Cognition Therapeutics Inc (CGTX) 2024 Q2 法說會逐字稿

Hello, and thank you for standing by. At this time, I would like to welcome you to the Cognition Therapeutics second-quarter 2024 earnings call. (Operator Instructions)

您好，感謝您的支持。現在，我歡迎您參加 Cognition Therapeutics 2024 年第二季財報電話會議。（操作員說明）

I would now like to turn the conference over to Tom Johnson. Please go ahead.

我現在想把會議交給湯姆·約翰遜。請繼續。

Thank you, operator, and good morning, everyone. Welcome to the Cognition Therapeutics second-quarter 2024 results conference call. With me today are Lisa Ricciardi, President and Chief Executive Officer; John Doyle, Chief Financial Officer; and Tony Caggiano, Chief Medical Officer.

謝謝接線員，大家早安。歡迎參加 Cognition Therapeutics 2024 年第二季業績電話會議。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；以及首席醫療官托尼·卡吉亞諾 (Tony Caggiano)。

This morning, the company issued a press release detailing its financial results for the second quarter and first half of the 2024 fiscal year. We encourage everyone to read this morning's press release as well as Cognition's quarterly report on Form 10-Q, annual report on Form 10-K and periodic reports on Form 8-K, which are 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 2024 財年第二季和上半年的財務業績。我們鼓勵大家閱讀今天早上的新聞稿以及 Cognition 的 10-Q 表格季度報告、10-K 表格年度報告和 8-K 表格定期報告，這些報告現已向 SEC 備案並可在我們的網站上獲取。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 by the Safe Harbor provisions of the Private Securities Litigation Reform Act. We caution listeners that during this 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 risks and uncertainties associated with the company's business. These forward-looking statements are qualified by cautionary statements contained in the Cognition press release and SEC filings, including its quarterly report on Form 10-Q and previous filings.

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，在這次電話會議中，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。這些前瞻性陳述受到 Cognition 新聞稿和 SEC 文件（包括其 10-Q 表格季度報告和先前文件）中包含的警示性陳述的限制。

This conference call contains time-sensitive information, which is accurate only 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.

本次電話會議包含時間敏感訊息，僅以本次直播日期為準。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 like to hand the call over to Lisa Ricciardi. Lisa?

說到這裡，我想將電話轉交給麗莎·裡恰爾迪。麗莎？

Thank you, Tom, and good morning, everyone. We appreciate your participation in Cognition Therapeutics' financial results conference call. Today, our CFO, John Doyle, and I will share prepared remarks on the company's progress and financial performance over the first half of the year, after which, we'll take your questions. For Q&A, we will be joined by our Chief Medical Officer and Head of R&D, Dr. Tony Caggiano.

謝謝你，湯姆，大家早安。我們感謝您參加 Cognition Therapeutics 的財務業績電話會議。今天，我和我們的財務長 John Doyle 將就公司上半年的進度和財務業績分享準備好的評論，然後我們將回答大家的問題。我們的首席醫療官兼研發主管 Tony Caggiano 博士將參加問答環節。

At Cognition Therapeutics, our focus is on the development of innovative, orally available drug candidates targeting age-related degenerative conditions of the CNS and retina. Our clinical programs include multiple Phase 2 trials for both early and mild to moderate Alzheimer's disease. We are also studying CT1812 in dementia with Lewy bodies and geographic atrophy, secondary to dry AMD.

在 Cognition Therapeutics，我們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。我們的臨床項目包括針對早期和輕度至中度阿茲海默症的多項 2 期試驗。我們也正在研究 CT1812 在路易氏體失智症和繼發於乾性 AMD 的地理萎縮中的作用。

Now during today's call, my formal remarks will be on the completed SHINE trial, and then on our next study to read out the SHIMMER trial. Let's begin with SHINE.

在今天的電話會議中，我的正式演講將是關於已完成的 SHINE 試驗，然後是我們的下一項研究，宣讀 SHIMMER 試驗。讓我們從SHINE開始。

Our SHINE study was a Phase 2 clinical trial, proof-of-concept study of CT1812 in mild to moderate Alzheimer's disease. This was our first proof-of-concept study. The trial enrolled a total of 153 adults with mild to moderate Alzheimer's disease. Participants were randomized to receive either placebo or oral doses of 100 or 300 milligrams of CT1812, and there were 51 participants in each arm of the study. Our primary purpose was to assess safety and tolerability after six months of daily dosing.

我們的 SHINE 研究是 CT1812 治療輕度至中度阿茲海默症的 2 期臨床試驗、概念驗證研究。這是我們的第一個概念驗證研究。該試驗總共招募了 153 名患有輕度至中度阿茲海默症的成年人。參與者被隨機分配接受安慰劑或口服 100 或 300 毫克 CT1812，研究的每組有 51 名參與者。我們的主要目的是評估每日給藥六個月後的安全性和耐受性。

We also evaluated multiple cognitive endpoints, including the ADAS-Cog 11, ADAS-Cog 13, cognitive composite and the MMSE. Functional improvement scales were included as were biomarker analyses.

我們也評估了多個認知終點，包括 ADAS-Cog 11、ADAS-Cog 13、認知複合和 MMSE。包括功能改善量表和生物標記分析。

In this study, participants who are treated with CT1812 for six months showed a consistent trend in slowing cognitive decline compared to placebo across all cognitive measures, the ADAS-Cog 11 and 13 cognitive composite at MMSE. On the most commonly used measures, the ADAS-Cog 11 and 13 scales, CT1812 treated participants showed a 39% slowing of cognitive decline after six months. Put SHINE results into context, the recently approved monoclonal antibodies demonstrated 25% to 30% slowing in an early patient population over 18 months. We were very encouraged by the 39% slowing in six months with a once-daily pill.

在這項研究中，接受 CT1812 治療 6 個月的參與者在所有認知測量（MMSE 的 ADAS-Cog 11 和 13 認知綜合）中均表現出與安慰劑相比認知衰退減緩的一致趨勢。在最常用的衡量標準（ADAS-Cog 11 和 13 量表）中，CT1812 治療的參與者在六個月後認知能力下降速度減緩了 39%。將 SHINE 結果結合起來，最近批准的單株抗體在 18 個月內對早期患者群體的治療效果減緩了 25% 至 30%。每天服用一次的藥物在六個月內減緩了 39%，這讓我們深受鼓舞。

Now furthermore, on the ADAS-Cog 11 and MMSE scale at day 98, the midpoint of the study, in the combined 100- and 300-milligram dose group, P-values of less than 0.05 were observed. Putting the full SHINE data readouts in context in the completed trial, participants on placebo in the intent-to-treat analysis worsened by 2.7 points as measured by ADAS-Cog 11. In the pooled 100- and 300-milligram dose group, there was a reduction of 1.66 points or 39% slower loss of cognition than in the placebo group.

此外，在第 98 天（研究中點）的 ADAS-Cog 11 和 MMSE 量表上，在 100 毫克和 300 毫克組合劑量組中，觀察到 P 值小於 0.05。將完整的 SHINE 數據讀數放在已完成的試驗中，根據 ADAS-Cog 11 的測量，意向治療分析中服用安慰劑的參與者病情惡化了 2.7 分。在 100 毫克和 300 毫克劑量組中，認知能力喪失比安慰劑組降低了 1.66 個百分點，即減緩了 39%。

Said another way, CT1812 rescued about 40% of the cognitive decline that participants could have experienced. In this trial, we used the functional measures of the ADCS-ADL or activities of daily living and the ADCS-CGIC, the Clinical Global Impression of Change.

換句話說，CT1812 挽救了參與者可能經歷的約 40% 的認知衰退。在本試驗中，我們使用了 ADCS-ADL（日常生活活動）和 ADCS-CGIC（臨床整體變化印象）的功能測量。

CT1812 demonstrated a slowing of loss of function towards the latter part of the trial. With 150 people enrolled or approximately 50 people per arm, the SHINE trial did not achieve statistical significance on the ADAS-Cog 11 scale. However, this is the important part. The multiple measures we assessed show a consistency across time and dose that is positive. It is this consistency that motivates us to look ahead to longer and larger trials.

CT1812 在試驗後期表現出功能喪失的速度減緩。SHINE 試驗招募了 150 人，每組約 50 人，但在 ADAS-Cog 11 量表上並未達到統計顯著性。然而，這是重要的部分。我們評估的多項措施顯示出在時間和劑量上的正向一致性。正是這種一致性激勵我們展望更長期、更大規模的試驗。

With regard to safety, CT1812 demonstrated a favorable safety and tolerability profile with most treatment adverse events being mild or moderate. The AEs were consistent with previous clinical experience. There was one case of asymptomatic ARIA-H and no cases of ARIA-E. At the 300-milligram dose, nine participants experienced treatment-emergent LFT increases greater than three times the upper limit of normal. These resolved after cessation of drug without evidence of serious liver injuries. Importantly, there were no LFT elevations observed in the 100-milligram dose. This data is all publicly available on our website.

在安全性方面，CT1812表現出良好的安全性和耐受性，大多數治療不良事件為輕度或中度。AE 與先前的臨床經驗一致。有 1 例無症狀 ARIA-H 病例，無 ARIA-E 病例。在 300 毫克劑量下，9 名參與者的治療引起的 LFT 增加超過正常上限的三倍。這些問題在停藥後得到解決，沒有嚴重肝損傷的證據。重要的是，在 100 毫克劑量中沒有觀察到 LFT 升高。這些數據均可在我們的網站上公開取得。

We are continuing to analyze the exploratory CSF biomarker program data. The study showed significant change in neurofilament light or NfL, and this is a marker of neurodegenerative disease. This occurred at the 300-milligram dose.

我們正在繼續分析探索性腦脊髓液生物標記計劃數據。研究顯示神經絲光或NfL發生顯著變化，這是神經退化性疾病的標誌。這種情況發生在 300 毫克劑量時。

We believe that this is evidence CT1812 acts as a synaptoprotective agent. Other CSF biomarkers assessed, including neurogranin, synaptotagmin, SNAP-25, p-Tau, total Tau and GFAP. We'll share more in the future as we continue analyzing biomarker data from this trial.

我們相信這是 CT1812 作為突觸保護劑發揮作用的證據。其他評估的腦脊髓液生物標記包括神經粒蛋白、突觸結合蛋白、SNAP-25、p-Tau、總 Tau 和 GFAP。當我們繼續分析該試驗的生物標記數據時，我們將在未來分享更多資訊。

Taken in total, we believe these findings provide evidence that the amyloid oligomer antagonism, a new and distinct mechanism for therapeutic intervention, may have a role as a monotherapy or a drug used in combination with approved drugs for the treatment of AD and other dementias. We met our key objectives of assessing safety, tolerability, and cognitive and functional changes.

總的來說，我們相信這些發現提供了證據，證明澱粉樣蛋白寡聚體拮抗作用是一種新的獨特的治療幹預機制，可能作為單一療法或與已批准的藥物聯合使用來治療AD 和其他癡呆症。我們實現了評估安全性、耐受性以及認知和功能變化的關鍵目標。

We learned that the 100-milligram dose showed good efficacy and had no incidence of elevated liver enzymes or discontinuations due to AEs. There were no new safety signals in the SHINE trial. We had a strong and consistent trend demonstrating potential efficacy as slowing cognitive decline in patients with mild to moderate disease. We believe the magnitude of effect is consistent with other drugs recently developed and approved. We believe the biomarker data supports the true slowing of neurodegeneration.

我們了解到，100 毫克劑量顯示出良好的療效，並且沒有發生肝酵素升高或因 AE 而停藥的情況。SHINE 試驗中沒有出現新的安全訊號。我們有一個強烈且一致的趨勢，證明了減緩輕度至中度疾病患者認知能力下降的潛在功效。我們相信效果的程度與其他最近開發和批准的藥物一致。我們相信生物標記數據支持神經退化性病變的真正減緩。

While in Philadelphia last week at the AAIC Conference, we had the opportunity to speak with multiple physicians and PIs from the SHINE trial. They were very supportive of the trial results and particularly the consistency of cognitive changes across the scale. They value the new safety information and profile of the 100-milligram dose group. Consistent with feedback from various investors, RPIs are interested in the next steps in terms of a new trial, duration dose, patient population, endpoints, and trial size. We also know that pharma groups having winnowed CNS programs over the years are now looking to add to their portfolios important CNS drugs.

上週在費城參加 AAIC 會議時，我們有機會與 SHINE 試驗的多位醫生和 PI 進行了交談。他們非常支持試驗結果，特別是整個範圍內認知變化的一致性。他們重視 100 毫克劑量組的新安全資訊和概況。與各投資者的回饋一致，RPI 對新試驗、持續劑量、患者群體、終點和試驗規模等後續步驟感興趣。我們也知道，多年來篩選中樞神經系統專案的製藥集團現在正在尋求在其產品組合中添加重要的中樞神經系統藥物。

For many, Alzheimer's disease is a top target. We continue to look -- we are looking forward to continuing our dialogue with these companies. Our next step is to convene a panel of leading neurologists to review our data best to finding and discuss their thinking on next steps in CT1812 drug development.

對許多人來說，阿茲海默症是首要目標。我們繼續尋找——我們期待繼續與這些公司對話。我們的下一步是召集一個由頂尖神經學家組成的小組來審查我們的數據，以最好地發現並討論他們對 CT1812 藥物開發後續步驟的想法。

I would like now to turn to the SHIMMER study, which is our next data readout. This Phase 2 trial with CT1812 enrolled 130 people with mild to moderate dementia with Lewy bodies or DLB. As a reminder, there are an estimated 1.5 million people in the US affected by DLB. And this disease is the second most common form of dementia. These patients are characterized by dementia, mobility issues, visual and sensory hallucinations, and significant GI issues. There are no currently approved treatment options.

我現在想談談 SHIMMER 研究，這是我們的下一個數據讀出。CT1812 的這項 2 期試驗招募了 130 名患有輕度至中度路易氏體失智症或 DLB 的患者。提醒一下，美國估計有 150 萬人受到 DLB 的影響。這種疾病是第二常見的癡呆症。這些患者的特徵是失智症、行動不便、幻視和感覺幻覺以及嚴重的胃腸道問題。目前沒有核准的治療方案。

From a pathological perspective, more than half of the DLB patients are estimated to both have alpha-synuclein and Abeta oligomers in their brain. We believe that CT1812 with its novel mechanism of action, protecting neurons from the pathogens from the toxicity of both pathogenic proteins, has the potential to treat DLB patients. This is a double-blind, randomized, three-arm study. Patients are randomized 1:1:1 with 100 or 300 milligrams of CT1812 or placebo.

從病理角度來看，估計超過一半的 DLB 患者大腦中同時存在 α-突觸核蛋白和 Abeta 寡聚體。我們相信，CT1812 以其新穎的作用機制，保護神經元免受病原體侵害，免受兩種致病蛋白的毒性影響，具有治療 DLB 患者的潛力。這是一項雙盲、隨機、三臂研究。患者以 1:1:1 的比例隨機接受 100 或 300 毫克 CT1812 或安慰劑。

This study is not powered to show significance. It is designed as a proof-of-concept study to determine the change in the MoCA -- that is the Montreal Cognitive Assessment scale -- after six months of receiving CT1812 or placebo. This trial is supported by nondiluted funding from the NIH, and the trial is being led by Dr. James Galvin from the University of Miami Miller School of Medicine.

這項研究沒有動力來顯示意義。它被設計為一項概念驗證研究，以確定接受 CT1812 或安慰劑六個月後 MoCA（即蒙特利爾認知評估量表）的變化。該試驗得到了美國國立衛生研究院 (NIH) 的非稀釋資金支持，試驗由邁阿密大學米勒醫學院的詹姆斯·加爾文 (James Galvin) 博士領導。

We have completed enrollment, and we expect to report top-line results by year-end. We believe the SHIMMER trial results will add to the understanding of CT1812's potential for treating neurodegenerative disease. As with AV patients in the SHINE trial, we look forward to providing patients and caregivers an effective, convenient option to slow the progress of DLB.

我們已經完成了註冊工作，預計將在年底前報告主要結果。我們相信 SHIMMER 試驗結果將加深人們對 CT1812 治療神經退化性疾病潛力的了解。與 SHINE 試驗中的 AV 患者一樣，我們期待為患者和照護者提供有效、便利的選擇來減緩 DLB 的進展。

Now a word about our other two trials. In brief, our START trial is actively recruiting participants with early Alzheimer's disease. Participants on stable background therapy with lecanemab and donanemab will be allowed to enroll in the trial. And we expect this will allow us to provide real-world evidence of CT1812 potential as monotherapy and in combination with monoclonal antibody treatments.

現在談談我們的另外兩個試驗。簡而言之，我們的 START 試驗正在積極招募患有早期阿茲海默症的參與者。使用 Lecanemab 和 donanemab 進行穩定背景治療的參與者將被允許參加試驗。我們預計這將使我們能夠提供 CT1812 作為單一療法以及與單株抗體治療相結合的潛力的真實世界證據。

We're also actively enrolling participants in our MAGNIFY study. This is a randomized, placebo-controlled Phase 2 study of 240 participants, who have dry age-related macular degeneration and measurable geographic atrophy. Over the treatment period, change in lesion size and best corrected visual acuity will be assessed to determine [of] CT1812 in slow vision loss.

我們也積極招募 MAGNIFY 研究的參與者。這是一項隨機、安慰劑對照的 2 期研究，共有 240 名參與者參加，這些參與者患有乾性老年黃斑部病變和可測量的地理萎縮。在治療期間，將評估病灶大小和最佳矯正視力的變化，以確定 CT1812 緩慢視力喪失的情況。

Now during this past year, Cognition scientists published multiple manuscripts and made at least nine presentations at medical and scientific converses. All the publications are available on our website.

在過去的一年裡，認知科學家發表了多篇手稿，並在醫學和科學對話中做了至少九次演講。所有出版物都可以在我們的網站上找到。

Importantly, the scientific evidence generated by our team has continued to support our development efforts, providing insights into proteins and biological processes impacted by CT1812 in neurologic and dry and ophthalmology conditions. In closing, in 2024, we have made significant progress advancing CT1812 and we believe this drug has the potential to be an important part of the developing paradigm for dementia treatments.

重要的是，我們團隊產生的科學證據繼續支持我們的開發工作，提供 CT1812 在神經系統、乾眼症和眼科疾病中影響的蛋白質和生物過程的見解。最後，到 2024 年，我們在 CT1812 方面取得了重大進展，我們相信這種藥物有潛力成為癡呆症治療開發範例的重要組成部分。

With that, I turn the call over to John Doyle for a review of our results.

說完，我將電話轉給約翰·道爾 (John Doyle)，讓他審核我們的結果。

Thank you, Lisa. For the first half of 2024, we continue to execute with financial stewardship by efficiently managing our resources and leveraging NIA grant funding to support our clinical programs. As of June 30, 2024, our cash and cash equivalents were approximately $28.5 million, and total grant funds remaining from the NIA were $57.3 million. The company estimates that it has sufficient cash to fund operations and capital expenditures into the second quarter of 2025.

謝謝你，麗莎。2024 年上半年，我們將繼續執行財務管理，有效管理我們的資源並利用 NIA 撥款來支持我們的臨床計畫。截至 2024 年 6 月 30 日，我們的現金和現金等價物約為 2,850 萬美元，NIA 剩餘的贈款總額為 5,730 萬美元。該公司估計有足夠的現金來為 2025 年第二季的營運和資本支出提供資金。

Research and development expenses were $11.6 million for the second quarter ended June 30, 2024, compared to $8.5 million for the comparable period in 2023. This increase was primarily related to higher costs associated with advancing our clinical programs, including Phase 2 trial activities, with contract research organizations and personnel costs.

截至 2024 年 6 月 30 日的第二季研發費用為 1,160 萬美元，而 2023 年同期為 850 萬美元。這一增長主要與推進我們的臨床計畫（包括第二階段試驗活動）、合約研究組織和人員成本相關的成本增加有關。

General and administrative expenses were $3.1 million for the second quarter ended June 30, 2024, compared to $3.3 million for the comparable period in 2023. The decrease was primarily related to lower professional services. The company reported a net loss of $7 million or $0.18 per basic and diluted share for the second quarter ended June 30, 2024, compared to a net loss of $4.7 million or $0.16 per basic and diluted share for the same period in 2023.

截至 2024 年 6 月 30 日的第二季一般及管理費用為 310 萬美元，而 2023 年同期為 330 萬美元。下降主要與專業服務減少有關。該公司報告稱，截至2024 年6 月30 日的第二季淨虧損為700 萬美元，即每股基本股和稀釋股0.18 美元，而2023 年同期淨虧損為470 萬美元，即每股基本股和稀釋股0.16 美元。

I'll now turn the call back over to the operator, who can open the call to 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。

Hi. This is Elaine Kim on for Charles Duncan. Thank you for taking our questions. So in the SHINE trial, the 100 mg dose did not meaningfully alter the Abeta 40 and 42 levels, while the 300 mg did -- but with the changes with the 100 mg dose perhaps being more pronounced after a year of dosing versus the six months? And I have a follow-up.

你好。我是伊萊恩金 (Elaine Kim) 替查爾斯鄧肯 (Charles Duncan) 發言。感謝您接受我們的提問。因此，在 SHINE 試驗中，100 毫克劑量並沒有顯著改變 Abeta 40 和 42 水平，而 300 毫克卻可以，但與服用六個月相比，100 毫克劑量的變化在一年後可能更加明顯？我有一個後續行動。

Tony, do you want to address that? Thank you, Elaine.

東尼，你想解決這個問題嗎？謝謝你，伊萊恩。

Yes. Hi, Elaine. You're right. The 100-milligram dose did not significantly alter the Abeta monomers in the same way that the 300-milligram dose had. I think a more relevant biomarker here is the NfL, which is a marker of general neurodegeneration where we saw a really robust change, both to the 300 mg and the 100 mg.

是的。嗨，伊萊恩。你說得對。100 毫克劑量並沒有像 300 毫克劑量那樣顯著改變 Abeta 單體。我認為這裡更相關的生物標記是 NfL，它是一般神經退化的標記物，我們在 300 毫克和 100 毫克劑量下都看到了非常強勁的變化。

The monomers, we believe, is part of the basic mechanism of our receptor, rather than a key part of the disease-modifying process that you see here. To further answer your question around longer trials, we do expect that with longer trials, such as 12- or 18-month trials, we would then begin to see more of the downstream biomarkers moving as well.

我們相信，單體是我們受體基本機制的一部分，而不是您在這裡看到的疾病緩解過程的關鍵部分。為了進一步回答您關於較長試驗的問題，我們確實預計，透過較長的試驗，例如 12 或 18 個月的試驗，我們將開始看到更多的下游生物標記發生變化。

Got it. Okay, that makes sense. Thank you. And for the follow-up, your cash runway is into the second quarter of 2025. How do you plan on lengthening that runway and support later-stage trials? And then maybe jumping the guns, but maybe up to Phase 3, how do you plan on doing that?

知道了。好吧，這是有道理的。謝謝。對於後續行動，您的現金跑道是 2025 年第二季。您計劃如何延長跑道並支持後期試驗？然後也許會操之過急，但也許到了第三階段，你打算怎麼做？

Yeah. Thank you, Elaine. I mean, there's a lot of things that we need to evaluate. There will be a lot of options available to us. So as we look to extend our runway, we'll certainly take all of those into consideration and move forward as we design the next stage of those trials.

是的。謝謝你，伊萊恩。我的意思是，我們需要評估很多事情。我們將有很多選擇。因此，當我們希望擴展我們的跑道時，我們肯定會考慮所有這些因素，並在設計這些試驗的下一階段時繼續前進。

Ram Selvaraju, H.C. Wainwright.

塞爾瓦拉朱 (Ram Selvaraju)，H.C.溫賴特。

Thanks very much for taking my questions. First of all, somewhat intellectually provocative one, if I may. There was some discussion at AAIC in Philadelphia last month about the potential applicability of GLP-1 receptor agonism to the treatment of Alzheimer's disease. Do you think there could be any synergistic activity of CT1812 with GLP-1 receptor agonist specifically in the context of Alzheimer's?

非常感謝您回答我的問題。首先，如果可以的話，有點智力上的挑釁性。上個月在費城舉行的 AAIC 會議上就 GLP-1 受體激動劑治療阿茲海默症的潛在適用性進行了一些討論。您認為 CT1812 與 GLP-1 受體激動劑在治療阿茲海默症時是否可能具有協同活性？

That's a very interesting question, Ram. Tony, any thoughts on that?

這是一個非常有趣的問題，拉姆。托尼，對此有什麼想法嗎？

Sure. Yeah, interesting. I think obviously, the world is very interested to see how the GLP-1s behaves in Alzheimer's disease. Given the mechanism of our drug is a very basic upstream interaction within the basic pathophysiology of Alzheimer's disease. We think CT1812 has the potential as a monotherapy as well as in conjunction with other therapies. We're certainly interested in seeing it with approved -- current approved to therapies. And if GLP-1 were to be approved for Alzheimer's disease, it would be very interesting to see how it acts together. So perhaps in the future, we'll see that data.

當然。是的，有趣。我認為顯然，全世界都非常有興趣了解 GLP-1 在阿茲海默症中的表現。鑑於我們藥物的機制是阿茲海默症基本病理生理學中非常基本的上游交互作用。我們認為 CT1812 具有作為單一療法以及與其他療法聯合使用的潛力。我們當然有興趣看到它獲得批准——目前已批准用於治療。如果 GLP-1 被批准用於治療阿茲海默症，那麼看看它如何協同作用將會非常有趣。所以也許在未來，我們會看到這些數據。

Great. And then just a quick follow-up. On the dosage, I was wondering if there were doses intermediate between the 100 and the 300 that you would consider assessing further in clinical development? Or if at this juncture, you've ruled that out. And if you were to study intermediate doses, which ones do you think are likely to be most appropriate?

偉大的。然後進行快速跟進。關於劑量，我想知道您是否會考慮在臨床開發中進一步評估 100 到 300 之間的中間劑量？或者，如果此時此刻，您已經排除了這種可能性。如果您要研究中間劑量，您認為哪些劑量可能最適合？

Yeah. So we do have intermediate doses being studied right now. In our START trial, which is the 540-participant study in early Alzheimer's disease, we have a 200-milligram dose. And in our MAGNIFY trial, which is the study in dry AMD, we also have the 200-milligram dose.

是的。所以我們現在確實正在研究中間劑量。在我們的 START 試驗中，這是一項有 540 名參與者參與的早期阿茲海默症研究，我們的劑量為 200 毫克。在我們的 MAGNIFY 試驗（針對乾性 AMD 的研究）中，我們也有 200 毫克的劑量。

And indeed, we introduced those doses a few years back for this very reason, believing that it might be a very nice, sweet spot, where we see really good efficacy but fewer adverse events. So those doses are already in the clinic, and it's likely that we'll see them again in the future.

事實上，我們幾年前正是出於這個原因引入了這些劑量，我們相信這可能是一個非常好的、最佳的點，我們看到了非常好的療效，但不良事件卻更少。所以這些劑量已經在診所使用，將來我們很可能會再次看到它們。

Mayank Mamtani, B. Riley.

Mayank Mamtani，B.Riley。

Hi. Can you hear me?

你好。你聽得到我嗎？

Yes, Mayank. Good morning.

是的，瑪雅克。早安.

This is Kevin Kuo for Mayank. Thanks for taking our questions.

我是 Mayank 的 Kevin Kuo。感謝您回答我們的問題。

Terrific. Yeah, hi, Kevin.

了不起。是的，嗨，凱文。

Hi. So now that we saw the detail from the SHINE trial, just wondering if you can talk about your expectation for your SHIMMER trial later this year and specifically, maybe your expectation for new [improvement] or other biomarkers that -- such as GFAP that may not be as relevant in different disease groups like Alzheimer, but maybe you have different actions in like DLB disease. And maybe if you can point to whether you still expect 300-milligram to have some liver enzyme signal? Thanks.

你好。現在我們已經看到了SHINE 試驗的細節，只是想知道您是否可以談談您對今年稍後的SHIMMER 試驗的期望，具體來說，也許您對新的[改進]或其他生物標誌物的期望-例如可能會出現的GFAP與阿茲海默症等不同疾病族群的相關性不高，但在 DLB 病等疾病中可能有不同的作用。也許您可以指出您是否仍期望 300 毫克有一些肝臟酵素訊號？謝謝。

So I think there were three questions, Kevin. You broke up in the middle. One is overall expectations for SHIMMER. Second, you were looking for a read on a number of the biomarkers. And the last thing you mentioned was the 300-milligram dose, what might be the profile of that dose. I'll turn those three questions over to Tony.

所以我認為有三個問題，凱文。你們中間就分手了。一是對SHIMMER的整體期望。其次，您正在尋找一些生物標誌物的讀物。您最後提到的是 300 毫克劑量，該劑量的概況可能是怎樣的。我會將這三個問題轉交給東尼。

Sure. Thank you. Right. So the SHIMMER study is designed very much like the SHINE study was, enrolling a similar number of individuals as the first proof-of-concept study where we're really looking again for safety and tolerability, and then for a clear and consistent trend that we can slow progression of the disease across multiple outcome measures. As we've announced previously, we're looking for a readout towards the end of this year.

當然。謝謝。正確的。因此，SHIMMER 研究的設計與 SHINE 研究非常相似，招募了與第一個概念驗證研究相似數量的個體，我們真正再次尋找安全性和耐受性，然後尋找清晰一致的趨勢我們可以通過多種結果指標來減緩疾病的進展。正如我們之前宣布的，我們正在尋找今年年底的讀數。

As far as the biomarkers go, I think as you've implied, the biomarker profile and changes within DLB are not nearly as well studied or predictable as they are currently in Alzheimer's disease. Having said that, we have a pretty robust program, where we're looking at changes in biomarkers from both CSF and blood, looking at canonical biomarkers as well as you've seen in our previous publications, proteomics and phosphoproteomics, looking at changes there. So we look forward to seeing those changes.

就生物標記而言，我認為正如您所暗示的那樣，DLB 中的生物標記概況和變化遠沒有像目前在阿茲海默症中那樣得到充分研究或預測。話雖如此，我們有一個非常強大的計劃，我們正在研究腦脊髓液和血液中生物標誌物的變化，研究典型的生物標記以及您在我們之前的出版物中看到的蛋白質組學和磷酸化蛋白質組學，研究那裡的變化。所以我們期待看到這些改變。

As far as the liver signal goes, we would expect the same thing in these individuals. These are folks who are nearly the same age. There's no reason we would expect to see anything different. So obviously, when that data reports out, we'll know that then.

就肝臟訊號而言，我們預期這些人也會出現同樣的情況。這些人年齡幾乎相同。我們沒有理由期望看到任何不同的東西。顯然，當數據報告出來時，我們就會知道。

Daniil Gataulin, Chardan.

丹尼爾·加陶林，查丹。

Yeah, hey, good morning, guys. Thank you for taking the question. Yeah, I have a couple. Yeah, good morning. First, on the SHINE, having had a bit of time to look through the data and now thinking about the next steps. What do you think are the key learnings from SHINE that you'll look to incorporate into the next trial outside of -- being a larger and the longer trial?

是的，嘿，早上好，夥計們。感謝您提出問題。是的，我有一對。是的，早安。首先，在 SHINE 上，我們花了一些時間查看數據，現在正在考慮下一步的步驟。您認為從 SHINE 中學到的關鍵經驗是什麼，您希望將其納入下一次試驗之外——規模更大、時間更長的試驗中？

Great question, Tony?

好問題，托尼？

Sure. Well, I think the key learnings, again, that we saw a very consistent and clear trend across all of the cognitive outcome measures that we can slow disease progression. More specifically, we see the magnitude of effect here as well as the variance. So this study now allows us to power future studies. Again, having seen nearly 40% decrease in progression as per the ADAS-Cog scales, we can now look to the next round of studies, which I anticipate will both be larger and longer. So that we can see these changes.

當然。嗯，我認為關鍵的教訓是，我們在所有認知結果測量中看到了非常一致和清晰的趨勢，我們可以減緩疾病的進展。更具體地說，我們在這裡看到影響的大小以及變異數。因此，這項研究現在使我們能夠為未來的研究提供動力。同樣，根據 ADAS-Cog 量表，進展減少了近 40%，我們現在可以期待下一輪研究，我預計研究將更大、更長。以便我們能夠看到這些變化。

We've also nicely identified a dose range, right, where we see effect without troublesome adverse events. Indeed, as Lisa mentioned, there are no discontinuations due to AEs in the 100-milligram dose and no changes in liver enzymes. So we have a very nice place to operate here for future studies.

我們也很好地確定了一個劑量範圍，在這個範圍內我們可以看到效果而不會出現麻煩的不良事件。事實上，正如 Lisa 所提到的，100 毫克劑量中沒有因 AE 而停藥，肝酵素也沒有變化。因此，我們在這裡有一個非常適合未來學習的地方。

Excellent. Got it. And another question, with the recent approvals in Alzheimer's, how did that affect the enrollment rate for your CT1812 trials? And related to that, what fraction of participants in the START trial do you expect to be on concurrent approved Alzheimer's disease medications?

出色的。知道了。另一個問題是，隨著最近阿茲海默症的批准，這對 CT1812 試驗的入組率有何影響？與此相關的是，您預計 START 試驗中的參與者中有多少比例會同時服用核准的阿茲海默症藥物？

Tony?

托尼？

Yeah. So the inclusion criteria or the patient population for the monoclonal antibodies, and for our SHINE participants were somewhat different, a little bit overlapping, but generally different. So I'm not sure it really impacted recruitment. I think overall, the -- having -- the general population is now very aware and interested that there are drugs available for Alzheimer's disease, has been a great asset. And people are coming into clinics and interested and inquiring. So overall, I'd say it was a boost. But again, it's a somewhat different population.

是的。因此，單株抗體和我們的 SHINE 參與者的納入標準或患者群體有些不同，有一點重疊，但總體上是不同的。所以我不確定這是否真的影響了招募。我認為總體而言，普通民眾現在非常意識到有藥物可用於治療阿茲海默症，並且對此很感興趣，這是一筆巨大的財富。人們走進診所並對此產生興趣並詢問。總的來說，我想說這是一個推動。但同樣，這是一個有些不同的人群。

As far as how many individuals will be randomized or will be on approved monoclonal antibodies within our START trial, that's still a little unknown. Obviously, one of the antibodies launched not long ago and we'll see how it penetrates the market. The other antibody just recently received approval and is just now launching, right? So we'll see.

至於在我們的 START 試驗中，有多少人將被隨機分配或將接受批准的單株抗體治療，這仍然是一個未知數。顯然，其中一種抗體是不久前推出的，我們將看看它如何滲透市場。另一種抗體最近剛剛獲得批准並且剛剛推出，對吧？所以我們拭目以待。

And within that study, we are stratifying all individuals, so that we'll have an even number of people on monoclonal antibodies across the different treatment groups. So we'll have a very good look at safety and tolerability of combined and depending on how many people were able to randomize, also potentially see if there are additive effects.

在這項研究中，我們將對所有個體進行分層，以便在不同治療組中使用單株抗體的人數為偶數。因此，我們將仔細研究組合的安全性和耐受性，並根據能夠隨機分組的人數，也可能看看是否有附加效應。

There are no further questions at this time. So I'll turn the call back over to Lisa Ricciardi, CEO.

目前沒有其他問題。因此，我會將電話轉回給執行長麗莎·裡恰爾迪 (Lisa Ricciardi)。

All right. Thank you. To conclude, we are focused on advancing our work to find a treatment to improve the lives of those afflicted with neurodegenerative diseases. The science is sound, we are compelled to move forward, and we continue to build evidence about what CT1812 can do for patients. Thank you for joining us today.

好的。謝謝。總之，我們致力於推進我們的工作，尋找一種治療方法來改善神經退化性疾病患者的生活。科學是合理的，我們必須繼續前進，我們將繼續收集證據證明 CT1812 可以為病人帶來什麼。感謝您今天加入我們。

[Today] has now concluded. You may now disconnect.

【今天】現已結束。您現在可以斷開連線。