我們對 2024 年第三季的營收資料仍然非常滿意。

Okay, great. Thank you so much, and congrats on the progress.

好的，太好了。非常感謝，並祝賀取得的進展。

Thank you.

謝謝。

Sean Kim, JonesTrading.

肖恩金，瓊斯交易公司。

Yeah, hi. Thank you for taking my questions. I guess, first question from me --

是的，嗨。感謝您回答我的問題。我想，我的第一個問題——

Hi, Sean.

嗨，肖恩。

Hi. My first question is that -- in light of recent safety issues reported with an FDA-approved therapy in geographic atrophy, would you please remind us if there has been any retinal vasculitis reported with any of suprachoroidal injections given thus far?

你好。我的第一個問題是，鑑於最近報告的 FDA 批准的地圖樣萎縮療法的安全性問題，您能否提醒我們，迄今為止進行的任何脈絡膜上註射是否有任何視網膜血管炎的報道？

And a related question is, in comparison to intravitreal injections, whether the suprachoroidal drug delivery approach might be intrinsically more likely or less prone to causing retinal vasculitis and related adverse effects.

一個相關的問題是，與玻璃體內注射相比，脈絡膜上給藥方法本質上是否更有可能或不太容易引起視網膜血管炎和相關不良反應。

Well, I think -- the first part of the question first -- as far as I know, certainly, with CLS-AX, we've had no events, no indication of any kind of inflammation including retinal vasculitis. So that is covering both the product itself, CLS-AX, the tyrosine kinase inhibitor, as well as the injection technique and the injection procedure. We've not seen any of that.

嗯，我認為 - 首先是問題的第一部分 - 據我所知，當然，對於 CLS-AX，我們沒有發生任何事件，沒有任何發炎的跡象，包括視網膜血管炎。這涵蓋了產品本身、CLS-AX、酪胺酸激酶抑制劑，以及注射技術和注射程序。我們還沒有看到這些。

And as far as I'm aware, we don't have any significant reports or any reports at all of retinal vasculitis. I'd have to double check that to be sure. But there's nothing that comes to mind in our partners' trials or in our previous trials, getting XIPERE approved, that that was a significant problem.

據我所知，我們沒有任何關於視網膜血管炎的重要報告或任何報告。我必須仔細檢查一下才能確定。但在我們合作夥伴的試驗或我們之前獲得 XIPERE 批准的試驗中，我們並沒有想到這是一個重大問題。

Certainly, if you look at the injection procedure itself, using our SCS Microinjector, it's been very reliable, safe, very repeatable. The physicians that are trained on it find that once they're trained on it -- and the training doesn't take all that long. It's not that complicated, but it is important.

當然，如果您使用我們的 SCS 顯微注射器觀察注射過程本身，您會發現它非常可靠、安全且可重複。接受過這方面培訓的醫生發現，一旦他們接受了這方面的培訓，而且培訓時間不會那麼長。這並不複雜，但很重要。

Once they're trained, they find it an easy procedure, a very acceptable procedure and very comparable in a sense to --from a patient experience and a physician experience to intravitreal injections. So retinal vasculitis has just not come up as a problem that I can recall in any of our clinical trials or our partners' clinical trials.

一旦他們接受了培訓，他們就會發現這是一個簡單的程序，一個非常容易接受的程序，並且在某種意義上非常類似於——從患者體驗和醫生體驗到玻璃體內注射。因此，我記得在我們的任何臨床試驗或我們合作夥伴的臨床試驗中，視網膜血管炎都沒有作為一個問題出現。

Now, to be fair, Regenxbio did have some inflammation in some of their earlier trials. But they've recently reported that with the topical steroids in their Phase 2 trial -- I believe it was in wet AMD -- they've seen no signs of inflammation. And I've certainly not heard of any reports of rescue -- retinal vasculitis.

現在，公平地說，Regenxbio 在早期的一些試驗中確實出現了一些發炎。但他們最近報告說，在第二階段試驗中使用局部類固醇——我相信是在濕性 AMD 中——他們沒有看到發炎跡象。我當然沒有聽過任何搶救的報告——視網膜血管炎。

Okay, that's helpful. Thank you. And related to the ODYSSEY trial, if I understand correctly, that one of the goals for the ODYSSEY trial is to define the fixed dosing schedule for potential Phase 3.

好的，這很有幫助。謝謝。與 ODYSSEY 試驗相關，如果我理解正確的話，ODYSSEY 試驗的目標之一是確定潛在第 3 階段的固定給藥方案。

Yes.

是的。

So my question is, what endpoint would dictate that dosing interval for Phase 3? Would it be the BCVA that are changed, or would it be more of a totality of data across different efficacy points?

所以我的問題是，什麼終點會決定第三階段的給藥間隔？改變的是 BCVA，還是更多的是不同功效點的數據總體？

I think the most important -- and certainly, from the FDA's point of perspective, the most important endpoint would be the BCVA. They certainly want to -- Dr. Chambers of the FDA is very focused, first and foremost, on vision preservation or vision improvement. And so I think the real most important factor would be the BCVA stability for the duration.

我認為最重要的——當然，從 FDA 的角度來看，最重要的終點是 BCVA。他們當然希望——FDA 的錢伯斯博士首先非常關注視力保護或視力改善。因此，我認為真正最重要的因素是 BCVA 在持續時間內的穩定性。

How long can we keep that BCVA stable without requiring any kind of supplemental intervention? So I think that's the most important thing. Other things like CST are important, but I think BCVA is the most important factor.

在不需要任何補充幹預的情況下，我們可以讓 BCVA 保持穩定多久？所以我認為這是最重要的。 CST 等其他因素也很重要，但我認為 BCVA 是最重要的因素。

Okay. Got you. And just a quick follow-up on that is -- just curious what your expectations might be for the aflibercept control arm in terms of that BCVA change for six months, specifically in the target population for the ODYSSEY trial.

好的。明白你了。對此的快速跟進是 - 只是好奇您對阿柏西普對照組六個月 BCVA 變化的期望是什麼，特別是 ODYSSEY 試驗的目標人群。

I'm not sure what to expect -- BCVA -- regarding BCVA. I would hope that -- I would expect -- not so much I would hope -- but I would expect if the patients are the typical patients that go into that, and they get dosed appropriately on label with aflibercept, they'll have a similar outcome.

我不確定關於 BCVA 會發生什麼。我希望——我希望——不是我希望的那麼多——但我希望如果患者是典型的患者，並且他們按照標籤上的阿柏西普適當服用劑量，他們將會有一個類似的結果。

There'll be a similar overall outcome to what you've seen with aflibercept dosed on label before in the hands of other people. I don't know why it would be any different in our hands than other people.

整體結果將與您之前在其他人手中使用標籤上劑量的阿柏西普所看到的類似。我不知道為什麼它在我們手中會與其他人有所不同。

We looked at how Vabysmo did versus aflibercept using aflibercept as their control in Phase 3. And we saw how Vabysmo did against that. And we think that we can do as well against aflibercept as Vabysmo did against aflibercept. But we believe that our dosing interval is going to be longer than Vabysmo has turned out to be in their Phase 3.

我們在第 3 階段研究了 Vabysmo 與使用阿柏西普作為對照的阿柏西普的對比。我們看到了 Vabysmo 對此的反應。我們認為我們可以像 Vabysmo 對抗阿柏西普那樣對抗阿柏西普。但我們相信我們的給藥間隔將比 Vabysmo 在第三階段的結果更長。

So I don't expect any difference in the way aflibercept patients respond to aflibercept other than what you've seen in other trials in wet AMD that enrolled a similar population.

因此，我預計阿柏西普患者對阿柏西普的反應不會與您在招募類似人群的其他濕性 AMD 試驗中看到的情況有任何差異。

Okay (multiple speakers)

好的（多個發言者）

It really does come down to the enrollment. What kind of patients are you putting in? Are you -- if you're putting in patients that really don't have strong signs of active disease, those patients are going to do really, really well because they may not have required any real intervention to begin with.

這確實取決於招生情況。你們收治的是什麼樣的病人？如果你讓那些確實沒有明顯活動性疾病跡象的患者入院，這些患者會做得非常非常好，因為他們可能一開始就不需要任何真正的干預。

There's lots of literature that will talk about patients that are relatively dry but diagnosed with the disease but no signs of active disease might go for a longer period of time between injections. But we're trying to make sure that the two groups have people that are responsive to anti-VEGFs and have active disease when they're enrolled. And then I think the outcome in the aflibercept group will be pretty consistent with history.

有許多文獻會討論那些相對乾燥但被診斷出患有這種疾病的患者，但在註射之間可能會持續較長一段時間，沒有活動性疾病的跡象。但我們正在努力確保這兩組的人在入組時對抗 VEGF 有反應並且患有活動性疾病。然後我認為阿柏西普組的結果將與歷史非常一致。

Okay. Great. Thank you.

好的。偉大的。謝謝。

Sure.

當然。

Rohit Bhasin, Needham & Company.

羅希特‧巴辛 (Rohit Bhasin)，李約瑟公司。

Hi, this is Rohit, on for [Serge]. Thanks for taking our questions.

大家好，我是羅希特，為 [Serge] 發言。感謝您回答我們的問題。

Rohit, how are you?

羅希特，你好嗎？

Hey, how's it going? Are you still evaluating potential new collaborations for the SCS Microinjector platform? And then is the current cash balance sufficient to get us to a top-line readout of ODYSSEY? Thanks.

嘿，怎麼樣？您還在評估 SCS 微注射器平台的潛在新合作嗎？那麼，目前的現金餘額是否足以讓我們取得 ODYSSEY 的營收數據？謝謝。

All right. I'll take the first part of that question, and I'll let Charlie take the second.

好的。我將回答該問題的第一部分，我將讓查理回答第二部分。

Yes. We are in discussions with other companies about potentially partnering in various disease states or with various therapeutic agents that we think might be useful delivered suprachoroidally. We conduct those kind of business development activities on a regular ongoing basis.

是的。我們正在與其他公司討論在各種疾病狀態下或與我們認為可能有用的脈絡膜上遞送的各種治療藥物的潛在合作夥伴關係。我們定期持續進行此類業務開發活動。

We don't jump into them lightly. We want to make sure they're very strategic and very positive for us and would be positive for the company. And so we need to make sure that we have the right terms, the right partner, and it fits our strategy for partnering.

我們不會輕易陷入其中。我們希望確保它們對我們非常具有戰略意義並且非常積極，並且對公司也將產生積極的影響。因此，我們需要確保我們擁有合適的條款、合適的合作夥伴，並且它符合我們的合作策略。

We typically try to partner in areas where the collaborator has technologies that we cannot access, that we don't have any expertise in. For example, gene therapy is not a core competency of us, of Clearside. So that's why we look to partner in the area of gene therapies in particular.

我們通常會嘗試在合作者擁有我們無法獲得的技術、我們沒有任何專業知識的領域進行合作。例如，基因治療不是我們 Clearside 的核心能力。這就是為什麼我們特別希望在基因治療領域合作。

But there could be other small molecules that are proprietary to other companies that want to be put into our suprachoroidal delivery system. And we're certainly open to that. And we have a constant set of conversations with people trying to put together the right deal that makes sense for us as well as for them.

但可能還有其他公司專有的其他小分子想要放入我們的脈絡膜上遞送系統。我們當然對此持開放態度。我們不斷與人們對話，試圖達成對我們和他們都有意義的正確交易。

And Charlie, I'll let you take the cash runway.

查理，我會讓你走現金跑道。

Thanks. Hey, Rohit. Yeah. So as we said, our data's coming -- plan to come Q3 next year, and our cash can get us into Q3 of next year. That's -- obviously, we want a cushion. And we can't, until we finish enrollment, know exactly within the quarter the data will come.

謝謝。嘿，羅希特。是的。正如我們所說，我們的數據即將到來 - 計劃明年第三季到來，我們的現金可以讓我們進入明年第三季。顯然，我們想要一個緩衝墊。在完成註冊之前，我們無法確切知道資料將在哪個季度出現。

But we will continue to look to extend our runway much past our -- when the data comes in, and that's what we're doing. I was looking at all dilutive and non-dilutive ways to extend our runway.

但當數據到來時，我們將繼續尋求將我們的跑道延伸到遠遠超出我們的範圍，這就是我們正在做的事情。我正在考慮所有稀釋和非稀釋的方法來延長我們的跑道。

Great. Thank you.

偉大的。謝謝。

Jack Padovano, Stifel.

傑克·帕多瓦諾，斯蒂菲爾。

Hi, this is Jack calling in for [Annabel].

嗨，我是傑克為[安娜貝爾]打來的電話。

Hi, Jack.

嗨，傑克。

Hi. Just a quick question from me. Could you briefly go over again some of the economics with your partners, and if there's any chance that you might be able to see some additional near-term expected catalysts or milestones from them?

你好。我只是問一個簡單的問題。您能否與您的合作夥伴簡要回顧一些經濟情況，以及您是否有機會從他們身上看到一些額外的近期預期催化劑或里程碑？

Charlie, is that something you would want to address?

查理，這是你想要解決的問題嗎？

Yeah. Sure. So as a reminder, we haven't announced or we're not allowed to announce particular milestones. But as some of these -- our collaborators are getting into Phase 3. Typically, there's Phase 3 development milestones that go with them.

是的。當然。提醒一下，我們尚未宣布或不允許宣布特定的里程碑。但隨著其中一些——我們的合作者正在進入第三階段。通常，他們也會有第三階段的開發里程碑。

But that's -- that would affect our EPS and revenues. But just don't forget that when we monetize our royalties with HCR, healthcare royalty, those milestones will get wrapped up and go towards the cap we have to pay.

但這會影響我們的每股盈餘和收入。但請不要忘記，當我們透過 HCR、醫療保健特許權使用費貨幣化時，這些里程碑將被完成並達到我們必須支付的上限。

If you remember, we took $32.5 million from them. And we'll have to pay 2.5 times that back, so approximately $180 million -- $81 million. So those -- any milestones that come in will go directly to HCR on our partnered programs.

如果你還記得的話，我們從他們那裡拿走了 3250 萬美元。我們必須償還 2.5 倍的費用，約 1.8 億美元至 8,100 萬美元。因此，任何里程碑事件都將直接進入 HCR 的合作專案。

Thanks.

謝謝。

Does that answer your question?

這是否回答你的問題？

Yeah.

是的。

Yi Chen, H.C. Wainwright.

陳毅, H.C.溫賴特。

Thank you for taking my questions. Your partner, Regenxbio, recently reports some progress with their candidate for [wet AMD]. I don't know if you can comment on whether their candidate in the future could potentially become a competitor to CLS-AX.

感謝您回答我的問題。您的合作夥伴 Regenxbio 最近報告了他們的 [濕性 AMD] 候選藥物的一些進展。不知道您能否評論一下他們的候選人未來是否有可能成為CLS-AX的競爭對手。

I'll take that question, Yi. I suppose it could. It depends, I think -- as I understand their therapy, their therapy is a gene therapy that generates a Lucentis-type molecule. And again, what CLS-AX does is a different mechanism of action than what the Regenx/AbbVie product would have, right?

我來回答這個問題，很容易。我想可以的。我認為這取決於——據我了解他們的療法，他們的療法是一種產生 Lucentis 型分子的基因療法。再說一遍，CLS-AX 的作用機制與 Regenx/AbbVie 產品的作用機制不同，對嗎？

So it's pretty much standard anti-VEGF therapy, just like Eylea, Vabysmo, et cetera, Lucentis. I think their potential claim to fame is they're going to last a long time in binding the circulating VEGF.

所以它幾乎是標準的抗 VEGF 療法，就像 Eylea、Vabysmo 等、Lucentis 一樣。我認為它們的成名潛力在於它們能夠長時間結合循環 VEGF。

From our perspective, we're taking a different mechanism -- mechanistic approach. And that is we're blocking the VEGF receptors 1, 2, and 3. So any circulating VEGF including -- if it's not completely bound, there's still circulating VEGFs. And they're binding, again, VEGF-A.

從我們的角度來看，我們正在採取不同的機制——機械方法。也就是說，我們正在阻斷 VEGF 受體 1、2 和 3。因此，任何循環 VEGF 包括——如果它沒有完全結合，仍然存在循環 VEGF。它們再次結合 VEGF-A。

And in many cases, there's an overexpression of patients once you start to bind the VEGF-A, especially on a longer-term treatment after a couple of years getting anti-VEGF-A therapy, that there's an overexpression of C and E in particular, which can cause potential neovascularization. So I think the -- while it's potentially competitive in that they're going after wet AMD, as are we with CLSA-X, I think they could be complementary, if you want to put a positive spin on it.

在許多情況下，一旦開始結合 VEGF-A，患者就會出現過度表達，尤其是在接受抗 VEGF-A 治療幾年後進行長期治療時，尤其是 C 和 E 過度表達，這可能導致潛在的新生血管形成。因此，我認為，儘管他們正在追趕濕 AMD，就像我們與 CLSA-X 一樣，但我認為，如果你想對此給予積極的支持，他們可能是互補的。

I think they'd be complementary because the mechanisms are different. And theirs would unlikely, based mechanistically, unlikely to address any -- those patients that become resistant to anti-VEGF-A therapy and because, in many cases, overexpression of C and E, while our mechanism through using a tyrosine kinase inhibitor would block all three VEGF receptors. So even if there was overexpression of C and E, we would be blocking the interaction of VEGF-C and E at the receptor sites.

我認為它們是互補的，因為機制不同。從機制上講，他們的方法不太可能解決任何對抗VEGF-A 療法產生抗藥性的患者，因為在許多情況下，C 和E 過度表達，而我們透過使用酪胺酸激酶抑制劑的機制會阻斷所有三種 VEGF 受體。因此，即使 C 和 E 過度表達，我們也會阻斷 VEGF-C 和 E 在受體位點的相互作用。

So I think there's room for multiple products. I often refer to this area as starting to develop the characteristics of cancer therapy, where there's multiple approaches, multiple products used for -- to treat a particular cancer. And I think it could be that the two products end up being able to be used together, rather than just competing straight up for all wet AMD patients.

所以我認為多種產品都有空間。我經常將這個領域稱為開始發展癌症治療的特徵，其中有多種方法、多種產品用於治療特定的癌症。我認為這兩種產品最終可能能夠一起使用，而不是直接針對所有濕性 AMD 患者進行競爭。

So I think there's room for both. And we'll see. The proof will be in the clinical data for both products.

所以我認為兩者都有空間。我們拭目以待。證據將體現在這兩種產品的臨床數據中。

Thanks. My next question is -- I don't know if you can comment on the prescription volume of XIPERE and whether your quarterly license revenue is correlated to the prescription volume.

謝謝。我的下一個問題是——我不知道您是否可以對 XIPERE 的處方量發表評論，以及您的季度許可收入是否與處方量相關。

Okay, I'll let Charlie handle that. That's his --

好吧，我會讓查理處理這件事。那是他的——

Yeah. So we don't have prescription information. I think those of you that track retina drugs -- difficult to get. So we can't give any guidance or trends on sales. We're contractually obligated to Bausch not to discuss unless they do. So until they start reporting out publicly the sales, I can't help you with that.

是的。所以我們沒有處方資訊。我認為你們這些追蹤視網膜藥物的人——很難找到。所以我們無法給出任何銷售方面的指導或趨勢。根據合約規定，除非 Bausch 這樣做，否則我們有義務不進行討論。因此，在他們開始公開報告銷售情況之前，我無法幫助您。

Got it. And lastly, could you comment on the potential timeline for your partner to obtain the approval of XIPERE in Australia?

知道了。最後，您能否評論一下您的合作夥伴在澳洲獲得 XIPERE 批准的潛在時間表？

Well, our understanding of the filing in Australia is that it's typically -- it's very similar to the United States in that your expectation should be about a 12-month review to approval cycle. And they filed a month or so ago, and so I would think they'll have news by this time next year.

嗯，我們對澳洲申請的理解是，它通常與美國非常相似，因為您的期望應該是大約 12 個月的審查到批准週期。他們大約一個月前提交了申請，所以我認為他們明年這個時候就會有消息。

That's kind of an educated guess on my part. But we do understand the Australian process for approval runs about -- in a similar timeline to the United States, which is about 12 months.

就我而言，這是一種有根據的猜測。但我們確實了解澳洲的審批流程與美國的審批流程類似，約 12 個月。

Got it. Thank you.

知道了。謝謝。

Okay, sure.

好吧，當然。

Thank you. We have reached the end of our question-and-answer session. So I'll now turn the call back over to Dr. Lasezkay for any closing comments he may have.

謝謝。我們的問答環節已經結束。因此，我現在將把電話轉回 Lasezkay 博士，詢問他可能有的任何總結意見。

Thank you. Thank you, all, for joining us on the call this afternoon. We really appreciate your continued interest in Clearside. We look forward to updating you on our progress throughout the year.

謝謝。謝謝大家今天下午參加我們的電話會議。我們非常感謝您對 Clearside 的持續關注。我們期待向您通報我們全年的進展。

And at that, operator, you can now disconnect the call. Thank you again, all.

接線員，您現在可以掛斷電話了。再次謝謝大家。

Thank you, sir. This concludes today's conference. You may disconnect your lines at this time, and we thank you for your participation.

謝謝你，先生。今天的會議到此結束。此時您可以斷開線路，我們感謝您的參與。