Ocular Therapeutix Inc (OCUL) 2022 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen. Thank you for standing by, and welcome to the Ocular Therapeutix Fourth Quarter and Year-End 2022 Earnings Conference Call. (Operator Instructions)

女士們先生們，下午好。感謝您的支持，歡迎來到 Ocular Therapeutix 2022 年第四季度和年終收益電話會議。 （操作員說明）

It is now my pleasure to turn the call over to Donald Notman, Chief Financial Officer of Ocular Therapeutix. Please go ahead, sir.

現在我很高興將電話轉給 Ocular Therapeutix 的首席財務官 Donald Notman。請繼續，先生。

Thank you, operator. Good afternoon, everyone, and thank you for joining us on our fourth quarter and year-end 2022 financial results and business update conference call.

謝謝你，運營商。大家下午好，感謝您加入我們的 2022 年第四季度和年底財務業績和業務更新電話會議。

This afternoon, after the close, we issued a press release providing an update on the company's product development programs and details of the company's financial results for the fourth quarter and year ended December 31, 2022. The press release can be accessed on the Investors portion of our website at investors.ocutx.com.

今天下午，收盤後，我們發布了一份新聞稿，提供了公司產品開發計劃的最新情況以及公司截至 2022 年 12 月 31 日的第四季度和年度財務業績的詳細信息。可在投資者部分訪問該新聞稿我們的網站 investors.ocutx.com。

Leading the call today will be Antony Mattessich, our President and Chief Executive Officer, who will provide an update on our pipeline development and the commercial progress of DEXTENZA. Also speaking on the call today will be Steve Meyers, our Senior Vice President, Commercial; and Dr. Rabia Ozden, our Chief Medical Officer.

我們的總裁兼首席執行官 Antony Mattessich 將主持今天的電話會議，他將介紹我們的管道開發和 DEXTENZA 商業進展的最新情況。今天在電話會議上發言的還有我們的商業高級副總裁 Steve Meyers；和我們的首席醫療官 Rabia Ozden 博士。

Following their remarks, I will provide an overview of the financial highlights for the quarter before turning the call back over to Antony for a summary and questions. For Q&A, we will be joined by Chris White, our Chief Business Officer; and Dr. Peter Kaiser, our Chief Medical Adviser, Retina.

在他們發表評論之後，我將概述本季度的財務亮點，然後再將電話轉回 Antony 進行總結和提問。對於問答環節，我們的首席商務官克里斯·懷特 (Chris White) 將加入我們的行列；和我們的 Retina 首席醫療顧問 Peter Kaiser 博士。

As a reminder, on today's call, certain statements we will be making may be considered forward-looking for the purposes of the Private Securities Litigation Reform Act of 1995. In particular, any statements regarding our regulatory and product development plans as well as our research activities are forward-looking statements. These statements are subject to a variety of risks and uncertainties that may cause actual results to differ from those forecasted, including those risks described in our most recent annual report on Form 10-K filed this afternoon with the SEC.

提醒一下，在今天的電話會議上，就 1995 年《私人證券訴訟改革法案》而言，我們將發表的某些聲明可能被視為前瞻性聲明。特別是關於我們的監管和產品開發計劃以及我們的研究的任何聲明活動是前瞻性陳述。這些聲明受各種風險和不確定性的影響，這些風險和不確定性可能導致實際結果與預測結果不同，包括我們今天下午向美國證券交易委員會提交的 10-K 表格的最新年度報告中描述的那些風險。

I will now turn the call over to Antony.

我現在將把電話轉給安東尼。

Thanks, Donald. The fourth quarter of 2022 was a tremendous success for Ocular Therapeutix and has set the stage for a very strong start to the year in 2023.

謝謝，唐納德。 2022 年第四季度對 Ocular Therapeutix 來說是巨大的成功，並為 2023 年的強勁開局奠定了基礎。

First, on the sales side, we finished the quarter with DEXTENZA net product revenue sales of $13.9 million compared with the same quarter of previous year sales of $12.2 million and sales over prior quarter of $11.9 million. That represents growth of approximately 14% and 17%, respectively. Total DEXTENZA net product revenue was $50.5 million, representing growth over prior year of approximately 20%. Most importantly, in the fourth quarter, we regained in-market sales momentum, and I'm pleased to report that this momentum has continued in the first couple of months this quarter.

首先，在銷售方面，我們本季度末的 DEXTENZA 淨產品收入銷售額為 1390 萬美元，而去年同期銷售額為 1220 萬美元，上一季度銷售額為 1190 萬美元。這分別代表了大約 14% 和 17% 的增長。 DEXTENZA 產品淨收入總額為 5050 萬美元，比上一年增長約 20%。最重要的是，在第四季度，我們重新獲得了市場銷售勢頭，我很高興地報告說，這種勢頭在本季度的前幾個月仍在繼續。

I will introduce you to our new Senior Vice President of Commercial in a few moments who will go through -- who will go over the reasons for the return to growth and our go-to-market strategy.

稍後我將向您介紹我們新任的商務高級副總裁，他將介紹恢復增長的原因和我們的進入市場戰略。

While we were very pleased to regain momentum with DEXTENZA, we are really seeing the potential value of our pipeline continue to emerge, following the recent data we shared on OTX-TKI, our axitinib-containing hydrogel implant for the treatment of wet AMD and other VEGF-mediated retinal diseases.

雖然我們很高興通過 DEXTENZA 重獲動力，但我們確實看到了我們管道的潛在價值不斷顯現，因為我們最近分享了關於 OTX-TKI 的數據，我們的含阿西替尼的水凝膠植入物用於治療濕性 AMD 和其他VEGF 介導的視網膜疾病。

On February 11, Dr. Andrew Moshfeghi presented the interim 10-month results from our Phase I study in the U.S. where we compared a single dose of OTX-TKI to EYLEA given every 8 weeks in patients with wet AMD. The results were spectacular as we saw no additional rescues up to month 10 of the 73% of patients who were rescue-free up to month 7, demonstrating potential best-in-class durability. We believe the $15 billion global market for wet AMD and diabetic retinopathy is driven by durability.

2 月 11 日，Andrew Moshfeghi 博士介紹了我們在美國進行的 I 期研究的 10 個月中期結果，我們比較了單劑量 OTX-TKI 與每 8 週給予濕性 AMD 患者的 EYLEA。結果是驚人的，因為我們看到 73% 的患者在第 7 個月之前沒有獲救，直到第 10 個月沒有額外的搶救，這證明了潛在的一流耐用性。我們相信 150 億美元的濕性 AMD 和糖尿病性視網膜病變全球市場是由耐用性驅動的。

While these results mean a great deal to Ocular Therapeutix and its shareholders, more importantly, they suggest a better future for patients suffering from VEGF-mediated retinal diseases, such as wet AMD, diabetic retinopathy and diabetic macular edema.

雖然這些結果對 Ocular Therapeutix 及其股東意義重大，但更重要的是，它們為患有 VEGF 介導的視網膜疾病（例如濕性 AMD、糖尿病性視網膜病變和糖尿病性黃斑水腫）的患者提供了更美好的未來。

In the case of wet AMD, it is well known that the vision gained seen when starting anti-VEGF treatments are not maintained over time in the real world. The primary reason for this is the lack of compliance caused by the injection burden of current antibody therapies like LUCENTIS and EYLEA.

在濕性 AMD 的情況下，眾所周知，在現實世界中，開始抗 VEGF 治療時獲得的視力不會隨著時間的推移而得到維持。主要原因是當前抗體療法（如 LUCENTIS 和 EYLEA）的注射負擔導致依從性不足。

In the real world, patients tend to miss necessary injections for a variety of reasons. Wet AMD patients are elderly and can find it difficult to get to retina offices on a 4 to 8 weekly basis, so appointments are missed or delayed and permanent vision loss occurs because of the damage caused when the medication wears off and the disease process return.

在現實世界中，患者往往會因為各種原因而錯過必要的注射。濕性 AMD 患者年齡較大，很難每週 4 到 8 次去視網膜辦公室，因此會錯過或延遲預約，並且由於藥物失效和疾病過程恢復時造成的損害而導致永久性視力喪失。

In the case of diabetic retinopathy where patients are generally of working age, the lack of urgency, given that disease may not have yet manifested and finding the time to get treated on a frequent basis, create real compliance challenges. In this population, the current standard of care is watchful waiting, and many patients frequently progress to more severe vision-destroying disease before seeking treatment, making the results -- the resulting diabetic macular edema, a leading cause of blindness among the working age population.

對於患者通常處於工作年齡的糖尿病性視網膜病變，缺乏緊迫感，因為該疾病可能尚未表現出來，並且經常找時間接受治療，這會帶來真正的合規性挑戰。在這一人群中，目前的護理標準是觀察等待，許多患者在尋求治療之前經常會發展為更嚴重的視力破壞性疾病，結果導致糖尿病性黃斑水腫成為工作年齡人群失明的主要原因.

In short, we believe the promise of a drug like OTX-TKI is not only about convenience but also about saving vision. If we can move durability from the current frequency of injections to at least 9 months and beyond, we believe we can keep people on treatment and maintain vision.

簡而言之，我們相信像 OTX-TKI 這樣的藥物的承諾不僅在於方便，還在於拯救視力。如果我們能夠將耐久性從目前的注射頻率提高到至少 9 個月甚至更長，我們相信我們可以讓人們繼續接受治療並保持視力。

Lastly, it is important to understand that OTX-TKI is a different paradigm than typical antibody treatments. Existing treatments, like LUCENTIS and EYLEA, are bolus injections where a large amount of antibodies, well above the amount needed for immediate efficacy, are injected into the vitreous that, over time, are eliminated from the vitreous until they drop below therapeutic levels, allowing the disease process to restart. They extend injection intervals by making the antibody larger and slower to eliminate or just by jamming more antibodies into the eye with each injection. Either way, you're still treating a chronic disease with pulsatile dosing.

最後，重要的是要了解 OTX-TKI 是一種不同於典型抗體治療的範例。現有的治療方法，如 LUCENTIS 和 EYLEA，是推注，將遠高於立即生效所需量的大量抗體注射到玻璃體中，隨著時間的推移，這些抗體會從玻璃體中清除，直到它們降至治療水平以下，從而允許病程重新開始。他們通過使抗體更大和更慢地消除或只是通過每次注射將更多抗體塞入眼睛來延長注射間隔。無論哪種方式，您仍在使用脈動劑量治療慢性疾病。

OTX-TKI is different. OTX-TKI is designed to deliver a continuous dose of axitinib, a potent inhibitor of VEGF, keeping drug concentrations above therapeutic levels for extended periods without the drug peaks and troughs of pulsatile dosing. We believe the results we recently shared bear this out and demonstrate that our hydrogel technology could allow us to maintain therapeutic levels of axitinib at continuous levels in the vitreous for durations of at least 10 months. This new paradigm would allow physicians and patients the comfort of knowing the drug is always onboard and can hopefully demonstrate that there's less variability in the retina over time and, more importantly, that vision gains from anti-VEGF therapy are maintained in the real world.

OTX-TKI 則不同。 OTX-TKI 旨在提供連續劑量的 axitinib，一種有效的 VEGF 抑製劑，使藥物濃度長時間保持在治療水平以上，而不會出現脈沖劑量的藥物峰值和谷值。我們相信我們最近分享的結果證實了這一點，並證明我們的水凝膠技術可以讓我們在玻璃體中將阿昔替尼的治療水平維持在連續水平至少 10 個月。這種新的範例將使醫生和患者知道藥物始終在船上而感到舒適，並有望證明隨著時間的推移視網膜的變異性較小，更重要的是，抗 VEGF 治療帶來的視力增益在現實世界中得以維持。

So what's next? We believe we have our proof of concept for OTX-TKI in wet AMD and, by extension, had gone a long way toward proof-of-concept and other VEGF-mediated retinal disease. Importantly, we also have a working formulation. We believe we'll be ready to enter the first pivotal trial in wet AMD as soon as the third quarter of this year. We are in ongoing discussions with the FDA regarding pivotal study designs and are very encouraged by the potential path forward both in wet AMD and diabetic retinopathy.

下一個是什麼？我們相信我們已經對濕性 AMD 中的 OTX-TKI 進行了概念驗證，並且通過擴展，在概念驗證和其他 VEGF 介導的視網膜疾病方面已經走了很長一段路。重要的是，我們還有一個可行的公式。我們相信我們將準備好在今年第三季度盡快進入濕 AMD 的第一個關鍵試驗。我們正在與 FDA 就關鍵研究設計進行討論，並對濕性 AMD 和糖尿病視網膜病變的潛在發展道路感到非常鼓舞。

We have also mentioned that commencing this trial is subject to financing, and we are considering a range of nondilutive or minimally dilutive funding options, but we have strong preference and are seeking to go forward with a potential strategic alliance.

我們還提到，開始這項試驗需要融資，我們正在考慮一系列非稀釋性或最低稀釋性的融資方案，但我們有強烈的偏好，並正在尋求建立潛在的戰略聯盟。

We have also stated our intention to begin a Phase III program for diabetic retinopathy in the first quarter of 2024, assuming positive top line data results from our ongoing Phase I clinical trial in diabetic retinopathy. The diabetic retinopathy program is a separate program with much more modest resource requirements than wet AMD. And consequently, we believe we could secure funding on our own without necessarily having a strategic alliance in place for our wet AMD program. We do, however, recognize that a potential strategic interested in our wet AMD program would also likely be interested in our diabetic retinopathy program. Our current plan is to commence the first pivotal trial in diabetic retinopathy in Q1 2024. Net-net, we believe we have a very valuable asset in OTX-TKI with a strong plan moving forward.

我們還表示，我們打算在 2024 年第一季度開始針對糖尿病性視網膜病變的 III 期計劃，假設我們正在進行的糖尿病性視網膜病變 I 期臨床試驗產生積極的頂線數據。糖尿病視網膜病變項目是一個獨立的項目，其資源需求比濕性 AMD 低得多。因此，我們相信我們可以自己獲得資金，而不必為我們的濕 AMD 計劃建立戰略聯盟。然而，我們確實認識到，對我們的濕性 AMD 計劃感興趣的潛在戰略也可能對我們的糖尿病視網膜病變計劃感興趣。我們目前的計劃是在 2024 年第一季度開始第一個糖尿病視網膜病變的關鍵試驗。Net-net，我們相信我們在 OTX-TKI 方面擁有非常寶貴的資產，並有一個強有力的計劃向前推進。

With that. Let me turn the call over to Steve Meyers, our new Senior Vice President, Commercial, to discuss more on DEXTENZA and our 2023 guidance.

接著就，隨即。讓我把電話轉給我們新的商業高級副總裁史蒂夫邁耶斯，討論更多關於 DEXTENZA 和我們的 2023 年指導。

Thank you, Antony. I joined Ocular Therapeutix 1 year ago, in March 2022. Prior to that, I served as Vice President, Sales, at Flexion Therapeutics. During my tenure at Flexion, I led a team of approximately 100 sales representatives. During that time, we launched a product with a very similar business model. Like DEXTENZA, it is cold chain, buy-and-bill, a similar price point and with many of the same clinical characteristics.

謝謝你，安東尼。我於 1 年前，即 2022 年 3 月加入 Ocular Therapeutix。在此之前，我曾擔任 Flexion Therapeutics 的銷售副總裁。在 Flexion 任職期間，我領導了一個由大約 100 名銷售代表組成的團隊。在那段時間裡，我們推出了一款商業模式非常相似的產品。與 DEXTENZA 一樣，它是冷鏈、購買和賬單、相似的價格點和許多相同的臨床特徵。

As many of you know, Ocular Therapeutix is poised to become a leader in the ophthalmology space, and I'm excited about the opportunities in front of us. Over this past year, we established a rigorous hiring process to assemble an experienced sales team that has deep buy-and-bill ophthalmology and surgical experience. We also adjusted our discounting strategy to meet the demands of the market. Finally, we've secured exceptional market access coverage for DEXTENZA, including 100% coverage on Medicare Part B, over 90% coverage in Medicare Advantage, and we'll be launching a new innovative program to accelerate the commercial book of business.

正如你們許多人所知，Ocular Therapeutix 有望成為眼科領域的領導者，我對我們面前的機遇感到興奮。在過去的一年裡，我們建立了嚴格的招聘流程，以組建一支經驗豐富的銷售團隊，該團隊擁有豐富的眼科和外科手術經驗。我們還調整了折扣策略以滿足市場需求。最後，我們為 DEXTENZA 確保了卓越的市場准入覆蓋率，包括 Medicare B 部分的 100% 覆蓋率， Medicare Advantage 超過 90% 的覆蓋率，我們將推出一項新的創新計劃，以加速商業業務。

Overall, we expect our market access coverage should allow more surgeons to treat more patients with the goal of supporting DEXTENZA to become a standard practice in ASCs and fuel growth of DEXTENZA product sales in 2023.

總體而言，我們預計我們的市場准入範圍應該允許更多的外科醫生治療更多的患者，目標是支持 DEXTENZA 成為 ASCs 的標準實踐，並在 2023 年推動 DEXTENZA 產品銷售的增長。

As we begin 2023, we're seeing continued momentum in January and February, with in-market billable units running more than 20% ahead of 2022 levels for the same period. We anticipate that with a full sales team and our strong market access, DEXTENZA sales will continue to grow in 2023.

隨著 2023 年的開始，我們在 1 月和 2 月看到了持續的勢頭，市場上可計費單位的運行速度比 2022 年同期水平高出 20% 以上。我們預計，憑藉完整的銷售團隊和強大的市場准入，DEXTENZA 的銷售額將在 2023 年繼續增長。

Based on these dynamics, the company is guiding initial DEXTENZA net product revenue for the full year 2023 to be between $55 million and $60 million, representing potential growth of approximately 10% to 20% over 2022.

基於這些動態，公司指導 DEXTENZA 2023年全年的初始淨產品收入在5500萬美元至6000萬美元之間，比2022年潛在增長約10%至20%。

With that, let me turn the call over to Rabia to discuss our pipeline in more depth.

有了這個，讓我把電話轉給 Rabia 來更深入地討論我們的管道。

Thanks, Steve. Let me begin with an update on our back-of-the-eye program, OTX-TKI.

謝謝，史蒂夫。讓我從我們的眼後部計劃 OTX-TKI 的更新開始。

As many of you saw a few weeks ago at the Angiogenesis, Exudation and Degeneration 2023 Virtual Meeting, we presented positive interim 10-month data from our U.S.-based Phase I trial of OTX-TKI being developed for the treatment of wet AMD and other retinal indications. This trial is a multicenter, prospective, masked, randomized, controlled trial in 21 subjects evaluating a 600-microgram OTX-TKI dose in a single implant containing axitinib compared to aflibercept administered every 8 weeks in controlled with wet AMD subjects previously treated with anti-VEGF therapy. The trial is designed to assess the safety, durability and tolerability of OTX-TKI and to assess preliminary biological activity in subjects by measuring anatomical and functional changes of the retina.

正如你們中的許多人在幾週前的血管生成、滲出和退化 2023 虛擬會議上所看到的那樣，我們展示了來自美國的 OTX-TKI I 期臨床試驗的 10 個月中期積極數據，該試驗正在開髮用於治療濕性 AMD 和其他疾病視網膜適應症。該試驗是一項針對 21 名受試者的多中心、前瞻性、設盲、隨機、對照試驗，在先前接受抗血管內皮生長因子治療。該試驗旨在評估 OTX-TKI 的安全性、耐用性和耐受性，並通過測量視網膜的解剖學和功能變化來評估受試者的初步生物活性。

Overall, we could not have been more pleased with the results. OTX-TKI was generally well tolerated with no drug-related ocular or systemic serious adverse events. Importantly, all OTX-TKI-treated subjects who were rescue-free at the month 7 interim analysis remained rescue-free, extending the 73% rescue-free rate up to month 10 and highlighting what we believe is best-in-class durability.

總的來說，我們對結果非常滿意。 OTX-TKI 通常耐受性良好，沒有藥物相關的眼部或全身嚴重不良事件。重要的是，所有在第 7 個月中期分析中未獲救的接受 OTX-TKI 治療的受試者仍未獲救，將 73% 的無救助率延長至第 10 個月，並突出了我們認為一流的耐用性。

Furthermore, we saw in the trial a 92% reduction in treatment burden for up to 10 months while demonstrating stable and sustained best-corrected visual acuity and central subfield foveal thickness, comparable with the aflibercept arm dosed every 8 weeks. We believe the data highlights the potential of OTX-TKI to become a differentiated product capable of providing a durable anti-VEGF response that improves upon today's standard of care in the management of wet AMD. As Antony noted, we are in active discussions with the FDA and believe that we will be in a position to initiate the pivotal trials in Q3 of 2023 for wet AMD and Q1 of 2024 for diabetic retinopathy.

此外，我們在試驗中看到長達 10 個月的治療負擔減少了 92%，同時表現出穩定和持續的最佳矯正視力和中心亞區中心凹厚度，與每 8 週給藥一次的阿柏西普組相當。我們相信這些數據突出了 OTX-TKI 成為差異化產品的潛力，該產品能夠提供持久的抗 VEGF 反應，從而改善當今濕性 AMD 管理的護理標準。正如 Antony 指出的那樣，我們正在與 FDA 進行積極討論，並相信我們將能夠在 2023 年第三季度針對濕性 AMD 和 2024 年第一季度針對糖尿病視網膜病變啟動關鍵試驗。

We were pleased to have initiated a Phase I trial of OTX-TKI in diabetic retinopathy in Q4 of 2022. This U.S.-based trial will have approximately 10 sites and will include 21 subjects randomized 2:1 in a masked session to either a 600-microgram OTX-TKI single implant containing axitinib or sham control. We believe the same attributes that make OTX-TKI a compelling product candidate for the treatment of wet AMD, the ease of use of an office-based injection and long-term durability could establish this as the first standard of care in the treatment of diabetic retinopathy.

我們很高興在 2022 年第 4 季度啟動了 OTX-TKI 治療糖尿病視網膜病變的 I 期試驗。這項基於美國的試驗將有大約 10 個地點，將包括 21 名受試者，在一次盲測中以 2:1 的比例隨機分配到 600-含有阿西替尼或假對照的微克 OTX-TKI 單一植入物。我們相信，使 OTX-TKI 成為治療濕性 AMD 的引人注目的候選產品的相同屬性、基於辦公室的注射劑的易用性和長期耐用性可以將其確立為治療糖尿病的首要護理標準視網膜病變。

Moving to our glaucoma program, OTX-TIC. We continue to actively enroll subjects in a U.S.-based Phase II clinical trial. This trial is a prospective, multicenter, masked, randomized, controlled trial evaluating the safety, tolerability and efficacy of OTX-TIC for the reduction of intraocular pressure in subjects with primary open-angle glaucoma or ocular hypertension.

轉到我們的青光眼項目 OTX-TIC。我們繼續積極招募受試者參加美國的 II 期臨床試驗。該試驗是一項前瞻性、多中心、設盲、隨機、對照試驗，評估 OTX-TIC 降低原發性開角型青光眼或高眼壓症患者眼內壓的安全性、耐受性和有效性。

In late 2022, due to observed elevations in intraocular pressure in the OTX-TIC 5-microgram treatment arm, we decided to terminate the enrollment in the 5-microgram treatment arm and continue forward with the OTX-TIC 26-microgram and restart treatment arms. The company expects that the Phase II clinical trial will now consist of approximately 86 subjects, approximately 35 subjects in the OTX-TIC 26-microgram treatment arm, 35 subjects in the DURYSTA arm 16 subjects that were previously enrolled in the OTX-TIC 5-microgram treatment arm. The trial is designed to observe the changes in diurnal intraocular pressure from baseline at 2, 6 and 12 weeks and follow-up duration of intraocular pressure response over time. We plan to release top line data for this Phase II clinical trial in Q4 of 2023.

2022 年底，由於觀察到 OTX-TIC 5 微克治療組的眼內壓升高，我們決定終止 5 微克治療組的招募，繼續使用 OTX-TIC 26 微克並重新啟動治療組.公司預計 II 期臨床試驗現在將包括約 86 名受試者，OTX-TIC 26 微克治療組約 35 名受試者，DURYSTA 組約 35 名受試者以及之前參加 OTX-TIC 5-的 16 名受試者微克治療臂。該試驗旨在觀察第 2、6 和 12 週的晝夜眼壓相對於基線的變化，以及隨時間推移眼壓反應的隨訪持續時間。我們計劃在 2023 年第四季度發布此 II 期臨床試驗的頂線數據。

Regarding our ocular surface disease programs, we remain committed to the development of our 2 dry eye programs, OTX-DED, a low-dose intracanalicular insert containing dexamethasone, for the short-term treatment of the signs and symptoms of dry eye disease. And OTX-CSI, a cyclosporine intracanalicular insert, for the chronic treatment of patients with dry eye disease. We intend to commence a small trial in the first half of 2023 to evaluate the performance of OTX-DED versus placebo inserts, namely fast-dissolving collagen plugs and no inserts at all. We plan to use the results of this trial to inform the selection of a more appropriate placebo comparator for both the OTX-DED and the OTX-CSI programs moving forward.

關於我們的眼表疾病項目，我們仍然致力於開發我們的 2 個乾眼項目 OTX-DED，這是一種含有地塞米鬆的低劑量眼內插入物，用於短期治療乾眼病的體徵和症狀。和 OTX-CSI，一種環孢菌素管內插入物，用於乾眼症患者的慢性治療。我們打算在 2023 年上半年開始一項小型試驗，以評估 OTX-DED 與安慰劑插入物的性能，即快速溶解的膠原蛋白塞和根本沒有插入物。我們計劃使用該試驗的結果為未來的 OTX-DED 和 OTX-CSI 計劃選擇更合適的安慰劑比較提供信息。

I would now like to turn the call back over to Donald to review our fourth quarter and year-end financial results.

我現在想把電話轉回給唐納德，以審查我們的第四季度和年終財務業績。

Thank you, Rabia. Total net revenue, which includes both gross DEXTENZA product revenue, net of discounts, rebates and returns, which the company refers to as total net product revenue, and collaboration revenue, was $14.1 million for the fourth quarter of 2022 and represents 18% growth over the prior quarter and 15% growth over the same period in 2021.

謝謝你，拉比亞。 2022 年第四季度的總淨收入為 1410 萬美元，包括 DEXTENZA 產品總收入，扣除折扣、回扣和退貨（該公司稱為總淨產品收入）和合作收入，同比增長 18%上一季度和 2021 年同期增長 15%。

DEXTENZA net product revenue was $13.9 million for the fourth quarter of 2022, an increase of approximately 17% sequentially over the prior quarter and up 14% over the comparable quarter of 2021. Net product revenue in the fourth quarter of 2021 included $0.1 million attributable to the sales of ReSure Sealant. Total net revenue for the full year 2022 was $51.5 million versus $43.5 million, an 18% increase.

DEXTENZA 2022年第四季度的產品淨收入為1390萬美元，比上一季度增長約17%，比2021年同期增長14%。2021年第四季度的產品淨收入包括10萬美元歸因於ReSure 密封劑的銷售。 2022 年全年的總淨收入為 5150 萬美元，比 4350 萬美元增長 18%。

Research and development expenses for the fourth quarter of 2022 were $13.5 million versus $12.6 million for the comparable period in 2021 driven primarily by an increase in personnel, offset by both a reduction in overall clinical trial expenses and a delay in the timing of clinical trials. Overall, R&D expenses for the full year increased $3.4 million to $53.5 million from $50.1 million in 2021, reflecting the trends identified previously.

2022 年第四季度的研發費用為 1350 萬美元，而 2021 年同期為 1260 萬美元，這主要是由於人員增加，但被總體臨床試驗費用的減少和臨床試驗時間的延遲所抵消。總體而言，全年研發費用從 2021 年的 5010 萬美元增加 340 萬美元至 5350 萬美元，反映了之前確定的趨勢。

Selling and marketing expenses in the fourth quarter of 2022 were $10.5 million as compared to $9.1 million for the comparable quarter of 2021, reflecting primarily an increase in field force personnel. Overall, selling and marketing expenses for the full year increased to $39.9 million from $35.2 million in 2021 driven primarily by increased personnel costs and increased spending on consulting, trade shows and conferences.

2022 年第四季度的銷售和營銷費用為 1050 萬美元，而 2021 年同期為 910 萬美元，這主要反映了外勤人員的增加。總體而言，全年的銷售和營銷費用從 2021 年的 3520 萬美元增加到 3990 萬美元，這主要是由於人員成本增加以及諮詢、貿易展覽和會議支出增加所致。

General and administrative expenses were $8.3 million for the fourth quarter of 2022 versus $7.5 million in the comparable quarter of 2021, primarily due to an increase in personnel-related costs, including stock-based compensation. Overall, G&A expenses for the full year increased $0.3 million to $32.2 million from $31.9 million in 2021, again, reflecting the trends identified previously.

2022 年第四季度的一般和行政費用為 830 萬美元，而 2021 年同期為 750 萬美元，這主要是由於與人事相關的成本增加，包括股票薪酬。總體而言，全年的 G&A 費用從 2021 年的 3190 萬美元增加了 30 萬美元至 3220 萬美元，再次反映了之前確定的趨勢。

The company reported a net loss for the fourth quarter of 2022 of $15.5 million or a loss of $0.20 per share on a basic basis and a loss of $0.24 per share on a diluted basis compared to a net loss of $3.9 million or a net loss of $0.05 per share on a basic basis and a loss of $0.23 per share on a diluted basis for the same period in 2021.

公司報告 2022 年第四季度淨虧損 1550 萬美元或每股基本虧損 0.20 美元，稀釋後每股虧損 0.24 美元，而淨虧損為 390 萬美元或淨虧損為2021 年同期基本每股虧損 0.05 美元，稀釋後每股虧損 0.23 美元。

Net loss in the fourth quarter of 2022 included a $5.2 million noncash item attributable to a decrease in the fair value of the derivative liability associated with the company's convertible notes as the price of its common stock decreased during the quarter. Noncash charges for stock-based compensation and depreciation and amortization were $4.7 million in the fourth quarter of 2022 versus $4.4 million for the same quarter in 2021.

2022 年第四季度的淨虧損包括一項 520 萬美元的非現金項目，這是由於本季度普通股價格下跌，導致與公司可轉換票據相關的衍生負債的公允價值下降。 2022 年第四季度基於股票的薪酬以及折舊和攤銷的非現金費用為 470 萬美元，而 2021 年同期為 440 萬美元。

Overall, the company reported a net loss of $71 million or a loss of $0.92 per share on a basic basis and a loss of $0.97 per share on a diluted basis for the full year ended December 31, 2022, versus a net loss of $6.6 million or a loss of $0.09 per share on a basic basis and a loss of $0.98 per share on a diluted basis in 2021.

總體而言，該公司報告截至 2022 年 12 月 31 日的全年淨虧損為 7100 萬美元或基本每股虧損 0.92 美元，攤薄後每股虧損 0.97 美元，而淨虧損為 660 萬美元或 2021 年基本每股虧損 0.09 美元，稀釋後每股虧損 0.98 美元。

As of March 1, 2023, the company had 77.5 million shares outstanding.

截至 2023 年 3 月 1 日，公司流通股為 7750 萬股。

This concludes my comments on our fourth quarter 2022 and year-end financial results, and I would like to turn the call back to Antony for some final thoughts.

我對我們 2022 年第四季度和年終財務業績的評論到此結束，我想把電話轉回給安東尼，聽聽他最後的想法。

Thanks, Donald. So before opening the call up for questions, let me give a quick summary.

謝謝，唐納德。因此，在開始提問之前，讓我快速總結一下。

We were excited to be able to share with the world our 10-month interim results from the U.S.-based Phase I trial for OTX-TKI in wet AMD, building further evidence of a potential product profile that could set the standard of care for durability in the treatment of wet AMD and diabetic retinopathy.

我們很高興能夠與世界分享我們在美國對濕性 AMD 進行的 OTX-TKI I 期試驗的 10 個月中期結果，進一步證明潛在的產品概況可以設定耐久性護理標準用於治療濕性 AMD 和糖尿病性視網膜病變。

We have initiated a Phase I trial of OTX-TKI for diabetic retinopathy and believe we may be positioned to commence our first pivotal trial in Q1 of 2024, subject to obtaining financing and the completion of ongoing discussions with the FDA. We should be positioned to initiate a pivotal trial of OTX-TKI for wet AMD in Q3 of 2023, subject to obtaining additional funding for the trial, including potentially a strategic alliance.

我們已經啟動了 OTX-TKI 治療糖尿病視網膜病變的 I 期試驗，並相信我們可能會在 2024 年第一季度開始我們的第一個關鍵試驗，前提是獲得融資並完成與 FDA 的持續討論。我們應該能夠在 2023 年第三季度啟動針對濕性 AMD 的 OTX-TKI 的關鍵試驗，前提是獲得額外的試驗資金，包括可能的戰略聯盟。

Enrollment continues in the Phase II trial of OTX-TIC in glaucoma, and we believe that we will be in a position to release top line data in Q4 of 2023.

OTX-TIC 在青光眼中的 II 期試驗繼續招募，我們相信我們將能夠在 2023 年第四季度發布頂線數據。

DEXTENZA has had a strong start to 2023 with in-market volumes running greater than 20% above prior year through the first 2 months of the year, and we have $102.3 million in cash as of December 31 and have guided cash runway to the middle of 2024.

DEXTENZA 在 2023 年開局強勁，今年前兩個月的市場成交量比去年同期增長 20% 以上，截至 12 月 31 日，我們擁有 1.023 億美元現金，並已將現金跑道引導至 2023 年中期2024.

With that, I will turn the call over to the operator for questions.

有了這個，我會把電話轉給接線員提問。

(Operator Instructions) First question comes from the line of Dane Leone with Raymond James.

（操作員說明）第一個問題來自 Dane Leone 和 Raymond James 的對話。

Congratulations on the progress. I'll keep it to one on my end. Just obligatory since you brought it up, where do you feel like you're in the process of evaluating potential partnership situations for OTX-TKI? And when do you feel, on a time basis, you're trying to move forward with the pivotal program? And what could be some options if you were not to find a potential partner for that asset to go into pivotal study?

祝賀你的進步。我會把它留到我這邊。既然你提出來了，你覺得你在評估 OTX-TKI 潛在合作夥伴關係的過程中有什麼感覺？在時間的基礎上，您什麼時候覺得您正在努力推進關鍵計劃？如果您不為該資產尋找潛在的合作夥伴以進行關鍵研究，那麼有哪些選擇？

Yes. Thanks, Dane. Well, we are in the middle of a process. We're talking to sort of all the people you would expect us to be speaking to. Obviously, it's premature to opine on our likelihood of getting to an agreement with any second partner. So we're happy with where we are in the process. Clearly, we're going to have to make a call at some point moving forward before we lock and load on the first pivotal in wet AMD.

是的。謝謝，戴恩。好吧，我們正處於一個過程中。我們正在與您希望我們與之交談的所有人交談。顯然，現在就我們與任何第二個合作夥伴達成協議的可能性發表意見還為時過早。所以我們對我們在這個過程中所處的位置感到滿意。顯然，在我們鎖定並加載濕 AMD 的第一個關鍵點之前，我們將不得不在前進的某個時刻做出決定。

The other option that we talked about, if we are not able to get the financing in place under the terms that we find agreeable or a strategic partnership under terms that we find agreeable, would be to go with diabetic retinopathy in the first quarter of 2024.

我們討論的另一個選擇是，如果我們無法根據我們認為合適的條款獲得融資或根據我們認為合適的條款獲得戰略合作夥伴關係，那麼我們將在 2024 年第一季度與糖尿病視網膜病變一起進行.

We mentioned before, we think the resource requirements of that are much less onerous than they are for wet AMD. Although wet AMD is still an open question. The guidance and some of the discussions we've had with the FDA really do open up possibilities for wet AMD programs that may not be as expensive as the classic noninferiority versus standard of care given according to its label.

我們之前提到過，我們認為它的資源需求比濕式 AMD 的資源需求要輕得多。儘管濕式 AMD 仍然是一個懸而未決的問題。我們與 FDA 進行的指南和一些討論確實為濕性 AMD 計劃開闢了可能性，這些計劃可能不像根據其標籤給出的經典非劣效性與護理標準一樣昂貴。

So that is the kind of the alternative idea that we have is to move forward with DR under essentially our own steam if we're not able to arrange a nondilutive or a minimally dilutive solution to wet AMD in the third quarter of 2023.

因此，如果我們無法在 2023 年第三季度為濕 AMD 安排非稀釋性或最低稀釋性解決方案，那麼我們的另一種想法就是在本質上以我們自己的方式推進 DR。

Our next question comes from the line of Jon Wolleben with JMP Securities.

我們的下一個問題來自 Jon Wolleben 與 JMP Securities 的對話。

I was wondering if you could give us a little more color around the discussions you're having with FDA and what is constituting the back and forth and if the recent guidance has impacted your discussions or your design plans. Just wondering, I think it's pretty clear, and Dr. Chambers has mentioned this publicly, that durability isn't sufficient to prove efficacy. But how do you demonstrate durability in your pivotal trial in the context of a noninferiority study? Any color there would be helpful.

我想知道你是否可以給我們更多關於你與 FDA 的討論的顏色，以及來回構成的內容，以及最近的指南是否影響了你的討論或你的設計計劃。只是想知道，我認為很明顯，Chambers 博士公開提到了這一點，即耐用性不足以證明療效。但是，如何在非劣效性研究的背景下證明關鍵試驗的持久性？那裡的任何顏色都會有所幫助。

Thank you, Jon. This is Rabia. As you mentioned, Jon, there is this new draft guidance recently issued by the FDA on wet AMD drug development. And we have been in active and constructive discussions with the FDA and recently had our Type C meeting. Therefore, this draft guidance was not new information to us, and we have been considering all the efficacy and the safety points made in the guidance. It was already in our plans with our discussions with the FDA. That's where we have a few pivotal designs in line with the guidance, and we'll continue our discussions with the FDA to have the best design ready for the initiation of the pivotal, as Antony mentioned, Q3 for the wet AMD and Q1 2024 for diabetic retinopathy.

謝謝你，喬恩。這是拉比亞。正如你提到的，Jon，FDA 最近發布了關於濕性 AMD 藥物開發的新指南草案。我們一直在與 FDA 進行積極和建設性的討論，最近舉行了我們的 C 類會議。因此，這份指南草案對我們來說並不是新信息，我們一直在考慮指南中提出的所有功效和安全要點。在我們與 FDA 的討論中，這已經在我們的計劃中。這就是我們根據指南進行一些關鍵設計的地方，我們將繼續與 FDA 進行討論，為關鍵的啟動做好最佳設計準備，正如 Antony 提到的，濕 AMD 第三季度和 2024 年第一季度糖尿病性視網膜病變。

Okay. And maybe one on DEXTENZA. Wondering what swing factors are playing to either being at the low or high end of the guidance for the year?

好的。也許還有一個在 DEXTENZA 上。想知道哪些搖擺因素會影響今年指導的低端或高端？

Could you repeat the question?

你能重複這個問題嗎？

The guidance of $55 million to $60 million for the year for DEXTENZA, just wondering what factors into your estimates to either be at the low or high end of the guidance? What needs to be done to be at the top end of that range?

DEXTENZA 今年的指導價為 5500 萬至 6000 萬美元，只是想知道您的估計是處於指導的低端還是高端的哪些因素？需要做什麼才能達到該範圍的頂端？

Sure. Well, clearly, our hope's to exceed that guidance. And we believe that we have programs and people in place that give us great expectation that we can do just that. Right now, at this point, our customers are still managing staff issues to return to full capacity. So we think right now, $55 million to $60 million is prudent guidance. Our hope is that we'll come back to the next earnings call with a run rate that makes us reconsider that.

當然。好吧，很明顯，我們希望超越該指導。我們相信，我們的項目和人員已經到位，這讓我們對我們能夠做到這一點抱有很大的期望。目前，在這一點上，我們的客戶仍在管理員工問題以恢復滿負荷運轉。所以我們現在認為，5500 萬至 6000 萬美元是謹慎的指導。我們的希望是，我們將以讓我們重新考慮的運行率回到下一次收益電話會議。

And our next question comes from the line of Caroline Palomeque with Berenberg.

我們的下一個問題來自 Caroline Palomeque 與 Berenberg 的對話。

Just a couple for me. So the first one would be on DEXTENZA revenue. Just wondering if you plan to break those out between the 2 revenue streams from ocular pain and inflammation and then the allergic conjunctivitis.

對我來說只是一對。所以第一個是關於 DEXTENZA 的收入。只是想知道您是否計劃將眼痛和炎症與過敏性結膜炎這兩個收入來源分開。

And then the second question I have is just that if you do decide to go with the alternative financing path, how much financing do you think you would need to progress the program for TKI in both wet AMD and DR?

然後我的第二個問題是，如果您決定採用替代融資途徑，您認為您需要多少資金才能在濕性 AMD 和 DR 中推進 TKI 計劃？

Well, as we mentioned, it would be premature to talk about -- so to the second part of the question first. It would be premature to speak about the actual amount that we would need until we actually have an approved protocol. You don't really know how to price up particularly the wet AMD. I think it's pretty clear, diabetic retinopathy, with that, that is likely to cost because I don't think there's too many variations on what the pivotal program might look like, not the case with wet AMD.

好吧，正如我們提到的，現在談論問題還為時過早——所以首先討論問題的第二部分。在我們真正獲得批准的協議之前談論我們需要的實際數量還為時過早。您真的不知道如何定價，尤其是濕 AMD。我認為很明顯，糖尿病性視網膜病變，這很可能會造成成本，因為我認為關鍵程序可能看起來沒有太多變化，濕性 AMD 的情況則不然。

I'm sorry, the first part of your question related to DEXTENZA, what was that again?

抱歉，您問題的第一部分與 DEXTENZA 有關，那又是什麼？

Yes. Just wondering if you plan on breaking out revenues between the different therapeutic areas within DEXTENZA.

是的。只是想知道您是否計劃在 DEXTENZA 的不同治療領域之間增加收入。

No, we won't plan to do that. What we've done essentially to consolidate around our higher or more reliable ROI was really to double-down into the surgical setting, to ensure that we have all hands on deck and really maximize the investment that we have with our field force. We will plan on launching into the office space with the really conjunctivitis indication but not in the very near future. So we won't be breaking that out because it really wouldn't be instructive.

不，我們不打算這樣做。我們所做的基本上是為了鞏固我們更高或更可靠的投資回報率，實際上是加倍努力進入手術環境，以確保我們全力以赴並真正最大化我們對現場人員的投資。我們將計劃進入具有真正結膜炎跡象的辦公空間，但不會在不久的將來。所以我們不會打破它，因為它真的沒有指導意義。

Our next question comes from the line of Joe Catanzaro with Piper Sandler.

我們的下一個問題來自 Joe Catanzaro 和 Piper Sandler 的台詞。

Maybe just following up on some of the earlier questions. I was just wondering how much is the potential strategic partnership for TKI contingent on defining and coming to an agreement with the FDA on what that clinical trial requirements would be for the pivotal wet AMD study? And then relatedly, I appreciate that you're guiding to a potential study initiation in the third quarter of this year. But when do you think you would be in a position to be able to communicate what that study would look like?

也許只是跟進一些較早的問題。我只是想知道，TKI 的潛在戰略合作夥伴關係在多大程度上取決於確定關鍵的濕性 AMD 研究的臨床試驗要求並與 FDA 達成協議？然後相關地，我感謝您指導今年第三季度的潛在研究啟動。但是你認為你什麼時候能夠傳達該研究的樣子？

We are very close, we believe, to coming to an understanding of what that pivotal program might look like. So we think that they'll dovetail nicely, the discussions that we're having with the potential strategics and what the pivotal look like. But you're absolutely right that it would really be hard to go into a true alliance unless people understood it what that program would look like, but luckily, we're pretty close.

我們相信，我們已經非常接近了解這個關鍵項目可能是什麼樣子了。所以我們認為他們會很好地吻合，我們正在討論潛在的戰略以及關鍵的樣子。但是你是絕對正確的，除非人們了解該程序的外觀，否則很難建立真正的聯盟，但幸運的是，我們非常接近。

(Operator Instructions) And this concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.

（操作員說明）今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。每個人，祝你有美好的一天。