Lexicon Pharmaceuticals Inc (LXRX) 2022 Q4 法說會逐字稿

Good afternoon, and welcome to the Lexicon Pharmaceuticals Fourth Quarter 2022 Earnings Conference Call. (Operator Instructions) Please note, this event is being recorded.

下午好，歡迎參加 Lexicon Pharmaceuticals 2022 年第四季度收益電話會議。 （操作員說明）請注意，正在記錄此事件。

I would now like to turn the conference over to Carrie Siragusa. Please go ahead.

我現在想把會議交給凱莉·西拉古薩。請繼續。

Thank you, Gary. Good afternoon, and welcome to the Lexicon Pharmaceuticals Fourth Quarter 2022 Financial Results Conference Call. Joining me today are Lonnel Coats, Lexicon's Chief Executive Officer; Jeff Wade, Lexicon's President and Chief Financial Officer; and Dr. Craig Granowitz, Lexicon's Senior Vice President and Chief Medical Officer.

謝謝你，加里。下午好，歡迎參加 Lexicon Pharmaceuticals 2022 年第四季度財務業績電話會議。今天加入我的是 Lexicon 首席執行官 Lonnel Coats； Jeff Wade，Lexicon 總裁兼首席財務官； Lexicon 高級副總裁兼首席醫療官 Craig Granowitz 博士。

Earlier this afternoon, Lexicon issued a press release announcing our financial results for the fourth quarter of 2022, which is available on our website at www.lexpharma.com and through our SEC filings. A webcast of this call, along with the slide presentation is available on our website. During this call, we will review the information provided in the release, provide a corporate update and then use the remainder of our time to answer your questions.

今天下午早些時候，Lexicon 發布了一份新聞稿，宣布我們 2022 年第四季度的財務業績，該新聞稿可在我們的網站 www.lexpharma.com 上以及通過我們向 SEC 提交的文件中獲取。我們的網站上提供了本次電話會議的網絡廣播以及幻燈片演示。在本次電話會議期間，我們將審查新聞稿中提供的信息，提供公司最新信息，然後利用剩餘時間回答您的問題。

Before we begin, let me remind you that we will be making forward-looking statements, including statements relating to the safety, efficacy, regulatory status and therapeutic and commercial potential of sotagliflozin, LX9211 and other drug candidates. These statements may include characterizations of the expected timing and results of clinical trials of sotagliflozin, LX9211 and our other drug candidates, and the regulatory status and market opportunity for those programs.

在開始之前，請允許我提醒您，我們將做出前瞻性聲明，包括與 sotagliflozin、LX9211 和其他候選藥物的安全性、有效性、監管狀況以及治療和商業潛力相關的聲明。這些聲明可能包括 sotagliflozin、LX9211 和我們其他候選藥物臨床試驗的預期時間和結果的特徵，以及這些項目的監管狀況和市場機會。

This call may also contain forward-looking statements relating to our growth and future operating results, discovery and development of our drug candidates, launch and commercialization plans for any approved products, strategic alliances and intellectual property as well as other matters that are not historical facts or information. Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements.

本次電話會議還可能包含與我們的增長和未來經營業績、候選藥物的發現和開發、任何已批准產品的上市和商業化計劃、戰略聯盟和知識產權以及其他非歷史事實相關的前瞻性陳述或信息。各種風險可能導致我們的實際結果與此類前瞻性陳述中明示或暗示的結果存在重大差異。

These risks include uncertainties related to our NDA for sotagliflozin in heart failure and our discussions with the FDA regarding sotagliflozin relating to heart failure and type 1 diabetes; the success of our commercialization efforts with respect to any approved products; the timing and results of clinical trials and preclinical studies of sotagliflozin, LX9211, and our other drug candidates; our dependence upon strategic alliances and other third-party relationships; our ability to obtain patent protection for our discoveries, limitations imposed by patents owned or controlled by third parties; and the requirements of substantial funding to conduct our planned research, development and commercialization activities. For a listed description of the risks and uncertainties that we face, please see the reports we have filed with the Securities and Exchange Commission.

這些風險包括與 sotagliflozin 治療心力衰竭的 NDA 相關的不確定性，以及我們與 FDA 關於 sotagliflozin 與心力衰竭和 1 型糖尿病相關的討論；我們對任何批准產品的商業化努力的成功； sotagliflozin、LX9211 和我們其他候選藥物的臨床試驗和臨床前研究的時間和結果；我們對戰略聯盟和其他第三方關係的依賴；我們為我們的發現獲得專利保護的能力、第三方擁有或控制的專利所施加的限制；以及進行我們計劃的研究、開發和商業化活動所需的大量資金。有關我們面臨的風險和不確定性的列出描述，請參閱我們向美國證券交易委員會提交的報告。

I would now like to turn the call over to Lonnel Coats.

我現在想把電話轉給 Lonnel Coats。

Thank you, Carrie. Good afternoon, everyone, and thank you for joining us on the call. Fourth quarter 2022 was another active period for both our lead programs, sotagliflozin, our dual SGLT1 and 2 inhibitor that we're developing for heart failure and LX9211, our AAK1 inhibitor that we're developing for neuropathic pain.

謝謝你，嘉莉。大家下午好，感謝您加入我們的電話會議。 2022 年第四季度是我們兩個主導項目的另一個活躍期，sotagliflozin（我們正在開發的用於心力衰竭的雙重 SGLT1 和 2 抑製劑）和 LX9211（我們正在開發的用於神經性疼痛的 AAK1 抑製劑）。

Starting with our LX9211 program for neuropathic pain. In June of last year, we have previously announced positive top line results from our Phase II proof-of-concept study in diabetic peripheral neuropathic pain. The final data demonstrated further significant benefits in both burning pain and on pain interference with sleep. In December, we announced top line results from a second Phase II proof-of-concept study of LX9211 in postherpetic neuralgia. These results demonstrated clear evidence of effect, further supporting the advancement and another indication within neuropathic pain. These results showed a consistent and statistically significant reduction in average daily pain score, or ADPS, compared to placebo throughout the dosing period as we have shared, not reaching statistical significance on the primary endpoint measured at week 6.

從我們針對神經性疼痛的 LX9211 項目開始。去年 6 月，我們之前宣布了糖尿病周圍神經病理性疼痛 II 期概念驗證研究的積極頂線結果。最終數據進一步證明了其在燒灼痛和疼痛干擾睡眠方面的顯著益處。 12 月，我們公佈了 LX9211 治療帶狀皰疹後神經痛的第二項 II 期概念驗證研究的主要結果。這些結果證明了效果的明確證據，進一步支持了神經性疼痛的進展和另一個跡象。正如我們所分享的，這些結果表明，與安慰劑相比，在整個給藥期間，平均每日疼痛評分（ADPS）持續且具有統計顯著性降低，但在第 6 週測量的主要終點並未達到統計顯著性。

One of the more exciting aspects of these results is the remarkable consistency seen across both Phase II studies, and we will share more today about the development plans already underway to move LX9211 forward to late-stage development. We continue to believe LX9211 represents an innovative approach to treating neuropathic pain and if approved, could provide a significant opportunity to improve the treatment landscape for the benefit of patients.

這些結果中更令人興奮的方面之一是兩項 II 期研究中所見的顯著一致性，今天我們將分享更多有關已在進行的開發計劃的信息，以將 LX9211 推進到後期開發。我們仍然相信 LX9211 代表了一種治療神經性疼痛的創新方法，如果獲得批准，可以為改善治療環境提供重要機會，造福患者。

Now turning to sotagliflozin. I'm pleased to say we had our late cycle review meeting with the FDA earlier this week for our NDA for the treatment of heart failure. The agency indicated that there were no substantial review issues and again confirmed that it has no plans to hold an advisory committee meeting. Therefore, we believe everything remains on track for our PDUFA target date on May 27, 2023. We look forward to continuing to work with the FDA throughout the remainder of the review period and are planning to commercially launch sotagliflozin in the U.S. in the first half of this year, preparations for which are already underway.

現在轉向索格列淨。我很高興地說，我們本週早些時候與 FDA 舉行了後期週期審查會議，討論我們治療心力衰竭的 NDA。該機構表示不存在實質性審查問題，並再次確認沒有計劃召開諮詢委員會會議。因此，我們相信一切都在 2023 年 5 月 27 日 PDUFA 目標日期的正軌上。我們期待在剩餘的審查期間繼續與 FDA 合作，併計劃上半年在美國商業推出 sotagliflozin今年的準備工作已經在進行中。

We continue to believe the unique data from our SOLOIST Worsening Heart Failure trial and patients recently hospitalized for heart failure may provide a point of clinical differentiation enabling a strong entry into the heart failure market. As a reminder, this past November, new data from the SOLOIST Worsening Heart Failure trial were presented at the American Heart Association Scientific Sessions demonstrating sotagliflozin significant effects on reducing cardiovascular mortality and the risk of hospital readmissions at 30 and 90 days following discharge after initial event. This was indeed a significant finding that we believe could provide tremendous benefits to patients, physicians, hospitals and payers, and help differentiate sotagliflozin within the current heart failure treatment paradigm.

我們仍然相信，我們的 SOLOIST 惡化心力衰竭試驗和最近因心力衰竭住院的患者的獨特數據可能會提供臨床差異點，從而使我們能夠強勢進入心力衰竭市場。提醒一下，去年 11 月，美國心臟協會科學會議上公佈了 SOLOIST 惡化心力衰竭試驗的新數據，表明索格列淨對降低心血管死亡率以及初始事件出院後 30 和 90 天的再入院風險具有顯著效果。這確實是一個重大發現，我們相信它可以為患者、醫生、醫院和付款人帶來巨大的好處，並有助於在當前心力衰竭治療模式中區分索格列淨。

I'm going to turn the call now over to Jeff, who will review the sotagliflozin program and the status of our commercial launch preparations. Jeff?

我現在將電話轉給傑夫，他將審查 sotagliflozin 計劃以及我們的商業上市準備工作的狀態。傑夫？

Thanks, Lonnel. There are 6.7 million people in the United States living with heart failure, a number that is expected to increase to 8 million by 2030. Heart failure is the leading cause of hospitalizations for Americans over 65 with more than 1 million hospitalizations for heart failure annually. Patients who are hospitalized for heart failure are highly likely to return with about 25% of patients being readmitted to the hospital within 30 days of discharge and about 65% within a year.

謝謝，朗內爾。美國有 670 萬人患有心力衰竭，預計到 2030 年這一數字將增加到 800 萬。心力衰竭是 65 歲以上美國人住院的主要原因，每年有超過 100 萬人因心力衰竭住院。因心力衰竭住院的患者很有可能再次入院，約 25% 的患者在出院後 30 天內再次入院，約 65% 的患者在一年內再次入院。

Hospital readmissions are burdensome for both patients and the health care system. Annual costs from heart failure are expected to increase to nearly $70 billion by 2030, with 80% of those costs due to hospitalizations. There is a substantial unmet need for better treatment options for patients, and as these data make clear a strong incentive for providers, hospitals and payers to identify new approaches to reduce hospital readmissions.

再入院對於患者和醫療保健系統來說都是負擔。到 2030 年，每年因心力衰竭造成的費用預計將增加到近 700 億美元，其中 80% 是住院費用。患者對更好的治療方案的需求尚未得到滿足，這些數據清楚地表明，醫療服務提供者、醫院和付款人有強烈的動機去尋找減少再入院的新方法。

Aligned with that incentive, our data from the Journal of the American College of Cardiology revealing a compelling reason to prioritize when patients are started on therapy in order to increase the likelihood that patients receive appropriate treatment following a hospitalization for heart failure. In particular, the data suggests that starting patients on therapy at the time of hospital discharge, results in a significantly higher percentage of patients receiving appropriate treatment at 60 to 90 days and at 12 months follow-up.

與這一激勵措施相一致，我們來自《美國心髒病學會雜誌》的數據揭示了一個令人信服的理由，即在患者開始治療時優先考慮，以增加患者因心力衰竭住院後接受適當治療的可能性。特別是，數據表明，在患者出院時開始接受治療，可以顯著提高患者在 60 至 90 天以及 12 個月隨訪時接受適當治療的比例。

Heart failure is a very large multibillion-dollar market that is poised for substantial growth. Along with increasing disease prevalence, this anticipated growth is being driven by new guidelines recently issued by major cardiology societies in the United States and elsewhere, recommending the use of SGLT inhibitors as an important element in the standard of care for treating heart failure.

心力衰竭是一個價值數十億美元的巨大市場，有望大幅增長。隨著疾病患病率的增加，這種預期的增長是由美國和其他地方的主要心髒病學會最近發布的新指南推動的，該指南建議使用 SGLT 抑製劑作為治療心力衰竭護理標準的重要組成部分。

Currently, of those 1.3 million hospitalizations a year due to heart failure, data suggest that fewer than 10% of patients are discharged with a prescription for an SGLT inhibitor. This provides an exceptional opportunity for sotagliflozin, given its unique data showing its significant impact on that transition of care patient population.

目前，在每年因心力衰竭住院的 130 萬人中，數據顯示只有不到 10% 的患者出院時服用了 SGLT 抑製劑處方。鑑於 sotagliflozin 獨特的數據顯示其對護理患者群體的轉變具有重大影響，這為 sotagliflozin 提供了絕佳的機會。

I will now turn the call over to Craig to provide a reminder on the unique data presented in November by Dr. Bertram Pitt at the American Heart Association Scientific Sessions, assessing sotagliflozin's effects in reducing cardiovascular mortality and the risk of hospital readmissions at 30 and 90 days following discharge from a heart failure hospitalization.

我現在將電話轉給 Craig，提醒您注意 Bertram Pitt 博士 11 月份在美國心臟協會科學會議上提出的獨特數據，該數據評估了 sotagliflozin 在降低心血管死亡率以及 30 歲和 90 歲再入院風險方面的效果因心力衰竭住院出院後幾天。

Thank you, Jeff. As you can see, a group of patients from the SOLOIST study, while improving in their clinical journey, remain at risk for future heart failure events, as Jeff has shown in the prior slides. As a reminder, the SOLOIST Worsening Heart Failure trial enrolled approximately 1,200 patients with heart failure who are either hospitalized or recently hospitalized and were transitioning out of the hospital. Double-blind randomized treatment began either in the hospital or within 3 days following hospital discharge. There are approximately 50% of patients in each of those 2 categories.

謝謝你，傑夫。正如您所看到的，SOLOIST 研究中的一組患者雖然在臨床歷程中有所改善，但仍面臨未來發生心力衰竭事件的風險，正如 Jeff 在之前的幻燈片中所示。提醒一下，SOLOIST 惡化心力衰竭試驗招募了約 1,200 名正在住院或最近住院並正在出院的心力衰竭患者。雙盲隨機治療在醫院內或出院後 3 天內開始。這 2 類中每一類都有大約 50% 的患者。

The primary endpoint for the trial was achieved with a statistically significant and clinically meaningful reduction of 33% in the composite of cardiovascular death, hospitalization for heart failure and urgent heart failure visits with the need to treat only 4 patients for 1 year to avoid 1 endpoint event, finding, which is unsurpassed within the SGLT inhibitor class.

該試驗的主要終點是心血管死亡、因心力衰竭住院和緊急心力衰竭就診的綜合死亡率顯著降低了 33%，具有統計學意義和臨床意義，僅需要治療 4 名患者 1 年即可避免 1 個終點事件、發現，這在 SGLT 抑製劑類別中是無與倫比的。

The objective of Dr. Pitt's post-hoc analysis was to evaluate the efficacy of sotagliflozin versus placebo at reducing hospital readmissions and mortality within 30 and 90 days post discharge from a heart failure hospitalization among those patients who began treatment on or before the date of discharge. As a reminder, there were no differences between the 2 groups for baseline characteristics or the primary end point.

Pitt 博士事後分析的目的是評估 sotagliflozin 與安慰劑相比，對於在出院當日或之前開始治療的患者因心力衰竭住院出院後 30 至 90 天內減少再入院和死亡率的功效。提醒一下，兩組之間的基線特徵或主要終點沒有差異。

Presented here are the results for cardiovascular death and heart failure-related events for 30 and 90 days post discharge. You can see the sotagliflozin arm in the blue color begins to separate from the placebo arm in red very early on and showed that treatment with sotagliflozin resulted in a significant relative risk reduction versus placebo of approximately 50% for readmission for nonfatal heart failure events and for the composite of cardiovascular death and readmission for heart failure at both 30 and 90 days following hospital discharge.

這裡展示的是出院後 30 天和 90 天的心血管死亡和心力衰竭相關事件的結果。您可以看到藍色的 sotagliflozin 組很早就開始與紅色的安慰劑組分開，並且表明，與安慰劑相比，使用 sotagliflozin 治療可顯著降低約 50% 的非致命性心力衰竭事件再入院風險和出院後 30 天和 90 天的心血管死亡和因心力衰竭再次入院的綜合數據。

The authors concluded that sotagliflozin significantly reduces the 30- and 90-day rates of cardiovascular mortality and heart failure-related events as well as total mortality by 90 days post discharge when administered prior to hospital discharge. The authors state that these findings are unique and underscore the benefits of early initiation of evidence-based heart failure therapy. Sotagliflozin is the first compound to demonstrate a reduction on both mortality and heart failure events or a treatment initiated during a heart failure hospitalization.

作者得出的結論是，出院前服用 sotagliflozin 後，可顯著降低 30 天和 90 天心血管死亡率和心力衰竭相關事件的發生率，以及出院後 90 天的總死亡率。作者指出，這些發現是獨特的，並強調了早期開始循證心力衰竭治療的好處。 Sotagliflozin 是第一個被證明可以降低死亡率和心力衰竭事件或心力衰竭住院期間開始的治療的化合物。

We certainly agree with the authors that these results have important implications for patient quality of life and health care costs. And as Jeff has already mentioned, expect these data to be key points of differentiation in the marketplace should sotagliflozin achieve regulatory approval.

我們當然同意作者的觀點，即這些結果對患者的生活質量和醫療保健費用具有重要影響。正如傑夫已經提到的，如果 sotagliflozin 獲得監管部門的批准，預計這些數據將成為市場差異化的關鍵點。

We also wanted to highlight 4 additional upcoming data releases at the American College of Cardiology's 72nd annual scientific sessions being held this coming weekend in New Orleans. This includes an important paper on the time to clinical benefit of sotagliflozin in heart failure patients, transitioning out of the hospital in the SOLOIST Worsening Heart Failure study by Dr. Verma, which concluded dual inhibition of SGLT2 and SGLT1 with sotagliflozin leads to an early and sustained reduction in outcomes in patients with heart failure that is apparent by 27 days post randomization. These data support and further extend the results of the AHA findings that we highlighted above for this high-cost and high-risk population. This is in addition to 3 additional poster presentations during the weekend at ACC, which you can see the dates and times for each in the slide.

我們還想重點介紹即將於本週末在新奧爾良舉行的美國心髒病學會第 72 屆年度科學會議上發布的另外 4 個數據。其中包括 Verma 博士在 SOLOIST 惡化心力衰竭研究中發表的一篇關於 sotagliflozin 在心力衰竭患者中獲得臨床益處的時間的重要論文，該研究得出的結論是，用 sotagliflozin 對 SGLT2 和 SGLT1 進行雙重抑制可導致早期和晚期心力衰竭患者的臨床獲益。心力衰竭患者的結局持續下降，這一點在隨機分組後 27 天就明顯可見。這些數據支持並進一步擴展了我們上面針對這一高成本和高風險人群強調的 AHA 研究結果。這是 ACC 週末另外 3 場海報展示的補充，您可以在幻燈片中查看每場海報的日期和時間。

I'll now turn the call back over to Jeff to share more on our commercial launch preparations.

現在我將把電話轉回傑夫，分享更多有關我們商業發布準備工作的信息。

Thank you, Craig. As Lonnel referenced earlier today, our commercial launch preparations for sotagliflozin have been well underway for the better part of 2022. The majority of the infrastructure to support a commercial launch in heart failure in the U.S. in the first half of 2023 is currently in place, including the full payer and medical teams who have been having appropriate preapproval information exchanges with key stakeholders since late last year. In addition, we brought on our sales leadership team towards the end of last year, and we are currently in the process of interviewing for the sales representative positions that we plan to bring on board closer to the anticipated PDUFA date in May. We feel confident that we will have the right talent and resources to be ready for a very successful commercial launch following regulatory approval.

謝謝你，克雷格。正如 Lonnel 今天早些時候提到的，我們的 sotagliflozin 商業上市準備工作在 2022 年的大部分時間裡一直在順利進行。支持 2023 年上半年在美國進行心力衰竭商業上市的大部分基礎設施目前已到位，包括自去年年底以來一直與主要利益相關者進行適當的預審批信息交流的全額付款人和醫療團隊。此外，我們在去年年底引入了銷售領導團隊，目前正在面試銷售代表職位，我們計劃在 5 月份預計 PDUFA 日期臨近時引入這些職位。我們相信，我們將擁有合適的人才和資源，為監管部門批准後的成功商業發布做好準備。

We will now turn briefly to our LX9211 program. LX9211 is a potent, highly selective small molecule inhibitor of a novel target, adapter-associated kinase 1 or AAK1. In a number of relevant animal models of neuropathic pain, LX9211 demonstrated consistent, significant reductions in pain scores, even when compared to positive controls such as gabapentin. LX9211 achieves high levels of drug in the CNS, and importantly, the mechanism of action of LX9211 is independent of the opioid pathway. In Phase I studies, LX9211 was shown to be well tolerated with a pharmacokinetic profile supportive of once-daily dosing. Lexicon has been granted fast track designation by the FDA and for diabetic peripheral neuropathic pain.

現在我們將簡要介紹一下 LX9211 程序。 LX9211 是一種有效的、高選擇性的小分子抑製劑，針對新靶標接頭相關激酶 1 或 AAK1。在許多相關的神經性疼痛動物模型中，即使與加巴噴丁等陽性對照相比，LX9211 也表現出一致、顯著的疼痛評分降低。 LX9211在中樞神經系統中實現了高水平的藥物，重要的是，LX9211的作用機制獨立於阿片類藥物途徑。在 I 期研究中，LX9211 被證明具有良好的耐受性，其藥代動力學特徵支持每日一次給藥。 Lexicon 已獲得 FDA 的快速通道指定，用於治療糖尿病周圍神經病理性疼痛。

From a market perspective, the neuropathic pain market is expected to grow by more than 13% worldwide between -- on an annual basis between 2020 and 2026, and is projected to be worth more than $13.2 billion. Currently, available therapies are limited by a lack of efficacy, side effects, and potential for abuse. As a result, there is a great opportunity for new and innovative treatments such as LX9211 to enter this growing market with great unmet need.

從市場角度來看，預計 2020 年至 2026 年間，全球神經性疼痛市場的年增長率將超過 13%，價值預計將超過 132 億美元。目前，可用的療法因缺乏療效、副作用和濫用的可能性而受到限制。因此，像 LX9211 這樣的創新療法有很大機會進入這個需求未得到滿足的不斷增長的市場。

I will now turn the call back to Craig to briefly review the key results from our Phase II studies in 2 distinct types of neuropathic pain that read out last year.

現在，我將把電話轉回克雷格，簡要回顧一下去年宣讀的針對兩種不同類型的神經性疼痛的 II 期研究的主要結果。

Thank you, Jeff. As we discussed during our last quarterly call, the primary endpoint of the RELIEF-DPN-1 study was achieved with a statistically significant reduction in the average daily pain score or ADPS, at week 6 compared to placebo in the low-dose arm. There was an absolute reduction in ADPS from baseline of 1.39 points with a p-value of 0.007 compared to placebo. The high-dose arm achieved a reduction from baseline of 1.27 points with a p-value of 0.03 compared to placebo, narrowly missing the significant threshold of 0.028 but showing consistent effects.

謝謝你，傑夫。正如我們在上一季度電話會議中討論的那樣，RELIEF-DPN-1 研究的主要終點是在第 6 週時與低劑量組的安慰劑相比，平均每日疼痛評分或 ADPS 顯著降低，具有統計學意義。與安慰劑相比，ADPS 相對於基線絕對降低了 1.39 點，p 值為 0.007。與安慰劑相比，高劑量組較基線降低了 1.27 個點，p 值為 0.03，略低於 0.028 的顯著閾值，但顯示出一致的效果。

As announced at the 16th Annual Pain Therapeutics Summit in Washington, D.C. this past November, not only did LX9211 achieved the primary objective of the study by reducing patients' average daily pain score, but the final data demonstrated significant positive effects of LX9211 on measures that are meaningful to patients suffering from diabetic peripheral neuropathic pain, including burning pain and sleep interference, which have a direct impact on patient quality of life, as is shown in the attached slides.

正如去年 11 月在華盛頓特區舉行的第 16 屆年度疼痛治療峰會上宣布的那樣，LX9211 不僅通過降低患者的平均每日疼痛評分實現了研究的主要目標，而且最終數據表明 LX9211 對以下措施具有顯著的積極作用：對於患有糖尿病周圍神經性疼痛（包括燒灼痛和睡眠干擾）的患者來說是有意義的，這些疼痛對患者的生活質量有直接影響，如所附幻燈片所示。

We also noted during the blinded 5-week placebo runoff period in the study, there was a gradual tapering of efficacy in both treatment arms with no evidence of rebound pain or withdrawal symptoms. There were no observed differences in treatment-emergent adverse events between the treatment and placebo arms during the runoff period and no drug-related serious adverse events or deaths were reported in the trial.

我們還注意到，在研究中為期 5 週的盲法安慰劑試驗期間，兩個治療組的療效逐漸減弱，沒有證據表明出現反跳痛或戒斷症狀。在試驗期間，治療組和安慰劑組之間在治療引起的不良事件方面沒有觀察到差異，並且試驗中沒有報告與藥物相關的嚴重不良事件或死亡。

Now turning to the results of our second Phase II proof-of-concept study in postherpetic neuralgia, RELIEF-PHN-1. As we announced in December during our call, reporting the top line results from the trial, LX9211 achieved a reduction in average daily pain score of 2.42 points from baseline at week 6 and compared to a reduction of 1.62 points in the placebo arm with a placebo-adjusted difference of 0.8 points and a p-value of $0.12.

現在轉向我們關於帶狀皰疹後神經痛的第二期概念驗證研究 RELIEF-PHN-1 的結果。正如我們在 12 月份的電話會議上宣布的那樣，報告了試驗的主要結果，LX9211 在第 6 週的平均每日疼痛評分較基線降低了 2.42 分，而安慰劑組則降低了 1.62 分- 調整後的差異為 0.8 個點，p 值為 0.12 美元。

Although these results did not achieve significance on the primary endpoint of the study, overall study results demonstrated clear evidence of effect and achieved our goal for this small 79-patient study that further support the further development of LX9211 in another neuropathic pain condition. As Lonnel mentioned, when reviewing the data of both the RELIEF-DPN-1, and RELIEF-PHN-1 studies, we noted a remarkable consistency across the study results. When placing the graphs from the 2 studies side-by-side, the separation from placebo and mean change from baseline create similarly shaped curves.

儘管這些結果在研究的主要終點上沒有達到顯著性，但總體研究結果顯示了明確的效果證據，並實現了我們對這項 79 名患者的小型研究的目標，進一步支持 LX9211 在另一種神經性疼痛疾病中的進一步開發。正如 Lonnel 提到的，在審查 RELIEF-DPN-1 和 RELIEF-PHN-1 研究的數據時，我們注意到研究結果具有顯著的一致性。將兩項研究的圖表並排放置時，與安慰劑的分離和與基線的平均變化會創建形狀相似的曲線。

In addition to the timing and the magnitude of clinical benefit, we observed an adverse event profile that was consistent across both trials. To summarize, treatment-emergent adverse events were generally mild to moderate. There were no drug-related serious adverse events in either study. Finally, dizziness was the most commonly reported treatment-emergent adverse event. What we did not observe in the safety profile of LX9211 were some of the limitations of current therapies for neuropathic pain, such as peripheral edema, increased appetite, blurred vision or dry mouth. The adverse events tended to occur early in treatment, suggesting the possibility that might be associated with the loading dose. And given the rapid onset of effect on ADPS, offering potential for further optimizing dosing for both tolerability and efficacy effects that we are currently exploring.

除了臨床獲益的時間和程度之外，我們還觀察到兩項試驗中不良事件的情況是一致的。總而言之，治療引起的不良事件通常為輕度至中度。兩項研究均未發生與藥物相關的嚴重不良事件。最後，頭暈是最常報告的治療引起的不良事件。我們在 LX9211 的安全性概況中沒有觀察到當前神經性疼痛療法的一些局限性，例如外周水腫、食慾增加、視力模糊或口乾。不良事件往往發生在治療早期，表明可能與負荷劑量有關。鑑於 ADPS 的快速起效，為進一步優化劑量以實現我們目前正在探索的耐受性和療效效果提供了潛力。

In conclusion, we have now completed 2 Phase II proof-of-concept studies of LX9211 that support AAK1 inhibition as a potential new mechanism of action for treating neuropathic pain. We believe that LX9211 has the potential to overcome many of the shortcomings of current therapies and could become a welcome new innovation for those suffering from neuropathic pain on a daily basis. This is a large and growing market with high unmet medical need. As a result, we are pursuing the rapid advancement of LX9211 into Phase III development for the treatment of neuropathic pain.

總之，我們現已完成 LX9211 的 2 項 II 期概念驗證研究，支持 AAK1 抑製作為治療神經性疼痛的潛在新作用機制。我們相信 LX9211 有潛力克服當前療法的許多缺點，並可能成為那些每天遭受神經性疼痛的人們歡迎的新創新。這是一個巨大且不斷增長的市場，醫療需求未得到滿足。因此，我們正在推動 LX9211 快速進入治療神經性疼痛的 III 期開發。

We are continuing the work to identify and optimize the proper dosing regimens, and we are preparing to engage in the dialogue with the FDA in the first half of this year on how best to advance the program into Phase III development as quickly and efficiently as possible. As we have shared previously, we believe this program would benefit from a partnership that offers the right strategic fit for our organization and stakeholders, and we are engaged in discussions in this regard, which we believe will yield a positive outcome. In the meantime, we are proceeding with our plans for further development without cause.

我們正在繼續努力確定和優化合適的給藥方案，並準備在今年上半年與 FDA 進行對話，討論如何盡可能快速有效地將該項目推進到 III 期開發。正如我們之前所分享的，我們相信該計劃將受益於為我們的組織和利益相關者提供正確戰略契合的合作夥伴關係，我們正在參與這方面的討論，我們相信這將產生積極的成果。與此同時，我們正在無緣無故地進行進一步發展的計劃。

I'd like to now turn the call back to Jeff to take us through the financial results for the fourth quarter of 2022.

我現在想把電話轉回傑夫，讓他向我們介紹 2022 年第四季度的財務業績。

Thank you, Craig. I will provide some key aspects of our fourth quarter 2022 financial results. More financial details can be found in the press release that we issued earlier today and our Form 10-K that will be filed shortly with the SEC.

謝謝你，克雷格。我將提供 2022 年第四季度財務業績的一些關鍵方面。更多財務細節可以在我們今天早些時候發布的新聞稿以及即將向 SEC 提交的 10-K 表格中找到。

We ended the year with $138.4 million in cash and investments. We believe that our existing capital resources provide us with the right level of funding to support continued commercial preparations, make appropriate investments in research and clinical development and move towards a potential LX9211 partnership. Our loan facility with Oxford Finance, which provides up to $100 million in additional borrowing capacity, gives us substantial financial flexibility as we prepare to embark upon the expected launch of sotagliflozin in the first half of this year.

年底，我們擁有 1.384 億美元的現金和投資。我們相信，我們現有的資本資源為我們提供了適當水平的資金來支持持續的商業準備，對研究和臨床開發進行適當的投資，並朝著潛在的 LX9211 合作夥伴關係邁進。我們與牛津金融公司的貸款安排可提供高達 1 億美元的額外借款能力，為我們準備今年上半年預計推出的 sotagliflozin 提供了巨大的財務靈活性。

We anticipate that our existing cash and investments together with capacity under the loan facility will provide us with sufficient resources to manage our operations well into the anticipated launch of sotagliflozin into the market, without taking into account any proceeds from or costs assumed by a partner in any partnership that we may establish for LX9211.

我們預計，我們現有的現金和投資以及貸款安排下的能力將為我們提供足夠的資源，以便在預計將 sotagliflozin 推向市場之前管理我們的運營，而無需考慮合作夥伴承擔的任何收益或成本。我們可能為 LX9211 建立的任何合作夥伴關係。

Now turning to our financial results for the fourth quarter. As indicated in our press release this afternoon, we had minimal revenues for the fourth quarters of both 2022 and 2021. Research and development expenses for the fourth quarter of 2022 decreased to $14 million from $16.5 million for the corresponding period in 2021 and for the full year decreased to $52.8 million from $55 million in 2021, primarily due to lower professional and consulting fees in 2022 related to preparation for submission of our application for regulatory approval to market sotagliflozin for heart failure.

現在轉向我們第四季度的財務業績。正如我們今天下午的新聞稿中所指出的，我們 2022 年和 2021 年第四季度的收入都很少。2022 年第四季度的研發費用從 2021 年同期的 1,650 萬美元減少到 1,400 萬美元，整個今年的費用從 2021 年的 5500 萬美元減少到 5280 萬美元，主要是由於 2022 年與準備提交監管批准上市 sotagliflozin 治療心力衰竭的申請相關的專業和諮詢費用較低。

Selling, general and administrative expenses for the fourth quarter of 2022 increased to $16.3 million from $8.8 million for the corresponding period in 2021 and for the full year, increased to $48.1 million from $32.3 million in 2021, primarily due to increases in salaries and benefits, professional and consulting costs and marketing costs relating to preparations for the commercial launch of sotagliflozin in heart failure.

2022 年第四季度的銷售、一般和管理費用從 2021 年同期的 880 萬美元增加到 1630 萬美元，全年的銷售、一般和管理費用從 2021 年的 3230 萬美元增加到 4810 萬美元，主要是由於工資和福利的增加，與準備用於心力衰竭的 sotagliflozin 商業上市相關的專業和諮詢成本以及營銷成本。

In total, net loss for the fourth quarter of 2022 was $30.5 million or $0.16 per share as compared to a net loss of $25.6 million or $0.17 per share in the corresponding period of 2021. Our net loss for the fourth quarters of 2022 and 2021 included noncash stock-based compensation expense of $3.3 million and $2.2 million, respectively. Net loss for the full year 2022 was $101.9 million or $0.62 per share as compared to a net loss of $87.8 million or $0.60 per share in 2021. For the full years of 2022 and 2021, net loss included noncash stock-based compensation expense of $11.5 million and $10.6 million, respectively.

總體而言，2022 年第四季度的淨虧損為 3050 萬美元，即每股 0.16 美元，而 2021 年同期的淨虧損為 2560 萬美元，即每股 0.17 美元。我們 2022 年第四季度和 2021 年的淨虧損包括非現金股票補償費用分別為 330 萬美元和 220 萬美元。 2022 年全年淨虧損為 1.019 億美元，即每股 0.62 美元，而 2021 年淨虧損為 8780 萬美元，即每股 0.60 美元。2022 年和 2021 年全年，淨虧損包括 11.5 美元的非現金股票補償費用分別為 100 萬美元和 1060 萬美元。

I would like to pause now and ask the operator to open up the call to take your questions.

我現在想暫停一下，請接線員接通電話，回答您的問題。

(Operator Instructions) Our first question is from Yigal Nochomovitz with Citi.

（操作員說明）我們的第一個問題來自花旗銀行的 Yigal Nochomovitz。

Moving on, we go to Yasmeen Rahimi with Piper Sandler.

接下來，我們和派珀·桑德勒 (Piper Sandler) 一起前往亞斯敏·拉希米 (Yasmeen Rahimi)。

Congratulations again on getting great presentation at the American Cardiology Conference this weekend. Team, I guess the question that I have for you first is, have you had any additional interactions with the FDA since -- in the last few months, is there additional meeting that's on the schedule between now and May 27? That would be great.

再次祝賀您在本週末的美國心髒病學會議上獲得精彩演講。團隊，我想我首先要問你們的問題是，自過去幾個月以來，從現在到 5 月 27 日之間，你們是否與 FDA 進行了任何額外的互動？那太好了。

And then in terms of timing and next plan for LX9211, just some strokes in terms of timing, which indication in terms of diabetic neuropathy pain, in terms of the size of the study and duration of the trial. So I appreciate you taking the questions. And any color on both of the topics would be greatly appreciated.

然後就 LX9211 的時間安排和下一步計劃而言，只是時間安排上的一些中風，這表明糖尿病神經病變疼痛，研究規模和試驗持續時間。所以我很感謝你提出問題。對於這兩個主題的任何顏色都將不勝感激。

Yes. Thank you for both questions. Let me start with the FDA. We had our late cycle meeting a couple of days ago, so I'm extremely pleased with those conversations. As I indicated, there are no issues with application. We're not going to advisory committee based on their feedback to us. We have literally moved into at this point in time. The next stage is into label negotiations, so we're very pleased about that. So we are well on target at this point to advance sotagliflozin toward market and approval. So I couldn't be more pleased with that conversation that just happened a couple of days ago.

是的。謝謝你的兩個問題。讓我從 FDA 開始。幾天前我們舉行了後期週期會議，所以我對這些對話非常滿意。正如我所指出的，應用程序沒有任何問題。我們不會根據他們向我們提供的反饋來成立諮詢委員會。我們實際上已經進入了這個時間點。下一階段是標籤談判，所以我們對此感到非常高興。因此，我們目前已經達到了將 sotagliflozin 推向市場並獲得批准的目標。所以我對幾天前剛剛發生的那次談話感到非常高興。

As for LX9211, conversations with partners have been ongoing. It was a robust process with very high interest, and we're narrowing it down. And I think the next stage for us is to move forward with our conversation with FDA on how best we advanced the program to Phase III. Depending on should we pull the trigger on the partnership here sooner or later, that will depend on certainly how we approach the FDA when that meeting is granted. So I think we're in very good shape to advance LX9211 once we get the FDA feedback on the Phase III program. and also make some determinations as we make advances on -- in discussions with potential partners.

至於LX9211，與合作夥伴的對話一直在進行中。這是一個穩健的過程，人們對此非常感興趣，我們正在縮小範圍。我認為我們的下一階段是繼續與 FDA 進行對話，討論如何最好地將項目推進到 III 期。取決於我們是否應該遲早啟動合作夥伴關係，這當然取決於當會議獲得批准時我們如何與 FDA 接觸。因此，我認為一旦我們得到 FDA 對 III 期項目的反饋，我們就處於推進 LX9211 的良好狀態。並在我們與潛在合作夥伴的討論中取得進展時做出一些決定。

Lonnel, maybe 2 additional questions to the great comments you just made. Want to ask, are there -- is there interest to do the partners -- wanted potential partner discussions would like to see FDA feedback? Or is it really not necessary to have that in place? And then in regards to the great rate cycle review with the FDA, what are the possible label outcomes in your view, just broad strokes in regards to that would be really appreciated. And I'll jump back into the queue.

Lonnel，對於您剛剛發表的精彩評論，也許還有兩個問題。想問一下，合作夥伴是否有興趣進行潛在合作夥伴討論，希望看到 FDA 的反饋？或者真的沒有必要這樣做嗎？然後，關於 FDA 的大利率週期審查，您認為可能的標籤結果是什麼，對此的大致描述將非常感激。我會跳回到隊列中。

All right, Yasmeen, you're causing trouble for me. We've entered into label negotiations, so I don't want to do that publicly. But I will say we're very pleased with the initial conversations. I think we are going to have a strong label. Anything would change between here and there, but the initial conversation with the agency, I think we're going to have a very good label. Everything we've laid out here today in terms of the position of sotagliflozin, I think the label should follow suit with that. And so I'm just going to call those conversations as very robust and very pleasing thus far.

好吧，亞斯明，你給我添麻煩了。我們已經進入標籤談判，所以我不想公開這樣做。但我想說我們對最初的對話非常滿意。我認為我們將擁有一個強大的標籤。任何事情都會發生變化，但與該機構的初步對話，我認為我們將擁有一個非常好的標籤。我們今天在這裡就 sotagliflozin 的地位列出的所有內容，我認為該標籤應該遵循這一點。因此，到目前為止，我認為這些對話非常有力且令人愉快。

As for partnership, no, they're not waiting for FDA feedback, but there's a chance that we may want to wait for that so that we know exactly how we want to go in and make sure we can determine the best value for the asset. But more importantly, I think there's an eagerness on all sides to try to keep advancing things appropriately. And my hope is that we can reach agreements, both with the agency in a timely manner and potential partner somewhere around the same time.

至於合作夥伴關係，不，他們不會等待 FDA 的反饋，但我們有可能想要等待，以便我們確切地知道我們想要如何進入並確保我們能夠確定資產的最佳價值。但更重要的是，我認為各方都渴望繼續適當地推進事情。我希望我們能夠及時與該機構以及大約在同一時間的潛在合作夥伴達成協議。

The next question is from Yigal Nochomovitz with Citi.

下一個問題來自花旗銀行的 Yigal Nochomovitz。

This is Carly on for Yigal. So for LX9211, in the plot you shared from RELIEF-DPN-1 and the RELIEF-PHN-1, I just wanted to kind of get your perspective on the overlapping error bars between drug and placebo. Obviously, you hit stat sig, but there seems to be a fair amount of overlap in the error bar. So just curious your thoughts on that. And as you think about the design for a Phase III, are there any additional steps you can take to minimize the placebo response?

這是伊格爾的卡莉。因此，對於 LX9211，在您從 RELIEF-DPN-1 和 RELIEF-PHN-1 中分享的圖中，我只是想了解您對藥物和安慰劑之間重疊誤差線的看法。顯然，您點擊了 stat sig，但錯誤欄中似乎有相當多的重疊。所以只是好奇你對此的想法。當您考慮第三階段的設計時，是否可以採取任何其他步驟來盡量減少安慰劑反應？

Great question, Carly. Let me turn it over to Craig.

好問題，卡莉。讓我把它交給克雷格。

Thank you, Carly, for the question. The error bars are really a reflection of the variability of the data and the size of the study. And that's why we did not achieve significance for example, in the PHN-1 study because while the magnitude of the effect size was even larger than we had forecasted to achieve statistical significance. And as a reminder, the reduction was 0.8 points in the ADPS score, which was greater than we had powered the study. The variability was also somewhat larger than we had anticipated.

謝謝卡莉提出的問題。誤差線實際上反映了數據的變異性和研究的規模。這就是為什麼我們沒有實現顯著性，例如在 PHN-1 研究中，因為雖然效應大小的幅度甚至比我們預測的達到統計顯著性還要大。提醒一下，ADPS 分數降低了 0.8 分，這比我們為這項研究提供的支持要高。變異性也比我們預期的要大一些。

We took a number of steps in the trial to minimize some of the variability. And one of the reasons why these studies in neuropathic pain are so difficult is patient variability, and we actually received quite a bit of positive feedback in the medical and scientific community for the design of the trial with prequalifying the patients with the run-in period, which as we've shared with this group before, actually undercuts the overall efficacy because by reducing variability, you are starting the patients already on placebo, which actually lowers their pain score because there is a strong placebo effect. So again, for full transparency and integrity of the data we're showing the error bars, but the data are statistically significant. And I think it is a reflection of the population that is being studied that there is that degree of variability.

我們在試驗中採取了許多步驟來盡量減少一些變異性。這些神經性疼痛研究如此困難的原因之一是患者的變異性，實際上，我們在醫學和科學界收到了相當多的積極反饋，以設計試驗並在磨合期對患者進行資格預審。正如我們之前與該小組分享的那樣，這實際上削弱了總體療效，因為通過減少變異性，您開始對已經服用安慰劑的患者進行治療，這實際上降低了他們的疼痛評分，因為存在很強的安慰劑效應。同樣，為了數據的完全透明度和完整性，我們顯示了誤差線，但數據具有統計顯著性。我認為這反映了正在研究的人群存在這種程度的變異性。

And as for -- as you start thinking about Phase III, we've learned quite a bit about how best to set up the Phase III study as well as you want to talk a little bit about the parameters.

至於——當你開始考慮第三階段時，我們已經了解了很多關於如何最好地建立第三階段研究的知識，以及你想談談的一些參數。

Yes. Thank you, Lonnel. So again, what we believe is that we're going to be having a program, not just a single study for Phase III, which is very consistent with other clinical trials. The feedback we've had is some of the questions that have been asked, the 12-week study is probably the duration of the trials and to continue to look at these run-in periods to further refine the patient population to minimize those patients that have significant day-to-day variability in their pain score and to better harmonize the ability of patients to accurately complete these forms.

是的。謝謝你，朗內爾。再說一遍，我們相信我們將有一個項目，而不僅僅是一項 III 期研究，這與其他臨床試驗非常一致。我們收到的反饋是一些已經提出的問題，為期 12 週的研究可能是試驗的持續時間，並繼續關注這些磨合期，以進一步細化患者群體，以盡量減少那些患者他們的疼痛評分存在顯著的日常變化，並更好地協調患者準確填寫這些表格的能力。

As a reminder, the primary endpoint is what's called a visual analog scale. You are asking the patient to remember back during the course of that day what is their average pain score measured on a scale of 0 to 9. So as you can imagine, it is a very qualitative endpoint. It's not a lab value, it's not a diagnostic test. It's a very subjective endpoint. So we want to make sure that we have patients that having consistent pain, significant or moderate to severe pain and a minimum of variability on day-to-day pain as well as consistent ability to effectively comprehend and complete the forms. But we've learned a lot in our Phase II program to be sure we're getting the right patient population that can give a consistent, accurate reflection of their pain state.

提醒一下，主要終點是所謂的視覺模擬量表。您要求患者回憶當天的平均疼痛評分（從 0 到 9）是多少。因此，正如您可以想像的那樣，這是一個非常定性的終點。這不是實驗室值，也不是診斷測試。這是一個非常主觀的終點。因此，我們希望確保患者有持續的疼痛，顯著或中度至重度疼痛，日常疼痛的變化最小，以及有效理解和填寫表格的能力一致。但我們在第二階段計劃中學到了很多東西，以確保我們獲得正確的患者群體，能夠一致、準確地反映他們的疼痛狀態。

Okay. Great. That's really helpful. And then we just also had one question on SOLOIST. We were wondering if the data looked essentially the same when you looked at the group that started sota while they were still in the hospital versus patients who started sota within 3 days of discharge. Curious if you presented that analysis.

好的。偉大的。這真的很有幫助。然後我們還有一個關於 SOLOIST 的問題。我們想知道，當您觀察仍在醫院時開始服用 Sota 的患者組與出院 3 天內開始服用 Sota 的患者時，數據是否本質上相同。很好奇您是否提出了該分析。

Yes. So Carly, I'll answer that one as well. I think we shared at the last earnings call and Dr. Pitt shared at the American Heart Association, it's a terrific question. And what you see is that there was no difference in the primary endpoint between those two groups of patients. So whether you start the patient before they leave the hospital or on the day, they leave the hospital, which is about half or 600 of those patients or you start the patients within 3 days after leaving the hospital, the primary endpoint of cardiovascular death, emergency unscheduled hospital readmission or emergency room visit are the same.

是的。卡莉，我也來回答這個問題。我想我們在上次財報電話會議上分享了這一點，皮特博士在美國心臟協會上也分享了這一點，這是一個很棒的問題。您看到的是，這兩組患者的主要終點沒有差異。因此，無論是在患者出院前還是在患者出院當天（大約有一半或 600 名患者）開始治療，還是在患者出院後 3 天內開始治療（心血管死亡的主要終點），緊急情況下的計劃外再次入院或急診室就診是相同的。

The group that we showed the 30- and 90-day 50% reduction in readmission is, again, are the patients coming back to the hospital? So by definition, that is patients that have not yet left the hospital and are coming back to the hospital. And I think you asked the right question because what we've shown is that overall, those patients are the same, whether in the primary end point, whether they are leaving the hospital or have left the hospital but you're still looking at a 50% reduction in the hard clinical endpoint of hospital readmission by 30 days.

我們展示的 30 天和 90 天再入院率減少 50% 的組是，患者會再次回到醫院嗎？所以根據定義，這是指尚未離開醫院並正在返回醫院的患者。我認為你問了正確的問題，因為我們所展示的是，總的來說，這些患者是相同的，無論是在主要終點，無論他們是要出院還是已經出院，但你仍在關注再入院的硬臨床終點縮短 30 天 50%。

The next question is from Joseph Stringer with Needham & Company.

下一個問題來自 Needham & Company 的 Joseph Stringer。

First one is on sota and HF. Just wondering if you could confirm that there were no additional requests for data from FDA sort of in and around the late cycle review meeting. And then the second one is on 9211. You mentioned you're in partnership discussion, but a lot will depend on your upcoming meeting with the FDA. So I guess, does this mean that you are in a position to initiate additional clinical trials of 9211 and potentially a Phase III program post interaction with FDA and without a partnership? And then I think in some of the prepared remarks, you mentioned that you're doing some work to optimize the proper dosing regimens. Can you just characterize what type of work that is? Is it modeling or otherwise?

第一個是 sota 和 HF。只是想知道您是否可以確認 FDA 在後期週期審查會議期間和前後沒有額外要求提供數據。第二個是關於 9211。您提到您正在進行合作夥伴討論，但很大程度上取決於您即將與 FDA 舉行的會議。所以我想，這是否意味著你們能夠在與 FDA 互動後且沒有合作夥伴關係的情況下啟動 9211 的額外臨床試驗以及可能的 III 期項目？然後我認為在一些準備好的發言中，您提到您正在做一些工作來優化適當的給藥方案。您能簡單描述一下這是什麼類型的工作嗎？是模特還是其他？

Joe, I'm going to try my best to remember all your questions, but I appreciate all three. The first one, in terms of the additional data, when you get past a late-cycle review meeting, your past life cycle review meeting. So in terms of additional data, no, there's not been any request for additional data from the FDA. We're at the stage now where we should be entering into label negotiations and discussions. So we're late in the process, that's what I would say.

喬，我會盡力記住你所有的問題，但我很感激這三個問題。第一個，就附加數據而言，當您通過後期週期審查會議，即過去的生命週期審查會議時。因此，就額外數據而言，FDA 沒有要求提供額外數據。我們現在正處於應該進入標籤談判和討論的階段。所以我們在這個過程中已經晚了，這就是我想說的。

As for LX9211 and moving into Phase III. We wouldn't want to do that until we have our FDA meeting, which we've requested. And as we know more about that, we'll certainly keep everybody informed of that. I would just characterize overall partnership conversations as good overall conversations, good progress with parties. It's always a challenge to make sure you line around value and align around timing of how value gets created. And my view of the world is we understand the value of our asset, and we won't do anything less than achieving that value.

至於LX9211，正在進入III期。在我們要求召開 FDA 會議之前，我們不想這樣做。隨著我們對此了解得更多，我們肯定會讓每個人都了解這一情況。我只是將整體夥伴關係對話描述為良好的整體對話，與各方取得良好進展。確保圍繞價值並圍繞價值創造的時間安排始終是一個挑戰。我對世界的看法是，我們了解我們資產的價值，並且我們不會做任何低於實現該價值的事情。

So I think we're in a good position both with sota in terms of where we are at the FDA, and we're in a good position to keep advancing sotagliflozin forward. That's what the FDA meeting is about. And I think once we conclude that, we should be in a position to advance it into Phase III. And my hope is, if we get alignment we'll be able to do that in some type of broad framework partnership. I think those were the three.

因此，我認為就我們在 FDA 的情況而言，我們在 sota 方面處於有利地位，而且我們也處於繼續推進 sotagliflozin 前進的有利地位。這就是 FDA 會議的目的。我認為一旦我們得出結論，我們就應該能夠將其推進到第三階段。我的希望是，如果我們達成一致，我們將能夠在某種類型的廣泛框架夥伴關係中做到這一點。我想那就是這三個。

This concludes our question-and-answer session. I would like to turn the conference back over to Lonnel Coats for any closing remarks.

我們的問答環節到此結束。我想將會議轉回給朗內爾·科茨 (Lonnel Coats) 發表閉幕詞。

Well, thank you, everyone, for joining us on today's call and for your continued support of Lexicon. I would like to close out by summarizing a couple of key milestones and events. First of LX9211 based on the completion of, as we've said, 2 proof-of-concept studies in diabetic peripheral neuropathic pain and postherpetic neuralgia, planning and preparations for a Phase III development program are underway and we will be able to share more about these plans as the year progresses.

好的，謝謝大家參加今天的電話會議並感謝大家對 Lexicon 的持續支持。最後，我想總結幾個關鍵的里程碑和事件。正如我們所說，LX9211 的首個基於糖尿病周圍神經病理性疼痛和帶狀皰疹後神經痛的 2 項概念驗證研究的完成，III 期開發計劃的規劃和準備工作正在進行中，我們將能夠分享更多信息隨著時間的推移這些計劃。

Second, we have successfully completed a life cycle review meeting with FDA for our new drug application for sotagliflozin heart failure and remain on track for our PDUFA date of May 27. And we plan to launch sotagliflozin in heart failure in the first half of 2023.

其次，我們已經成功地與 FDA 完成了針對 sotagliflozin 心力衰竭新藥申請的生命週期審查會議，並繼續按計劃完成 5 月 27 日的 PDUFA 日期。我們計劃在 2023 年上半年推出用於心力衰竭的 sotagliflozin。

Finally, importantly, Lexicon is in a strong position -- cash position with the ability to fund operations well past the initial launch of sotagliflozin and heart failure, if approved. This has been a tremendous quarter for the company and for our stakeholders, and we expect these milestones to only increase value for all of our stakeholders in 2023. Look forward to continuing to communicate events out to you as they occur. Thank you very much for joining us.

最後，重要的是，Lexicon 處於有利地位——現金狀況良好，如果獲得批准，有能力在 sotagliflozin 首次推出和心力衰竭之後為運營提供資金。對於公司和我們的利益相關者來說，這是一個重要的季度，我們預計這些里程碑只會在 2023 年為我們所有利益相關者增加價值。期待在事件發生時繼續向您通報。非常感謝您加入我們。

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

會議現已結束。感謝您參加今天的演講。您現在可以斷開連接。