Filana Therapeutics, Inc. (FLNA) 2024 Q2 法說會逐字稿

Welcome to Cassava Science's report for the second-quarter 2024. (Operator Instructions) As a reminder, this webcast is being recorded.

歡迎閱讀木薯科學公司2024年第二季報告。（操作說明）提醒：本次網路直播正在錄製。

During this call and the question-and-answer session afterwards, representatives of Cassava Sciences may make what are known as forward-looking statements. A forward-looking statement is one of that is not a historical fact. Forward-looking statements are not guarantees, and they involve risks, uncertainties, and assumptions. Such statements represent current expectations or beliefs concerning future events or future performance.

在本次電話會議及隨後的問答環節中，Cassava Sciences 的代表可能會發表所謂的前瞻性聲明。前瞻性陳述是指並非歷史事實的陳述。前瞻性陳述並非保證，且涉及風險、不確定性和假設。此類陳述代表了對未來事件或未來表現的當前預期或信念。

Forward-looking statements are predictions only based upon information currently available to the company. Actual events or results could differ materially from those made in any forward-looking statements due to a number of factors, risks, and uncertainties.

前瞻性陳述僅是基於公司目前掌握的資訊而做出的預測。由於諸多因素、風險和不確定性，實際事件或結果可能與任何前瞻性聲明中所述內容有重大差異。

Please refer to Cassava Science's recent filings with the SEC, including Form 10-K, for a description of the factors that could cause the events or results to differ materially from those made in forward-looking statements. Importantly, this conference call contains time-sensitive information that is accurate only as of the date of the live webcast, August 8, 2024. Except as required by law, the company undertakes no obligation to revise or update any forward-looking statements to reflect events and circumstances after the date of this webcast.

請參閱 Cassava Science 最近向美國證券交易委員會提交的文件，包括 10-K 表格，以了解可能導致事件或結果與前瞻性聲明中所述內容有重大差異的因素。重要的是，本次電話會議包含有時效性的信息，這些信息僅在 2024 年 8 月 8 日網絡直播當天有效。除法律另有規定外，本公司不承擔任何義務對本次網路直播日期之後發生的事件和情況進行修訂或更新任何前瞻性聲明。

It is now my pleasure to turn today's meeting over to Rick Barry, Executive Chairman of the Board of Directors. The floor is yours.

現在我很高興將今天的會議交給董事會執行主席里克·巴里先生。現在輪到你發言了。

Thank you, Judith. Good morning and thank you for joining us. With me today are three key members of the Cassava team: Doctor Jim Kupiec, our Chief Medical Officer; Eric Shoen, Cassava's Chief Financial Officer; and Chris Cook, our General Counsel and internal Swiss Army knife. You'll be meeting other talented players on the team in the future.

謝謝你，朱迪絲。早安，感謝各位的參與。今天陪同我出席的有 Cassava 團隊的三位關鍵成員：首席醫療官 Jim Kupiec 博士；Cassava 首席財務官 Eric Shoen；以及我們的總法律顧問兼內部瑞士軍刀 Chris Cook。未來你還會遇到隊上其他有才華的球員。

We have a lot of material to cover this morning, so I'll get right to it.

今天早上我們要講的內容很多，所以我這就直接進入正題。

By now you have, hopefully, seen the press release that we put out this morning that discusses some of our progress during the second quarter. Specifically, we highlighted the progress in our Phase 3 trials. The execution of these trials has been impressive. We expect our last patient, last visit in our ReTHINK trial in early Q4 and a top-line readout of the data by year end.

希望您現在已經看到了我們今天早上發布的新聞稿，其中討論了我們在第二季度取得的一些進展。具體來說，我們重點介紹了我們在 3 期試驗中的進展。這些試驗的執行情況令人印象深刻。我們預計 ReTHINK 試驗的最後一名患者將在第四季初完成最後一次訪視，並在年底前公佈初步數據結果。

We also expect our second Phase 3 trial, ReFOCUS, to read out in mid-year. We remain optimistic about the results of these trials. We think they are well-powered to demonstrate a statistically significant difference between the drug and placebo arms, but investors should keep in mind that no one can correctly forecast the results of any trial. There are, of course, no guarantees.

我們也預計第二項 3 期試驗 ReFOCUS 的結果將在年中公佈。我們對這些試驗結果仍然保持樂觀。我們認為他們有足夠的統計效力來證明藥物組和安慰劑組之間存在統計上的顯著差異，但投資者應該記住，沒有人能夠正確預測任何試驗的結果。當然，這並不能保證什麼。

Earlier in the second quarter, Cassava raised $123 million from the warrants that we distributed to shareholders in January. The warrants allowed shareholders to invest directly in the company or to sell their warrants in the open market. The funds that we raised from the program significantly strengthened our balance sheet.

第二季初，Cassava 透過 1 月向股東分發的認股權證籌集了 1.23 億美元。認股權證允許股東直接投資公司，或在公開市場上出售其認股權證。該項目籌集的資金極大地改善了我們的資產負債表。

As a reminder, several of us inside the company converted all or a portion of our warrants into stock, including me. I converted every warrant that was available to me. Suffice it to say that we are believers. We expect to end 2024 with a cash balance of between $117 million and $127 million, which will allow us enough liquidity to get past our Phase 3 readouts, and by the way, that cache number includes the impact of our potential settlement which I will discuss shortly.

提醒一下，公司內部有好幾個人，包括我，都把全部或部分認股權證轉換成了股票。我把所有能取得的授權書都兌換了電子授權書。總之，我們都是信徒。我們預計到 2024 年底，現金餘額將在 1.17 億美元至 1.27 億美元之間，這將使我們有足夠的流動性來度過第三階段的讀數階段。順便說一句，這個現金餘額數字包含了我們潛在的和解協議的影響，我稍後會討論這一點。

We are very grateful for the confidence that investors have demonstrated in Cassava. Just last week, we announced that we are lengthening our open-label extension trials for both our Phase 2 and Phase 3 patients. I want to take a minute to explain why we thought this was important.

我們非常感謝投資者對Cassava的信任。就在上週，我們宣布將延長 2 期和 3 期患者的開放標籤擴展試驗。我想花點時間解釋一下我們為什麼認為這件事很重要。

Prior to making this change, patients who participated in our Phase 2 program had the opportunity, but not the requirement, to remain on our drug simufilam for an additional two years. After being on the drug, in some cases for four years, some of these Phase 2 patients were losing access to it.

在做出這項改變之前，參與我們 2 期計畫的患者有機會（但並非必須）繼續服用我們的藥物西莫菲拉姆兩年。有些二期臨床試驗患者在接受藥物治療長達四年後，失去了獲得藥物的機會。

In our Phase 3 program, patients had the opportunity to go on simufilam for 12 months after completing the trial. It is important for our patients to have continued access to our drug. Just imagine being the patient or the loved one of a patient who was on the drug and had perceived that the patient had received the benefit from the drug, but who'd exhausted the duration of the open-label extension.

在我們的 3 期臨床試驗中，患者有機會在完成試驗後接受 simufilam 治療 12 個月。確保我們的患者能夠持續獲得我們的藥物至關重要。試想一下，如果你是正在服用這種藥物的患者或患者的親人，並且感覺患者已經從這種藥物中受益，但是開放標籤擴展期已經結束，你會作何感想？

After asking patients to take the inherent risk of joining our clinical trials, we felt it was unfair to those patients to not continue to offer them the option to continue at least until we knew the results of our Phase 3 programs, and the FDA had the opportunity to review our results.

在要求患者承擔參與我們臨床試驗的固有風險之後，我們認為，至少在我們了解 3 期試驗結果並且 FDA 有機會審查我們的結果之前，不繼續為這些患者提供繼續參與的選擇，是對這些患者的不公平的。

Honestly, the decision to expand our open-label trials was not a hard one. It was driven by our clinical team who carefully listened to the investigators at our clinical sites. Cassava needs to prepare for success, and even though it will add significant cost over the next two to three years, it is absolutely the best thing we could do for our patients.

說實話，擴大開放標籤試驗的決定並不難做。這是由我們的臨床團隊推動的，他們認真聽取了我們臨床試驗點的研究人員的意見。木薯需要為成功做好準備，儘管在未來兩到三年內會增加大量成本，但這絕對是我們能為病人做的最好的事情。

It bears repeating that 89% of the patients in our trials have elected to continue on the open-label extensions. You may have also noticed that we added further cognition and plasma biomarker monitoring every 6 months for patients who choose to continue on our open-label extension trial. We're doing that because the data we generate could have real value in helping us understand the potential long-term impact of simufilam.

值得重申的是，我們試驗中 89% 的患者選擇繼續參加開放標籤擴展試驗。您可能也注意到，對於選擇繼續參加我們開放標籤擴展試驗的患者，我們每 6 個月增加一次認知和血漿生物標記監測。我們這樣做是因為我們產生的數據可能具有真正的價值，可以幫助我們了解西莫菲拉姆的潛在長期影響。

Our Phase 3 program has been very well executed and on track. Doctor Kupiec will tell you more about that shortly.

我們的第三階段計畫執行得非常順利，進展順利。庫皮克醫生稍後會詳細解釋。

Now, we must plan for success. Continuing our open-label extension trials was one way for planning for success, but in the coming months you will see others. You will notice an uptick in our R&D spending during the second half of the year. Some of that increased spending will be devoted to preparation for the commercial launch of our drug.

現在，我們必須為成功做好計劃。繼續進行開放標籤擴展試驗是規劃成功的一種方式，但在接下來的幾個月裡，您將會看到其他方式。您會注意到，我們下半年的研發支出將會增加。增加的部分支出將用於為我們藥物的商業上市做準備。

We are currently ramping up our active pharmaceutical ingredient purchases, securing increased outsource manufacturing capacity and exploring distribution capabilities. We have to plan for Cassava's successful transition from a development stage company to a commercial enterprise. What we cannot accept is for us to fail the drug. There is an overwhelming need for Alzheimer's patients to have a drug that has the profile that simufilam has displayed so far in its development. We cannot let patients and their loved ones down.

我們目前正在加強活性藥物成分的採購力度，確保增加外包生產能力，並探索分銷管道。我們必須為Cassava從一家發展階段公司成功轉​​型為商業企業做好規劃。我們絕對不能接受的是，我們在藥物研發方面失敗。阿茲海默症患者迫切需要一種像西莫菲拉姆在研發過程中所展現的那種療效的藥物。我們不能讓患者及其親人失望。

In today's press release, we discussed the $40 million reserve we are taking for potential settlement with the Securities and Exchange Commission. This statement does not mean that we have an agreement in principle with the SEC yet, but it does mean that we now have enough information to understand what our exposure could be if we do come to a resolution with the SEC that will end their investigation of the company.

在今天的新聞稿中，我們討論了我們為可能與美國證券交易委員會達成和解而預留的 4000 萬美元儲備金。這份聲明並不意味著我們已經與美國證券交易委員會達成原則性協議，但這確實意味著我們現在掌握了足夠的信息，可以了解如果我們與美國證券交易委員會達成和解，結束他們對公司的調查，我們可能會面臨哪些風險。

I should add that we are continuing to have constructive conversations with both the SEC and the Department of Justice. There really isn't more we can say about this now, but we hope to be able to do so before long. We are not taking charge of this magnitude lightly. $40 million is an awful lot of money for anyone, let alone a company of our size, but it is our goal to put our past behind us and focus entirely on our mission, developing a best-in-class treatment for Alzheimer's patients.

我還要補充一點，我們正在繼續與美國證券交易委員會和司法部進行建設性對話。目前我們對此真的沒有什麼可說的了，但我們希望不久之後就能有更多消息。我們絕不會輕率地承擔如此重大的責任。 4000萬美元對任何人來說都是一筆巨款，更何況對我們這樣規模的公司而言。但我們的目標是放下過去，全心全意地專注於我們的使命，為阿茲海默症患者開發一流的治療方法。

Many of you have likely read the letter I wrote to the Cassava community after becoming Executive Chair on July 17. In that letter, I told the story of my original connection to Alzheimer's disease, the father of a good friend named Buddy, whose life was cut short by the disease. Since I wrote that letter, I've come to understand that nearly everyone has a buddy story, and here at Cassava, each of our people has many buddy stories.

你們中的許多人可能都讀過我於 7 月 17 日就任執行主席後寫給木薯社區的信。在那封信中，我講述了我與阿茲海默症的最初聯繫，我的一位好朋友巴迪的父親因這種疾病而英年早逝。自從我寫了那封信之後，我才明白幾乎每個人都有一段關於朋友的故事，而在Cassava，我們每個人都有很多關於朋友的故事。

Before July 17, I thought Cassava had a good management team in place, but now I appreciate how great the team really is. What I see is a group of determined and dedicated people who come to work each day because they are committed to making a difference in the lives of patients and their families, and that is what motivates us.

在 7 月 17 日之前，我認為 Cassava 已經擁有一支優秀的管理團隊，但現在我才真正體會到這支球隊有多好。我看到的是一群意志堅定、盡職盡責的人，他們每天來上班，是因為他們致力於改變病人及其家人的生活，而這正是激勵我們的動力。

As you might imagine, I had a lot to think about before taking on this challenge. Cassava Sciences has been through an awful lot the last few years, and frankly, some of our wounds may have been self-inflicted, while some clearly have not. Most of you are probably familiar with the expression that what doesn't kill you makes you stronger.

正如你所想，在接受這項挑戰之前，我有很多事情需要考慮。過去幾年，木薯科學公司經歷了許多可怕的事情，坦白說，我們的一些傷痛可能是自找的，而有些傷痛顯然不是。你們大多數人可能都熟悉「凡殺不死你的，必使你更強大」這句諺語。

Our company has been the subject of intense scrutiny for the past three years. Today, we are a stronger company because of it. We are thinking ahead to what we could create and not dwelling on the various challenges we have faced in the past. For me, the opportunity to work alongside people who are so focused on bringing what could be a game changing therapy to patients who are in dire need of one was too great for me to ignore.

過去三年，我們公司一直受到密切關注。正因如此，我們今天才成為更強大的公司。我們著眼於未來可以創造什麼，而不是糾結於過去面臨的各種挑戰。對我來說，能有機會與那些致力於為急需治療的患者帶來可能改變遊戲規則的療法的人們一起工作，這樣的機會實在太難得了，我無法錯過。

For more than three decades, Dr. Kupiec has been intimately involved in drug development for companies like Pfizer, Sanofi, and Ciba-Geigy. Before joining Cassava in 2021, Jim served as Vice President, Global Clinical Leader for Parkinson's disease, and Clinical Head of the Neuroscience Research Unit at Pfizer. I should add that Dr. Kupiec is one of the key reasons why I joined the Board of Cassava in 2021.

三十多年來，庫皮克博士一直密切參與輝瑞、賽諾菲和汽巴-嘉基等公司的藥物開發工作。在 2021 年加入 Cassava 之前，Jim 曾擔任輝瑞公司副總裁、全球帕金森氏症臨床負責人和神經科學研究部門臨床負責人。我還要補充一點，庫皮克博士是我在 2021 年加入 Cassava 董事會的關鍵原因之一。

JIm also serves the Independent Review Committee, the IRC at Target ALS, also known as Lou Gehrig's disease, another neurodegenerative disorder, and he serves it pro bono. The truth is that Jim's experience in running trials like this is so deep he's probably forgotten more about running a Phase 3 trial than most people will have ever learned.

Jim 也擔任 Target ALS（又稱盧伽雷氏症，另一種神經退化性疾病）獨立審查委員會 (IRC) 的職務，並且是義務服務。事實上，吉姆在進行此類試驗方面的經驗非常豐富，他可能已經忘記了比大多數人一生所學到的還要多的關於開展 3 期試驗的知識。

I've asked Doctor Kupiec to walk you through our Phase 3 program so that you understand how well controlled and rigorous this program is. Jim.

我已經請庫皮克醫生向您詳細介紹我們的第三階段項目，以便您了解該項目的控制有多嚴格。吉姆。

Yeah, hey, thanks, Rick, for the introduction, and good morning, everyone. This is Jim Kupiec, Chief Medical Officer of Cassava Sciences.

是啊，嘿，謝謝瑞克的介紹，大家早安。這位是卡薩瓦科學公司的首席醫療官吉姆·庫皮克。

As Rick stated, I've been actively involved in drug development efforts at various companies for over 30 years, and I've had a particular focus on investigational drugs for the treatment of neurologic diseases since the late 1990s. I've worked on teams that have successfully developed drugs and brought them to the pharmacy shelves. However, developing new medicines for neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, or ALS has more often than not been associated with failure.

正如里克所說，30多年來，我一直積極參與各家公司的藥物研發工作，自1990年代末期以來，我一直特別關注用於治療神經系統疾病的試驗性藥物。我曾參與多個藥物研發團隊，並成功將這些藥物推向市場，最後上架銷售。然而，開發治療阿茲海默症、帕金森氏症或肌萎縮側索硬化症等神經退化性疾病的新藥往往以失敗告終。

The clinical outcomes or end points that we assess in randomized clinical studies are associated with large variants, and Phase 2 studies and AD studies had to be quite large, to hopefully show enough of a treatment signal to then justify a very large Phase 3 financial investment. When I led these Phase 2 and Phase 3 programs in the past, we frequently did not know until the end of a large Phase 3 study that the drug had failed. And this was always sad for both patients, and everyone involved in the research efforts.

我們在隨機臨床研究中評估的臨床結果或終點與較大的變異相關，因此 2 期研究和 AD 研究必須規模相當大，才能有望顯示足夠的治療訊號，從而證明 3 期研究的巨額資金投入是合理的。過去我領導這些二期和三期計畫時，我們經常直到大型第三期研究結束才知道藥物失敗了。這對患者和所有參與研究工作的人來說，始終是一件令人難過的事。

Drug development for neurologic diseases began to change dramatically around 2018, with the advent of ultra-sensitive, fluid-based biomarkers, a technologic advancement that many have characterized as the biomarker revolution for brain diseases. Biomarkers allow us to examine the machinery inside the cells, brain cells of patients with Alzheimer's disease.

2018 年左右，隨著超靈敏的液體生物標記的出現，神經系統疾病的藥物研發開始發生巨大變化，這項技術進步被許多人稱為腦部疾病的生物標記革命。生物標記使我們能夠檢查阿茲海默症患者腦細胞內部的機制。

Why is this important? All of us in the research community understand that drug-induced changes in the most basic cellular functions must occur first if one expects to also see cognitive benefit later on.

為什麼這很重要？研究界的所有人都明白，如果希望日後也能看到認知上的益處，那麼藥物引起的細胞最基本功能的改變必須先發生。

In January 2021, I accepted an offer from Cassava to design and execute the simufilam Phase 3 program in patients with mild to moderate Alzheimer's disease. I was very excited and I considered this a great opportunity to leverage both my many years of Alzheimer's disease trial experience, and the availability of these new biomarkers to design a true, state of the art Phase 3 program that my colleagues in the research community would view as a new gold standard.

2021 年 1 月，我接受了 Cassava 公司的邀請，負責設計和執行針對輕度至中度阿茲海默症患者的 simufilam 第三階段計畫。我感到非常興奮，並認為這是一個絕佳的機會，可以利用我多年在阿茲海默症試驗方面的經驗，以及這些新的生物標誌物的可用性，設計一個真正的、最先進的 3 期臨床試驗項目，讓研究界的同行們將其視為新的黃金標準。

Soon after my arrival, we had a successful into Phase 2 meeting with the FDA in which they agreed that we had enough evidence to justify transition to Phase 3. I designed two Phase 3 studies and had them reviewed by key colleagues and leaders in the field to ensure they were both scientifically rigorous and operationally feasible.

我到任後不久，我們與 FDA 成功舉行了第二階段會議，他們同意我們有足夠的證據證明可以過渡到第三階段。我設計了兩項 3 期研究，並請該領域的主要同事和領導者進行審查，以確保它們在科學上嚴謹且在操作上可行。

Then the FDA proved each protocol via a regulatory procedure called the Special Protocol Assessment, or SPA. I took advantage of the biomarker revolution. A very unique design element for these studies was to require a plasma-based, phosphorylated tau biomarker level to confirm abnormal neuropathology instead of a PET scan, and PET scans are expensive, and they can have a significant negative impact on rapid study recruitment. We were in the lead with this strategy, and other sponsors have subsequently started to do the same thing.

然後，FDA 透過一項名為「特殊方案評估」（SPA）的監管程序對每個方案進行了驗證。我充分利用了生物標誌革命帶來的機會。這些研究的一個非常獨特的設計元素是要求使用基於血漿的磷酸化 tau 生物標記物水平來確認異常神經病理學，而不是進行 PET 掃描，而 PET 掃描很昂貴，並且可能會對快速招募研究對象產生重大負面影響。我們率先採用了這種策略，其他贊助商隨後也開始跟進。

In 2021, we selected Premier Research as the CRO to help operationalize the two studies. I've worked with many CROs during my career, and I have to tell you that Premier has been outstanding, and they have worked as hard and diligently on these studies as my own team.

2021年，我們選擇Premier Research作為CRO，以協助進行這兩項研究。在我職業生涯中，我曾與許多 CRO 合作過，我必須說，Premier 非常出色，他們在這些研究中付出的努力和勤奮程度不亞於我的團隊。

Countless hours were spent selecting and vetting high-quality investigators to conduct these studies here in the US and also in Canada, Puerto Rico, Australia, and South Korea. We selected Clario, a company with two decades of experience assessing PET and MRI scans in patients with Alzheimer's disease, and they would evaluate the thousands of images we would collect in this program.

我們花了無數個小時來挑選和審查高品質的研究人員，讓他們在美國、加拿大、波多黎各、澳洲和韓國進行這些研究。我們選擇了 Clario 公司，該公司在評估阿茲海默症患者的 PET 和 MRI 掃描方面擁有二十年的經驗，他們將評估我們在此計畫中收集的數千張影像。

We selected Cygnet Health, a stellar leader in the field of radar training, radar assessments, to ensure each cognitive and functional assessment at the clinical sites was conducted against a gold standard. Similar high-performance companies were selected to collect and analyze safety lab values, ECGs, and even patient compliance with study book.

我們選擇了雷達訓練和雷達評估領域的傑出領導者 Cygnet Health，以確保臨床現場的每一次認知和功能評估都按照黃金標準進行。選擇類似的高績效公司來收集和分析安全實驗室值、心電圖，甚至病人對研究手冊的依從性。

Now with everything in place, including IRB approvals, we began to screen and recruit patients in late 2021. We have about 170 committed research sites worldwide, and in less than two years, we have recruited over 1900 patients in both studies. Over 555 patients have completed their participation in the 52-week ReTHINK study. And over 420 patients have completed their participation in the 76-week ReFOCUS study for over a total of 975 completers.

現在一切準備就緒，包括獲得 IRB 批准，我們在 2021 年底開始篩選和招募患者。我們在全球擁有約 170 個致力於研究的基地，在不到兩年的時間裡，我們在兩項研究中招募了超過 1900 名患者。超過 555 名患者已完成為期 52 週的 ReTHINK 研究。超過 420 名患者完成了為期 76 週的 ReFOCUS 研究，完成研究的患者總數超過 975 人。

It's important to note that there is no overlap of clinical research sites between the two studies. The studies have a separate, completely different set of investigators supporting the research. As just mentioned, the ReTHINK study is 52 weeks in length, and it evaluates the potential cognitive and functional benefits in the film in patients with mild to moderate Alzheimer's disease.

值得注意的是，這兩項研究的臨床研究地點並沒有重疊。這些研究由另一組完全不同的研究人員提供支持。正如剛才所提到的，ReTHINK 研究為期 52 週，旨在評估該影片對輕度至中度阿茲海默症患者的潛在認知和功能益處。

Half of the 800 plus patients were randomized to simufilam, and half were randomized to placebo. Approximately 70% of the randomized patients have mild dementia, and approximately 30% of the randomized patients have moderate dementia.

800 多名患者中，一半被隨機分配到西莫菲拉姆組，另一半被隨機分配到安慰劑組。大約 70% 的隨機分組患者患有輕度癡呆症，約 30% 的隨機分組患者患有中度癡呆症。

A substantial number of patients in the ReTHINK study have also agreed to have their plasma analyzed for key Alzheimer's disease biomarkers. These blood samples will be analyzed by a completely independent, clear, certified, accredited laboratory.

ReTHINK 研究中的相當一部分患者也同意對其血漿進行分析，以檢測阿茲海默症的關鍵生物標記。這些血液樣本將由完全獨立、透明、經過認證和認可的實驗室進行分析。

Cassava, Premier, and our other collaborators have worked very closely to ensure the integrity of this entire study. I wanted this program to be the best I had ever created or worked on. We review data from research sites, monitor any errors that occur. We work closely with the IRBs to ensure the sites are properly conducting their efforts in a way that's consistent with good clinical practice.

Cassava、Premier 和我們的其他合作者密切合作，以確保整個研究的完整性。我希望這個程式是我創作或參與過的最棒的程式。我們會審核研究站點的數據，並監控出現的任何錯誤。我們與倫理審查委員會密切合作，以確保各研究中心以符合良好臨床實務的方式正確開展工作。

We conduct routine audits; we review and assess all safety reports and we document everything. We call this doing it by the book. We know that the FDA and other regulatory authorities expect this of us, and will they themselves conduct audits of Cassava, our CRO, our other collaborators, and many of our research sites.

我們會進行例行審核；我們會審查和評估所有安全報告，並記錄所有事項。我們稱之為按章辦事。我們知道 FDA 和其他監管機構對我們抱有這樣的期望，他們自己也會對我們的合約研究機構 Cassava、我們的其他合作方以及我們的許多研究機構進行審計。

I need to highlight that the patients, their physician investigators, all of us a Cassava, and Premier remain completely blinded to what treatment each patient is taking. Once the last patient has passed his or her last visit in the fall, we will work quickly and thoroughly to ensure that all minor inconsistencies or questions in the database are addressed.

我需要強調的是，患者、他們的醫生研究人員、我們所有 Cassava 和 Premier 的成員都完全不知道每個患者正在接受什麼治療。一旦最後一位患者在秋季完成最後一次就診，我們將迅速徹底地開展工作，以確保資料庫中所有細微的不一致或疑問都得到解決。

We will confirm the accuracy of each and every piece of data. This includes, for example, all clinical data, cognitive assessment data, lab and ECG data, imaging data. Once we are satisfied, the database will be blocked, and at that point, we cannot make any changes to its content. Data lock has always been a significant and dramatic milestone for me on any of the programs that I've led.

我們將核實每項數據的準確性。例如，這包括所有臨床數據、認知評估數據、實驗室和心電圖數據、影像數據。一旦我們滿意，資料庫將被鎖定，屆時我們將無法對其內容進行任何更改。在我所領導的所有專案中，資料鎖定一直都是一個意義重大且令人振奮的里程碑。

Premier Research will make this happen, at which point the locked and blinded database, including blinded biomarker results, will be shared with the biostatisticians at the Pentara Corporation, along with the treatment codes. This will allow them to break the blind and determine whether simufilam is effective.

Premier Research 將負責實現這一目標，屆時，包括盲法生物標記結果在內的鎖定和盲法資料庫將與 Pentara 公司的生物統計學家共享，同時也提供治療代碼。這將使他們能夠打破盲法，並確定西莫菲拉姆是否有效。

Everyone at Cassava and Premier continued to marrying blinded during this analytical period by Pentara. Pentara is the premier independent biostatistics group working on AD studies in my opinion. And that of many others. Once Dr. Suzanne Hendrix and her team members at Pentara conclude they have properly analyzed all the data, they will call us to set up a meeting to go over all their analysis, positive or negative. We will then prepare a public disclosure, and we're committed to doing this by the end of the year.

在 Pentara 的分析期間，Cassava 和 Premier 的每個人都繼續盲目地結婚。在我看來，Pentara 是從事阿茲海默症研究的首屈一指的獨立生物統計學團隊。還有很多其他人也遇到了同樣的問題。一旦 Suzanne Hendrix 博士和她在 Pentara 的團隊成員認為他們已經正確分析了所有數據，他們就會打電話給我們安排一次會議，討論他們所有的分析結果，無論是積極的還是消極的。之後我們將準備一份公開披露文件，我們承諾在年底前完成這項工作。

Moving ahead, the second Phase 3 study is the ReFOCUS study, and that has recruited over 1,100 patients. This study and the ReTHINK study are very similar in that patient selection is the same. However, the ReFOCUS study is 76 weeks in length, and there are 3 different treatments to which a patient can be randomized, 2 doses of simufilam and placebo.

接下來，第二項 3 期研究是 ReFOCUS 研究，該研究招募了 1,100 多名患者。這項研究和 ReTHINK 研究非常相似，因為患者的選擇方式相同。然而，ReFOCUS 研究持續 76 週，患者可以隨機分配到 3 種不同的治療方案、2 種劑量的西莫菲拉姆和安慰劑。

As the study is six months longer in duration, we expect topline results to report out mid-year 2025. The ReFOCUS study is also different in that many patients have the option of participating in a number of sub-studies, which evaluate the impact of simufilam on CSF fluid biomarkers, plasma biomarkers, amyloid PET imaging, tau PET imaging, and brain volume changes as determined by MRI.

由於研究的持續時間比預期長六個月，我們預計主要結果將於 2025 年年中公佈。ReFOCUS 研究的另一個不同之處在於，許多患者可以選擇參與多項子研究，這些子研究評估西莫菲拉姆對腦脊髓液生物標記、血漿生物標記、澱粉樣蛋白 PET 成像、tau 蛋白 PET 成像以及 MRI 確定的腦容量變化的影響。

The goal of these sub-studies is to demonstrate that simufilam has the potential to modify the underlying disease process of Alzheimer's disease. Patients in both Phase 3 studies have the option then of rolling over into the open-label extension study. As Rick shared, some 89% of patients have elected to do just that. As Chief Medical Officer for Cassava, I am ultimately responsible for the safety of these patients, and I spent a lot of time reviewing all types of safety, lab, and ECG reports, along with the medical monitor at Premier.

這些子研究的目標是證明西莫菲拉姆有可能改變阿茲海默症的潛在疾病過程。參與這兩項 3 期研究的患者可以選擇轉入開放性標籤擴展研究。正如里克所說，約有 89% 的患者選擇了這樣做。作為 Cassava 的首席醫療官，我最終對這些患者的安全負有責任，我花了大量時間與 Premier 的醫療監察員一起審查各種安全、實驗室和心電圖報告。

When a patient reports a new medical condition or symptom, this is called an adverse event for the purpose of regulatory filings. I'm pleased to report that no serious adverse event has yet been linked to study drugs in any of our Phase 2 or Phase 3 studies.

當患者報告新的疾病或症狀時，出於監管備案的目的，這被稱為不良事件。我很高興地報告，在我們所有的 2 期或 3 期研究中，尚未有任何嚴重不良事件與研究藥物有關。

A huge amount of safety data has now been shared on two separate occasions with the Data Safety Monitoring Board, or DSMB, who have instructed us to continue the studies without change. This Board is composed of very experienced, independent clinical scientist and a statistician, and they are charged with reviewing all safety data, even if they feel obligated to look at any unblinded safety data behind closed doors, as per their charter and a strict set of rules that enable such an assessment.

目前已兩次向資料安全監測委員會（DSMB）提交了大量安全數據，DSMB 指示我們繼續進行研究，無需做出任何變更。該委員會由經驗豐富的獨立臨床科學家和統計學家組成，負責審查所有安全數據，即使他們根據其章程和一套嚴格的規則，有義務在閉門會議中查看任何未進行盲法的安全數據，以便進行此類評估。

They are tasked to advise Cassava on how best to ensure the safety of our study participants, and if any changes in the conduct of the study are required. This is yet an extra step we've taken to ensure patient safety. The DSMB has already met twice, and we will meet again for the third time next month.

他們的任務是向 Cassava 提供建議，說明如何最好地確保研究參與者的安全，以及是否需要對研究的進行方式進行任何更改。這是我們為確保病人安全而採取的另一項額外措施。資料安全監測委員會 (DSMB) 已經召開過兩次會議，下個月我們將再次召開第三次會議。

Rick, that's my update for Phase 3 that I wanted to share, but if I may, I'd like to share a final personal note. I was excited when I joined Cassava, but I'm even more excited and optimistic now about simufilam and its chance of success in Phase 3. Simufilam continues to be safe and well-tolerated in a very large number of patients.

Rick，這就是我想和大家分享的第三階段最新進展，但如果可以的話，我還想分享一些個人感想。加入 Cassava 時我很興奮，但現在我對 simufilam 及其在第三階段試驗中取得成功的機會更加興奮和樂觀。Simufilam 在大量患者中仍然安全且耐受性良好。

Plus, the data from the 24-month open label Phase 2 safety study was remarkable in that patients with mild dementia apparently had no significant decline during that two-year treatment period. If this is true, and replicated in Phase 3, it would represent an exceptional achievement and a significant event in the field.

此外，為期 24 個月的開放標籤 2 期安全性研究的數據非常引人注目，因為輕度失智症患者在兩年的治療期間似乎沒有明顯的病情惡化。如果這是真的，並且在第三階段得到驗證，那將代表著一項非凡的成就，也是該領域的一件大事。

So thanks for everybody on the line for your attention. I look forward to sharing our results with you at the end of the year. Rick, back to you.

感謝各位線上收聽。我期待在年底與您分享我們的研究成果。瑞克，把鏡頭交還給你。

Thanks so much for that, Jim.

非常感謝你，吉姆。

I'm now going to ask Eric Schoen, Chief Financial Officer, to discuss our second-quarter results and our financial projections for the remainder of '24.

現在我將請財務長埃里克·舍恩討論我們第二季度的業績以及我們對 2024 年剩餘時間的財務預測。

Thanks, Rick.

謝謝你，里克。

On the cash front, we ended the June quarter with $207.3 million in cash. That balance is expected to be sufficient for operations through the conclusion of both ongoing Phase 3 trials and into calendar 2026, even after considering the potential $40 million loss contingency recorded in Q2 to resolve the SEC investigation that was discussed by Rick.

現金方面，截至6月底，我們持有現金2.073億美元。即使考慮到里克提到的，為解決美國證券交易委員會的調查，第二季度提列的潛在損失準備金 4000 萬美元，預計該餘額也足以支撐公司運營直至正在進行的第三階段試驗結束，並延續到 2026 年。

Rick also covered the successful completion of our warrant distribution during the second quarter. During the duration of the program, a total of approximately 3.8 million warrants were exercised. As a result, the company sold 5.7 million common shares at $22 per share for gross proceeds totaling $126.3 million. After offering costs, net proceeds to the company were $123.6 million.

Rick 也介紹了我們在第二季成功完成認股權證分發的情況。在該計畫實施期間，總共行使了約 380 萬張認股權證。因此，該公司以每股 22 美元的價格出售了 570 萬股普通股，總收益達 1.263 億美元。扣除發行費用後，公司淨收益為 1.236 億美元。

There are currently no remaining warrants outstanding. The warrant program was a really good boost for the balance sheet. We were pleased to offer our shareholders a dividend which gave them the choice to sell their warrants and receive cash or to exercise their warrants and increase their equity stake in the company.

目前已無未執行的逮捕令。認股權證計畫對資產負債表起到了很好的提振作用。我們很高興向股東派發股息，股東可以選擇出售認股權證並獲得現金，或行使認股權證並增加其在公司的股權。

On the cash spend side, net cash used in operations during the six months ended June 30, 2024, was $37.4 million. This was in line with our previous guidance. Net cash used in operations for the second half of 2024 is expected to be between $80 million and $90 million, including an estimated $40 million loss contingency related to fully resolving the SEC investigation.

在現金支出方面，截至 2024 年 6 月 30 日的六個月期間，營業活動中使用的現金淨額為 3,740 萬美元。這與我們先前的指導方針一致。預計 2024 年下半年經營活動使用的淨現金將在 8,000 萬美元至 9,000 萬美元之間，其中包括與徹底解決美國證券交易委員會調查相關的約 4,000 萬美元損失準備金。

Considering the spending level, we believe we will end the year with between $117 million to $127 million in cash. Net income was $6.2 million in Q2, compared to a net loss of $26.4 million for the same period in 2023. Net income resulted from a change in fair value of warrant liabilities, a non-cash item.

考慮到支出水平，我們認為年底現金餘額將在 1.17 億美元至 1.27 億美元之間。第二季淨收入為 620 萬美元，而 2023 年同期淨虧損為 2,640 萬美元。淨利源自於認股權證負債公允價值的變動，這是一個非現金項目。

This warrant gain was partially offset by the estimated SEC loss contingency settlement and cost to conduct the Phase 3 clinical program as well as other studies with simufilam. Research and development expenses for Q2 were $15.2 million. This compared to $25 million for the same period in 2023. R&D expenses decreased due primarily to the completion of patient screening and enrollment for our Phase 3 clinical program in the fall of 2023.

此次認股權證收益部分被美國證券交易委員會預計的損失或有結算費用以及開展 3 期臨床項目和其他西莫菲拉姆研究的成本所抵消。第二季研發費用為1520萬美元。相較之下，2023 年同期為 2,500 萬美元。研發費用下降主要是因為我們的 3 期臨床計畫在 2023 年秋季完成了病患篩選和招募。

Now I'll turn it back to Rick.

現在我把麥克風交還給瑞克。

Thank you, Eric. Okay, operator, could you please open the line for questions?

謝謝你，埃里克。好的，接線員，請開通提問線好嗎？

(Operator Instructions) Roy Soumit, Jones Research.

（操作說明）Roy Soumit，Jones Research。

Good morning, everyone, and thank you for providing all the details, Rick. Three questions. One is, on the discontinuation dropout rate of about 20% to 22%, could you describe us what was the key driver for that? Was it dose reduction, discontinuation due to any controversy related to the drug, any details would be great.

各位早安，里克，謝謝你提供所有細節。三個問題。一是，關於 20% 到 22% 的輟學率，您能否描述一下造成這種情況的關鍵因素是什麼？是劑量減少，還是因為與該藥物相關的任何爭議而停藥？任何細節都將不勝感激。

And the second is, the ADAS-Cog12, I suppose was designed more, with mild to moderate patients versus ADAS-Cog14. Now that we know a good chance that mild patients would show the benefit is ADAS-Cog12 still the appropriate endpoint and, if FDA gave any guidance, if only one of the co-primary hits, so what would be the regulatory path forward?

其次，ADAS-Cog12 的設計似乎更多是針對輕度至中度患者，而 ADAS-Cog14 則不然。既然我們知道輕症患者很有可能從中受益，那麼 ADAS-Cog12 是否仍然是合適的終點？如果 FDA 給了任何指導，如果只有一項共同主要療效指標，那麼監管方面的下一步該如何進行？

Okay, I think I've got it. Probably I'm going to ask Jim, I think to answer your questions. He's probably better prepared for it, Jim.

好的，我想我明白了。我可能會問吉姆，讓他來回答你的問題。吉姆，他可能已經做好了更充分的準備。

Yeah, let me see. I have the ADAS-Cog question. The first question was about the dropout rate. The dropout rate that we've seen in both of the two studies is about 20%, slightly more than 20% in the longer study. As is common in these studies, the most typical reason for a dropout is because of what I call study fatigue, patient fatigue, they withdraw consent, patients are moving someplace, study this, it's not just the patient involved in the study, but also a partner, a study partner, and they oftentimes are just weary from coming back and forth to the research center.

嗯，讓我看看。我有一個關於ADAS-Cog的問題。第一個問題是關於輟學率的。這兩項研究中我們看到的退出率約為 20%，較長的研究的退出率略高於 20%。在這些研究中，最常見的退出原因是所謂的“研究疲勞”或“患者疲勞”，他們撤回知情同意，患者搬到其他地方，研究不僅涉及患者本人，還涉及伴侶、研究夥伴，他們往往只是因為往返研究中心而感到疲憊。

So if you look at, let's say, other studies that have recently been reported and approved FDA, such as [adicatalab, or licatamab or dinatamab]. Again, the most common reason for dropouts is not adverse events, but withdrawal of consent.

所以，如果你看看，比如說，其他一些最近報告並獲得FDA批准的研究，例如：[adicatalab、或 licatamab 或 dinatamab]。再次強調，導致退學的最常見原因不是不良事件，而是撤回同意。

With regards to ADAS-Cog12, that's a good question. If we were going to an even earlier population like a mild cognitive impairment, we might use ADAS-Cog13 or 14, but for mild to moderate population, ADAS-Cog12 is more than adequate. The agency agrees as part of our earlier discussion a few years ago. And I think there was a third question. Can you please repeat that?

關於 ADAS-Cog12，這是一個很好的問題。如果我們要針對更早期的群體，例如輕度認知障礙患者，我們可能會使用 ADAS-Cog13 或 14，但對於輕度至中度認知障礙患者，ADAS-Cog12 就足夠了。該機構同意，這是我們幾年前早期討論的一部分。我想還有第三個問題。請您再說一次好嗎？

If you had any discussion with the FDA, if you hit only one of the core primary endpoints, not both Cog-12 and ADL.

如果您與 FDA 進行任何討論，如果您只達到了核心主要終點之一，而不是 Cog-12 和 ADL 兩個終點。

We've not had such a discussion at this point.

目前我們還沒有進行過這樣的討論。

Thank you for taking the questions.

感謝您回答這些問題。

Vernon Bernardino, H.C. Wainwright.

弗農·貝爾納迪諾，H.C. 溫賴特。

Hi, good morning and thanks for taking my question, Rick and Jim, I also want to welcome you to Cassava. Look forward to your activities in helping grow the company.

嗨，早安，里克和吉姆，感謝你們回答我的問題，我也想歡迎你們加入Cassava。期待您為公司發展做出貢獻。

I have a couple of questions, Rick. I know you can't go into the details as far as the SEC investigation, but I do want to press a little bit in the sense that could you remind us again what the SEC is investigating and what are the drivers of the $40 million dollar amount for the estimated loss contingency that you're recording?

里克，我有幾個問題。我知道您不能透露美國證券交易委員會調查的細節，但我確實想追問一下，您能否再次提醒我們一下美國證券交易委員會正在調查什麼，以及您記錄的 4000 萬美元預計損失準備金的驅動因素是什麼？

Well, I think you know the investigation began in 2021 after the citizen's petition was filed, and there were all kinds of allegations raised in that in that petition. The settlement, if we reach one, all I can say is it will end the investigation. And the commission seems to be most focused on the fact that the company raised money sometime in the, I can't remember now if it's the fourth quarter or the beginning of '21. And that seems to be really what they're focused on.

我想你應該知道，調查始於 2021 年，當時有人提交了公民請願書，而那份請願書中提出了各種各樣的指控。如果達成和解，我只能說這將結束調查。委員會似乎最關注的是該公司在某個時間點籌集了資金，我現在記不清是 2021 年第四季還是年初了。而這似乎正是他們關注的重點。

Okay, perfect. The second question I have for you, Dr. Kupiec, it's great that you've added the biomarkers to the Phase 3 studies. Regarding those biomarkers, will that be part of question one would be the top part of the top-line announcement for ReTHINK, and are some of those biomarkers going to be, let's say not necessarily targeted but perhaps ones that would answer some of the controversy that arose from the Phase 2 results, the early Phase 2 results that led to the indictment charges against a former adviser.

好的，完美。庫皮克博士，我的第二個問題是，您把生物標記添加到 3 期研究中真是太好了。關於這些生物標誌物，它們是否會成為 ReTHINK 頂級公告中第一個問題的核心內容？這些生物標記中是否會有一些，比如說不一定是針對特定目標的，但或許可以解答一些從 2 期試驗結果中引發的爭議，也就是導致對一位前顧問提起訴訟的早期 2 期試驗結果。

As there's controversy about those results, I don't want to get into the indictment itself, but with these biomarkers, it seems like there'd be an opportunity for the Phase 3 results to answer any lingering questions as far as not necessarily duplicating those results, but perhaps confirming the directionality of those biomarkers?

由於這些結果有爭議，我不想深入討論起訴書本身，但有了這些生物標誌物，似乎第三階段的結果有機會回答任何懸而未決的問題，不一定是要重複這些結果，而是或許可以確認這些生物標誌物的方向性？

Rick, you want to take that question?

瑞克，你想回答這個問題嗎？

I was sorry I was going to let you in on it, Jim.

吉姆，我很抱歉要讓你知道這件事。

Oh, okay, thanks, Rick. That's a really good set of questions. Thank you so much. So in our Phase 3 study, we have a number of biomarkers. There's in plasma in particular we're hoping, I cannot absolutely promise, but we are hoping that our plasma biomarker assessment from in patients from ReTHINK will be available at the end of the year, at the same time, we have cognitive data to present publicly. That is our hope and we're working to that end.

哦，好的，謝謝你，瑞克。這真是一組很好的問題。太感謝了。因此，在我們的 3 期研究中，我們有許多生物標記。特別是血漿方面，我們希望（我不能完全保證），ReTHINK 研究患者的血漿生物標記評估結果能在年底前公佈，同時，我們也有認知數據要公開展示。這是我們的願望，我們正在為此努力。

The types of biomarkers we're going to be looking at in Phase 3 will look at some of the basic abnormalities of cell function in patients who have Alzheimer's disease, the, phosphorylation of tau, the inflammatory changes that have been seen, and the degeneration of axons, for example, in patients with Alzheimer's disease.

我們將在第三階段研究的生物標記類型將著眼於阿茲海默症患者的一些基本細胞功能異常，例如 tau 蛋白的磷酸化、已觀察到的發炎變化以及軸突的退化。

This is the type of biomarkers that can be looked at in the plasma very accurately and with great precision. And they are the common ones that are being examined by most of the companies who are doing this type of work. There are also biomarkers that we can do in CSF, but that's part of the ReFOCUS study, and that we won't have those until sometime in the second half of next year in all likelihood.

這類生物標記可以在血漿中進行非常準確、非常精確的檢測。而這些正是從事這類工作的大多數公司正在研究的常見問題。我們也可以檢測腦脊髓液中的生物標記物，但這是 ReFOCUS 研究的一部分，而且很可能要等到明年下半年才能獲得這些結果。

But yes, to your question, we're hoping to have some biomarker data available later on this year. These, remember, these biomarkers, we're collecting them at various time points in a 52-week ReTHINK study. The data that you raised from Phase 2, much of it, from CSF done in Professor Wong's lab was in a 28-day study. And one of the things that we did a number of years ago was have an independent laboratory, Quanterix. I want to remind you of this, Quanterix did an assessment of a biomarker called pTau 181, which was in vogue then.

是的，回答您的問題，我們希望今年稍後能獲得一些生物標記數據。請記住，這些生物標誌物，我們正在為期 52 週的 ReTHINK 研究的不同時間點收集它們。您在第 2 期臨床試驗中提出的數據，大部分來自 Wong 教授實驗室進行的腦脊髓液研究，為期 28 天。幾年前，我們做的一件事就是成立了一個獨立的實驗室，Quanterix。我想提醒您，Quanterix 公司曾對一種名為 pTau 181 的生物標記進行評估，當時很受歡迎。

And then show and did show a significant statistically significant change. There's a small number of subjects in each of the treatment groups. So this is a double-blind study looking at placebo versus two doses of drugging. The data was in fact, significant, and I just want to remind you that, and, we're hoping to not only replicate that type of benefit, but also expand and augment it with a longer study and using perhaps more.

然後，結果顯示，並且確實顯示了具有統計意義的顯著變化。每個治療組的受試者人數都很少。這是一項雙盲研究，比較安慰劑與兩種劑量藥物的效果。事實上，數據意義重大，我只是想提醒大家這一點，而且，我們希望不僅能夠複製這種益處，還能透過更長的研究和使用更多樣本來擴大和增強這種益處。

I'll call it more contemporary blood-based biomarkers that are now available. So hopefully that will answer your question.

我稱之為目前可用的更現代的基於血液的生物標記。希望這能解答你的疑問。

No, that's fantastic. And I asked those questions because I don't know if everybody remembers. I'm sure you are very familiar with the data. A lot of the results happen very quickly within those 28 days, and that is part of the strength of the simufilam that you see the effects right away. As a follow up to Roy's question regarding ADAS-Cog12.

不，那太棒了。我問這些問題是因為我不知道大家是否都記得。我相信您對這些數據非常熟悉。許多效果會在 28 天內迅速顯現，這也是西莫菲蘭的功效之一，讓你能立即看到效果。作為 Roy 關於 ADAS-Cog12 問題的後續問題。

I was wondering if you could go a little bit into, obviously, it'd be great to get these patients on treatment with some simufilam as early as possible. But with the statistical plan of these pastry studies, I was wondering if you could describe a little bit, if not, perhaps, at least characterize your statistical plan. And the targeting of what kind of patients, you will be announcing, at least on the top line, level, for ReTHINK, and maybe even ReFOCUS.

我想請您稍微談談，顯然，如果能儘早讓這些患者接受西莫菲拉姆治療，那就太好了。但是關於這些糕點研究的統計方案，我想知道您是否可以稍微描述一下，如果不能，至少能否概括一下您的統計方案。至於您將在 ReTHINK 甚至 ReFOCUS 的整體層面上宣布針對哪些類型的患者，您又會作何表態呢？

So the analysis in these types of studies, you have to do what's called a modified intent to treat analysis, which means you include everybody in the analysis who has taken at least one dose of drug and has had at least one follow-up visit in order to determine whether or not cognition or function has changed.

因此，在這些類型的研究中，必須進行所謂的改良意向性治療分析，這意味著要將所有至少服用過一次藥物並至少進行過一次隨訪的人都納入分析，以確定認知或功能是否發生了變化。

For example, if somebody takes the bottle of pills, and then they just disappear, they lost the follow-up, they would not be included. But otherwise, everybody else, be they either have mild dementia or moderate dementia, will be included in that analysis. That is our primary analysis, that is what the FDA expects. There will be certainly subgroup analysis that we will do.

例如，如果有人拿走了藥瓶，然後就消失了，他們就失去了後續追踪，不會被納入研究範圍。但除此之外，其他所有人，無論患有輕度癡呆症或中度癡呆症，都將納入分析。這是我們的主要分析，也是FDA的預期。我們一定會進行分組分析。

They're not the primary analysis, though, and the secondary analysis will look at patients who have sort of different types of dementia, mild dementia and moderate dementia, patients who have this variable or that variable. There's quite a number of subgroup analysis. I suspect that the time that we, have the public disclosure later this year, we'll have most of that data and we'll provide as much as we can, and that's my promise to you.

不過，這些並不是主要分析，次要分析將著眼於患有不同類型癡呆症的患者，輕度癡呆症和中度癡呆症，以及具有這種變數或那種變數的患者。有很多亞組分析。我估計，到今年晚些時候我們公開披露這些信息時，我們將掌握大部分數據，我們會盡可能多地提供這些信息，這是我對你們的承諾。

Thank you for providing that insight and taking my questions. I look forward to the day. I'll get back in the queue. Thank you.

感謝您提供如此獨到的見解並解答我的問題。我期待著那一天的到來。我重新排隊。謝謝。

Thanks, Vernon.

謝謝你，弗農。

Elemer Piros, Rodman & Renshaw.

埃萊默·皮羅斯、羅德曼和倫肖。

Yes, good morning. Maybe a little bit of follow-up to Dr. Kupiec. What I'd like to understand is the statistical analysis plan of the co-primary endpoints and that has been locked down and agreed with the FDA. And if you could provide just some details about How the analysis is going to be performed on the two primary endpoints.

是的，早安。或許需要對庫皮克博士進行一些後續跟進。我想了解的是共同主要終點的統計分析計劃，該計劃已經確定並與 FDA 達成協議。如果您能提供一些關於如何對兩個主要終點進行分析的詳細資訊就更好了。

Jim, you're very popular today.

吉姆，你今天很受歡迎。

Yeah, I guess so. So the statistical analytical plan has been written in conjunction with statisticians at both Premier who will be analyzing the safety data, and Doctor Hendrix, Dr. Mallinckrodt, at Pentara Corporation, they will be analyzing our data set for efficacy. They, to your question, they will be doing a modeling approach to our patients, which is very typical.

嗯，我想也是。因此，統計分析計劃是由 Premier 公司的統計學家和 Pentara 公司的 Hendrix 博士、Mallinckrodt 博士共同製定的，他們將分析安全數據，並分析我們的數據集以評估療效。至於你的問題，他們將對我們的患者進行建模分析，這很常見。

It's a very sophisticated approach as opposed to what we call simple statistics, and, they'll be doing that analysis, they have -- we have written the statistical analytical plan. We are done with the statistical analytical plan internally. It is now sitting at the FDA. We're waiting for the commentary on it.

這是一種非常複雜的方法，與我們所說的簡單統計方法截然不同，他們將進行這種分析，我們已經編寫了統計分析計劃。我們內部的統計分析計劃已經完成。目前它正等待美國食品藥物管理局（FDA）的審批。我們正在等待相關評論。

Assuming that they approve, then we will basically lock it down and sign off on it, and we'll be done. But clearly, and to the essence of your questions, it needs to be completely done. So that the analysis is pre-specified before we even get close to the data log date, so I don't know if that's what you're looking for but, hopefully, I've answered your question.

假設他們批准，那麼我們基本上就會敲定並簽字，然後就完成了。但很顯然，也是你問題的核心，這件事必須徹底完成。因此，分析是在接近資料日誌日期之前預先指定的，所以我不知道這是否是您想要的，但希望我已經回答了您的問題。

Yes. Maybe just one additional, follow up to that is that both of these primary endpoints would have to meet at the level of less than 0.5. Is that correct for it to be successful?

是的。或許還需要補充一點，這兩個主要終點都必須達到小於 0.5 的水平。這樣才算成功嗎？

That is correct. That is correct.

沒錯。沒錯。

And maybe just to bring in Chris if we could. How did you arrive to the figure of a potential settlement of $40 million? Was that based on some precedents? How did that figure come about as an estimate?

如果可以的話，或許還可以把克里斯也請過來。你是如何得出4000萬美元的潛在和解金額這個數字的？這是有先例可循的嗎？這個數字是如何估算出來的？

I appreciate the question, but we've said everything we can about our ongoing discussions with the SEC, and we have reserved $40 million but as we indicated we're still in discussions with the SEC and it really wouldn't be appropriate to get them more details.

感謝您的提問，但我們已經就與美國證券交易委員會的持續討論說明了一切，並且已經預留了 4000 萬美元，但正如我們所說，我們仍在與美國證券交易委員會進行討論，現在向他們透露更多細節並不合適。

Okay. Thank you. And maybe one last question to Rick. You alluded to that there was a demand to expand the, expanded access program to be on the one year. What precipitated that? Was it more like clinicians demand or patients slash family demand that you observed, if you could provide a little bit of color there.

好的。謝謝。也許我還能問里克最後一個問題。你曾暗示，有人要求將擴大准入計畫延長至一年。是什麼導致了這種情況？您觀察到的情況比較是臨床醫師的要求，還是病人或家屬的要求？能否請您詳細描述一下？

I think the honest answer is, it was a lot of things. So we heard from the sites that patients were going off and they wanted to stay on the drug. We heard that loud and clear through the clinical team, and I got to tell you, I have received quite a few emails from the patient community, generally from loved ones of patients who are on the drug or that were on the trial are now on the extension trial and you know they weren't begging to continue, but they very clearly wanted to continue.

我認為誠實的答案是，原因有很多。我們從一些網站了解到，患者正在停藥，但他們仍然想繼續服用這種藥物。我們從臨床團隊那裡清楚地聽到了這一點，而且我必須告訴你，我收到了來自患者群體的不少電子郵件，通常是來自正在服用該藥物或曾經參加試驗、現在正在參加擴展試驗的患者的親屬，你知道，他們並不是懇求繼續，但他們非常明確地希望繼續。

They understood the constraints of us being a small company and this being very costly, so it was a lot of things that led to it, but like I said, it was an easy decision. I mean it's just the right thing to do for patients and to me it struck me as cruel to have somebody on a drug for that long and they think that they're getting a benefit from it and we're taking them off, so it's driven by a lot of factors.

他們理解我們作為一家小公司的局限性，以及這項工程成本很高，所以有很多因素促成了這件事，但就像我說的，這是一個很容易的決定。我的意思是，這對病人來說才是正確的做法，在我看來，讓病人長期服用某種藥物，而他們認為自己從中受益，現在我們卻讓他們停藥，這很殘忍，所以這是由很多因素驅動的。

Yeah. And, Rick, I can imagine that you received quite a bit of an interest. I mean, this is one of the only handful of pivotal programs ongoing in Alzheimer's from potential partners. Can you describe some of the dynamics of those in the past and what would be your anticipation once data is available?

是的。里克，我能想像你受到了不少關注。我的意思是，這是目前為數不多的由潛在合作夥伴開展的阿茲海默症關鍵性計畫之一。您能否描述一下過去這些事件的一些動態，以及一旦獲得數據後，您對此有何預期？

Oh boy, yeah, I don't think I want to go too far into it but, realistically, I would not expect us to see. I wouldn't expect to see a partnership before we have Phase 3 data. And if you think about it from the other side, if this is a big pharma company, some business development officer would have to take the risk of walking into a CEO's office and saying, hey, I want to make a bet on this company.

哦，天哪，是的，我不想深入探討這個問題，但實際上，我並不認為我們會看到這種情況。在獲得第三階段數據之前，我預計不會出現合作關係。換個角度想，如果這是一家大型製藥公司，那麼某個業務拓展人員就必須冒著風險走進首席執行官的辦公室，說：“嘿，我想投資這家公司。”

We don't have data yet, most of the deals you see with big pharma these days are very expensive, and they're expensive because they're averse and they wait until there's a Phase 3 result or there's an FDA approval. So it's, I guess, the best I could say is stay tuned.

我們目前還沒有相關數據，如今與大型製藥公司達成的大多數交易都非常昂貴，之所以昂貴，是因為他們比較謹慎，總是等到 3 期臨床試驗結果出來或者獲得 FDA 批准後才會出手。所以，我想我能說的最好的話就是敬請期待。

Okay, certainly will. Thank you so much.

好的，一定會的。太感謝了。

Matt [Nectrob], Private Investor.

Matt [Nectrob]，私人投資者。

Hello. First off, that was a great update. It's nice to have Jim talking about some of the details on the trials. And I wanted to thank you personally for focusing on the patients and extending the open labels. I think that was a great decision and made a lot of families, much more calm and happy. And I'd like to congratulate the entire team. It's been quite a journey the last three years, but you guys did an incredible job getting Smith from to the doorstep of a completed Phase 3 trial.

你好。首先，這次更新非常棒。很高興吉姆能談談審判的一些細節。我還要親自感謝您關注患者並延長開放標籤期。我認為那是一個非常明智的決定，讓許多家庭更平靜幸福。我謹向整個團隊表示祝賀。過去三年真是一段漫長的旅程，但你們做得非常出色，讓史密斯從最初的治療階段走到了完成三期臨床試驗的門檻。

I have two related questions. So some estimates say there's about 46 million patients worldwide with Alzheimer's, 6.5 million in the US, and 11 million in Europe. Have you guys analyzed the worldwide demand for simufilam if there's a successful Phase 3 readout and FDA approval. And can you give any additional color on what steps you're taking to ensure simufilam can be delivered to patients quickly after the FDA approval and scale worldwide.

我有兩個相關的問題。據估計，全球約有 4,600 萬阿茲海默症患者，其中美國有 650 萬，歐洲有 1,100 萬。你們有沒有分析過，如果西莫菲拉姆（simufilam）的3期臨床試驗結果成功並獲得FDA批准，全球對該藥物的需求？您能否進一步說明一下，為了確保在獲得 FDA 批准後能夠迅速將西莫菲拉姆（simufilam）提供給患者並在全球範圍內推廣，您正在採取哪些步驟？

Yeah, it's very timely question. So we don't have a Chief Commercial Officer here. We're a small company, but we're interviewing several different firms to do the commercial plan for us in fact it's two or three calls I think scheduled today on that very topic, so. It's that's going to be the best way for us to do it and then at that point we'll decide do we need to have a Chief Commercial Officer and build a commercial team here or not but that we'll take a look at.

是的，這個問題問得非常及時。所以我們這裡沒有首席商務官。我們是一家小公司，但我們正在面試幾家不同的公司來為我們制定商業計劃。事實上，我認為今天就安排了兩到三次關於這個主題的電話會議。這將是我們能做到的最好方法，到那時我們再決定是否需要設立首席商務官並組建商務團隊，我們將對此進行考察。

Whereas the demand depends on the label, obviously. And as far as preparing for it, I mean, the first thing we have to do, and I made reference to it in my remarks, is, we have to beef up the API or the active pharmaceutical ingredient, and we've done that.

顯然，需求取決於品牌。至於準備工作，我的意思是，我們首先要做的，也是我在演講中提到的，就是要加強 API 或活性藥物成分，而我們已經做到了這一點。

We're also looking at -- we have a manufacturer right now that is making. Making an adequate number of tablets, but for the demand that you know we're internally forecasting, it's not enough, so we're looking at other sources for that manufacturing.

我們目前也在關注——我們現在已經找到一家製造商正在生產。我們生產了足夠數量的平板電腦，但對於我們內部預測的需求而言，這還不夠，所以我們正在尋找其他生產來源。

Okay, so you mean like a new company that can scale up successfully to a worldwide scale?

好的，所以你的意思是說，像那種能夠成功擴展到全球規模的新公司？

Yeah, or another plant within the same company that you know would have greater capacity, but yeah, a second source and the second source might have to be a lot larger.

是的，或是同一公司內另一家產能較大的工廠，但是，第二個來源可能需要更大一些。

Okay, that's all I have.

好了，我只有這些。

So I think that was our last question. I just want to say we really appreciate you joining us today. And I want everybody to remember our goal is to bring the best in class for Alzheimer's patients. That's why we're here. Thanks for listening, have a good day.

我想這就是我們最後一個問題了。我只想說，我們非常感謝您今天能來。我希望大家記住，我們的目標是為阿茲海默症患者提供一流的治療。這就是我們來這裡的原因。謝謝收聽，祝您今天愉快。

This does now conclude today's teleconference. You may now disconnect your lines at this time. Thank you for your participation.

今天的電話會議到此結束。現在您可以斷開線路了。感謝您的參與。