Larimar Therapeutics Inc (LRMR) 2021 Q1 法說會逐字稿

Good morning, and welcome to the Larimar Therapeutics conference call. (Operator Instructions). Please be advised that this call is being recorded at the Company's request and a replay will be available on the Company's website. I would now like to turn the call over to Mr. Chase Oswald of LifeSci Advisors. Please go ahead.

早安，歡迎參加Larimar Therapeutics電話會議。 （接線生指示）。請注意，應本公司要求，本次電話會議正在錄音，錄音回放將在公司網站上提供。現在，我想將電話會議交給LifeSci Advisors的Chase Oswald先生。請開始。

Thank you, operator; and thank you, all, for participating in today's conference call. Before we start, I would like to point out that there is a slide deck that will accompany today's presentation. This slide deck can be viewed using the webcast link provided on the Investors page of the Larimar Therapeutics website.

謝謝接線員，也謝謝大家參加今天的電話會議。在開始之前，我想指出，今天的簡報將附帶一份幻燈片。您可以透過 Larimar Therapeutics 網站「投資者」頁面上提供的網路直播連結觀看此投影片。

Also posted on this webpage is a news release issued earlier today announcing data from Larimar's Phase 1 double-blind, placebo-controlled multiple ascending dose clinical trial evaluating CTI-1601 in Friedreich's ataxia patients.

該網頁上還發布了今天早些時候發布的新聞稿，公佈了 Larimar 公司第一階段雙盲、安慰劑對照多劑量遞增臨床試驗的數據，該試驗評估了 CTI-1601 對弗里德賴希共濟失調患者的療效。

I'd like to remind all listening that some of the information contained in the news release and on this conference call contain forward-looking statements that are based on the Company's beliefs and assumptions and on information currently available to management.

我想提醒所有聽眾，新聞稿和電話會議中包含的一些資訊包含前瞻性陳述，這些陳述基於公司的信念和假設以及管理層目前掌握的資訊。

All statements contained in the news release and on this call, other than statements of historical fact, are forward-looking statements including, but not limited to: statements regarding the expectations and assumptions regarding the future of the business; the Company's ability to develop and commercialize CTI-1601 and other planned product candidates; the Company's planned research and development efforts; and other matters regarding the Company's business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations.

新聞稿和本次電話會議中包含的所有陳述，除歷史事實陳述外，均為前瞻性陳述，包括但不限於：關於業務未來預期和假設的陳述；公司開發和商業化 CTI-1601 和其他計劃候選產品的能力；公司計劃的研究和開發工作；以及有關公司業務戰略、資本使用、經營成果和財務狀況以及未來經營計劃和目標的事項。

In some cases, you can identify forward-looking statements by the words may, will, could, would, should, expect, intend, plan, anticipate, believe, estimate, predict, project, potential, continue, ongoing, or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words.

在某些情況下，您可以透過可能、將會、可以、會、應該、預期、打算、計劃、預期、相信、估計、預測、預期、潛在、繼續、正在進行或這些術語的否定形式或其他類似術語來識別前瞻性陳述，儘管並非所有前瞻性陳述都包含這些字詞。

These statements involve risks, uncertainties, and other factors that may cause actual results, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements.

這些聲明涉及風險、不確定性和其他因素，可能導致實際結果、績效或成就與這些前瞻性聲明表達或暗示的資訊有重大差異。

These risks, uncertainties, and other factors include, among others: the success, cost and timing of the Company's product development activities, nonclinical studies and clinical trials, including CTI-1601 clinical milestones, that clinical trial results may differ from the final clinical trial results, that earlier non-clinical and clinical data and testing of CTI-1601 may not be predictive of the results or success of clinical trials; and that clinical trial data are subject to differing interpretations and assessments; the ongoing impact of the COVID-19 pandemic on the Company's clinical trials, manufacturing, regulatory and nonclinical study timelines, ability to raise additional capital and general economic conditions; the Company's ability to optimize and scale CTI-1601's manufacturing process; the Company's ability to obtain regulatory approval for CTI-1601 and future product candidates; the Company's ability to develop sales and marketing capabilities, whether alone or with potential future collaborators, and successfully commercialize any approved product candidates; the Company's ability to raise the necessary capital to conduct its product development activities; and other risks described in the filings made by the Company with the Securities and Exchange Commission, including but not limited to the Company's periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q, and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov.

這些風險、不確定性和其他因素包括但不限於：公司產品開發活動、非臨床研究和臨床試驗的成功、成本和時間，包括 CTI-1601 臨床里程碑，臨床試驗結果可能與最終臨床試驗結果不同，CTI-1601 的早期非臨床和臨床數據和測試可能無法預測臨床試驗的結果或成功；臨床試驗數據可能受到不同的解釋和評估；疫情對公司臨床試驗、製造、監管和非臨床研究時間表、籌集額外資本的能力和一般經濟狀況的持續影響；公司優化和擴展 CTI-1601 製造流程的能力；公司獲得 CTI-1601和未來產品候選物的監管批准的能力；公司單獨或與潛在未來合作夥伴共同開發銷售和營銷能力，並成功將任何獲批產品候選物商業化的能力；公司籌集開展產品開發活動所需資金的能力；以及公司向美國證券交易委員會提交的文件中所述的其他風險，包括但不限於公司向美國證券交易委員會提交或提供的定期報告，包括 10-KQ 報告www.sec.gov 上查閱。

These forward-looking statements are based on a combination of facts and factors currently known by the Company and its projections of the future, about which it cannot be certain. As a result, the forward-looking statements may not prove to be accurate. These forward-looking statements are based on information currently available to management, and the Company assumes no obligation to update any forward-looking statements, except as required by law.

這些前瞻性陳述是基於公司目前已知的事實和因素以及公司對未來的預測，但公司無法確定這些預測。因此，這些前瞻性陳述可能並不準確。這些前瞻性陳述是基於管理層目前掌握的信息，除非法律要求，否則公司不承擔更新任何前瞻性陳述的義務。

With that, I'd like to turn the call over to Dr. Carole Ben-Maimon, President and CEO of Larimar Therapeutics. Please go ahead, Carole.

接下來，我想把電話轉給Larimar Therapeutics公司總裁兼執行長Carole Ben-Maimon博士。 Carole，請講。

Thanks, Chase. Good morning, everyone, and thanks to all of you who are listening. In addition to Chase, I am also joined by our Chief Medical Officer, Dr. Nancy Ruiz; and our Chief Financial Officer, Mike Celano, who will be available during the question-and-answer session following my presentation.

謝謝，Chase。大家早安，感謝所有聆聽我演講的人。除了Chase之外，我的嘉賓還有我們的首席醫療官Nancy Ruiz博士和財務長Mike Celano，他們將在我演講後的問答環節中出席。

For those of you who don't know Larimar, we are a clinical stage biotechnology company developing a novel protein replacement therapy platform for Friedreich's ataxia and other complex rare diseases. We were founded by Dr. Mark Payne and Tom Hamilton; and at the end of 2016, Deerfield Management made the initial investment. We went public through a reverse merger and accompanying PIPE in May 2020 with a shareholder base made up of high-quality institutional investors.

對於那些不了解Larimar的人來說，我們是一家臨床階段的生物技術公司，致力於開發一種用於治療弗里德賴希共濟失調症和其他複雜罕見疾病的新型蛋白質替代療法平台。我們由Mark Payne博士和Tom Hamilton創立；2016年底，Deerfield Management進行了初步投資。我們於2020年5月透過反向合併和伴隨的PIPE上市，股東基礎由高品質的機構投資者組成。

As I previewed above, our lead program is in Friedreich's ataxia, or FA, a rare and terribly debilitating genetic disorder. To address the unmet medical needs in FA, we are developing CTI-1601, a recombinant fusion protein designed to treat the root cause of the disease. Patients with FA are deficient in a protein called frataxin. Frataxin is a protein that is active in the mitochondria of the cell. CTI-1601 is intended to deliver frataxin to the mitochondria in patients suffering from FA.

正如我上面所述，我們的重點項目是弗里德賴希共濟失調症（Friedreich's ataxia，簡稱 FA），這是一種罕見且極其嚴重的遺傳性疾病。為了滿足 FA 領域尚未滿足的醫療需求，我們正在開發 CTI-1601，這是一種重組融合蛋白，旨在治療該疾病的根本病因。 FA 患者缺乏一種名為 frataxin 的蛋白質。 Frataxin 是一種在細胞粒線體中活躍的蛋白質。 CTI-1601 旨在將 frataxin 遞送至 FA 患者的粒線體。

We recently completed dosing in two Phase 1 trials. These trials were a placebo-controlled single ascending dose trial and a placebo-controlled multiple ascending dose trial evaluating CTI-1601 in patients with Friedreich's ataxia. The primary purpose of today's call is to announce the exciting data these trials have generated, which show dose-dependent increases in frataxin levels in all evaluated tissues with daily dosing of CTI-1601. The frataxin levels observed in these tissues actually met or exceeded the levels we would expect to see in phenotypically normal heterozygous carriers of FA.

我們最近完成了兩項1期臨床試驗的給藥。這兩項試驗分別是安慰劑對照的單次遞增劑量試驗和安慰劑對照的多次遞增劑量試驗，旨在評估CTI-1601對弗里德賴希共濟失調患者的療效。今天召開電話會議的主要目的是宣布這些試驗產生的激動人心的數據，這些數據表明，在每日服用CTI-1601的情況下，所有評估組織中的frataxin水平均呈劑量依賴性增加。在這些組織中觀察到的frataxin水平實際上達到或超過了我們預期在表型正常的FA雜合子攜帶者中觀察到的水平。

We believe this data demonstrates proof of concept for CTI-1601. In addition, the data also indicates that CTI-1601 is generally well tolerated when administered daily for 13 days. Looking forward, we believe we are well-positioned financially to build on these promising results as we ended the first quarter with over $81 million in cash, which provides for a projected runway into the first half of 2022.

我們相信這些數據證明了CTI-1601的概念驗證。此外，數據還表明，CTI-1601在每日服用13天的情況下通常耐受性良好。展望未來，我們相信，我們擁有充足的財務實力，能夠在這些令人欣喜的業績基礎上再接再厲，因為截至第一季末，我們擁有超過8,100萬美元的現金，預計可支撐我們持續到2022年上半年。

Now, before we dive into the details of our data and trial design, I wanted to first highlight the key findings from our Phase I program. With regards to safety, we saw that repeated subcutaneous injections of CTI-1601 appeared to have been generally well tolerated at doses up to 100 milligrams administered daily for up to 13 doses.

在深入探討數據和試驗設計細節之前，我想先強調我們I期臨床試驗的關鍵發現。在安全性方面，我們發現，CTI-1601皮下重複注射，每日劑量高達100毫克，最多注射13次，整體耐受性良好。

When looking at pharmacodynamic data, we saw dose-dependent increases in frataxin levels from baseline compared to placebo controls in all evaluated tissues with daily dosing of CTI-1601. And finally, our pharmacokinetic analyses, together with the PD data I just mentioned, support evaluating a once-daily dosing regimen for CTI-1601.

藥效動力學數據表明，與安慰劑對照組相比，所有評估組織中每日服用CTI-1601的患者，其frataxin水平均較基線呈劑量依賴性升高。最後，我們的藥物動力學分析以及我剛才提到的藥效動力學數據支持評估CTI-1601每日一次給藥方案。

Before I leave this slide, I'd like to highlight one of the most important findings from this study. Notably, frataxin levels in buccal cells for the two highest dose groups were equal to, or in excess of, those we would expect to see in heterozygous carriers who show no signs of the disease. Given that insufficient frataxin levels are the root cause of Friedreich's ataxia, we believe that these exciting findings demonstrate proof of concept for CTI-1601.

在結束這張投影片之前，我想先強調這項研究中最重要的發現之一。值得注意的是，兩個最高劑量組的口腔細胞中 Frataxin 的水平等於或高於我們預期在沒有疾病跡象的雜合子攜帶者中觀察到的水平。鑑於 Frataxin 水平不足是弗里德賴希共濟失調的根本原因，我們相信這些令人興奮的發現為 CTI-1601 提供了概念驗證。

So, now that I've introduced the main takeaways of today's presentation, I want to take a moment to provide some context for the detailed data I'll be presenting by giving some background on Friedreich's ataxia and CTI-1601. Friedreich's ataxia is a rare, terribly debilitating disease, caused by a genetic defect that results in insufficient levels of frataxin -- a key mitochondrial protein.

既然我已經介紹了今天演講的要點，我想花點時間介紹一下弗里德賴希共濟失調和CTI-1601的背景，為即將呈現的詳細數據提供一些背景資訊。弗里德賴希共濟失調症是一種罕見且極其嚴重的疾病，由一種基因缺陷導致粒線體關鍵蛋白－Frataxin水平不足所致。

It is important to note that the vast majority of patients with FA have some normal frataxin. They just don't have enough frataxin. Past studies have shown that patients with FA produce only about 20% to 40% of normal frataxin levels depending on the tissue, sampling technique, and assay utilized.

值得注意的是，絕大多數FA患者的frataxin水平是正常的，只是他們體內的frataxin不足。過去的研究表明，FA患者的frataxin水平僅為正常水平的20%至40%，具體取決於組織、採樣技術和所使用的檢測方法。

FA is a terrible disease. This deficiency of frataxin causes patients, who are born appearing to be healthy, to develop heart disease and progressive neurological symptoms that will eventually force them into a wheelchair 7 to 10 years after diagnosis. The life expectancy for these patients is between 30 to 50 years of age with the primary cause of death being cardiomyopathy.

FA 是一種可怕的疾病。這種 Frataxin 基因的缺乏會導致患者（這些患者出生時看似健康）患上心臟病，並出現漸進性的神經系統症狀，最終導致他們在確診後 7 至 10 年內不得不坐上輪椅。這些患者的預期壽命在 30 至 50 歲之間，主要死因是心肌病變。

If FA is truly a systemic disease, every cell in the body that has mitochondria has frataxin. In addition to the neurologic dysfunction and cardiac disease, patients with FA develop diabetes; they can go blind and deaf; and they lose the ability to speak. There is a substantial unmet medical need in FA as there are no approved therapies available and current treatment options are limited to symptom management.

如果FA確實是一種全身性疾病，那麼體內每個含有粒線體的細胞都含有frataxin。除了神經功能障礙和心臟疾病外，FA患者還會患上糖尿病；他們可能失明、失聰；甚至失去說話能力。由於目前尚無核准的療法，且目前的治療方案僅限於症狀治療，FA存在大量未滿足的醫療需求。

In response to this unmet medical need, we are developing CTI-1601, a recombinant fusion protein. Through the administration of CTI-1601, we are aiming to address the root cause of Friedreich's ataxia by delivering mature frataxin protein to the mitochondria.

為了滿足這項尚未滿足的醫療需求，我們正在開發重組融合蛋白CTI-1601。透過施用CTI-1601，我們旨在將成熟的frataxin蛋白遞送至粒線體，從而解決弗里德賴希共濟失調的根本原因。

To understand how CTI-1601 does this, it's first important to understand the structure of endogenous frataxin. If you look on the left side of the slide, you can see that frataxin, which is coded in the nucleus, produced in the cytoplasm, and then transported into the mitochondria, is originally coded as what I like to call, a pro protein.

要理解CTI-1601是如何做到這一點的，首先要了解內源性frataxin的結構。如果你看幻燈片的左側，你可以看到frataxin在細胞核中編碼，在細胞質中產生，然後被運送到粒線體，它最初被編碼為我喜歡稱之為的「前體蛋白」。

This pro protein includes mitochondrial targeting sequence, or MTS, that carries the protein across the mitochondrial membrane. Once in the mitochondria, the MTS is cleaved off by the mitochondrial processing peptidase enzyme allowing mature frataxin to accumulate within the organelle to function.

這種前驅蛋白包含粒線體靶向序列（MTS），該序列負責攜帶蛋白質穿過粒線體膜。一旦進入粒線體，MTS就會被粒線體加工勝肽酶裂解，使成熟的frataxin能夠在細胞器內累積並發揮作用。

Now if you look to the right side of the slide, you can see what's significant about CTI-1601. This recombinant protein has been designed to allow exogenously administered frataxin to cross the cell membrane and the mitochondrial membrane. This is accomplished by attaching a cell penetrating peptide or CPP, a small amino acid sequence to the mitochondrial targeting sequence and not to the frataxin molecule itself. This maintains the cleavage site between the MTS and the frataxin molecule.

現在，如果您看投影片的右側，您就能看到 CTI-1601 的重要性。這種重組蛋白的設計允許外源性 frataxin 穿過細胞膜和粒線體膜。這是透過將細胞穿透勝肽或 CPP（一種短氨基酸序列）連接到粒線體靶向序列而不是 frataxin 分子本身來實現的。這保留了 MTS 和 frataxin 分子之間的切割位點。

By maintaining this cleavage site, once CTI-1601 enters the mitochondria, the mitochondrial processing peptidase can now cleave off the cell penetrating peptide and the MTS, leaving the active frataxin molecule in the mitochondria. We believe that attaching the CPP to the MTS and preserving that cleavage site is what constitutes the secret sauce of CTI-1601.

透過保留此裂解位點，一旦 CTI-1601 進入粒線體，粒線體加工勝肽酶就能裂解細胞穿透勝肽和 MTS，將活性 frataxin 分子留在粒線體中。我們相信，將 CPP 連接到 MTS 並保留該裂解位點正是 CTI-1601 的秘密武器。

So, now that I've set the stage by describing how CTI-1601's mechanism of action directly addresses the root cause of FA, I would like to introduce the design of our Phase I program and talk in-depth about the exciting data I previewed earlier in the call.

因此，既然我已經透過描述 CTI-1601 的作用機制如何直接解決 FA 的根本原因做好了準備，我想介紹一下我們第一階段計劃的設計，並深入討論我在電話會議早些時候預覽的令人興奮的數據。

As you can see on this slide, our Phase I program includes two double-blind, placebo-controlled trials in patients with FA. The first of these trials is a SAD study that evaluated the safety of single subcutaneous injections of CTI-1601. This trial has been completed with data from the study showing that single subcutaneous injections of CTI-1601 appear to be generally well tolerated at doses up to 100 milligrams.

正如您在這張投影片上看到的，我們的I期項目包括兩項針對FA患者的雙盲安慰劑對照試驗。其中一項試驗是SAD研究，評估了單次皮下注射CTI-1601的安全性。該試驗已經完成，研究數據顯示，單次皮下注射CTI-1601在高達100毫克的劑量下似乎整體耐受性良好。

Eligible patients from the SAD trial had the opportunity to screen for a MAD trial, which is the primary focus of today's call. Patients in this trial were randomized to receive multiple increasing doses of CTI-1601 or placebo, administered subcutaneously over 13 days. The primary endpoints of the trial were safety and tolerability with secondary endpoints including frataxin levels in buccal cells and platelets as well as pharmacokinetic analyses. Dosing in the trial was completed in the first quarter of the year.

SAD 試驗符合條件的患者有機會篩選 MAD 試驗，這也是今天電話會議的主要內容。此試驗的患者隨機分配接受 CTI-1601 或安慰劑的多次遞增劑量治療，皮下注射給藥，給藥時間為 13 天。該試驗的主要終點是安全性和耐受性，次要終點包括口腔黏膜細胞和血小板中的 Frataxin 水平以及藥物動力學分析。該試驗的給藥已於今年第一季完成。

Here on this slide, you'll notice that 16 of the 28 patients who participated in the SAD study went on to enroll in our MAD trial. This is important as the MAD study was conducted during the pandemic throughout the winter and required patients and their caregivers to travel from across the country to the single clinical research unit where the study was conducted. Once there, patients and their caregivers had to remain in the unit for more than three weeks.

在這張投影片上，您會注意到，參與 SAD 研究的 28 名患者中，有 16 名後來加入了我們的 MAD 試驗。這一點非常重要，因為 MAD 研究是在疫情期間整個冬季進行的，需要患者及其照顧者從全國各地趕到進行研究的單一臨床研究單位。到達那裡後，患者及其照顧者必須在該單位停留三週以上。

The fact that 16 out of 28 patients were willing to endure this is really a tribute to the patients' commitment and tenacity; and we want to thank them for their participation and perseverance.

28名患者中有16名願意忍受這一切，這確實證明了患者的承諾和毅力；我們要感謝他們的參與和堅持。

The MAD trial had three cohorts, with Cohort 1 enrolling six patients into the active arm, and Cohorts 2 and 3 each enrolling seven patients into the active arm. Collectively, the three cohorts enrolled seven patients into the placebo group.

MAD 試驗分為三個隊列，其中隊列 1 招募了 6 名患者進入有效組，隊列 2 和隊列 3 各招募了 7 名患者進入有效組。三個隊列共招募了 7 名患者進入安慰劑組。

Moving on to Slide 9, you can see that as we moved from Cohort 1 to Cohort 3 in the MAD trials, we increased both the dose of CTI-1601 as well as the frequency of administration. Patients in Cohort 1 were dosed with 25 milligrams daily for four days, and then every third day after that until day 13.

翻到第9張投影片，您可以看到，在MAD試驗中，隨著隊列1到隊列3的推進，我們增加了CTI-1601的劑量和給藥頻率。隊列1的患者每天服用25毫克，連續服用四天，之後每三天服用一次，直到第13天。

In Cohort 2, we doubled the dose of CTI-1601 to 50 milligrams and administered the protein daily for seven days before moving to a once-every-other-day dosing schedule until day 13. Finally, patients in Cohort 3 were given a 100 milligram dose daily for 13 consecutive days.

在第 2 組中，我們將 CTI-1601 的劑量加倍至 50 毫克，並連續 7 天每天注射該蛋白質，然後改為每隔一天注射一次，直到第 13 天。最後，第 3 組的患者連續 13 天每天服用 100 毫克劑量。

Looking now at the bottom half of the slide, I'll briefly explain how we will be presenting the data for each Cohort. You'll notice from the tables that for Cohort 1, we will be showing frataxin levels at baseline, day 4, and day 13 in both buccal cells and platelets; while in Cohorts 2 and 3, the data presented for these tissues will be from baseline, day 7, and day 13.

現在請看投影片的下半部分，我將簡要解釋我們將如何呈現每個隊列的資料。您將從表格中註意到，對於隊列1，我們將顯示口腔黏膜細胞和血小板在基線、第4天和第13天的frataxin水平；而對於隊列2和3，我們將呈現這些組織在基線、第7天和第13天的數據。

Looking at the data in this way allows us to capture the final day of the daily dosing period for both Cohorts 1 and 2, which will be informative for the design of subsequent studies. Per the study protocols, skin biopsies were collected only at baseline and day 13. Thus, those are the two time points we will be looking at for this tissue in all three cohorts. In addition, skin biopsies were optional; the patients could elect not to have them performed.

透過這種方式查看數據，我們可以捕捉到隊列1和隊列2每日給藥期的最後一天，這將為後續研究的設計提供參考。根據研究方案，僅在基線和第13天採集皮膚活檢樣本。因此，我們將在這三個隊列中分別觀察這兩個時間點的組織樣本。此外，皮膚活檢是可選的；患者可以選擇不進行。

Here on Slides 10 and 11, you can see the demographics and disease characteristics of patients who participated in the MAD trial. I won't go through the data in detail now as the slides are posted on our website for those interested in taking a deeper dive. I will, however, point out that the patient demographics in the MAD trial were similar to those in the SAD trial, which is obviously not surprising given that there were 16 patients who participated in both studies.

在第10和11張投影片上，您可以看到參與MAD試驗的患者的人口統計特徵和疾病特徵。我現在不會詳細講解這些數據，因為投影片已經發佈在我們的網站上，方便有興趣深入了解的人查看。不過，我要指出的是，MAD試驗的患者人口統計學特徵與SAD試驗相似，考慮到這兩項研究都涉及16名患者，這顯然並不奇怪。

Additionally, approximately half of the patients enrolled in our trials used a wheelchair to move around and thus are considered non-ambulatory. This is different than many of the Phase 2, 3 trials to date in FA where patients who participated were required to be ambulatory.

此外，我們試驗中約有一半的患者使用輪椅出行，因此被視為無法行走。這與迄今為止許多 FA 的 2 期和 3 期試驗不同，這些試驗要求參與試驗的患者必須能夠行走。

Having these patients in our Phase 1 trials as well as our open-label extension, the Jive study, will provide important data on the long-term safety and tolerability of CTI-1601 as well as potentially allow detection of the signal of efficacy in this population.

讓這些患者參與我們的 1 期試驗以及開放標籤擴展研究 Jive，將提供有關 CTI-1601 的長期安全性和耐受性的重要數據，並可能檢測出該族群的療效訊號。

On Slide 12, you will see the data I previewed at the beginning of the call, which shows that daily subcutaneous injections of CTI-1601 resulted in dose-dependent increases in frataxin levels from baseline compared to placebo. The data you are looking at now is from buccal cells, but as you will see in a moment, these data are consistent with what we saw in all evaluated tissues.

在第12張投影片上，您將看到我在電話會議開始時預覽的數據，該數據顯示，與安慰劑組相比，每日皮下注射CTI-1601可導致frataxin水平相對於基線呈劑量依賴性增加。現在您看到的數據來自口腔細胞，但正如您稍後將看到的，這些數據與我們在所有評估組織中觀察到的情況一致。

Looking in more detail now, we can start with the graph on the left, which shows absolute frataxin concentrations in collected buccal cells normalized to total protein. The points on the graph represent the median from each group while the error bars represent the 25th and 75th percentiles.

現在更詳細地看，我們可以從左邊的圖開始，該圖顯示了收集的頰黏膜細胞中 Frataxin 的絕對濃度，並以總蛋白為標準。圖上的點代表每組的中位數，而誤差線代表 25 和 75 個百分位數。

You will also notice that as we move from baseline to the next measurement, which, again, was day 4 for the 25-milligram dose group, and day 7 for the 50-milligram and 100-milligram dose groups, we see an increase in frataxin levels in the second two highest dose groups with the highest median frataxin level being in the 100-milligram dose group -- the highest dosing group.

您還會注意到，當我們從基線移動到下一個測量值時，同樣，25 毫克劑量組為第 4 天，50 毫克和 100 毫克劑量組為第 7 天，我們看到第二高劑量組的 frataxin 水平有所增加，其中最高中位 frataxin 水平出現在 100 毫克劑量組 - 即劑量最高的組。

That said, in the 100-milligram dose group, we saw an approximately 2.5-fold increase in frataxin levels from baseline. Importantly, we see little to no change in frataxin levels in the placebo group or in the 25-milligram dose group, which received the lowest dose of CTI-1601.

也就是說，在100毫克劑量組中，我們發現frataxin水平較基線增加了約2.5倍。重要的是，在安慰劑組或接受最低劑量CTI-1601的25毫克劑量組中，我們發現frataxin水平幾乎沒有變化。

I'd like to draw your attention now to what was seen between day 7 and day 13 measurements as this shows something that is a bit subtle but quite informative. You can see from the graph that between day 7 and day 13, frataxin levels in the 100-milligram dose group remained relatively constant, while the frataxin levels in the 50-milligram dose group decreased.

現在我想請大家注意一下第7天到第13天的測量結果，因為這顯示了一些雖然微妙但很有啟發性的信息。從圖中可以看出，在第7天到第13天之間，100毫克劑量組的frataxin水準保持相對穩定，而50毫克劑量組的frataxin水準則有所下降。

The important thing to remember here is that patients in the 50-milligram dose group were receiving CTI-1601 daily for the first seven days, but then they were switched to receiving the protein every other day between day 7 and day 13. Conversely, patients in the 100-milligram dose group received both a higher dose of CTI-1601 and remained on the daily administration schedule throughout the 13 days. This is important because it suggests that a once-daily-dosing schedule may be appropriate for subsequent studies.

這裡要記住的是，50毫克劑量組的患者在前七天每天接受CTI-1601治療，但之後在第7天至第13天之間改為每隔一天接受一次蛋白質治療。相反，100毫克劑量組的患者接受了更高劑量的CTI-1601，並在13天內保持每日給藥方案。這一點很重要，因為它表明每日一次的給藥方案可能適合後續研究。

Turning our attention now to the graph on the right, we see the same data but presented as a change from baseline, so this represents the additional frataxin that is being supplied by administration of CTI-1601. Once again, we see little to no change from baseline in buccal cell frataxin levels from patients in the placebo group or the 25-milligram dose group.

現在將注意力轉向右側的圖表，我們看到相同的數據，但以與基線相比的變化形式呈現，因此這代表了使用 CTI-1601 後額外補充的 frataxin。我們再次觀察到，安慰劑組和 25 毫克劑量組患者的頰細胞 frataxin 水平與基線相比幾乎沒有變化。

On day 7, when both the 50-milligram and 100-milligram dose groups were on daily dosing schedules, we see increases in frataxin levels with the greatest increase coming from patients in the 100-milligram dose group. As I will show you in a moment, these frataxin levels are at or above what we would see in heterozygous who show no signs of the disease.

第7天，當50毫克和100毫克劑量組都以每日給藥方案給藥時，我們發現frataxin水平有所升高，其中100毫克劑量組患者的升高幅度最大。我稍後會向大家展示，這些frataxin水平等於或高於沒有疾病跡象的雜合子患者的水平。

On Slide 13, you can see the frataxin levels measured in skin biopsies, which were collected both at baseline and on day 13. These results are consistent with what we saw in buccal cells but with a more pronounced, approximately, 3-fold increase in frataxin levels compared to baseline in patients in the 100-milligram dose group.

在第 13 張投影片上，您可以看到在基線和第 13 天收集的皮膚活檢樣本中測得的 frataxin 水平。這些結果與我們在頰細胞中看到的結果一致，但與 100 毫克劑量組患者的基線相比，frataxin 水平更加明顯，增加了約 3 倍。

The increases in frataxin levels observed were once again dose-dependent, with daily dosing, with little to no change from baseline seen in the placebo group or the 25-milligram dose group.

觀察到的 Frataxin 水平的增加再次表現出劑量依賴性，每日服用劑量與安慰劑組或 25 毫克劑量組的基線相比幾乎沒有變化。

On Slide 14, you can see the results we obtained from platelets, which were the last tissue we evaluated. While results here were generally consistent with what was seen in other tissues, we did see a good deal of variability in the baseline measurements of all groups.

在第14張投影片上，您可以看到我們從血小板（我們最後評估的組織）獲得的結果。雖然這裡的結果與其他組織的結果基本一致，但我們確實發現所有組別的基線測量值存在很大的差異。

However, when looking at change from baseline in the 100-milligram dose group in the graph on the right, it becomes clear that we are, once again, seeing increases in frataxin levels at the highest dose when compared to placebo.

然而，當觀察右側圖表中 100 毫克劑量組相對於基線的變化時，很明顯，與安慰劑相比，我們再次看到最高劑量下的 frataxin 水平有所增加。

Now if we look here on Slide 15, we can see a different representation of the data with a bit more detail on how increases in frataxin levels from baseline correlated with CTI-1601 dose. The three graphs represent the change from baseline on day 13 with each bar representing an individual patient.

現在，如果我們查看第15張投影片，我們可以看到不同的數據呈現方式，其中更詳細地展示了frataxin水平相對於基線的增加與CTI-1601劑量之間的相關性。這三張圖表分別代表了第13天相對於基線的變化，每個長條圖代表一位患者。

As you can see from the color coding, as you move from left to right, the largest increases from baseline tended to come from higher dosing cohorts with more frequent dosing. Collectively, these patient level data further support the dose-dependent effects of CTI-1601 that were observed with daily dosing in all tissues studied.

從顏色編碼可以看出，從左到右，與基線相比增幅最大的往往是劑量較高、給藥頻率較高的組別。總體而言，這些患者層級數據進一步支持了 CTI-1601 的劑量依賴性效應，該效應在所有研究組織中均觀察到，且每日給藥均有效。

So, once we established that we could increase frataxin levels in peripheral tissues, we then asked ourselves two questions. The first being, are peripheral frataxin levels clinically relevant; and the second being, how do the frataxin levels we achieved with CTI-1601 administration in our clinical trial compare to frataxin levels from healthy controls and heterozygous carriers, who show no signs of the disease.

因此，一旦我們確定可以提高外周組織中的 frataxin 水平，我們便會問自己兩個問題。首先，週邊 frataxin 水平是否具有臨床相關性？其次，我們在臨床試驗中透過 CTI-1601 給藥達到的 frataxin 水平與健康對照組和雜合子攜帶者（未表現出疾病跡象）的 frataxin 水平相比如何。

To answer the first question, we were able to look at the literature, which has shown that frataxin levels in buccal cells and blood are predictive of disease severity. It has been shown that the lower the frataxin level in these tissues, the longer the GAA repeat, and the earlier the onset of the disease.

為了回答第一個問題，我們查閱了文獻，這些文獻表明，口腔黏膜細胞和血液中的frataxin水平可以預測疾病的嚴重程度。研究表明，這些組織中的frataxin水平越低，GAA重複序列越長，疾病的發病時間也越早。

Further, while published data varies on the level of frataxin in patients, we have referenced a study that shows that patients with FA produce approximately 20% to 40% of normal frataxin levels in buccal cells and blood; while heterozygous carriers, who show no disease symptoms, display frataxin levels that are about 50% of those seen in healthy controls.

此外，雖然已發表的數據在患者的 frataxin 水平上有所不同，但我們引用的一項研究表明，FA 患者的頰細胞和血液中產生的 frataxin 水平約為正常水平的 20% 至 40%；而沒有疾病症狀的雜合攜帶者產生的 frataxin 水平約為對照組健康的 50%。

Collectively, these findings suggest that peripheral frataxin levels are clinically relevant, highlighting the significance of the results we have presented here today.

總的來說，這些發現表明外周 frataxin 水平具有臨床相關性，突顯了我們今天在此提出的結果的意義。

Now to answer our second question, we can look at data from a non-interventional study we began conducting prior to the Coronavirus pandemic. This study, which included healthy controls, measured frataxin levels in buccal cells using the same sampling technique and assay employed in our Phase 1 MAD trial. While we ended up terminating this non-interventional study due to the COVID-related restrictions, we have data from the first eight healthy control subjects.

現在，為了回答我們的第二個問題，我們可以查看我們在新冠疫情之前開始進行的一項非干預性研究的數據。這項研究納入了健康對照者，並使用與第一期MAD試驗相同的採樣技術和檢測方法測量了口腔細胞中的frataxin水平。雖然由於新冠疫情相關的限制，我們最終終止了這項非干預性研究，但我們保留了前八名健康對照者的數據。

If you look at the graph on the right, you will notice the dashed green line, which represents 60% of the median frataxin levels measured in these eight healthy controls. You can see from this graph that patients in the 50-milligram and 100-milligram dose groups both achieved median frataxin levels at or above this line, which notably exceeds the frataxin levels we would expect to see in buccal cells of phenotypically normal heterozygous carriers.

如果你觀察右側的圖表，你會注意到一條綠色虛線，它代表了這八名健康對照者測得的 Frataxin 中位數水準的 60%。從圖中可以看出，50 毫克和 100 毫克劑量組的患者均達到了或高於這條線的 Frataxin 中位水平，這顯著超過了我們預期在表型正常的雜合子攜帶者口腔細胞中看到的 Frataxin 水平。

Although others have reported toxicity with very high levels of frataxin, the levels we are reporting here do not approach the levels reported in those studies. As we advance the development program for CTI-1601, we will continue to monitor frataxin levels in these tissues and optimize dosing regimen.

儘管其他研究已報告過高濃度的frataxin會導致毒性，但我們在此報告的濃度與這些研究報告的濃度相差甚遠。隨著CTI-1601開發計畫的推進，我們將繼續監測這些組織中的frataxin濃度，並優化給藥方案。

Given what is known about the predictive nature of buccal frataxin levels on neurological function in FA patients, we believe this favorable comparison speaks to the significance of our Phase 1 results and the extent to which they demonstrate proof of concept for our clinical program.

鑑於已知的頰部 Frataxin 水平對 FA 患者神經功能的預測性質，我們相信這種有利的比較說明了我們第一階段結果的重要性以及它們在多大程度上證明了我們臨床計劃的概念證明。

Looking forward, we are planning to collect additional data from healthy controls in a separate non-interventional study, utilizing the same sampling techniques in our proprietary assay, in order to better inform CTI-1601's continued clinical development.

展望未來，我們計劃在單獨的非干預研究中從健康對照者收集更多數據，利用我們專有檢測中的相同採樣技術，以便更好地為 CTI-1601 的持續臨床開發提供資訊。

Shifting gears a bit now, I'd like to talk about some of the safety findings from our MAD trial. Based on these findings, CTI-1601 appears to be generally well tolerated when administered daily for 13 days. Of the 27 patients who enrolled in the MAD trial, 26 completed the study, with one patient in the 50-milligram dose group withdrawing after experiencing mild-to-moderate nausea and vomiting.

現在稍微轉換一下話題，我想談談我們MAD試驗的一些安全性發現。基於這些發現，CTI-1601在每日服用13天的情況下，整體耐受性良好。在參與MAD試驗的27名患者中，有26名完成了研究，50毫克劑量組的一名患者因出現輕度至中度噁心和嘔吐而退出。

Notably, we observed no serious adverse events, important medical events, or treatment-related severe adverse events in the trial. The most common adverse events were mild and moderate injection site reactions. At least one injection site reaction was noted in 43% of placebo patients and in 100% of CTI-1601 patients. I should also note that the number and severity of adverse events did not increase with increasing exposure to CTI-1601.

值得注意的是，我們在試驗中未觀察到嚴重不良事件、重要醫療事件或與治療相關的嚴重不良事件。最常見的不良事件是輕度和中度注射部位反應。 43% 的安慰劑組患者和 100% 的 CTI-1601 組患者至少出現一次注射部位反應。我還應該指出，不良事件的數量和嚴重程度並沒有隨著 CTI-1601 暴露劑量的增加而增加。

Shifting our focus now to our pharmacokinetic analyses, we found that CTI-1601 was quickly absorbed following subcutaneous administration. Notably, we saw dose-proportional increases in exposure with increasing doses of CTI-1601 and a mean half-life of approximately 11 hours. Although we have flexibility and can increase the dose if necessary, these analyses support evaluating a once-daily dosing regimen for CTI-1601.

現在我們將重點轉移到藥物動力學分析上，發現CTI-1601皮下給藥後吸收迅速。值得注意的是，我們發現暴露量隨CTI-1601劑量的增加而呈劑量比例增加，平均半衰期約為11小時。雖然我們擁有靈活性，可以根據需要增加劑量，但這些分析支持評估CTI-1601的每日一次給藥方案。

So, to summarize our top-line Phase 1 findings, repeated subcutaneous injections of CTI-1601 appeared to be generally well tolerated at doses up to 100 milligrams administered daily for 13 days, with no serious adverse events reported in either of the SAD or MAD trials.

因此，總結我們第一階段的頂級研究結果，在 13 天內每天注射高達 100 毫克的 CTI-1601 劑量下，反覆皮下注射似乎普遍耐受性良好，並且在 SAD 或 MAD 試驗中均未報告嚴重不良事件。

Pharmacodynamic assessments showed that daily subcutaneous administrations of CTI-1601 resulted in dose-dependent increases in frataxin levels from baseline compared to placebo in all evaluated tissues, which included buccal cells, skin, and platelets. This finding was particularly notable given that frataxin levels in buccal cells have been shown to correlate with neurological function in patients with FA.

藥效動力學評估顯示，與安慰劑相比，每日皮下注射 CTI-1601 可導致所有評估組織（包括口腔細胞、皮膚和血小板）中 Frataxin 水平較基線呈劑量依賴性升高。鑑於口腔細胞中 Frataxin 水平已被證實與 FA 患者的神經功能相關，這項發現尤其顯著。

Moreover, we were able to achieve frataxin levels that exceed the frataxin levels we would expect to see in phenotypically normal carriers of the FA gene, based on data in eight healthy controls obtained from a noninterventional trial, using our collection techniques and proprietary assay.

此外，基於從非干預試驗中獲得的八個健康對照的數據，使用我們的收集技術和專有檢測方法，我們能夠實現超過我們預期在 FA 基因表型正常的攜帶者中看到的 frataxin 水平的 frataxin 水平。

Finally, our pharmacokinetic assessments showed that CTI-1601 was quickly absorbed with dose-proportional exposure, supporting the evaluation of once-daily dosing in future clinical studies. Collectively, we believe these results demonstrate proof of concept for CTI-1601 as they established its ability to deliver the critical protein to peripheral tissues that patients with FA are missing.

最後，我們的藥物動力學評估表明，CTI-1601 吸收迅速，且劑量與暴露量成正比，支持在未來的臨床研究中評估每日一次給藥方案。總而言之，我們認為這些結果為 CTI-1601 的概念驗證提供了依據，因為它們證實了 CTI-1601 能夠將關鍵蛋白質遞送至 FA 患者缺失的周邊組織。

Let me switch gears for a moment. We have several events coming up this year. In particular, we are planning to discuss these data and our future clinical development plans with both the FDA and the European Medicines Agency.

我先換個話題。我們今年有幾項活動。特別是，我們計劃與美國食品藥物管理局 (FDA) 和歐洲藥品管理局 (EMA) 討論這些數據以及我們未來的臨床開發計劃。

As you may also have seen in our 10-Q filed last night, we have an ongoing 180-day nonhuman primate study in which mortalities were observed in the highest dose groups. FDA is aware of these findings, and as dosing in this study is ongoing, we continue to collect relevant data and we'll share it with the agency prior to the initiation of future clinical trials.

正如您可能在我們昨晚提交的10-Q報告中看到的，我們正在進行一項為期180天的非人靈長類動物研究，其中在最高劑量組中觀察到了死亡。 FDA已獲悉這些發現，並且由於這項研究的劑量測定仍在進行中，我們將繼續收集相關數據，並將在未來臨床試驗開始前與FDA共享。

While the cause of these findings has not yet been determined, what I can say now is that, based on all of the information we have from our clinical and nonclinical programs to date, plus extensive input from toxicologists and other relevant experts, we do not expect these nonclinical findings to impact our previously disclosed timelines with regards to our Jive open-label extension and pediatric MAD trials, both of which we expect to initiate in the second half of the year.

雖然這些發現的原因尚未確定，但我現在可以說的是，根據我們迄今為止從臨床和非臨床項目中獲得的所有信息，加上毒理學家和其他相關專家的大量意見，我們預計這些非臨床發現不會影響我們之前披露的有關 Jive 開放標籤擴展和兒科 MAD 試驗的時間表，這兩項試驗都預計將在今年下半年啟動。

Looking a bit further down the road, we are planning for a global pivotal study as early as the second half of 2022. In addition, we will also be engaging in conversations with the regulatory authorities so that we are pursuing the most expeditious development path in an attempt to provide access to CTI-1601 as soon as it's feasible.

放眼未來，我們計劃最快在2022年下半年開展一項全球關鍵性研究。此外，我們還將與監管機構進行溝通，以尋求最快捷的開發路徑，爭取在可行的情況下盡快提供CTI-1601的使用權。

Let's now refocus on the clinical program. Slide 21 provides an overview of our Jive trial, which is a multicenter open-label extension trial that we expect to initiate in the second half of the year. Patients from both our SAD and MAD trials will be eligible to screen for Jive as will patients from a pediatric MAD trial, which is also expected to begin in the second half.

現在讓我們重新關注臨床項目。幻燈片21概述了我們的Jive試驗，這是一項多中心開放標籤擴展試驗，我們預計將於今年下半年啟動。參加SAD和MAD試驗的患者將有資格接受Jive的篩檢，參加兒科MAD試驗的患者也有資格接受篩檢，該試驗也預計將於下半年啟動。

While the exact dosing levels evaluated in Jive will be determined based on additional analysis from our Phase 1 program, we expect to treat patients in Jive for up to 24 months with any necessary extensions. We expect to enroll up to 50 patients who will likely be given once-daily doses of CTI-1601 administered subcutaneously.

雖然在 Jive 中評估的特定劑量水平將基於我們 I 期計畫的進一步分析來確定，但我們預計在 Jive 中對患者的治療將持續長達 24 個月，並可能根據需要延長治療時間。我們預計將招募最多 50 名患者，他們可能接受每日一次皮下注射 CTI-1601 的治療。

While there will be no placebo group for the Jive trial, we will utilize an external control arm derived from the Critical Path Institute data. The primary endpoint of Jive will be safety and tolerability, while key secondary endpoints include long-term measurements of frataxin levels and efficacy assessments. The long-term data we gain from this study will be very useful as we work to advance the CTI-1601 development program.

雖然 Jive 試驗不設安慰劑組，但我們將使用基於關鍵路徑研究所 (Critical Path Institute) 數據的外部對照組。 Jive 的主要終點是安全性和耐受性，而關鍵的次要終點包括 Frataxin 水平的長期測量和療效評估。我們從這項研究中獲得的長期數據將對我們推進 CTI-1601 開發項目大有裨益。

Now before we move to Q&A, I just wanted to, once again, sum up the key findings and conclusion from our Phase 1 data. First, we saw that repeated subcutaneous injections of CTI-1601 appear to have been generally well tolerated at doses up to 100 milligrams administered daily for 13 days. Second, we saw dose-dependent increases in frataxin levels from baseline compared to placebo controls in all evaluated tissues with daily dosing. And third, our pharmacokinetic and pharmacodynamic analyses support evaluating a once-daily dosing regimen for CTI-1601.

在進入問答環節之前，我想再次總結我們一期臨床試驗數據的關鍵發現和結論。首先，我們發現，連續13天，每日高達100毫克的CTI-1601皮下重複注射似乎整體耐受性良好。其次，與安慰劑對照組相比，我們發現每日給藥後，所有評估組織中的frataxin水平均從基線水平呈劑量依賴性增加。第三，我們的藥物動力學和藥效動力學分析支持評估CTI-1601的每日一次給藥方案。

As I mentioned several times throughout the call, the frataxin levels achieved in buccal cells with CTI-1601 administration were equal to, or in excess of, those we would expect to see in heterozygous carriers, who show no signs of disease. Given that insufficient frataxin levels are the root cause of Friedreich's ataxia, we believe that these exciting findings demonstrate proof of concept for CTI-1601.

正如我在電話會議中多次提到的，使用CTI-1601後，口腔細胞中達到的frataxin水平與雜合子攜帶者（無疾病體徵）的預期水平相當，甚至更高。鑑於frataxin水平不足是弗里德賴希共濟失調的根本原因，我們相信這些令人興奮的發現為CTI-1601的概念驗證提供了基礎。

It is also important to note that, to the best of our knowledge, CTI-1601 is the only drug candidate in clinical development that is designed to supplement frataxin levels in patients with FA, thus addressing the root cause of the disease.

值得注意的是，據我們所知，CTI-1601 是臨床開發中唯一旨在補充 FA 患者 Frataxin 水平的候選藥物，從而解決該疾病的根本原因。

Finally, I would like to take a minute to acknowledge that none of the progress we have discussed here today would have been possible without the commitment of our patients; the great work being done by the Friedreich's Ataxia Research Alliance; or the talent of our employees, partners, and investigators. I am extremely grateful for all of these individuals for the important roles they have played in advancing CTI-1601's clinical development.

最後，我想藉此機會感謝大家，如果沒有病患的付出、弗里德賴希共濟失調研究聯盟的傑出貢獻，以及我們員工、合作夥伴和研究人員的才華，我們今天在此討論的這些進展都不可能實現。我衷心感謝所有這些人，感謝他們在推進 CTI-1601 臨床開發過程中發揮的重要作用。

With that, I'd like to extend one last thank you to all of those listening to our call today. We will now open the call to questions. Operator?

最後，我想向今天收聽我們電話會議的所有人致以最後的感謝。現在開始提問環節。接線生？

(Operator Instructions). Myles Minter, William Blair.

（操作員指令）。 Myles Minter，William Blair。

Congrats on the data; it's really nice to see this frataxin expression and it's a great outcome for patients really. My first question is on cohort two. It seems as if there's been a slight decline in expression from day seven to day 13 across the tissues. I'm just trying to clarify whether that's just due to the reduction in the dosing frequency in week two versus week one.

恭喜數據！看到frataxin的表達真是太好了，這對患者來說真的是一個很好的結果。我的第一個問題是關於第二組。似乎從第7天到第13天，各組織中的表現略有下降。我只是想弄清楚這是否僅僅是因為第二週的給藥頻率相對於第一週有所降低。

Or is that variability in the frataxin expression of the patients or maybe even the assay? And is it safe to say that when you switch those patients over to Jive, they will all be pushing up to the 100 mg dose? That's the first one.

或者，這與患者 frataxin 表現量的差異有關，甚至可能是檢測方法的差異？是否可以肯定地說，當您將這些患者轉用 Jive 治療後，他們都會將劑量提高到 100 毫克？這是第一個問題。

Hi, Myles. It's good to hear your voice. So, we believe that the decrease in cohort two between day seven and 13 is because those patients were switched to every other day dosing. So, we do believe that it's probably going to at least initially be a daily dose of CTI-1601 that is required. And we think that's borne out by the 100 mg dose group where you really don't see that decrease. And so, yes, we do think it's because of the change in regimen, which was part of the reason why we designed the trial the way we did.

你好，Myles。很高興聽到你的聲音。所以，我們認為第二組患者在第7天到第13天之間用藥量的減少是因為這些患者改為隔日給藥。所以，我們確實認為，至少在最初階段，可能需要每天服用CTI-1601。我們認為100毫克劑量組證實了這一點，在該組中，你確實沒有看到用藥量的減少。所以，是的，我們確實認為這是因為治療方案的改變，這也是我們設計試驗的原因之一。

With regard to Jive being 100 mg, we really can't answer that question yet. We're still looking at a whole bunch of other pieces of data. This is really top-line data and there's still a lot of number crunching that needs to go on looking at the pharmacodynamic data by patient, looking at it by weight, things like that. So, I don't think we really know at this point what dose will be in Jive. But I do think it's fair to say that it is likely to be daily dosing, at least initially.

關於Jive的劑量是否為100毫克，我們目前還無法回答這個問題。我們仍在研究大量其他數據。這確實是關鍵數據，還需要進行大量的數據分析，例如分析患者的藥效動力學數據、體重數據等等。所以，我認為我們目前還不清楚Jive的劑量是多少。但我認為至少在初期階段，可以肯定地說，它很可能是每天服用。

Okay, that makes sense. And then on the injection site reaction frequency -- I'm wondering whether the incidence rates changed over the two-week treatment period. Did they occur more frequently or with greater severity upfront as opposed to dosing throughout that second week? Any indications there?

好的，這說得通。然後關於注射部位反應的頻率——我想知道在兩週的治療期間，發生率是否有變化。與第二週的治療相比，注射部位反應在治療初期是否更頻繁或更嚴重？有什麼跡象嗎？

Not that we can tell right now. It was pretty random. Some patients -- like we said, all the patients on the active had at least one, but not every time they injected did they have an injection site reaction. And I don't think they necessarily changed with frequency.

目前我們還無法確定。這相當隨機。有些患者－就像我們之前說的，所有接受活性藥物治療的患者至少都會出現一次反應，但並非每次注射都會出現注射部位反應。而且我認為這些反應不一定會隨著頻率而改變。

We have not looked yet at site. We actually administered the drug at four sites, both thighs and either side of the abdomen, and those sites were rotated, which is pretty traditional with subcutaneous injections. And so, we still have to look at things like site of administration. But these injection site reactions were really very transient and were, like I said, mild or moderate.

我們還沒有研究注射部位。實際上，我們在四個部位注射了藥物，包括大腿兩側和腹部兩側，這些部位是輪換的，這在皮下注射中很常見。所以，我們還是需要研究注射部位等因素。但這些注射部位的反應確實非常短暫，而且就像我說的，是輕度或中度的。

Okay. The last one before I jump back in the queue, just on the monkey tox. I know you can't really comment too much on it, but when you notified the FDA of this, was there any back-and-forth commentary with the agency that we should be aware about? And then when you're going to update the agency?

好的。在我回到話題之前，最後一個問題是關於猴毒性的。我知道您不能對此發表太多評論，但是當您將此事通知FDA時，我們之間是否有任何需要注意的反覆溝通？您什麼時候會向FDA報告最新進展？

And can you give us a sense for the dose ranges that the mortalities occurred at in the monkey relative to that that you're using in the clinic, say the 100 mg dose in those patients?

您能否告訴我們，相對於您在臨床中使用的劑量，猴子死亡時的劑量範圍是多少，比如說那些患者使用的 100 毫克劑量？

Yes, so we don't really like to give a lot of detail with our conversations with FDA. But I can tell you that they have been notified and they're okay with us submitting the data when we need to and when we're ready to. The trial is still ongoing, so until it's complete and we can get all our data in, I think it's premature to continue to have a lot of conversation with the agency. Because we have to obviously determine what we think is the cause and make sure that we have all of the data.

是的，所以我們不太願意透露與FDA溝通的細節。但我可以告訴你，他們已經收到通知，並同意我們在需要時和準備好時提交資料。試驗仍在進行中，所以在試驗完成並收集所有數據之前，我認為現在繼續與FDA進行大量溝通還為時過早。因為我們顯然必須確定我們認為的病因，並確保我們掌握了所有數據。

With regard to dose, I wouldn't focus on dose; I would focus on exposure because that's what's really relevant and what most of the regulatory authorities will look at. And from the standpoint of exposure, we don't have the exposure yet in the 180-day because they're still being dosed, it's still ongoing.

關於劑量，我不會關注劑量本身；我會關注暴露量，因為這才是真正相關的，也是大多數監管機構會關注的。從暴露量的角度來看，我們還沒有在180天內獲得暴露量，因為它們仍在給藥，仍在進行中。

But we did complete, as you well know, a 90-day study. And based on the exposure seen in that study, we do have significant safety margins. And so -- and it's the same species of monkey, it's the same size monkey. So, I would anticipate that what we saw in the 90-day is relevant. And like I said, we have significant safety margins.

但如你們所知，我們確實完成了一項為期90天的研究。根據這項研究中觀察到的暴露情況，我們確實有相當的安全裕度。而且──而且是同一物種、相同大小的猴子。所以我預期我們在90天內觀察到的情況是相關的。正如我所說，我們有相當的安全裕度。

Jonathan Wolleben, JMP Securities.

喬納森·沃萊本，JMP 證券。

Good morning and thanks for taking the questions and congrats on the data. Just a few from me. When we take a look at the baseline frataxin levels, I'm wondering if this is consistent with what you would expect based on some of the other characteristics, like you mentioned 50% of patients being non-ambulatory.

早安，感謝您回答問題，也恭喜您獲得的數據。我只說幾點。當我們查看基線frataxin水平時，我想知道這是否與您根據其他一些特徵所預期的結果一致，例如您提到的50%的患者無法行走。

Yes, I think it is -- it's really hard to compare frataxin levels across trials because they use different sampling techniques and there's different assays. And I think what's really consistent is that patients usually have somewhere around 20%. We've said 20% to 40%, but I think if you talk to the patient community, they actually think it's closer to 20% or maybe even a little bit less.

是的，我認為是這樣——很難比較不同試驗中的frataxin水平，因為它們使用的採樣技術不同，檢測方法也不同。我認為真正一致的是，患者的frataxin水平通常在20%左右。我們之前說的是20%到40%，但我認為如果你和患者群體交流，他們實際上認為這個比例更接近20%，甚至可能更低。

But I do think it's consistent. And as you saw, it's consistent between patients. I mean, the baseline numbers all look pretty similar in all the different tissues with the exception of platelets, which seem to have more variability.

但我確實認為它是一致的。如你所見，不同患者之間也保持一致。我的意思是，除了血小板之外，所有不同組織的基線數值看起來都非常相似，血小板似乎變化更大。

Was there anything besides dose when you look across demographics or patient characteristics for those who seem to have more frataxin observed? And then when you think about the time course -- obviously it's very short right now and we only have two time points. But do you think there's a leveling off here already? Or do you expect to see more increases over time if you continue to dose?

當您查看人口統計或患者特徵，發現那些似乎觀察到 Frataxin 水平較高的患者時，除了劑量之外，還有其他因素嗎？然後，當您考慮時間進程時——顯然現在很短，我們只有兩個時間點。但是，您認為現在已經趨於平穩了嗎？或者，如果您繼續增加劑量，您是否預計隨著時間的推移會看到更多的成長？

Yes, it's a hard question to answer, Jonathan, and a good one and an important one. I think we really need to get into the Jive study and go out further to know whether we're actually at steady-state or not. There is a theory that frataxin has a longer half-life than probably CTI-1601 does. And even then iron sulfur cluster enzymes may even have a longer half-life.

是的，喬納森，這個問題很難回答，而且是個好問題，一個重要的問題。我認為我們真的需要深入研究Jive的研究，進一步了解我們是否真的處於穩態。有一種理論認為，frataxin的半衰期可能比CTI-1601更長。即便如此，鐵硫簇酶的半衰期也可能更長。

So, I think until we actually get into a chronic dosing like we will in the Jive study, it's really hard to know whether we could even at some point switch to every other day -- or whether we see we're really at steady-state and we need to dose daily. But I think we need more data.

所以，我認為，在我們真正像 Jive 研究中那樣進入慢性服藥模式之前，很難確定我們是否可以在某個時候改為隔天服藥——或者我們是否真的達到了穩定狀態，需要每天服藥。但我認為我們需要更多數據。

I guess last one from me to that point, do you have any sense, based on literature or natural history, when seeing these increases in levels might translate to some kind of clinical benefits? Thanks.

我想問最後一個問題，根據文獻或自然史，您是否認為這些水平的升高可能轉化為某種臨床益處？謝謝。

Yes, I don't because nobody else has replaced frataxin. So, we've really, at least historically -- I mean, in the animals you actually see it relatively quickly. We do, as you may recall, have some clinical data. We did timed 25 foot walk for those patients who could walk. We did the nine-hole peg repeatedly. We've also looked at speech and modified FARS. That data has not yet been analyzed. It is in the process and we will be releasing that data later in the year. And so, I think that will give us some hint.

是的，我不這麼認為，因為還沒有其他藥物取代Frataxin。所以，至少從歷史上看，我們確實在動物實驗中觀察到了相對較快的效果。你可能還記得，我們​​確實有一些臨床數據。我們為那些可以行走的患者進行了25英尺的計時行走。我們反覆進行了九孔樁測試。我們也研究了言語和改良的FARS（臉部表情評估量表）。這些數據尚未分析。分析正在進行中，我們將在今年稍後發布。所以，我認為這會給我們一些提示。

Like we've said -- I've said many times, after 13 days I really don't anticipate to see a clinical outcome. But, obviously, we are going to look and evaluate that data. And then once we get into the Jive study we'll be able to compare some of that clinical data to our natural history -- to the natural history database and to our control arm.

就像我們說過的──我已經說過很多次了──13天後我真的不指望能看到臨床結果。但顯然，我們會查看並評估這些數據。一旦我們進入Jive研究，我們就能將一些臨床數據與我們的自然史——自然史資料庫和對照組——進行比較。

Looking forward to it. Congrats again on the data today.

非常期待。再次恭喜今天的數據。

Thanks, Jonathan. Thanks for the questions.

謝謝喬納森。謝謝你的提問。

Yatin Suneja, Guggenheim Partners.

蘇內賈 (Yatin Suneja)，古根漢合夥人事務所。

Hey guys, thank you for taking my question and on the excellent presentation. Just a couple from me. So, it seems like you are emphasizing that only in buccal cells you are achieving frataxin levels that are similar or exceed the heterozygous carrier. What about skin and/or platelets?

大家好，感謝您回答我的問題，也感謝您精彩的演講。我只想提幾點。所以，您似乎強調只有在口腔細胞中，Frataxin 的水平才能與雜合子攜帶者相似甚至超過後者。那麼皮膚和/或血小板呢？

Yes. So, Yatin, nice to hear your voice again. The reason we talk about buccal cells is because that's the only data we have -- first from the literature it's really just buccal cells. But as importantly, it's the fact that we did this noninterventional study and we didn't do skin biopsies or platelets; we just did buccal cells. And so, that's where we have that control.

是的。 Yatin，很高興再次聽到你的聲音。我們之所以討論頰細胞，是因為這是我們目前僅有的數據──首先，從文獻來看，其實只有頰細胞。但同樣重要的是，我們進行了這項非干預性研究，沒有進行皮膚活檢或血小板取樣；我們只進行了頰細胞取樣。所以，這就是我們能夠控制的。

We are going to be doing a noninterventional study looking at healthy volunteers where we will be collecting skin and platelets and buccal cells. But it's not because we're so much emphasizing the buccal cells, it's because that's the data we have at this point.

我們將進行一項非干預性研究，研究對象為健康志願者，我們將收集皮膚、血小板和口腔細胞。但我們並非特別強調口腔細胞，而是因為我們目前掌握的數據有限。

I think actually skin is highly relevant. I'm sure you know buccal cells are mucosal membranes, so those cells turn over very quickly. And skin is a much more stable tissue. As well as the sampling techniques, when you do buccal swabs, how hard you swab, how long you swab. Obviously we tried to control that and we were at a single unit. So, it was a bit easier to control it in our study.

我認為皮膚實際上與此密切相關。我相信你們知道，口腔細胞是黏膜，所以這些細胞更新非常快。而皮膚是一種較穩定的組織。此外，還有採樣技術，例如進行口腔拭子採樣時，擦拭的力道、擦拭的時間。顯然，我們試圖控制這些因素，而且我們在一個單位進行。所以，在我們的研究中，控制起來比較容易一些。

But skin biopsies are routine, you are using a specific device, so you always get the same amount of tissue and the same depth of tissue. And so, I actually think the skin biopsies are really interesting. And obviously in those tissues we saw threefold increase between baseline and day 13. So, I actually really like the skin.

但皮膚切片檢查是常規檢查，需要使用特定的設備，所以每次取的組織量和深度都是一樣的。所以，我覺得皮膚切片真的很有趣。很明顯，從基線到第13天，我們發現這些組織的細胞數量增加了三倍。所以，我其實很喜歡皮膚切片檢查。

Platelets I think are a little less indicative, and I think I've said this before to you, because they are intravascular. And we know the drug gets into the intravascular space and we know it is absorbed quickly and the half-life is about 11 hours. So, I think platelets are variable for a whole host of reasons and I think probably not as relevant because they are not really a peripheral tissue. Buccal swabs and skin are peripheral tissues and we show that the process protein is in those tissues.

我認為血小板的指示性稍差一些，我想我之前跟你說過，因為它們存在​​於血管內。我們知道藥物會進入血管內空間，吸收很快，半衰期約11小時。所以，我認為血小板的變化有很多原因，而且我認為可能不那麼重要，因為它們實際上不是周邊組織。口腔拭子和皮膚是周邊組織，我們發現過程蛋白存在於這些組織中。

Got it, got it. And then with regard to the dosing, it seems like the 100 mg, given that it was daily, seemed to be a very consistent and robust increase in frataxin level across all measured tissues. Do you intend to go higher or do you think you have a pretty good handle so either a 50 mg on a daily basis or 100 mg on a daily basis is the go-forward dose? Or do you think you need to go higher because you are achieving the threshold that you need to achieve?

明白了，明白了。然後關於劑量，考慮到每日服用100毫克，似乎在所有測量組織中，Frataxin水平都出現了非常一致且強勁的上升。您打算提高劑量嗎？還是您認為您已經掌握了相當好的控制方法，所以每天50毫克或100毫克是未來的劑量？或者您認為您需要提高劑量，因為您已經達到了需要達到的閾值？

Yes, I think that's right. I don't think we need to go higher. Whether we do 50 or 100 I think has yet to be seen. Like I said, we want to do some more detailed analysis looking at some of the detailed demographics and characteristics of the individual patients. But I do think daily dosing is likely, at least initially, until we see what happens out 30 days and 60 days kind of thing. And we're still looking at dose, but I do think that we -- I don't believe we need to go higher. I think we've achieved where we want to go.

是的，我想是對的。我認為我們不需要增加劑量。至於我們到底是增加50劑量還是100劑量，我認為還有待觀察。就像我說的，我們想做一些更詳細的分析，了解個別患者的一些詳細人口統計和特徵。但我確實認為每日給藥是可能的，至少在初期是這樣，直到我們觀察30天和60天的情況。我們仍在研究劑量，但我確實認為我們不需要增加劑量。我認為我們已經達到目標了。

And also given the fact that -- granted at multiples -- high multiples people have described -- especially the viral gene therapy folks have described some toxicity, I think we don't want to be at two or three times what a normal person is walking around with. We want to be somewhere between that -- 60% and 80% of normal would be what I think and that's exactly where we are.

而且考慮到——當然，人們描述的倍數很高——尤其是病毒基因療法的研究人員描述了一些毒性，我認為我們不希望病毒感染量達到正常人的兩到三倍。我們希望病毒感染量介於正常水平的60%到80%之間——我認為是正常水平的60%到80%，而我們現在的情況正是如此。

Just one final question. Do we know the protein concentration or FXN in healthy and heterozygous in all of these three evaluated measures?

最後一個問題。我們是否知道在這三個評估指標中，健康和雜合子組的 FXN 蛋白濃度是多少？

So, there's data out there on -- and it's highly variable depending upon the assay and the sampling techniques. As I said earlier, we are going -- in my script, we are going to be doing a noninterventional study using our assay techniques and our proprietary assay so that we have that data going forward. And as we go into Jive we'll be able to compare it to similar pieces of information.

所以，現在有很多數據——而且這些數據會根據檢測方法和採樣技術的不同而有很大差異。正如我之前所說，我們將——在我的方案中，我們將使用我們的檢測技術和專有檢測方法進行一項非干預性研究，以便我們能夠獲得這些數據。當我們進入 Jive 時，我們將能夠將其與類似的資訊進行比較。

But the best data is really in buccal cells and was published out of -- I think out of CHOP. And that's really where the best data comes from. But like I said, it uses a different assay.

但最好的數據實際上是關於口腔細胞的，而且是在——我想是CHOP——發表的。最好的數據確實來自那裡。但就像我說的，它使用了不同的檢測方法。

Very helpful. Sorry, one more question if I may. You also looked at the gene expression in the buccal cell. When we might be able to see that data or anything you could share on that?

非常有幫助。抱歉，請容許我再問一個問題。您也研究了口腔細胞的基因表現。我們什麼時候能看到這些數據，或是您能分享一些相關資訊嗎？

Yes, we don't have that data back yet. And it's going to be some time. Those assays are not as simple and as straightforward as you might think. Plus also analyzing them, because we looked at a whole host of different genes. So, that data probably won't be available until the second half of the year.

是的，我們還沒有拿到這些數據。這還需要一些時間。這些檢測不像你想像的那麼簡單直接。而且由於我們研究了大量不同的基因，還需要分析。所以，這些數據可能要等到今年下半年才能出來。

Very good. Thank you so much.

非常好。非常感謝。

Patrick Dolezal, LifeSci Capital.

帕特里克·多爾扎爾（Patrick Dolezal），LifeSci Capital。

Congrats on the great data. Could you just help us think about the relationship between buccal, skin cells and platelets and the presence of frataxin and some of the other important tissues and assays such as CNS, heart and skeletal muscle? And to the extent that it's possible -- I know it's really tricky -- but how much do each of those tissues ultimately contribute to some of the various clinical endpoints in FA?

恭喜您獲得如此出色的數據。您能否幫助我們思考一下頰黏膜、皮膚細胞、血小板與 Frataxin 以及其他一些重要組織和檢測（例如中樞神經系統、心臟和骨骼肌）之間的關係？如果可能的話——我知道這確實很難——但這些組織最終對 FA 中的各種臨床終點分別貢獻了多少呢？

Hi, Patrick. So, the best data -- the buccal cells have been -- there's some really good publications out there; I think we reference it in our deck. There's some really good publications that look at buccal cell frataxin levels and compare them to the GAA repeat, which many of you know is the longer the GAA repeat the more severe -- the earlier the onset of the disease and the more severe the disease is.

你好，派崔克。所以，關於頰細胞的最佳數據——已經有一些非常好的出版物了；我想我們在我們的簡報中引用了它們。有一些非常好的出版物研究了頰細胞的frataxin水平，並將其與GAA重複序列進行了比較。你們很多人都知道，GAA重複序列越長，病情就越嚴重──發病越早，病情就越嚴重。

So, buccal frataxin levels do correlate with the GAA repeat as well as severity of disease as measured by modified FARS. And so, there is that correlation there. It is really hard to know to then transition that obviously into cardiac and skeletal muscle and CNS.

因此，口腔Frataxin水平確實與GAA重複以及改良FARS測量的疾病嚴重程度有關。所以，存在這種相關性。很難將其轉化為心肌、骨骼肌和中樞神經系統。

But we believe that CTI-1601 will be taken up based on the amount of mitochondria in a given tissue. So, more mitochondrial-rich tissues will take up more CTI-1601 simply because they process more of the protein. And we do know from our basic science data and our cytochemistry plus all the animal data, that CTI-1601 does really go everywhere in the cell. So, as long as it's getting into the mitochondria it should be processed there.

但我們相信，CTI-1601 的吸收取決於特定組織中粒線體的數量。因此，富含粒線體的組織吸收更多的 CTI-1601 只是因為它們能處理更多的蛋白質。而且，根據我們的基礎科學數據、細胞化學以及所有動物實驗數據，我們確實知道 CTI-1601 確實能進入細胞的任何地方。所以，只要它進入了粒線體，就應該在那裡被處理。

Got it, thanks. And I guess if you could provide a bit more detail on the endpoints and the timing of those assessments in the Jive study. And any granularity as to when you could potentially provide an update from that data set would be helpful. And I guess in a more general sense I'm just trying to get at what does the timing look like for initial clinical assessments with CTI-1601.

明白了，謝謝。我想，如果您能提供一些關於Jive研究中終點和評估時間的更多細節，那就更好了。如果您能提供關於何時可能提供該數據集更新的詳細信息，那將非常有幫助。我想從更廣義的角度來理解，我只是想了解CTI-1601的初步臨床評估時間安排。

Yes, that's a good question. So, that study is still being designed, although we'll look at all of the things that routinely people look at -- modified FARS, 25 foot walk in those patients who can perform the 25 foot walk, nine-hole peg. We will be looking at speech, as we did here, and how we design that will be interesting because it will be based on some of the data we collected in the MAD study. And then we are also -- obviously safety is a huge endpoint in Jive.

是的，這是個好問題。所以，這項研究仍在設計中，儘管我們會觀察人們常規檢查的所有方面——改良的FARS，以及那些能夠完成25英尺步行和九孔釘的患者進行的25英尺步行。我們將觀察言語，就像我們在這裡所做的那樣，我們如何設計這項研究將會很有趣，因為它將基於我們在MAD研究中收集的一些數據。然後，我們當然也——顯然，安全性是Jive的一個重要終點。

From the standpoint of timing -- and obviously also frataxin levels. So, we'll also be looking at maintaining frataxin levels over time. And as some of the others have alluded to, making it seem whether we should change the regimen, whether we add daily dosing or at steady-state, or whether we may be increasing over time if you dose for longer than 13 days. So, you might be able to actually decrease the frequency of dosing.

從時間角度來看——顯然也包括 Frataxin 水平。因此，我們也會關注如何長期維持 Frataxin 水平。正如其他一些人所提到的，我們需要考慮是否應該改變治療方案，是增加每日劑量還是維持穩定劑量，或者如果服藥時間超過 13 天，我們是否可以逐漸增加劑量。所以，實際上可以降低服藥頻率。

So, all of that will be data coming out of the Jive. I can't really tell you exactly when we'll be able to provide data because this trial is still being designed. But more importantly, we have to initiate the sites. It won't be a cohort-driven study like this is; patients will come in over time.

所以，所有這些數據都將來自 Jive。我無法確切告訴您我們何時能夠提供數據，因為這項試驗仍在設計中。但更重要的是，我們必須啟動試驗點。這不會像本研究一樣是一項隊列驅動的研究；患者會隨著時間的推移而陸續加入。

So, it will really depend on site initiation and patient enrollment, which we have said will start the second half of this year. Once we see how long it takes us to get the sites initiated I think we can give you a better read on how long -- when the data will come.

所以，這實際上取決於試驗點的啟動和患者入組情況，我們之前說過這些工作將於今年下半年開始。等我們了解了啟動試驗點需要多長時間後，我想就能更了解數據何時會出來。

Got it. That's super helpful. Thank you.

明白了。這太有幫助了。謝謝。

Myles Minter, William Blair.

邁爾斯·明特、威廉·布萊爾。

Yes, thanks for the follow-up. Just following on from John's question. I think he was trying to get at the baseline frataxin levels in ambulatory versus non-ambulatory patients. Did you actually see a difference in the frataxin level increase in those two patient populations of CTI-1601?

是的，謝謝你的後續提問。我接著John的問題繼續問。我認為他想了解門診患者和非門診患者的基線frataxin水平。你真的觀察到CTI-1601治療後這兩組患者中frataxin水平的升高有差異嗎？

Myles, we haven't actually -- I don't think we've looked at that data yet. We will -- I mean, that's an important question. But it's somewhat definitional who was ambulatory and who was non-ambulatory. When you go and get a chance and go into the demographics you're going to see that half the population was wheelchair-bound, so clearly non-ambulatory.

邁爾斯，我們實際上還沒有——我想我們還沒有看過這些數據。我們會的——我的意思是，這是一個重要的問題。但在某種程度上，誰能走動，誰不能走動，這都是定義問題。如果你有機會去研究人口統計數據，你會發現一半的人口是坐輪椅的，所以顯然不能走動。

But the other half of the population, if I recall, I think only two patients didn't use an assisted device. So, most of those patients were walking with walkers and some had a cane but very few. And these patients were pretty far along.

但我記得，剩下的一半患者中，只有兩位患者沒有使用輔助設備。所以，這些患者大多都使用助行器行走，有些患者有拐杖，但很少。而這些患者的步態相當平穩。

It's really hard in this population -- it's not like a spinal cord injury, right, where you are walking one day and not walking the next. We will be looking -- I think what we'll probably also be looking at is frataxin levels based on modified FARS, which is a more -- maybe a more continuous scale to be looking at. But we haven't analyzed the data to that detail yet. We will be but we haven't.

對這類人群來說，這真的很難——這不像脊髓損傷，對吧，今天能走路，明天就走不了了。我們會觀察——我想我們可能還會觀察基於改良FARS的frataxin水平，這是一個更——或許是一個更連續的觀察尺度。但我們還沒有對數據進行如此詳細的分析。我們會做的，但目前還沒有。

Okay, cool. And then a more technical question. Was the eight patients you have, the healthy control frataxin levels, was that data run on the same immunoassay as the CTI-1601 treated patient biopsies? Or were they two different assays and then you superimposed the data on them?

好的，很酷。接下來是一個更技術性的問題。您研究的這八名患者，健康對照者的 Frataxin 水平數據，是否與接受 CTI-1601 治療的患者活檢數據採用相同的免疫分析方法？還是說，它們是兩種不同的分析方法，然後您將資料疊加在一起？

They were identical assays. It was the same assay at the same site, identical assay -- as well as the sampling technique. It was a different site, but the sampling technique was identical as well.

它們是相同的檢測結果。是同一地點進行的相同檢測，檢測方法也相同——採樣技術也相同。雖然地點不同，但採樣技術也相同。

Okay, beautiful. Congrats on the data again and thanks for the questions.

好的，太棒了！再次恭喜你所獲得的數據，也感謝你的提問。

This concludes the question-and-answer session. I would like to turn the conference back over to Carol Ben-Maimon for any closing remarks.

問答環節到此結束。我想將會議交還給卡羅爾·本-邁蒙，請她做最後發言。

I'd just like to thank everybody for listening to the call and participating and thanks to everybody for the questions. We are obviously very excited about the data and we look forward to continuing to progress the clinical development program. Again, thanks to everybody for coming and thanks to the patients who participated in the trial.

我只想感謝大家收聽電話會議並參與討論，也感謝大家的提問。我們對這些數據感到非常興奮，並期待繼續推進臨床開發計畫。再次感謝大家的到來，也感謝參與試驗的患者。

This concludes today's conference call. You may disconnect your lines. Thank you for participating and have a pleasant day.

今天的電話會議到此結束。您可以掛斷電話了。感謝您的參與，祝您有愉快的一天。