Ocular Therapeutix Inc (OCUL) 2024 Q4 法說會逐字稿

Good morning, and welcome to the Ocular Therapeutix fourth quarter 2024 earnings conference call. (Operator Instructions) As a reminder, this conference call is being recorded and will be available for replay on the Investor Relations section of the Ocular Therapeutix website.

早安，歡迎參加 Ocular Therapeutix 2024 年第四季財報電話會議。（操作員指示）提醒一下，本次電話會議正在錄音，可在 Ocular Therapeutix 網站的投資者關係部分重播。

I would now like to turn the call over to Ocular Therapeutix's Vice President of Investor Relations, Bill Slattery Jr. Please go ahead, Mr. Slattery.

現在我想將電話轉給 Ocular Therapeutix 的投資者關係副總裁 Bill Slattery Jr.。請繼續，Slattery 先生。

Good morning, everyone, and thank you for joining us today. Earlier this morning, we issued a press release and filed our annual report on Form 10-K outlining our financial results and business updates for the fourth quarter and full year of 2024 along with several updates to our registrational program for AXPAXLI in wet AMD.

大家早安，感謝大家今天加入我們。今天早些時候，我們發布了一份新聞稿，並提交了 10-K 表格年度報告，概述了我們 2024 年第四季度和全年的財務業績和業務更新，以及我們對濕性 AMD 中 AXPAXLI 註冊計劃的幾項更新。

Ocular Therapeutix's Executive Chairman, President, and CEO, Dr. Pravin Dugel, will summarize recent business highlights before we move to our question-and-answer session. Joining Dr. Dugel for the Q&A portion of the call will be Donald Notman, Chief Financial Officer and Chief Operating Officer; Sanjay Nayak, Chief Strategy Officer; and Steve Meyers, Chief Commercial Officer.

Ocular Therapeutix 的執行主席、總裁兼執行長 Pravin Dugel 博士將在我們進入問答環節之前總結最近的業務亮點。財務長兼營運長唐納德‧諾特曼 (Donald Notman)、首席策略長桑傑‧納亞克 (Sanjay Nayak) 和商務長史蒂夫‧邁耶斯 (Steve Meyers) 將與杜格爾博士一起參加電話會議的問答環節。

We refer everyone to this morning's press release and our Form 10-K for a comprehensive update of fourth quarter and full year 2024 financial and business results.

我們請大家參閱今天上午的新聞稿和我們的 10-K 表格，以全面了解 2024 年第四季度和全年財務和業務業績。

During today's call, certain statements we will be making constitute forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially as a result of variety of factors, including risks and uncertainties identified in the Risk Factors section of our annual report on Form 10-K and our other SEC filings.

在今天的電話會議中，我們將做出的某些聲明根據 1995 年《私人證券訴訟改革法案》的安全港條款構成前瞻性聲明。由於多種因素，包括我們 10-K 表年度報告和我們向美國證券交易委員會提交的其他文件中「風險因素」部分中確定的風險和不確定性，實際結果可能存在重大差異。

With that, I'd like to hand the call over to Dr. Pravin Dugel to review our recent updates. Pravin?

說到這裡，我想把電話交給 Pravin Dugel 博士來回顧我們最近的更新。普拉文？

Thank you, Bill, and thank you to everyone for joining us today. 2024 was a transformational year for Ocular Therapeutix. We sharpened our focus and embraced a single, bold mission: to redefine the retina experience. Today, disrupting the treatment paradigm in wet AMD is our top priority and we are executing with speed, precision and confidence to bring AXPAXLI to patients who need a more sustainable and effective treatment option.

謝謝你，比爾，也謝謝今天加入我們的所有人。 2024 年是 Ocular Therapeutix 轉型的一年。我們集中精力，肩負起一個大膽的使命：重新定義視網膜體驗。如今，顛覆濕性 AMD 的治療模式是我們的首要任務，我們正以快速、精準和信心執行，將 AXPAXLI 帶給需要更永續和更有效治療方案的患者。

Despite established and effective treatments for wet AMD, the burden of frequent dosing leads up to a 40% of patients discontinuing treatment in the first year alone effectively allowing themselves to go blind. Patients deserve better and AXPAXLI has the potential to become the standard of care by offering a long-lasting flexible treatment option.

儘管對濕性 AMD 有成熟有效的治療方法，但頻繁服藥的負擔導致多達 40% 的患者僅在第一年就停止治療，這實際上導致他們失明。患者應該得到更好的治療，AXPAXLI 有可能透過提供長期靈活的治療選擇成為治療標準。

And wet AMD is just the beginning. With compelling early clinical results in non-proliferative diabetic retinopathy and diabetic macular edema, we see a significant opportunity to expand into these and other highly prevalent retinal indications where millions of patients remain untreated.

濕性 AMD 只是一個開始。憑藉非增生性糖尿病視網膜病變和糖尿病黃斑水腫的早期臨床結果，我們看到了擴展到這些和其他高度流行的視網膜適應症的巨大機會，數百萬患者仍未得到治療。

This morning, we announced several exciting updates that enhance and accelerate our registrational program for AXPAXLI, positioning us incredibly well as we move toward clinical data and a potential NDA submission. Let's get right to it.

今天上午，我們宣布了幾個令人興奮的更新，這些更新增強並加速了我們針對 AXPAXLI 的註冊計劃，使我們在獲取臨床數據和提交潛在 NDA 的過程中處於非常有利的位置。讓我們開始吧。

First, we recently received FDA approval for an amendment to our special protocol agreement for SOL-1 that incorporates redosing in all patients at week-52 and week-76. We believe this amendment unlocks the potential for AXPAXLI to secure an unprecedented six to 12 month dosing label in wet AMD, showcasing what we believe to be best-in-class durability.

首先，我們最近獲得了 FDA 批准，對 SOL-1 特殊方案協議進行修訂，該協議要求所有患者在第 52 週和第 76 週重新服藥。我們相信，這項修正案將使 AXPAXLI 有可能在濕性 AMD 中獲得前所未有的 6 至 12 個月的劑量標籤，展示我們認為一流的耐用性。

The impact of this cannot be overstated. The most recent approvals in this indication extend durability by about two weeks in most patients, yet they have rapidly gained market share and generated significant revenues in a very short period of time.

其影響無論如何強調也不為過。該適應症的最新批准將大多數患者的抗藥性延長了約兩週，但它們在很短的時間內迅速獲得了市場份額並產生了可觀的收入。

With AXPAXLI, we're talking about a different orbit altogether with the potential to extend durability by months. As part of this amendment, the 36-week primary endpoint for SOL-1 remains unchanged, but we're required to maintain masking until week 52 to provide additional information on durability up to and to allow potential label permitting redosing at 12 months. As a result, we now expect to report topline data in the first quarter of 2026.

有了 AXPAXLI，我們談論的是一個完全不同的軌道，有可能將耐用性延長數月。作為此次修訂的一部分，SOL-1 的 36 週主要終點保持不變，但我們需要維持掩蔽直至第 52 週，以提供有關耐用性的更多信息，並允許在 12 個月時重新給藥的潛在標籤。因此，我們現在預計將在 2026 年第一季報告營收數據。

While this slightly shifts the timeline for SOL-1 topline data, we believe the long-term benefits of this strategy are tremendous and will be abundantly clear at the end of this call. Most importantly, this strategy should allow us to accelerate our timeline for a comprehensive regulatory submission for AXPAXLI in wet AMD, as I will describe. Moreover, we expect the additional data for repeat dosing will provide valuable insights into AXPAXLI extended durability, potentially supporting even greater flexibility on the product label.

雖然這稍微改變了 SOL-1 頂線數據的時間表，但我們相信這一策略的長期利益是巨大的，並且將在本次電話會議結束時變得非常清晰。最重要的是，這項策略應該使我們能夠加快對濕性 AMD 中的 AXPAXLI 進行全面監管提交的時間表，正如我將要描述的那樣。此外，我們預期重複給藥的額外數據將為 AXPAXLI 延長耐用性提供有價值的見解，從而可能支持產品標籤的更大靈活性。

SOL-1, a trial that many thought would never be enrolled, completed randomization in December 2024, well ahead of expectations, with 344 subjects randomized across more than 100 clinical sites in the US and Argentina.

SOL-1 是一項許多人認為永遠不會參與的試驗，該試驗於 2024 年 12 月完成了隨機分組，遠遠超出了預期，在美國和阿根廷的 100 多個臨床地點對 344 名受試者進行了隨機分組。

Trial conduct is now our top priority. We are thrilled to report that subject retention has been exceptional to date, and the vast majority of rescue treatments, as we have reviewed on a masked basis, remain in-line with the prespecified criteria established in the SOL-1 protocol.

審判的進行現在是我們的首要任務。我們很高興地報告，迄今為止，受試者的保留率非常高，並且我們在盲測基礎上審查的絕大多數救援治療仍然符合 SOL-1 協議中建立的預定標準。

We have also optimized SOL-R, our non-inferiority study, to align with the changes in SOL-1. Because redosing is now incorporated in SOL-1 and retention in the trial is exceptional to date, we are reducing the size of SOL-R from 825 subjects to approximately 555 subjects randomized while maintaining robust statistical power of 90% to evaluate a primary endpoint base on our expectations of how AXPAXLI will perform.

我們也優化了非劣效性研究 SOL-R，以與 SOL-1 的變化保持一致。由於重新給藥現已納入 SOL-1，且迄今為止試驗中的保留率非常高，我們將 SOL-R 的規模從 825 名受試者減少到大約 555 名隨機受試者，同時保持 90% 的穩健統計能力，以根據我們對 AXPAXLI 表現的預期來評估主要終點。

SOL-R was initially designed to include 825 subjects to meet the minimum FDA requirements to receive an unrestricted label for redosing. Now that subjects in SOL-1 are also being re-dosed, we're afforded the flexibility to reduce the number of subjects in SOL-R. This reduction should accelerate the SOL-R timeline for reporting data, enhance capital efficiency and maintain the scientific rigor needed for regulatory approval.

SOL-R 最初設計為納入 825 名受試者，以滿足 FDA 獲得無限制重新用藥標籤的最低要求。現在 SOL-1 的受試者也正在重新服藥，我們可以靈活地減少 SOL-R 中的受試者數量。這一減少應該會加速 SOL-R 數據報告時間表，提高資本效率並保持監管批准所需的科學嚴謹性。

Remember that SOL-R is a non-inferiority trial comparing AXPAXLI administered every 24 weeks against 2 milligram of aflibercept administered every eight weeks. The primary endpoint is the mean change in best corrected visual acuity, or BCVA, at week 56. And patients will be followed until week 104 for safety.

請記住，SOL-R 是一項非劣效性試驗，比較每 24 週注射一次的 AXPAXLI 與每 8 週注射一次的 2 毫克阿柏西普。主要終點是第 56 週最佳矯正視力（BCVA）的平均變化。為確保安全，我們將對患者進行追蹤直至第 104 週。

Importantly, as per the protocol agreed to by the FDA, the non-inferiority margin for the AXPAXLI arm at the lower bound is minus 4.5 letters of mean BCVA when compared to 2 milligram of aflibercept dosed every eight weeks. This is also in line with the FDA's draft guidance, which we are adhering to by incorporating an 8 milligram aflibercept masking compared to our arm with the exact same dosing frequency as the AXPAXLI arm.

重要的是，根據 FDA 同意的協議，與每八週服用 2 毫克阿柏西普相比，AXPAXLI 組的下限非劣效性邊界為平均 BCVA 的負 4.5 個字母。這也符合 FDA 的指導草案，我們遵循該草案，在我們的群體中加入 8 毫克阿柏西普掩蔽劑，給藥頻率與 AXPAXLI 組完全相同。

Additionally, our prespecified supplemental injection criteria are strategically designed to ensure trial integrity and preserve clinical relevance. These criteria are consistent with previous non-inferiority studies and include a combination of vision loss and OCT changes. By aligning these standard non-inferiority trial rescue protocols, we believe the SOL-R study remains well positioned to demonstrate AXPAXLI's durability and effectiveness in a repeat dosing setting.

此外，我們預先指定的補充注射標準經過策略性設計，以確保試驗的完整性並保持臨床相關性。這些標準與先前的非劣效性研究一致，包括視力喪失和 OCT 變化的組合。透過調整這些標準的非劣效性試驗救援方案，我們相信 SOL-R 研究仍可很好地證明 AXPAXLI 在重複給藥環境中的持久性和有效性。

SOL-R enrollment continues to be strong. We previously announced 311 subjects enrolled across various stages of loading and randomization as of January 10, 2025. This momentum puts us in a great position to advance our registrational program efficiently and effectively.

SOL-R 的報名人數持續強勁。我們先前宣布，截至 2025 年 1 月 10 日，已有 311 名受試者入組，經歷了不同的負荷和隨機化階段。這種勢頭使我們處於有利地位，可以有效率、有效地推進我們的註冊計劃。

Here at Ocular, our clinical trial design strategy using the loading phase to select patients for randomization and thereby potentially derisking our patient populations has been a key differentiator. We designed SOL-1 and SOL-R to work together with each trial seeking to answer critical questions about AXPAXLI durability, repeatability and flexibility.

在 Ocular，我們的臨床試驗設計策略是使用負荷階段來選擇隨機化的患者，從而潛在地降低患者群體的風險，這是一個關鍵的區別因素。我們設計了 SOL-1 和 SOL-R，以便與每次試驗協同工作，以尋求回答有關 AXPAXLI 耐用性、可重複性和靈活性的關鍵問題。

These studies were developed to be complementary and not redundant, ensuring that together they provide a robust clinical data set that could support both regulatory approval and commercial adoption.

這些研究是互補的而不是多餘的，確保它們共同提供強大的臨床數據集，可以支持監管部門的批准和商業應用。

SOL-1 is focused on durability, evaluating whether a single dose of AXPAXLI can maintain vision for 36 weeks compared to a single 2 milligram aflibercept injection. This study was designed to establish superiority and to set a new benchmark for long-term efficacy in wet AMD treatment. With the recent SPA amendment incorporating 52 week and 76 week redosing, SOL-1 now also provides important insights into extended treatment intervals and long-term redosing potential.

SOL-1 專注於耐久性，評估與單次 2 毫克阿柏西普注射相比，單劑量 AXPAXLI 是否能夠維持視力 36 週。這項研究的目的是確定其優越性並為濕性 AMD 治療的長期療效設定新的基準。隨著最近的 SPA 修正案納入 52 週和 76 週的重複給藥，SOL-1 現在也提供了有關延長治療間隔和長期重複給藥潛力的重要見解。

SOL-R, on the other hand, is designed to address more frequent repeat dosing and potential real world applicability. By comparing AXPAXLI every 24 weeks to 2 milligram aflibercept every eight weeks, SOL-R evaluates how AXPAXLI performs relative to a common, but burdensome, treatment regimen.

另一方面，SOL-R 旨在解決更頻繁的重複給藥和潛在的現實世界適用性。透過比較每 24 週服用一次 AXPAXLI 與每 8 週服用一次 2 毫克阿柏西普，SOL-R 評估了 AXPAXLI 相對於常見但繁重的治療方案的表現。

The study is structured to provide critical evidence supporting the feasibility of an every six months treatment paradigm, one that we believe is aligned to preferences of retinal specialists and that could dramatically reduce the burden of care for patients and caregivers alike.

該研究旨在提供關鍵證據，支持每六個月一次的治療模式的可行性，我們相信這符合視網膜專家的偏好，並且可以大大減輕患者和照護者的照護負擔。

Both studies were thoughtfully aligned with regulatory guidance. So one supported by SPA and SOL-R validated by Type C written response received from the FDA in August 2024 along with a subsequent written response received from the FDA in December 2024. Importantly, neither study utilizes sham for masking, adhering to the FDA's clear stance that sham can introduce bias expressed through the agency's written feedback and public comments.

這兩項研究均經過深思熟慮並符合監管指導。因此，由 SPA 和 SOL-R 支持並經 C 型驗證的方案於 2024 年 8 月從 FDA 收到書面回复，並於 2024 年 12 月從 FDA 收到後續書面回复。重要的是，這兩項研究均未使用虛假手段進行掩蓋，這符合 FDA 的明確立場，即虛假手段可能會引入偏見，這種偏見透過該機構的書面回饋和公眾評論表達出來。

The FDA previously agreed that together SOL-1 and SOL-R could constitute two adequate and well-controlled trials to support a potential NDA and label for AXPAXLI in wet AMD. Pending a successful outcome, we intend to submit our NDA after the SOL-R 56-week primary endpoint is reached.

FDA 先前同意，SOL-1 和 SOL-R 可以構成兩項充分且控制良好的試驗，以支持 AXPAXLI 在濕性 AMD 中的潛在 NDA 和標籤。在等待成功結果的情況下，我們打算在達到 SOL-R 56 週主要終點後提交我們的 NDA。

By integrating these complementary approaches, seeking to demonstrate both best-in-class durability in SOL-1 and sustained repeat dosing in SOL-R, we believe we are enhancing the potential for successful trials that support a differentiated commercially attractive label.

透過整合這些互補的方法，尋求證明 SOL-1 中一流的耐用性和 SOL-R 中持續的重複給藥，我們相信我們正在增強支持差異化商業吸引力標籤的成功試驗的潛力。

The dual nature of these trials allow us to generate a comprehensive clinical data set that has the potential to support a strong regulatory submission and a compelling value proposition for patients, retina specialists and payers.

這些試驗的雙重性質使我們能夠產生全面的臨床數據集，該數據集有可能支持強有力的監管提交以及對患者、視網膜專家和付款人的引人注目的價值主張。

Beyond wet AMD, we see a tremendous opportunity for AXPAXLI in non-proliferative diabetic retinopathy, or NPDR, and diabetic macular edema, or DME. Diabetic retinopathy is the leading cause of blindness in the working age population in the US. Despite the availability of anti-VEGF therapies, fewer than 1% of the 6.3 million NPDR patients in the US receive treatment today, largely due to the burden of frequent injections.

除了濕性 AMD 之外，我們還看到 AXPAXLI 在非增生性糖尿病視網膜病變 (NPDR) 和糖尿病黃斑水腫 (DME) 方面有著巨大的發展機會。糖尿病視網膜病變是美國工作年齡人口失明的主要原因。儘管有抗 VEGF 療法，但目前美國 630 萬 NPDR 患者中只有不到 1% 接受治療，這主要是由於頻繁注射的負擔。

AXPAXLI has the potential to transform this landscape. Our proof-of-concept HELIOS trial demonstrated compelling results for AXPAXLI in both NPDR and DME. In this trial, we showed that a single AXPAXLI injection may prevent vision threatening complications for up to 12 months. Additionally, all patients in the AXPAXLI arm that had DME saw improvement at week 48.

AXPAXLI 有潛力改變這種狀況。我們的概念驗證 HELIOS 試驗證明了 AXPAXLI 在 NPDR 和 DME 中均取得了令人信服的結果。在本次試驗中，我們表明單次 AXPAXLI 注射可預防長達 12 個月的視力威脅性併發症。此外，AXPAXLI 組所有患有 DME 的患者在第 48 週均出現改善。

So what does this mean? That means that I, as a retina physician, can say to a patient, your risk with diabetic retinopathy of developing vision-threatening complication year upon year is 30% to 40%. However, if you come to see me just once or twice a year, much like you go to a dentist for teeth cleaning, I may be able to reduce that risk to almost zero. That is a powerful message.

那麼這意味著什麼？這意味著，身為視網膜醫生，我可以告訴患者，患有糖尿病視網膜病變的患者每年發生視力威脅性併發症的風險為 30% 至 40%。然而，如果您每年來看我一兩次，就像去看牙醫洗牙一樣，我可能能夠將這種風險降低到幾乎為零。這是一個強而有力的訊息。

I'm happy to inform you today that we expect to receive FDA feedback on our clinical trial design for NPDR and DME in the first half of this year, paving the way for our next steps in these important indications. Following receipt of the FDA feedback, we look forward to sharing with you our clinical trial design for these underserved vision-threatening indications.

今天我很高興地通知大家，我們預計將在今年上半年收到 FDA 對我們針對 NPDR 和 DME 的臨床試驗設計的反饋，為我們在這些重要適應症方面的下一步行動鋪平道路。收到 FDA 回饋後，我們期待與您分享這些服務不足的視力威脅適應症的臨床試驗設計。

We continue to operate from a position of financial strength with a cash balance of $392 million as of December 31, 2024. We remain laser-focused on execution of SOL-1 and SOL-R. Our disciplined and prudent approach means that we are well-financed and believe we have sufficient cash to fund our planned operating expenses, debt service obligations and capital expenditures into 2028, fully funding our registrational trials in wet AMD and leaving us well positioned to execute on our broader strategic objectives.

我們繼續保持財務實力雄厚，截至 2024 年 12 月 31 日，現金餘額為 3.92 億美元。我們仍然專注於 SOL-1 和 SOL-R 的執行。我們嚴謹而審慎的做法意味著我們資金充足，並相信我們有足夠的現金來支付我們到 2028 年的計劃運營費用、債務償還義務和資本支出，為我們在濕性 AMD 領域的註冊試驗提供全額資金，並讓我們能夠很好地執行我們更廣泛的戰略目標。

Our current cash projections do not factor in the impact of clinical trial activities in NPDR and DME as the scope of that program is dependent on FDA feedback. That said, and to be very clear, we do not currently intend to raise additional capital this year.

我們目前的現金預測沒有考慮 NPDR 和 DME 臨床試驗活動的影響，因為該計劃的範圍取決於 FDA 的回饋。話雖如此，但需要明確的是，我們目前不打算今年籌集額外資金。

2024 was a year of transformation for Ocular Therapeutix. And 2025 is shaping up to be even more impactful. What differentiates us is not just the speed and intensity, but also the precision and exceptionally high quality of our execution.

2024 年是 Ocular Therapeutix 轉型的一年。2025 年的影響將更加深遠。我們的獨特之處不僅在於速度和強度，還在於執行的精確度和極高的品質。

In less than one year, we have built a world-class team, advanced a groundbreaking asset and executed a registrational program that puts us in a position of strength as we move toward topline data and a potential regulatory submission and approval.

在不到一年的時間裡，我們組建了一支世界一流的團隊，推進了一項突破性的資產，並執行了一項註冊計劃，這使我們在獲得頂線數據和潛在的監管提交和批准時處於優勢地位。

Today, we shared several updates designed to enhance and accelerate the AXPAXLI registrational program, further derisking our path to approval. To summarize: First, the FDA approved an amendment to the SOL-1 SPA to incorporate redosing at weeks 52 and 76, increasing potential label flexibility to every six to 12 months.

今天，我們分享了幾項旨在增強和加速 AXPAXLI 註冊計劃的更新，進一步降低我們獲得批准的風險。總結一下：首先，FDA 批准了 SOL-1 SPA 的修正案，將第 52 週和第 76 週的重新給藥納入其中，將潛在的標籤靈活性提高到每六到十二個月一次。

Second, due to the requirement to maintain masking until redosing at 52 weeks, we now expect topline data for SOL-1, including the 36-week primary endpoint, will be released in the first quarter of 2026.

其次，由於要求維持掩蔽直至 52 週重新給藥，我們現在預計 SOL-1 的頂線數據（包括 36 週主要終點）將於 2026 年第一季發布。

Third, SOL-1 retention has been outstanding to date. And the vast majority of rescue treatments reviewed on a masked basis have been in accordance with the prespecified criteria of the protocol.

第三，SOL-1 保留至今一直非常出色。並且，絕大多數以盲法審查的救援治療均符合協議的預先指定的標準。

Fourth, as a result of our updated SOL-1 strategy for redosing, SOL-R has been streamlined with a target randomization reduced from 825 to 555 subjects. This should accelerate the time to both SOL-R data and regulatory filings for AXPAXLI in wet AMD, all the while maintaining strong statistical powering of 90% based on our expectations of how AXPAXLI will perform.

第四，由於我們更新了 SOL-1 重新給藥策略，SOL-R 已簡化，目標隨機化受試者從 825 名減少到 555 名。這應該會加快 AXPAXLI 在濕性 AMD 中的 SOL-R 數據和監管備案的時間，同時根據我們對 AXPAXLI 表現的預期，保持 90% 的強大統計功效。

Fifth, the non-inferiority margin for SOL-R is set at 4.5 letters, and standard rescue criteria have been prespecified to align with regulatory guidance.

第五，SOL-R 的非劣效邊界設定為 4.5 個字母，並已預先指定標準救援標準以符合監管指南。

Sixth, enrollment has been excellent across both trials. SOL-1 completed randomization ahead of schedule in December. And we previously announced SOL-R enrollment of 311 subjects across various stages of loading and randomization as of January 10, 2025.

第六，兩次試驗的入學率都非常高。SOL-1 於 12 月提前完成隨機化。我們先前宣布，截至 2025 年 1 月 10 日，SOL-R 將招募 311 名處於不同負荷和隨機化階段的受試者。

Seventh, AXPAXLI's opportunity extends beyond wet AMD, and we expect FDA feedback on the clinical trial design for NPDR and DME in the first half of this year.

第七，AXPAXLI 的機會不僅限於濕性 AMD，我們預計 FDA 將在今年上半年對 NPDR 和 DME 的臨床試驗設計提供回饋。

And eight, Ocular Therapeutix is well financed and has cash runway into 2028. We do not intend to finance this year. We're maintaining strong capital efficiency as we advance toward key clinical readouts and a potential NDA submission in wet AMD.

第八，Ocular Therapeutix 資金充足，現金流可維持到 2028 年。我們今年不打算融資。隨著我們向濕性 AMD 的關鍵臨床讀數和潛在的 NDA 提交邁進，我們保持著強大的資本效率。

We are redefining the retina experience, setting a new standard in treatment durability, flexibility and long-term outcomes. With strong execution, regulatory alignment and clinical momentum, we're well-positioned to become a leading retina company.

我們正在重新定義視網膜體驗，為治療的耐用性、靈活性和長期效果設定新的標準。憑藉強大的執行力、監管協調和臨床勢頭，我們有能力成為領先的視網膜公司。

Thank you for your time and continued support. Operator, we are now ready to take questions.

感謝您的時間和持續的支持。接線員，我們現在可以回答問題了。

(Operator Instructions) Tazeen Ahmad, Bank of America.

（操作員指示） Tazeen Ahmad，美國銀行。

Hi, guys. Good morning. Thanks for the updates. A couple of questions for me. Pravin, just given the stats that you provided about the continued strength of what you're seeing blinded in SOL-1 in terms of patient staying in the study as well as the redosing rates coming in as you would have expected from your prespecified criteria, can you give us a little bit more color about why you think it makes sense to make these changes, especially right now?

嗨，大家好。早安.感謝您的更新。我有幾個問題。Pravin，鑑於您提供的統計數據，您在 SOL-1 中看到的盲法在患者留在研究中以及重新給藥率方面持續強勁，正如您根據預先指定的標準所預期的那樣，您能否給我們稍微詳細說明一下為什麼您認為進行這些改變是有意義的，尤其是現在？

And then, secondly, in terms of making SOL-R a smaller study, just given the high demand that there has been clearly for patients to want to be in the study, can you talk about the reasons of why it wouldn't make sense anymore to have a study of this size just to add a little bit more cushion to the data set that we're expecting? And then, I have one follow-up. Thanks.

其次，關於將 SOL-R 研究規模縮小，考慮到患者參與研究的需求明顯很高，您能否談談為什麼僅僅為了給我們預期的數據集增加一點緩衝而進行這種規模的研究已經沒有意義了？然後，我還有一個後續問題。謝謝。

Thank you, Tazeen. Good morning to you, and again, thank you for your question. What you've raised is a really important point and let me try and give a comprehensive answer. And I think this really speaks to the way we've designed our SOL programs and I include both.

謝謝你，塔津。早安，再次感謝您的提問。您提出的問題非常重要，請允許我嘗試給出一個全面的答案。我認為這確實說明了我們設計 SOL 程式的方式，我將兩者都包括在內。

These are complementary trials, and I dare say that this is revolutionary and I think really quite historic. I think everyone in the world expected us to have SOL-1 and SOL-2, which really has been the tradition. In every -- in just about every trial that I know, it's been the same trial done twice.

這些都是互補的試驗，我敢說這是革命性的，而且我認為確實具有歷史意義。我認為世界上每個人都期望我們擁有 SOL-1 和 SOL-2，這確實已經成為傳統。在每一次──幾乎在我所知道的每一次審判中，同一場審判都會進行兩次。

The second trial certainly is good to get the product approved and confirm the first trial. But when you think about it, it's terribly inefficient, because it really doesn't add any extra information whatsoever. Instead what we've designed is two trials that are always to be taken together and are absolutely complementary in the information they provide.

第二次試驗當然有利於獲得產品認可並確認第一次試驗的結果。但如果你仔細想想，你會發現它效率極低，因為它實際上沒有添加任何額外的資訊。相反，我們設計的是兩項始終一起進行的試驗，它們提供的資訊是絕對互補的。

And this I think is a unique and, I dare say, a revolutionary historic concept that will allow for efficiency both in terms of the logistics of the trials, the commercial applicability of the product, as well as the regulatory pathway. The bottom line in what we announced today, the bottom line is that we will potentially get AXPAXLI to patients faster and with a better label.

我認為這是一個獨特的，我敢說是一個革命性的歷史概念，它將在試驗的物流、產品的商業適用性以及監管途徑方面提高效率。我們今天宣布的底線是，我們將有可能以更快的速度將 AXPAXLI 帶給患者，並為其提供更好的標籤。

So let me go through the sequence of events. Two things happened. The first is that the FDA approved our redosing SPA amendment for SOL-1 at week 52 and 56. The second thing that happened is that we noted that the retention in SOL-1 was absolutely superb, under masking, of course. So based on these two events, we're able to increase the efficiency of both studies.

那麼讓我來回顧一下事件的經過。發生了兩件事。首先，FDA 批准了我們在第 52 週和第 56 週對 SOL-1 重新給藥的 SPA 修正案。發生的第二件事是，我們注意到 SOL-1 中的保留絕對非常出色，當然在掩蔽的情況下。因此，基於這兩項事件，我們得以提高這兩項研究的效率。

In SOL-1, what we're able to do is to get information on the first year on the durability and flexibility of the drug, because now we have information at month nine, which is the primary endpoint that remains unchanged, and at month 12.

在 SOL-1 中，我們能夠做的是獲取第一年有關藥物耐用性和靈活性的信息，因為現在我們有第九個月的信息，這是保持不變的主要終點，以及第 12 個月的信息。

And in the second year with redosing, what we're able to do in SOL-1 is to maximize the exposure of the drug to patients and satisfy many of the FDA's safety requirements. So immediately, SOL-1 became a much more efficient clinical trial.

而在第二年重新給藥時，我們在 SOL-1 中能夠做的就是最大限度地提高藥物對患者的暴露量，並滿足 FDA 的許多安全要求。因此，SOL-1 立即成為一項更有效率的臨床試驗。

And with that in mind, we're able to pass down that efficiency to SOL-R the way these trials were designed. So no longer did we need 825 patients in SOL-R, we could maximize efficiency in terms of our resources as well as in terms of getting the filing to the FDA by reducing the size from 825 patients to 555 patients, while maintaining the integrity of the statistics.

考慮到這一點，我們能夠按照這些試驗的設計方式將這種效率傳遞給 SOL-R。因此，我們不再需要 SOL-R 中的 825 名患者，我們可以透過將患者人數從 825 名減少到 555 名患者來最大限度地提高資源效率以及向 FDA 提交申請的效率，同時保持統計數據的完整性。

The impact of this is that we will potentially have a much better label, a label that is a superiority label with flexibility of six months to 12 months. And the second impact, equally important of course, is that we will get to market potentially faster and more efficiently than we were able to before. So both of those things terribly important in terms of the impact of what's happened today.

這樣做的影響是，我們將有可能擁有一個更好的標籤，一個具有 6 個月到 12 個月靈活性的優質標籤。第二個影響當然也同樣重要，那就是我們將比以前更快、更有效地進入市場。因此，就今天發生的事情的影響而言，這兩件事都非常重要。

What I want to note, very importantly also, that the primary endpoint remains unchanged. Remember, the primary endpoint of SOL-1 is at nine months. That remains unchanged. The statistics remain unchanged completely. What we added today, what we announced today were completely added efficiency bonuses. These are complementary trials designed to work together and I believe they work together absolutely beautifully.

我想指出的是，同樣非常重要的是，主要終點保持不變。請記住，SOL-1 的主要終點是九個月。這一點保持不變。統計數據完全保持不變。我們今天增加的、今天宣布的完全是增加的效率獎金。這些都是旨在協同工作的互補試驗，我相信它們協同工作的效果絕對完美。

Okay. That's super helpful. And my one follow-up is that, given that, as you said, the primary endpoint stays the same, can you give us a sense of what the FDA might be looking for from redosing now in SOL-1?

好的。這非常有幫助。我的一個後續問題是，鑑於您所說的主要終點保持不變，您能否讓我們了解 FDA 現在在 SOL-1 中重新給藥可能尋求什麼？

Well, again, the redosing allows for us in the first year to look to get information regarding flexibility and durability of the drug. Now, we'll have information at month nine. Again, that's the primary endpoint, which remains absolutely unchanged.

嗯，再次強調，重新給藥可以讓我們在第一年就獲得有關藥物靈活性和耐用性的信息。現在，我們將獲得第九個月的資訊。再次強調，這是主要終點，它絕對保持不變。

But additionally, we'll also have information at month 12 regarding durability of the drug. So potentially, there's flexibility in the label for month nine as well as month 12. And as I mentioned, with the redosing in the second year, there's more exposure of the drug to the patients. Therefore, we'll have even more data in regards to safety.

此外，我們還將在第 12 個月獲得有關藥物耐久性的信息。因此，第九個月和第十二個月的標籤可能會具有靈活性。正如我所提到的，隨著第二年重新用藥，患者接觸藥物的機會更多。因此，我們將獲得更多有關安全的數據。

The beauty of this is that when you think about the efficiency of SOL-1 with a single injection in the first year, we'll have information for month nine and month 12, and with repeat dosing for the second year, we'll have increased safety information with more exposure of the drug to patients.

這樣做的好處是，當您考慮第一年單次注射 SOL-1 的功效時，我們將獲得第九個月和第十二個月的信息，而第二年重複注射時，我們將獲得更多的安全性信息，讓患者更多地接觸該藥物。

Okay. Thank you for all the color.

好的。謝謝你帶來的所有色彩。

Thank you, Tazeen.

謝謝你，塔津。

Biren Amin, Piper Sandler.

比倫阿明、派珀桑德勒。

Yeah. Hi, guys. Thanks for taking my question, and congrats on all the updates. So maybe Pravin, let me just start with SOL-1. What was the rationale for dosing at week 76? I understand the week 52 dosing, but I was trying to understand, I guess, the rationale for week 76.

是的。嗨，大家好。感謝您回答我的問題，並祝賀所有更新。那麼也許 Pravin，讓我從 SOL-1 開始。第 76 週給藥的理由是什麼？我了解第 52 週的劑量，但我想了解第 76 週的劑量的原理。

And then, second question is, for SOL-1, will all patients receive redosing at week 52 and week 76 regardless of the arm, including the control arm? And also, will those patients with prior rescues receive redosing at week 52 and week 76?

然後，第二個問題是，對於 SOL-1，無論屬於哪一組（包括對照組），所有患者是否都會在第 52 週和第 76 週接受重新給藥？此外，那些之前接受過搶救的患者是否會在第 52 週和第 76 週重新接受治療？

Biren, good morning, and thank you for your question. The answer for the first one is very simple, we wanted to maximize again the exposure of the drug to patients to satisfy the FDA safety requirements, thus redosing at week 56 -- at week 52, -- week 52 and week 76 with the study ending at week 104.

Biren，早安，感謝您的提問。第一個問題的答案很簡單，我們希望再次最大限度地增加藥物對患者的暴露量，以滿足 FDA 的安全要求，因此在第 56 週、第 52 週、第 52 週和第 76 週重新給藥，研究在第 104 週結束。

The answer to your second question, yes, every patient will be redosed at week 52 and at week 76. The redosing will occur with the same drug that the patient was randomized to regardless of rescue. And that's very important. The answer to your question is, yes, everybody will be redosed at week 52 and week 76 with the original drug that they were randomized to. I hope that answers your question. Thank you, Biren.

對於你的第二個問題，答案是肯定的，每個病人都會在第 52 週和第 76 週重新服藥。無論是否進行救援，重新給藥的藥物都是與患者隨機服用的藥物相同的藥物。這非常重要。您的問題的答案是，是的，每個人都會在第 52 週和第 76 週重新服用他們隨機服用的原始藥物。我希望這能回答你的問題。謝謝你，Biren。

That does. And I just got a follow-up. So on SOL-R, as a result of these changes, you clearly reduced the size to 555 patients, which I think -- was that primarily due to the safety data that you're generating from SOL-1? Because I think now you would have another 172 patients that are redosed with AXPAXLI from SOL-1, whereas I think you reduced the need for the patients to be redosed with SOL-R by about 108 patients within AXPAXLI arm.

確實如此。我剛剛收到了後續訊息。因此，在 SOL-R 上，由於這些變化，您明確將規模縮減至 555 名患者，我認為這主要是因為您從 SOL-1 產生的安全資料嗎？因為我認為現在您將有另外 172 名患者從 SOL-1 中重新服用 AXPAXLI，而我認為您將 AXPAXLI 組中需要重新服用 SOL-R 的患者減少了約 108 名。

And Biren, again, thank you. You're exactly right. Your explanation is exactly correct. What we did was we designed SOL-R originally to have 825 patients to satisfy the FDA safety requirements. And with the redosing amendment that we were able to get from the FDA, we were able to satisfy the safety requirements with both studies combined with the ability to reduce the number of patients from 825 patients to 555 patients, while still maintaining the statistical significance.

再次感謝 Biren。你說得完全正確。你的解釋完全正確。我們所做的是，我們最初設計 SOL-R 是為了容納 825 名患者，以滿足 FDA 的安全要求。透過 FDA 獲得的重新劑量修正，我們能夠滿足兩項研究的安全要求，同時能夠將患者人數從 825 名減少到 555 名，同時仍保持統計意義。

So your -- answer to your question is exactly correct. Thank you.

所以你對這個問題的答案是完全正確的。謝謝。

Got it. And then maybe one last question. I guess from a timeline standpoint, were these changes to SOL-1 and SOL-R underway or made when the Board constructed your performance base package on Ocular share price hitting -- I think there are four different targets between $15 and $30.

知道了。也許還有最後一個問題。我想從時間軸的角度來看，這些 SOL-1 和 SOL-R 的改變是正在進行中還是在董事會根據 Ocular 股價制定績效基礎方案時做出的——我認為在 15 美元到 30 美元之間有四個不同的目標。

So I guess I want to understand if these changes provide increased confidence on hitting those performance targets?

所以我想了解這些變化是否能增強實現這些績效目標的信心？

Yeah. So Biren, again, thank you very much for the question. The answer obviously, we have discussions with the FDA that are ongoing and we want to keep those discussions confidential. We don't discuss them publicly as with my discussions with the Board.

是的。所以，Biren，再次非常感謝你的提問。答案顯然是，我們正在與 FDA 進行討論，我們希望對這些討論保密。我們不會像我與董事會討論的那樣公開討論這些問題。

But suffice it to say that our confidence as a company in the success of these trials are higher than ever. And certainly my confidence particularly is higher than ever and you'll see that everything in this company is aligned to make sure that we ensure the success of both trials. Thank you.

但可以說，我們公司對這些試驗的成功比以往任何時候都更有信心。當然，我的信心比以往任何時候都高，你會看到公司裡的一切都協調一致，以確保兩次試驗都成功。謝謝。

Great. Thanks for taking my questions.

偉大的。感謝您回答我的問題。

Absolutely.

絕對地。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

Great. Thanks. Good morning, and thanks for taking our questions. So for the -- just to maybe clarify, for the redosing of patients in SOL-1, is that just for the FDA safety requirement for redosing, or do you need to show anything for efficacy in that protocol in the second year? And then, I have a follow-up.

偉大的。謝謝。早安，感謝您回答我們的問題。因此，也許需要澄清的是，對於 SOL-1 中的患者重新用藥，這僅僅是 FDA 對重新用藥的安全要求，還是需要在第二年證明該方案的有效性？然後，我有一個後續問題。

Colleen, good morning, and thank you for your question. The answer is that it really is for the safety requirement for the FDA. However, what it does allow us to do, again, is get information given this -- because remember, it's not just the matter of taking the second year separately, but also taking the second year in regard to how it affects the first year.

科琳，早安，謝謝你的提問。答案是，這確實是出於 FDA 的安全要求。然而，它確實允許我們再次獲取資訊 - 因為請記住，這不僅僅是單獨考慮第二年的問題，而且還要考慮第二年如何影響第一年。

So what it allows us to do is to get that extra information that we will now have not only at month nine, but also at month 12. So it does allow for the flexibility that we hope to get in the label because we have additional information now at month 12 as well as month nine. But again, we will satisfy the safety requirements, but we will also gain additional information in the second year regarding redosing.

因此，它使我們能夠獲得額外的信息，這些信息不僅在第九個月，而且在第十三個月也能獲得。因此，它確實允許我們希望在標籤中獲得的靈活性，因為我們現在在第 12 個月和第 9 個月擁有附加資訊。但同樣，我們將滿足安全要求，但我們也將在第二年獲得更多有關重新給藥的資訊。

So this is not a requirement for hitting the primary endpoint. I want to make that very, very clear. It's important to emphasize that nothing about the original primary endpoint changes. The primary endpoint remains at month nine and the statistics remain the same. This is added efficiency today.

所以這不是達到主要終點的要求。我想把這一點講得非常清楚。需要強調的是，原始主要終點沒有任何改變。主要終點仍為第九個月，統計數據不變。這就是今天增加的效率。

Got it. That's helpful. Thank you. And then, I know when you first shared the SOL-R trial design last summer, I think it was a 48-week endpoint and then -- but that was prior to talking to the FDA. Now, you're talking about a 56-week endpoint.

知道了。這很有幫助。謝謝。然後，我知道當您去年夏天第一次分享 SOL-R 試驗設計時，我認為它是一個 48 週的終點 - 但那是在與 FDA 交談之前。現在，您正在談論 56 週的終點。

So can you just talk about what drove that change and what that means for your dosing schedule, which I believe AXPAXLI is [still being dosed] every 24 weeks? So just kind of talk about that 56-week endpoint, please.

那麼，您能否談談是什麼導致了這種變化，以及這對您的給藥時間表意味著什麼？我相信 AXPAXLI 仍然是每 24 週服用一次？那麼請簡單談談 56 週終點吧。

Yeah. Thank you, Colleen. So you're exactly right. I think the first time you might have heard about the 48-week endpoint for SOL-R was in our June Investor Day. And I want to emphasize, if you go back and check your notes then, we made it absolutely clear that we were proposing the SOL-R clinical trial design at risk.

是的。謝謝你，科琳。所以你說得完全正確。我想您第一次聽說 SOL-R 的 48 週終點是在我們 6 月的投資者日。我想強調的是，如果你回去檢查你的筆記，你會發現我們非常清楚地表明，我們提出的 SOL-R 臨床試驗設計是有風險的。

And I think those two words, at risk, were mentioned quite a few times in that meeting. And the reason we did that is we made it very clear, very transparently that we had not yet gone to the FDA for formal approval regarding this trial design. That's why it was at risk.

我認為「處於危險之中」這兩個詞在那次會議上被提到過很多次。我們這樣做的原因是，我們非常清楚、非常透明地表示，我們尚未就該試驗設計向 FDA 尋求正式批准。這就是它處於危險之中的原因。

Now, we did subsequently go to the FDA and the FDA came back and told us that they preferred a primary endpoint at week 52 or later. And as you know, we have a history of doing everything per the FDA. We wanted to make sure that we did it with a minimal amount of risk possible.

現在，我們隨後去了 FDA，FDA 回覆說他們更喜歡將主要終點設定在第 52 週或更晚。如您所知，我們一直嚴格按照 FDA 的要求做事。我們希望確保以盡可能小的風險完成此事。

In fact, we wouldn't want to take any risk as far as our regulatory pathway is concerned. So then, we decided, given their preference to pick week 56, and the FDA has now accepted in writing our proposal to pick the primary endpoint for SOL-R at week 56.

事實上，就監管途徑而言，我們不想冒任何風險。因此，我們決定，考慮到他們傾向於選擇第 56 週，FDA 現在已經書面接受了我們的提議，將第 56 週作為 SOL-R 的主要終點。

I hope that answers your question, Colleen.

我希望這能回答你的問題，科琳。

Great. Thanks. And last one, just any timelines for SOL-R recruitment now in light of the decrease in the study size?

偉大的。謝謝。最後一個問題，鑑於研究規模的縮小，現在 SOL-R 招募有什麼時間表嗎？

Yeah. So Colleen, we did give an update at JPM, as was said in my prepared statements. Since then, what I can tell you is that we've been thrilled with the recruitment of SOL-R, and we will give you an update when appropriate, but it may be a little bit too early at this point. But thank you for your question.

是的。因此，科琳，我們確實在 JPM 提供了最新消息，正如我在準備好的聲明中所說的那樣。從那時起，我可以告訴你的是，我們對 SOL-R 的招募感到非常興奮，我們會在適當的時候向你提供最新消息，但現在可能還為時過早。但感謝您的提問。

Understood. Thanks for taking our questions.

明白了。感謝您回答我們的問題。

Thank you.

謝謝。

Kelly Shi, Jefferies.

Kelly Shi，傑富瑞集團。

Hi, this is [Clara] on for Kelly. Thanks for taking our question, and congrats on the update. So you mentioned that you intend to submit NDA after 56-week primary endpoints of SOL-R is reached. So I understand that the primary endpoints do not change, but also just trying to understand whether you would expect to have some long-term redosing durability data in SOL-1 as well by that time?

大家好，我是凱利 (Kelly) 的 [克拉拉 (Clara)]。感謝您回答我們的問題，並祝賀更新。所以您提到您打算在達到 SOL-R 的 56 週主要終點後提交 NDA。所以我理解主要終點不會改變，但也只是想了解您是否希望到那時在 SOL-1 中也會有一些長期重複給藥耐久性數據？

And also just want to clarify whether the FDA requires that portion of data to support the redosing flexibility portion on the label? Thank you.

另外，我只是想澄清一下，FDA 是否要求該部分數據來支持標籤上的重新服用彈性部分？謝謝。

Clara, good morning, and thank you for your question. Very important questions, and I want to make it very clear as to what the FDA requirements are for NDA submission versus the information that we'll gather. To be very, very clear, what the FDA requires for the NDA submission is hitting the primary endpoint in both studies.

克拉拉，早安，謝謝你的提問。非常重要的問題，我想非常清楚地說明 FDA 對 NDA 提交的要求以及我們將收集的資訊。非常明確的是，FDA 對 NDA 提交的要求是達到兩項研究的主要終點。

So again, the primary endpoint for SOL-1 at month nine remains the same. The primary endpoint for SOL-R is at week 56. And our intention is that with presumably a positive study at week 56 with SOL-R, we will submit the NDA application to the FDA. That is unchanged. We just expect given the announcements today that SOL-R will be recruited with more efficiency given the fact that the sample size is smaller.

因此，SOL-1 在第九個月的主要終點保持不變。SOL-R 的主要終點是第 56 週。我們的目的是，假設 SOL-R 第 56 週的研究結果呈陽性，我們將向 FDA 提交 NDA 申請。這一點沒有改變。我們只是根據今天的公告預計，鑑於樣本量較小，SOL-R 的招募效率將會更高。

Now, in regards to your other questions regarding other requirements, yes, the FDA does have safety requirements as you're aware. They will be fulfilled with the combination of patients in the second year in both SOL-1 and SOL-R.

現在，關於您關於其他要求的其他問題，是的，正如您所知，FDA 確實有安全要求。他們將在第二年透過 SOL-1 和 SOL-R 的組合來實現患者的需求。

In addition to that, we will also have a significant amount of information that we believe we can leverage for commercial success. And some of which you've already talked about and we've already talked about, which is the redosing of this drug that is now available both in SOL-1 and in SOL-R.

除此之外，我們還將擁有大量訊息，我們相信可以利用這些資訊來取得商業成功。其中一些您已經談過了，我們也已經談過了，那就是重新服用這種藥物，現在 SOL-1 和 SOL-R 都可以使用。

And remember, we also have a numeric analysis that we're able to do with the third arm in SOL-R, which compares this drug to high dose EYLEA. Now that is not for statistical analysis, that's for numeric analysis, but you can imagine we will have between these two studies a significant amount of data that is not necessarily required by the FDA, certainly it's not required for approval or NDA submission, but we can leverage for our commercial advantage, and we do intend to do that.

請記住，我們也可以對 SOL-R 中的第三個分支進行數值分析，將該藥物與高劑量 EYLEA 進行比較。現在這不是用於統計分析，而是用於數值分析，但你可以想像，在這兩項研究之間我們將擁有大量數據，這些數據不一定是 FDA 所要求的，當然也不是批准或 NDA 提交所要求的，但我們可以利用這些數據來獲得商業優勢，我們確實打算這樣做。

Thank you for your question, Clara.

謝謝你的提問，克拉拉。

Thank you.

謝謝。

Sean McCutcheon, Raymond James.

肖恩麥卡琴、雷蒙德詹姆斯。

Hi, guys. Thanks for taking the question. So for SOL-R, could you give some detail on what you think the FDA expectations are, what your expectations are for what would be an acceptable number of rescues and timing of rescues regardless of if you hit the non-inferior -- land within the non-inferiority margin? Thanks.

嗨，大家好。感謝您回答這個問題。那麼對於 SOL-R，您能否詳細說明一下您認為 FDA 的期望是什麼，您對可接受的救援次數和救援時間的期望是什麼，無論您是否達到非劣效性 - 在非劣效性範圍內？謝謝。

Sean, good morning, and thank you for your question. Your question is a very important question, of course. So let me discuss rescues. We mentioned today, I just want to make clear that the non-inferiority margin was 4.5 letters. And I just want to emphasize that, that is because we're exactly in guidelines with the FDA. We've always done that and we expect to do that with everything that we do in regards to study design.

肖恩，早安，謝謝你的提問。當然，您的問題是一個非常重要的議題。那麼就讓我來討論一下救援。我們今天提到，我只是想明確指出非劣效邊界是 4.5 個字母。我只想強調這一點，那是因為我們完全遵循 FDA 的指導方針。我們一直都是這樣做的，我們希望在研究設計方面所做的每一件事中都這樣做。

In regards to the rescues, we have not detailed the rescue criteria as yet for competitive reasons, but we will do so. But here's what I can tell you. We will detail those when appropriate. You can expect the rescue criteria to be of no surprise. They will be absolutely in line with the traditional rescue criteria that you've seen in the past.

關於救助，由於競爭原因，我們尚未詳細說明救助標準，但我們會這樣做。但我可以告訴你的是。我們將在適當的時候詳細說明這些內容。您可以預料救援標準不會令人意外。它們絕對會符合大家過去所見的傳統救援標準。

The FDA has given very clear guidelines of what they think about rescues, not just for us, but for all studies. The FDA has clearly stated, and this was stated most recently by Dr. Boyd in the American Academy of Ophthalmology meeting, that the first rescue in a non-inferiority study will be allowed as long as it doesn't affect the primary endpoint.

FDA 對他們對救援的看法給出了非常明確的指導方針，不僅適用於我們，也適用於所有研究。FDA 已明確表示，而且最近 Boyd 博士在美國眼科學會會議上也表示，只要不影響主要終點，非劣效性研究中的第一次救援是允許的。

And that is a period of approximately three months or so as a rule of thumb before the primary endpoint. All other rescues will be subject to review. And again, that's been stated for a number of years now. That is no different than any other clinical trial, and that is a general statement that still stands.

根據經驗，這是到達主要終點之前大約三個月左右的時間。所有其他救援行動都將接受審查。再說一遍，這個說法已經說了很多年了。這與任何其他臨床試驗沒有什麼不同，這是一個仍然成立的普遍說法。

However, what I can tell you is that I believe we will have a huge advantage due to the design of our clinical trials. Remember, these are complementary clinical trials. And remember that SOL-R will never be reviewed by any regulatory agency without a positive SOL-1 study.

然而，我可以告訴你的是，我相信我們的臨床試驗設計將為我們帶來巨大的優勢。請記住，這些是補充臨床試驗。請記住，如果沒有積極的 SOL-1 研究，SOL-R 永遠不會被任何監管機構審查。

And when these rescues for SOL-R are being evaluated, it will be evaluated in the context of a positive SOL-1 study. So, the regulatory agencies will have a very clear idea that this drug will last for nine to 12 months based on a positive SOL-1 result.

當評估 SOL-R 的這些救援措施時，將在積極的 SOL-1 研究背景下進行評估。因此，監管機構將非常清楚地知道，根據 SOL-1 的陽性結果，這種藥物的療效將持續 9 到 12 個月。

So again, the rescues will be reviewed in context of a positive SOL-1 study, which will define the durability of this drug, which I will think will be very much to our advantage. Again, this also emphasizes the advantage that we have of having these two complementary studies.

因此，我們將在積極的 SOL-1 研究背景下審查救援措施，這將確定這種藥物的持久性，我認為這對我們非常有利。再次，這也強調了我們進行這兩項互補研究的優點。

Thanks for your question, Sean.

謝謝你的提問，肖恩。

Thank you.

謝謝。

Jon Wolleben, Citizens JMP.

喬恩‧沃勒本 (Jon Wolleben)，公民 JMP。

Hey, thanks for taking the questions, Pravin. Two from us. Can you discuss the change in powering for SOL-R now for the primary? And then, stepping back, it seems like these changes have two big implications. One is the accelerate potential timing to a filing, but then also the new label information.

嘿，謝謝你回答這個問題，Pravin。我們有兩個。您能討論一下目前 SOL-R 主供電系統發生的變化嗎？然後，退一步來看，這些變化似乎有兩大影響。一是加速提交申請的潛在時間，二是新的標籤資訊。

But how do you think about the importance of those two? Because my expectation would be if you get a year on the label, the docs could treat and [extend], as they do anyway. So how much value is that 52 weeks in the label versus just getting to market quicker?

但您如何看待這兩者的重要性？因為我的期望是，如果標籤上有一年有效期，那麼醫生可以進行治療和[延長]，就像他們無論如何都會做的那樣。那麼，與更快進入市場相比，52 週的標籤價值有多大？

Jon, good morning, and thank you for your questions. Again, very important question. Look, as far as the SOL-R powering is concerned, we haven't guided you to that publicly. But what I can tell you is nothing changes. We had the 825 patient number to satisfy the FDA safety requirements.

喬恩，早安，謝謝你的提問。再次強調，這是一個非常重要的問題。瞧，就 SOL-R 供電而言，我們還沒有公開指導您。但我可以告訴你的是，什麼都沒有改變。我們有 825 名患者，以滿足 FDA 的安全要求。

The powering and the statistics really do not change at all. We're able to reduce the size because of the redosing amendment that was approved by the FDA for SOL-1. The statistics remain very robust and unchanged for us.

動力和統計數據確實根本沒有改變。由於 FDA 批准了 SOL-1 的重新劑量修正，我們得以縮小尺寸。對我們來說，統計數據仍然非常強勁且沒有變化。

In regards to your second question regarding labeling, look, as a physician, I can tell you as someone who has practiced for the last 30 years, the label becomes very important for several reasons. One is scientific. It gives you the scientific data of what this drug does, which would be very important to see.

關於您關於標籤的第二個問題，作為一名醫生，作為一個從業 30 年的人，我可以告訴您，標籤變得非常重要，原因有幾個。一是科學性。它為您提供了這種藥物作用的科學數據，這非常重要。

The opportunity is there in this study to find out the durability of this drug in a scientific manner. And that is very valuable information for physicians and for patients and for payers alike. The second reason for the labeling is really for the payers, and it will give us a huge commercial advantage.

這項研究提供了一個機會，以科學的方式找出這種藥物的耐用性。這對醫生、病人和付款人來說都是非常有價值的資訊。貼標籤的第二個原因實際上是為了付款人，它將給我們帶來巨大的商業優勢。

So our goal strategically is to have the best label that the market has seen, a label that is the superiority label, which will be the first and only of its kind potentially and one with a great deal of flexibility of dosing from six months to 12 months.

因此，我們的策略目標是擁有市場上最好的標籤，即優越性標籤，它可能是同類中第一個也是唯一一個標籤，並且具有從 6 個月到 12 個月的劑量靈活性。

Thanks for your question, Jon.

謝謝你的提問，喬恩。

Thanks, Pravin.

謝謝，普拉文。

Yi Chen, H.C. Wainwright.

陳毅，H.C.溫賴特。

Thank you for taking my question. With respect to the NPDR and DME, once you get the FDA feedback on clinical trial design, how quickly do you anticipate to advance those two indications into clinical trials? And do you intend to advance both indications concurrently? Thank you.

感謝您回答我的問題。關於 NPDR 和 DME，一旦您收到 FDA 對臨床試驗設計的回饋，您預計多快將這兩項適應症推進到臨床試驗階段？您是否打算同時推進這兩項適應症？謝謝。

Yi, good morning. Again, thank you for your question. I'm glad you asked about NPDR and DME, and I'm glad that you put those together because I think it's very important to emphasize that with the HELIO study, we have shown absolutely everything to you, which is every single eye of every single patient.

易，早安。再次感謝您的提問。我很高興您詢問了 NPDR 和 DME，也很高興您將它們放在一起，因為我認為強調這一點非常重要，透過 HELIO 研究，我們向您展示了所有內容，即每位患者的每一隻眼睛。

And what you'll see there is not only a remarkable result in non-proliferative diabetic retinopathy, or NPDR, but also in diabetic macular edema, or DME. In fact, every single patient who had diabetic macular edema on entry of that study improved.

您不僅會看到非增生性糖尿病視網膜病變（NPDR）的顯著效果，還會看到糖尿病黃斑水腫（DME）的顯著效果。事實上，參與研究的每位患有糖尿病性黃斑水腫的患者病情都有所改善。

And what you saw in the Angiogenesis meeting is a remarkable presentation by Dr. Ehlers, where he showed that very clearly that these patients with fluid improved significantly after a single injection after 48 weeks. And so our goal is to pursue not just NPDR, but also DME.

您在血管生成會議上看到的是 Ehlers 博士的精彩演講，他非常清楚地表明，這些液體患者在 48 週後進行一次注射後病情得到明顯改善。因此，我們的目標不僅是追求 NPDR，還要追求 DME。

How the trial will be designed? Yi, we don't know yet, because we will still meet with the FDA formally. We committed to doing that in the first half of this calendar year. That has not changed. How quickly we will implement? That depends on that meeting, so I can't say now.

試驗將如何設計？易，我們還不知道，因為我們仍將與 FDA 正式會面。我們承諾在今年上半年實現這一目標。這一點沒有改變。我們將多快實施？這取決於那次會議，所以我現在不能說。

But what I can say and what we did say is that we are financed very, very efficiently. We are very disciplined, in our financial expenditures. And our intent is to keep the projections the way they are, which is that we are financed into 2028. And at this point, we do not have any intention of requiring any additional funding this year and that remains.

但我可以說並且我們也確實說過，我們的資金非常非常有效率。我們在財務支出方面非常自律。我們的目的是維持現有的預測，即我們的資金能夠維持到 2028 年。目前，我們今年還不打算要求任何額外資金。

Thank you for your question, Yi.

謝謝你的提問，Yi。

Greg Harrison, Scotiabank.

加拿大豐業銀行的格雷格·哈里森。

Hey, good morning, and thanks for taking the question. Curious what your expectations are for the percentage of patients that could show durability to 52 weeks without rescue in SOL-1 and to what extent do you think it could be used that way in practice?

嘿，早上好，感謝您回答這個問題。好奇您對 SOL-1 中無需搶救就能維持 52 週的患者比例的期望是多少，以及您認為在實踐中它可以在多大程度上以這種方式使用？

Greg, good morning, and thank you for your question. The data, first of all, it's very, very valuable information and we don't shy away from this at all because not only because it's very valuable, but we believe that we're going to win quite honestly.

格雷格，早安，謝謝你的提問。首先，數據是非常非常有價值的訊息，我們根本不迴避這一點，因為這不僅是因為它非常有價值，而且我們相信我們會非常誠實地獲勝。

We believe that there are a number of patients that will go to 52 weeks. And this is based on the US study. In the US study, we had 60% of patients that went that long with a single injection, and that was in a non-enhanced patient population.

我們相信有很多患者會堅持到 52 週。這是基於美國的研究。在美國的研究中，60% 的患者只需注射一次就能維持那麼長時間，而且這屬於未接受增強治療的患者群體。

As you know, in previous discussions, we've gone through how painstakingly and thoughtfully we have selected our patients in a bespoke manner for each study to derisk the patient selection and derisk the outcomes. And the 60% that I quote to you, it really is in a unselected non-enriched patient population. So we're very confident of what we will show at week 12.

如您所知，在先前的討論中，我們已經討論瞭如何為每項研究精心而周到地選擇患者，以降低患者選擇的風險並降低結果的風險。我向您引用的 60% 確實存在於未經選擇的非富集患者群體中。因此，我們對第 12 週的表現非常有信心。

Remember that there are drugs that are in the market now that are approved on label for a two week or so extension, some going to four months, with not very many patients that have actually crossed that threshold in their study.

請記住，現在市場上有些藥物的標籤批准延長兩週左右，有些藥物的標籤批准延長至四個月，但研究中真正跨越這個門檻的患者並不多。

So from our point of view, we're going to provide very valuable information here to physicians, payers and patients alike, and we have the opportunity to have the best-in-class label as well. Thank you, Greg, for your question.

因此，從我們的角度來看，我們將向醫生、付款人和患者提供非常有價值的信息，並且我們也有機會獲得一流的標籤。格雷格，謝謝你的提問。

Thank you. This concludes our question-and-answer session. I'll now turn the call back to Dr. Pravin Dugel for closing remarks.

謝謝。我們的問答環節到此結束。現在我將把電話轉回給 Pravin Dugel 博士，請他作結束語。

Once again, I'd like to thank everyone for taking the time to join us on our call today. We look forward to updating you on our progress. And if you have any follow-up questions, please reach out to Bill Slattery, our Vice President of Investor Relations. Have a great day everybody. Thank you.

我再次感謝大家今天抽出時間來參加我們的電話會議。我們期待向您通報我們的進展。如果您有任何後續問題，請聯絡我們的投資者關係副總裁 Bill Slattery。祝大家有個愉快的一天。謝謝。

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

今天的會議到此結束。此時您可以斷開您的線路，感謝您的參與。