Viking Therapeutics Inc (VKTX) 2023 Q1 法說會逐字稿

Welcome to the Viking Therapeutics' First Quarter 2023 Financial Results Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded today, April 26, 2023. I would now like to turn the conference over to Viking's Manager of Investor Relations, Stephanie Diaz. Please go ahead, Stephanie.

歡迎參加 Viking Therapeutics 2023年第一季度財務業績電話會議。 （操作員說明）提醒一下，本次電話會議將於今天 2023 年 4 月 26 日進行錄製。我現在想將會議轉交給 Viking 的投資者關係經理 Stephanie Diaz。請繼續，斯蒂芬妮。

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, April 26, 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.

在我們開始之前，我想提醒您，在 2023 年 4 月 26 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。

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.

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 first quarter of 2023, and provide an update on recent progress with our clinical programs and operations. The first quarter of 2023 was an exciting time at Viking with important progress announced across multiple clinical programs.

今天，我們將回顧我們 2023 年第一季度的財務業績，並提供我們臨床項目和運營的最新進展。 2023 年第一季度是 Viking 激動人心的時刻，多個臨床項目宣布了重要進展。

With respect to VK2809, our lead thyroid hormone receptor beta agonist for the treatment of NASH and fibrosis, early in the quarter, we announced completion of enrollment in our Phase IIb VOYAGE trial and we expect to announce top line data from the primary endpoint in this study in the second quarter of 2023.

關於 VK2809，我們用於治療 NASH 和纖維化的主要甲狀腺激素受體 β 激動劑，在本季度初，我們宣布完成 IIb 期 VOYAGE 試驗的註冊，我們預計將在本季度公佈主要終點的頂級數據2023年第二季度學習。

With respect to our newest clinical program, the dual GLP-1 and GIP receptor agonist, VK2735, for the potential treatment of metabolic disorders, last month, we announced data from our first clinical study of this compound, a Phase I single ascending dose and multiple ascending dose study in healthy volunteers. As we'll discuss in a few minutes, the results were encouraging with mean weight loss of up to 18 pounds observed following 28 days of treatment. We plan to initiate a Phase II study of VK2735 in patients with obesity in mid-2023.

關於我們最新的臨床項目，雙重 GLP-1 和 GIP 受體激動劑 VK2735，用於潛在治療代謝紊亂，上個月，我們公佈了該化合物的第一項臨床研究的數據，即 I 期單次遞增劑量和在健康志願者中進行多次遞增劑量研究。正如我們將在幾分鐘後討論的那樣，治療 28 天后觀察到的平均體重減輕高達 18 磅的結果令人鼓舞。我們計劃於 2023 年年中在肥胖患者中啟動 VK2735 的 II 期研究。

In addition, we announced the initiation of a new clinical study to evaluate a novel oral formulation of this compound.

此外，我們宣布啟動一項新的臨床研究，以評估該化合物的新型口服製劑。

With respect to our third ongoing clinical program, the novel thyroid hormone beta receptor agonist, VK0214, our Phase Ib trial evaluating this compound for the treatment of X-linked adrenoleukodystrophy continues to enroll and we expect to report the results from this study in the second half of the year.

關於我們正在進行的第三個臨床項目，即新型甲狀腺激素 β 受體激動劑 VK0214，我們評估該化合物治療 X 連鎖腎上腺腦白質營養不良的 Ib 期試驗繼續招募，我們希望在第二個項目中報告這項研究的結果半年。

Late in the quarter, we also completed the successful public offering of common stock, raising gross proceeds of approximately $288 million that we plan to use for the continued advancement of each of our programs through key clinical milestones. I'll provide further details on our operations and development activities after we review our first quarter 2023 financial results.

本季度末，我們還成功完成了普通股的公開發行，募集資金總額約為 2.88 億美元，我們計劃將其用於通過關鍵的臨床里程碑繼續推進我們的每個項目。在我們審查 2023 年第一季度的財務業績後，我將提供有關我們的運營和開發活動的更多詳細信息。

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

為此，我會將電話轉給 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-Q filing with the Securities and Exchange Commission, which we expect to file today. I'll now go over our financial results for the first quarter ended March 31, 2023.

謝謝，布萊恩。連同我的評論，我想建議參與者參考 Viking 向美國證券交易委員會提交的 10-Q 表格，我們預計今天將提交該表格。我現在將回顧我們截至 2023 年 3 月 31 日的第一季度的財務業績。

Our research and development expenses for the 3 months ended March 31, 2023, were $11 million compared to $12.6 million for the same period in 2022. The decrease was primarily due to decreased expenses related to clinical studies, preclinical studies and third-party consultants, partially offset by increased expenses related to salaries and benefits, stock-based compensation and regulatory services.

我們截至 2023 年 3 月 31 日止三個月的研發費用為 1100 萬美元，而 2022 年同期為 1260 萬美元。減少的主要原因是與臨床研究、臨床前研究和第三方顧問相關的費用減少，部分被與工資和福利、股票薪酬和監管服務相關的費用增加所抵消。

Our general and administrative expenses for the 3 months ended March 31, 2023, were $9.5 million compared to $3.7 million for the same period in 2022. The increase was primarily due to increased expenses related to legal and patent services, stock-based compensation, and salaries and benefits.

截至 2023 年 3 月 31 日止三個月，我們的一般和行政費用為 950 萬美元，而 2022 年同期為 370 萬美元。增加的主要原因是與法律和專利服務、股票補償和工資和福利。

For the 3 months ended March 31, 2023, Viking reported a net loss of $19.5 million or $0.25 per share compared to a net loss of $16.1 million or $0.21 per share in the corresponding period of 2022. The increase in net loss and net loss per share for the 3 months ended March 31, 2023, was primarily due to the increased general and administrative expenses noted previously, partially offset by increased interest income compared to the same period of 2022.

截至 2023 年 3 月 31 日止三個月，維京報告淨虧損 1950 萬美元或每股 0.25 美元，而 2022 年同期淨虧損 1610 萬美元或每股 0.21 美元。淨虧損和每股淨虧損增加截至 2023 年 3 月 31 日止三個月的份額，主要是由於之前提到的一般和行政費用增加，部分被與 2022 年同期相比增加的利息收入所抵消。

Turning to the balance sheet. At March 31, 2023, Viking held cash, cash equivalents and short-term investments totaling $135.7 million compared to $155.5 million as of December 31, 2022. The company's Q1 2023 cash balance does not account for the completion of a public offering of common stock, resulting in gross proceeds of approximately $288 million that was completed at the end of the first quarter and closed on April 3, 2023. Pro forma, including this offering, our end of quarter cash, cash equivalents and short-term investments were approximately $406 million.

轉向資產負債表。截至 2023 年 3 月 31 日，Viking 持有的現金、現金等價物和短期投資總額為 1.357 億美元，而截至 2022 年 12 月 31 日為 1.555 億美元。該公司 2023 年第一季度的現金餘額不計入普通股公開發行的完成情況，導致在第一季度末完成並於 2023 年 4 月 3 日結束的總收益約為 2.88 億美元。備考，包括此次發行在內，我們的季度末現金、現金等價物和短期投資約為 406 美元百萬。

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. As mentioned in my opening comments, the first quarter of 2023 was an exciting time at Viking. In recent weeks, we announced positive data from a Phase I study in healthy volunteers with our newest clinical program, the dual incretin receptor agonist, VK2735. These results, which I will discuss in more detail shortly, have served to broaden our presence in metabolic diseases and diversify our pipeline, further increasing the value of the company.

謝謝，格雷格。正如我在開場白中提到的那樣，2023 年第一季度對 Viking 來說是一個激動人心的時刻。最近幾週，我們公佈了一項針對健康志願者的 I 期研究的積極數據，該研究採用我們最新的臨床項目雙腸促胰島素受體激動劑 VK2735。我將在稍後詳細討論的這些結果有助於擴大我們在代謝疾病領域的影響力並使我們的產品線多樣化，從而進一步提高公司的價值。

We are very pleased to begin the second quarter from a position of clinical momentum, financial strength, and optimism for upcoming data. I'll now provide an overview of progress with our clinical programs, beginning with our (inaudible) compound, VK2809 for NASH and fibrosis.

我們很高興從臨床動力、財務實力和對即將到來的數據的樂觀態度開始第二季度。我現在將概述我們的臨床項目的進展，從我們的（聽不清）化合物 VK2809 開始，用於 NASH 和纖維化。

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. A prior 12-week Phase IIa trial evaluating VK2809 in patients with hypercholesterolemia and nonalcoholic fatty liver disease, successfully achieved both its primary and secondary end points, demonstrating significant reductions in liver fat and plasma lipids. Cohorts treated with VK2809 experienced up to 60% mean relative reduction in liver fat content and 88% of patients receiving VK2809 experienced at least a 30% relative reduction in liver fat content.

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。一項為期 12 週的 IIa 期試驗評估了 VK2809 在高膽固醇血症和非酒精性脂肪肝患者中的療效，成功實現了主要和次要終點，表明肝臟脂肪和血漿脂質顯著降低。用 VK2809 治療的隊列經歷了高達 60% 的肝臟脂肪含量平均相對減少，88% 接受 VK2809 的患者經歷了至少 30% 的肝臟脂肪含量相對減少。

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 of VK2809. 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.

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。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。

We believe VK2809's activation of the thyroid hormone beta receptor provides unique therapeutic benefits for patients with NASH. Perhaps 1 of the most important additional benefits of this compound is its ability to reduce plasma lipids, including LDL cholesterol, triglycerides and atherogenic proteins, all of which have been correlated with increased cardiovascular risk. It is important to note that a number of studies evaluating other NASH development programs have demonstrated elevations in these lipids following treatment. In contrast, patients in Viking's 12-week Phase IIa study experienced robust reductions in these lipids suggesting that VK2809 may offer a cardioprotective benefit.

我們相信 VK2809 對甲狀腺激素β受體的激活為 NASH 患者提供了獨特的治療益處。也許這種化合物最重要的額外好處之一是它能夠降低血漿脂質，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增加有關。重要的是要注意，許多評估其他 NASH 開發計劃的研究已經證明這些脂質在治療後升高。相比之下，Viking 為期 12 週的 IIa 期研究中的患者經歷了這些脂質的強勁下降，這表明 VK2809 可能具有心臟保護作用。

We believe VK2809's broad lipid-lowering properties combined with its safety, excellent tolerability, significant liver fat reduction and oral route of administration, establishes it as a best-in-class therapeutic for the treatment of NASH. Based on the promising results from our Phase IIa trial, the company initiated the VOYAGE Phase IIb study. This trial 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.

我們相信 VK2809 廣泛的降脂特性與其安全性、出色的耐受性、顯著的肝脂肪減少和口服給藥途徑相結合，使其成為治療 NASH 的一流藥物。基於我們 IIa 期試驗的有希望的結果，公司啟動了 VOYAGE IIb 期研究。該試驗是一項隨機、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。

Up to 25% of patients may have F1 fibrosis provided that they also possess at least 1 additional risk factor. The primary endpoint of the VOYAGE study will evaluate changes in liver fat from baseline to week 12 in patients treated with VK2809 as compared to patients receiving placebo. Secondary and exploratory objectives include the evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of treatment.

多達 25% 的患者可能患有 F1 纖維化，前提是他們還具有至少 1 個額外的危險因素。 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 治療的患者從基線到第 12 週的肝臟脂肪變化。次要和探索性目標包括評估治療 52 週後通過肝活檢評估的組織學變化。

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

在第一季度，我們宣布完成了 VOYAGE 研究的註冊，我們期待在今年第二季度分享主要結果，包括試驗的主要終點。

I'll now turn to our newest clinical program, highlighted by a compound called VK2735, which we believe has the potential for the treatment of various metabolic disorders, such as obesity, NASH and certain rare diseases. VK2735 is a dual agonist of the glucagon-like peptide-1, or GLP-1 receptor and the glucose-dependent insulinotropic polypeptide, or GIP receptor. Initial in vivo data from our dual agonist program demonstrated improvements in weight loss, glucose control and insulin sensitivity among diet-induced obese mice following treatment with Viking's compounds as compared to a GLP-1 mono agonist when administered at the same dose for the same period of time.

現在我將談談我們最新的臨床項目，其中重點介紹了一種名為 VK2735 的化合物，我們相信它具有治療各種代謝紊亂的潛力，例如肥胖症、NASH 和某些罕見疾病。 VK2735 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。來自我們的雙激動劑計劃的初步體內數據表明，與在同一時期以相同劑量給藥的 GLP-1 單激動劑相比，飲食誘導的肥胖小鼠在使用 Viking 化合物治療後體重減輕、葡萄糖控制和胰島素敏感性有所改善的時間。

In addition, the observed reductions in liver fat content were generally larger among animals treated with our compounds relative to those observed among animals treated with a GLP-1 mono agonist. Based on these in vivo and other preclinical data, we initiated a Phase I single ascending dose and multiple ascending dose clinical trial of VK2735. The single ascending dose portion of the study enrolled healthy men and women and evaluated escalating single doses of VK2735.

此外，與用 GLP-1 單激動劑治療的動物相比，在用我們的化合物治療的動物中觀察到的肝脂肪含量降低通常更大。基於這些體內和其他臨床前數據，我們啟動了 VK2735 的 I 期單次遞增劑量和多次遞增劑量臨床試驗。該研究的單次遞增劑量部分招募了健康男性和女性，並評估了 VK2735 的遞增單次劑量。

The multiple ascending dose portion enrolled healthy men and women with a minimum body mass index of 30 kilograms per meter squared. In the multiple ascending dose portion of the study, subjects received VK2735 once weekly for 28 days. During the first quarter, we were pleased to announce the results from this study with VK2735 demonstrating promising safety, tolerability, a predictable PK profile and positive signs of clinical benefit.

多次遞增劑量部分招募了體重指數至少為每平方米 30 公斤的健康男性和女性。在研究的多次遞增劑量部分，受試者每週接受一次 VK2735，持續 28 天。在第一季度，我們很高興地宣布了這項 VK2735 研究的結果，表明其具有良好的安全性、耐受性、可預測的藥代動力學特徵和臨床獲益的積極跡象。

Key takeaways from the single ascending dose portion of the study were that single doses of VK2735 were safe and well tolerated, and that the compound's PK profile demonstrated favorable characteristics in humans. Following single subcutaneous doses, VK2735 demonstrated the half-life of approximately 170 to 250 hours, a T-MAX ranging from 75 to 90 hours and excellent therapeutic exposures.

該研究單劑量遞增部分的主要結論是，單劑量 VK2735 是安全且耐受性良好的，而且該化合物的 PK 曲線在人體中表現出良好的特性。單次皮下給藥後，VK2735 的半衰期約為 170 至 250 小時，T-MAX 範圍為 75 至 90 小時，具有出色的治療暴露。

In the 28-day multiple ascending dose portion of the study, VK2735 demonstrated encouraging safety and tolerability, and positive signs of clinical activity. All cohorts receiving VK2735 demonstrated reductions in mean body weight from baseline ranging up to 7.8%. Cohorts receiving VK2735 also demonstrated reductions in mean body weight relative to placebo, ranging up to 6%.

在研究的 28 天多次遞增劑量部分，VK2735 表現出令人鼓舞的安全性和耐受性，以及臨床活動的積極跡象。所有接受 VK2735 治療的隊列均顯示平均體重較基線降低高達 7.8%。接受 VK2735 的隊列也顯示相對於安慰劑的平均體重減輕，幅度高達 6%。

Statistically significant differences compared to placebo were maintained or improved at the day 43 follow-up time point, 21 days after the last dose of VK2735 was administered. Importantly, VK2735 demonstrated encouraging safety and tolerability following repeated dosing. 98% of observed adverse events were reported as mild or moderate and 99% of gastrointestinal-related adverse events were also reported as mild or moderate.

在第 43 天的隨訪時間點，即最後一次 VK2735 給藥後 21 天，與安慰劑相比，統計學上的顯著差異得以維持或改善。重要的是，VK2735 在重複給藥後表現出令人鼓舞的安全性和耐受性。 98% 的觀察到的不良事件報告為輕度或中度，99% 的胃腸道相關不良事件也報告為輕度或中度。

In addition, all cohorts treated with VK2735 demonstrated improvements in plasma glucose levels relative to placebo, though, not all cohorts achieved statistical significance. We believe the tolerability data from this study indicates that higher doses may be achieved with longer titration windows, and we plan to evaluate further dose escalation in subsequent studies.

此外，與安慰劑相比，所有接受 VK2735 治療的隊列都顯示出血漿葡萄糖水平的改善，但並非所有隊列都達到了統計學顯著性。我們相信這項研究的耐受性數據表明，通過更長的滴定窗口可以獲得更高的劑量，我們計劃在後續研究中評估進一步的劑量遞增。

Turning to our future plans for VK2735. Based on the positive results generated in the Phase I study, we plan to initiate a Phase II trial in patients with obesity in mid-2023. Concurrent with the announcement of the Phase I data just described, we also announced the initiation of a Phase I clinical study to evaluate an oral tablet formulation of VK2735. We believe the tablet formulation represents a significant potential expansion of the program's overall value and utility.

轉向我們對 VK2735 的未來計劃。基於 I 期研究產生的積極結果，我們計劃在 2023 年年中啟動針對肥胖患者的 II 期試驗。在公佈剛剛描述的 I 期數據的同時，我們還宣布啟動 I 期臨床研究，以評估 VK2735 的口服片劑配方。我們相信片劑配方代表了該項目整體價值和效用的顯著潛在擴展。

In vivo data to date suggests that therapeutic plasma levels of VK2735 may be achieved via oral dosing, and we expect both the subcutaneous formulation and the oral formulation to provide unique benefits to patients. The ability to select either subcutaneous or oral dosage forms of VK2735 creates attractive potential treatment options and further extends the reach of this important program. The oral study is an extension of the Phase I study discussed a moment ago.

迄今為止的體內數據表明，VK2735 的治療血漿水平可以通過口服給藥達到，我們預計皮下製劑和口服製劑都能為患者提供獨特的益處。選擇 VK2735 的皮下或口服劑型的能力創造了有吸引力的潛在治療選擇，並進一步擴大了這一重要計劃的範圍。口頭研究是剛才討論的第一階段研究的延伸。

This portion of the study is a randomized, double-blind, placebo-controlled study in healthy volunteers, who have a minimum body mass index of 30 kilograms per meter squared. Subjects will receive daily oral doses for 28 days. The primary objective of the study is to evaluate the safety, tolerability and pharmacokinetics of VK2735 following 28 days of oral dosing.

這部分研究是一項隨機、雙盲、安慰劑對照研究，對像是健康志願者，這些志願者的最低體重指數為每平方米 30 公斤。受試者將接受每日口服劑量，持續 28 天。該研究的主要目的是評估口服給藥 28 天后 VK2735 的安全性、耐受性和藥代動力學。

Exploratory endpoints include changes in body weight and plasma glucose. We believe the results from this study could potentially be available in the second half of 2023.

探索性終點包括體重和血漿葡萄糖的變化。我們相信這項研究的結果可能會在 2023 年下半年公佈。

I will now provide an update on our third clinical candidate, VK0214. This is Viking's second orally available small molecule thyroid hormone receptor beta agonist, and it is currently being evaluated in a Phase Ib clinical trial in patients with X-linked adrenoleukodystrophy or X-ALD. X-ALD is a rare and often fatal metabolic disorder. Patients with X-ALD have genetic mutations that impact the function of a peroxisomal transporter of very long chain fatty acids.

我現在將提供我們的第三個臨床候選藥物 VK0214 的最新信息。這是 Viking 的第二種口服小分子甲狀腺激素受體 β 激動劑，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。 X-ALD 是一種罕見且通常致命的代謝紊亂。 X-ALD 患者的基因突變會影響極長鏈脂肪酸的過氧化物酶體轉運蛋白的功能。

When transporter function is impaired, patients are unable to efficiently metabolize very long chain fatty acids and the resulting accumulation of these compounds is believed to contribute to the onset and progression of X-ALD. In a prior 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).

當轉運蛋白功能受損時，患者無法有效代謝超長鏈脂肪酸，據信由此產生的這些化合物的積累會導致 X-ALD 的發作和進展。在之前對 100 多名健康志願者進行的 I 期研究中，VK0214 顯示出劑量依賴性暴露，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。

VK0214 also demonstrated an encouraging safety and tolerability profile with no serious adverse events reported and no treatment or dose-related signals observed for GI side effects, vital signs or cardiovascular measures.

VK0214 還表現出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 GI 副作用、生命體徵或心血管指標的治療或劑量相關信號。

Following these favorable results, 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 patients. 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, tolerability and pharmacokinetics of VK0214 administered once daily orally for 28 days.

在取得這些有利結果後，Viking 開始了 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 是最常見的 X-ALD 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 VK0214 每天一次口服給藥 28 天的安全性、耐受性和藥代動力學。

The study also includes an exploratory assessment of changes in plasma levels of very long chain fatty acids. This study continues to enroll, and we expect to report the initial results later this year.

該研究還包括對極長鏈脂肪酸血漿水平變化的探索性評估。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。

Moving to other corporate updates. Late in the first quarter, we completed a successful public offering of common stock, raising gross proceeds of approximately $288 million. We were happy to see the receptivity and enthusiasm from investors and are grateful for their support as we continue advancing our pipeline programs. As Greg mentioned earlier, pro forma for the offering, our end of quarter cash balance was approximately $400 million. This enables the company to further invest in pipeline programs, both existing and new and places Viking in a position of strength in discussions with potential corporate partners.

轉到其他公司更新。第一季度末，我們成功完成了普通股的公開發行，募集資金總額約為 2.88 億美元。我們很高興看到投資者的接受度和熱情，並感謝他們在我們繼續推進管道計劃時的支持。正如 Greg 之前提到的，我們的季度末現金餘額約為 4 億美元。這使公司能夠進一步投資於現有和新的管道項目，並使 Viking 在與潛在企業合作夥伴的討論中處於有利地位。

In conclusion, the first quarter of 2023 proved to be an exceptional quarter for Viking. We announced completion of enrollment in the VOYAGE study of VK2809 in patients with NASH and fibrosis, and we expect to report data for the primary endpoint of the study later this quarter. We also announced the first human data from our dual GLP-1, GIP receptor agonist, VK2735, demonstrated promising safety and tolerability and exciting reductions in body weight. We look forward to initiating a U.S. Phase II study in obesity in mid-2023.

總之，事實證明，2023 年第一季度對 Viking 來說是一個非凡的季度。我們宣布完成了針對 NASH 和纖維化患者的 VK2809 VOYAGE 研究的註冊，我們預計將在本季度晚些時候報告該研究的主要終點數據。我們還公佈了來自我們的雙 GLP-1、GIP 受體激動劑 VK2735 的第一份人體數據，證明了其具有良好的安全性和耐受性，並且令人興奮地減輕了體重。我們期待在 2023 年年中啟動一項美國肥胖症 II 期研究。

We also further expanded the reach of this program by announcing the initiation of a study using an oral tablet formulation from which we expect to report results toward the end of the year.

我們還宣布啟動一項使用口服片劑配方的研究，進一步擴大了該計劃的範圍，我們預計將在年底報告結果。

With our VK0214 program, we continued enrolling our Phase Ib study in patients with adrenomyeloneuropathy and we anticipate reporting data from this study later in the year.

通過我們的 VK0214 計劃，我們繼續在腎上腺髓系神經病患者中進行 Ib 期研究，我們預計將在今年晚些時候報告這項研究的數據。

Finally, we significantly strengthened our balance sheet in the quarter through a successful offering of common stock, which resulted in proceeds of over $280 million. Our current runway extends well beyond each of the clinical catalysts outlined here. We feel fortunate and grateful to be in the position we're in and look forward to providing additional updates as they're available.

最後，我們通過成功發行普通股顯著加強了本季度的資產負債表，募集資金超過 2.8 億美元。我們目前的跑道遠遠超出了此處概述的每個臨床催化劑。我們感到幸運和感激能夠處於我們所處的位置，並期待在可用時提供更多更新。

This concludes our prepared comments for today. Thanks again for joining us, and we'll now open the call for questions. Operator?

我們今天準備好的評論到此結束。再次感謝您加入我們，我們現在將開始提問。操作員？

(Operator Instructions) Today's first question comes from Steve Seedhouse with Raymond James.

（操作員說明）今天的第一個問題來自 Steve Seedhouse 和 Raymond James。

I had a few on the oral formulation of the GLP-1, GIP. First, just you haven't shared in preclinical data. So I wanted to ask, in general, if the expectation would be you could get the sort of exposure and ultimately efficacy levels that would be equivalent to the injectable or what specifically would be the expectations in terms of potency of what you could achieve at peak in humans? And then also with that compound, is this something that would lend itself to like a titration schema as well? Or are you essentially looking at flat doses in the Phase I?

我有一些關於 GLP-1、GIP 的口服製劑。首先，只是你們沒有分享臨床前數據。所以我想問，總的來說，如果期望是你可以獲得與註射劑相當的那種暴露和最終療效水平，或者在峰值時你能達到的效力方面的具體期望是什麼在人類？然後還有那個化合物，這是否也適合滴定模式？或者你基本上是在看第一階段的固定劑量？

Steve, thanks for the questions. With the exposures, yes, I don't think we expect the exposures to achieve the same level that are observed with the subcu formulation. Maybe I'll be proven wrong, but I don't think we'll get there. It's almost a different product. I would consider the oral formulation, maybe for someone who first doesn't want to start with an injectable or for someone who maybe has a BMI 32 to 34 or something that might be adequately addressed with an oral formulation or potentially in a maintenance setting where you start with the subcu and then transition on an oral. So there's a lot of different ways that it could be used. But my own guess is that we probably won't see the same exposures with the oral. What's the second question?

史蒂夫，謝謝你的問題。對於曝光，是的，我不認為我們期望曝光達到與 subcu 配方觀察到的相同水平。也許我會被證明是錯誤的，但我認為我們不會到達那裡。這幾乎是一個不同的產品。我會考慮口服製劑，也許對於那些一開始不想注射的人，或者對於 BMI 可能在 32 到 34 之間的人，或者可以通過口服製劑充分解決的問題，或者可能處於維護環境中的人你從 subcu 開始，然後過渡到 oral。所以有很多不同的方式可以使用它。但我自己的猜測是，我們可能不會看到與口腔相同的暴露。第二個問題是什麼？

Titration, yes. So yes, we will titrate in the upcoming study. So the first cohorts, flat dosing and subsequent cohorts will titrate up.

滴定，是的。所以是的，我們將在即將進行的研究中進行滴定。因此，第一個隊列、固定劑量和後續隊列將逐步增加。

Okay. So it's just 1 dose of -- 1 tablet dose that you just give multiple pills, I guess, in that case?

好的。所以它只是 1 劑 - 1 片劑量，我猜，在那種情況下，你只需要服用多片藥片？

That's right. Yes. The first cohort is 2.5 mg and that's flat. And then from there, they dose up. I mean first week will be 2.5 and then the remaining 3 weeks would be a higher dose. And then as you go on through the cohorts, you kind of titrate up per week.

這是正確的。是的。第一組為 2.5 毫克，持平。然後從那裡開始，他們開始服用。我的意思是第一周將是 2.5，然後剩下的 3 週將是更高的劑量。然後當你繼續通過隊列時，你每週都會滴定。

Okay. A couple more just because it's a really interesting program. Obviously, you mentioned maintenance dosing is 1 option. That's just given how many people in the next decade are likely to be gravitating towards using incretin. I imagine there'd be some enormous group of patients coming on or having been on injectables. I'm curious if you're going to gather that type of maintenance data in the Phase I, can you take patients that you already treated with the injectable and start them on oral and see how they do? And then I just have 1 more on the program after, if I could.

好的。多幾個只是因為它是一個非常有趣的程序。顯然，您提到維持劑量是一種選擇。這只是考慮到未來十年可能會有多少人傾向於使用腸促胰島素。我想會有一大群病人正在接受或接受過注射治療。我很好奇你是否打算在第一階段收集那種類型的維護數據，你能否讓你已經接受過注射治療的患者開始口服治療，看看他們的表現如何？如果可以的話，之後我還有 1 個關於程序的內容。

Yes. No, thanks. In this study, we're really just trying to see if the formulation will provide exposures and what levels compared to subcu. So I think in the future, those transition type studies would be really important and really interesting, but this is just the first one, and we're just going to see how the exposures turn out.

是的。不，謝謝。在這項研究中，我們實際上只是想看看該配方是否會提供暴露量，以及與 subcu 相比的水平。所以我認為在未來，那些過渡類型的研究會非常重要而且非常有趣，但這只是第一個，我們只是要看看曝光結果如何。

Okay. And then the Phase I, I think you guys were -- injectable at least you were collecting MRI-PDFF data, and there are maybe some other biomarkers in there that weren't ready for the initial top line. So can you just comment on -- you have the guidance in place with the oral data. Should there -- is there any other data either from the clinical injectable study beyond the top line that you've already announced that would be coming here in near term that we should keep an eye out for?

好的。然後是第一階段，我認為你們是——至少你們正在收集 MRI-PDFF 數據是可注射的，而且那裡可能還有一些其他生物標誌物還沒有為最初的頂線做好準備。那麼你能不能評論一下——你有口頭數據的指導。是否應該 - 除了您已經宣布的頂級臨床注射研究之外，是否還有其他數據會在短期內出現，我們應該密切關注？

Yes. Thanks, Steve. We'll probably be reporting more data a little bit later in the year, potentially at Obesity Week, but we don't have any near-term, nothing imminent there. But you're right, we did have a number of biomarkers in liver fat in the study.

是的。謝謝，史蒂夫。我們可能會在今年晚些時候報告更多的數據，可能是在肥胖週上，但我們沒有任何近期的數據，沒有什麼是迫在眉睫的。但你是對的，我們在研究中確實有一些肝臟脂肪的生物標誌物。

Our next question today comes from Joon Lee with Truist Securities.

我們今天的下一個問題來自 Truist Securities 的 Joon Lee。

Congrats on the progress. What really stood out from the healthy volunteer study of VK2735 was how key the tolerability profile was. So is that -- is that just a function of the study being a small Phase I study? Or is there some mechanistic hypotheses as to why 2735 may be better tolerated and with possibly better weight loss? And I have a follow-up question.

祝賀進步。從 VK2735 的健康志願者研究中真正脫穎而出的是耐受性概況的重要性。那麼，這是否只是該研究作為 I 期小型研究的一個功能？或者是否有一些關於為什麼 2735 可能具有更好的耐受性和可能更好的減肥效果的機制假設？我有一個後續問題。

Joon, thanks. Yes, so I don't really know. It was a small study, so you could argue that maybe we're just looking at small numbers. What was interesting with the tolerability was that there wasn't really a dose-related change in tolerability as you went up. I think the highest dose cohort actually had really, really good tolerability, better than some of the earlier cohorts.

俊，謝謝。是的，所以我真的不知道。這是一項小型研究，所以你可能會爭辯說也許我們只是在研究小數字。耐受性的有趣之處在於，當你上升時，耐受性並沒有真正與劑量相關的變化。我認為最高劑量的隊列實際上具有非常非常好的耐受性，比一些早期的隊列更好。

So mechanistically, I know people have talked about arrest in recruitment being 1 thing that might lead to improved tolerability if you can have a sustained effect on GLP-1 without arrest in recruitment. You could see maybe an increase in efficacy without necessarily issues with nausea. But I don't know -- otherwise, I don't know that mechanistically it was anything obvious that would explain it.

所以從機制上講，我知道人們已經談到招募中的停滯是一件事，如果你可以在招募中停滯的情況下對 GLP-1 產生持續影響，那麼這可能會導致耐受性提高。您可能會看到療效有所提高，但不一定會出現噁心問題。但我不知道——否則，我不知道從機械上來說，有什麼明顯的東西可以解釋它。

Fair enough. And both Lee and Novo have historically done head-to-head trials of their GLPs, at least for diabetes. Do you have any plans to do a head-to-head trial of VK2735 against other obesity drugs?

很公平。 Lee 和 Novo 都曾對他們的 GLP 進行過面對面的試驗，至少是針對糖尿病。您是否有計劃對 VK2735 與其他肥胖藥物進行頭對頭試驗？

Yes, great question. I think it's a really good idea as we move further through the program, but this upcoming Phase II will not have an active comparator in it. It's just placebo. But I do think that's something important for the future just to see how they compare.

是的，很好的問題。隨著我們進一步推進該計劃，我認為這是一個非常好的主意，但即將到來的第二階段將不會有一個活躍的比較器。這只是安慰劑。但我確實認為這對未來很重要，只是看看它們如何比較。

Our next question today comes from Annabel Samimy with Stifel.

我們今天的下一個問題來自 Stifel 的 Annabel Samimy。

So I want to ask about the titration period that you're considering for Phase II. I mean, already, it looked like you had some good tolerability. It looks like you have some very good weight loss already within 28 weeks. So I guess I'm wondering why you would want to push that further and what kind of titration schedule might we be looking at?

所以我想問一下你為第二階段考慮的滴定期。我的意思是，看起來你的耐受性很好。看起來您在 28 週內已經有一些非常好的減肥效果。所以我想我想知道你為什麼要進一步推動它，我們可能會考慮什麼樣的滴定時間表？

So I guess that's the first question. And is this the same exact molecule as 2735? Are you changing the balance between GLP-1 or GIP in any way as you go into the oral if you don't have the same, I guess, target exposure? And then I have 1 more follow-up.

所以我想這是第一個問題。這是與 2735 完全相同的分子嗎？如果你沒有相同的，我猜，目標曝光，你是否在進入口服時以任何方式改變 GLP-1 或 GIP 之間的平衡？然後我還有 1 個跟進。

Yes. It's the same molecule, Annabel, in the oral and the subcu. And we're titrating in the 28-day study really because we've not dosed with this compound before, so we don't know if there are any differences in tolerability, and we're doing fewer cohorts. So in the subcu, we did have -- the first 2 cohorts were flat dosing, and then we titrated and here the first cohort is going to be flat and then we titrate. But nothing obvious that suggests we have to titrate.

是的。它是相同的分子，Annabel，在口腔和亞細胞中。我們在為期 28 天的研究中進行了滴定，因為我們之前沒有服用過這種化合物，所以我們不知道耐受性是否存在任何差異，而且我們正在做更少的隊列。所以在 subcu 中，我們確實有 - 前 2 個隊列是固定劑量，然後我們滴定，這裡第一個隊列將是平坦的，然後我們滴定。但沒有明顯的跡象表明我們必須滴定。

And to your point, I think the tolerability was really, really promising in the subcu, but it's just first study. And we know that GLP-1 agonism is tied to nausea and GI side effects. So we just want to try to control for that as best as possible.

就你的觀點而言，我認為在 subcu 中的耐受性真的非常有前途，但這只是第一次研究。我們知道 GLP-1 激動作用與噁心和胃腸道副作用有關。所以我們只想盡可能地控制它。

I guess, to be more specific, why do you feel like you need to go higher on the dosing if you've sort of attained some pretty competitive results as it is with good tolerability?

我想，更具體地說，如果您已經獲得了一些相當有競爭力的結果，因為它具有良好的耐受性，為什麼您覺得需要更高的劑量？

In the oral are you talking about?

在口頭上你在說什麼？

No, in the injectable for Phase II.

不，在第二階段的注射劑中。

In the injectable, yes, we're going to go up to 15 milligrams because the 10-milligram was very well tolerated and maybe the 15 will work better. We won't know until we get there. But that was the reason we were considering adding that 15-milligram cohort to the 28-day study, but we decided to just stop the study here and put that into the Phase II, and we'll titrate up to it. But I don't think there's anything -- I don't think we're necessarily pushing anything with increasing the dose to 15.

在註射劑中，是的，我們將增加到 15 毫克，因為 10 毫克的耐受性非常好，也許 15 毫克會更好。在我們到達那里之前我們不會知道。但這就是我們考慮將 15 毫克隊列添加到 28 天研究中的原因，但我們決定停止這裡的研究並將其放入第二階段，我們將逐漸增加。但我不認為有什麼——我不認為我們必須通過將劑量增加到 15 來推動任何事情。

Okay. And then if I can ask on VK2809. I mean, you have some pretty good validation from a competing program. But I guess, some of the KOLs we spoke to, 1 of the things that they brought up with it, they were a little bit surprised that there was not just NASH reduction, but they also were able to show fibrotic improvement as early as year 1. So how do you really think about this? And would you expect the same for yourself if your seemingly superior liver fat reduction holds up in VOYAGE? Were you as surprised with the fibrotic effect within 52 weeks, given that it's more of a downstream process from the fat reduction?

好的。然後我是否可以在 VK2809 上詢問。我的意思是，您從競爭程序中得到了一些很好的驗證。但我想，我們採訪過的一些 KOL，他們提出的一些事情，他們有點驚訝，不僅 NASH 減少了，而且他們早在 2017 年就能夠顯示出纖維化改善1. 那麼你是怎麼看待這件事的呢？如果您在 VOYAGE 中看似出色的肝臟脂肪減少效果，您會期望自己也有同樣的表現嗎？考慮到它更多是減脂的下游過程，您是否對 52 週內的纖維化效應感到驚訝？

Well, I don't know. I think the -- yes and no, I guess. I mean the fibrosis improvement endpoint is traditionally a more difficult end point to show improvement on, but we know that the mechanism demonstrates in animal models, reduction in collagen load and improvement in fibrosis. And whether or not that's secondary to fat reduction, I don't think we know and haven't seen that published anywhere.

嗯，我不知道。我認為 - 是和否，我猜。我的意思是纖維化改善終點傳統上是一個更難顯示改善的終點，但我們知道該機制在動物模型中證明，膠原蛋白負荷減少和纖維化改善。不管這是否是減脂的次要因素，我認為我們不知道也沒有看到任何地方發表過。

So we weren't totally surprised. I guess you could argue that it's too short a window and this is more a metabolic targeting mechanism. But everything we've seen in animals suggests that it should actually do both. It should help with NASH resolution and improve fibrosis.

所以我們並不完全感到驚訝。我想你可能會爭辯說它的窗口太短，而這更像是一種代謝靶向機制。但是我們在動物身上看到的一切都表明它實際上應該做到這兩點。它應該有助於解決 NASH 並改善纖維化。

Okay. Great. If I can squeeze in 1 more. Any thoughts about how long this $406 million will take you out to?

好的。偉大的。如果我能再擠進 1 個。有沒有想過這 4.06 億美元會讓你花多長時間？

Yes. Annabel, certainly, we're covered, as Brian mentioned earlier, well beyond all the catalysts in our 3 development programs. We wouldn't point to an exact year, but certainly well beyond 2 years out and well beyond.

是的。 Annabel，當然，正如 Brian 之前提到的，我們的覆蓋範圍遠遠超出了我們 3 個開發計劃中的所有催化劑。我們不會指出確切的年份，但肯定會超過 2 年，甚至更久。

And our next question today comes from Jay Olson at Oppenheimer.

我們今天的下一個問題來自 Oppenheimer 的 Jay Olson。

Congrats on all the progress, and thank you for the update. Maybe just a follow-up on VK2809. Can you just talk about what we should expect to see in the top line results besides MRI-PDFF? Will we see change in LDL cholesterol levels? And then I guess, can you just talk about sort of the GI tolerability of VK2809? It seems like that's potentially an important feature for your molecule. And then I had a follow-up, if I could, please.

祝賀所有的進步，並感謝您的更新。也許只是 VK2809 的跟進。你能談談除了 MRI-PDFF 之外，我們應該期望在頂級結果中看到什麼嗎？我們會看到低密度脂蛋白膽固醇水平的變化嗎？然後我想，您能談談 VK2809 的胃腸道耐受性嗎？這似乎是您的分子的一個潛在重要特徵。然後我有一個後續行動，如果可以的話，請。

Sure. Thanks, Jay. The -- with the initial data, we would plan to have the liver fat by MRI-PDFF and then a lipid panel, so likely LDL, trigs and if we get the atherogenic proteins, Lp(a) and ApoB, we'll report those as well as well as safety and tolerability. The GI profile to date has been excellent. We haven't really seen anything different from placebo. And there's no reason to think that we would see differences in the VOYAGE population, but we don't have the data, so I can't say for sure yet. But there's nothing that would lead us to believe that there would be any sort of a GI signal with the compound. It's exceptionally well tolerated.

當然。謝謝，傑伊。有了初始數據，我們計劃通過 MRI-PDFF 獲得肝臟脂肪，然後是脂質面板，很可能是 LDL、trigs，如果我們獲得致動脈粥樣化蛋白、Lp(a) 和 ApoB，我們將報告這些以及安全性和耐受性。迄今為止的 GI 概況非常好。我們還沒有真正看到與安慰劑有什麼不同。並且沒有理由認為我們會看到 VOYAGE 人群的差異，但我們沒有數據，所以我還不能肯定地說。但沒有什麼能讓我們相信這種化合物會產生任何類型的 GI 信號。它的耐受性非常好。

Okay. Great. That's super helpful. And then if you could maybe help us frame for investors what a best case scenario might look like with regards to MRI-PDFF and any other endpoints that we should be watching, including safety and tolerability? And then what you would see as the most important differentiating points from resmetirom? That would be great.

好的。偉大的。這非常有幫助。然後，如果你能幫助我們為投資者構建關於 MRI-PDFF 和我們應該關注的任何其他端點（包括安全性和耐受性）的最佳案例場景是什麼樣的？那麼您認為與 resmetirom 最重要的區別點是什麼？那太好了。

Yes. Thanks, Jay. Well, I think the internal hurdle that we're using is a 30% mean reduction in liver fat. If we can see treatment groups showing a 30% mean reduction, that would be our success hurdle. Obviously, higher is better. We saw really nice reductions in the Phase IIa study. I'm not sure I would expect that level of efficacy in this study just because it's a larger study and you often see a penalty when you are in larger populations. But if we see 30%, I think there's a lot of precedent that suggests that translates to a higher probability of histologic benefit.

是的。謝謝，傑伊。好吧，我認為我們正在使用的內部障礙是肝臟脂肪平均減少 30%。如果我們能看到治療組平均減少 30%，那將是我們成功的障礙。顯然，越高越好。我們在 IIa 期研究中看到了非常好的減少。我不確定我是否會期望這項研究的療效水平只是因為它是一項更大的研究，而且當你在更大的人群中時，你經常會看到懲罰。但如果我們看到 30%，我認為有很多先例表明這轉化為組織學獲益的可能性更高。

I think there's plenty of room for multiple of the same mechanism to coexist in NASH. I think there will be differentiation among products and they're probably switching. I think our tolerability profile is outstanding, and our efficacy has been exceptionally strong so far. So I think we're comfortable with where we would be competitively.

我認為 NASH 中有很多相同機制共存的空間。我認為產品之間會有差異，它們可能正在轉換。我認為我們的耐受性非常出色，到目前為止我們的功效非常強大。所以我認為我們對我們的競爭優勢感到滿意。

And our next question today comes from Andy Hsieh with William Blair.

我們今天的下一個問題來自 Andy Hsieh 和 William Blair。

Congratulations on all the achievements this quarter. So Brian, you mentioned a couple of times about the activities in liver fat at least in the preclinical model from these dual agonist candidates, including 2735. So I'm curious if that was by design or it's an observation that you just observe as you advance these candidates from preclinical to clinical settings?

祝賀本季度取得的所有成就。所以布賴恩，你至少在這些雙重激動劑候選藥物（包括 2735）的臨床前模型中多次提到了肝臟脂肪的活動。所以我很好奇這是設計使然還是你在觀察時觀察到的將這些候選人從臨床前推進到臨床環境？

Yes. It's -- thanks, Andy. It's -- I think the liver fat change from this mechanism, because there are no receptors in the liver, is probably most tied to weight loss and insulin sensitivity -- improving insulin sensitivity. So I don't think there's necessarily a direct effect on liver fat. It's more tied to weight loss. But in animals, we did see really interesting data, typically generally always better than a GLP-1 mono agonist and comparable to better than another dual agonist.

是的。這是 - 謝謝，安迪。這是——我認為肝臟脂肪從這種機制中改變，因為肝臟中沒有受體，可能與體重減輕和胰島素敏感性最相關——提高胰島素敏感性。所以我認為這不一定會對肝臟脂肪產生直接影響。它與減肥更相關。但在動物身上，我們確實看到了非常有趣的數據，通常通常總是優於 GLP-1 單激動劑，並且與另一種雙重激動劑相當。

So we're really excited about the potential there. I think that the models we looked at were generally the diet-induced obese mouse. So if you're skinnier or your body weight is lower, liver fat's lower, you probably wouldn't see as large an effect since the effect is driven by weight loss, but pretty interesting characteristic.

所以我們對那裡的潛力感到非常興奮。我認為我們看到的模型通常是飲食誘導的肥胖小鼠。所以如果你更瘦或者你的體重更低，肝臟脂肪更低，你可能不會看到那麼大的效果，因為效果是由減肥驅動的，但是非常有趣的特徵。

Got it. We've gotten some questions from investors about relative contribution of weight loss from either fat or lean body mass. Do you have a good handle from the Phase I study about the proportion that's -- the observed weight loss is coming from?

知道了。我們從投資者那裡收到了一些關於脂肪或瘦體重減輕體重的相對貢獻的問題。從第一階段的研究中，你對觀察到的體重減輕的比例有很好的把握嗎？

We don't. We didn't do any DEXA scans in this study. So we don't have the relative change in weight. We do from the animals, we saw predominantly a reduction in fat and not muscle, but I think it's been shown in other studies that when you lose a certain amount of weight, you do start to cut into muscle. But we didn't see that in any of the animal studies that we conducted. And we unfortunately just didn't look at it in this study.

我們沒有。我們在這項研究中沒有進行任何 DEXA 掃描。所以我們沒有重量的相對變化。我們從動物身上做的，我們看到主要是脂肪減少而不是肌肉減少，但我認為其他研究表明，當你減掉一定量的體重時，你確實開始減少肌肉。但是我們在我們進行的任何動物研究中都沒有看到這一點。不幸的是，我們在這項研究中並沒有關注它。

Great. Is that something that you'll look at in the Phase II study?

偉大的。這是你將在 II 期研究中看到的東西嗎？

Not currently, no. It's a 13-week study. So we don't have a plan to do DEXA scans in the upcoming study. It might be something we'd look at in a longer-term study.

目前沒有，沒有。這是一項為期 13 週的研究。所以我們沒有計劃在即將進行的研究中進行 DEXA 掃描。這可能是我們要在長期研究中看到的東西。

Got it. Got it. That's helpful. And then maybe lastly, for the oral formulation versus subcu, could you kind of help us think about the amount in terms of dosing from these 2 formulations on a relative sense?

知道了。知道了。這很有幫助。然後也許最後，對於口服製劑與 subcu，你能幫助我們從相對意義上考慮這兩種製劑的劑量嗎？

Yes. The oral will push up a little bit higher. We're going -- I think the plan is to go to 20 milligrams with the oral. So not a huge amount higher than the planned dose to phase -- for the Phase II and the subcu.

是的。口腔會向上推高一點。我們要去 - 我認為計劃是口服 20 毫克。因此，對於 II 期和 subcu，不會比計劃的階段劑量高出很多。

(Operator Instructions) Our next question comes from Yale Jen with Laidlaw & Co.

（操作員說明）我們的下一個問題來自 Yale Jen 和 Laidlaw & Co。

Congrats on the progress so far. Just a few quick questions. The first 1 probably is about housekeeping. In terms of SG&A, first quarter, that seems significantly higher than prior quarters. Should we anticipate that to be a normal or this is generally a onetime situation?

祝賀目前取得的進展。只是幾個簡單的問題。第一個可能是關於家務管理的。就 SG&A 而言，第一季度似乎明顯高於前幾個季度。我們應該預料到這是正常的還是這通常是一次性的情況？

Yes. Thanks, Yale. That's primarily due to -- it is not something you should expect to see moving forward. That's really due to timing of some legal expenses and those should be reduced moving forward, and you wouldn't expect that to be the run rate moving forward.

是的。謝謝，耶魯。這主要是因為——你不應該期望看到它向前發展。這實際上是由於一些法律費用的時間安排，這些費用應該在未來減少，你不會期望這是未來的運行率。

Okay. Great. And a follow-up question here again about the 2735 Phase II study. Could you give us a sort of overall view about what you anticipate to do for that study? Anything you can review in terms of the study design?

好的。偉大的。還有一個關於 2735 II 期研究的後續問題。你能給我們一個關於你希望為這項研究做些什麼的總體看法嗎？關於研究設計，您有什麼可以回顧的嗎？

Yes. The study design is a 13-week study with flat dosing in the lowest dose cohort and then titrated dosing in the higher dose cohorts. The top dose right now is targeting 15 milligrams, and we'll do a stepwise titration up there. It's 13 weeks in duration. So you'd be at the top dose for, I think, 3 to 4 weeks at the end there. The primary endpoint will be change in body weight.

是的。該研究設計是一項為期 13 週的研究，在最低劑量隊列中採用固定劑量，然後在較高劑量隊列中滴定劑量。目前最高劑量的目標是 15 毫克，我們將逐步調整到那裡。持續時間為 13 週。所以我認為你會在最後 3 到 4 週內處於最高劑量。主要終點將是體重的變化。

And how big the study might be in terms of size?

就規模而言，這項研究可能有多大？

Yes, we haven't disclosed that, but I would say 150 or so or 100 to 150 would be the target there.

是的，我們沒有透露，但我會說 150 左右或 100 到 150 將是那裡的目標。

Great. That's very helpful. Maybe the last question here is that you mentioned that about -- with the cash in hand, you might also contemplate some additional pipeline expansions. I know you want to be focused, but nevertheless, was there anything in your mind that could be explored going forward?

偉大的。這很有幫助。也許這裡的最後一個問題是你提到的——有了手頭的現金，你可能還會考慮一些額外的管道擴展。我知道你想集中註意力，但儘管如此，你心中有什麼可以繼續探索的嗎？

Yes, we have a lot of things we're working on, but we haven't disclosed, but we typically spend time in an area as little money as possible on some of these nascent programs and the ones that show promise, we bring forward. I think 2735 is a good example of that. And as things mature appropriately, we'll have more to say about them.

是的，我們正在做很多事情，但我們沒有透露，但我們通常會在一個領域花費盡可能少的錢在其中一些新興項目和那些顯示出希望的項目上，我們提出.我認為 2735 就是一個很好的例子。隨著事情的適當成熟，我們將有更多的話要說。

And our next question today comes from Justin Zelin with BTIG.

我們今天的下一個問題來自 BTIG 的 Justin Zelin。

Congrats on all the progress. Maybe just a follow-up on the Phase II for the dual agonist here. You mentioned 13 weeks of active dosing. Will you continue to follow up the patients past the 13 weeks and for further longer-term data? Would we have to look towards another study here? And I have some follow-ups.

祝賀所有的進步。也許只是這裡雙重激動劑的第二階段的後續行動。您提到了 13 週的主動給藥。您會在 13 週後繼續對患者進行隨訪並獲取更長期的數據嗎？我們需要在這裡尋找另一項研究嗎？我有一些後續行動。

Yes. To answer the second question, yes, I think longer data would come from a subsequent study of 26 weeks or longer, not that that's the next study, but we plan to get through this study first. The follow-up period in this study, I believe, is 4 weeks. So you come back, I think -- well, multiple times you come back after the 13-week treatment period, but I think the last follow-up is at week 17 and Marianne is nodding in agreement here. Marianne is our COO. So anyway, that's the duration.

是的。要回答第二個問題，是的，我認為更長的數據將來自 26 週或更長時間的後續研究，而不是下一項研究，但我們計劃首先完成這項研究。我相信，這項研究的隨訪期是 4 週。所以你回來了，我想——好吧，你在 13 週的治療期後回來了很多次，但我認為最後一次隨訪是在第 17 週，瑪麗安在這裡點頭表示同意。瑪麗安是我們的首席運營官。所以無論如何，這就是持續時間。

Great. And from the Phase I data, did you notice anything in the PK/PD profile that suggests that it might be different from what we've seen with the tirzepatide compound. I'm just curious if there was anything that appeared in that data set yet? Or is it too early to tell?

偉大的。從 I 期數據中，您是否注意到 PK/PD 配置文件中的任何內容表明它可能與我們在 tirzepatide 化合物中看到的不同。我只是好奇該數據集中是否出現了任何內容？還是現在說還為時過早？

Yes. It's really hard to make those comparisons because the -- obviously, they weren't head-to-head in the population that we've seen published for. The tirzepatide compound is just a different population than we looked at. We do see, I think, a later T-max, longer half life, and I think our exposures are improved. But again, very difficult to make those sorts of comparisons in the absence of a head-to-head data set.

是的。進行這些比較真的很難，因為 - 顯然，他們在我們所看到的人口中並沒有正面交鋒。 tirzepatide 化合物與我們看到的只是一個不同的群體。我認為，我們確實看到了更晚的 T-max、更長的半衰期，而且我認為我們的暴露有所改善。但同樣，在沒有頭對頭數據集的情況下很難進行此類比較。

Great. And I'll ask 1 last question. Further down the road, do you see any potential to run a combination with the 2809 and the dual agonist potentially in a NASH study?

偉大的。我會問最後一個問題。在未來的道路上，您是否認為有可能在 NASH 研究中聯合使用 2809 和雙重激動劑？

Yes, it's not something we've talked much about. But if we were to do something like that, I think we talk about it if and when we have data on it.

是的，這不是我們談論太多的事情。但如果我們要做那樣的事情，我想我們會在有數據的情況下討論它。

And our next question today comes from Naz Rahman with Maxim Group.

我們今天的下一個問題來自 Maxim Group 的 Naz Rahman。

Just really quickly on the oral. What gives you confidence on the timing of the initial data for second half of '23? Like are you guys seeing any potential competition or any issues recruiting patients with all the, I guess, various GLP-1 studies ongoing?

口頭上真的很快。是什麼讓您對 23 年下半年初始數據的時間安排充滿信心？就像你們看到任何潛在的競爭或招募患者的任何問題一樣，我猜，正在進行的各種 GLP-1 研究？

Yes. We think we can get the data in the second half. We feel confident about that. Luckily, obesity is the largest market ever. So we shouldn't have problems with recruiting, but I don't know, we haven't had many competitive issues at this point.

是的。我們認為我們可以在下半場獲得數據。我們對此充滿信心。幸運的是，肥胖是有史以來最大的市場。所以我們在招聘方面不應該有問題，但我不知道，目前我們還沒有遇到太多競爭問題。

Right. How many sites are there? And for this study are all the sites also in Australia?

正確的。有多少網站？對於這項研究，是否所有地點也在澳大利亞？

Yes. It's actually an extension of the earlier study, the single ascending dose and multiple ascending dose study, it's the same site. It's a single site in Australia. The Phase II study will be here in the United States.

是的。它實際上是早期研究的延伸，單次遞增劑量和多次遞增劑量研究，它是同一地點。它是澳大利亞的一個站點。 II 期研究將在美國進行。

Got it. Are you seeing, like, I guess, like faster rates enrollment or I guess, like higher rates of interest versus when you initially started your injectable studies?

知道了。我猜你是否看到了更快的註冊率，或者我猜，與你最初開始注射研究時相比，你看到了更高的利率？

I think it's maybe too early to say there. I don't know the answer to that question.

我認為現在說可能還為時過早。我不知道那個問題的答案。

And ladies and gentlemen, this concludes our question-and-answer session. I'd like to turn the conference back over to Stephanie Diaz for any closing remarks.

女士們，先生們，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)，聽取任何閉幕詞。

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 good 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。祝你下午好。

Thank you. This concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines, and have a wonderful day.

謝謝。今天的電話會議到此結束。感謝大家出席今天的演講。您現在可以斷開線路，度過美好的一天。