Kodiak Sciences Inc (KOD) 2023 Q4 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Kodiak Sciences business update webcast and conference call. (Operator Instructions) Please be advised that today's conference is being recorded.

美好的一天，感謝您的支持。歡迎收看 Kodiak Sciences 業務更新網路廣播和電話會議。（操作員指示）請注意，今天的會議正在錄製中。

I would now like to hand the conference over to your first speaker today, John Borgeson, Chief Financial Officer. Please go ahead.

現在我想將會議交給今天的第一位發言人，財務長約翰‧博爾格森 (John Borgeson)。請繼續。

Thank you for joining our conference call and webcast to discuss recent business updates at Kodiak. I am John Borgeson, Kodiak's Chief Financial Officer. Joining me today are Victor Perlroth, Chairman and CEO; and Pablo Velazquez-Martin, Senior Vice President of Clinical Research and Development.

感謝您參加我們的電話會議和網路廣播，討論 Kodiak 的最新業務動態。我是科迪亞克財務長約翰·博爾格森。今天與我一起出席的還有董事長兼執行長 Victor Perlroth；以及臨床研究與發展資深副總裁 Pablo Velazquez-Martin。

After our prepared remarks, we will open the call for Q&A. The webcast portion of this call contains a slide presentation that we will refer to during the call. Those following along on the phone who wish to access the slide portion of this presentation may do so on the Investors and Media section of our website, and an archive of this webcast will be available shortly after the event on our website.

在我們準備好發言後，我們將開始問答環節。本次電話會議的網路廣播部分包含我們將在電話會議期間參考的幻燈片簡報。那些透過電話關注並希望存取本簡報幻燈片部分的人可以在我們網站的投資者和媒體部分進行操作，並且該網路廣播的存檔將在活動結束後不久在我們的網站上提供。

We'd also like to remind you that remarks made on this call today include forward-looking statements about Kodiak that are subject to risks and uncertainties, and which are outlined on this slide. For a more complete description of these and other material risks can be found in Kodiak's filings with the Securities and Exchange Commission, including its 10-K for the year ended December 31, 2023, which has been filed with the SEC, and we encourage you to read those carefully. I will note that Kodiak does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events, or otherwise.

我們也想提醒您，今天的電話會議中發表的言論包括有關 Kodiak 的前瞻性陳述，這些陳述存在風險和不確定性，本投影片對此進行了概述。有關這些風險和其他重大風險的更完整描述，請參閱 Kodiak 向美國證券交易委員會提交的文件，包括已向 SEC 提交的截至 2023 年 12 月 31 日的年度 10-K，我們鼓勵您仔細閱讀這些內容。我要指出的是，科迪亞克不承擔公開更新任何前瞻性聲明的義務，無論是由於新資訊、未來事件或其他原因。

Now I'm pleased to turn the call over to Victor Perlroth, Kodiak's CEO. Victor?

現在我很高興將電話轉給 Kodiak 執行長 Victor Perlroth。勝利者？

Thank you, John. Good afternoon, everyone. Thanks for joining us. I trust many of you have read Kodiak's press release this morning announcing our recent business updates together with our financial snapshot. The goal for today's discussion is to provide additional context and color around some of our most recent activities and our going forward plan. And we will welcome your questions at the end.

謝謝你，約翰。大家下午好。感謝您加入我們。我相信你們中的許多人已經閱讀了科迪亞克今天早上的新聞稿，其中宣布了我們最近的業務更新以及我們的財務快照。今天討論的目標是為我們最近的一些活動和未來計劃提供更多背景和色彩。最後我們歡迎您提出問題。

We're a retina-focused company. Retina is a challenging area for innovation, but there should be an increasing return to focus in time and dedication. At Kodiak, we sit atop 10-plus years of fine-tuning of our ABC Platform in our company, also enabled to listen and to have the courage to make the important course corrections needed to get us to the finish line with medicines that are meaningful for patients and therefore valuable.

我們是一家專注於視網膜的公司。視網膜是一個具有挑戰性的創新領域，但人們應該越來越多地投入時間和奉獻精神。在 Kodiak，我們在公司 ABC 平台上進行了 10 多年的微調，也使我們能夠傾聽並有勇氣進行重要的路線修正，使我們能夠以有意義的藥物到達終點線對於患者來說因此很有價值。

The sector is concentrated with only Roche and Regeneron as dominant players. There's room for another major player and that remains our aspiration. We look forward today to providing you the broad view.

此領域主要集中在羅氏（Roche）和再生元（Regeneron）兩家公司。還有另一個主要參與者的空間，這仍然是我們的願望。我們期待今天為您提供廣闊的視野。

Today, we are at a point of departure, and we are in motion. We have a portfolio of three clinical programs. Two programs our ABC Platform-derived with its core science of durability, and one program is platform independent. We think this pipeline represents a healthy diversification, both in terms of the opportunity and risk.

今天，我們正處於出發點，我們正在前進。我們擁有三個臨床項目的組合。我們的 ABC 平台有兩個程式以其耐用性的核心科學而衍生，其中一個程式是獨立於平台的。我們認為，無論是在機會還是風險方面，這條管道都代表著健康的多元化。

For some of you listening today may say I'm not smart enough to know whether Kodiak's ABC Platform represents a disruptive innovation that can deliver for patients, and frankly, for investors or not. For you, let us show you, but in the meantime, you don't have to believe in the ABC Platform to recognize that KSI-101 represents itself of potential important, new, branded molecule for retina, highly potent on two powerful mechanisms for patients with inflammation and some residual fluid.

今天聽眾中的一些人可能會說，我不夠聰明，不知道 Kodiak 的 ABC 平台是否代表了一項顛覆性創新，可以為患者帶來好處，坦白說，也可以為投資者帶來好處。對於您，讓我們向您展示，但與此同時，您不必相信 ABC 平台就能認識到 KSI-101 代表了視網膜潛在的重要、新型、品牌分子，它在兩種強大的機制上非常有效有炎症和一些殘留液體的患者。

We call it a greenfield market opportunity in the program building as it does already from the base of bioactivity, efficacy, and safety, seeing in the KSI-501 program, sharing as it does the same protein. Kodiak can be a tremendously successful company and investment opportunity on the basis of KSI-101 alone.

我們稱之為專案建設中的綠地市場機會，因為它已經從生物活性、功效和安全性的基礎出發，在 KSI-501 專案中看到，共享相同的蛋白質。僅憑 KSI-101，Kodiak 就可以成為一家非常成功的公司和投資機會。

But for ourselves, we are big believers also in our ABC Platform. Why? Durability remains a key unmet need and want durability for all patients, as an inception regimen as a maintenance for treatment-naive patients and treatment-experienced. And you want the durability without sacrificing immediacy, potency, or safety.

但對我們自己來說，我們也非常相信 ABC 平台。為什麼？耐久性仍然是一個關鍵的未滿足的需求，所有患者都希望耐久性，作為初始治療方案，作為初治患者和有治療經驗的患者的維持方案。您希望在不犧牲即時性、效力或安全性的情況下獲得耐用性。

They say the real test is whether you give the drug to your mother or grandmother. At this stage not being marketed, we provide our investigational medicines in context of our clinical trials, but our design, we're proud of the ABC platform, our novel proteins, our bioconjugates, our underlying science and design for durability.

他們說真正的考驗是你是否將藥物給你的母親或祖母。在這個尚未上市的階段，我們在臨床試驗的背景下提供我們的研究藥物，但我們的設計，我們為ABC 平台、我們的新型蛋白質、我們的生物結合物、我們的基礎科學和耐用性設計感到自豪。

And now the important adjustments we've made to the tarcocimab product that improved manufacturability in a prefilled syringe and we believe may also enhance the utility of the product and which we have also already flowed into the KSI-501 manufactured material as well.

現在，我們對 tarcocimab 產品進行了重要調整，提高了預充式註射器的可製造性，我們相信也可以提高該產品的實用性，並且我們也已經將其融入 KSI-501 製造材料中。

We believe now is the time to implement these changes, given the additional clinical studies we plan to conduct, and the FDA has agreed that these additional clinical studies are sufficient to bridge the former material to the go-to-market material, which we like to commercialize going for.

我們認為現在是實施這些改變的時候了，因為我們計劃進行額外的臨床研究，而 FDA 已經同意這些額外的臨床研究足以將以前的材料與我們喜歡的上市材料聯繫起來商業化的目的。

Tarcocimab, then, and also KSI-501, these represent state of the art molecules. And based on our review of our data and these design enhancements, I think these medicines meet the grandmother tests.

Tarcocimab 以及 KSI-501 代表了最先進的分子。根據我們對數據的審查和這些設計改進，我認為這些藥物符合祖母測試。

And when you look commercially, given the rapid pace now of our planned development for tarcocimab and KSI-501, while, yes, there is a commercial complexity, we are the innovator here and we believe there can be a strong demand for our medicines in their unique design, science, and their unique performance in the retina marketplace.

當你看商業時，考慮到我們目前計劃開發的tarcocimab 和KSI-501 的快速步伐，雖然，是的，存在商業複雜性，但我們是這裡的創新者，我們相信，我們的藥物可能會有強勁的需求他們獨特的設計、科學以及在視網膜市場上的獨特表現。

Kicking it back to the top level across these three, what I call late phase programs, there's also a significant amount of operational synergy in moving these three programs forward together. And as we'll see where useful, we can even run them in the same study or studies with low incremental costs per group.

將這三個項目（我稱之為後期項目）重新推回到最高水平，在共同推動這三個項目方面也存在大量的營運協同作用。正如我們將看到的，我們甚至可以在同一個研究或每組增量成本較低的研究中運行它們。

So where are we in today? Let's start with an overview of where we are. Number one, from a cash position. We have an attractive cash position today as of Q4. Number two, when we look at Kodiak, we see three late phase programs. And number three, our intention is to bring these three programs to meaningful inflections within our cash runway. So for tarcocimab, we have three positive Phase 3 studies that have been completed in diabetic retinopathy, in retinal vein occlusion, and in wet AMD.

那我們今天在哪裡？讓我們先概述一下我們所處的位置。第一，來自現金狀況。截至第四季度，我們目前的現金狀況頗具吸引力。第二，當我們看 Kodiak 時，我們看到三個後期項目。第三，我們的目的是讓這三個項目在我們的現金跑道上實現有意義的轉變。因此，對於 tarcocimab，我們在糖尿病視網膜病變、視網膜靜脈阻塞和濕性 AMD 方面已經完成了三項積極的 3 期研究。

We have strong and consistent six-month durability signal and favorable safety seen across the pivotal program. We have regulatory alignment now that's been achieved on a bridging strategy for our go-to-market formulation. The Phase 3 study, GLOW2 in diabetic retinopathy is now actively recruiting patients, and we've added as an additional arm tarcocimab into DAYBREAK to validate the durability in wet AMD to strengthen tarcocimab's competitive position and to bolster our ex-US regulatory dossier.

我們在整個關鍵計劃中看到了強烈且一致的六個月耐久性訊號和良好的安全性。我們現在已經在我們的上市配方的橋接策略上實現了監管協調。糖尿病視網膜病變的 GLOW2 3 期研究目前正在積極招募患者，我們已將 tarcocimab 作為額外的手臂添加到 DAYBREAK 中，以驗證濕性 AMD 的耐久性，以增強 tarcocimab 的競爭地位並支持我們的前美國監管檔案。

For 501, the Phase 1 study in DME met our objectives. We're developing it towards the high prevalence retinal vascular diseases, okay, to bring durability and the extra mechanisms to their -- we've created enhanced formulation from tarcocimab's commercial manufacturing scale-up with many potential benefits. And we're in the process of gaining or finalizing FDA alignment on the design of the Phase 3 DAYBREAK study in wet AMD and targeting an enrollment to start mid-year.

對於 501，DME 的第一階段研究達到了我們的目標。我們正在針對高盛行率的視網膜血管疾病開發它，好吧，為它們帶來耐久性和額外的機制——我們已經從特可昔單抗的商業生產規模中創造了增強的配方，具有許多潛在的好處。我們正在獲得或最終確定 FDA 對濕性 AMD 3 期 DAYBREAK 研究設計的一致性，並計劃在年中開始招募。

And for our diversified, let's say, KSI-101 program, we're developing it in a new area, macular edema associated with inflammation. We see it as a greenfield opportunity outside of the established anti-VEGF class and with risks and opportunities uncoupled from our ABC Platform and from our other two molecules.

對於我們的多元化項目，比如說 KSI-101 項目，我們正在一個新領域進行開發，即與發炎相關的黃斑水腫。我們將其視為已建立的抗 VEGF 類別之外的一個新機遇，並且風險和機會與我們的 ABC 平台和我們的其他兩種分子無關。

Our Phase 1b study is planned for the second quarter to identify two dose levels that we will then rapidly progress into pivotal studies. And we are in the process of gaining FDA alignment on the design of dual Phase 2b/3 pivotal studies, which also are planned for initiation this year.

我們的 1b 期研究計劃在第二季度進行，以確定兩個劑量水平，然後我們將迅速進入關鍵研究。我們正在就雙期 2b/3 期關鍵研究的設計獲得 FDA 的認可，這些研究也計劃於今年啟動。

Turning to slide 6. Tarcocimab is our most advanced program and we're one successful trial away from filing for registration in a success scenario in the trial GLOW2 will be conducted in a patient population of diabetic retinopathy. Our tarcocimab already showed a clear win in our GLOW1 study. GLOW2 is actively recruiting patients.

轉到投影片 6。Tarcocimab 是我們最先進的項目，我們距離申請註冊僅差一項試驗的成功，GLOW2 試驗將在糖尿病視網膜病變患者群體中進行。我們的 tarcocimab 在 GLOW1 研究中已經顯示出明顯的勝利。GLOW2 正積極招募患者。

At the same time, we plan to advance KSI-501 and KSI-101 rapidly into pivotal studies this year. The Phase 1 study of KSI-501 demonstrated positive signals on efficacy and safety and support further development. We are in discussion with the FDA on the study design of the Phase 3 DAYBREAK study in wet AMD and plan to initiate it as soon as regulatory alignment is achieved targeting mid-2024.

同時，我們計劃今年將 KSI-501 和 KSI-101 迅速推進關鍵研究。KSI-501 的 1 期研究顯示了有效性和安全性的正面訊號，並支持進一步的發展。我們正在與 FDA 討論濕性 AMD 3 期 DAYBREAK 研究的設計，並計劃在 2024 年中期實現監管協調後立即啟動研究。

We also intend to advance KSI-101 into a Phase 1 dose-finding study in the second quarter of this year to identify the two dose levels we want to be using in our dual pivotals. We're in the process of gaining regulatory feedback on the pivotal program design, and we hope to initiate two Phase 2b studies later this year.

我們還打算在今年第二季將 KSI-101 推進到 1 期劑量探索研究，以確定我們希望在雙關鍵藥物中使用的兩個劑量水平。我們正在收集關鍵項目設計的監管回饋，我們希望在今年稍後啟動兩項 2b 期研究。

Our goal is to have four pivotal studies ongoing later this year across the three programs; to service a broad and powerful BLA for tarcocimab; to service a new and powerful BLA for KSI-101; and one is half of what's needed for KSI-501 BLA.

我們的目標是在今年稍後對這三個項目進行四項關鍵研究；為 tarcocimab 提供廣泛而強大的 BLA 服務；為 KSI-101 提供新的、強大的 BLA；一個是 KSI-501 BLA 所需的一半。

Turning to slide 7. Now let's turn to our most advanced clinical program, tarcocimab. Tarcocimab is an anti-VEGF antibody biopolymer conjugate, or ABC medicine, built on the ABC platform to provide extended durability. It's been studied in six pivotal studies, three of which met their primary endpoints across the indications, diabetic retinopathy, retinal vein occlusion, and wet AMD. My view is tarcocimab can bring six-month durability to the majority of patients across the diseases.

轉到投影片 7。現在讓我們來看看我們最先進的臨床項目—特可昔單抗。Tarcocimab 是一種抗 VEGF 抗體生物聚合物綴合物，或 ABC 藥物，建立在 ABC 平台上，可提供更長的耐用性。六項關鍵研究對此進行了研究，其中三項在糖尿病視網膜病變、視網膜靜脈阻塞和濕性 AMD 等適應症上達到了主要終點。我的觀點是，特可昔單抗可以為大多數疾病的患者帶來六個月的持久性。

And that we can get there as an initiating therapy, not a maintenance therapy, and without leaving any patients behind irrespective of disease severity. That's the future as we see it. In our GLOW1 study in diabetic retinopathy, tarcocimab demonstrated for the first time among anti-VEGFs that six-month dosing can successfully treat DR patients by improving the disease severity scores and in reducing risk of vision-threatening complications by about 90%.

我們可以將其作為起始治療，而不是維持治療，無論疾病嚴重程度如何，都不會留下任何患者。這就是我們所看到的未來​​。在我們針對糖尿病視網膜病變的GLOW1 研究中，tarcocimab 在抗VEGF 藥物中首次證明，六個月的給藥可以透過改善疾病嚴重程度評分並將威脅視力的併發症的風險降低約90% 來成功治療DR患者。

In our BEACON study in retinal vein occlusion, tarcocimab demonstrated we could bring all RVO patients to once every two-month dosing versus the current standard of care, which is monthly dosing. And importantly, in the second six months of the study, tarcocimab was studied head-to-head against aflibercept on the same individualized dosing regimen. Approximately half of tarcocimab-treated patients were injection-free in the second six-months compared to about one-third of aflibercept-treated patients.

在我們針對視網膜靜脈阻塞的 BEACON 研究中，特可昔單抗證明我們可以讓所有 RVO 患者每兩個月給藥一次，而目前的護理標準是每月給藥一次。重要的是，在研究的後六個月中，在相同的個體化給藥方案下，對特可西單抗與阿柏西普進行了頭對頭研究。大約一半接受特可昔單抗治療的患者在後六個月內不再接受注射，而接受阿柏西普治療的患者中這一比例約為三分之一。

Over the entire one year of treatment, tarcocimab-treated patients achieved comparable vision anatomic outcomes with meaningfully fewer injections compared to aflibercept-treated patients, five versus seven.

在整個一年的治療過程中，與阿柏西普治療的患者相比，接受特可昔單抗治療的患者在註射次數明顯減少的情況下獲得了相當的視力解剖結果，分別為5 例和7 例。

Lastly, in our DAYLIGHT study in wet AMD, tarcocimab met its primary endpoints and demonstrated that intensive monthly dosing of tarcocimab was the safe and well-tolerated. These are important studies in big indications. Nonetheless, in our tarcocimab program, they are a point of departure, and their value comes when you finish things.

最後，在我們針對濕性 AMD 的 DAYLIGHT 研究中，tarcocimab 達到了主要終點，並證明每月密集給藥 tarcocimab 是安全且耐受性良好的。這些都是大適應症的重要研究。儘管如此，在我們的 tarcocimab 計劃中，它們是一個出發點，當您完成事情時，它們的價值就會體現出來。

So to that end, we have also, as I mentioned, made adjustments to the tarcocimab product that improve the manufacturability and may also enhance the utility of the product. And we have received FDA feedback that one additional successful pivotal study using the go-to-market material is sufficient to bridge the clinical scale material to the go-to-market material.

為此，正如我所提到的，我們也對特可昔單抗產品進行了調整，以提高可製造性，並可能增強產品的效用。我們收到 FDA 的回饋，即使用上市材料的另一項成功的關鍵研究足以將臨床規模材料與上市材料聯繫起來。

Not just to bring our go-to-market formulation -- not just to bridge our go-to-market formulation, but as of today, we have three positive Phase 3 studies of tarcocimab in three different diseases. And we will need one more successful pivotal study in one of these indications to file for approval.

不僅僅是為了將我們的製劑推向市場——不僅僅是為了將我們的製劑推向市場，而且截至今天，我們已經對特可昔單抗在三種不同疾病中進行了三項積極的3期研究。我們需要針對這些適應症之一進行一項更成功的關鍵研究來申請批准。

We plan to evaluate -- turning to slide 8, tarcocimab in two new Phase 3 studies, the GLOW2 study in diabetic retinopathy, and the DAYBREAK study in wet AMD. We've obtained FDA feedback on the study design of GLOW2, and it is already actively enrolling patients. The idea behind GLOW2 was to have a very high probability of success study.

我們計劃在兩項新的 3 期研究（糖尿病視網膜病變的 GLOW2 研究和濕性 AMD 的 DAYBREAK 研究）中評估 - 轉向幻燈片 8，tarcocimab。我們已經獲得 FDA 對 GLOW2 研究設計的回饋，並且已經在積極招募患者。GLOW2 背後的想法是獲得非常高的研究成功機率。

Therefore, the study designed for GLOW2 builds from GLOW1 and I see it as having a high real and perceived probability of success, so from an investor standpoint, I don't think you need to wait around to see the results to have some early confidence.

因此，為GLOW2 設計的研究是在GLOW1 的基礎上建立的，我認為它具有很高的真實和感知的成功機率，因此從投資者的角度來看，我認為您不需要等待看到結果才能有一些早期信心。

In addition, and after much consideration, we also intend to study tarcocimab as the second investigational arm in our wet AMD DAYBREAK study with three purposes: first, to demonstrate conclusively tarcocimab's durability in wet AMD; second, to strengthen tarcocimab's competitive position, given the importance of wet AMD in the anti-VEGF market; and third, to bolster tarcocimab's ex-US regulatory dossier. We're in the process of obtaining FDA feedback on the study design of DAYBREAK and hope to initiate recruitment mid-2024.

此外，經過深思熟慮，我們還打算將 tarcocimab 作為濕性 AMD DAYBREAK 研究中的第二個研究小組進行研究，其目的有三個：首先，最終證明 tarcocimab 在濕性 AMD 中的耐久性；其次，考慮到濕性 AMD 在抗 VEGF 市場中的重要性，加強 tarcocimab 的競爭地位；第三，加強 tarcocimab 的前美國監管檔案。我們正在收集 FDA 對 DAYBREAK 研究設計的回饋，並希望在 2024 年中期啟動招募。

Turning to slide 9, the GLOW2 study design built from the successful GLOW1 study, with the benefit of a third monthly loading dose at week four, as highlighted on the slide. We believe the three monthly loading dose regimen provides greater flexibility to patients and is nice to have as part of our VLA package. The primary endpoint is the proportion of eyes with two steps of greater improvement on DRSS at week 48, the same as GLOW1.

轉向投影片 9，GLOW2 研究設計是在成功的 GLOW1 研究的基礎上建立的，其優點是在第四週進行第三個月的負荷劑量，如幻燈片中突出顯示的那樣。我們相信三個月負荷劑量方案為患者提供了更大的靈活性，並且很高興將其作為我們 VLA 方案的一部分。主要終點是第 48 週時 ​​DRSS 出現兩級更大改善的眼睛比例，與 GLOW1 相同。

Turning to slide 10. Now let's turn to KSI-501, our second investigational medicine. 501 is a first-in-class, bispecific antibody biopolymer conjugate, or ABC, that inhibits both IL-6 and VEGF. IL-6 is a pro-inflammatory cytokine and growth factor implicated in pathophysiology of retinal vascular diseases. It is known to stimulate defective angiogenesis both by upregulating VEGF and by a VEGF-independent pathways.

轉到投影片 10。現在讓我們來看看我們的第二種研究藥物 KSI-501。 501 是一款一流的雙特異性抗體生物聚合物綴合物 (ABC)，可抑制 IL-6 和 VEGF。IL-6 是一種促發炎細胞因子和生長因子，與視網膜血管疾病的病理生理學有關。眾所周知，它可以透過上調 VEGF 和不依賴 VEGF 的途徑來刺激有缺陷的血管生成。

It is associated with anti-VEGF treatment resistance, as well as disease progression in AMD, DR, and RVO. 501 is designed with three tiers of innovation: first, a two-target mechanism, potently inhibiting both the dominant VEGF pathway and the IL-6 inflammation pathway; two, the potential for six-month durability based on Kodiak's ABC Platform; and three, an enhanced KSI-501 formulation, informed from tarcocimab's commercial manufacturing skill.

它與抗 VEGF 治療抗藥性以及 AMD、DR 和 RVO 的疾病進展有關。 501的設計具有三層創新：一是雙標靶機制，強效抑制主導的VEGF路徑與IL-6發炎路徑；二、基於 Kodiak 的 ABC 平台的六個月耐用性的潛力；第三，改良的 KSI-501 配方，源自 tarcocimab 的商業製造技術。

We believe the three tiers of innovation position KSI-501 well to address the unmet needs in high prevalence retinal vascular diseases, such as the need to target disease mechanisms beyond VEGF and the need for extended durability. As I mentioned above, the KSI-501 program is the result of the fine-tuning of our ABC Platform in the company over the past 10-plus years, and the program itself is a fast-forward. The design, the manufacturing, the clinical planning, and the operational expertise.

我們相信，三層創新使 KSI-501 能夠很好地解決高盛行率視網膜血管疾病中未滿足的需求，例如針對 VEGF 以外的疾病機制的需求以及延長耐久性的需求。正如我上面提到的，KSI-501專案是我們公司ABC平台十多年來微調的結果，專案本身是一個快轉。設計、製造、臨床規劃和營運專業知識。

Turning to slide 11. This slide is a reminder of the substantial variability in response to today's anti-VEGF standard of care agents, and therefore the need to bring additional disease mechanisms beyond VEGF into other therapies. As you can see from this data generated in our own pivotal wet AMD study, there is substantial interpatient variability in their response to anti-VEGF monotherapy, both in terms of visual acuity gains and fluid reduction.

轉到投影片 11。這張投影片提醒人們，當今抗 VEGF 標準護理藥物的反應存在很大差異，因此需要將 VEGF 以外的其他疾病機制引入其他療法。從我們自己的關鍵濕性 AMD 研究中產生的數據可以看出，患者對抗 VEGF 單一療法的反應存在很大的差異，無論是在視力增加還是液體減少方面。

A substantial proportion of patients underperform in vision and/or anatomical improvement compared to the mean responses, which highlights the need for additional mechanisms of action, and we believe KSI-501 can play an important role here.

與平均反應相比，相當大比例的患者在視力和/或解剖學改善方面表現不佳，這凸顯了對額外作用機制的需要，我們相信 KSI-501 可以在這裡發揮重要作用。

Turning to slide 12. The anti-IL-6 VEGF trap bispecific protein in KSI-501 has a unique design that enables it to potently inhibit one or more VEGF dimers and two IL-6 molecules simultaneously. The VEGF trap portion mimics the native receptor and binds multiple targets, including VEGF-1, VEGF-A, VEGF-B, and placental growth factor. The anti-IL-6 antibody binds IL-6, therefore inhibiting both IL-6 trans and cis signaling by its binding to soluble and membrane bound IL-6 receptors, respectively. Inhibition of IL-6 blocks IL-6 mediated inflammation and immune activation and normalizes blood retinal barriers.

轉到投影片 12。KSI-501 中的抗 IL-6 VEGF 捕獲雙特異性蛋白具有獨特的設計，使其能夠同時有效抑制一個或多個 VEGF 二聚體和兩個 IL-6 分子。VEGF 捕獲部分模仿天然受體並結合多個標靶，包括 VEGF-1、VEGF-A、VEGF-B 和胎盤生長因子。抗 IL-6 抗體結合 IL-6，因此透過其分別與可溶性和膜結合 IL-6 受體結合來抑制 IL-6 反式和順式訊號傳導。IL-6 的抑制可阻斷 IL-6 介導的發炎和免疫激活，並使血液視網膜屏障正常化。

Turning to slide 13. We conducted a Phase 1A, 1B-type study in DME patients that is now complete. The study was a multiple ascending dose study in DME patients, both treatment-naive and pre-treated patients. Four dose levels were studied in the phase one. Each subject received three monthly doses and was followed for 24 weeks, which allowed us to evaluate the safety, tolerability, and bioactivity signals of KSI-501.

轉到投影片 13。我們在 DME 患者中進行了一項 1A、1B 期研究，現已完成。該研究是一項針對 DME 患者（包括未接受治療和接受過治療的患者）的多次劑量遞增研究。第一階段研究了四種劑量水平。每位受試者每月接受三個月的劑量，並追蹤 24 週，這使我們能夠評估 KSI-501 的安全性、耐受性和生物活性訊號。

Turning to slide 14. We are pleased with the Phase 1 study results, where KSI-501 demonstrated strong visual acuity gains in both treatment-naive and pre-treated DME patients that were sustained over the 24-week study period. It also demonstrated meaningful CST reductions in patients.

轉到投影片 14。我們對 1 期研究結果感到滿意，其中 KSI-501 在未接受治療和接受過治療的 DME 患者中顯示出顯著的視力提高，並且在 24 週的研究期間持續有效。它還表明患者的 CST 顯著降低。

Though this was a small patient sample size, so we should try not to over-interpret the results, but rather we look for the essential signals that suggest this could be a molecule with meaningful therapeutic effects. The Phase 1 study also demonstrated that repeated monthly dosing of 501 was safe and well-tolerated. Overall, we think the Phase 1 study results support further clinical development of the 501 program.

儘管這是一個很小的患者樣本量，所以我們應該盡量不要過度解釋結果，而是尋找表明這可能是具有有意義的治療效果的分子的基本信號。第一階段研究也表明，每月重複服用 501 是安全且耐受性良好的。總體而言，我們認為 1 期研究結果支持 501 計畫的進一步臨床開發。

Turning to slide 15, we're planning to advance KSI-501 into a Phase 3 study in wet AMD called DAYBREAK later this year. There is abundant preclinical and clinical evidence for the role of IL-6 in choroidal neovascularization, both in terms of driving disease pathogenesis and also in mediating treatment response to anti-VEGF agents and disease reactivations.

轉向幻燈片 15，我們計劃在今年稍後將 KSI-501 推進濕性 AMD 的第 3 期研究，稱為 DAYBREAK。有豐富的臨床前和臨床證據證明 IL-6 在脈絡膜新生血管形成中的作用，無論是在驅動疾病發病機制方面，還是在介導抗 VEGF 藥物的治療反應和疾病再活化方面。

We believe three-tiered innovation designed into KSI-501, as mentioned before, namely the bispecific mechanism of action, the potential for the six-month durability based on the ABC platform, and the enhanced formulation, position the molecule well to address the unmet needs in wet AMD.

我們相信，如前所述，KSI-501 設計的三層創新，即雙特異性作用機制、基於ABC 平台的六個月耐久性潛力以及增強的配方，使該分子能夠很好地解決未滿足的問題濕 AMD 的需求。

The DAYBREAK study is intended to be a non-inferiority study to evaluate the efficacy, durability, and safety of KSI-501 and tarcocimab in wet AMD against aflibercept 2mg. Both 501 and tarcocimab will be dosed on extended regimen from every four to 24 weeks while aflibercept 2mg will be dosed per label.

DAYBREAK 研究旨在成為一項非劣效性研究，旨在評估 KSI-501 和 tarcocimab 相對於 aflibercept 2mg 在濕性 AMD 中的療效、持久性和安全性。501 和 tarcocimab 都將以每 4 至 24 週的延長療程給藥，而阿柏西普 2mg 將按標籤給藥。

The study will use the go-to-market formulations for both 501 and tarcocimab that improve the manufacturability in a pre-filled syringe, and they also enhance the utility of the products. We are currently in conversation with the FDA to obtain feedback on the study design for DAYBREAK and intend to initiate enrollment as soon as alignment is achieved, targeting mid-2024.

該研究將使用 501 和 tarcocimab 的上市配方，以提高預填充注射器的可製造性，並且還增強產品的實用性。我們目前正在與 FDA 進行對話，以獲取有關 DAYBREAK 研究設計的回饋，並打算在達成協議後立即開始入組，目標是 2024 年中期。

Turning to slide 16. Now we'll turn our attention to our third investigational medicine, KSI-101. This is the unconjugated protein portion of KSI-501 with the same anti-IL-6 and VEGF trap design and its unique features as we mentioned previously. This is a greenfield development opportunity for us as it focuses on a market outside the established anti-VEGF market.

轉到投影片 16。現在我們將注意力轉向我們的第三種研究藥物 KSI-101。這是 KSI-501 的未結合蛋白部分，具有與我們之前提到的相同的抗 IL-6 和 VEGF 陷阱設計及其獨特功能。這對我們來說是一個全新的發展機會，因為它專注於現有抗 VEGF 市場以外的市場。

KSI-101 also is independent from ABC Platform with opportunities and risks uncoupled from the platform, which presents a healthy diversification. With its bispecific anti-inflammatory mechanism of action, high potency on both targets, and high formulation strength at 100 milligrams per ml, this is a powerful medicine, and we are exploring it through difficult conditions, what we call the uveitic complex of diseases, that as hallmark. have macular edema -- that's retinal edema, and inflammation, and for which no intravitreal biologic therapies exist today.

KSI-101也獨立於ABC平台，機會與風險與平台脫鉤，呈現健康的多元化。憑藉其雙特異性抗炎作用機制、對兩個靶點的高效力以及每毫升100 毫克的高配方強度，這是一種強大的藥物，我們正在通過困難的條件（我們稱之為葡萄膜炎複合體疾病）來探索它，以此為標誌。患有黃斑水腫－即視網膜水腫和炎症，目前尚無玻璃體內生物療法。

Turning to slide 17. Current treatments for patients with macular edema associated with retinal inflammation show limited efficacy and many undesirable and potentially serious side effects. Treatment is generally nonspecific, such as steroids and immunomodulators. There is only one approved biologic therapy, adalimumab, which is an anti-TNF alpha agent that is administered systemically, but it also is associated with limited treatment efficacy and serious side effects.

轉到投影片 17。目前對患有與視網膜發炎相關的黃斑水腫患者的治療效果有限，並且存在許多不良且潛在的嚴重副作用。治療通常是非特異性的，例如類固醇和免疫調節劑。只有一種被批准的生物療法，即阿達木單抗，它是一種全身給藥的抗 TNF α 藥物，但它也具有有限的治療效果和嚴重的副作用。

There are no approved intravitreal biologic therapies today that target the underlying disease mechanism. We believe this disease area is prime for a powerful, safe, and effective branded intravitreal biologic therapy to change the treatment paradigm.

目前還沒有針對潛在疾病機制的經批准的玻璃體內生物療法。我們相信，該疾病領域是強大、安全、有效的品牌玻璃體內生物療法的主要領域，可以改變治療模式。

Turning to slide 18. We plan to advance KSI-101 into a dose-finding Phase 1b study in the second quarter of this year to identify the two dose levels to progress into our pivotals. We are currently in the process of obtaining FDA feedback on the design of the pivotal program here for KSI-101 and hope to initiate two Phase 2b/3 pivotal studies later in 2024.

轉到投影片 18。我們計劃在今年第二季將 KSI-101 推進到劑量探索 1b 期研究，以確定進入關鍵階段的兩個劑量水平。我們目前正在獲取 FDA 對 KSI-101 關鍵項目設計的回饋，並希望在 2024 年稍後啟動兩項 2b/3 期關鍵研究。

Turning to slide 19 and summarizing. In summary, we're excited to be on plan to advance our three clinical programs into Phase 3 studies in 2024, with GLOW2 for tarcocimab already in the rolling, with DAYBREAK up next, and bringing forward two of our molecules, KSI-501 as well as tarcocimab.

轉到投影片 19 並進行總結。總而言之，我們很高興計劃在 2024 年將我們的三個臨床項目推進到 3 期研究，其中用於 tarcocimab 的 GLOW2 已經在滾動中，接下來是 DAYBREAK，並將我們的兩個分子 KSI-501 作為以及塔可昔單抗。

And then, dual pivotals for KSI-101 in planning. We are at a point of departure and we're in motion, and we have our eyes focused on delivering meaningful Phase 3 BLA-facing value inflection points within our current cash runway.

然後，KSI-101 的雙重樞紐正在規劃中。我們正處於一個出發點，我們正在行動，我們的重點是在我們當前的現金跑道內提供有意義的、面向 BLA 的第 3 階段的價值拐點。

Now we will open the floor to analysts for questions. Operator?

現在我們將請分析師提問。操作員？

(Operator Instructions) Michael Yee, Jefferies.

（操作員說明）Michael Yee，Jefferies。

Hi, good afternoon. This is Jiajun Wen on the line for Michael Yee. Thanks for taking my questions. I have two questions regarding the 501 bispecific pivotal study. I noticed that there are multiple arms for tarcocimab and KSI-501 in that study. I wonder if those patients will be randomized to each of the arms at the beginning or they would be treated as needed and give them more flexibility of dosing. And what's your estimate of the sample size?

嗨，下午好。我是 Michael Yee 的 Wen Jiajun。感謝您回答我的問題。我有兩個關於 501 雙特異性關鍵研究的問題。我注意到該研究中有多個針對 tarcocimab 和 KSI-501 的研究。我想知道這些患者是否會在開始時被隨機分配到每個組，或者他們會根據需要接受治療並給予他們更大的劑量靈活性。您對樣本量的估計是多少？

And second question is, can you clarify if you plan to include data from the [DAYPARK] the phase -- the pivotal study for 501 as well in the same BLA filing of tarcocimab?

第二個問題是，您能否澄清一下，您是否計劃將來自 [DAYPARK] 階段（501 的關鍵研究）的數據也包含在 tarcocimab 的同一份 BLA 申請中？

Thanks. But to try to make sure that we understood the question. It's around the DAYBREAK study, and that study is planned to include aflibercept as the comparator and then to include arms for tarcocimab as well as KSI-501. So the first objective of including an experimental arm with tarcocimab in this study is it's very efficient economically for us and operationally. But also the data from the study, will, yes, be included in the BLA filing for tarcocimab.

謝謝。但要盡力確保我們理解這個問題。這是圍繞 DAYBREAK 研究進行的，該研究計劃包括阿柏西普作為比較藥物，然後包括 tarcocimab 和 KSI-501 的治療組。因此，在本研究中納入 tarcocimab 實驗組的首要目標是，它對我們來說在經濟和操作上都非常有效。是的，該研究的數據也將包含在 tarcocimab 的 BLA 備案中。

So our objective on the timing of the DAYBREAK study and also the GLOW2 study are for those studies to finish at approximately the same time and to see the same BLA. So that's an important element.

因此，我們對 DAYBREAK 研究和 GLOW2 研究的時間安排的目標是讓這些研究大致在同一時間完成並獲得相同的 BLA。所以這是一個重要的因素。

Then on the study design for DAYBREAK, we're still in discussions with FDA to make sure that we get to the study that meets our needs. Our objective is to include durability for both tarcocimab and the KSI-501 and to be able to go from monthly dosing all the way through six-month dosing to be able to showcase the power of our ABC Platform medicines from the standpoint of immediacy, but also their powerful durability.

然後，關於 DAYBREAK 的研究設計，我們仍在與 FDA 進行討論，以確保我們的研究能夠滿足我們的需求。我們的目標是包括 tarcocimab 和 KSI-501 的耐久性，並且能夠從每月給藥一直到六個月給藥，以便能夠從即時性的角度展示我們 ABC 平台藥物的力量，但是還有它們強大的耐用性。

So does that mean that you would have multiple arms of tarcocimab as well as 501. And that essentially requires a big study for you to run?

那麼這是否意味著您將擁有 tarcocimab 和 501 的多個分支。這本質上需要您進行大量研究才能進行？

We haven't disclosed the precise design of the study yet. As you know, within ophthalmology, the regulatory landscape is evolving. One of our core objectives for the DAYBREAK study is that it be cost effective. Kodiak has a substantial amount of experience running many of these studies in the big diseases in retina. And so obviously, we're going to trying not to have more groups than we need to have to be able to like achieve our objectives. So let's stay tuned and see where we come out on the study design.

我們尚未透露該研究的具體設計。如您所知，在眼科領域，監管環境正在不斷發展。我們 DAYBREAK 研究的核心目標之一是它具有成本效益。科迪亞克在針對視網膜重大疾病進行許多此類研究方面擁有豐富的經驗。顯然，我們將盡量避免擁有超出實現目標所需數量的團體。因此，讓我們繼續關注，看看我們的研究設計結果如何。

Got it. Thank you.

知道了。謝謝。

Michael DiFiore, Evercore ISI.

邁克爾·迪菲奧裡，Evercore ISI。

Hi, guys. Thanks for doing the call and for taking my question. A few questions from me. Number one, regarding the upcoming Phase 3 DAYBREAK trial. I know the design is currently being finalized, but if you could provide any color on what dose will be used. And a follow-up question to that is how is the enhanced KSI-501 formulation different from the formulation used in the recent prior Phase 1 DNA study? And I have a follow-up.

嗨，大家好。感謝您撥打電話並回答我的問題。我有幾個問題。第一，關於即將進行的第 3 階段 DAYBREAK 試驗。我知道設計目前正在最終確定，但您是否可以提供有關將使用的劑量的任何顏色。後續問題是增強型 KSI-501 配方與最近的 1 期 DNA 研究中使用的配方有何不同？我有一個後續行動。

For the DAYBREAK study, the plan is to use a similar 100 microliter volume. So therefore, it will be driven by the formulation strength of the formulations themselves. So both the tarcocimab and the KSI-501 formulations are 50 mg per ml strength. For this pivotal at 100 microliters, so there'll be 5 milligrams each.

對於 DAYBREAK 研究，計劃使用類似的 100 微升體積。因此，它將由配方本身的配方強度所驅動。因此，tarcocimab 和 KSI-501 製劑的濃度均為 50 mg/ml。對於這個關鍵的 100 微升，所以每個是 5 毫克。

And each one of those molecules will be in their, what we call, kind of go-to-market formulation or commercial scale-up formulation, which, as we've mentioned, does include adjustments from what was tested previously with tarcocimab in our pivotal program and also what was used in the Phase 1 program for KSI-501.

這些分子中的每一種都將採用我們所說的一種上市製劑或商業放大製劑，正如我們所提到的，其中確實包括對我們之前用特可昔單抗進行的測試的調整。以及KSI-501 第一階段計畫中所使用的內容。

So as I said, we're at an important point of departure as we step into these new studies with these adjusted and enhanced formulations, and we're excited to be able to showcase what these molecules can do in these next set of pivotals.

正如我所說，當我們透過這些調整和增強的配方進入這些新研究時，我們正處於一個重要的出發點，我們很高興能夠展示這些分子在下一組關鍵中的作用。

Got it. Got it. That's helpful. And I guess my follow-up question is, I just want to clarify why exactly tarcocimab is being added as an active comparator in the DAYBREAK trial. Is it correct to assume that the FDA is not requiring this, and that Kodiak is proactively doing this in order to have dosing flexibility on the label?

知道了。知道了。這很有幫助。我想我的後續問題是，我只是想澄清為什麼在 DAYBREAK 試驗中將 tarcocimab 添加為活性比較劑。假設 FDA 不要求這樣做，而 Kodiak 主動這樣做是為了在標籤上實現劑量彈性，這樣的假設是否正確？

We really struggled somewhat with what to do to finish the tarcocimab program. And I would say it took us some months to figure out what we wanted our plan to be. And on the one hand, we wanted to lean into additional work in wet AMD because that represents a large part of the market, right, for the anti-VEGFs. On the other hand, we didn't want to run the study where, let's say, different stakeholders or investors were worried about the probability of success because we have so much hanging on the outcome.

我們確實在如何完成 tarcocimab 專案方面遇到了一些困難。我想說的是，我們花了幾個月的時間才弄清楚我們想要的計劃是什麼。一方面，我們希望在濕性 AMD 領域進行更多工作，因為這代表了抗 VEGF 市場的很大一部分。另一方面，我們不想在不同的利害關係人或投資者擔心成功的可能性的情況下進行這項研究，因為我們對結果有太多的把握。

So in the end, we decided to run the GLOW2 study as our core study for approval for tarcocimab which we can -- which will have a very high probability of success given that it's essentially the same study as GLOW1, which was a tremendously successful outcome.

因此，最後，我們決定將 GLOW2 研究作為我們批准 tarcocimab 的核心研究，因為它與 GLOW1 本質上是相同的研究，因此成功的可能性非常高，而 GLOW1 是一個非常成功的結果。

And then, in addition, we decided that we would tuck in an additional group into the pivotal study we wanted to run for KSI-501. So economically, it's very cash efficient to tuck that in, having decided to run that additional wet AMD study then we'll end up with the DAYLIGHT study as a successful study, and we hope the DAYBREAK study also as a successful study for tarcocimab. And our overall package will then include five successful, we hope, pivotal studies for tarcocimab.

此外，我們也決定將額外的小組納入我們想要為 KSI-501 進行的關鍵研究中。因此，從經濟角度來看，將其納入其中是非常經濟的，在決定進行額外的濕性AMD 研究後，我們最終會將DAYLIGHT 研究作為一項成功的研究，我們希望DAYBREAK 研究也作為tarcocimab 的一項成功研究。我們的整體計畫將包括五項成功的、我們希望的、針對特可昔單抗的關鍵研究。

And at the same time, we're checking a box for KSI-501, and it will be the first in its two pivotal studies that we'll need to file for BLA. So if you think about Kodiak's program with three what I call late-phase molecules, right, with all of them being run in pivotal studies starting imminently, that's the philosophy that we're bringing to the next several years of Kodiak's development.

同時，我們正在勾選 KSI-501，這將是我們需要提交 BLA 的兩項關鍵研究中的第一個。因此，如果你考慮一下科迪亞克的項目，其中包含三種我稱之為後期分子的項目，對吧，所有這些分子都在即將開始的關鍵研究中運行，這就是我們為科迪亞克未來幾年的開發帶來的理念。

Got it. Very helpful. Thanks so much.

知道了。非常有幫助。非常感謝。

Anupam Rama, JPMorgan.

阿努帕姆‧拉瑪，摩根大通。

Hi. Thanks for taking our question. This is actually Malcolm on for Anupam. So just one from us. What is being assumed in terms of milestones between now and your -- the end of your cash runway into 2026?

你好。感謝您提出我們的問題。這實際上是 Malcolm 為 Anupam 所做的。所以我們只提供一份。從現在到 2026 年現金跑道結束之間的里程碑假設是什麼？

Well, certainly, the completion of the two tarcocimab pivotals as well as the completion of the 501 pivotal. And we're in discussions with FDA currently on the design of the Phase 2b/3 studies for 101 and depending a little bit on those designs and how they translate into enrollment, we're hopeful that we'll be able to get those studies out in that timeframe as well.

嗯，當然，兩個 tarcocimab 關鍵藥物的完成以及 501 關鍵藥物的完成。我們目前正在與 FDA 討論 101 的 2b/3 期研究的設計，並且根據這些設計以及它們如何轉化為入組，我們希望能夠獲得這些研究也在那個時間範圍內。

Great. Thank you.

偉大的。謝謝。

Andrea Tan, Goldman Sachs.

安德里亞·譚，高盛。

Thanks for taking the question. Two for us, please. Maybe as a follow-up to a prior comment, recognizing that the potency remains the same between the two formulations that you have, can you share what -- or maybe speak to what data you've seen that supports that durability of the original formulation will carry over as you transition from the biopolymer conjugate to now a mix of the conjugate plus three antibody?

感謝您提出問題。請給我們兩個。也許作為先前評論的後續行動，認識到您擁有的兩種配方之間的效力保持不變，您能否分享什麼 - 或者也許談談您所看到的支持原始配方耐久性的數據當您從生物聚合物綴合物過渡到現在綴合物加三種抗體的混合物時，會保留下來嗎？

Thanks, Andrea. Well, that's a good question. We believe more broadly that disease variability in patients is what drives durability more strongly than the amount of conjugate that we have. So, for example, in our Phase 1b study, we tested 2.5 mgs versus 5 mgs of fully conjugated material, and there's very little distinction between the durability that we saw in the 2.5 milligram dose and the 5 milligram dose.

謝謝，安德里亞。嗯，這是個好問題。我們更廣泛地認為，患者的疾病變異性比我們擁有的綴合物的數量更能促進耐久性。例如，在我們的 1b 期研究中，我們測試了 2.5 毫克與 5 毫克完全結合材料，並且我們在 2.5 毫克劑量和 5 毫克劑量中看到的耐久性之間幾乎沒有區別。

So as we bring the level of conjugate down on the margin to allow a broader amount of free protein, we believe that we can bring the best of both worlds into both the tarcocimab and the KSI-501 formulations without impacting durability and creating a powerful medicine for patients.

因此，當我們稍微降低結合物的水平以允許更多量的遊離蛋白質時，我們相信我們可以將特可昔單抗和KSI-501 配方中的優點結合起來，而不會影響耐久性並創造出一種強效藥物對於患者。

Got it. And then just maybe one quickly on the Phase 1 data that you have seen in DME for the 16 patients from the Phase 1. Could you just share -- speak a little bit more about what gives you the confidence to move directly from that in the 16 patients to a Phase 3 trial now in wet AMD?

知道了。然後可能只是快速了解您在 DME 中看到的第一階段 16 名患者的第一階段數據。您能否分享一下——更多地談談是什麼讓您有信心從 16 名患者的試驗直接轉向目前針對濕性 AMD 的 3 期試驗？

Well, that's a good question. The important point about the Phase 1 study with KSI-501 was to gauge safety as well as to gauge bioactivity in terms of vision and OCT. And given the broad overlap across the retinal vascular diseases and with the existing agents, the idea of starting in DME where you can see predictable responses of bioactivity and safety and then using that kind of as a point of departure into any number of the different diseases.

嗯，這是個好問題。KSI-501 第一階段研究的重點是評估安全性以及評估視力和 OCT 方面的生物活性。考慮到視網膜血管疾病和現有藥物的廣泛重疊，從 DME 開始的想法是，您可以看到生物活性和安全性的可預測反應，然後使用這種作為研究許多不同疾病的起點。

So I mean the four reasons that give us confidence to move directly into Phase 3 in wet AMD, based on the KSI-501 Phase 1 is one, I mean, the durability profile of the platform; two, the dual mechanism of action, right, with best-in-class VEGF inhibition from the trap and where we also target IL-6, which is a known culprit of suboptimal response and reactivation of disease in wet AMD.

因此，我的意思是，讓我們有信心直接進入基於 KSI-501 第 1 階段的濕 AMD 第 3 階段的四個原因是，我的意思是，平台的耐用性；第二，雙重作用機制（右），具有來自陷阱的一流 VEGF 抑製作用，並且我們還靶向 IL-6，IL-6 是濕性 AMD 中反應欠佳和疾病重新激活的已知罪魁禍首。

Third is our enhanced formulation. And four, the 10 years of design, the manufacturing in the clinical and the operational experience that we have, the three INDs, the three molecules in clinical phase, the two first in-human studies, the eight clinical trials, seven of them pivotal. So we're not starting from scratch here. And furthermore, in the future, we may be thinking of exploring KSI-501 in DME and RVO as well.

第三是我們的強化配方。第四，我們擁有的 10 年設計、臨床製造和營運經驗、三個 IND、處於臨床階段的三個分子、兩項首次人體研究、八項臨床試驗，其中七項是關鍵的。所以我們並不是從頭開始。此外，未來我們可能還會考慮在 DME 和 RVO 中探索 KSI-501。

Got it. Okay. Thanks so much.

知道了。好的。非常感謝。

Gena Wang, Barclays.

王吉娜，巴克萊銀行。

Thank you for taking my question. Victor, based on current data, do you believe 501 is better than tarcocimab? And a related question is for DAYBREAK, other than being cost-effective to avoid running an independent Phase 3 study for tarcocimab, will you try to design in a way to power to show the clinical benefit differences between 501 versus tarcocimab?

感謝您回答我的問題。Victor，根據目前的數據，您認為 501 比 tarcocimab 更好嗎？DAYBREAK 的一個相關問題是，除了避免對 tarcocimab 進行獨立的 3 期研究具有成本效益之外，您是否會嘗試以一種方式進行設計，以有力地顯示 501 與 tarcocimab 之間的臨床益處差異？

I don't think it's important whether tarcocimab or 501, whether one is better than the other. There's clearly an opportunity for, let's say, twice a year in the majority of patient anti-VEGF agent and tarcocimab just needs to get pushed over the finish line. And why don't we see how physicians like it.

我認為特可昔單抗還是501，哪個比另一個更好並不重要。顯然，對於大多數患者來說，每年有兩次抗 VEGF 藥物和 tarcocimab 的機會，只需將其推過終點線即可。為什麼我們不看看醫生們有多喜歡它呢？

And by running GLOW2 and having that tuck-in group in the DAYBREAK study in wet AMD, we're going to be creating a useful amount of data for physicians for tarcocimab. It's not our objective to power a distinction between tarcocimab and 501 in DAYBREAK.

透過執行 GLOW2 並讓該小組參與濕性 AMD 的 DAYBREAK 研究，我們將為醫生​​創建大量有用的 tarcocimab 數據。我們的目標並不是在 DAYBREAK 中區分 tarcocimab 和 501。

I mean if 501 showed maybe some trend that it was better than aflibercept or better than tarcocimab, we see that as very positive because we're obsoleting those agents with our own agent. And the question there for the 501 program is it's going to need a second pivotal. And so at what point do we think it would be useful and important to start that such that it's a molecule that could be on a point or path to enter the market. I mean, if both molecules perform as we hope, right, tarcocimab and 501, showing a differentiated durability profile, and they both meet the primary endpoint, it's a problem that we would be delighted to have.

我的意思是，如果 501 顯示出某種趨勢，表明它比阿柏西普或塔可昔單抗更好，我們認為這是非常積極的，因為我們正在用我們自己的藥物取代這些藥物。501 計劃的問題是它需要第二個關鍵點。因此，我們認為在什麼時候開始這樣做是有用且重要的，這樣它就可以成為進入市場的某個點或路徑上的分子。我的意思是，如果特可昔單抗和501 這兩種分子都如我們所希望的那樣發揮作用，顯示出不同的耐久性特徵，並且它們都滿足主要終點，那麼我們會很高興遇到這個問題。

Okay. Thank you.

好的。謝謝。

Ellie Merle, UBS.

艾莉·梅爾，瑞銀。

It's Sam on for Ellie. We just had two questions. I guess, first, where do you think about how IL-6 inflammation is -- or like where do you think IL-6 inflammation is particularly relevant in the context of this space? And then I'll ask my second after.

山姆替艾莉上場。我們只有兩個問題。我想，首先，您如何看待 IL-6 發炎——或者您認為 IL-6 發炎在該領域的哪些方面特別相關？然後我會問我的第二個。

Well, I think we believe that it's broadly relevant, both within the high-prevalence diseases that represent the anti-VEGF market, and we believe it's highly relevant outside of that into what we call sort of that greenfield area of macular edema and inflammation or the uveitic complex. And we believe those are two different opportunities, and that's why we have two different molecules to be able to develop into both of them, right? So the KSI-101 allows us to have the protein alone, which is really a sledgehammer, highly potent on the two mechanisms at a very high formulation strength, that should have a strong immediacy.

嗯，我認為我們相信它具有廣泛的相關性，無論是在代表抗VEGF 市場的高盛行率疾病中，還是在我們所說的黃斑水腫和發炎的未開發區域或其他領域都具有高度相關性。我們相信這是兩個不同的機會，這就是為什麼我們有兩種不同的分子能夠發展成這兩種，對嗎？因此，KSI-101 使我們能夠單獨擁有蛋白質，這實際上是一把大錘，以非常高的配方強度對兩種機制非常有效，應該具有很強的即時性。

So we're excited about that. And obviously IL-6 plays a very important role in driving the macular edema in those patients and also in driving the inflation. Within the retinal vascular diseases, inflammation clearly plays an important role.

所以我們對此感到興奮。顯然，IL-6 在驅動這些患者的黃斑水腫以及驅動膨脹方面發揮著非常重要的作用。在視網膜血管疾病中，發炎顯然起著重要作用。

I think the question though, when you think about the drug development, what is necessary to show in a pivotal program and do you want to play around for several years in Phase 2 studies, trying to explore what large subgroups within, say, wet AMD, right, or what large subgroup within DME, right, where that inflammation is driving elements of the efficacy or the lack of efficacy in those patients.

不過，我認為問題是，當您考慮藥物開發時，在關鍵計劃中需要展示什麼，您是否想在第二階段研究中進行數年，試圖探索濕性 AMD 中的哪些大亞組，對，或者DME中的哪個大亞組，對，發炎是影響這些患者療效或缺乏療效的因素。

So rather than take that approach, what we're planning to do is to run the non-inferiority pivotals to get the molecule approved in the different indications based on our expertise in running those studies and then work either in parallel or in smaller studies or investigator-sponsored studies or post-approval to be able to really tie patients with high inflammation to the drug to be able to show some improved level of efficacy.

因此，我們不採取這種方法，而是計劃運行非劣效性關鍵點，根據我們運行這些研究的專業知識，使該分子在不同的適應症中獲得批准，然後並行或在較小的研究中進行工作，或研究者發起的研究或批准後能夠真正將高發炎患者與藥物聯繫起來，從而能夠顯示出一定程度的療效改善。

But we don't think we need to do that in a Phase 2 setting. We can drive these molecules for approval in the noninferiority setting and then work with physicians to showcase the special contribution of the mechanism.

但我們認為我們不需要在第二階段的環境中這樣做。我們可以推動這些分子在非劣效性環境中獲得批准，然後與醫生合作展示機制的特殊貢獻。

Okay. Great. Makes a lot of sense. And then just a quick follow-up. For DAYBREAK, you mentioned dosing 501 every four to 24 weeks and then dosing aflibercept according to label. What is your perspective on the recent FDA draft guidance regarding the use of the comparable dosing regimen in terms of like dosing frequency with the active comparator?

好的。偉大的。很有道理。然後進行快速跟進。對於 DAYBREAK，您提到每 4 至 24 週服用 501，然後根據標籤服用阿柏西普。您對 FDA 最近關於使用類似給藥方案（在與活性比較藥物相似的給藥頻率方面）的指南草案有何看法？

Yeah. Well, that's a good question. I think we've been in constant communication with the agency for all three clinical programs. And we'll confirm the study design once we have all the information necessary. And that's really all we want to share for now in terms of the specifics. It's needless to say, but the final study design for all of our pivotals will be based on feedback from the FDA.

是的。嗯，這是個好問題。我認為我們一直在與該機構就所有三個臨床項目保持持續溝通。一旦我們掌握了所有必要的信息，我們將確認研究設計。這就是我們現在想要分享的具體細節。不用說，我們所有關鍵點的最終研究設計都將基於 FDA 的回饋。

I do think historically, looking back, Kodiak has driven innovation within study design with FDA successfully for ourselves and other companies have followed our example. And at this stage, we're in discussion, and we'll see where we end up.

我確實認為，從歷史上看，Kodiak 已經成功地推動了 FDA 的研究設計創新，其他公司也紛紛效仿我們的榜樣。在這個階段，我們正在討論，我們會看看最終結果如何。

Great. Thank you so much.

偉大的。太感謝了。

(Operator Instructions) Daniil Gataulin, Chardan.

（操作員說明）Daniil Gataulin，Chardan。

Hey. Good afternoon and thank you for taking the question. I have one on 501 in wet AMD. Specifically for the second pivotal study, are you guiding for -- as regards of any timelines when you plan on starting that trial? And will that also include tarcocimab? Or do you plan to generate tarcocimab data from DAYBREAK first before initiating the second study?

嘿。下午好，感謝您提出問題。我有一張 501 濕 AMD 的。特別是對於第二項關鍵研究，您是否對計劃開始試驗的時間表有指導？這也包括特可昔單抗嗎？或者您是否計劃在開始第二項研究之前先從 DAYBREAK 產生 tarcocimab 資料？

Yeah, we don't -- we haven't -- we haven't disclosed, and we don't have a complete plan for the second study of wet AMD. We know that we have -- that we need one for approval for 501 in that case, but we haven't thought -- we haven't disclosed until we have a plan of its sequential or is it somewhat overlapped between the two studies.

是的，我們沒有——我們沒有——我們沒有透露，我們也沒有針對濕性 AMD 的第二次研究的完整計劃。我們知道，在這種情況下，我們需要一個批准 501 的方案，但我們沒有想到，直到我們制定了一個連續的計劃，或者兩項研究之間有一些重疊，我們才披露這一情況。

Got it. And I have another quick question on what do you think are the potential consequences if the customer does not succeed in a DAYBREAK study?

知道了。我還有另一個簡單的問題，如果客戶在 DAYBREAK 研究中沒有成功，您認為潛在的後果是什麼？

Well, I guess -- we believe that tarcocimab can be an important medicine for patients with wet AMD. But rather than just relying on the results of the DAYLIGHT study where we dose monthly, we've decided that it makes sense to demonstrate that by having a full group in DAYBREAK.

嗯，我想──我們相信特可昔單抗可以成為濕性 AMD 患者的重要藥物。但我們不只是依賴每月一次的 DAYLIGHT 研究結果，而是決定透過在 DAYBREAK 中建立一個完整的小組來證明這一點是有意義的。

So if we didn't meet the endpoint in DAYBREAK then physicians would not feel excited to use it in wet AMD or presumably maybe based on having two unsuccessful studies in wet AMD, we might not be able to get approval in the indication. So it represents a bet that we're making. We're optimistic and we think it can drive substantial demand in wet AMD for tarcocimab and be really important.

因此，如果我們沒有達到 DAYBREAK 的終點，那麼醫生就不會興奮地將其用於濕性 AMD，或者可能基於兩項濕性 AMD 的不成功研究，我們可能無法獲得該適應症的批准。所以它代表了我們正在做的一個賭注。我們很樂觀，我們認為它可以推動濕性 AMD 對 tarcocimab 的大量需求，而且非常重要。

So in some way, introducing tarcocimab into the DAYBREAK study is a gamble, but it's one that's educated based on our detailed review of our data and also the adjustments that we've made to the go-to-market material and also our, I suppose, expertise or lessons learned from having run six pivotal so far. So we're excited to run tarcocimab in DAYBREAK and to see the data and hopefully to include that and to share that with the community and we think it can be really powerful.

因此，在某種程度上，將 tarcocimab 引入 DAYBREAK 研究是一場賭博，但這是一個基於我們對數據的詳細審查以及我們對上市材料和我們的，我所做的調整的教育。 ，從運行的六次中獲得的專業知識或經驗教訓至關重要。因此，我們很高興能夠在 DAYBREAK 中運行 tarcocimab 並查看數據，並希望將其納入其中並與社區分享，我們認為它非常強大。

Got it. Thank you very much.

知道了。非常感謝。

Thank you. And I'm not showing any further question at this time. I would now like to turn it back to our CEO, Victor Perlroth, for any closing remarks.

謝謝。目前我不會提出任何進一步的問題。現在我想請我們的執行長 Victor Perlroth 發表結束語。

I think we're done. Thanks very much. We look forward to people digesting all of this new information about Kodiak and our plans and look forward to the next steps of information, especially on the new study designs as we finalize them. Thanks. Thanks so much.

我想我們已經完成了。非常感謝。我們期待人們消化有關 Kodiak 和我們計劃的所有新信息，並期待下一步的信息，特別是我們最終確定的新研究設計。謝謝。非常感謝。

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.

感謝您參加今天的會議。這確實結束了該程式。您現在可以斷開連線。大家，祝你有美好的一天。