Eloxx Pharmaceuticals Inc (ELOX) 2020 Q4 法說會逐字稿

Good afternoon, everyone, and welcome to the Eloxx Pharmaceuticals Fourth Quarter and Full Year 2020 Earnings Webcast and Conference Call. Today's call is being recorded.

大家下午好，歡迎收看 Eloxx Pharmaceuticals 第四季度和 2020 年全年收益網絡直播和電話會議。今天的通話正在錄音中。

At this time, I would like to turn the call over to Barbara Ryan, Eloxx Investor Relations. Please begin.

此時，我想將電話轉給 Eloxx 投資者關係部的 Barbara Ryan。請開始。

Thank you, Victor. Welcome, and thank you for joining us this afternoon for a review of Eloxx Pharmaceuticals' Fourth Quarter and Full Year 2020 Financial Results and Business Update. Joining me this afternoon are Dr. Greg Williams, our Chief Executive Officer; Neil Belloff, Chief Operating Officer and General Counsel; Dr. Tom Haverty, our Chief Medical Officer; Dr. Matthew Goddeeris, Vice President of Research; and Stephen MacDonald, our Vice President of Finance and Accounting.

謝謝你，維克多。歡迎並感謝您今天下午加入我們，回顧 Eloxx Pharmaceuticals 的第四季度和全年 2020 年財務業績和業務更新。今天下午加入我的是我們的首席執行官 Greg Williams 博士； Neil Belloff，首席運營官兼總法律顧問；我們的首席醫療官 Tom Haverty 博士；研究副總裁 Matthew Goddeeris 博士；以及我們的財務和會計副總裁 Stephen MacDonald。

Before we begin, I would like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in our most recent annual report on Form 10-K filed with the Securities and Exchange Commission, as well as our other reports filed with the SEC. Any forward-looking statements represent our views as of today, March 11, 2021 only. A replay of this call will be available on the company's website, www.eloxxpharma.com, following the call.

在我們開始之前，我想提醒您，在本次電話會議期間做出的任何非歷史陳述都被視為前瞻性陳述，符合 1995 年《私人證券訴訟改革法案》的含義。實際結果可能與所示結果存在重大差異由於各種重要因素，包括我們最近向美國證券交易委員會提交的 10-K 表格年度報告的風險因素部分中討論的因素，以及我們向美國證券交易委員會提交的其他報告，這些陳述導致這些陳述。任何前瞻性陳述僅代表我們截至今天，即 2021 年 3 月 11 日的觀點。電話會議結束後，公司網站 www.eloxxpharma.com 將提供此次電話會議的重播。

It is now my great pleasure to turn the call over to Dr. Greg Williams, Chief Executive Officer of Eloxx Pharmaceuticals.

現在我很高興將電話轉給 Eloxx Pharmaceuticals 首席執行官 Greg Williams 博士。

Thank you, Barbara, and welcome to Eloxx's Fourth quarter and Full Year 2020 Earnings Webcast and Conference Call. We are continuing to advance our clinical and scientific programs for our ERSG library. Our highest priority is to complete our Phase II clinical trials for ELX-02 in cystic fibrosis, and we are on track to report top line data in the first half of this year. We believe that these proof-of-concept data will be a substantial value inflection point for our company.

謝謝芭芭拉，歡迎收看 Eloxx 的第四季度和 2020 年全年收益網絡直播和電話會議。我們正在繼續推進我們的 ERSG 圖書館的臨床和科學計劃。我們的首要任務是完成囊性纖維化 ELX-02 的 II 期臨床試驗，我們有望在今年上半年報告一線數據。我們相信，這些概念驗證數據將成為我們公司的重要價值轉折點。

As we previously shared, we are pleased that ELX-02 Phase II clinical trials independent safety review committees have included several planned meetings and allowed dose escalation up to the fourth and highest dose level. To date, no drug-related serious adverse events have been reported. We are conducting these global trials at top CF clinical trial sites and are grateful that the Cystic Fibrosis Foundation has recently expanded their financial support beyond the U.S. to provide increased funding for our global ELX-02 Phase II clinical trial program. The expressed level of interest and support from top investigators, trial sites, and patient advocacy groups has been a fantastic benefit to the program.

正如我們之前分享的那樣，我們很高興 ELX-02 II 期臨床試驗獨立安全審查委員會包括了幾次計劃中的會議，並允許將劑量升級到第四個和最高劑量水平。迄今為止，尚未報告與藥物相關的嚴重不良事件。我們正在頂級 CF 臨床試驗地點進行這些全球試驗，並感謝囊性纖維化基金會最近將其財政支持擴大到美國以外，為我們的全球 ELX-02 II 期臨床試驗計劃提供更多資金。頂級研究人員、試驗地點和患者權益團體表達的興趣和支持水平對該計劃來說是一個巨大的好處。

Previously, we've shared that we continue to evaluate with additional clinical trial sites in other countries where patient enrollment may be feasible. We are pleased to report that we are opening additional clinical trial sites in Australia and Canada. As you know, the cystic fibrosis foundation has launched a $500 million Path to a Cure initiative aimed at finding cures for all CF patients. The foundation's initiative is prioritizing innovative approaches for individuals who do not respond to currently available treatments. This includes those with nonsense mutations, such as G542X, which is the focus of our ELX-02 Phase II clinical trials.

此前，我們曾分享過，我們將繼續在其他國家/地區的其他臨床試驗地點進行評估，這些國家/地區的患者招募可能是可行的。我們很高興地報告，我們將在澳大利亞和加拿大開設更多的臨床試驗中心。如您所知，囊性纖維化基金會發起了一項耗資 5 億美元的治愈之路計劃，旨在為所有 CF 患者尋找治愈方法。該基金會的倡議是為那些對目前可用的治療沒有反應的個人優先考慮創新方法。這包括那些具有無義突變的，例如 G542X，這是我們 ELX-02 II 期臨床試驗的重點。

Patients with nonsense mediated cystic fibrosis represent about 12% of the CF population, according to the Cystic Fibrosis Foundation. The potential ability of an investigational drug such as ELX-02 to restore functional CFTR protein production in these patients could be a major advance and substantially improve the length and quality of their lives. We believe that ELX-02 has the potential to be an important disease-modifying therapy for these patients, who feel left behind and have few, if any, treatment options. We are committed to advancing the development of ELX-02 as quickly as possible.

根據囊性纖維化基金會的數據，無意義介導的囊性纖維化患者約佔 CF 人群的 12%。研究藥物如 ELX-02 恢復這些患者功能性 CFTR 蛋白生產的潛在能力可能是一項重大進步，並大大改善他們的生命長度和質量。我們相信 ELX-02 有潛力成為這些患者的重要疾病緩解療法，這些患者感到被遺忘並且幾乎沒有治療選擇（如果有的話）。我們致力於盡快推進 ELX-02 的開發。

Substantial advances have been made in the treatment of patients with cystic fibrosis with the introduction of disease-modifying therapies, including the recent triple combination, TRIKAFTA, from Vertex. While the benefits to patients have evolved as monotherapy transitioned to combinations, and most recently to the triple combo, there remains a high unmet medical need among the 12% of patients with nonsense-mediated disease, for whom there is no approved therapy. These difficult-to-treat patients are often the most severely afflicted by this disease.

隨著疾病改善療法的引入，包括最近來自福泰（Vertex）的三聯組合 TRIKAFTA ，囊性纖維化患者的治療取得了實質性進展。雖然隨著單一療法過渡到聯合療法，以及最近過渡到三聯療法，對患者的益處已經發生變化，但在 12% 的無意義介導疾病患者中仍然存在高度未滿足的醫療需求，這些患者沒有獲得批准的治療方法。這些難以治療的患者往往是受這種疾病折磨最嚴重的。

Patients with an F508del are another difficult-to-treat population where a single agent, Kalydeco, was not effective. The next-generation combination products, ORKAMBI and SYMDEKO, demonstrated a clinically important benefit in these patients. There was a 5 to 11 millimole per liter reduction in sweat chloride concentration for ORKAMBI, and a reduction of 10 millimole per liter for SYMDEKO. These changes were associated with increases in FEV1 in the low to mid-single digits. TRIKAFTA, the triple-combo therapy, has moved the needle even higher, with sweat chloride concentration reductions from 42 to 45 millimole per liter, which were associated with 10% to 14% increases in FEV1.

F508del 患者是另一個難以治療的人群，其中單一藥物 Kalydeco 無效。下一代組合產品 ORKAMBI 和 SYMDEKO 在這些患者中顯示出臨床上重要的益處。對 ORKAMBI 汗液氯化物濃度減低 5 至 11 毫摩爾/升，而對 SYMDEKO 減低 10 毫摩爾/升。這些變化與低到中等個位數的 FEV1 增加有關。三聯療法 TRIKAFTA 的針頭更高，汗液氯化物濃度從每升 42 毫摩爾降至 45 毫摩爾，這與 FEV1 增加 10% 至 14% 有關。

We are evaluating ELX-02 as a single agent for another difficult-to-treat cystic fibrosis patient population, those with the G542X mutation on 1 or both alleles. Our CF Phase II program consists of 2 open-label trials, one for clinical investigators enrolling patients at sites in Europe, Israel, and Australia; the second enrolling patients in the United States and Canada. Both trials focus on CF patients with at least one G542X nonsense mutation. As I mentioned earlier, our global trials are being partially funded by the Cystic Fibrosis Foundation, and our protocol has been endorsed by the CFS Therapeutic Development Network, the largest cystic fibrosis clinical trials network in the world. In Europe, our protocol has been endorsed by the ECFS Clinical Trial Network.

我們正在評估 ELX-02 作為另一種難以治療的囊性纖維化患者群體的單一藥物，即那些在一個或兩個等位基因上具有 G542X 突變的患者。我們的 CF II 期項目包括 2 個開放標籤試驗，一個是供臨床研究人員在歐洲、以色列和澳大利亞招募患者；第二次在美國和加拿大招募患者。這兩項試驗都集中在至少有一個 G542X 無義突變的 CF 患者身上。正如我之前提到的，我們的全球試驗部分由囊性纖維化基金會資助，我們的方案得到了 CFS 治療開發網絡的認可，該網絡是世界上最大的囊性纖維化臨床試驗網絡。在歐洲，我們的協議已獲得 ECFS 臨床試驗網絡的認可。

The FDA has granted ELX-02 an orphan designation for cystic fibrosis, which confer certain important benefits to support development of medicines for underserved patient populations. ELX-02 has demonstrated pronounced CFTR readthrough in plasmid, HBE, FRT and transgenic mouse models. We've worked extensively with the HUB, Hubrecht Organoid Technology, to better understand ELX-02's activity across the cystic fibrosis nonsense patient population in their library of patient-derived organoids. ELX-02 demonstrates significant restoration of CFTR activity in patient-derived organoids, representing over 75% of all nonsense alleles.

FDA 已授予 ELX-02 囊性纖維化孤兒藥稱號，這賦予了某些重要的好處，以支持為服務不足的患者群體開發藥物。 ELX-02 已在質粒、HBE、FRT 和轉基因小鼠模型中展示了顯著的 CFTR 通讀。我們與 HUB、Hubrecht Organoid Technology 廣泛合作，以更好地了解 ELX-02 在其患者衍生類器官庫中對囊性纖維化無意義患者群體的活動。 ELX-02 表明患者來源的類器官中 CFTR 活性顯著恢復，佔所有無義等位基因的 75% 以上。

Our screening programs continue to evaluate opportunities to advance ELX-02 and other novel molecules from our ERSG library for new indications. As our R&D team continues to advance these programs, we expect an acceleration in the pace of publishing our results in important scientific and medical journals. As a result of our progress, we've had 6 scientific manuscripts published since April 2020, and we expect the steady cadence of publications for ELX-02 and our ERSG library to continue.

我們的篩選計劃繼續評估從我們的 ERSG 庫中推進 ELX-02 和其他新分子的機會，以獲得新的適應症。隨著我們的研發團隊繼續推進這些項目，我們預計在重要的科學和醫學期刊上發表我們的成果的步伐會加快。由於我們的進步，自 2020 年 4 月以來，我們已經發表了 6 篇科學手稿，我們預計 ELX-02 和我們的 ERSG 圖書館的穩定出版節奏將繼續下去。

In January, the results of our renal impairment trial were published in the Journal of Clinical Pharmacology, and the results of our Phase Ib multiple ascending dose trial evaluating the safety and pharmacokinetics of ELX-02 in healthy subjects were published in the journal Clinical Pharmacology in Drug Development. In February, a scientific manuscript was published in the Journal of Cystic Fibrosis on the results of our evaluation of ELX-02 mediated readthrough, using the CFTR dependent forskolin-induced swelling assay across the selection of G542X homozygous and heterozygous patient-derived organoids. In October 2020, our senior medical consultant, Professor Eitan Kerem, MD, a globally renowned cystic fibrosis expert, published a review of ELX-02 in the journal Expert Opinion on Investigational Drugs. We also had a scientific manuscript published in the Journal of Experimental Eye Research, which demonstrated the achievement of an important proof-of-concept milestone from our ongoing IND-enabling studies, demonstrating restoration of protein production in the eye when injected intravitreally in a mouse model. In a few moments, Dr. Matt Goddeeris, our Vice President of Research, will provide you with some highlights from these most recent publications.

1 月，我們的腎功能損害試驗結果發表在《臨床藥理學雜誌》上，我們評估 ELX-02 在健康受試者中的安全性和藥代動力學的 Ib 期多次遞增劑量試驗的結果發表在《臨床藥理學》雜誌上藥物開發。 2 月，一份科學手稿發表在囊性纖維化雜誌上，內容涉及我們對 ELX-02 介導的通讀的評估結果，使用 CFTR 依賴性毛喉素誘導的腫脹測定來選擇 G542X 純合子和雜合子患者來源的類器官。 2020 年 10 月，我們的高級醫學顧問、全球知名的囊性纖維化專家 Eitan Kerem 教授醫學博士在《研究藥物專家意見》雜誌上發表了對 ELX-02 的綜述。我們還在 Journal of Experimental Eye Research 上發表了一篇科學手稿，證明了我們正在進行的支持 IND 的研究取得了一個重要的概念驗證里程碑，證明了在小鼠玻璃體內註射時眼睛中蛋白質生產的恢復模型。稍後，我們的研究副總裁 Matt Goddeeris 博士將為您提供這些最新出版物的一些亮點。

We continue to be focused on delivering value to shareholders, while fulfilling our mission to provide treatment options to patients with high unmet medical needs in the most safe and expeditious manner. We are the most advanced company tackling the great challenge of developing potential new therapies for nonsense mutations, and there's a high level of interest and enthusiasm in the scientific and clinical community for our programs, as well as in the business community. We will continue to pursue partnerships where appropriate to expand our therapeutic footprint, accelerate our progress and advance our pipeline.

我們繼續專注於為股東創造價值，同時履行我們的使命，即以最安全、最快捷的方式為醫療需求未得到滿足的患者提供治療選擇。我們是應對開發針對無意義突變的潛在新療法的巨大挑戰的最先進的公司，科學界和臨床界以及商界對我們的項目有著高度的興趣和熱情。我們將繼續尋求適當的合作夥伴關係，以擴大我們的治療足跡，加快我們的進步並推進我們的產品線。

We ended the fourth quarter of 2020 with $24.7 million in cash and cash equivalents, and we are on target to deliver top line data for ELX-02 in cystic fibrosis in the first half of this year. We have a strong and experienced team with expertise in clinical drug development, basic research, and regulatory affairs. I'm highly confident that we have the capabilities and the resources needed to deliver on our goals.

我們以 2470 萬美元的現金和現金等價物結束了 2020 年第四季度，我們的目標是在今年上半年提供 ELX-02治療囊性纖維化的頂級數據。我們擁有一支強大且經驗豐富的團隊，在臨床藥物開發、基礎研究和法規事務方面具有專業知識。我非常有信心我們擁有實現目標所需的能力和資源。

I would now like to turn the call over to Dr. Matt Goddeeris, our Vice President of Research, who will expand on our recent publications and ongoing research activities.

我現在想將電話轉給我們的研究副總裁 Matt Goddeeris 博士，他將詳細介紹我們最近的出版物和正在進行的研究活動。

Thank you, Greg. We continue to advance our preclinical efforts across our ERSG library of molecules, working with our research partners to advance our programs. As Greg mentioned, we are pleased to have had several of our scientific manuscripts published in leading peer-reviewed journals and plan to continue to present our findings at scientific conferences.

謝謝你，格雷格。我們繼續推進我們在 ERSG 分子庫中的臨床前工作，與我們的研究夥伴合作推進我們的項目。正如 Greg 提到的，我們很高興我們的幾篇科學手稿在領先的同行評審期刊上發表，併計劃繼續在科學會議上展示我們的發現。

In February, we published a scientific manuscript in the Journal of Cystic Fibrosis title Targeting G542X CFTR Nonsense Alleles with ELX-02 Restore CFTR Function in Human-Derived Intestinal Organoids. This manuscript details the work we performed using G542X patient-derived organoids. As you know, G542X is the most common nonsense mutation in the population of people living with cystic fibrosis. Like other nonsense mutations, the G542X change introduces an early translation stop in the CFTR gene, leading to a truncated and unstable protein product. Current modulator therapies designed to improve CFTR activity are ineffective when CFTR protein is not being made.

2 月，我們在囊性纖維化雜誌上發表了一篇科學手稿，標題為 Targeting G542X CFTR Nonsense Alleles with ELX-02 Restore CFTR Function in Human-Derived Intestinal Organoids。這份手稿詳細介紹了我們使用 G542X 患者來源的類器官進行的工作。如您所知，G542X 是囊性纖維化患者中最常見的無義突變。與其他無義突變一樣，G542X 變化在 CFTR 基因中引入了早期翻譯終止，導致截短且不穩定的蛋白質產物。當前旨在提高 CFTR 活性的調節劑療法在未製造 CFTR 蛋白時無效。

To overcome this, cells must be able to ignore or read through this stop signal to produce full-length CFTR. ELX-02 is a compound that interacts with the ribosome to induce mRNA readthrough. Across many experiments, we observed that ELX-02 can produce active CFTR protein in organoids with G542X mutations. While no CFTR activity is found in these G542X organoids when untreated, an increase in activity is seen with increasing amounts of ELX-02. We also observed that ELX-02 increases the CFTR mRNA transcript, the molecule used to produce the protein, about fivefold in some cases. As ELX-02 advances to the clinic for people with CF due to G542X mutations, we will continue to test the molecule with other types of nonsense mutations to determine if they, too, may benefit from this approach.

為了克服這個問題，細胞必須能夠忽略或讀取這個停止信號以產生全長 CFTR。 ELX-02 是一種與核醣體相互作用以誘導 mRNA 通讀的化合物。在許多實驗中，我們觀察到 ELX-02 可以在具有 G542X 突變的類器官中產生活性 CFTR 蛋白。雖然未經處理時在這些 G542X 類器官中未發現 CFTR 活性，但隨著 ELX-02 量的增加，活性會增加。我們還觀察到，在某些情況下，ELX-02 增加了 CFTR mRNA 轉錄物（用於產生蛋白質的分子）大約五倍。隨著 ELX-02 進入臨床治療因 G542X 突變導致的 CF 患者，我們將繼續用其他類型的無義突變測試該分子，以確定他們是否也可以從這種方法中受益。

As Greg mentioned, we also recently published results from 2 important trials from our ELX-02 Phase I program. In January, the results from our renal impairment study were published in the Journal of Clinical Pharmacology. The pharmacokinetics of ELX-02 tell us that the compound is excreted from the body unchanged in the urine, recognizing that some of our potential target population may have reduced kidney function. This clinical study is a critical piece in our ability to dose adjust based on renal function. In this study, we evaluated pharmacokinetics and safety in participants with varying degrees of renal impairment, and the results demonstrate the relationship between plasma exposure and a key measure of kidney function, EGFR.

正如 Greg 提到的，我們最近還發布了 ELX-02 I 期項目的兩項重要試驗的結果。一月份，我們的腎功能損害研究結果發表在《臨床藥理學雜誌》上。 ELX-02 的藥代動力學告訴我們，該化合物以原形從尿液中排出體外，認識到我們的一些潛在目標人群可能腎功能下降。這項臨床研究是我們根據腎功能調整劑量的能力的關鍵部分。在這項研究中，我們評估了不同程度腎功能不全參與者的藥代動力學和安全性，結果證明了血漿暴露與腎功能的關鍵指標 EGFR 之間的關係。

A second manuscript was published in January in the Journal of Clinical Pharmacology in Drug Development covering our multiple ascending-dose trial. This study included 62 healthy volunteers and covered the dose range we are evaluating in our cystic fibrosis trial. We found that ELX-02 plasma exposure was dose proportional, with no apparent accumulation and no severe or serious adverse events reported. Together, these clinical studies and our preclinical efforts laid the groundwork for our currently ongoing Phase II trials.

第二份手稿於 1 月發表在藥物開發臨床藥理學雜誌上，涵蓋了我們的多次遞增劑量試驗。這項研究包括 62 名健康志願者，涵蓋了我們在囊性纖維化試驗中評估的劑量範圍。我們發現 ELX-02 血漿暴露與劑量成正比，沒有明顯的蓄積，也沒有報告嚴重或嚴重的不良事件。這些臨床研究和我們的臨床前工作共同為我們目前正在進行的 II 期試驗奠定了基礎。

Our preclinical progress applying novel compounds from our ERSG library of readthrough compounds in autosomal dominant polycystic kidney disease, ADPKD, and inherited retinal disorders, continue. In building the models to evaluate the ADPKD nonsense patient population, we enlisted the support of Dr. Benjamin Freedman, Associate Professor of the Division of Nephrology at the University of Washington. Dr. Freedman is an expert in differentiating induced pluripotent stem cells into 3-dimensional kidney organoids, capable of modeling CIS formation observed in ADPKD. We have modeled the most prevalent ADPKD nonsense mutations in these cells, and we anticipate providing updates on ELX-02's ability to prevent or reduce cysts in these organoids, along with other program progress, over the coming year.

我們將 ERSG 通讀化合物庫中的新化合物應用於常染色體顯性多囊腎病、ADPKD 和遺傳性視網膜疾病的臨床前進展仍在繼續。在建立評估 ADPKD 無意義患者群體的模型時，我們獲得了華盛頓大學腎臟科副教授 Benjamin Freedman 博士的支持。 Freedman 博士是將誘導多能幹細胞分化為三維腎臟類器官的專家，能夠模擬在 ADPKD 中觀察到的 CIS 形成。我們已經對這些細胞中最普遍的 ADPKD 無義突變進行了建模，我們預計在來年提供有關 ELX-02 預防或減少這些類器官囊腫的能力的更新，以及其他項目的進展。

Our inherited retinal disorder program continues to focus on pre-IND enabling work, sustained release formulations, and evaluation of novel disease models through research collaborations. The inherited retinal disorder landscape is genetically diverse. However, we believe that a single-agent readthrough approach may be able to broadly address multiple different inherited retinal disorders, provided they are caused by nonsense mutations.

我們的遺傳性視網膜疾病項目繼續專注於 IND 前支持工作、緩釋製劑以及通過研究合作評估新疾病模型。遺傳性視網膜疾病景觀具有遺傳多樣性。然而，我們認為單一試劑通讀方法可能能夠廣泛解決多種不同的遺傳性視網膜疾病，前提是它們是由無義突變引起的。

In order to expand our ocular research footprint and ensure we are evaluating the most relevant cellular and animal models of nonsense mediated blindness, we have established research collaborations with ocular disease experts at the University of Maryland, University of Wisconsin, and UCLA, and look forward to sharing more results as the programs progress.

為了擴大我們的眼科研究足跡並確保我們正在評估無意義介導失明的最相關細胞和動物模型，我們與馬里蘭大學、威斯康星大學和加州大學洛杉磯分校的眼病專家建立了研究合作關係，並期待隨著項目的進展，分享更多的成果。

As always, our latest publications and presentations can be found on our website.

與往常一樣，我們的最新出版物和演示文稿可以在我們的網站上找到。

I would now like to ask Steve MacDonald, our Vice President of Finance and Accounting, to provide a review of our fourth quarter and full year 2020 financial results.

我現在想請我們的財務和會計副總裁史蒂夫·麥克唐納 (Steve MacDonald) 回顧我們 2020 年第四季度和全年的財務業績。

Thanks, Matt. As of December 31, 2020, the company had total cash and cash equivalents of $24.7 million, which we believe will fund the company's operations through top line data in cystic fibrosis and into the fourth quarter of 2021.

謝謝，馬特。截至 2020 年 12 月 31 日，公司現金和現金等價物總額為 2470 萬美元，我們認為這將通過囊性纖維化的一線數據為公司的運營提供資金，直至 2021 年第四季度。

For the quarter ended December 31, 2020, the company incurred a net loss of $6.1 million or $0.15 per share, as compared to a net loss of $11.6 million, or $0.29 per share, for the same period in 2019.

截至 2020 年 12 月 31 日止季度，公司淨虧損 610 萬美元或每股 0.15 美元，而 2019 年同期淨虧損 1160 萬美元或每股 0.29 美元。

Noncash stock compensation expense totaled $1.3 million, with $1.1 million allocated to G&A and $200,000 to R&D. Fourth quarter 2020 R&D expense totaled $2.6 million, compared to $5.9 million for the same period in 2019. The quarter-to-quarter R&D expense decrease was driven by reduced headcount and related salaries for the 2020 period, as well as decreases in certain clinical and preclinical research costs. G&A expense for the fourth quarter of 2020 was $3.1 million, which decreased from $5.6 million for the same period in 2019, due to lower headcount and professional services costs.

非現金股票補償費用總計 130 萬美元，其中 110 萬美元分配給 G&A，200,000 美元分配給研發。 2020 年第四季度研發費用總計 260 萬美元，而 2019 年同期為 590 萬美元。研發費用環比下降的原因是 2020 年期間員工人數和相關工資減少，以及某些臨床和臨床前研究費用。由於員工人數和專業服務成本下降，2020 年第四季度的 G&A 費用為 310 萬美元，低於 2019 年同期的 560 萬美元。

For the full year ended December 31, 2020, the company incurred a net loss of $34.6 million, or $0.86 per share, as compared to a net loss of $50.9 million, or $1.34 per share, for 2019. Noncash stock compensation expense totaled $8.7 million, with $1 million allocated to R&D, $5.6 million to G&A, and $2.1 million to the corporate realignment in February 2020.

截至 2020 年 12 月 31 日的全年，公司淨虧損 3460 萬美元，即每股虧損 0.86 美元，而 2019 年淨虧損為 5090 萬美元，即每股虧損 1.34 美元。非現金股票補償費用總計 870 萬美元，其中 100 萬美元分配給研發，560 萬美元分配給 G&A，210 萬美元分配給 2020 年 2 月的企業重組。

Full year 2020 R&D expense totaled $14.6 million, compared to $26.3 million for 2019. The year-to-year R&D expense decrease was driven by reduced headcount and related salaries for the 2020 period, as well as reduced costs relating to certain clinical and preclinical research activities. G&A expense for the full year 2020 was $14.8 million, which decreased from $24.2 million in 2019, due to lower headcount and professional services costs.

2020 年全年研發費用總計 1460 萬美元，而 2019 年為 2630 萬美元。研發費用同比下降的原因是 2020 年期間員工人數和相關工資減少，以及與某些臨床和臨床前研究相關的成本減少活動。由於員工人數和專業服務成本下降，2020 年全年的 G&A 費用為 1480 萬美元，低於 2019 年的 2420 萬美元。

Full year modeling purposes, our total shares of common stock outstanding as of December 31, 2020, were $40,157,000.

就全年建模而言，截至 2020 年 12 月 31 日，我們已發行的普通股總額為 40,157,000 美元。

This concludes the fourth quarter and full year 2020 financial comments, and I'll turn the call back to Greg.

第四季度和 2020 年全年財務評論到此結束，我將把電話轉回給格雷格。

Thank you, Steve. It's our highest priority to complete our Phase II proof-of-concept clinical trials in cystic fibrosis. We are on track to report top line data in the first half of this year. We believe that these data will be a major value inflection point for our company.

謝謝你，史蒂夫。完成囊性纖維化的 II 期概念驗證臨床試驗是我們的首要任務。我們有望在今年上半年報告收入數據。我們相信這些數據將成為我們公司的一個主要價值拐點。

We are pleased that the independent safety review committees of our ELX-02 Phase II proof-of-concept clinical trials have allowed dose escalation up to the highest dose level, and that to date, no drug-related serious adverse events have been reported. The patient population we are studying has few, if any, treatment options, and the potential for ELX-02 to restore the production of CFTR protein could be a substantial advance and meaningfully improve the quality and length of their lives.

我們很高興我們的 ELX-02 II 期概念驗證臨床試驗的獨立安全審查委員會允許將劑量增加到最高劑量水平，並且迄今為止，沒有報告與藥物相關的嚴重不良事件。我們正在研究的患者群體幾乎沒有治療選擇，如果有的話，ELX-02 恢復 CFTR 蛋白生產的潛力可能是一個重大進步，並有意義地改善他們的生活質量和壽命。

We are laser-focused on assuring that we, our investigators, and global clinical sites can accomplish these goals, and we are pleased to be opening additional clinical sites in Australia and Canada. We are also gratified that the FDA has granted orphan drug designation for ELX-02 for the treatment of cystic fibrosis, which confers several important benefits to the ELX-02 program.

我們專注於確保我們、我們的研究人員和全球臨床站點能夠實現這些目標，我們很高興在澳大利亞和加拿大開設更多的臨床站點。我們也很高興 FDA 已授予 ELX-02 孤兒藥指定用於治療囊性纖維化，這為 ELX-02 計劃帶來了幾個重要的好處。

Beyond cystic fibrosis, we continue to advance our portfolio of novel ERSG molecules. Several of these compounds demonstrate encouraging levels of readthrough activity and tolerability, supporting their further therapeutic development in multiple disease states. As we continue to advance our programs, there has been a marked acceleration in the number of scientific manuscripts being published in important journals, and we continue to present meaningful data at scientific conferences.

除了囊性纖維化，我們繼續推進我們的新型 ERSG 分子組合。其中一些化合物表現出令人鼓舞的通讀活性和耐受性水平，支持它們在多種疾病狀態下的進一步治療發展。隨著我們繼續推進我們的計劃，在重要期刊上發表的科學手稿數量明顯增加，我們繼續在科學會議上展示有意義的數據。

We thank you for joining us on our fourth quarter 2020 earnings call, and we look forward to continuing to update you on our progress. Operator, you may now open the call for questions. Thank you.

感謝您加入我們的 2020 年第四季度財報電話會議，我們期待繼續向您通報我們的最新進展。接線員，您現在可以打開電話提問。謝謝。

(Operator Instructions) Our first question will come from the line of Ted Tenthoff from Piper Sandler.

（操作員說明）我們的第一個問題將來自 Piper Sandler 的 Ted Tenthoff。

Great. I want to get a sense for what would you see as a win in these, gee, in these (inaudible) immune patients, or (inaudible) patients, pardon me. There's nothing really that works that well there, so what do you kind of see as sort of the threshold for success?

偉大的。我想了解一下，在這些（聽不清）免疫患者或（聽不清）患者中，你認為這些勝利是什麼，請原諒我。那裡沒有什麼真正有效的東西，那麼您認為成功的門檻是什麼？

Ted, thanks for the question. So when we think about patients with no meaningful therapy, no available therapies, we think about ORKAMBI-like and SYMDEKO-like performance as being the threshold for clinically meaningful changes. And those compounds also represent a reasonable threshold for regulatory approval.

泰德，謝謝你的提問。因此，當我們考慮沒有有意義治療、沒有可用治療的患者時，我們將類似 ORKAMBI 和類似 SYMDEKO 的表現視為具有臨床意義的變化的閾值。這些化合物也代表了監管批准的合理門檻。

Just to remind you, ORKAMBI came in with sweat chloride concentration reductions in the 5 to 11 millimole per liter range. And in bigger studies over longer periods of time, ORKAMBI was associated with FEV1 increases in the range of 2.7% to about 5.6%. SYMDEKO was a little better, with overall sweat chloride concentration reductions in the range of about 10, with FEV1 increases in the range of about 4%.

提醒您，ORKAMBI 的汗液氯化物濃度降低了 5 至 11 毫摩爾/升。在更長時間的更大規模研究中，ORKAMBI 與 FEV1 增加 2.7% 至約 5.6% 相關。 SYMDEKO 稍好一些，總體汗液氯化物濃度降低了約 10，FEV1 增加了約 4%。

So from our Phase II study, we would be looking for a threshold of sweat chloride concentration reductions that would be ORKAMBI and SYMDEKO-like, that would be in the 5 millimole per liter concentration reduction.

因此，根據我們的 II 期研究，我們將尋找 ORKAMBI 和 SYMDEKO 樣的汗液氯化物濃度降低閾值，即每升濃度降低 5 毫摩爾。

And our next question will come from the line of Michelle Gilson from Canaccord.

我們的下一個問題將來自 Canaccord 的 Michelle Gilson。

I guess kind of building on Ted's questions here, could you maybe give us a sense of what the variability is, day-to-day, of sweat chloride, I guess, intra-patient variability? And then also, what are you planning to report? What are the data that we're going to get, other than, I guess, sweat chloride, in initial safety data? How many patients and in -- will you -- obviously, you're at the highest-dose cohort, but will you report data from all the dose cohorts, and what territories as well? And then also, I guess, building on that question, what's a good result, is it important to see a dose response? Obviously, for the cystinosis data, we didn't quite see a dose response, so I'm just curious if that's going to be important in CF.

我想在這裡建立在 Ted 的問題之上，您能否讓我們了解汗液氯化物的日常變異性是什麼，我猜是患者體內的變異性？還有，你打算報告什麼？在初始安全數據中，除了我猜的氯化汗液之外，我們將獲得哪些數據？有多少患者和 - 你會 - 顯然，你處於最高劑量組，但你會報告所有劑量組的數據，以及哪些地區？然後，我想，基於這個問題，什麼是好的結果，看到劑量反應很重要嗎？顯然，對於胱氨酸病數據，我們沒有看到劑量反應，所以我很好奇這在 CF 中是否重要。

Thanks, Michelle. We appreciate the questions. You've asked a few there, so I will try to take them in turn, see if I've captured them all.

謝謝，米歇爾。我們感謝您提出問題。你在那裡問了幾個，那我就試著依次拿下，看看我是不是都抓到了。

First, you asked about what would be some of the variability, maybe inter and intrapatient associated with sweat chloride concentration changes. And the literature tells us it wouldn't be surprising to see changes around 8 or 9 millimoles per liter, kind of up and down. So it's important to have sufficient numbers to be able to really tease out that 5 to 10 threshold that we'd be looking for in terms of ORKAMBI or SYMDEKO-like responses.

首先，您詢問了一些變異性，可能與汗液氯化物濃度變化相關的患者間和患者內。文獻告訴我們，看到每升 8 或 9 毫摩爾左右的變化並不奇怪，有點上下。因此，重要的是要有足夠的數字才能真正梳理出我們在 ORKAMBI 或 SYMDEKO 類響應方面尋找的 5 到 10 個閾值。

We're not today providing updates on our exact enrollment and the details of what our top line data will consist of, but we will be providing those in the future. We will be pooling data across our clinical sites in Europe, Israel, and now Australia. We'll also be adding data from the U.S., as well as from Canada, so we'll give you a broad data set that represents the body of data that's available at that point in time.

我們今天不會提供有關我們確切註冊的更新以及我們的頂線數據將包含的詳細信息，但我們將在未來提供這些信息。我們將匯集我們在歐洲、以色列和現在澳大利亞的臨床站點的數據。我們還將添加來自美國和加拿大的數據，因此我們將為您提供一個廣泛的數據集，代表當時可用的數據主體。

And we would anticipate seeing a dose response. With cystinosis, we did see a good response at 1 milligram per kilogram. We didn't see any response to all 0.5. We saw a good response at 1. When we got to the higher dose of 2, we had 2 responders, but there was an issue with the third patient. We think we identified a threshold for activity in the cystinosis trial. But with more patients in the CF trial, we would expect there to be a more clear-cut dose response across the 4 different doses that we're evaluating.

我們預計會看到劑量反應。對於胱氨酸病，我們確實看到了每公斤 1 毫克的良好反應。我們沒有看到對所有 0.5 的任何響應。我們在 1 時看到了良好的反應。當我們達到更高的劑量 2 時，我們有 2 名反應者，但第三名患者出現了問題。我們認為我們確定了胱氨酸病試驗中的活動閾值。但是隨著 CF 試驗中的更多患者，我們預計在我們正在評估的 4 種不同劑量中會有更明確的劑量反應。

I'm not showing any further questions in the queue. I'd like to turn the call back over to Greg for any closing remarks.

我不會在隊列中顯示任何其他問題。我想將電話轉回給格雷格，聽取任何結束語。

Well, thank you. We really appreciate your interest and your attention in Eloxx. It's an exciting time for us. We remain on target to report top line results in the first half of this year, and we're looking forward to updating you as we continue to progress. Thank you.

嗯，謝謝。我們非常感謝您對 Eloxx 的興趣和關注。這對我們來說是一個激動人心的時刻。我們的目標仍然是在今年上半年報告最高業績，我們期待著在我們繼續取得進展的同時向您通報最新情況。謝謝。

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

女士們，先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。