Viking Therapeutics Inc (VKTX) 2024 Q1 法說會逐字稿

Welcome to the Viking Therapeutics first-quarter 2024 financial results conference call. (Operator Instructions) As a reminder, this conference call is being recorded today, April 24, 2024.

歡迎參加 Viking Therapeutics 2024 年第一季財務業績電話會議。(操作員指示) 提醒一下，本次電話會議於今天（2024 年 4 月 24 日）錄製。

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

現在，我想將會議交給 Viking 的投資者關係經理 Stephanie Diaz。請繼續，史蒂芬妮。

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。今天與我一起參加的是 Viking 總裁兼執行長 Brian Lian；以及 Viking 的財務長 Greg Zante。

Before we begin, I'd like to caution that comments made during this conference call today, April 24, 2024, will contain forward-looking statements under the Safe Harbor provisions of the US Private Securities Litigation Reform Act of 1995, including statements about Viking's expectations regarding its development activities, timelines, 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，我想提醒一下，今天（2024 年 4 月 24 日）在電話會議上發表的評論將包含根據美國 1995 年私人證券訴訟改革法安全港條款的前瞻性陳述，包括有關 Viking 對其開發活動、時間表和里程碑的期望的陳述。前瞻性陳述受風險和不確定因素的影響，可能導致實際結果產生重大不利差異，且報告的結果不應被視為未來績效的指標。

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.

這些前瞻性陳述僅代表今日的觀點，本公司不承擔修改或更新今天所作任何聲明的義務。我鼓勵您查看該公司向美國證券交易委員會提交的有關這些事項和其他事項的所有文件。

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

現在我將電話轉給 Brian Lian 來聽取他的初步評論。

Thanks, Stephanie, and good afternoon to everyone listening in by phone or on the webcast. Today, we'll review our financial results for the first quarter ended March 31, 2024, and provide an update on recent progress with our clinical programs and operations. During the first quarter, Viking announced positive results from two of the company's key pipeline programs. First, our Phase 2 VENTURE study evaluating our dual GLP-1 and GIP receptor agonist VK2735 in patients with obesity, successfully achieved its primary endpoint and all secondary endpoints, demonstrating statistically significant reductions in body weight at all doses as compared to placebo.

謝謝斯蒂芬妮，祝透過電話或網路廣播收聽的各位聽眾下午好。今天，我們將回顧截至 2024 年 3 月 31 日第一季的財務業績，並提供有關我們的臨床計劃和營運的最新進展的最新資訊。第一季度，維京宣佈公司兩個主要管道項目取得了積極成果。首先，我們的第 2 階段 VENTURE 研究評估了我們的雙重 GLP-1 和 GIP 受體激動劑 VK2735 在肥胖患者中的應用，成功實現了其主要終點和所有次要終點，與安慰劑相比，所有劑量的體重均有統計學上顯著降低。

Also during the quarter, the company announced results from a Phase 1 clinical trial evaluating an oral tablet formulation of VK2735. This study demonstrated encouraging safety and tolerability as well as promising weight loss following 28 days of once-daily dosing. The company plans to advance both of these programs into further development later this year.

此外，在本季度，該公司還公佈了評估 VK2735 口服片劑配方的第 1 階段臨床試驗的結果。這項研究表明，該藥物具有令人鼓舞的安全性和耐受性，經過28天的每日一次服用後，體重減輕效果良好。該公司計劃在今年稍後進一步推進這兩個項目的開發。

In addition, during the first quarter, the company completed the final biopsies in the Phase 2b VOYAGE study evaluating the novel thyroid hormone receptor beta agonist VK2809 in patients with NASH and fibrosis. We expect to report the biopsy results from this study later this quarter.

此外，第一季度，該公司完成了 2b 期 VOYAGE 研究的最終活檢，該研究評估了新型甲狀腺激素受體β激動劑 VK2809 對 NASH 和纖維化患者的療效。我們預計將在本季稍後報告這項研究的活檢結果。

Finally, during the quarter, Viking completed a public offering of common stock raising gross proceeds of approximately $630 million. These funds substantially strengthen the company's balance sheet and will support our plans to aggressively develop our pipeline.

最後，在本季度，維京完成了普通股公開發行，籌集總收益約 6.3 億美元。這些資金大大增強了公司的資產負債表，並將支持我們積極開發產品線的計劃。

I'll provide further details on our operations and development activities after we review our financial results for the first quarter of 2024. For that, I'll turn the call over to Greg Zante, Viking's Chief Financial Officer.

在我們審查 2024 年第一季的財務業績後，我將提供有關我們的營運和開發活動的更多詳細資訊。為此，我將把電話轉給 Viking 的財務長 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 later today.

謝謝，布萊恩。結合我的評論，我想建議參與者參考維京向美國證券交易委員會提交的 10-Q 表，我們預計將在今天晚些時候提交該表。

I'll now go over our results for the first quarter ended March 31, 2024. Research and development expenses were $24.1 million for the three months ended March 31, 2024, compared to $11 million for the same period in 2023. The increase was primarily due to increased expenses related to manufacturing for our drug candidates, preclinical studies, clinical studies, stock-based compensation, salaries and benefits, and services provided by third-party consultants.

我現在將回顧截至 2024 年 3 月 31 日的第一季業績。截至 2024 年 3 月 31 日的三個月，研發費用為 2,410 萬美元，而 2023 年同期為 1,100 萬美元。增加的主要原因是與我們的候選藥物製造、臨床前研究、臨床研究、股票薪酬、工資和福利以及第三方顧問提供的服務相關的費用增加。

General and administrative expenses were $10 million for the three months ended March 31, 2024, compared to $9.5 million for the same period in 2023. The increase was primarily due to increased expenses related to stock-based compensation, salaries and benefits, and services provided by third-party consultants, partially offset by decreased expenses related to legal and patent services.

截至 2024 年 3 月 31 日的三個月的一般及行政費用為 1000 萬美元，而 2023 年同期為 950 萬美元。成長的主要原因是股票薪酬、工資和福利以及第三方顧問提供的服務相關費用的增加，但部分被法律和專利服務相關費用的減少所抵消。

For the three months ended March 31, 2024, Viking reported a net loss of $27.4 million or $0.26 per share compared to a net loss of $19.5 million or $0.25 per share in the corresponding period in 2023. The increase in net loss for the three months ended March 31, 2024, was primarily due to the increase in research and development expenses and general and administrative expenses noted previously, partially offset by increased interest income compared to the same period in 2023.

截至 2024 年 3 月 31 日的三個月，維京報告淨虧損為 2,740 萬美元或每股 0.26 美元，而 2023 年同期淨虧損為 1,950 萬美元或每股 0.25 美元。截至 2024 年 3 月 31 日的三個月的淨虧損增加主要是由於先前提到的研發費用以及一般及行政費用的增加，但與 2023 年同期相比，利息收入的增加部分抵消了這一增加。

Turning to the balance sheet, at March 31, 2024, Viking held cash, cash equivalents, and short-term investments of $963 million compared to $362 million as of December 31, 2023. First-quarter balance reflects receipt of gross proceeds of $630 million from the company's public offering, which closed on March 4, 2024.

談到資產負債表，截至 2024 年 3 月 31 日，維京持有的現金、現金等價物和短期投資為 9.63 億美元，而截至 2023 年 12 月 31 日為 3.62 億美元。第一季餘額反映了該公司於 2024 年 3 月 4 日結束的公開發行所獲得的總收益 6.3 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萊恩。

Thanks, Greg. The first quarter of 2024 was an eventful quarter as we received and reported the results from two key clinical trials, our Phase 2 VENTURE trial evaluating subcutaneous VK2735 in patients with obesity and our Phase 1 clinical trial evaluating an oral tablet formulation of VK2735 in healthy volunteers. Both studies were successful, demonstrating promising weight loss and favorable safety and tolerability and we look forward to advancing both of these programs into further development later this year.

謝謝，格雷格。2024 年第一季是一個多事之秋，因為我們收到並報告了兩項關鍵臨床試驗的結果，即我們的第 2 階段 VENTURE 試驗，評估肥胖患者皮下注射 VK2735 的效果，以及我們的第 1 階段臨床試驗，評估健康志願者服用 VK2735 口服片劑的效果。兩項研究都取得了成功，顯示出良好的減肥效果和良好的安全性和耐受性，我們期待在今年稍後推進這兩個項目的進一步發展。

As we have recently reviewed the results from each of these studies on separate conference calls, I'll briefly review key takeaways in my prepared comments and refer you to our February 27, and March 26, press releases for more details. In addition, I'm happy to provide further detail in the Q&A portion of the call.

由於我們最近在單獨的電話會議上審查了每項研究的結果，我將在準備好的評論中簡要回顧一下關鍵要點，並請您參閱我們 2 月 27 日和 3 月 26 日的新聞稿以了解更多詳細信息。此外，我很高興在電話問答部分提供更多詳細資訊。

I will first provide an update on our subcutaneous formulation of VK2735 for obesity. VK2735 is a dual agonist of the glucagon like peptide-1 or GLP-1 receptor and the glucose dependent insulinotropic polypeptide or GIP receptor.

我將首先介紹我們用於治療肥胖症的 VK2735 皮下製劑的最新情況。VK2735 是胰高血糖素樣勝肽 1 或 GLP-1 受體和葡萄糖依賴性胰島素促泌多肽或 GIP 受體的雙重激動劑。

In the first quarter of 2023, we announced positive results from a Phase 1 single ascending dose and multiple ascending dose study of VK2735. This study demonstrated the promising safety, tolerability, and pharmacokinetics of VK2735 when administered as a weekly subcutaneous injection for four weeks. In addition, subjects in the study demonstrated up to 7.8% weight loss from baseline after 28 days with no signs of plateau.

2023 年第一季度，我們公佈了 VK2735 第 1 期單次遞增劑量和多次遞增劑量研究的正面結果。這項研究證明了 VK2735 每週皮下注射四週後具有良好的安全性、耐受性和藥物動力學。此外，研究中的受試者在 28 天後體重較基線下降了 7.8%，並且沒有出現平台期的跡象。

Based on these positive results, Viking initiated a Phase 2 trial called the VENTURE trial to evaluate VK2735 in patients with obesity. The VENTURE trial was a randomized double-blind, placebo-controlled, multi-center study that evaluated the safety, tolerability, pharmacokinetics, and weight loss efficacy of VK2735 administered subcutaneously once weekly for 13 weeks.

基於這些積極成果，Viking 啟動了一項名為 VENTURE 試驗的 2 期試驗，以評估 VK2735 對肥胖患者的作用。VENTURE 試驗是一項隨機雙盲、安慰劑對照、多中心研究，評估了每週一次皮下注射 VK2735 共 13 週的安全性、耐受性、藥物動力學和減肥效果。

In the first quarter, Viking announced positive top line results from the VENTURE study. This trial successfully achieved its primary endpoint and all secondary endpoints with patients receiving VK2735, demonstrating reductions in body weight at all doses compared with placebo. For the primary endpoint, patients receiving VK2735 demonstrated statistically significant reductions in mean body weight from baseline ranging up to 14.7% as well as statistically significant reductions in mean body weight relative to placebo ranging up to 13.1%.

第一季度，維京公佈了 VENTURE 研究的積極營收結果。該試驗在接受 VK2735 治療的患者中成功實現了其主要終點和所有次要終點，表明與安慰劑相比，所有劑量的患者體重均有所減輕。對於主要終點，接受 VK2735 治療的患者的平均體重與基線相比具有統計學顯著下降，降幅高達 14.7%，與安慰劑相比，平均體重具有統計學顯著下降，降幅高達 13.1%。

Statistically significant differences compared to placebo were observed for all VK2735 doses starting at week one and were maintained throughout the course of the study. Weight loss in all treated cohorts was progressive through 13 weeks and did not show evidence of plateauing. We believe this suggests that further weight loss could be achieved through extended dosing beyond the 13-week treatment period of this study.

從第一週開始，所有 VK2735 劑量與安慰劑相比都出現了統計學上的顯著差異，並且在整個研究過程中都保持了這種差異。所有接受治療的患者的體重在 13 週內都呈現漸進式下降，且沒有停滯的跡象。我們相信這表明透過在本研究的 13 週治療期之後延長用藥可以實現進一步的減肥。

Additionally, the VENTURE study showed VK2735 treatment to be safe and well-tolerated over the 13-week trial with the majority of treatment-emergent adverse events being characterized as mild or moderate. Based on the Phase 2 VENTURE results as well as prior Phase 1 results, Viking plans to meet with the FDA later this quarter to discuss next steps in the development of VK2735. In addition to the subcutaneous formulation, the company is also developing a novel oral tablet formulation of VK2735. We believe a tablet formulation could represent an attractive treatment option for patients with obesity, and we see this as an important potential expansion of the overall opportunity for the program.

此外，VENTURE 研究表明，在為期 13 週的試驗中，VK2735 治療是安全且耐受性良好的，大多數治療中出現的不良事件被描述為輕度或中度。根據第 2 階段 VENTURE 結果以及先前的第 1 階段結果，Viking 計劃在本季度晚些時候與 FDA 會面，討論 VK2735 開發的下一步。除了皮下製劑外，該公司還在開發 VK2735 的新型口服錠劑製劑。我們相信，片劑配方可能為肥胖患者提供一種有吸引力的治療選擇，並且我們認為這是該計劃整體機會的一個重要的潛在擴展。

Last year, we initiated an extension of the previously reported subcutaneous Phase 1 study to incorporate an evaluation of our tablet formulation. The oral portion of this study is a randomized, double-blind, placebo-controlled study in healthy adults with a minimum body mass index of 30 kilograms per meter square. Primary objective is to evaluate the safety and tolerability of VK2735 administered as a tablet once daily for 28 days. Secondary and exploratory objectives include an evaluation of the pharmacokinetics of orally administered VK2735, as well as various pharmacodynamic measures, including changes in body weight and other metrics.

去年，我們啟動了先前報告的皮下第一階段研究的延伸，以納入對我們的片劑配方的評估。此項研究的口服部分是一項針對體重指數至少為每平方公尺 30 公斤的健康成年人進行的隨機、雙盲、安慰劑對照研究。主要目的是評估每天一次服用 VK2735 片劑連續服用 28 天的安全性和耐受性。次要和探索性目標包括評估口服 VK2735 的藥物動力學，以及各種藥效學測量，包括體重和其他指標的變化。

During the first quarter, we reported the initial data from this study. With respect to safety and tolerability, oral VK2735 was shown to be safe and well-tolerated following once-daily dosing for up to 28 days at doses that were titrated up to 40 milligrams. Among subjects receiving VK2735, all treatment-emergent adverse events were reported as mild or moderate in severity with the majority, 76%, reported as mild.

第一季度，我們報告了這項研究的初步數據。就安全性和耐受性而言，口服 VK2735 被證明是安全且耐受性良好的，每日一次給藥長達 28 天，劑量逐漸增加至 40 毫克。在接受 VK2735 治療的受試者中，所有治療中出現的不良事件的嚴重程度均為輕度或中度，其中大多數（76%）報告為輕度。

Overall, no clinically meaningful differences were reported for gastrointestinal adverse events among subjects treated with VK2735 compared with placebo. And importantly, to date, no serious adverse events have been reported in this study.

總體而言，與安慰劑相比，接受 VK2735 治療的受試者的胃腸道不良事件並未發現具有臨床意義的差異。重要的是，迄今為止，該研究尚未報告任何嚴重不良事件。

In addition to safety and tolerability, an exploratory assessment of change in body weight was conducted. Subjects receiving oral VK2735 demonstrated dose-dependent reductions in body weight ranging up to 5.3% from baseline. Placebo-adjusted reductions in bodyweight reached up to 3.3% from baseline. Body weight reductions compared with baseline and placebo were statistically significant at the highest dose evaluated. In addition, weight loss during the 28-day window of this study was progressive at the 20 milligram and 40 milligram dose levels with no plateau observed.

除了安全性和耐受性之外，還對體重變化進行了探索性評估。接受口服 VK2735 的受試者表現出劑量依賴性體重下降，與基線相比最高下降幅度達 5.3%。經安慰劑調整後，體重較基線下降幅度達 3.3%。與基線和安慰劑相比，在評估的最高劑量下，體重減輕具有統計意義。此外，在本研究的 28 天期間，20 毫克和 40 毫克劑量水平的體重減輕是漸進性的，沒有觀察到平台期。

Given the promising weight loss signal observed in this study, along with the excellent tolerability profile thus far, Viking is pursuing further dose escalation. In addition, based on the encouraging trajectory of weight loss and the lack of a plateau at 28 days for the higher dose cohorts, we believe that further benefits might be anticipated from longer dosing periods. To this end, we are proceeding with plans for a Phase 2 trial in patients with obesity and we expect to initiate this study later this year. Details on study design will be provided as we get closer to study initiation.

鑑於本研究中觀察到的令人鼓舞的減肥訊號，以及迄今為止優異的耐受性特徵，Viking 正在進一步增加劑量。此外，基於令人鼓舞的減重軌跡以及高劑量組在 28 天時沒有達到穩定期，我們相信更長的給藥期可能會帶來更多益處。為此，我們正在製定針對肥胖患者的第二階段試驗計劃，並預計今年稍後啟動這項研究。隨著研究的開始，我們將提供有關研究設計的詳細資訊。

I will now turn to our most advanced clinical program, VK2809 for the treatment of NASH and fibrosis. VK2809 is an orally available small molecule agonist of the thyroid hormone receptor that is selective for liver tissue as well as the beta isoform of the receptor.

現在我將談談我們最先進的臨床項目 VK2809，用於治療 NASH 和纖維化。VK2809 是一種口服的甲狀腺激素受體小分子激動劑，對肝臟組織以及受體的β同工型具有選擇性。

Last May, we announced positive top-line results from the Phase 2b VOYAGE study of VK2809. The VOYAGE study is a randomized, double-blind, placebo-controlled, multi-center international trial designed to assess the efficacy, safety, and tolerability of VK2809 in patients with biopsy-confirmed NASH and fibrosis. Enrollment included patients with at least 8% liver fat as measured by magnetic resonance imaging, proton density fat fraction, as well as F2 and F3 fibrosis.

去年五月，我們公佈了 VK2809 第 2b 期 VOYAGE 研究的正面頂線結果。VOYAGE 研究是一項隨機、雙盲、安慰劑對照、多中心國際試驗，旨在評估 VK2809 對活檢確診的 NASH 和纖維化患者的療效、安全性和耐受性。入選患者包括以磁振造影、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。

Last May we reported that this study had successfully achieved its primary endpoint with patients receiving VK2809, demonstrating statistically significant reductions in liver fat content from baseline to week 12 as compared with placebo. The median relative change from baseline in liver fat among patients treated with VK2809 ranged from 38% to 55% after 12 weeks.

去年五月我們報道過，這項研究已成功實現其主要終點，接受 VK2809 治療的患者與接受安慰劑治療的患者相比，從基線到第 12 週肝臟脂肪含量顯著降低。接受 VK2809 治療的患者在 12 週後肝臟脂肪相對於基線的中位數相對變化範圍為 38% 至 55%。

In addition, up to 85% of patients receiving VK2809 experienced at least a 30% reduction in liver fat. This level of efficacy is associated with a greater likelihood of histologic benefit in NASH. As in prior studies, VK2809-treated patients also achieved statistically significant reductions in LDL cholesterol, triglycerides, and atherogenic lipoproteins. We believe these results indicate that VK2809 has the potential to provide longer-term cardioprotective benefits.

此外，在接受 VK2809 治療的患者中，多達 85% 的肝臟脂肪減少了至少 30%。這種療效程度與 NASH 中更大的組織學益處可能性有關。與先前的研究一樣，接受 VK2809 治療的患者的 LDL 膽固醇、三酸甘油酯和動脈粥樣硬化脂蛋白也實現了統計學上顯著的降低。我們相信這些結果表明 VK2809 有可能提供更長期的心臟保護益處。

The initial VOYAGE data also served to further establish VK2809's promising safety and tolerability profile. 94% of treatment related adverse events among patients receiving VK2809 were reported as mild or moderate. Discontinuations due to adverse events were low and balanced among placebo and treatment arms. In particular, VK2809 demonstrated excellent gastrointestinal tolerability with similar rates of nausea, diarrhea, stool frequency, and vomiting observed among VK2809-treated patients compared to placebo.

初始 VOYAGE 數據也進一步證實了 VK2809 良好的安全性和耐受性。在接受 VK2809 治療的患者中，94% 的治療相關不良事件被報告為輕度或中度。因不良事件而停藥的病例很少，且安慰劑組和治療組之間的平衡。具體來說，VK2809 表現出優異的胃腸道耐受性，與安慰劑組患者相比，接受 VK2809 治療的患者的噁心、腹瀉、排便頻率和嘔吐發生率相似。

Last November, Viking presented additional data from this study at the annual meeting of the American Association for the Study of Liver Diseases. These new data demonstrated robust liver fat reductions among patients with or without type 2 diabetes as well as those having either F2 or F3 fibrosis. Among patients with type 2 diabetes, at week 12, reductions from baseline in liver fat ranged from 36% to 54%, which was comparable to the reductions observed among patients without type 2 diabetes.

去年 11 月，Viking 在美國肝病研究協會年會上展示了這項研究的更多數據。這些新數據表明，患有或不患有第 2 型糖尿病的患者以及患有 F2 或 F3 纖維化的患者肝臟脂肪均顯著減少。在患有第 2 型糖尿病的患者中，第 12 週時，肝臟脂肪相對於基線的減少量為 36% 至 54%，與非 2 型糖尿病患者的減少量相當。

Treatment with VK2809 also demonstrated potent reductions in liver fat among patients with either F2 or F3 fibrosis with liver fat reductions ranging up to approximately 58% from baseline. Thus, these results indicate that neither the presence of type 2 diabetes nor the presence of F2 or F3 fibrosis meaningfully impact VK2809's efficacy in reducing liver fat. During the first quarter, we completed the final biopsies in the VOYAGE study and remain on track to report the histology data from this study later this quarter.

VK2809 治療也證實 F2 或 F3 纖維化患者的肝臟脂肪顯著減少，肝臟脂肪減少量較基線最高可達約 58%。因此，這些結果表明，2 型糖尿病、F2 或 F3 纖維化的存在都不會對 VK2809 減少肝臟脂肪的功效產生重大影響。在第一季度，我們完成了 VOYAGE 研究的最終活檢，並將在本季度稍後報告該研究的組織學數據。

I'll now provide a brief update on our second thyroid hormone receptor beta agonist, VK0214, which is currently being evaluated in a Phase 1b trial in patients with X-linked adrenoleukodystrophy or X-ALD. Like VK2809, VK0214 is also an orally available, small molecule that is selective for the beta isoform of the thyroid hormone receptor.

現在我將簡要介紹我們的第二種甲狀腺激素受體β激動劑 VK0214，該藥物目前正在對 X 連鎖腎上腺腦白質營養不良症 (X-ALD) 患者進行 1b 期試驗評估。與 VK2809 一樣，VK0214 也是一種口服小分子，對甲狀腺激素受體的 β 異構體具有選擇性。

X-ALD is a rare and debilitating metabolic disorder that is caused by genetic mutations that disable the function of the proximal transporter of very long-chain fatty acids. As a result, patients are unable to efficiently metabolize very long-chain fatty acids, and the accumulation of these compounds is believed to contribute to the onset and progression of X-ALD.

X-ALD 是一種罕見且使人衰弱的代謝紊亂，是由基因突變引起的，導致極長鏈脂肪酸近端轉運蛋白的功能喪失。因此，患者無法有效代謝長鏈脂肪酸，而這些化合物的累積被認為是導致 X-ALD 的發生和進展的原因。

In a prior Phase 1 study in 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. 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.

在先前對健康志願者進行的第 1 階段研究中，VK0214 表現出劑量依賴性暴露、無累積證據且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 LDL 膽固醇、三酸甘油酯、載脂蛋白 B 和脂蛋白 A 均有所降低。

The ongoing Phase 1b study of VK0214 is being conducted in patients with the adrenomyeloneuropathy or AMN form of X-ALD, which is the most common form of the disorder. This trial is a randomized, double-blind, placebo-controlled, multi-center study in adult male patients with AMN. The primary objectives of the study are to evaluate the safety, tolerability, and pharmacokinetics of VK0214 administered orally once daily for 28 days. The study also includes an exploratory assessment of changes in plasma levels of very long-chain fatty acids. The company expects to report the top-line results from this trial in mid-2024.

正在進行的 VK0214 1b 期研究正在針對患有腎上腺脊髓神經病變或 AMN 形式的 X-ALD 患者進行，這是該疾病最常見的形式。該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。研究的主要目的是評估 28 天每天口服一次 VK0214 的安全性、耐受性和藥物動力學。該研究還包括對血漿極長鏈脂肪酸水平變化的探索性評估。該公司預計將在 2024 年中期報告此次試驗的最終結果。

Finally, during the first quarter, the company successfully completed an underwritten public offering of common stock. The gross proceeds to Viking from this offering were approximately $630 million. As Greg indicated a few moments ago, these funds have strengthened our balance sheet, which as of the end of the quarter held approximately $963 million in cash, significantly extending our runway. This provides the company with the resources to aggressively develop our programs through important clinical milestones.

最後，該公司在第一季成功完成了普通股的承銷公開發行。維京從此次發行中獲得的總收益約為 6.3 億美元。正如格雷格剛才所說，這些資金增強了我們的資產負債表，截至本季末，我們的資產負債表持有約 9.63 億美元現金，大大延長了我們的跑道。這為公司提供了資源，使我們能夠透過重要的臨床里程碑積極開發我們的專案。

In conclusion, during the first quarter, Viking reported positive data from two key clinical trials of our lead obesity program, VK2735. The Phase 2 VENTURE study demonstrated up to an approximately 15% reduction in body weight from baseline following 13 weeks of dosing by weekly subcutaneous injection as well as promising safety and tolerability. The Phase 1 study of the oral tablet formulation of VK2735 demonstrated excellent safety and tolerability and positive signs of clinical activity with subjects reporting mean weight loss of up to 5.3% from baseline following 28 days of oral dosing.

總之，在第一季度，維京報告了我們領先的肥胖計畫 VK2735 的兩項關鍵臨床試驗的積極數據。階段 2 VENTURE 研究表明，經過 13 週的每週皮下注射給藥後，體重相對於基線下降了約 15%，並且具有良好的安全性和耐受性。VK2735 口服片劑的 1 期研究證明其具有出色的安全性和耐受性，並顯示出積極的臨床活性，受試者報告稱，口服 28 天后，平均體重較基線減輕高達 5.3%。

We plan to meet with regulators to discuss the path forward for each of these programs, and we expect to initiate further clinical trials with each later this year. We also plan to report data from the Phase 2b VOYAGE study of our thyroid hormone beta receptor agonist, VK2809, in biopsy-confirmed NASH and fibrosis later this quarter. The initial data from this study successfully achieved the primary endpoint and affirmed the VK2809's potent efficacy in reducing liver fat, along with its favorable tolerability and safety profile. We recently completed the final biopsies in the VOYAGE study and look forward to reporting data on histologic changes assessed after 52 weeks of treatment later this quarter.

我們計劃與監管機構會面，討論每個項目的未來發展方向，並預計今年稍後啟動進一步的臨床試驗。我們也計劃在本季稍後報告我們的甲狀腺激素β受體激動劑VK2809在活檢證實的NASH和纖維化中的第2b階段VOYAGE研究的數據。研究的初步數據成功實現了主要終點，並證實了 VK2809 在減少肝臟脂肪方面的強大功效，以及其良好的耐受性和安全性。我們最近完成了 VOYAGE 研究的最後一次活檢，並期待在本季度稍後報告 52 週治療後評估的組織學變化數據。

Finally, we expect to announce data from our Phase 1b study of VK0214 for the treatment of adrenomyeloneuropathy midyear. To support our maturing pipeline, the Company ended the quarter with a strong balance sheet of $963 million.

最後，我們預計將在年中公佈用於治療腎上腺脊髓神經病變的 VK0214 1b 期研究的數據。為了支持我們不斷成熟的產品線，該公司在本季結束時擁有 9.63 億美元的強勁資產負債表。

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

今天的準備評論到此結束。非常感謝您加入我們，現在我們開始提問。

(Operator Instructions) Joon Lee, Truist.

(操作員指示) Joon Lee，Truist。

Hey, congrats on the quarter and thanks for taking our questions. Sarcopenia is getting a lot of attention these days and some companies are talking about adding SARM to GLP. You certainly have your share of experiences with SARM and sarcopenia in general. Any thoughts on bringing back 5211 as an add-on strategy? And I have a follow-up.

嘿，恭喜本季取得的成績，並感謝您回答我們的問題。肌少症最近受到了廣泛關注，一些公司正在討論將 SARM 添加到 GLP 中。您肯定對 SARM 和肌少症有著豐富的經驗。對將 5211 作為附加策略重新推出有何想法？我還有一個後續問題。

Hey, Joon. Yeah, thanks for the question. Yeah, it is, I think, getting to be more popular in the conversation. What we have always said and hasn't really changed is it's hard to understand the clinical significance of the loss in muscle and whether that actually has an impact on function or feeling or survival, which are what are typically used for approval. But it's a good point that 5211 compound is the most potent SARM that we're aware of, and to the extent muscle loss is considered to be clinically relevant more so in the pharmacologic setting versus the regular diet and exercise setting. It could be something that's really useful.

嘿，俊。是的，謝謝你的提問。是的，我認為它在談話中越來越受歡迎。我們一直在說，而且實際上沒有改變的是，很難理解肌肉損失的臨床意義，以及這是否真的會對功能、感覺或生存產生影響，而這些通常是獲得批准的依據。但有一點值得注意，即 5211 化合物是我們所知的最有效的 SARM，就肌肉損失在臨床上的相關性而言，在藥理學環境下比在常規飲食和運動環境下更為重要。它可能真的很有用。

Okay. Looking forward to your update on that. Can you update us on where you are with the oral VK2735 dosing and what the stopping criteria or the maximum dose that you tend to test for the oral?

好的。期待您的更新。您能否告訴我們口服 VK2735 的劑量情況以及您傾向於測試口服的停止標準或最大劑量是什麼？

Yeah. Thanks, Joon. It's ongoing still and we are planning to continue dose escalation until we either get to some sort of -- some reason for stopping it or maybe a plateau on the exposures or a plateau on the weight change or some tolerability issue. And so we'll probably have more to say about that around the middle of the year when we have data from the additional cohorts.

是的。謝謝，Joon。這項工作仍在進行中，我們計劃繼續增加劑量，直到找到某種停止治療的理由，或者達到暴露量的穩定期，或者體重變化的穩定期，或者達到某種耐受性問題。因此，當我們在今年年中獲得更多群體的數據時，我們可能會對此有更多評論。

Great. And one final question. A steady state, say around half-year mark, is it your expectation that VK2735 would drive percent weight loss greater than tirzepatide? Or would it be similar to tirzepatide and what is the basis for your thinking. Thank you.

偉大的。最後一個問題。穩定狀態，比如說半年左右，您是否預期 VK2735 會比 tirzepatide 帶來更大的體重減輕百分比？或者它與 tirzepatide 相似，您的想法的依據是什麼。謝謝。

Sorry, on the -- were you talking about the oral or -- what?

抱歉，您是在談論口頭還是—什麼？

Yeah, for injectable, let's say, subcutaneous.

是的，對於注射來說，比如說皮下注射。

For the subcutaneous, well, it seems that at any given dose, the exposures are significantly higher. And so whether it would be better or comparable, hard to say, but I think at any given dose, we should have a greater load onboard without -- in our view, without a meaningful change in the tolerability profile. So how that translates, I think, we'd have to see a longer study before making a call on that.

對於皮下注射，似乎在任何給定劑量下，暴露量都明顯較高。因此，很難說它是否會更好或具有可比性，但我認為在任何給定劑量下，我們都應該有更大的負荷，而 - 在我們看來，耐受性特徵不會發生有意義的變化。所以我認為，我們必須進行更長時間的研究才能得出這個結論，具體如何解釋呢？

Roger Song, Jefferies.

傑富瑞（Jefferies）的羅傑·宋（Roger Song）。

Hi, team. This is Kambiz on for Roger. Maybe on VK2809, what's the general translatability of the 12-week MRI-PDFF result into later histology endpoints? And are you planning to move the program into -- the NASH program into Phase 3 yourself? Or do you intend to partner?

大家好。這是 Kambiz 為 Roger 表演的。也許在 VK2809 上，12 週 MRI-PDFF 結果對後期組織學終點的一般可轉換性是什麼？您是否計劃親自將 NASH 計劃推進至第 3 階段？或您有合作意願？

And then maybe as a third and final question, how do you think the thyroid beta agonist market will develop? There's kind of been some recent evidence that GLP-1s, both dual GLP-1 and GIP and dual GLP-1 glucagon agonist have shown potentially fibrosis improvement. So just your thoughts on how that market will develop and will be really helpful. Thank you.

那麼也許是第三個也是最後一個問題，您認為甲狀腺β激動劑市場會如何發展？最近有一些證據表明，GLP-1（雙重 GLP-1 和 GIP 以及雙重 GLP-1 胰高血糖素激動劑）已顯示出潛在的纖維化改善作用。因此，您對於該市場將如何發展的想法將會非常有幫助。謝謝。

Yeah. Thanks, Kambiz. So with the translatability for liver fat to histologic improvement, generally, it has been shown that reducing liver fat, particularly above that 30% relative reduction threshold has led to improved odds of histologic benefit. There are some exceptions to that. But generally, there are more examples of that proving out than not.

是的。謝謝，Kambiz。因此，隨著肝臟脂肪向組織學改善的轉化，一般而言，已證明減少肝臟脂肪，特別是超過 30% 的相對減少閾值，可以提高組織學益處的幾率。但也有一些例外。但總體來說，證明這一點的例子比證明不正確的例子多。

And I think it's more of a compound-by-compound situation when you try to translate the precise liver fat reduction to histologic improvement. I think the best comparator for us would be the other thyroid agonist that was recently approved. It showed in the -- somewhere in the teens range for NASH resolution and it did show some improvement in fibrosis. So to the extent we have a similar or better liver fat reduction, I think that would be the range we would be looking at for NASH resolution and fibrosis improvement.

我認為，當您嘗試將精確的肝臟脂肪減少轉化為組織學改善時，這更多的是一個化合物一個化合物的情況。我認為對我們來說最好的比較對像是最近批准的另一種甲狀腺激動劑。結果表明，NASH 的解決程度在十幾歲的範圍內，並且纖維化確實有所改善。因此，如果我們的肝臟脂肪減少程度相似或更好，我認為這將是我們在 NASH 解決和纖維化改善方面所關注的範圍。

With respect to the overall market, yeah, it does seem like there is a rapid expansion of the GLP-1 utilization. And so that probably does create some headwind on the uptake of new NASH drugs, but we've not had an approved drug for NASH. So now that we do, I think it's going to be really important to see how the first few quarters mature there. And maybe there is a backlog of people waiting to try it and a backlog of clinicians waiting to do prescribe it. So unknown right now. It's hard to hard to project. But it is true that the GLP-1s are getting more and more utilization.

就整體市場而言，GLP-1 的利用率確實似乎正在迅速擴大。這可能確實會對新型 NASH 藥物的採用造成一些阻力，但我們尚未獲得批准的 NASH 藥物。所以既然我們現在已經這樣做了，我認為觀察前幾季的成熟情況非常重要。也許還有一大堆人等著嘗試這種療法，還有一大堆臨床醫生等著開這種處方。現在還不清楚。這很難進行預測。但 GLP-1 的用途確實越來越廣泛。

And there's a middle question in there, I think, I skipped.

我想這中間還有一個問題，我跳過了。

Yeah, just some plans on Phase 3 for your NASH program, kind of, intend to do it solo or maybe search -- seek a partner?

是的，您對 NASH 專案第 3 階段有一些計劃，是打算單獨進行還是尋找合作夥伴？

Yeah. Yeah, great. So we plan to do is receive the data from the VOYAGE study, and then we'll schedule an end-of-Phase 2 meeting with the FDA for later this year and get the current view of registration endpoints and any trial design suggestions, might -- the agency might have. And I think we'll have to see what the data look like, but we'll be probably looking for a partner with the program, but hard to say without having a look at the data first.

是的。是的，很棒。因此，我們計劃接收 VOYAGE 研究的數據，然後我們將安排在今年稍後與 FDA 舉行第 2 階段結束會議，並了解註冊終點的當前情況以及該機構可能有的任何試驗設計建議。我認為我們必須看看數據是什麼樣的，但我們可能會尋找該計劃的合作夥伴，但如果不先看數據就很難說。

Annabel Samimy, Stifel.

安娜貝爾·薩米 (Annabel Samimy)，Stifel。

Hi, and thanks for taking my questions. I have two. On the oral, so when you think about the additional doses for the oral, which you know already has shown some pretty respectable weight loss metrics, how are you balancing how you push the dose versus the manufacturing capacity issues? We are getting a lot of questions around that, given the supply problems that current manufacturers have with their own therapies right now. So I just wanted to know if you're going into this on with that thought in mind.

你好，感謝您回答我的問題。我有兩個。關於口服，當您考慮口服的額外劑量時，您知道它已經顯示出一些相當可觀的減肥指標，您如何平衡劑量與製造能力問題？鑑於目前製造商自身療法的供應問題，我們收到了許多相關問題。所以我只是想知道您是否帶著這個想法去做這件事。

And on the second is, I guess, given some of the additional benefits that weight lost drugs are having, whether it's on CV risk or hypertension or kidney disease and now sleep apnea, are there any additional trials or subpopulations that you can be baking into your later-stage development programs to position yourself competitively, even at a minimum from a payer perspective, as this space evolves without having to do Phase 4 trials, but at least have some kind of idea or a metric in the late-stage trials that you're already designing? So those are my questions for now.

第二，我想，考慮到減肥藥具有的一些額外好處，無論是心血管風險、高血壓、腎臟疾病還是現在的睡眠呼吸暫停，是否有任何額外的試驗或亞群可以融入到您的後期開發計劃中，以使自己處於競爭地位，至少從付款人的角度來看，隨著這個領域的發展，無需進行第 4 階段試驗，但至少在您已經設計的後期試驗中有一些想法或後期試驗？這就是我目前的問題。

Thanks, Annabel. Yeah. For the second question, we'll probably focus mostly on obesity as the primary or early indication, but all of the subsets that you just mentioned and the successes in those populations are really important. So to the extent we could add a cohort with dyslipidemia or something like that to look at effects on plasma lipids that might have a read through the cardiovascular benefit. That maybe -- we're primarily, though, looking at the weight loss indication for the Phase 3 program.

謝謝，安娜貝爾。是的。對於第二個問題，我們可能主要關注肥胖作為主要或早期指徵，但您剛才提到的所有子集以及這些人群中的成功都非常重要。因此，在某種程度上，我們可以添加一個患有血脂異常或類似疾病的隊列，以觀察對血漿脂質的影響，這可能會對心血管產生益處。那可能——但我們主要關注的是第三階段計畫的減重指標。

With respect to manufacturing, it's an area that, yeah, we're acutely aware of it. And I think -- a couple of things. We're right now in this very acute stage where these compounds have just been recently approved for weight loss and there is just overwhelming demand and the supply isn't quite there.

關於製造業，是的，我們非常清楚這個領域。我認為有幾件事。我們現在正處於一個非常關鍵的階段，這些化合物剛剛被批准用於減肥，需求非常巨大，但供應還不夠。

We don't consider that to be a terminal state. We do see from the existing companies in the space, ramp-up in manufacturing capacity. We know on the contractor side, there is a massive attention being paid to this issue. And so I think the supply dynamics will probably evolve over the next few years. Still going to be a difficult challenge, but I think we're not in a permanent shortage state, we don't think.

我們不認為那是一個終結狀態。我們確實看到該領域現有公司的製造能力正在提升。我們知道，承包商方面非常關注這個問題。因此我認為未來幾年供應動態可能會改變。這仍然是一個艱鉅的挑戰，但我認為我們並沒有處於永久短缺的狀態，我們不這麼認為。

Jay Olson, Oppenheimer.

傑伊奧爾森、奧本海默。

Oh, hey. Congrats on all the progress and thank you for providing this update. For subcu VK2735, what kind of data should we expect in 2Q? And do you think you'll have enough data to support less frequent dosing? And then what are your latest thoughts on a Phase 2b study? And then I had a follow-up question, if I could.

哦，嘿。恭喜您取得的所有進展並感謝您提供此更新。對於 subcu VK2735，我們應該期待第二季什麼樣的數據？您是否認為您有足夠的數據來支持減少服藥頻率？那麼您對第 2b 階段研究的最新想法是什麼？如果可以的話，我還有一個後續問題。

Yeah. Thanks, Jay. So we'll -- we haven't received the final data from the study. So we would be looking for the lipid data, some of the PK data, the exposure data after -- four and six weeks after the last dose. That sort of thing, I think, would be important for us to understand and what's the proper forum for presentation. Maybe some of it would trickle into earnings updates or corporate presentations, but probably, later in the year, we would have a presentation at a medical conference.

是的。謝謝，傑伊。所以我們還沒有收到該研究的最終數據。因此，我們會尋找脂質數據、一些 PK 數據以及最後一次服藥後四週和六週的暴露數據。我認為，這類事情對於我們了解並理解什麼是適合展示的論壇很重要。也許其中一些會逐漸融入盈利更新或公司演示中，但很可能在今年晚些時候，我們會在醫學會議上進行演示。

And with respect to less-frequent dosing, I mean, that's part of the PK data that we will receive. If it looks like we're in a therapeutic range at some period after the last dose, maybe that will be a feasible strategy and we would look to incorporate that into subsequent trial. So really important data coming out of the PK dataset.

關於較低頻率的給藥，我的意思是，這是我們將收到的 PK 數據的一部分。如果在最後一次服藥後的某個時期我們看起來處於治療範圍內，也許這將是一個可行的策略，我們會考慮將其納入後續試驗。因此，PK 資料集中得出的數據確實非常重要。

Okay, great. Thanks. And latest thoughts on the Phase 2b study?

好的，太好了。謝謝。對第 2b 階段研究的最新想法是什麼？

Phase 2b study, yeah, we're going to have a Type C meeting with the FDA later this quarter. And so we would hope to be able to start the next -- Phase 2b study seems likely but we would look to start to that later in the year. Probably, fourth quarter would be the timing for that study.

是的，第 2b 階段研究，我們將在本季稍後與 FDA 舉行 C 類會議。因此，我們希望能夠開始下一階段的研究——第 2b 階段的研究似乎有可能，但我們希望在今年稍後開始。很可能第四季是進行此項研究的時間點。

Okay. Great, thanks. And if I could ask one more question, given the positive data you've already presented for both injectable and oral VK2735, what additional cards would you like to turnover before seeking a partner or potential strategic transaction?

好的。太好了，謝謝。如果我可以再問一個問題，鑑於您已經提供的注射和口服 VK2735 的積極數據，在尋求合作夥伴或潛在戰略交易之前，您還想交出哪些額外的牌？

Well, I think more data is always helpful to potential partners, but we don't view it as a gating for us to have meaningful conversations. And I'm not sure it's necessarily gating for others to have meaningful conversations with us. But generally, the larger partners like to see more data as programs evolve. But again, I don't think that's a mandatory requirement right now.

嗯，我認為更多的數據總是對潛在合作夥伴有幫助的，但我們不認為它會阻礙我們進行有意義的對話。而且我不確定這是否一定會阻礙其他人與我們進行有意義的對話。但一般來說，較大的合作夥伴希望隨著專案的發展看到更多的數據。但我仍然認為這目前並不是一項強制性要求。

Andrew Hsieh, William Blair.

安德魯謝、威廉布萊爾。

Great, guys. Thanks for taking our questions. So the first one I have is really on the potential framework for duration for the Phase 2 subcutaneous study maybe from two directions. One is really on maybe the GLP tox, maybe you can provide us with an update regarding how long you can dose this upcoming study based on all the GLP tox that you've done to date?

太棒了，夥計們。感謝您回答我們的問題。所以我的第一個問題其實是關於第二階段皮下研究持續時間的潛在框架，可能從兩個方向來考慮。一個可能是關於 GLP 毒性，也許您可以根據您迄今為止所做的所有 GLP 毒性，向我們提供有關您可以對即將進行的研究進行多長時間的更新信息？

And then secondarily -- it's mostly like a philosophical question on how you view the importance of seeing a pretty consistent plateauing, just to get the maximum weight loss data. Just in terms of derisking the program, is it important to see the plateauing?

其次，這更像是一個哲學問題，即您如何看待看到相當一致的平台期的重要性，以便獲得最大的減肥數據。僅從降低專案風險的角度來說，看到穩定期是否重要？

Yeah. Thanks, Andy. For the plateau, from what we've seen right now, the Phase 2b studies that were performed with semaglutide and tirzepatide had not plateaued prior to the registration studies being initiated. So it's hard to really know how the FDA will judge the assessment of a plateau when the currently approved drugs did not reach that in their Phase 2b studies. So that's one of the things we hope to learn a little bit about in the upcoming Type C meeting.

是的。謝謝，安迪。對於平台期，從我們目前看到的情況來看，使用 semaglutide 和 tirzepatide 進行的 2b 期研究在註冊研究開始之前尚未達到平台期。因此，當目前核准的藥物在其 2b 期研究中未達到平台期時，很難真正知道 FDA 將如何判斷平台期的評估。所以這是我們希望在即將召開的 C 類會議上了解的事情之一。

With the tox coverage, we're finished with the chronic tox. So we don't have a limitation toxicity wise or GLP tox study limitation on duration. So we could dose as long as we'd like. And I think, probably, six months or nine months would be the two most likely candidates for duration of the Phase 2b.

透過毒性覆蓋，我們已經完成了慢性毒性的處理。因此，我們沒有毒性限製或 GLP 毒性研究的持續時間限制。因此我們可以按照自己的意願服用任意劑量。我認為，第 2b 階段最有可能的持續時間是六個月或九個月。

Got it. That's helpful. Since we're talking about the upcoming discussion with the FDA, I'm just curious if you have any lingering questions or actually items, you'd like to discuss with the agency around midyear?

知道了。這很有幫助。既然我們正在談論即將與 FDA 進行的討論，我很好奇您是否還有任何疑問或實際事項想要在年中與該機構進行討論？

Well, we're not going to disclose the nature of the conversations, but we're interested in study design and duration and going back to your question about understanding the ideal duration prior to Phase 3. So those are those are our key questions.

好吧，我們不會透露談話的性質，但我們對研究設計和持續時間感興趣，回到你關於了解第三階段之前的理想持續時間的問題。這些都是我們的關鍵問題。

Got it. Okay. And lastly, the Gannex dispute, obviously, we're expecting NASH data coming up. So curious if there's any sort of procedural things that we should anticipate with the IP dispute there?

知道了。好的。最後，關於 Gannex 的爭議，顯然，我們期待 NASH 數據即將公佈。所以很好奇我們是否應該預見那裡的知識產權糾紛的一些程序性的事情？

Yeah. So we would expect a ruling on the dispute sometime this quarter, but hard to speculate since it's an ongoing litigation.

是的。因此，我們預計本季某個時候將對該爭議作出裁決，但由於這是一場正在進行的訴訟，因此很難猜測。

Steve Seedhouse, Raymond James.

史蒂夫西德豪斯、雷蒙德詹姆斯。

Hi, thank you. This is Nick on for Steve. We have a question related to Annabel's on manufacturing. Are you able to specify what materials or factors are most gaining to ramp up commercial supply of 2735? And would this only be a potential issue for the higher doses of the oral formulation? Thank you.

你好，謝謝。這是尼克，代替史蒂夫。我們有一個與 Annabel 的製造業相關的問題。您能否具體說明哪些材料或因素對增加 2735 的商業供應最有好處？這是否只是口服製劑較高劑量時的潛在問題？謝謝。

Yeah, I think it's an issue for all doses. When we look at the currently approved drugs, they're difficult to start because of shortages. So I think all doses, it's relevant to today.

是的，我認為這對所有劑量來說都是一個問題。看看目前批准的藥物，由於短缺，它們很難開始上市。所以我認為所有劑量都與今天相關。

With respect to overall, what is the -- where the greatest shortage, I mean, they're throughout the supply chain, solvents, whatever is needed for solid phase synthesis, fill and finish materials, so it's a pretty thorough shortfall right now. But again, we don't think that's going to be a terminal state for this class of compounds. When you look at the market opportunity, that incentive is pretty high to figure out these problems.

就總體而言，最嚴重的短缺是什麼？ 我的意思是，整個供應鏈中都存在短缺，溶劑、固相合成所需的一切，以及填充和完成材料，所以現在短缺的情況非常嚴重。但我們再次不認為這將成為該類化合物的終極狀態。當你看到市場機會時，解決這些問題的動機就會相當大。

(Operator Instructions) Thomas Smith, Leerink Partners.

(操作員指示)Thomas Smith，Leerink Partners。

Hey, guys. Good afternoon. Thanks for taking the questions. Just ahead of the VOYAGE study readout, can you remind us of what your expectations are on the two histology endpoints, fibrosis improvement, and NASH resolution? And can you comment on what data you expect to have available at the top line versus data sets that you expect to receive later or perhaps say for presentation at a medical meeting?

嘿，大家好。午安.感謝您回答這些問題。在 VOYAGE 研究數據公佈之前，您能否提醒我們您對兩個組織學終點、纖維化改善和 NASH 解決的期望是什麼？您能否評論一下，您期望在頂線獲得哪些數據，以及您期望稍後收到哪些數據集，或者可能在醫學會議上展示哪些數據集？

Yeah. Thanks, Tom. So on the hurdles, what we've always thought is if we can show a NASH resolution delta in that low- to mid-teens rate for treated versus placebo. And for the proportion of patients with a one-point improvement without worsening of NASH, similarly, low-double digits -- although with fibrosis, I would be -- I would not be expecting statistical significance just because the numbers are smaller. But those would be the key hurdles that we're looking for with the data set.

是的。謝謝，湯姆。因此，對於這些障礙，我們一直在思考的是，我們是否可以顯示治療組與安慰劑組相比在低至中等十幾歲比率上的 NASH 緩解差異。對於 NASH 沒有惡化、但有 1 分改善的患者比例，同樣，也是低兩位數（儘管患有纖維化，但我認為是這樣），我不會僅僅因為數字較小就期待統計意義。但這些正是我們在資料集中尋找的關鍵障礙。

With respect to what would be available and when, well, those are the primary components of the data that we'll receive. We will be receiving probably a little later data on paired biopsy reads, what -- is someone's NASH better, unchanged, or worse at the end of the treatment period, that kind of thing since those take a little bit longer to evaluate.

至於什麼時候可以提供什麼數據，嗯，這些就是我們將收到的數據的主要組成部分。我們可能稍後會收到配對活檢讀數的數據，例如某人的 NASH 在治療期結束時是好轉、不變還是惡化，諸如此類的事情，因為這些需要更長的時間來評估。

Understood. That's helpful. And then just for oral 2735, can you just clarify, do you expect to report data from the ongoing higher-dose cohort once that's available? Or is it possible that you could had some additional higher dose cohorts before we see any incremental data from the study?

明白了。這很有幫助。然後僅針對口服 2735，您能否澄清一下，您是否希望在獲得正在進行的高劑量組數據後報告數據？或者，在我們看到研究的任何增量數據之前，是否有可能您可以進行一些額外的更高劑量組？

Probably more the latter. So we don't just kind of drip data out. We would probably want to report what we have when the study is completed rather than cohort by cohort.

或許後者更多。所以我們並不是只是簡單地輸出資料。我們可能希望在研究完成時報告我們的研究成果，而不是逐批報告。

Yale Jen, Laidlaw & Co.

耶魯仁萊德勞公司

Good afternoon and thanks for taking the questions. Brian, you're talking about that 2735 later on will be presented at the medical conferences. Just curious anything in mind at this point that you are thinking.

下午好，感謝您回答問題。布萊恩，您說的是 2735 稍後將在醫學會議上展示。只是好奇您此時心裡在想什麼。

Yeah. Thanks, Yale. Last year, we presented the Phase 1 data at Obesity Week and so that would seem like a good candidate. We haven't submitted anything but that would seem like a good candidate for data presentation.

是的。謝謝，耶魯。去年，我們在肥胖週上展示了第一階段的數據，所以這似乎是一個很好的候選人。我們尚未提交任何內容，但這似乎是資料呈現的一個很好的候選人。

Okay, that's helpful. And a follow-up question here is that for the subcu version, do you think that here one is the auto injector? Are you guys already working on that? And secondly, is that -- do you anticipate any kind of bridging PK study in between before you're heading to a more pivotal study?

好的，這很有幫助。這裡的後續問題是，對於 subcu 版本，您認為這裡有一個自動注射器嗎？你們已經開始做這件事了嗎？其次，在進行更關鍵的研究之前，您是否預期會進行任何類型的橋接 PK 研究？

Yeah, great question, Yale. We will be using the pen-type device, and we would hope that's available prior to initiation of the next clinical study. But we're not going to let that be a gating factor. So if the device is not ready, we would plan to start the study with vial and syringe and then transition on to the auto-injector.

是的，耶魯大學提出這個問題，非常好。我們將使用筆型設備，我們希望它能夠在下一次臨床研究開始之前投入使用。但我們不會讓其成為限制因素。因此，如果設備尚未準備好，我們計劃先使用小瓶子和注射器開始研究，然後過渡到自動注射器。

But do you anticipate at one point, even -- whether you start earlier, before that, or later, that you need a bridging study for that? Or do you think that PK data could be supportive?

但是，您是否預料到，在某個時候——無論您是在此之前、之前還是之後開始，您都需要為此進行一項銜接研究？或者您認為 PK 數據能夠提供支援？

Well, no, I don't think we would need a bridging study at this point. That's not we're contemplating. I mean, if we have to do one, we would, but I don't think that's going to be requirement. We would transition people.

嗯，不，我認為我們現在不需要進行橋接研究。這不是我們正在考慮的。我的意思是，如果我們必須做一件事，我們會這麼做，但我不認為這會是要求。我們會使人轉變。

Okay, great. Thanks. And congrats on progress this quarter.

好的，太好了。謝謝。並祝賀本季取得的進展。

Thanks a lot, Yen.

非常感謝，Yen。

Justin Zelin, BTIG.

BTIG 的賈斯汀·澤林 (Justin Zelin)。

Thanks for taking the questions and congrats on the progress. Brian, you just mentioned -- for the VOYAGE study for fibrosis, you mentioned that there might be a few patients here. And can you just remind us if the study is powered to show a difference in fibrosis in the study? And I have a follow-up.

感謝您回答問題，並祝賀您的進展。布萊恩，您剛才提到—對於纖維化的 VOYAGE 研究，您提到這裡可能有幾個患者。您能否提醒我們一下，這項研究是否有能力顯示研究中纖維化的差異？我還有一個後續問題。

Yeah. Thanks, Justin. It wasn't powered on fibrosis. It was powered on NASH resolution rates, and I'm not sure we ever disclosed the power. It's in the 80% range to show approximately a 20% delta on NASH resolution. But it was not designed around fibrosis, since that generally requires quite a bit larger end than we have in this study.

是的。謝謝，賈斯汀。它不是由纖維化提供動力的。它的動力來自 NASH 解決率，我不確定我們是否曾經揭露過這種動力。它在 80% 的範圍內，顯示 NASH 解析度大約有 20% 的增量。但它不是圍繞著纖維化設計的，因為這通常需要比我們在本研究中更大的末端。

Understood. That's helpful. And maybe I'll ask you -- I don't think any others have asked yet. Just expectations on 0214 for X-ALD, what would be a success here in your view for the Phase 1b?

明白了。這很有幫助。也許我會問你——我想還沒有其他人問過。只是對 X-ALD 0214 的期望，您認為第 1b 階段的成功是什麼？

Yeah, yeah. So we have previously shown with that compound somewhere in the in the 20% range on LDL reduction and in the 20% range for ApoB and [in LipoA]. So we know it's effective at lipid reduction. And we also looked at very long chain fatty acids in the healthy volunteers. It's kind of tough to look because they're healthy volunteers. They don't really have abnormalities and very long chain fatty acids, but we did see some reductions in very long-chain fatty acids in the prior Phase 1 experience.

是啊是啊。因此，我們先前已經證明，該化合物可以降低 LDL 約 20%，降低 ApoB 約 20%。[在 LipoA 中]。所以我們知道它能有效降低脂質。我們也觀察了健康志願者體內的長鏈脂肪酸。由於他們都是健康的志願者，所以看起來有點難以接受。它們實際上並沒有異常和極長鏈脂肪酸，但我們在先前的第 1 階段經驗中確實看到極長鏈脂肪酸減少。

So if we can see somewhere in the mid- to high-teens on the very long chain fatty acid reduction, that would be pretty interesting. Hopefully, more than that, but that would be probably the gating factor to consider further development in X-linked adrenoleukodystrophy.

因此，如果我們能夠看到長鏈脂肪酸的減少量達到中高水平，那將會非常有趣。希望不止於此，但這可能是考慮 X 連鎖腎上腺腦白質營養不良進一步發展的限制因素。

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。我想將會議交還給史蒂芬妮·迪亞茲，請她作最後發言。

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。我們期待在接下來的幾個月中再次為您更新。祝您下午愉快。

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

會議現已結束。感謝您參加今天的演講。您現在可以斷開連線。