Cognition Therapeutics Inc (CGTX) 2023 Q4 法說會逐字稿

Hello, everyone, and welcome to Cognition Therapeutics fourth quarter 2023 earnings call. Please note that this call is being recorded. I'd now like to hand over to our first speaker for today, Mike Moyer. Please go ahead.

大家好，歡迎參加 Cognition Therapeutics 2023 年第四季財報電話會議。請注意，此通話正在錄音。現在我想請今天的第一位發言人 Mike Moyer 發言。請繼續。

Thank you, operator, and good morning, everyone. Welcome to the Cognition Therapeutics fourth quarter and year end 2023 results conference call. With me today are Lisa Ricciardi, President and Chief Executive Officer; John Doyle, Chief Financial Officer; and Dr. Tony Caggiano, Chief Medical Officer.

謝謝接線員，大家早安。歡迎參加 Cognition Therapeutics 第四季和 2023 年底業績電話會議。今天與我在一起的有總裁兼執行長麗莎‧裡恰爾迪 (Lisa Ricciardi)；約翰‧多伊爾，財務長；和首席醫療官 Tony Caggiano 博士。

This morning the company issued a press release detailing its 2023 fourth quarter and year-end results. We encourage everyone to read this morning's press release as well as Cognition's annual report on Form 10-K, which is now filed with the SEC and available on our website. In addition, this conference call is being webcast through the company's website and will be archived for 30 days.

今天上午，該公司發布新聞稿，詳細介紹了 2023 年第四季和年終業績。我們鼓勵大家閱讀今天早上的新聞稿以及 Cognition 的 10-K 表格年度報告，該報告現已向 SEC 提交並可在我們的網站上取得。此外，本次電話會議正在透過公司網站進行網路直播，並將存檔30天。

Please note that certain information discussed on the call today is covered under the Safe Harbor provisions of the Private Securities Litigation Reform Act. We caution listeners that during the call, management will be making forward-looking statements. Actual results could differ materially from those stated or implied by these forward-looking statements due to the risks and uncertainties associated with the company's business.

請注意，今天電話會議中討論的某些資訊受《私人證券訴訟改革法案》的安全港條款管轄。我們提醒聽眾，在電話會議期間，管理階層將做出前瞻性聲明。由於與公司業務相關的風險和不確定性，實際結果可能與這些前瞻性陳述中明示或暗示的結果有重大差異。

These forward-looking statements are qualified by the cautionary statements contained in Cognition's press release and SEC filings, including its annual report on Form 10-K previous filings. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast. Cognition undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call.

這些前瞻性陳述受到 Cognition 新聞稿和 SEC 文件（包括其先前提交的 10-K 表格年度報告）中包含的警示性聲明的限制。本次電話會議包含時間敏感訊息，僅截至本次直播之日準確。Cognition 不承擔修改或更新任何前瞻性陳述以反映本次電話會議之後發生的事件或情況的義務。

With that, I would now like to turn the call over to Lisa Ricciardi.

現在，我想將電話轉給麗莎·裡恰爾迪。

Mike, thank you. Good morning, everyone. Welcome to Cognition Therapeutics earnings conference call covering our 2023 results and highlights from recent weeks. On today's call, John Doyle and I will share prepared remarks on the company's progress, and then we'll be joined by Dr. Tony Caggiano, our Chief Medical Officer and Head of R&D to take your questions.

麥克，謝謝你。大家，早安。歡迎參加 Cognition Therapeutics 財報電話會議，會議內容涵蓋了我們 2023 年的業績以及最近幾週的亮點。在今天的電話會議上，我和 John Doyle 將分享有關公司進展的準備好的評論，然後我們的首席醫療官兼研發主管 Tony Caggiano 博士將加入我們，回答大家的問題。

Cognition's focus is the development of innovative orally available drug candidates targeting age-related degenerative diseases of the central nervous system and retina. Our current clinical programs build on our expertise from the Sigma-2 receptor, which regulates cellular functions disrupted by neuro degenerative diseases.

Cognition 的重點是開發與年齡相關的中樞神經系統和視網膜退化性疾病的創新口服候選藥物。我們目前的臨床計畫建立在 Sigma-2 受體的專業知識之上，該受體調節因神經退化性疾病而破壞的細胞功能。

Our drug candidate, our leading drug candidate, is currently in the clinic being tested for Alzheimer's disease and Dementia with Lewy Bodies also referred to as DLB. In Alzheimer's disease, we're setting both early stage patients and patients with mild to moderate disease. We're also studying CT1812 and geographic atrophy secondary to dry age-related AMD or dry AMD as it is known, modulating the Sigma-2 receptor complex with a brain penetrant small molecule drug candidate is a unique approach differentiated from other companies developing treatments in both neurodegenerative and ophthalmology diseases.

我們的候選藥物，我們的領先候選藥物，目前正在診所進行阿茲海默症和路易氏體失智症（也稱為 DLB）的測試。在阿茲海默症方面，我們既針對早期患者，也針對輕度至中度疾病的患者。我們也正在研究CT1812 和繼發於乾性老年性AMD 或乾性AMD 的地理萎縮，用腦滲透性小分子候選藥物調節Sigma-2 受體複合物是一種獨特的方法，有別於其他正在開發治療方法的公司。神經退化性疾病和眼科疾病。

Now an update on our trials. Our SHINE study is a Phase 2 clinical trial of CT1812 that completed enrollment of 153 patients with mild to moderate Alzheimer's disease. Patients were randomized one to one to one to receive placebo or oral doses 100 or 300 milligrams of drug. We expect top line data in mid-24 after the last patient has completed six months treatment, and we anticipate presenting our more detailed findings at the Alzheimer's Association International Conference or AAIC meeting later in the summer.

現在更新我們的試驗。我們的 SHINE 研究是 CT1812 的 2 期臨床試驗，已完成 153 名輕度至中度阿茲海默症患者的入組。患者以一對一的方式隨機接受安慰劑或口服 100 或 300 毫克藥物。我們預計在最後一名患者完成六個月治療後的24 日中旬獲得最重要的數據，並且我們預計在夏季晚些時候的阿茲海默症協會國際會議或AAIC 會議上展示我們更詳細的研究結果。

Now the question at the forefront of everyone's mind, of course, is what would we consider to be a success in SHINE? As an objective measure, we consider the results from the most recently approved disease-modifying antibody intravenous infusion therapy, Lecanemab, in which treated participants had a 1.4 point difference in ADAS-Cog14 over 18 months.

當然，現在每個人心中最關心的問題是，我們認為什麼是 SHINE 的成功？作為客觀衡量標準，我們考慮了最近批准的緩解疾病抗體靜脈輸注療法 Lecanemab 的結果，其中接受治療的參與者在 18 個月內的 ADAS-Cog14 方面有 1.4 分的差異。

And we exceeded this in our preliminary analysis of the first 24 patients in SHINE, where we saw a 3 point difference in the slowing of cognitive decline compared to placebo on the ADAS-Cog11, just after six months. Results similar to our preliminary analysis of the initial 24 patients would represent a clinically meaningful outcome. Endpoints in SHINE include safety, changes in cognitive and functional scores, including the ADAS-Cog11, the neuro-psyche test battery, the ABCS activities of daily living. In addition, we would look to corroborate CT8112 activity and its brain penetrant target engagement through the analysis of biomarkers.

我們在對 SHINE 的前 24 名患者進行的初步分析中超越了這一目標，僅在六個月後，我們發現與安慰劑相比，ADAS-Cog11 的認知能力下降速度減緩了 3 個百分點。與我們對最初 24 名患者的初步分析類似的結果將代表具有臨床意義的結果。SHINE 的終點包括安全性、認知和功能評分的變化，包括 ADAS-Cog11、神經心理測驗電池、日常生活的 ABCS 活動。此外，我們希望透過生物標記分析來證實 CT8112 活性及其腦滲透靶點參與。

Before moving on, I would like to acknowledge the support of our study participants and their caregivers, our clinical trial investigators, CRO partners and collaborators at the NIH National Institute of Aging. We look forward to seeing the full study results later this year.

在繼續之前，我要感謝我們的研究參與者及其照護者、我們的臨床試驗研究者、CRO 合作夥伴以及 NIH 國家老化研究所的合作者的支持。我們期待在今年稍後看到完整的研究結果。

And let me turn to our shimmer study, a Phase 2 US based trial of CT1812 in mild to moderate Dementia with Lewy Bodies or DLB. An estimated 1.4 million people are affected by DLB making the disease the second most common form of dementia. There are no currently approved treatment options and few drugs are being studied for this condition.

讓我談談我們的 shimmer 研究，這是一項在美國進行的 CT1812 治療輕度至中度路易氏體失智症或 DLB 的 2 期試驗。據估計，有 140 萬人受到 DLB 的影響，使該疾病成為第二常見的癡呆症。目前還沒有批准的治療方案，並且正在研究針對這種情況的藥物很少。

Now we know from the literature that more than half of DLB patients are estimated to have voiced both amyloid beta and alpha-synuclein oligomers in their brain. CT1812 has been shown to protect neurons from the toxicity of both amyloid beta and alpha-synuclein pathogenic proteins, and thus it has the potential to treat this sizable population of DLB patients with co-pathology.

現在我們從文獻中得知，估計超過一半的 DLB 患者大腦中同時表達了 β 澱粉樣蛋白和 α-突觸核蛋白寡聚體。CT1812 已被證明可以保護神經元免受 β 澱粉樣蛋白和 α-突觸核蛋白致病蛋白的毒性，因此它有潛力治療大量患有共病理的 DLB 患者。

The SHIMMER trial was also supported by non-dilutive funding from the NIA and it's being led by Dr. Jim Galvan, our primary investigator at the University of Miami, School of Medicine, as well as the Lewy Body Dementia Association or LBDA, whose centers of excellence are among the sites enrolling patients. We aim to complete enrollment and present top line data in the second half of the year. Again, we extend our thanks to patients, caregivers, our clinical trial investigators, our CRO partners and the NIA.

SHIMMER 試驗也得到了NIA 的非稀釋資金支持，該試驗由吉姆·加爾文(Jim Galvan) 博士領導，他是我們在邁阿密大學醫學院以及路易體癡呆協會(LBDA) 的首席研究員，該協會的研究中心優秀的網站包括招募病患的網站。我們的目標是在今年下半年完成註冊並提供頂線資料。我們再次向患者、照護者、我們的臨床試驗研究者、我們的 CRO 合作夥伴和 NIA 表示感謝。

The prior trials, as I've discussed, are being run in a mild to moderate patient population. Our START trial is a 540 patient Phase 2 study of CT1812 in adults with early Alzheimer's disease in collaboration with the Alzheimer's Clinical Trials Consortium or the ACTC. The START trial is measuring the efficacy and tolerability of CT1812 in subjects with mild cognitive impairment or early disease who have elevated amyloid beta.

正如我所討論的，先前的試驗是在輕度至中度患者群體中進行的。我們的 START 試驗是與阿茲海默症臨床試驗聯盟 (ACTC) 合作，對患有早期阿茲海默症的成年人進行的一項 540 名患者參與的 CT1812 2 期研究。START 試驗正在測量 CT1812 在患有輕度認知障礙或早期疾病、β-澱粉樣蛋白升高的受試者中的療效和耐受性。

We received grant support totaling $81 million for this trial from the NIA, and we are very pleased to join forces and collaborate with the ACTC. In 2023, we initiated site activations and the START trial is now actively recruiting from centers of excellence within the ACTC network. We and our collaborators on this study made the decision to allow participants on stable background therapy with Lecanemab to enroll and start. We believe this decision will provide real-world evidence of CT1812 in combination therapy.

我們從 NIA 獲得了總計 8,100 萬美元的資助支持，我們非常高興能夠與 ACTC 聯手合作。2023 年，我們啟動了站點激活，並且 START 試驗目前正在積極從 ACTC 網路內的卓越中心招募人員。我們和我們在這項研究中的合作者決定允許接受 Lecanemab 穩定背景治療的參與者註冊並開始。我們相信這項決定將為 CT1812 聯合治療提供真實世界的證據。

I will now turn to our opportunity for CT1812 in ophthalmic conditions, specifically dry AMD and geographic atrophy. Dry AMD is estimated to account for up to 90% of the population with age-related macular degeneration. The advanced form of the disease, known as geographic atrophy, can lead to progressive and permanent vision loss and an estimated 1 million people in the US have geographic atrophy.

我現在將談談 CT1812 在眼科疾病中的機會，特別是乾性 AMD 和地圖樣萎縮。據估計，乾性 AMD 佔年齡相關性黃斑部病變人群的 90%。這種疾病的晚期形式稱為地理萎縮，可導致進行性和永久性視力喪失，估計美國有 100 萬人患有地理萎縮。

So looking at this opportunity, we have evidence from genome-wide studies, from preclinical studies, from clinical biomarker data as well as from results of our Alzheimer's studies that demonstrate treatment with CT1812 may have a beneficial impact on the proteins implicated in dry AMD.

因此，著眼於這個機會，我們從全基因組研究、臨床前研究、臨床生物標記數據以及阿茲海默症研究結果中獲得證據，證明 CT1812 治療可能對乾性 AMD 相關的蛋白質產生有益影響。

The magnify study is a randomized placebo-controlled Phase 2 trial expected to enroll approximately 240 people who have been diagnosed with dry AMD with measurable geographic atrophy. Over the treatment period, change in GA lesion size as well as other measures of safety and efficacy will be assessed to determine if CT1812 can slow macular degeneration.

magnify 研究是一項隨機安慰劑對照 2 期試驗，預計招募約 240 名被診斷出患有乾性 AMD 並伴隨可測量的地理萎縮的患者。在治療期間，將評估 GA 病灶大小的變化以及其他安全性和有效性指標，以確定 CT1812 是否可以減緩黃斑部病變。

In addition, we have added measures of visual (technical difficulty) to assess the impact of our drug on vision. We believe the level of interest investigators and participants have shown in the magnified trial indicate that an effective oral treatment option will be well received. And as more treatment options become available, we believe ophthalmologists will move towards combination therapies.

此外，我們還增加了視覺測量（技術難度）來評估我們的藥物對視力的影響。我們相信，研究人員和參與者在擴大試驗中所表現出的興趣程度表明，有效的口服治療方案將受到廣泛歡迎。隨著更多治療選擇的出現，我們相信眼科醫生將轉向聯合療法。

Might our drug be synergistic with complement approaches, this is to be determined. Beyond our clinical trial work, our scientific and medical teams have been active in 2023. Cognition scientists published two manuscripts and made 11 presentations at medical and scientific congresses this past year. The scientific evidence generated by our team has continued to support our clinical development efforts, providing insights into proteins and biological processes impacted by CT1812 in Alzheimer's, Parkinson's disease, and dry AMD.

我們的藥物是否可能與補體方法產生協同作用，這仍有待確定。除了臨床試驗工作外，我們的科學和醫療團隊在 2023 年也很活躍。去年，認知科學家發表了兩篇手稿，並在醫學和科學大會上做了 11 次演講。我們團隊產生的科學證據繼續支持我們的臨床開發工作，提供有關 CT1812 在阿茲海默症、帕金森氏症和乾性 AMD 中受 CT1812 影響的蛋白質和生物過程的見解。

In closing, I'm proud of the progress we have made in advancing CT1812 toward important value-driving milestones for 2024. We believe that CT1812 can be an important part of the development paradigm for dementia treatment. And we are unwavering in our commitment to developing new therapies for neurodegenerative diseases.

最後，我對我們在推動 CT1812 邁向 2024 年重要的價值驅動里程碑方面所取得的進展感到自豪。我們相信CT1812可以成為癡呆症治療開發範例的重要組成部分。我們堅定不移地致力於開發神經退化性疾病的新療法。

With that, I turn the call to John Doyle to review our financial results.

說完，我打電話給約翰·道爾（John Doyle），讓他審查我們的財務表現。

Thank you, Lisa. During 2023, we continue to execute our financial stewardship. We efficiently managed our resources and leveraged our grant funding and our at-the-market offering facility with Cantor Fitzgerald and B. Riley Securities to support our clinical programs.

謝謝你，麗莎。2023 年，我們將繼續履行財務管理職責。我們有效地管理我們的資源，並利用我們的贈款資金以及我們與 Cantor Fitzgerald 和 B. Riley 證券的市場發行設施來支持我們的臨床計畫。

Recently, we concluded a new $11.5 million underwritten public offering that's expected to provide funding for our existing clinical trials and bolster our balance sheet by extending cash runway through May 2025. With that context, let us now proceed to the financials for the fiscal year 2023.

最近，我們完成了一項新的 1,150 萬美元承銷公開發行，預計將為我們現有的臨床試驗提供資金，並透過將現金跑道延長至 2025 年 5 月來增強我們的資產負債表。在此背景下，我們現在來看看 2023 財年的財務狀況。

Research and development expenses were $37.2 million for the year ended December 31, 2023, compared to $30.3 million for 2022. The increase was primarily related to higher costs associated with Phase 2 trial activities with contract research organizations, personnel and preclinical research, partially offset by decreased manufacturing costs.

截至 2023 年 12 月 31 日止年度的研發費用為 3,720 萬美元，而 2022 年為 3,030 萬美元。這一增長主要與合約研究組織、人員和臨床前研究的第二階段試驗活動相關的成本增加有關，但部分被製造成本的下降所抵消。

General and administrative expenses were $13.5 million for the year ended December 31, 2023, compared to $13.2 million for 2022. The increase was primarily related to higher employee compensation and benefits, driven by increased head count and equity-based compensation, partially offset by decreased director and officer liability insurance and other expenses.

截至 2023 年 12 月 31 日止年度的一般及行政費用為 1,350 萬美元，而 2022 年為 1,320 萬美元。這一增長主要與員工薪酬和福利的增加有關，這是由於員工人數和股權薪酬的增加所致，但部分被董事和高級管理人員責任保險和其他費用的減少所抵消。

The company reported a net loss of $25.8 million or $0.86 per basic and diluted share for the year ended December 31, 2023, compared to a net loss of $21.4 million or $0.91 per basic and diluted share for 2022. Cash and cash equivalents as of December 31, 2023, were approximately $29.9 million and total grant funds remaining from the NIA were $67.5 million.

該公司報告截至2023年12月31日的年度淨虧損為2,580萬美元，或每股基本股和稀釋股0.86美元，而2022年的淨虧損為2,140萬美元，或每股基本股和稀釋股0.91美元。截至 2023 年 12 月 31 日，現金及現金等價物約為 2,990 萬美元，NIA 剩餘贈款總額為 6,750 萬美元。

I will now turn the call back over to the operator, who can open the call for questions. Operator?

我現在將把電話轉回給接線員，接線員可以打開電話詢問問題。操作員？

(Operator Instructions) Charles Duncan, Cantor Fitzgerald.

（操作員說明）查爾斯鄧肯、坎托菲茨傑拉德。

Hey, good morning, Lisa and team. Congratulations on the progress. Could be a transformational year. Thanks for taking our questions. I had a couple of questions regarding SHINE and then -- yes, on the program for 1812. I guess, you mentioned a point change that would be clinically meaningful and I agree with you. However, I would argue that actually a lower point change may also be clinically meaningful given that you have an oral compound. And given that you are seeing that in a very short time relative to the antibodies, and so I guess I would ask you about, smaller change being impactful and possibly even if it's seen in a more mild patient population. And then can you update us on [completer] rate for SHINE?

嘿，早上好，麗莎和團隊。祝賀取得的進展。可能是轉型的一年。感謝您回答我們的問題。我有幾個關於 SHINE 的問題，然後——是的，關於 1812 年的節目。我想，您提到了一個具有臨床意義的點變化，我同意您的觀點。然而，我認為，考慮到您有口服化合物，實際上較低的點變化也可能具有臨床意義。鑑於您在相對於抗體而言很短的時間內看到了這一點，所以我想我會問您，較小的變化是否會產生影響，即使它出現在較輕的患者群體中也是如此。那麼您能否向我們介紹 SHINE 的[完成者]費率的最新情況？

Morning, Charles. Good to talk to you. I'm going to turn your question over to Tony and spoiler alert. I will not update you on the complete rate for SHINE. When the study is fully completed, we'll provide more information.

早上好，查爾斯。很高興和你說話。我要把你的問題轉給東尼，劇透警告。我不會向您更新 SHINE 的完整費率。研究完全完成後，我們將提供更多資訊。

Good question. We agree with you, Charles. There is a lot of meaning and changes that are less than the 3 points that folks talk about a lot. Indeed, if you look at the Lecanemab data, as Lisa mentioned, there was a 1.44 point change over 18 months and at six months, they had about a 0.5 point change. And this is really at the current benchmark for what could be seen in the disease modifying therapy.

好問題。我們同意你的觀點，查爾斯。除了人們經常談論的這三點之外，還有很多意義和變化。事實上，如果你看一下 Lecanemab 數據，正如 Lisa 所提到的，18 個月內發生了 1.44 個點的變化，而在 6 個月內，它們發生了約 0.5 個點的變化。這確實是當前疾病修飾療法的基準。

Now we're optimistic that we'll have very good results based on our preliminary results, which we've reported previously. But indeed, there is success, great success short of that benchmark. We have several secondary measures, which how those follow, if the preponderance of those secondary measures follow directionally with the primary. Obviously, that would strengthen changes that are more modest.

現在，我們樂觀地認為，根據我們先前報告的初步結果，我們將取得非常好的結果。但事實上，除了這個基準之外，還有成功，巨大的成功。我們有幾個次要措施，如果這些次要措施的優勢與主要措施有方向性，那麼這些措施將如何遵循。顯然，這將加強更溫和的改變。

That's very helpful, Tony. And then thinking about the mechanism is the Sigma-2 Ligand. It would seem to me that the drugs may have even greater activity or signal-to-noise in more mild patient population. And so excited to see the START trial progress.

這非常有幫助，托尼。然後思考這個機制就是Sigma-2 Ligand。在我看來，這些藥物在較輕的患者群體中可能具有更大的活性或訊號雜訊比。很高興看到 START 試驗的進展。

I guess I'm wondering when you could anticipate an update out of that trial? I know that you're not fully engaged in conducting it. But wouldn't it be great to see activity in an even earlier stage patient with Alzheimer’s? Thanks.

我想我想知道您什麼時候可以預期該試驗的更新？我知道你並沒有完全投入執行。但是，如果能在早期阿茲海默症患者身上看到活性，豈不是很棒嗎？謝謝。

Charles, this is Lisa. Your point is well-taken. At this time, I believe, there is no interim planned for START. I believe that all that Tony and his ACTC colleagues. And in consistent with our previous trials, we're not reporting any interim updates on enrollment or things of that nature. So as for now, we'll continue to provide communication that says it's enrolling. And if there's anything else to communicate, we'll let you know. But we found it's more effective for us to say when the trial's done, it's done and not to provide partial progress.

查爾斯，這是麗莎。你的觀點很好理解。我認為目前尚無 START 的臨時計劃。我相信託尼和他的 ACTC 同事的一切。與我們先前的試驗一致，我們不會報告任何有關註冊或類似性質的臨時更新。因此，就目前而言，我們將繼續提供有關正在註冊的資訊。如果還有其他需要溝通的內容，我們會通知您。但我們發現，當試驗完成時，我們說它已經完成，而不是提供部分進展，這對我們來說更有效。

Okay, that's fair. Last question and sorry to hop back to SHINE, and that is following the six month treatment period, could you remind us what happens with those patients? Are they given an opportunity to continue onto treatment? And if so, have any done that?

好吧，這很公平。最後一個問題，很抱歉回到 SHINE，那是在六個月的治療期之後，您能提醒我們這些病人會發生什麼事嗎？他們是否有機會繼續接受治療？如果是的話，有人這樣做過嗎？

We do not have an open-label extension at this time. So after six months of treatment, folks are followed for another month for safety. And then the study is completed.

我們目前沒有開放標籤擴展。因此，經過六個月的治療後，為了安全起見，人們還要再追蹤一個月。然後研究就完成了。

Charles, to be honest, we have wanted to do an open label extension, but the economics were prohibitive for a company of our size. And so that's something we're considering as we look forward. It's a great question. Something the team would -- likely should be in a position to do.

查爾斯，說實話，我們一直想進行開放標籤擴展，但對於我們這種規模的公司來說，經濟性令人望而卻步。這就是我們在展望未來時正在考慮的事情。這是一個很好的問題。團隊可能應該能夠做的事情。

Yes, understood. Hopefully, good data will change that. Thanks for taking our questions.

是的，明白了。希望好的數據能夠改變這一點。感謝您回答我們的問題。

Yes. Thanks, Charles.

是的。謝謝，查爾斯。

Jay Olson, Oppenheimer.

傑·奧爾森，奧本海默。

Hey, congrats on the progress and thanks for taking the questions. Can you talk about the patient's baseline characteristics in the SHINE study? And also can you just describe how you plan to share the top-line results of the SHINE study? Would that be in a press release or a medical meeting? And then I had a follow on. Thank you.

嘿，祝賀您取得的進展，並感謝您提出問題。您能談談 SHINE 研究中患者的基線特徵嗎？您能否描述一下您計劃如何分享 SHINE 研究的主要結果？這會出現在新聞稿或醫學會議中嗎？然後我就有了後續。謝謝。

Yeah, good morning, Jay. Good to hear from you. Tony, I'll let you take these questions.

是的，早安，傑伊。很高興聽到你的消息。東尼，我讓你回答這些問題。

Sure. Yeah. We do not have baseline characteristics for this study as yet. Still, blinded [in] and data is obviously not yet been locked in and analyzed. The plan to read out the data -- we'll have a top line read obviously soon after we get it. And then the plan is to fill out the full dataset at the AAIC meeting at the end of July this year. Obviously, that's timing dependent (technical difficulty) when we get the data, but that's the current plan.

當然。是的。我們還沒有這項研究的基線特徵。儘管如此，數據顯然還沒有被鎖定和分析。讀出資料的計畫－在我們拿到資料後很快就會讀出頂行。然後計劃在今年 7 月底的 AAIC 會議上填寫完整的數據集。顯然，當我們獲取數據時，這取決於時間（技術難度），但這是目前的計劃。

Great. Thank you for that. And then Rick, and just as a follow-up, can you just talk about the level of interest you've seen from investigators and the progress you're making in site activation for the START study?

偉大的。謝謝你。然後，Rick，作為後續行動，您能談談您從研究人員那裡看到的興趣程度以及您在 START 研究的站點激活方面取得的進展嗎？

Yeah, the sites are top sites around the country that CACTC network. Absolutely top sites. I always say to investors day if your family member was sick, these are the places you'd want to go. And so there is a lot of enthusiasm. I don't have it top of my head the number of active sites.

是的，這些網站是 CACTC 網路全國範圍內的頂級網站。絕對是頂級網站。我總是對投資人說，如果你的家人生病了，這些就是你想去的地方。因此，人們有很大的熱情。我不知道活躍站點的數量。

But we are making progress and they are keen to have the opportunity to study an oral drug for their early patient population. So from our perspective, it's positive. We're looking to get that study fully enrolled and completed. It's a big study and it's a long study, but we're making positive progress and met with enthusiasm by the PIs.

但我們正在取得進展，他們渴望有機會為早期患者群體研究口服藥物。所以從我們的角度來看，這是正面的。我們希望該研究能夠完全註冊並完成。這是一項大型研究，也是一項長期研究，但我們正在取得積極進展，並受到 PI 的熱情歡迎。

So great. Thanks so much for taking the questions and congrats on the progress.

很好。非常感謝您提出問題並祝賀取得的進展。

Thanks, Jay.

謝謝，傑伊。

Mayank Mamtani, B. Riley Securities.

Mayank Mamtani，B. Riley 證券。

Good morning, team. Thanks for taking my question and appreciate the comprehensive update. Maybe just quickly on the Phase 2 SHINE study. Could you comment on your expectation for rate of ARIA? And if you do have any understanding on how the split of mild and moderate patients are going to be in the SHINE study? Obviously, with your earlier 24 patient cohort breaking out mild and moderate was not possible. But in this larger cohort that could be a possibility. And then I have a couple of follow-ups.

早上好，團隊。感謝您提出我的問題並感謝全面的更新。也許很快就可以進行第二階段 SHINE 研究。您能評論一下您對 ARIA 利率的預期嗎？您是否了解 SHINE 研究中輕度和中度患者的劃分？顯然，對於您之前的 24 名患者群組來說，突破輕度和中度是不可能的。但在這個更大的群體中，這可能是一種可能性。然後我有一些後續行動。

Good morning, Mayank. I'm going to let Tony take your question.

早上好，瑪雅克。我讓托尼回答你的問題。

Yes. So taking it the second part first, we will be doing an analysis of how folks -- their scores entering breaking down between mild and moderate or more severe and less severe and how that impacts their change on our outcome measures come. And then (technical difficulty) the first question. (multiple speakers)

是的。因此，首先考慮第二部分，我們將分析人們的分數如何在輕度和中度或更嚴重和較不嚴重之間劃分，以及這如何影響他們對我們結果指標的變化。然後（技術難度）第一個問題。（多個發言者）

So yes, yes. So we don't expect the base on our mechanism of action and that ARIA will be an issue. With antibody therapies pulling amyloid from brain and blood vessels and the rest of the vasculature, you would expect to see those findings. We do not. However, obviously, the full safety picture of our drug will come out as we do complete studies.

所以是的，是的。因此，我們預期我們的行動機制和 ARIA 不會成為問題。透過抗體療法從大腦和血管以及脈管系統的其餘部分中提取澱粉樣蛋白，您會期望看到這些發現。我們不。然而，顯然，隨著我們完成研究，我們藥物的完整安全情況將會顯現出來。

I understood. And then in regards to your recent EEG proteomics and even brain volume data, that has been helpful to understand Sigma-2 receptor biology. Any specific biomarker data you'd have in the top line for both readouts that is worth paying attention to, if you could point to that, Tony, that will be great.

我明白了。然後，關於您最近的腦電圖蛋白質組學甚至大腦體積數據，這有助於了解 Sigma-2 受體生物學。兩個讀數的頂行中值得關注的任何特定生物標記數據，如果你能指出這一點，托尼，那就太好了。

Yes, sure. So we'll be reporting out basically the same biomarkers that we did from the preliminary read and those are the canonical biomarkers that you would expect to see changes in monomer, synapse proteins, that GFAP, NFL, et cetera. And then as we did previously, we'll be doing complete proteomic analyses from the cerebral spinal fluid and plasma of these individuals to look at more refined measures of target engagement and disease modification. So we'll be doing pretty much the same thing we did in the preliminary read as well as expanded based on what we've learned in the intervening time.

是的，當然。因此，我們將報告與初步閱讀中基本相同的生物標記物，這些是您期望看到單體、突觸蛋白、GFAP、NFL 等變化的規範生物標記。然後，就像我們之前所做的那樣，我們將對這些個體的腦脊髓液和血漿進行完整的蛋白質組分析，以研究目標參與和疾病修飾的更精細的測量方法。因此，我們將做與初步閱讀中所做的幾乎相同的事情，並根據我們在中間時間學到的知識進行擴展。

Great. And then on the Phase 2 magnify study, how has the initial investigator feedback then -- I know you're doing well with site activation, but just if you are able to comment on study enrollment? And then lastly, on financials, how much of expected grant funding is baked into your runway guidance? So we could have aptly model the next four to five quarters of cash flow. Thanks again for taking the questions.

偉大的。然後在第二階段放大研究中，最初的研究者反饋如何——我知道你在網站激活方面做得很好，但如果你能夠對研究註冊發表評論呢？最後，在財務方面，有多少預期撥款資金納入了您的跑道指導？因此，我們可以適當地對未來四到五個季度的現金流進行建模。再次感謝您提出問題。

Yeah. You're welcome, Mayank. With regard to magnify, there is tremendous enthusiasm in the clinical research community for the trial as well as from patients. So there is a positive momentum in that study. And like our other studies, we don't provide guidance on enrollment. They are a very enthusiastic group of PIs in patients so we can tell you that much. And on the grants, John?

是的。不客氣，瑪雅克。關於magnify，臨床研究界和患者都對這項試驗抱持著極大的熱情。所以這項研究有正面的勢頭。與我們的其他研究一樣，我們不提供註冊指導。他們是一群非常熱心的患者 PI，所以我們可以告訴您這麼多。關於補助金，約翰？

With respect to the grant funding, Mayank, so we expect to complete the SHIMMER grant fund this year as we ramp up that trial. And then the remaining balance of that will be dedicated to [Magna] to START trial as we progress through '24 and '25.

關於撥款資金，Mayank，我們預計在今年加大試驗力度時完成 SHIMMER 撥款基金。然後，隨著我們在「24 年」和「25 年」的進展，剩餘的餘額將專門用於 [Magna] 的 START 試驗。

So Mayank, your question was about the $67 million in the press release we identified. Is that right? And how much of that is baked into the runway? Yeah, as you know, Mike, that the grants are drawn down as the studies are completed. So it's really a function of the progress we make in those studies. How quickly that grant funding is absorbed.

Mayank，你的問題是關於我們確定的新聞稿中的 6700 萬美元。是對的嗎？其中有多少被烘焙到跑道上？是的，麥克，如你所知，研究完成後補助金就會被提取。所以這實際上是我們在這些研究中取得的進展的結果。吸收贈款資金的速度有多快。

Got it. That's helpful. Thanks again for taking our questions and looking forward to an exciting next few months as well.

知道了。這很有幫助。再次感謝您提出我們的問題，並期待接下來的幾個月令人興奮。

Yes. Thank you. We are as well. Thank you.

是的。謝謝。我們也是。謝謝。

As of right now, we don't have any raised hands. So I'd now like to hand it back over to the management for their final remarks.

截至目前，我們還沒有任何人舉手。所以我現在想把它交還給管理階層，讓他們發表最後的評論。

Terrific. To conclude, we're looking forward to our continued progress in important Phase 2 data readouts in 2024. We believe our science is sound, and we continue to build evidence supporting CT1812's potential for patients. We're positioned to achieve and deliver on multiple clinical milestones, and we're focused on creating long-term value for our shareholders. Thank you for joining us today.

了不起。總之，我們期待 2024 年重要的第二階段資料讀出繼續取得進展。我們相信我們的科學是合理的，我們將繼續收集證據來支持 CT1812 對患者的潛力。我們致力於實現並實現多個臨床里程碑，並專注於為股東創造長期價值。感謝您今天加入我們。

(technical difficulty) today's conference call. You may now all disconnect. Have a good day.

（技術難度）今天的電話會議。你們現在可以斷開連結了。祝你有美好的一天。

Thank you.

謝謝。

Goodbye.

再見。