Viking Therapeutics Inc (VKTX) 2022 Q4 法說會逐字稿

Welcome to the Viking Therapeutics Fourth Quarter and Full Year 2022 Financial Results Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded today, February 8, 2023.

歡迎參加 Viking Therapeutics 第四季度和 2022 年全年財務業績電話會議。 （操作員說明）提醒一下，本次電話會議將於今天（2023 年 2 月 8 日）進行錄製。

I would now like to turn the conference over to Viking's Manager of Investor Relations, Stephanie Diaz. Please go ahead.

我現在想將會議轉交給 Viking 的投資者關係經理 Stephanie Diaz。請繼續。

Hello, and thank you all for participating in today's call. Joining me today is Brian Lian, Viking's President and CEO; and Greg Zante, Viking's CFO.

大家好，感謝大家參加今天的電話會議。今天加入我的是 Viking 總裁兼首席執行官 Brian Lian； Viking 的首席財務官 Greg Zante。

Before we begin, I'd like to caution that comments made during this conference call today, February 8, 2023, will contain forward-looking statements under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including statements about Viking's expectations regarding its development activities, time lines and milestones. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and adversely and reported results should not be considered as an indication of future performance. These forward-looking statements speak only as of today's date, and the company undertakes no obligation to revise or update any statement made today. I encourage you to review all of the company's filings with the Securities and Exchange Commission concerning these and other matters.

在我們開始之前，我想提醒您，在 2023 年 2 月 8 日今天的電話會議上發表的評論將包含根據 1995 年美國私人證券訴訟改革法案安全港條款作出的前瞻性陳述，包括關於維京公司的陳述對其開發活動、時間表和里程碑的期望。前瞻性陳述受風險和不確定因素的影響，可能導致實際結果出現重大不利差異，報告的結果不應被視為未來業績的指標。這些前瞻性陳述僅在今天發表，公司不承擔修改或更新今天發表的任何陳述的義務。我鼓勵您查看公司向證券交易委員會提交的關於這些和其他事項的所有文件。

I'll now turn the call over to Brian Lian for his initial comments.

我現在將電話轉給 Brian Lian，聽取他的初步評論。

Thanks, Stephanie, and good afternoon to everyone dialed in by phone or listening on the webcast.

謝謝，斯蒂芬妮，下午好，所有通過電話撥入或收聽網絡廣播的人。

Today, we'll review our financial results for the fourth quarter and full year 2022 and provide an update on recent progress with our clinical programs and operations. 2022 was an exciting year for Viking as we expanded our development pipeline and advanced each of our 3 clinical programs.

今天，我們將回顧第四季度和 2022 年全年的財務業績，並提供我們臨床項目和運營的最新進展。 2022 年對維京人來說是激動人心的一年，因為我們擴大了開發渠道並推進了我們的 3 個臨床項目。

With respect to VK2809, our lead drug candidate for the treatment of NASH and fibrosis, we recently announced completion of enrollment in our Phase IIb VOYAGE trial, and we expect to announce top line data from this study in the second quarter of 2023. In addition, the Phase I trial evaluating our newest program, the dual GLP-1 and GIP receptor agonist VK2735 for the potential treatment of metabolic disorders is continuing. We expect to report the initial data from this trial later this quarter. And finally, the Phase Ib clinical trial evaluating VK0214 for the treatment of X-linked adrenoleukodystrophy also continues to enroll and we expect to complete this study later this year.

關於我們治療 NASH 和纖維化的主要候選藥物 VK2809，我們最近宣布完成 IIb 期 VOYAGE 試驗的註冊，我們預計將在 2023 年第二季度公佈這項研究的主要數據。此外，評估我們最新項目的 I 期試驗，雙重 GLP-1 和 GIP 受體激動劑 VK2735 用於代謝紊亂的潛在治療正在繼續。我們預計將在本季度晚些時候報告該試驗的初始數據。最後，評估 VK0214 治療 X 連鎖腎上腺腦白質營養不良的 Ib 期臨床試驗也在繼續招募，我們預計將在今年晚些時候完成這項研究。

Our clinical advancements have significantly strengthened Viking's position as a leader in the development of novel class-leading therapeutics for the treatment of metabolic disorders, and we look forward to reporting data from each of these 3 clinical programs this year. I'll provide further details on our operations and development activities after we review our fourth quarter and full year 2022 financial results.

我們的臨床進展顯著加強了 Viking 作為開發治療代謝紊亂的一流新型療法的領導者的地位，我們期待著今年報告這三個臨床項目的數據。在我們審查第四季度和 2022 年全年財務業績後，我將提供有關我們運營和開發活動的更多詳細信息。

With that, I'll turn the call over to Greg Zante, Viking's Chief Financial Officer.

有了這個，我將把電話轉給 Viking 的首席財務官 Greg Zante。

Thanks, Brian. In conjunction with my comments, I'd like to recommend that participants refer to Viking's Form 10-K filing with the Securities and Exchange Commission, which we expect to file shortly.

謝謝，布萊恩。結合我的意見，我想建議參與者參考 Viking 向美國證券交易委員會提交的 10-K 表格，我們預計很快就會提交。

I'll now go over our results for the fourth quarter and full year ended December 31, 2022, beginning with the results for the quarter. Our research and development expenses for the 3 months ended December 31, 2022, were $16.2 million compared to $9.8 million for the same period in 2021. The increase was primarily due to increased expenses related to preclinical studies, manufacturing for the company's drug candidates, clinical studies, stock-based compensation and salaries and benefits, partially offset by decreased expenses related to third-party consultants.

我現在將回顧我們截至 2022 年 12 月 31 日的第四季度和全年的業績，首先是本季度的業績。我們截至 2022 年 12 月 31 日止三個月的研發費用為 1620 萬美元，而 2021 年同期為 980 萬美元。增加的主要原因是與臨床前研究、公司候選藥物的製造、臨床相關的費用增加研究、基於股票的薪酬以及薪金和福利，部分被與第三方顧問相關的費用減少所抵消。

Our general and administrative expenses for the 3 months ended December 31, 2022, were $4.1 million compared to $2.7 million for the same period in 2021. The increase was primarily due to increased expenses related to legal services, stock-based compensation and salaries and benefits, partially offset by decreased expenses related to third-party consultants. For the 3 months ended December 31, 2022, Viking reported a net loss of $19.6 million or $0.26 per share compared to a net loss of $12.4 million or $0.16 per share in the corresponding period in 2021. The increase in net loss and net loss per share for the 3 months ended December 31, 2022, was primarily due to the increase in research and development and general and administrative expenses noted previously compared to the same period of 2021.

截至 2022 年 12 月 31 日止三個月，我們的一般和行政費用為 410 萬美元，而 2021 年同期為 270 萬美元。增加的主要原因是與法律服務、股票薪酬以及薪金和福利相關的費用增加，部分被與第三方顧問相關的費用減少所抵消。截至 2022 年 12 月 31 日止三個月，維京報告淨虧損 1960 萬美元或每股 0.26 美元，而 2021 年同期淨虧損 1240 萬美元或每股 0.16 美元。淨虧損和每股淨虧損增加截至 2022 年 12 月 31 日止三個月的份額，主要是由於與 2021 年同期相比，之前提到的研發以及一般和行政費用有所增加。

I'll now go over results for the 2022 full fiscal year. Our research and development expenses for the year ending December 31, 2022, were $54.2 million compared to $45 million for the same period in 2021. The increase was primarily due to increased expenses related to manufacturing for the company's drug candidates, preclinical studies, salaries and benefits and stock-based compensation, partially offset by decreased expenses related to third-party consultants and clinical studies. Our general and administrative expenses for the year ending December 31, 2022, were $16.1 million compared to $10.7 million for the same period in 2021. The increase was primarily due to increased expenses related to legal services, stock-based compensation, salaries and benefits and insurance, partially offset by decreased expenses related to professional services and third-party consultants.

我現在將回顧 2022 年整個財政年度的結果。我們截至 2022 年 12 月 31 日止年度的研發費用為 5420 萬美元，而 2021 年同期為 4500 萬美元。增加的主要原因是與公司候選藥物製造、臨床前研究、工資和福利和基於股票的補償，部分被與第三方顧問和臨床研究相關的費用減少所抵消。截至 2022 年 12 月 31 日止年度，我們的一般和行政費用為 1610 萬美元，而 2021 年同期為 1070 萬美元。增加的主要原因是與法律服務、股票薪酬、薪金和福利相關的費用增加以及保險，部分被與專業服務和第三方顧問相關的費用減少所抵消。

For the year ending December 31, 2022, Viking reported a net loss of $68.9 million or $0.90 per share compared to a net loss of $55 million or $0.71 per share in the corresponding period in 2021. The increase in net loss and net loss per share for the year ended December 31, 2022, was primarily due to the increase in research and development and general administrative expenses, noted previously. Turning to the balance sheet. At December 31, 2022, Viking held cash, cash equivalents and short-term investments totaling $155 million compared to $202 million as of December 31, 2021.

截至 2022 年 12 月 31 日止年度，維京報告淨虧損 6890 萬美元或每股 0.90 美元，而 2021 年同期淨虧損 5500 萬美元或每股 0.71 美元。淨虧損和每股淨虧損增加截至 2022 年 12 月 31 日止年度，主要是由於研發和一般管理費用的增加，如前所述。轉向資產負債表。截至 2022 年 12 月 31 日，Viking 持有現金、現金等價物和短期投資總額為 1.55 億美元，而截至 2021 年 12 月 31 日為 2.02 億美元。

This concludes my financial review, and I'll now turn the call back over to Brian.

我的財務審查到此結束，現在我將把電話轉回給布賴恩。

Thanks, Greg. 2022 was an exciting year for Viking as we expanded our development footprint and made continued progress with our existing clinical programs.

謝謝，格雷格。 2022 年對 Viking 來說是激動人心的一年，因為我們擴大了發展足跡，並在現有臨床項目上取得了持續進展。

Over the past 12 months, Viking not only advanced its 2 existing clinical programs, but building on our expertise in metabolic disorders, we announced the addition of a new internally developed clinical program with VK2735.

在過去的 12 個月裡，Viking 不僅推進了其 2 個現有的臨床項目，而且基於我們在代謝紊亂方面的專業知識，我們宣布增加了一個新的內部開發的 VK2735 臨床項目。

I'll now provide an overview of our progress with each of these 3 programs, beginning with our lead compound, VK2809, for NASH and fibrosis. VK2809 is an orally available, small molecule agonist of the thyroid hormone receptor that is selected for liver tissue as well as the beta isoform of the receptor. We believe activation of the thyroid hormone beta receptor provides unique therapeutic benefits for patients with NASH and that the data to date point to VK2809 as a best-in-class therapeutic for this indication. Data from the company's prior 12-week Phase IIa trial in patients with hypercholesterolemia and nonalcoholic fatty liver disease support the promise of VK2809. This trial successfully achieved both its primary and secondary endpoints and demonstrating significant reductions in liver fat and plasma lipids. Further, the trial demonstrated that cohorts treated with VK2809 experienced up to 60% mean relative reductions in liver fat content and that 88% of patients receiving VK2809 experienced at least a 30% relative reduction of liver fat content. Importantly, the reductions in liver fat were durable with the majority of patients remaining responders 4 weeks after completion of dosing. This study also demonstrated the promising safety and tolerability profile of VK2809.

我現在將概述我們在這 3 個項目中的每一個項目的進展，從我們用於 NASH 和纖維化的先導化合物 VK2809 開始。 VK2809 是一種可口服的甲狀腺激素受體小分子激動劑，被選用於肝組織以及該受體的 β 亞型。我們相信甲狀腺激素β受體的激活為 NASH 患者提供了獨特的治療益處，並且迄今為止的數據表明 VK2809 是該適應症的同類最佳治療藥物。該公司之前對高膽固醇血症和非酒精性脂肪肝患者進行的為期 12 週的 IIa 期試驗的數據支持 VK2809 的前景。該試驗成功實現了主要和次要終點，並證明肝臟脂肪和血漿脂質顯著減少。此外，該試驗表明，接受 VK2809 治療的隊列的肝臟脂肪含量平均相對減少了 60%，接受 VK2809 治療的患者中有 88% 的肝臟脂肪含量至少減少了 30%。重要的是，肝臟脂肪的減少是持久的，大多數患者在完成給藥後 4 週仍保持反應。該研究還證明了 VK2809 的安全性和耐受性。

No serious adverse events were reported and the rate of GI disturbances such as nausea and diarrhea was lower among VK2809-treated patients when compared to patients treated with placebo. Perhaps one of the most distinguishing features of VK2809 is its unique effect on plasma lipids, including LDL cholesterol, triglycerides and atherogenic proteins, all of which have been correlated with cardiovascular risk. Various studies evaluating other NASH development programs have demonstrated elevation of these lipids following treatment. By comparison, patients in Viking's 12-week Phase IIa study experienced robust reductions in these plasma lipids, suggesting that VK2809 may offer a cardioprotective benefit. For all of these reasons, we believe VK2809's broad lipid-lowering properties combined with its safety, excellent tolerability and significant liver fat reduction and oral route of administration, establish it as a leading drug candidate for the treatment of NASH.

與接受安慰劑治療的患者相比，接受 VK2809 治療的患者未報告嚴重不良事件，噁心和腹瀉等胃腸道疾病的發生率較低。也許 VK2809 最顯著的特徵之一是它對血漿脂質的獨特作用，包括低密度脂蛋白膽固醇、甘油三酯和致動脈粥樣硬化蛋白，所有這些都與心血管風險相關。評估其他 NASH 開發計劃的各種研究表明，這些脂質在治療後會升高。相比之下，Viking 為期 12 週的 IIa 期研究中的患者經歷了這些血漿脂質的大幅降低，這表明 VK2809 可能具有心臟保護作用。由於所有這些原因，我們相信 VK2809 廣泛的降脂特性與其安全性、出色的耐受性和顯著的肝脂肪減少以及口服給藥途徑相結合，使其成為治療 NASH 的主要候選藥物。

Following successful completion of our Phase IIa trial, Viking initiated the VOYAGE study, a Phase IIb trial designed to evaluate VK2809 in patients with biopsy-confirmed NASH and fibrosis. VOYAGE is a randomized, double-blind, placebo-controlled, multicenter international trial designed to assess the efficacy, safety and tolerability of VK2809 in patients with biopsy-confirmed NASH and fibrosis. The target population includes patients with at least 8% liver fat content as measured by magnetic resonance imaging proton density fat fraction as well as F2 and F3 fibrosis. Up to 25% of patients may have F1 fibrosis, provided that they also possess at least one additional risk factor.

在我們的 IIa 期試驗成功完成後，Viking 啟動了 VOYAGE 研究，這是一項 IIb 期試驗，旨在評估 VK2809 在經活檢證實的 NASH 和纖維化患者中的療效。 VOYAGE 是一項隨機、雙盲、安慰劑對照、多中心國際試驗，旨在評估 VK2809在經活檢證實的 NASH 和纖維化患者中的療效、安全性和耐受性。目標人群包括通過磁共振成像質子密度脂肪分數以及 F2 和 F3 纖維化測量的肝臟脂肪含量至少為 8% 的患者。多達 25% 的患者可能患有 F1 纖維化，前提是他們還具有至少一個額外的危險因素。

The primary endpoint of the VOYAGE study will evaluate the change in liver fat content from baseline to week 12 in patients treated with VK2809 as compared to patients receiving placebo. Secondary objectives include the evaluation of histologic changes by hepatic biopsy after 52 weeks of treatment.

VOYAGE 研究的主要終點將評估與接受安慰劑的患者相比，接受 VK2809 治療的患者肝臟脂肪含量從基線到第 12 週的變化。次要目標包括在治療 52 週後通過肝活檢評估組織學變化。

Earlier this quarter, we announced completion of enrollment in VOYAGE, and we look forward to sharing top line results, including the trial's primary endpoint during the second quarter of this year.

本季度早些時候，我們宣布完成 VOYAGE 的註冊，我們期待分享主要結果，包括今年第二季度試驗的主要終點。

I'll now provide an update on our newest clinical candidate, VK2735 for the potential treatment of various metabolic disorders such as obesity, NASH and certain rare diseases. VK2735 arose from our internal research, leveraging our in-house metabolic expertise to design and evaluate new compounds with promising therapeutic potential. This compound is a dual agonist of the glucagon-like peptide-1, or GLP-1 receptor and the glucose dependent insulinotropic polypeptide, or GIP receptor. Initial data from this program presented at the Annual Meeting of The Obesity Society in 2021 demonstrated that GIP receptor activity improved upon the metabolic effects achieved through activation of the GLP-1 receptor alone. Specific findings included improvements observed in weight loss, glucose control and insulin sensitivity among diet-induced obese mice following treatment with Viking compounds as compared to a GLP-1 mono-agonist when administered at the same dose for the same period of time. In addition, the observed reductions in liver fat content were generally larger among animals treated with our compounds relative to the liver fat reductions observed among animals treated with a GLP-1 mono-agonist.

我現在將提供有關我們最新臨床候選藥物 VK2735 的最新信息，該候選藥物可用於治療各種代謝紊亂，例如肥胖症、NASH 和某些罕見疾病。 VK2735 源自我們的內部研究，利用我們內部的代謝專業知識來設計和評估具有廣闊治療潛力的新化合物。該化合物是胰高血糖素樣肽-1 或 GLP-1 受體和葡萄糖依賴性促胰島素多肽或 GIP 受體的雙重激動劑。在 2021 年肥胖協會年會上公佈的該項目的初步數據表明，GIP 受體活性改善了通過單獨激活 GLP-1 受體實現的代謝效應。具體發現包括在用 Viking 化合物治療後觀察到的體重減輕、葡萄糖控制和胰島素敏感性方面的改善，與在相同時間段以相同劑量給藥的 GLP-1 單激動劑相比。此外，相對於在用 GLP-1 單激動劑治療的動物中觀察到的肝脂肪減少，在用我們的化合物治療的動物中觀察到的肝脂肪含量減少通常更大。

In 2022, Viking announced the initiation of a Phase I clinical trial of VK2735. This trial is a randomized, double-blind, placebo-controlled, single ascending and multiple ascending dose study. The single ascending dose portion of the study is designed to enroll healthy adults while the multiple ascending dose portion is designed to enroll healthy adults with a minimum body mass index of 30 kilograms per meter square. Primary objectives of the study include an evaluation of safety and tolerability of single and multiple doses of VK2735 delivered subcutaneously as well as the identification of doses suitable for further clinical development. The trial will also evaluate the pharmacokinetics of VK2735 following single and multiple doses.

2022年，維京宣布啟動VK2735的I期臨床試驗。該試驗是一項隨機、雙盲、安慰劑對照、單次遞增和多次遞增劑量研究。該研究的單次遞增劑量部分旨在招募健康成年人，而多次遞增劑量部分旨在招募體重指數至少為每平方米 30 公斤的健康成年人。該研究的主要目標包括評估單次和多次皮下給藥 VK2735 的安全性和耐受性，以及確定適合進一步臨床開發的劑量。該試驗還將評估單次和多次給藥後 VK2735 的藥代動力學。

Exploratory pharmacodynamic assessments include evaluations of changes in body weight and liver fat content after 4 weeks of once-weekly administration. This study is ongoing, and we expect to report initial results later this quarter.

探索性藥效學評估包括評估每週一次給藥 4 週後體重和肝臟脂肪含量的變化。這項研究正在進行中，我們預計將在本季度晚些時候報告初步結果。

Our third clinical candidate is VK0214, which is currently being evaluated in a Phase Ib clinical trial in patients with X-linked adrenoleukodystrophy or X-ALD. VK0214 is Viking's second orally available, small molecule thyroid hormone receptor beta agonist in clinical development. X-ALD is a rare and often fatal metabolic disorder caused by genetic mutations that impact the function of peroxisomal transporter of very long chain fatty acids. As a result of the mutations, transporter function is impaired, and patients are unable to efficiently metabolize very long chain fatty acids. The resulting accumulation of these compounds is believed to contribute to the onset and progression of clinical signs and symptoms in patients with X-ALD.

我們的第三個臨床候選藥物是 VK0214，目前正在 X 連鎖腎上腺腦白質營養不良或 X-ALD 患者的 Ib 期臨床試驗中對其進行評估。 VK0214 是 Viking 的第二種口服小分子甲狀腺激素受體 β 激動劑，處於臨床開發階段。 X-ALD 是一種罕見且通常致命的代謝紊亂，由影響極長鏈脂肪酸過氧化物酶體轉運蛋白功能的基因突變引起。由於突變，轉運蛋白功能受損，患者無法有效代謝超長鏈脂肪酸。這些化合物的累積被認為有助於 X-ALD 患者臨床體徵和症狀的發作和進展。

In a prior 14-day Phase I study in more than 100 healthy volunteers, VK0214 demonstrated dose-dependent exposures, no evidence of accumulation and a half-life consistent with anticipated once-daily dosing. Subjects who received VK0214 experienced reductions in LDL cholesterol, triglycerides, apolipoprotein B and lipoprotein (a). This study also demonstrated VK0214's encouraging safety and tolerability. No serious adverse events were reported, and no treatment or dose-related signals were observed for GI side effects, vital signs or cardiovascular measures.

在之前對 100 多名健康志願者進行的為期 14 天的 I 期研究中，VK0214 表現出劑量依賴性暴露，沒有蓄積證據，半衰期與預期的每日一次給藥一致。接受 VK0214 治療的受試者的低密度脂蛋白膽固醇、甘油三酯、載脂蛋白 B 和脂蛋白 (a) 有所降低。該研究還證明了 VK0214 令人鼓舞的安全性和耐受性。沒有報告嚴重的不良事件，也沒有觀察到胃腸道副作用、生命體徵或心血管指標的治療或劑量相關信號。

Following completion of the Phase I study, Viking initiated the Phase Ib study of VK0214 in patients with the adrenomyeloneuropathy or AMN form of X-ALD. AMN is the most common form of X-ALD, affecting approximately 50% of those with the disease. The Phase Ib trial is a randomized, double-blind, placebo-controlled multicenter study in adult male patients with AMN. The primary objectives of the study are to evaluate the safety and tolerability of VK0214 administered orally once-daily for 28 days. The study also includes an evaluation of the pharmacokinetics of VK0214 in AMN patients as well as an exploratory assessment of changes in plasma levels of very long chain fatty acids. Pending a blinded review of preliminary data, additional dosing cohorts may be pursued. This study continues to enroll, and we expect to report the initial results later this year.

I 期研究完成後，Viking 啟動了 VK0214 在腎上腺髓系神經病或 AMN 形式的 X-ALD 患者中的 Ib 期研究。 AMN 是 X-ALD 的最常見形式，影響大約 50% 的患者。 Ib 期試驗是一項針對成年男性 AMN 患者的隨機、雙盲、安慰劑對照多中心研究。該研究的主要目的是評估連續 28 天每天口服一次 VK0214 的安全性和耐受性。該研究還包括評估 VK0214 在 AMN 患者中的藥代動力學，以及對極長鏈脂肪酸血漿水平變化的探索性評估。在對初步數據進行盲法審查之前，可能會尋求額外的給藥隊列。這項研究繼續招募，我們預計將在今年晚些時候報告初步結果。

Turning to financials. Our balance sheet remains strong. And as Greg discussed, we completed the year with approximately $155 million in cash. We currently anticipate that our overall R&D expenses in 2023 will be approximately in line with our 2022 R&D expenses. We believe our current cash resources provide sufficient runway to advance each of our clinical programs into later-stage development.

轉向財務。我們的資產負債表依然強勁。正如格雷格所討論的那樣，我們在這一年結束時獲得了大約 1.55 億美元的現金。我們目前預計，我們 2023 年的總體研發費用將與 2022 年的研發費用大致持平。我們相信，我們目前的現金資源提供了足夠的跑道，可以將我們的每個臨床項目推進到後期開發階段。

In closing, I wish to emphasize the significant transformation that has taken place at Viking over the past couple of years, which accelerated in 2022. Building on our initial success with our lead program, VK2809, Viking has evolved from a company with a single clinical program to a company advancing 3 distinct clinical candidates for a range of metabolic indications.

最後，我想強調 Viking 在過去幾年中發生的重大轉變，並在 2022 年加速。在我們的主導項目 VK2809 取得初步成功的基礎上，Viking 已經從一家擁有單一臨床實驗室的公司發展而來計劃向一家公司推進 3 種不同的臨床候選藥物，用於一系列代謝適應症。

In 2023, we expect to report clinical data from each of these 3 programs. With respect to VK2809 for the treatment of NASH and fibrosis, we have now completed enrollment in our Phase IIb VOYAGE trial, and we expect to report initial data in the second quarter. Our Phase I study evaluating the dual GLP-1/GIP agonist VK2735 is ongoing, and we expect to report the initial data from this study later this quarter. And our Phase Ib trial evaluating VK0214 in X-ALD patients continues to enroll, and we expect to report data from this trial later this year. This concludes our prepared comments for today.

2023 年，我們預計將報告這 3 個項目的臨床數據。關於用於治療 NASH 和纖維化的 VK2809，我們現在已經完成了 IIb 期 VOYAGE 試驗的註冊，我們預計將在第二季度報告初步數據。我們評估雙重 GLP-1/GIP 激動劑 VK2735 的 I 期研究正在進行中，我們預計將在本季度晚些時候報告這項研究的初始數據。我們在 X-ALD 患者中評估 VK0214 的 Ib 期試驗繼續招募，我們預計將在今年晚些時候報告該試驗的數據。我們今天準備好的評論到此結束。

Thanks again for joining us, and we'll now open the call for questions. Operator?

再次感謝您加入我們，我們現在將開始提問。操作員？

(Operator Instructions) Our first question will come from Joon Lee of Truist.

（操作員說明）我們的第一個問題將來自 Truist 的 Joon Lee。

According to clinicaltrials.gov, the target enrollment for the healthy volunteer study for 2735 is 80 subjects across 6 cohorts in Part A and 5 cohorts in Part B. Have you now exceeded your target enrollment and/or maybe add more cohorts? I'm just asking because the estimated completion date is stated as December.

根據 clinicaltrials.gov，針對 2735 名健康志願者研究的目標招募對像是 A 部分的 6 個隊列和 B 部分的 5 個隊列中的 80 名受試者。您現在是否超出了目標招募人數和/或可能增加更多隊列？我只是問，因為預計完成日期為 12 月。

Joon, thanks for the question. No, we haven't added any additional cohorts. It's just a little slower than we'd like, but there's nothing. We didn't -- we haven't prolonged anything.

俊，謝謝你的提問。不，我們沒有添加任何其他隊列。它只是比我們想要的慢一點，但什麼也沒有。我們沒有——我們沒有延長任何時間。

And you're still enrolling? Or have you now completed enrollment for the healthy volunteer study?

你還在招生？或者您現在已經完成健康志願者研究的註冊了嗎？

We haven't said -- what we've said is we'll have the results this quarter. But you got to keep in mind that the trial is 28 days of treatment, then there's a, I believe, a 60-day follow-up window. So it's a long window there.

我們還沒有說——我們說的是我們將在本季度獲得結果。但你必須記住，試驗是 28 天的治療，然後是，我相信，一個 60 天的隨訪窗口。所以這是一個很長的窗口。

And one last question. Are you enrolling both male and female for the multi-dose portion or is it just men?

最後一個問題。多劑量部分是否同時招收男性和女性，還是只招收男性？

It's both.

兩者都是。

Our next question comes from Steven Seedhouse of Raymond James.

我們的下一個問題來自 Raymond James 的 Steven Seedhouse。

Just wanted to ask a couple, first on 2735. So the decisions on dose escalation based on the (inaudible), it's -- I guess they're looking at safety and laboratory data. I just wanted to confirm, is that laboratory data that goes into the dose escalation decision, just all safety? Or would it include something like serum triglycerides to assess pharmacodynamic activity.

只想問一對夫婦，首先是 2735。所以關於劑量升級的決定是基於（聽不清），我猜他們正在查看安全性和實驗室數據。我只是想確認，用於劑量遞增決策的實驗室數據是否完全安全？或者它會包括血清甘油三酯之類的東西來評估藥效學活性。

No, it's pretty much a safety-driven determination. They have PK as well, but it's pretty much safety and not really any pharmacodynamic measures on efficacy.

不，這幾乎是一種安全驅動的決定。他們也有 PK，但它非常安全，實際上沒有任何藥效學措施。

Okay. And just to parlay Joon's question. So did you end up fully enrolling 5 cohorts in the MAD portion? Or was it less than 5 cohorts ultimately?

好的。只是為了回答 Joon 的問題。那麼，您是否最終在 MAD 部分完全招收了 5 個隊列？還是最終少於 5 個隊列？

Well, we haven't said exactly how many have been. It's ongoing now. So -- yes, we just haven't disclosed that, Steve.

好吧，我們還沒有說到底有多少。現在正在進行中。所以 - 是的，我們只是沒有透露，史蒂夫。

Okay. Maybe on the pharmacology of that molecule, I'm curious, there's a lot of folks digging in, including us on relative activity across these 2 receptor targets. Can you comment on -- if you look at the GLP-1 activity in isolation, and compare that to native GLP-1 activity, are you more or less or equipotent versus the native peptide -- specifically on GLP-1? I'm just trying to isolate that variables.

好的。也許關於該分子的藥理學，我很好奇，有很多人在研究這兩個受體靶點的相對活性，包括我們在內。您能否評論一下——如果您單獨觀察 GLP-1 活性，並將其與天然 GLP-1 活性進行比較，您是否或多或少或等效於天然肽——特別是在 GLP-1 上？我只是想隔離那些變量。

Yes. Yes. That's a good question. I think most of these compounds, not just ours, but most of them are less potent on GLP-1. I think the one we looked most at on that receptor was semaglutide, and we're pretty similar to semaglutide. I don't recall the numbers off the top of my head, but we're pretty darn close on that.

是的。是的。這是個好問題。我認為這些化合物中的大多數，不僅是我們的，而且大多數對 GLP-1 的效力都較低。我認為我們在該受體上關注最多的是 semaglutide，我們與 semaglutide 非常相似。我不記得我腦海中浮現出的數字，但我們已經非常接近了。

Okay. Yes. And (inaudible) as well. So that's interesting. Okay. And then just on TR beta, obviously, lots of focus on that mechanism these days. We've been getting questions again lately on just the dose selection in the VOYAGE study. So I was hoping you could just articulate what key aspect or aspects of the therapeutic window for this mechanism. Are you trying to optimize by testing a series of doses, including lower doses than in the prior Phase IIa study?

好的。是的。還有（聽不清）。這很有趣。好的。然後就在 TR beta 上，很明顯，現在很多人都關注這個機制。我們最近再次收到關於 VOYAGE 研究中劑量選擇的問題。所以我希望你能清楚地闡明這種機制的治療窗口的哪些關鍵方面。您是否試圖通過測試一系列劑量來優化，包括比之前的 IIa 期研究更低的劑量？

Yes, yes. So the prior 12-week Phase II study, when we looked at the -- all of the data, the efficacy data, the changes in lipids, those kinds of things, there were 3 cohorts, 5 mg a day, 10 mgs every other day and 10 mg daily. And we looked at all the data, they all look pretty similar. And so it suggested that we were sort of on the far right of the dose response curve. Maybe that's incorrect, but that's certainly what it looked like to us. And so we felt that we had room to come down in dose. And we know that the FDA always likes to have a handle on what the minimally effective dose is. And so we looked back at prior studies and what looked like was that 1 milligram dose when you look at the Phase I data, it starts to look like it's affecting lipids. And so we thought that, that would probably be the minimally effective dose. And we then dosed up from there to include a top dose of 10 mg every other day, which was overlapping with the 12-week study. And that -- we thought that was largely equal to the 5 mg daily and the 10 mg daily. So -- and we just spread it out between those, but that was kind of the rationale.

是的是的。因此，之前的 12 週 II 期研究，當我們查看所有數據、療效數據、血脂變化等時，有 3 個隊列，每天 5 毫克，每隔 10 毫克一天和每天 10 毫克。我們查看了所有數據，它們看起來都非常相似。所以它表明我們有點位於劑量反應曲線的最右邊。也許這是不正確的，但這肯定是我們的樣子。所以我們覺得我們有降低劑量的空間。我們知道 FDA 總是喜歡掌握最低有效劑量是多少。因此，我們回顧了之前的研究，當您查看 I 期數據時，看起來像是 1 毫克劑量，它開始看起來像是在影響脂質。所以我們認為，這可能是最低有效劑量。然後我們從那裡增加劑量，包括每隔一天 10 毫克的最高劑量，這與 12 週的研究重疊。那——我們認為這在很大程度上等於每天 5 毫克和每天 10 毫克。所以 - 我們只是將它分散在那些之間，但這是一種基本原理。

Our next question comes from Joe Pantginis of H.C. Wainwright.

我們的下一個問題來自 H.C. 的 Joe Pantginis。溫賴特。

Brian, I don't think it's too early to ask this question, but as you look towards a potential Phase III for 2809, obviously, the clinical trial community has been gaining in their understanding and traction with TR beta on 2 different fronts with 2 different assets. So I guess with the other asset being a little more mature, how would you consider or what kinds of things are you considering to handle regarding, say, competition for patients to enroll into your pivotal study?

布賴恩，我認為現在問這個問題還為時過早，但當你展望 2809 的潛在 III 期時，顯然，臨床試驗社區已經在 2 個不同的領域對 TR beta 有了更深入的理解和關注，其中 2不同的資產。所以我想隨著其他資產更加成熟，你會如何考慮或者你正在考慮處理什麼樣的事情，比如，競爭患者參加你的關鍵研究？

Well, I think that there are enough patients out there to enroll Phase III studies even if there is an approved agent with the same mechanism. And we've seen that in the diabetes space in the past with multiple approved GLP-1s, there are still trials enrolling GLP-1 agonists and plenty of other indications that share those characteristics. So I mean NASH is hard to enroll under any circumstances, but I don't think competition will be a significant problem there. It's just a hard -- the hard side to enroll anyway.

好吧，我認為即使有具有相同機制的獲批藥物，也有足夠的患者參加 III 期研究。我們已經看到，在過去有多種 GLP-1 獲批的糖尿病領域，仍有試驗招募 GLP-1 激動劑和許多其他具有這些特徵的適應症。所以我的意思是 NASH 在任何情況下都很難註冊，但我認為競爭不會成為那裡的重大問題。無論如何，這只是一個困難的方面。

The next question comes from Jay Olson of Oppenheimer.

下一個問題來自奧本海默的傑伊·奧爾森。

This is [Cheng] on the line for Jay. Congrats on the progress. Maybe a couple from us. First on 2809. I think in the Phase IIa study, you showed the GI toxicity or GI adverse events were actually lower in the [treatment] groups. So can you maybe just remind us if this is something related to the liver targeting property of 2809? And how should we expect the GI tolerability to play out in the VOYAGE study? And maybe related to that, do you see a path forward to combine 2809 with maybe all GLP-1 in the future? And I have a follow-up for 2735.

我是 Jay 的 [Cheng]。祝賀進步。也許我們有一對。首先是 2809。我認為在 IIa 期研究中，你顯示 [治療] 組的 GI 毒性或 GI 不良事件實際上較低。那麼您能否提醒我們這是否與 2809 的肝臟靶向特性有關？我們應該如何期待 GI 耐受性在 VOYAGE 研究中發揮作用？也許與此相關，您是否看到未來將 2809 與可能所有 GLP-1 結合起來的道路？我有 2735 的跟進。

Yes, to answer the second question first. Yes, I think the 2809 could be combined with a variety of different compounds and [oral] GLP-1s would -- could be one of those. With respect to the GI tolerability, we just haven't seen anything like that in any of the prior studies. And I don't know that it's necessarily because it's liver-targeted just something we haven't seen.

是的，先回答第二個問題。是的，我認為 2809 可以與多種不同的化合物結合使用，[口服] GLP-1 可能就是其中之一。關於 GI 耐受性，我們在之前的任何研究中都沒有看到類似的東西。而且我不知道這一定是因為它是針對肝臟的，而我們還沒有看到。

Okay. And for 2735, maybe just following a previous question, I know there was like a few dose cohorts were initiated maybe in the second half of last year. So just wondering, for the upcoming readout, should we expect to see data from all cohorts or only some of the cohorts?

好的。對於 2735，也許只是在回答之前的問題之後，我知道可能在去年下半年啟動了一些劑量隊列。所以只是想知道，對於即將到來的讀數，我們應該期望看到來自所有隊列還是僅部分隊列的數據？

Yes. We hope to have the data from all the cohorts. It's been -- I know it's been slower than everybody would like, including us, the holidays kind of broke that up a little bit as well. And then we had a couple of cohorts that got split. And since it's a Phase I unit, it is not necessarily available to have patients come in the next day if they miss a day. So that has just dragged out some of the cohorts. But we do believe we'll have the data this quarter from all the cohorts.

是的。我們希望獲得所有隊列的數據。它一直 - 我知道它比每個人都希望的要慢，包括我們，假期也有點打破了它。然後我們有幾個隊列被分開了。而且由於它是一期單位，如果患者錯過一天，則不一定可以讓他們第二天來。所以這只是拖出了一些隊列。但我們確實相信我們將在本季度獲得所有隊列的數據。

The next question comes from Andy Hsieh of William Blair.

下一個問題來自威廉·布萊爾的謝家華。

So obviously, there's a lot of movement in the NASH space recently. Just curious about your thinking in terms of the correlation between liver fat reduction or the magnitude of that and leading to fibrosis from a histological perspective.

很明顯，最近 NASH 領域有很多動作。從組織學的角度來看，您對肝臟脂肪減少或減少程度與導致纖維化之間的相關性的看法感到好奇。

Yes. Thanks, Andy. I think it's a fairly well-established correlation between reduction in liver fats and improvement in overall histology, including fibrosis, and that's been shown in pharmacological studies but also in weight loss studies. But there are exceptions. There are some mechanisms that have been shown to reduce liver fat and haven't resulted in other histologic improvements. And I don't know why that is. But most of them would appear to show the -- that when you reduce liver fat, particularly above 30% relative reduction, you have higher odds of success on NASH resolution and fibrosis improvement.

是的。謝謝，安迪。我認為肝臟脂肪減少與整體組織學改善（包括纖維化）之間存在相當明確的相關性，藥理學研究和減肥研究都證明了這一點。但也有例外。有一些機制已被證明可以減少肝臟脂肪，但不會導致其他組織學改善。我不知道為什麼會這樣。但他們中的大多數似乎表明——當你減少肝臟脂肪，特別是相對減少 30% 以上時，你在 NASH 解決和纖維化改善方面成功的機率更高。

Got it. That's helpful. Going on to the 2735 program, maybe as a whole, looking at your in-house compounds, as you anticipate the readout from the Phase I SAD/MAD study and also indication selection. I'm just curious about kind of the potential to advance other assets, right? There's -- I forgot, maybe like half a dozen or so development candidates that you presented. And I'm curious if there's any sort of special unique characteristics that might be good for a specific indication, same thing for 2735, anything that you saw there that would position you well for potentially rare disease versus other bigger metabolic diseases?

知道了。這很有幫助。繼續 2735 計劃，也許作為一個整體，查看您的內部化合物，因為您預期 I 期 SAD/MAD 研究的讀數以及適應症選擇。我只是對推進其他資產的潛力感到好奇，對嗎？有——我忘記了，也許你提出了六個左右的開發候選人。我很好奇是否有任何特殊的獨特特徵可能對特定適應症有益，2735 也是如此，你在那裡看到的任何東西都可以讓你更好地應對潛在的罕見疾病而不是其他更大的代謝疾病？

Yes. That's a good question, Andy. We've looked at a whole bunch of these, and we continue to explore different peptides. And we have sort of a scoring system that we've used and that has helped guide us to make some decisions on which compounds to prioritize. And that kind -- that's kind of the early part of the discovery work. And then we look at the in vivo data, PK and efficacy models to help prioritize. As far as the indications to select, I think just globally, when you look at the opportunities for the mechanism, it's NASH, diabetes, obesity and then a couple of smaller indications. And we would like to view the opportunities kind of like we look at with the thyroid beta agonist where we've got 2809 and a bigger opportunity, NASH and then VK0214 in the orphan indication. I think if we were able to parallel that with the dual agonist, and we had something in large indication and a different molecule in a smaller indication, that would be ideal. And I think we'll be pursuing that as we move forward.

是的。這是個好問題，安迪。我們研究了一大堆這些，我們繼續探索不同的肽。我們有一種我們已經使用過的評分系統，它幫助指導我們就優先考慮哪些化合物做出一些決定。那種 - 這是發現工作的早期部分。然後我們查看體內數據、PK 和功效模型以幫助確定優先順序。就選擇的適應症而言，我認為就全球而言，當您查看該機制的機會時，它是 NASH 、糖尿病、肥胖症，然後是幾個較小的適應症。我們希望看到的機會有點像我們看到的甲狀腺β激動劑，我們有 2809 和更大的機會，NASH，然後是孤兒適應症中的 VK0214。我認為，如果我們能夠將其與雙激動劑平行，並且我們有一些大適應症和不同分子的小適應症，那將是理想的。我認為我們會在前進的過程中追求這一點。

The next question comes from Yale Jen of Laidlaw & Co.

下一個問題來自 Laidlaw & Co. 的 Yale Jen。

In terms of 2735, we understand that, obviously, after the data release, you will make some additional decisions and pending on that outcome. But nevertheless, would you give me a top sort of (inaudible) view what you possibly anticipate to do after the data release in this quarter?

就 2735 而言，我們了解到，顯然，在數據發布之後，您將做出一些額外的決定並等待結果。但是，儘管如此，您能否給我一個頂級的（聽不清）觀點，在本季度數據發布後您可能期望做什麼？

Yes. Thanks, Yale. Well, we would hope to pursue an IND in the U.S. following completion of this study. And so we would hope to pursue that sometime by around the midyear time point and then proceed from there. And we'll have more information and details around the plans for Phase II once we release the Phase I data.

是的。謝謝，耶魯。好吧，我們希望在完成這項研究後在美國進行 IND。因此，我們希望在年中時間點左右的某個時候進行，然後從那裡開始。一旦我們發布第一階段數據，我們將獲得有關第二階段計劃的更多信息和細節。

The next question comes from Scott Henry of ROTH Capital.

下一個問題來自 ROTH Capital 的 Scott Henry。

Just a couple of questions. First, spending in the quarter was a little higher than earlier in the year. How should we think about spending in 2023 relative to 2022 and perhaps the cadence throughout the year as far as the quarters?

只是幾個問題。首先，本季度的支出略高於今年早些時候。我們應該如何考慮 2023 年相對於 2022 年的支出，以及全年乃至各季度的節奏？

Scott, I think we did make the comment, Brian, did in the earlier comments that our R&D expenses will be pretty consistent we expect in '23 versus '22 in total for the year. So I think those drive most of our spending, the R&D expenses do. So I guess we could think about our spending lining up pretty closely with our R&D expenditure. So if we're -- we look at that pretty consistently, I think.

斯科特，我想我們確實發表了評論，布賴恩，在早些時候的評論中說我們的研發費用將與我們預期的 23 年和 22 年的總支出相當一致。所以我認為這些推動了我們的大部分支出，研發費用確實如此。所以我想我們可以考慮我們的支出與我們的研發支出非常接近。因此，如果我們——我認為我們會非常一致地看待這一點。

Okay. And consistent through the year as well, any trends we should factor in?

好的。並且在這一年中也保持一致，我們應該考慮哪些趨勢？

No, I'd say pretty evenly throughout the year, just looking at the plans ahead. So yes, I would say pretty evenly.

不，我會說全年相當均勻，只是看看未來的計劃。所以是的，我會說非常均勻。

Okay. Great. That's helpful. And Brian, sort of a big-picture question. Clearly, the valuation of the company has changed over the last 3 months. Does that impact your strategy with some of these assets going forward just in terms of development, perhaps how long you keep them in the options that are available to you?

好的。偉大的。這很有幫助。布賴恩，這是一個大問題。顯然，該公司的估值在過去 3 個月內發生了變化。這是否會影響您的戰略，其中一些資產僅在開發方面向前發展，也許您將它們保留在您可用的選項中多長時間？

Scott, well, not really. We've always said that when we look at some of these large indications like NASH, it would be preferable to have a larger party involved in Phase III and beyond. And that's still our preference. I think as the market cap changes, you might have more opportunities to do things yourselves. But that doesn't change our preference to have a partner involved in later-stage studies.

斯科特，嗯，不是真的。我們一直說，當我們研究一些像 NASH 這樣的大適應症時，最好讓更多的人參與 III 期及以後的研究。這仍然是我們的偏好。我認為隨著市值的變化，你可能有更多機會自己做事。但這並沒有改變我們對讓合作夥伴參與後期研究的偏好。

Okay. Great. And final question, just with regards to 2735, obviously, obesity is a very hot indication right now in significant market. Is there anything in your safety profile or your expected safety profile that would make it better or worse than similar agents out there? I mean, diabetes is certainly a more straightforward market, but obesity, just wondering how it compares to other similar class agents.

好的。偉大的。最後一個問題，就 2735 而言，顯然，肥胖目前在重要市場上是一個非常熱門的指標。在您的安全概況或您預期的安全概況中，是否有任何東西會使其比現有的類似藥物更好或更差？我的意思是，糖尿病當然是一個更直接的市場，但肥胖症，只是想知道它與其他同類藥物相比如何。

I think on tolerability, it's a challenge to differentiate. If you modulate the GLP-1 receptor because it's hard to extricate efficacy from nausea with that mechanism. And so I think the plus is that clinicians and patients both are aware of that titration seems to help, and it's generally transient. It happens early. And if you can get through the first month or 2 of dosing, then you're probably past most of those tolerability issues. And I think there is receptivity to -- or at least acceptance of tolerability issues if you are confident that you're going to lose weight, and that's the big differentiating feature of these agents is they just induce profound weight loss. So I think it's hard to separate on tolerability when you have this mechanism, but I think it's okay given the familiarity and most patients will accept it if they know they're going to lose weight.

我認為在耐受性方面，差異化是一個挑戰。如果你調節 GLP-1 受體，因為很難用這種機制從噁心中解脫出來。所以我認為加號是臨床醫生和患者都知道滴定似乎有幫助，而且通常是短暫的。它發生得很早。如果您能熬過給藥的第一個月或第二個月，那麼您可能已經解決了大部分耐受性問題。而且我認為，如果您確信自己會減肥，就會接受——或者至少接受耐受性問題，而這些藥物的最大區別在於它們只會導致嚴重的減肥。所以我認為當你有這種機制時很難區分耐受性，但我認為考慮到熟悉度，這是可以的，如果大多數患者知道他們會減肥，他們會接受它。

The next question comes from Justin Zelin of BTIG.

下一個問題來自 BTIG 的 Justin Zelin。

Congrats on the progress. I'll add a question on 2735. So obviously, you're going to be looking at safety, tolerability, PK and PD here. Do you think that you'll be able to see some signs of efficacy in 4 weeks here? Or do you think you'll probably need to look at a longer time period on drug to start seeing some weight loss?

祝賀進步。我將在 2735 上添加一個問題。很明顯，您將在這裡查看安全性、耐受性、PK 和 PD。您認為在這裡 4 週內您能看到一些療效跡象嗎？還是您認為您可能需要服用更長時間的藥物才能開始減輕體重？

Justin, that's a great question. I think 28 days is really hard to see weight loss in. So we're going to be looking most at tolerability, PK, informing us for what sort of regimen we take forward into a Phase II study. When we look at the potential pharmacodynamic measures, body weight is of the greatest interest of people. And I think the hurdle we're really looking at there is if we can show efficacy that looks similar to a GLP-1 mono-agonist, I think that would be pretty exciting. And generally, that's in the sub-2% range, 1% to 2% over 28 days. We feel that, that would be exciting because we know that we're hitting GIP and we know in the animals, we see a clear separation from GLP-1 mono-agonist, and we believe that, that's going to augment the activity of GLP-1, but we just don't know whether or not that's going to be fully observed or observable in a treatment course as short as 28 days. So we're trying to be pretty conservative on the expectations for efficacy there since it's such a short study.

賈斯汀，這是一個很好的問題。我認為 28 天真的很難看到體重減輕。所以我們將最關注耐受性、PK，告訴我們在 II 期研究中採用什麼樣的養生法。當我們研究潛在的藥效學指標時，體重是人們最感興趣的。而且我認為我們真正關注的障礙是，如果我們能夠顯示類似於 GLP-1 單激動劑的功效，我認為那將是非常令人興奮的。通常，這在 2% 以下的範圍內，在 28 天內為 1% 至 2%。我們認為，這將是令人興奮的，因為我們知道我們正在打擊 GIP，並且我們知道在動物身上，我們看到與 GLP-1 單激動劑的明顯分離，我們相信，這將增強 GLP 的活性-1，但我們只是不知道這是否會在短短 28 天的治療過程中被完全觀察到或可觀察到。因此，由於這是一項如此短的研究，我們正試圖對那裡的療效期望保持相當保守的態度。

The next question comes from Naz Rahman of Maxim Group.

下一個問題來自 Maxim Group 的 Naz Rahman。

And I have a few, but I'll focus on 0214 kind of (inaudible) a little bit. What the data expected later this year, could you just kind of walk us through what you're sort of hoping to see in the study or what you're looking for?

我有一些，但我會稍微關注 0214 類（聽不清）。今年晚些時候的數據預期是什麼，你能告訴我們你希望在研究中看到什麼或者你正在尋找什麼嗎？

Yes. With this study, we're going to be looking -- it's a Phase Ib study. So we'll look at safety and tolerability and PK in the patient population. We saw really encouraging tolerability and pharmacodynamic effects in shorter study in healthy volunteers, but they didn't have adrenoleukodystrophy. So we'll look at PK and see if there are any differences. And on the pharmacodynamic side, we'll look at changes in very long chain fatty acids, which are believed to contribute to the course of disease in these patients. Those will be the main areas of focus.

是的。通過這項研究，我們將進行研究——這是一項 Ib 期研究。因此，我們將研究患者群體的安全性和耐受性以及 PK。我們在健康志願者的短期研究中看到了真正令人鼓舞的耐受性和藥效學效果，但他們沒有腎上腺腦白質營養不良。因此，我們將查看 PK，看看是否存在任何差異。在藥效學方面，我們將研究極長鏈脂肪酸的變化，據信這會導致這些患者的病程。這些將是重點關注的主要領域。

Just could you remind us, are you looking at any like notable biomarkers in these patients?

您能否提醒我們，您是否正在研究這些患者的任何類似顯著生物標誌物？

Yes. I think very long chain fatty acids would be the key biomarker and we'd be looking at there. Yes.

是的。我認為非常長鏈的脂肪酸將是關鍵的生物標誌物，我們會在那裡尋找。是的。

Okay. Got it. On the study line, could you also remind us if you plan on enrolling the third cohort in the study?

好的。知道了。在研究線上，您能否也提醒我們您是否計劃在研究中招募第三個隊列？

Oh, the third dosing cohort. Well, we have 3 cohorts now. It's a placebo and then (inaudible). And when we have enough data to make a decision, we may or may not add a higher dose cohort.

哦，第三個給藥隊列。好吧，我們現在有 3 個隊列。這是安慰劑，然後是（聽不清）。當我們有足夠的數據來做出決定時，我們可能會或可能不會添加更高劑量的隊列。

Got it. And when you release the data, are you going to release the data from the cohort separately? Or are you just going to wait until you have data from all 3 cohorts release at once?

知道了。當你發布數據時，你會單獨發布隊列的數據嗎？還是您要等到所有 3 個隊列的數據同時發布？

It's a parallel design. So we would really solve the data together.

是平行設計。所以我們真的會一起解決數據。

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

我們的問答環節到此結束。我想將會議轉回給斯蒂芬妮·迪亞茲 (Stephanie Diaz) 作閉幕詞。

Thank you again for your participation and continued support of Viking Therapeutics. We look forward to updating you again in the coming months. Have a great afternoon.

再次感謝您的參與和對 Viking Therapeutics 的持續支持。我們期待在未來幾個月再次為您更新。祝你下午愉快。

The conference has now concluded. Thank you for attending today's presentation, and 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了。