Viking Therapeutics Inc (VKTX) 2024 Q3 法說會逐字稿

Welcome to the Viking Therapeutics third-quarter 2024 financial results conference call. (Operator Instructions) As a reminder, this conference is being recorded today, October 23, 2024.

歡迎參加 Viking Therapeutics 2024 年第三季財務業績電話會議。 （操作員說明）謹此提醒，本次會議將於今天（2024 年 10 月 23 日）進行錄製。

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

現在我想將會議轉交給 Viking 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。今天加入我的是 Viking 總裁兼執行長 Brian Lian；格雷格·贊特 (Greg Zante)，Viking 的財務長。

Before we begin, I'd like to caution that comments made during this conference call today, October 23, 2024, 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，我想提醒大家，在今天（2024 年10 月23 日）的電話會議上發表的評論將包含1995 年美國私人證券訴訟改革法案安全港條款下的前瞻性聲明，包括有關Viking 的聲明關於其開發活動、時間表和里程碑的期望。前瞻性陳述存在風險和不確定性，可能導致實際結果出現重大和不利的差異，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. I'll now turn the call over to Brian Lian for his initial comments.

這些前瞻性陳述僅代表今天的情況，本公司不承擔修改或更新今天所做的任何陳述的義務。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及其他事項的所有文件。我現在將把電話轉給 Brian Lian，徵求他的初步意見。

Thanks, Stephanie, and good afternoon to everyone listening in by phone or on the webcast. Today, we'll review our financial results for the three and nine months ended September 30, 2024, and provide an update on recent progress with our clinical programs and operations.

謝謝斯蒂芬妮，祝所有透過電話或網路廣播收聽的人下午好。今天，我們將回顧截至 2024 年 9 月 30 日的三個月和九個月的財務業績，並提供我們臨床計畫和營運的最新進展。

The first three quarters of 2024 have been data-rich for Viking, with the company delivering positive data from four clinical programs as well as promising in vivo data from a new preclinical program. Beginning in the first quarter, we announced positive results from the Phase 2 VENTURE trial evaluating subcutaneous VK2735 for the treatment of obesity. This trial demonstrated impressive reductions in body weight after 13 weeks of treatment.

2024 年前三個季度對 Viking 來說數據豐富，該公司提供了四個臨床項目的積極數據以及新的臨床前項目的有希望的體內數據。從第一季開始，我們宣布了評估皮下注射 VK2735 治療肥胖的 2 期 VENTURE 試驗的正面結果。該試驗表明，經過 13 週的治療後，體重明顯下降。

We also announced the initial results from a 28-day Phase 1 trial, evaluating a novel oral formulation of this compound, showing excellent tolerability and encouraging reductions in body weight. During the second quarter, the company announced histology results from the Phase 2b VOYAGE study evaluating VK2809 for the treatment of NASH and fibrosis. This study successfully achieved its primary secondary and exploratory endpoints, showing reductions in liver fat at 12 weeks, an improvement in NASH resolution rate and fibrosis after two weeks.

我們也發表了為期 28 天的 1 期試驗的初步結果，評估了該化合物的新型口服製劑，顯示出優異的耐受性並令人鼓舞地減輕體重。第二季度，該公司公佈了 2b 期 VOYAGE 研究的組織學結果，該研究評估 VK2809 治療 NASH 和纖維化的作用。該研究成功實現了其主要次要和探索性終點，顯示 12 週時肝臟脂肪減少，兩週後 NASH 緩解率和纖維化有所改善。

Also during the second quarter, Viking announced in vivo results from a series of internally developed dual agonist of the amylin and calcitonin receptors. These compounds demonstrated body weight reductions, decreased food intake and improved metabolic profile in animal models.

同樣在第二季度，Viking 宣布了一系列內部開發的胰淀素和降鈣素受體雙重激動劑的體內結果。這些化合物在動物模型中顯示出體重減輕、食物攝取量減少和代謝狀況改善。

Finally, subsequent to the end of the third quarter, we announced positive results from a 28-day Phase 1b trial of VK0214 in patients with X-linked adrenoleukodystrophy or X-ALD. Results from this study showed VK0214 to be safe and well tolerated following once-daily oral dosing over the 28-day treatment period. In addition, significant reductions were observed in plasma levels of very long chain fatty acids and other lipids as compared to placebo.

最後，在第三季末之後，我們宣布了 VK0214 在 X 連鎖腎上腺腦白質營養不良或 X-ALD 患者中進行的為期 28 天的 1b 期試驗的積極結果。這項研究的結果表明，在 28 天的治療期內，每日口服一次 VK0214 是安全且耐受性良好的。此外，與安慰劑相比，觀察到極長鏈脂肪酸和其他脂質的血漿水平顯著降低。

We are proud of the clinical progress we've made this year and look forward to further advancement of our pipeline programs in the quarters ahead. I'll have additional comments on our operations and development activities after we review our financial results for the third quarter and nine months ending September 30.

我們對今年的臨床進展感到自豪，並期待在未來幾季進一步推進我們的管道項目。在我們審查第三季和截至 9 月 30 日的九個月的財務業績後，我將對我們的營運和開發活動發表更多評論。

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

為此，我將把電話轉給 Viking 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 Viking 向美國證券交易委員會提交的 10-Q 表格，我們預計將在今天晚些時候提交該文件。

I'll now go over our results for the third quarter and nine months ended September 30, 2024, beginning with the results for the quarter. Research and development expenses were $22.8 million for the three months ended September 30, 2020, compared to $18.4 million for the same period in 2023. The increase was primarily due to increased expenses related to manufacturing for the company's drug candidates, stock-based compensation, salaries, and benefits and regulatory services, partially offset by decreased expenses related to preclinical studies and clinical studies.

我現在將回顧我們第三季和截至 2024 年 9 月 30 日的九個月的業績，從本季的業績開始。截至 2020 年 9 月 30 日的三個月，研發費用為 2,280 萬美元，而 2023 年同期為 1,840 萬美元。部分被臨床前研究和臨床研究相關費用的減少所抵銷。

General and administrative expenses were $13.8 million for the three months ended September 30, 2024, compared to $8.9 million for the same period in 2023. The increase was primarily due to increased expenses related to stock-based compensation, legal and patent services, services provided by third-party consultants and insurance.

截至2024 年9 月30 日的三個月，一般及行政費用為1,380 萬美元，而2023 年同期為890 萬美元。費用增加由第三方顧問和保險。

For the three months ended September 30, 2024, Viking reported a net loss of $24.9 million or $0.22 per share compared to a net loss of $22.5 million or $0.23 per share in the corresponding period in 2023. The increase in net loss for the three months ended September 30, 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9 月30 日的三個月，維京報告淨虧損2,490 萬美元，即每股0.22 美元，而2023 年同期淨虧損為2,250 萬美元，即每股0.23 美元。增加截至2024年9月30日，主要是由於先前提到的研發費用以及一般和管理費用的增加，部分被利息收入與2023年同期相比的增加所抵消。

I'll now go over our results for the 9 months ended September 30, 2024.

現在我將回顧截至 2024 年 9 月 30 日的 9 個月的表現。

Our research and development expenses for the nine months ended September 30, 2024, were $70.7 million compared to $43.3 million for the same period in 2023. The increase was primarily due to increased expenses related to manufacturing for our drug candidates, clinical studies, stock-based compensation, preclinical studies and salaries and benefits.

截至2024 年9 月30 日的九個月，我們的研發費用為7,070 萬美元，而2023 年同期為4,330 萬美元。增加。

Our general and administrative expenses for the nine months ended September 30, 2024, were $34 million compared to $28.2 million for the same period in 2023. The increase was primarily due to increased expenses related to stock-based compensation, salaries and benefits, services provided by third-party consultants and insurance, partially offset by decreased expenses related to legal and patent services.

截至2024 年9 月30 日的九個月，我們的一般和管理費用為3,400 萬美元，而2023 年同期為2,820 萬美元。的費用增加第三方顧問和保險費用的增加，部分被法律和專利服務相關費用的減少所抵銷。

For the nine months ended September 30, 2024, Viking reported a net loss of $74.5 million or $0.69 per share compared to a net loss of $61.3 million or $0.66 per share in the corresponding period in 2023.

截至 2024 年 9 月 30 日的九個月，Viking 報告淨虧損 7,450 萬美元，即每股 0.69 美元，而 2023 年同期淨虧損為 6,130 萬美元，即每股 0.66 美元。

The increase in net loss for the nine months ended September 30, 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9月30日的九個月淨虧損增加，主要是由於前面提到的研發費用以及一般和管理費用的增加，部分被利息收入與2023年同期相比的增加所抵銷。

Turning to the balance sheet. At September 30, 2024, Viking held cash, cash equivalents and short-term investments of $930 million compared to $362 million as of December 31, 2023.

轉向資產負債表。截至2024年9月30日，Viking持有現金、現金等價物及短期投資為9.3億美元，截至2023年12月31日為3.62億美元。

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. I'll now provide a summary of recent clinical highlights and outline next steps with our pipeline programs. I'll begin with Viking's lead obesity program, VK2735, a dual agonist of the glucagon-like peptide 1, or GLP-1 receptor and the glucose-dependent insulin atrophic polypeptide, or GIP receptor.

謝謝，格雷格。現在，我將總結最近的臨床亮點，並概述我們的管道計劃的後續步驟。我將從 Viking 的主要肥胖項目 VK2735 開始，它是胰高血糖素樣肽 1（或 GLP-1 受體）和葡萄糖依賴性胰島素萎縮性多肽（或 GIP 受體）的雙重激動劑。

The company's initial Phase 1 single and multiple ascending dose trial for this compound demonstrated the promising safety, tolerability and pharmacokinetics of VK2735 when administered as a weekly subcutaneous injection for up to four weeks. Subjects in the study demonstrated up to approximately 8% weight loss from baseline after 28 days with no signs of plateau.

該公司對該化合物的初步 1 期單次和多次遞增劑量試驗證明，當每週皮下注射給藥長達四週時，VK2735 具有良好的安全性、耐受性和藥物動力學。研究中的受試者在 28 天後體重較基線減輕了約 8%，且沒有出現平台期跡象。

Following these results, the company initiated a Phase 2 study of VK2735, known as the VENTURE trial. This trial was a randomized, double-blind, placebo-controlled multicenter study that evaluated the safety, tolerability, pharmacokinetics and weight loss efficacy of VK2735, administered subcutaneously once weekly for 13 weeks. In the first quarter of this year, Viking announced positive top line results from the VENTURE study.

根據這些結果，該公司啟動了 VK2735 的第二階段研究，即 VENTURE 試驗。該試驗是一項隨機、雙盲、安慰劑對照的多中心研究，評估了 VK2735 的安全性、耐受性、藥物動力學和減肥功效，每週皮下注射一次，持續 13 週。今年第一季度，Viking 宣布了 VENTURE 研究的正面頂線結果。

With respect to the study's primary endpoint, patients receiving VK2735 demonstrated statistically significant reductions in mean body weight from baseline, ranging up to 14.7%. Statistically significant differences compared to placebo were also observed for all VK2735 doses starting at week 1 and maintained throughout the course of the study.

關於研究的主要終點，接受 VK2735 治療的患者的平均體重較基線出現統計顯著下降，幅度高達 14.7%。從第 1 週開始，所有 VK2735 劑量與安慰劑相比也觀察到統計學上的顯著差異，並在整個研究過程中保持差異。

Weight loss in all treated cohorts was progressive through 13 weeks and did not show evidence of plateauing, suggesting that further weight loss could potentially be achieved through extended dosing beyond the 13-week period of this study. Regarding safety and tolerability, VK2735 was shown 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, generally occurring early in the course of treatment, and primarily related to expected GI effects resulting from activation of the GLP-1 receptor.

所有治療組的體重減輕在 13 週內都在進展，並且沒有顯示出平台期的證據，這表明透過在本研究的 13 週之後延長給藥時間，有可能實現進一步的體重減輕。關於安全性和耐受性，VK2735 在為期13 週的試驗中被證明是安全的且耐受性良好，大多數治療中出現的不良事件被描述為輕度或中度，通常發生在治療過程的早期，並且主要與預期相關GLP-1 受體活化導致胃腸道效應。

This summer, we submitted an abstract describing the results of the VENTURE study for presentation at the Annual Meeting of the Obesity Society, also known as ObesityWeek. The results will be highlighted in a poster session at the conference scheduled for the evening of November 3. Following completion of the VENTURE study, we requested a Type C meeting with the FDA to help us plan for next steps in the development of VK2735.

今年夏天，我們提交了一份描述 VENTURE 研究結果的摘要，並在肥胖協會年會（也稱為肥胖週）上進行展示。結果將在定於 11 月 3 日晚舉行的會議的海報會議上重點介紹。

Based on written feedback from the agency, we intend to advance VK2735 into Phase 3 development for obesity. To this end, we have scheduled an end of Phase 2 meeting with the agency later this quarter, which will serve to inform our next steps in the Phase 3 plan for the program.

根據該機構的書面回饋，我們打算將 VK2735 推進到肥胖症的 3 期開發。為此，我們計劃在本季稍後與該機構舉行第二階段會議，這將為我們該計劃第三階段計劃的下一步行動提供資訊。

Concurrent with the execution of the VENTURE trial for subcutaneous VK2735, Viking also conducted a Phase 1 study to evaluate an oral tablet formulation. The company believes the tablet formulation could represent an attractive treatment option for patients who are hesitant to initiate injection-based therapy or for those seeking to maintain the weight loss they have already achieved. A key advantage in this regard is the potential to transition patients from the subcutaneous formulation to an oral formulation, which utilizes the same molecule.

在進行皮下注射 VK2735 的 VENTURE 試驗的同時，Viking 也進行了一項 1 期研究來評估口服片劑配方。該公司認為，對於那些對開始注射療法猶豫不決的患者或那些尋求維持已實現的減肥效果的患者來說，片劑配方可能是一種有吸引力的治療選擇。在這方面的一個關鍵優勢是有可能將患者從皮下製劑轉變為使用相同分子的口服製劑。

Viking believes this may reduce the risk of unexpected safety or tolerability challenges and could be an attractive option for both patients and clinicians. The Phase 1 study was a randomized, double-blind, placebo-controlled study in healthy adults with a minimum body mass index of 30 kilograms per meter squared. The primary objective was to evaluate the safety and tolerability of VK2735 administered as a tablet once daily for 28 days.

Viking 認為，這可能會降低意外安全性或耐受性挑戰的風險，並且對於患者和臨床醫生來說可能是一個有吸引力的選擇。第一階段研究是一項隨機、雙盲、安慰劑對照研究，對像是體重指數最低為每平方公尺 30 公斤的健康成年人。主要目的是評估 VK2735 片劑的安全性和耐受性，每天一次，持續 28 天。

Secondary and exploratory objectives include an evaluation of the pharmacokinetics of oral VK2735 as well as changes in body weight and other metrics. In the first quarter, we reported the initial data from this study which demonstrated that VK2735 was safe and well tolerated following once-daily oral dosing for up to 28 days at doses of up to 40 milligrams.

次要和探索性目標包括評估口服 VK2735 的藥物動力學以及體重和其他指標的變化。在第一季度，我們報告了這項研究的初步數據，該數據表明，在每日一次口服劑量高達 40 毫克、持續長達 28 天后，VK2735 是安全且耐受性良好的。

Among subjects receiving VK2735, all treatment-emergent adverse events were reported as mild or moderate in severity with the majority reported as mild. No clinically meaningful differences were reported for gastrointestinal adverse events among subjects treated with VK2735 compared with placebo. In addition, patients receiving oral VK2735 demonstrated dose-dependent reductions in body weight, reaching up to approximately 5.3% from baseline.

在接受 VK2735 治療的受試者中，所有治療引起的不良事件的嚴重程度均報告為輕度或中度，其中大多數報告為輕度。與安慰劑相比，接受 VK2735 治療的受試者中胃腸道不良事件未報告有臨床意義的差異。此外，接受口服 VK2735 治療的患者表現出劑量依賴性體重減輕，較基線降低約 5.3%。

Weight loss over the 28-day window of this study was progressive at the 20-milligram and 40-milligram dose levels with no plateau observed. Given the promising weight loss all observed, along with the excellent tolerability profile at doses of up to 40 milligrams per day, the company elected to continue dose escalation at doses of 60 milligrams, 80 milligrams and 100 milligrams per day.

在本研究的 28 天窗口內，20 毫克和 40 毫克劑量水平的體重減輕是漸進的，沒有觀察到平台期。鑑於所有觀察到的有希望的減肥效果，以及每天高達 40 毫克劑量的出色耐受性，該公司選擇繼續以每天 60 毫克、80 毫克和 100 毫克的劑量遞增劑量。

As with the VENTURE Phase 2 study results, we submitted a late-breaking abstract describing the Phase 1 trial for presentation at the ObesityWeek conference. This submission was accepted for poster presentation, which is scheduled for the evening of November 3. As the next step, we plan to initiate a 13-week Phase 2 study in obesity later this year.

與 VENTURE 2 期研究結果一樣，我們提交了一份描述 1 期試驗的最新摘要，以便在 ObesityWeek 會議上展示。該提交內容已被接受進行海報展示，海報展示時間定於 11 月 3 日晚間。

We'll provide details regarding study design as we get closer to trial initiation. I'll now turn to VK2809, Viking's 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.

當我們接近試驗啟動時，我們將提供有關研究設計的詳細資訊。我現在談談 VK2809，這是 Viking 的口服小分子甲狀腺激素受體激動劑，該受體被選用於肝組織以及該受體的 β 亞型。

During the second quarter, we announced positive histology results from the 52-week Phase 2b VOYAGE study of VK2809 in patients with NASH and fibrosis. This study was 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.

在第二季度，我們宣布了 VK2809 在 NASH 和纖維化患者中進行的為期 52 週的 2b 期 VOYAGE 研究的積極組織學結果。該研究是一項隨機、雙盲、安慰劑對照的多中心國際試驗，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。

Last year, Viking announced the initial data from VOYAGE, reporting that the study had successfully achieved its primary end point with patients receiving VK2809 demonstrating statistically significant reductions in liver fat content from baseline to week 12 as compared with placebo.

去年，Viking 公佈了 VOYAGE 的初步數據，報告稱該研究已成功實現其主要終點，接受 VK2809 治療的患者與安慰劑相比，肝臟脂肪含量從基線到第 12 週出現了統計上顯著的降低。

In June of this year, Viking announced the successful achievement of the trial's secondary endpoints evaluating histologic changes assessed by hepatic biopsy after 52 weeks of treatment. The histology results showed that patients receiving VK2809 experienced clinically and statistically significant improvements in NASH resolution rate, fibrosis stage and the combination endpoint of NASH resolution and fibrosis improvement.

今年 6 月，Viking 宣布成功實現了該試驗的次要終點，該終點評估了治療 52 週後透過肝臟活檢評估的組織學變化。組織學結果顯示，接受 VK2809 治療的患者在 NASH 消退率、纖維化階段以及 NASH 消退和纖維化改善的組合終點方面經歷了臨床和統計學上的顯著改善。

On the endpoint of NASH resolution without worsening of fibrosis, VK28090- patients demonstrated resolution rates ranging from 63% to 75% compared with 29% for placebo. On the secondary endpoint evaluating the proportion of patients demonstrating at least a one-stage improvement in fibrosis with no worsening of NASH. The proportion of VK2809-treated patients achieving this endpoint range from 44% to 57%, compared with 34% for placebo.

在 NASH 消退且纖維化未惡化的終點上，VK28090 患者的消退率範圍為 63% 至 75%，而安慰劑組為 29%。次要終點評估纖維化至少出現一階段改善且 NASH 未惡化的患者比例。接受 VK2809 治療的患者達到此終點的比例為 44% 至 57%，而安慰劑組為 34%。

On the secondary endpoint evaluating the proportion of patients experiencing both the resolution of NASH and at least a 1-stage improvement in fibrosis. The proportion of VK2809-treated patients achieving both measures ranged from 40% to 50% compared with 20% for placebo.

次要終點評估 NASH 消退和纖維化至少 1 階段改善的患者比例。接受 VK2809 治療的患者達到這兩項指標的比例為 40% 至 50%，而安慰劑組為 20%。

VK2809 also demonstrated an encouraging safety and tolerability profile through 52 weeks of treatment with minimal differences reported when compared to the previous results from week 12. The majority of treatment-related adverse events among patients receiving VK2809 were reported as mild or moderate.

VK2809 在52 週的治療中也表現出令人鼓舞的安全性和耐受性，與先前第12 週的結果相比，報告的差異很小。事件報告為輕度或中度。

VK2809 also demonstrated excellent gastrointestinal tolerable through 52 weeks of treatment with similar rates of nausea, diarrhea, stool frequency and vomiting reported for VK2809 treated patients as compared to placebo. Earlier this fall, we submitted the results of the VOYAGE study for presentation at the 2024 Annual Meeting of the American Association for the Study of Liver Disease or AASLD in November. These results have been accepted for an oral presentation, which is scheduled for November 19.

在 52 週的治療中，VK2809 也表現出優異的胃腸道耐受性，與安慰劑相比，VK2809 治療患者的噁心、腹瀉、大便頻率和嘔吐發生率相似。今年秋天早些時候，我們提交了 VOYAGE 研究結果，以便在 11 月舉行的美國肝病研究協會 (AASLD) 2024 年年會上進行展示。這些結果已被接受進行口頭報告，定於 11 月 19 日進行。

In addition, earlier this quarter, we submitted an end of Phase 2 meeting package to the FDA regarding a proposed Phase 3 study plan for VK2809. Earlier this week, we received written responses from the agency, and we are in the process of reviewing them and evaluating next steps for the program. Turning now to our fourth clinical program. we recently reported the results from a 28-day Phase 1b trial of our small molecule drug candidate, VK0214 in patients with the rare neuromuscular disorder called X-linked adrenoleukodystrophy or X-ALD. Like VK2809, VK0214 is an orally available small molecule that is selected for the beta isoform of the thyroid hormone receptor.

此外，本季度早些時候，我們向 FDA 提交了關於 VK2809 擬議的 3 期研究計劃的 2 期結束會議包。本週早些時候，我們收到了該機構的書面回复，我們正在對其進行審查並評估該計劃的後續步驟。現在轉向我們的第四個臨床項目。我們最近報告了我們的小分子候選藥物 VK0214 在患有罕見神經肌肉疾病（稱為 X 連鎖腎上腺腦白質營養不良或 X-ALD）患者中進行的為期 28 天的 1b 期試驗的結果。與 VK2809 一樣，VK0214 是一種口服小分子，針對甲狀腺激素受體的 β 異構體進行選擇。

X-ALD is a rare and debilitating metabolic disorder that is caused by genetic mutations that disable the function of peroxisomal transporter of very long chain fatty acids. As a result, patients are unable to efficiently metabolize these assets and their accumulation 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性疾病，由基因突變導致超長鏈脂肪酸過氧化物酶體轉運蛋白功能喪失而引起。因此，患者無法有效地代謝這些物質，並且它們的累積被認為有助於 X-ALD 的發病和進展。

Our Phase 1b trial was a multicenter, randomized, double-blind, placebo-controlled international study in adult male patients with the adrenomyeloneuropathy or AMN form of X-ALD. The study enrolled patients across 3 cohorts. Placebo and VK0214 doses of 20 grams and 40 milligrams daily.

我們的 1b 期試驗是一項多中心、隨機、雙盲、安慰劑對照的國際研究，對像是患有腎上腺脊髓神經病變或 AMN 型 X-ALD 的成年男性患者。該研究招募了 3 個隊列的患者。安慰劑和 VK0214 劑量分別為每天 20 克和 40 毫克。

The primary objectives were to evaluate the safety and tolerability of VK0214 in subjects with AMN. Exploratory objective was to evaluate the effects of VK0214 and plasma levels of very long-chain fatty acids in this population. Results from this study showed VK0214, safe and well tolerated following once-daily oral dosing over the 28-day treatment period.

主要目標是評估 VK0214 在 AMN 受試者中的安全性和耐受性。探索性目標是評估 VK0214 和極長鏈脂肪酸血漿水平對該族群的影響。這項研究的結果表明，在 28 天的治療期內，每天口服一次 VK0214 是安全且耐受性良好的。

In addition, significant reductions were observed in plasma levels of very long chain fatty acids and other lipids compared to placebo. Treatment with VK0214 resulted in significant reductions in mean very long chain fatty acid levels at both the 20-milligram and 40-milligram doses compared to this now.

此外，與安慰劑相比，觀察到極長鏈脂肪酸和其他脂質的血漿水平顯著降低。與現在相比，20 毫克和 40 毫克劑量的 VK0214 治療均導致平均極長鏈脂肪酸水平顯著降低。

Plasma levels of the important 26 carbon very long chain fatty acid will reduce by approximately 38% relative to placebo. In addition, subjects who received BK0214 experienced reductions in other important plasma lipids. Mean reductions relative to baseline and placebo were observed for LDL-cholesterol apolipoprotein B and lipoprotein A following 28 days of treatment. In this study, VK0214 demonstrated encouraging safety and tolerability with treatment-emergent adverse events generally reported as mild to moderate. We are very pleased with the outcome of this study.

與安慰劑相比，重要的 26 碳超長鏈脂肪酸的血漿濃度將降低約 38%。此外，接受 BK0214 治療的受試者的其他重要血漿脂質也有所降低。治療 28 天后，觀察到 LDL-膽固醇載脂蛋白 B 和脂蛋白 A 相對於基線和安慰劑的平均降低。在這項研究中，VK0214 表現出令人鼓舞的安全性和耐受性，治療中出現的不良事件通常報告為輕度至中度。我們對這項研究的結果非常滿意。

We're continuing to receive data from the study and will determine next steps for the program following a review of the complete data. Finally, as we move forward with our clinical programs, we're fortunate to have a strong balance sheet providing the runway to execute on key clinical objectives with each program.

我們將繼續接收該研究的數據，並將在審查完整數據後確定該計劃的後續步驟。最後，當我們推進臨床項目時，我們很幸運擁有強大的資產負債表，為每個項目的關鍵臨床目標的執行提供了基礎。

In conclusion, 2024 has been an exciting year for Viking as we have delivered positive results from four clinical programs: trials for subcutaneous VK2735 oral VK2735, VK2809 and VK0214, each successfully achieved their study endpoints. In addition to executing these programs, we continue to explore new opportunities with innovative pilot programs.

總之，2024 年對Viking 來說是令人興奮的一年，因為我們從四個臨床計畫中取得了積極的成果：皮下注射VK2735、口服VK2735、VK2809 和VK0214 的試驗，每個計畫都成功實現了其研究終點。除了執行這些計劃外，我們還繼續透過創新試點計劃探索新的機會。

To that end, Viking recently announced a new internally developed amylin agonist program for the treatment of obesity.

為此，Viking 最近宣布了一項新的內部開發的胰淀素激動劑計劃，用於治療肥胖症。

We are excited about the potential for this new program and look forward to sharing updates as it advances. Looking ahead with respect to our obesity programs, for subcutaneous VK2735, we're actively preparing for an end of Phase 2 meeting with the FDA, which will take place later this quarter following which we plan to initiate a Phase 3 study.

我們對這個新計劃的潛力感到興奮，並期待隨著它的進展分享最新資訊。展望我們的肥胖計劃，對於皮下注射 VK2735，我們正在積極準備與 FDA 舉行的第 2 階段會議，會議將於本季度晚些時候舉行，隨後我們計劃啟動第 3 階段研究。

For oral VK2735, we are preparing to present additional data at ObesityWeek next month, and we plan to initiate a 13-week Phase 2 study later this year. With respect to VK2809, for the treatment of NASH and fibrosis, we are evaluating next steps following our recent receipt of written responses to an end of Phase 2 meeting with the FDA regarding the registration path for this program.

對於口服 VK2735，我們準備在下個月的 ObesityWeek 上提供更多數據，並計劃在今年稍後啟動一項為期 13 週的 2 期研究。至於 VK2809，用於治療 NASH 和纖維化，我們正在評估後續步驟，因為我們最近收到了針對該計畫註冊路徑的第二階段會議結束時與 FDA 的書面答覆。

With our small molecule VK0214 or X-ALD, we await final data from this program and we'll decide next steps once we had a chance to review the full data package.

對於我們的小分子 VK0214 或 X-ALD，我們正在等待該計劃的最終數據，一旦我們有機會審查完整的數據包，我們將決定下一步的步驟。

Finally, with $930 million in cash and equivalents at the end of the third quarter, we believe we have the financial resources required to reach clinical milestones for each of our programs, and we look forward to reporting further progress in the quarters ahead. This concludes our prepared comments for today.

最後，截至第三季末，我們擁有 9.3 億美元的現金和等價物，我們相信我們擁有實現每個專案臨床里程碑所需的財務資源，我們期待在未來幾季報告進一步的進展。我們今天準備的評論到此結束。

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

非常感謝您加入我們，我們現在開始提問。操作員？

(Operator Instructions) Joon Lee, Truist.

（操作員指示）Joon Lee，真理論者。

Regarding the end of Phase 2 meeting for the subcu VK2735 in this quarter, what are some things you'd like to iron out with the FDA? And how quickly would you be able to start Phase 3 after that? And also as a quick follow-up, is your amylin agonist DACRA? Or is it just semantics, what you call it? And how are you benchmarking your agonist vis-a-vis what's out there, whether it's called amylin agonist or DACRA?

關於 subcu VK2735 第 2 階段會議將於本季結束，您希望與 FDA 解決哪些問題？之後您能多快開始第三階段？另外，作為快速跟進，您的胰淀素激動劑 DACRA 是嗎？或者這只是語義，你怎麼稱呼它？您如何將您的激動劑與現有藥物（無論是胰淀素激動劑還是 DACRA）進行比較？

Yes. Thanks, Joon. With the amylin agonist jazz, it is also hitting calcitonin. So it's a dual amylin and calcitonin receptor agonist. And we generally benchmark against known amylin agonists.

是的。謝謝，瓊。隨著胰淀素激動劑爵士樂的出現，它也打擊降鈣素。所以它是一種胰島澱粉樣多勝肽和降鈣素受體雙重激動劑。我們通常以已知的胰淀素激動劑為基準。

We use pramlintide, we use cagrilintide. So we generally use compounds that are sort of the bellwethers as far as mechanism. With respect to the end of Phase 2 meeting with FDA, it's -- we will review the proposed protocol, the proposed doses, the proposed trial size, all of those things. And then try and understand if there's anything that we overlooked or anything that the FDA recommends to include in the study. So just a little feedback on the proposed trial designs.

我們使用普蘭林肽，我們使用卡格林肽。因此，我們通常使用在機制方面屬於領頭羊的化合物。關於與 FDA 的第二階段會議結束，我們將審查擬議的方案、擬議的劑量、擬議的試驗規模，所有這些事情。然後嘗試了解是否有任何我們忽略的內容或 FDA 建議納入研究的內容。所以只是對擬議的試驗設計的一點回饋。

Annabel Samimy, Stifel.

安娜貝爾·薩米米，斯蒂菲爾。

You've talked about the potential for monthly dosing in the past. Will we be seeing that PK data? And will you be incorporating that into the Phase 3 program? Or is a separate trial? And I guess the same question for oral dosing, you're exploring additional -- are you exploring additional dosing regimens and given its continued activity post dosing?

您過去曾談到每月給藥的可能性。我們會看到 PK 數據嗎？您會將其納入第三階段計劃嗎？還是單獨審判？我想對於口服給藥也是同樣的問題，您正在探索額外的給藥方案，並考慮到給藥後其持續的活性？

Yes. With the monthly dose, we will have some PK data in the VENTURE poster. And we think that the PK data do support monthly dosing, not going to disclose too much of what's in the poster, but we think that monthly dosing is very feasible.

是的。有了每月的劑量，我們將在 VENTURE 海報中看到一些 PK 數據。我們認為PK數據確實支持每月給藥，不會在海報中透露太多內容，但我們認為每月給藥是非常可行的。

As far as the inclusion of a monthly regimen in the Phase 3 program, we'll probably do a stand-alone there not included in the Phase 3, the statistical treatment gets more challenging when you transition mid-study to monthly. So we would probably target a stand-alone there to start as soon as we can.

至於在第3 階段計劃中包含每月一次的治療方案，我們可能會單獨進行第3 階段中未包含的治療方案，當您從研究中期過渡到每月一次時，統計處理會變得更具挑戰性。因此，我們可能會盡快以獨立的方式開始。

Okay. And for the orally, you looking at different dosing regimens given its activity posting that you saw in the 4-week study?

好的。對於口服藥物，您根據您在為期 4 週的研究中看到的活性信息，正在考慮不同的給藥方案？

We may -- we'll disclose the 13-week study design once we get closer to the actual study initiation.

一旦接近實際研究啟動，我們可能會揭露為期 13 週的研究設計。

Okay. Great. And just if I could have another question. Can you talk about the I guess the infrastructure and capacity build that you have to do to run these next trials? Or have you committed to increasing your personnel at this stage?

好的。偉大的。如果我還有另一個問題就好了。你能談談我猜你必須做的基礎設施和能力建設才能進行接下來的試驗嗎？或是現階段您是否已承諾增加人員？

What are your expectations for how that expands your infrastructure rate.

您對如何擴展基礎設施速率有何期望？

Yes. Thanks, Annabel. We've typically relied heavily on external vendors. I think that's been -- it works very well for us, and it's been an efficient model for us. That said, we've been pretty aggressively adding to the staff now.

是的。謝謝，安娜貝爾。我們通常嚴重依賴外部供應商。我認為這對我們來說非常有效，對我們來說是一個有效的模式。也就是說，我們現在一直在積極地增加員工。

We've added in regulatory affairs, clinical development, manufacturing, formulation, clinical operations, market access, quality statistics. So it's a pretty broad-based increase in staff here. And we've continued to grow and we're continuing to add. So the Phase 3 trial is a lot different than the Phase 2 trial, and we're going to be prepared for it.

我們增加了監管事務、臨床開發、製造、配方、臨床操作、市場准入、品質統計。因此，這裡的員工人數大幅增加。我們一直在不斷成長，而且還在增加。因此，第三階段試驗與第二階段試驗有很大不同，我們將為此做好準備。

Steve Seedhouse, Raymond James.

史蒂夫席德豪斯，雷蒙德詹姆斯。

A couple of protocol questions. Just for the Phase 3 study. I'm wondering how you think about the pros and cons of whether it will be necessary or advisable to have like an active control arm in this study with one of the commercially available mechanisms and if that's a conversation that you anticipate having with FDA.

幾個協議問題。僅用於第三階段研究。我想知道您如何看待在這項研究中使用一種市售機制的主動控制臂是否必要或明智的利弊，以及您是否希望與 FDA 進行對話。

Yes. Thanks, Steve. Right now, we're planning to do a placebo-controlled study. I think an active comparator study would be of interest in a future study. But in these first 2 studies, it will be placebo-controlled.

是的。謝謝，史蒂夫。現在，我們計劃進行一項安慰劑對照研究。我認為未來的研究會對積極的比較研究感興趣。但在前兩項研究中，它將是安慰劑對照的。

Okay. Sounds good. And then on amylin clinical development strategy question as well, just how early in the development program? Or how are you thinking in general about testing that combination with, in this case, 2735, or I guess you could use another clip, but how are you thinking about when it's appropriate and best to start looking at the combinations?

好的。聽起來不錯。然後還有關於胰淀素臨床開發策略的問題，開發計畫的早期階段是多久？或者您通常如何考慮使用 2735 來測試該組合，或者我猜您可以使用另一個剪輯，但是您如何考慮何時開始查看這些組合是合適且最好的？

Yes. In our view, the amylin -- the greatest value with that mechanism is in conjunction with another mechanism. And typically, what you see is a nice improvement in efficacy when you add it on top of another mechanism with a GLP-1, you see a 50% bump or so.

是的。在我們看來，胰淀素－此機制的最大價值在於與另一種機制的結合。通常，當您將其添加到具有 GLP-1 的另一種機制之上時，您會看到功效有了很大的提高，您會看到大約 50% 的提升。

So if you were to add it on to a dual agonist, and it showed a similar improvement, that would likely be the best in the industry efficacy profile, and so that's something that we think is really a high-value exercise to proceed with. So we'll be hopefully bringing a compound into the clinic in 2025.

因此，如果您將其添加到雙激動劑中，並且它顯示出類似的改善，那麼這可能是行業中最好的功效，因此我們認為這確實是一項高價值的工作。因此，我們預計在 2025 年將一種化合物引入臨床。

And we would look at single agent but rapidly follow that with potential combinations.

我們會關注單一藥物，但很快就會關注潛在的組合。

And just a follow-up on that, is that something that using the same approach you've used with 2735, you could formulate orally and and co-formulate with your oral in future studies?

後續的問題是，是否使用與 2735 相同的方法，您可以在未來的研究中口頭制定並與您的口頭共同製定？

We think so, yes.

我們認為是的。

Okay. And just lastly, I just want to clarify, it's sort of an obvious statement that you press release, but I was hoping you could elaborate that you think further benefits from the oral dosing might be anticipated with longer dosing periods. But the press release does say based on observations in the Phase 1 study. So anything you can elaborate on or say about like just what observations you're referring to there, what specific data points led you to conclude it.

好的。最後，我只是想澄清一下，這是您新聞稿中的一個明顯的聲明，但我希望您能詳細說明您認為口服給藥的進一步益處可能會隨著給藥時間的延長而增加。但新聞稿確實是基於第一階段研究的觀察。因此，您可以詳細說明或說出的任何內容，例如您在那裡提到的觀察結果，哪些具體數據點引導您得出結論。

Yes. When you look at the trajectory at those -- what's been reported so far, the 20- and the 40-milligram cohorts, the slopes were still negative. And 20 days is such a short window to look at. So we think extending the dosing window would likely extend the trajectory further. That's really what we're referring to there.

是的。當你觀察那些 20 毫克和 40 毫克組的軌跡時（到目前為止所報導的），斜率仍然是負值。 20 天是一個很短的時間窗口。因此，我們認為延長給藥窗口可能會進一步延長軌跡。這確實是我們所指的。

Okay. And so that's a reference to the already disclosed 40 mg data essentially and not.

好的。因此，這實質上是對已經披露的 40 毫克數據的參考，但並非如此。

That's right. That's right. Yes. We haven't disclosed anything with the subsequent cohorts.

這是正確的。這是正確的。是的。我們還沒有向後續團隊透露任何資訊。

Roger Song, Jefferies.

羅傑·宋，杰弗里斯。

Great. So maybe with the clarification, Brian. So can you confirm that you already completed the dose escalation for your oral 2735 up to 1 milligram. And if that's the case, could you qualitatively comment on the dose response on the way off and the (inaudible) rate for the high dose.

偉大的。也許需要澄清一下，布萊恩。那麼您能否確認您已經完成了口服 2735 的劑量升級至 1 毫克？如果是這樣的話，您能否對停藥時的劑量反應和高劑量的（聽不清楚）率進行定性評論。

Yes, Roger. We did dose up to 100 milligrams. And I think we'll leave the further disclosure of the results to the poster. It's only in about 10 days. So we're probably going to limit further communication there.

是的，羅傑。我們的劑量高達 100 毫克。我認為我們將把結果的進一步披露留給發布者。只剩下10天左右了。所以我們可能會限制那裡的進一步溝通。

The Phase 1 study was it tended to provide sufficient information to plan and execute a Phase 2 study, and we think that it was successful in that regard, and we look forward to getting the Phase 2 underway as soon as possible.

第一階段研究旨在為計劃和執行第二階段研究提供足夠的信息，我們認為它在這方面是成功的，我們期待盡快啟動第二階段研究。

Got it. Yes. That makes sense. And then in terms of the capacity, maybe focusing on the manufacturing, understanding you probably already have the capacity for the clinical trial for subcu Phase 3 and then for the oral Phase 2. Just curious for the past couple of months, what have you done to further increase the manufacturing capacity for those candidates?

知道了。是的。這是有道理的。然後就能力而言，也許專注於製造，了解您可能已經具備進行 subcu 3 期臨床試驗和口服 2 期臨床試驗的能力。的製造能力？

Can we -- have you started to think about the potential commercial capacity?

您是否開始考慮潛在的商業能力？

Yes. Thanks, Roger. Yes, you're right. We do currently have on hand sufficient drug supplies to support our planned development activities for both the formulations on subcu and the oral. And in the meantime, as we proceed forward, we continue to have dialogue with the key global peptide suppliers and are working toward long-term supply agreements, and we are confident that we will be in a position to supply a blockbuster size product at the appropriate time.

是的。謝謝，羅傑。是的，你說得對。我們目前手頭上確實有足夠的藥物供應來支持我們計劃的 subcu 和口服製劑的開發活動。同時，隨著我們的前進，我們繼續與全球主要的勝肽供應商進行對話，並正在努力達成長期供應協議，我們有信心能夠以驚人的速度供應重磅級產品。

Jay Olson, Oppenheimer.

傑·奧爾森，奧本海默。

Congrats on all the progress. Can you comment on what level of safety and tolerability you would like to see for the 100-milligram dose that might enable testing higher oral doses in the Phase 2 study?

祝賀所有的進展。您能否評論一下您希望 100 毫克劑量的安全性和耐受性達到什麼水平，以便在 2 期研究中測試更高的口服劑量？

Yes. We need the tolerability decisions up to the dose level review team that means after completion of every cohort. And there was never a recommendation from that team to discontinue escalation. So we feel very comfortable with the tolerability profile.

是的。我們需要劑量水平審查小組做出耐受性決定，這意味著在每個隊列完成後。該團隊從未建議停止升級。所以我們對耐受性感到非常滿意。

Okay. Great. And then recognizing that commercial launch is years away, you recently indicated that a synthetic manufacturing route with an external supplier could be outlined by the end of the year. Could you please comment on how those discussions are going? And any other updates on the manufacturing front?

好的。偉大的。然後您認識到商業發布還需要數年時間，您最近表示可能會在年底前概述與外部供應商的合成製造路線。您能否評論一下這些討論的進展？製造方面還有其他更新嗎？

Yes. Thanks, Jay. So as I've mentioned a minute ago, we do continue to have dialogue with global peptide suppliers who can scale up. And some of that discussion is focused on various synthetic routes. So all of that is in progress in and under active development.

是的。謝謝，傑伊。正如我剛才提到的，我們確實繼續與能夠擴大規模的全球勝肽供應商進行對話。其中一些討論集中在各種合成路線上。因此，所有這些都在積極開發中。

So when we make a decision for the route that will be utilized for scale up we'll talk more about it, but all of that is still in process as we speak.

因此，當我們決定用於擴大規模的路線時，我們會更多地討論它，但在我們發言時，所有這些仍在進行中。

Okay. Great. And maybe one big picture question. As you think about the total value for VK2735, can you just talk about how that value is split between the subcu and oral forms?

好的。偉大的。也許還有一個大問題。當您考慮 VK2735 的總價值時，您能否談談該價值如何在 subcu 和口頭形式之間分配？

Yes. It's an interesting question. And oftentimes, it depends on who you ask. We view the the really anchor piece to the franchise is the subcutaneous formulation with the oral being a very nice add-on, but unlikely to be the the major modality. And when you look at the utilization right now, we're probably going to exceed $40 billion in total revenue from the current obesity drugs.

是的。這是一個有趣的問題。通常，這取決於你問的是誰。我們認為該系列的真正支柱是皮下製劑，口服製劑是一個非常好的補充，但不太可能成為主要形式。當你看看現在的使用率時，我們從目前的肥胖藥物中獲得的總收入可能會超過 400 億美元。

And so those are rapidly expanding, and we'll continue to do so. in the absence of an oral, which is some time off. So to think an oral would come in and dominate, I don't know how likely that is. We see the oral is probably a 20% opportunity and the injectable is probably an 80% opportunity.

因此，這些正在迅速擴大，我們將繼續這樣做。在沒有口頭的情況下，這是一段時間的休息。因此，如果認為口頭形式會出現並佔據主導地位，我不知道這種可能性有多大。我們看到口服可能有 20% 的機會，注射可能有 80% 的機會。

Justin Zelin, BTIG.

賈斯汀·澤林，BTIG。

Congrats on the progress. Brian, on the subcu injectable with the Phase 3 coming up, would you look to use an auto-injector format for that study? Or could you talk to us about if you're looking to transition to an auto-injector what that might entail, whether you need a separate study for that? And I have a follow-up.

祝賀取得的進展。 Brian，關於即將進行第三階段的 subcu 注射劑，您會考慮在該研究中使用自動注射器形式嗎？或者您能否與我們談談，如果您想過渡到自動注射器，這可能需要什麼，是否需要為此進行單獨的研究？我有一個後續行動。

Yes. Thanks, Justin. So we haven't talked much about the trial design, but we will be using an auto-injector in that study. If it's available soon enough, we would utilize that from the onset of the study. If not, we would seek to transition people from a vial in a syringe to the auto-injector.

是的。謝謝，賈斯汀。因此，我們沒有過多討論試驗設計，但我們將在該研究中使用自動注射器。如果它夠快可用，我們將從研究一開始就利用它。如果沒有，我們將尋求將人們從注射器小瓶過渡到自動注射器。

Okay. Great. So it sounds like you might be in discussions with securing some of the auto-injector materials in order to prepare for that.

好的。偉大的。因此，聽起來您可能正在討論確保一些自動注射器材料的安全，以便為此做好準備。

Oh, yes, yes. That's right.

哦，是的，是的。這是正確的。

Okay. Excellent. And then just a question on the X-ALD. Remembering correctly, the FDA considered the recent study to be a Phase 2 study. Would that mean that if you're looking to progress that into clinical development, the next step would be like a registrational study?

好的。出色的。然後是關於 X-ALD 的問題。沒記錯的話，FDA 認為最近的研究是第 2 期研究。這是否意味著，如果您希望將其推進臨床開發，下一步將類似於註冊研究？

Yes, good question. That's what we think. Typically, you look at these biomarker studies initially in this indication anyway and then proceed to a registration study, whether it's Phase 2, 3 or a Phase 3. So that would be our expectation here as well, likely focused on more of a functional or a quality of life endpoint, not just the very long chain fatty assets. That's been the historical path forward in X-ALD.

是的，好問題。這就是我們的想法。通常情況下，您會先在該適應症中查看這些生物標記研究，然後繼續進行註冊研究，無論是第2 期、第3 期還是第3 期。地關注功能性或功能性研究。這就是 X-ALD 的歷史發展之路。

(Operator Instructions) Thomas Smith, Leerink Partners.

（操作員說明）Thomas Smith，Leerink Partners。

Thanks for the update. First on oral 2735, looking forward to seeing the data at ObesityWeek. Brian, I just wanted to follow up on an earlier question. And I know you commented back in September that the dose level review committee hasn't met yet to review the data from the 100 mg cohort. So wondering if you could just comment on whether they met at this point and clarify whether there's still any potential or desire to explore a higher dose level here in the Phase 1 setting, or is this is something you may consider doing in the Phase 2?

感謝您的更新。首先是口服2735，期待在ObesityWeek看到數據。布萊恩，我只是想跟進之前的問題。我知道您在 9 月評論說，劑量水平審查委員會尚未開會審查 100 毫克隊列的數據。因此，想知道您是否可以評論一下他們是否在這一點上相遇，並澄清是否仍有潛力或願望在第一階段的環境中探索更高的劑量水平，或者這是您可能考慮在第二階段做的事情？

Yes. It's -- so getting to the root of the question would be dose higher. I think it's certainly possible to dose higher, and I guess we would really disclose that when we start the Phase 2 study. There was nothing in the initial read of the data that would indicate we'd be precluded from dosing up. But we'd rather refrain any further comment until we present the actual data at the OBD conference.

是的。因此，要找到問題的根源就需要更高的劑量。我認為劑量更高當然是可能的，而且我想當我們開始第二階段研究時我們會真正披露這一點。最初讀取的數據中沒有任何內容表明我們將被排除服用劑量。但在 OBD 會議上提供實際數據之前，我們寧願避免發表任何進一步評論。

Got it. Okay. That makes sense. And then for maybe a quick question on 2809 in NASH and looking forward to the late-breaking data there at ASLD. Can you maybe tease some of the additional data and analysis we can look forward to seeing at the liver meeting and then, any update on how you're thinking strategically about the next steps with that program perhaps with respect to engaging partners?

知道了。好的。這是有道理的。然後可能會問一個關於 NASH 中 2809 的快速問題，並期待 ASLD 的最新數據。您能否透露一些我們期待在肝臟會議上看到的額外數據和分析，然後，您如何策略性地思考該計劃的後續步驟（可能涉及合作夥伴）？

Yes. Thanks, Tom. We'll certainly look at the histologic changes, I think that's the thing most people are interested in changes in fibrosis. Any differences response among the various severities of fibrosis, any differences in response depending on baseline characteristics with liver fat as well. So that would be sort of, I think, of interest to look at.

是的。謝謝，湯姆。我們當然會關注組織學變化，我認為這是大多數人對纖維化變化感興趣的事情。不同嚴重程度的纖維化之間的任何差異反應，任何反應差異也取決於肝臟脂肪的基線特徵。所以我認為這應該是值得關注的。

Next steps here, we've always felt that the NASH program would be best handled in conjunction with a larger pharma collaborator. And that's the way we still feel about it. So we'll review the responses we received from the FDA and proceed from there.

下一步，我們一直認為 NASH 計畫最好與更大的製藥合作夥伴一起處理。這就是我們現在的感受。因此，我們將審查從 FDA 收到的答复，並從那裡繼續進行。

I-Eh Jen, Laidlaw & Company.

I-Eh Jen，萊德勞公司。

Congrats on the progress. Just two here. The first one is in terms of 2809, you got a FDA feedback and you're reviewing it. Just curious, any surprises versus what's your expectation? And would that impact anything on the potential partnering you may have.

祝賀取得的進展。這裡只有兩個。第一個是 2809，你收到了 FDA 的回饋，你正在審查它。只是好奇，與您的期望相比，有什麼驚喜嗎？這會對您可能擁有的潛在合作夥伴產生任何影響嗎？

And then I have a followup.

然後我有一個後續行動。

No, good question. We just received those responses within the last 48 hours, and we're reviewing them. No real surprises or unexpected comments in them thus far, but still in process of looking at them.

不，好問題。我們剛剛在過去 48 小時內收到了這些回复，並且正在對其進行審核。到目前為止，它們還沒有真正的驚喜或意外的評論，但仍在研究中。

Okay. Great. And maybe just 1 follow-up here, which is that in the recent EASD meeting, there's a lot of talk about the amylin as well as the defined once the readout could be available in the fourth quarter or year-end of this year, what do you think the potential readout or impact you might have on your program, or you're thinking about the design or not? So any color on there?

好的。偉大的。也許這裡只有一個後續行動，那就是在最近的 EASD 會議上，有很多關於胰淀素的討論，以及一旦讀數可以在今年第四季度或年底提供的定義，什麼您認為您的程序可能會產生潛在的讀數或影響，或者您是否正在考慮設計？那麼上面有什麼顏色嗎？

Well, yes, we think the mechanism is really exciting. And when you think about the effect on appetite and feeding behavior, it seems to act via a different mechanism than GLP-1 and GIP. So you should see a nice add-on effect. So I would expect to see exciting data when it's reported later this year. And I think that would bode well for our own program if we're able to combine it successfully with VK2735 or other things in the pipeline.

嗯，是的，我們認為這個機制真的很令人興奮。當您考慮對食慾和進食行為的影響時，您會發現它似乎透過與 GLP-1 和 GIP 不同的機制發揮作用。所以你應該會看到一個不錯的附加效果。因此，我預計今年稍後報告時會看到令人興奮的數據。我認為，如果我們能夠將其與 VK2735 或其他正在開發中的產品成功結合，這對我們自己的計劃來說是個好兆頭。

So far, what we've seen from amylin looks really promising, and that's one of the reasons we're excited about it.

到目前為止，我們從胰島澱粉樣蛋白中看到的東西看起來確實很有希望，這也是我們對此感到興奮的原因之一。

Hardik Parikh, JPMorgan.

哈迪克·帕里克，摩根大通。

I just wanted to ask you -- first question is just a clarification. I just want to make sure, in the Phase 1 trial, you have or you have not tested doses above 100 milligrams in the oral format? And then the second one is just more of a high-level question. I think we saw a number of kind of competitive readouts in obesity, for example, at EASD. I just wanted to get your overall thoughts on what you learned out of those data readouts from Novo and Roche and so forth.

我只是想問你——第一個問題只是一個澄清。我只是想確定一下，在第 1 期試驗中，您是否測試過超過 100 毫克的口服劑量？第二個問題只是更高層次的問題。我認為我們在肥胖症方面看到了多種競爭性的結果，例如在 EASD。我只是想了解您對從 Novo 和 Roche 等公司的數據讀數中了解到的總體想法。

Yes. Thanks, Hardik. We went up in the oral -- the subsequent cohorts were 60 milligrams, 80 milligrams and 100 milligrams. And like I said earlier, we'll have the data in about 1.5 weeks. With respect to ASD, a lot of really interesting programs in the space is really, really hot right now.

是的。謝謝，哈迪克。我們增加了口服劑量——隨後的組別分別是 60 毫克、80 毫克和 100 毫克。正如我之前所說，我們將在大約 1.5 週內獲得數據。就 ASD 而言，該領域有許多非常有趣的項目現在非常非常熱門。

But I guess what was I think converting to us is that we do feel like we have two of the best programs with respect to mode of delivery, the injectable and the oral. And so there was nothing at the conference that would lead us to believe otherwise. Everything is still pretty early right now. But I think we feel good coming out of both ADA and EASD about the value of the pipeline today, and we're looking forward to the subsequent studies with both the formulations of VK2735 and with the amylin program.

但我想我認為轉向我們的是，我們確實覺得我們在交付方式方面有兩個最好的項目，即註射和口服。因此，會議上沒有任何事情會讓我們產生相反的看法。現在一切都還很早。但我認為我們對 ADA 和 EASD 今天管道的價值感到滿意，我們期待 VK2735 配方和胰島澱粉樣多肽計劃的後續研究。

Alex Ramsey, William Blair.

亞歷克斯·拉姆齊，威廉·布萊爾。

So I have two questions, if you don't mind, and I could ask them one time. So our first question is about the maintenance opportunity for VK2735, and specifically, we're curious about how you think about the booking in the setting and really more from a philosophical standpoint.

所以我有兩個問題，如果你不介意的話，我可以問一次。因此，我們的第一個問題是關於 VK2735 的維護機會，具體來說，我們很好奇您如何看待環境中的預訂，以及更多從哲學的角度來看。

So just to provide a little more context, the question is driven on my observation that the weight loss setting, the goal is to stimulate for work deficit, but that dynamic will differ in the main setting or the goal is more boosting equilibrium. So we're just wonder how you think about the dosing that setting? And my quarters key questions that you're asking and how are you designing experiments to address those questions around thing.

因此，為了提供更多背景信息，問題是根據我的觀察而提出的，即減肥設定的目標是刺激工作赤字，但這種動態在主要設定中會有所不同，或者目標是更多地促進平衡。所以我們只是想知道您如何看待該設定的劑量？我的宿舍是您提出的關鍵問題，以及您如何設計實驗來解決這些問題。

Yes. Thanks, Alex. With the monthly regimen, we view it as really more of a maintenance regimen than a weight-loss regimen. And so it would be an option for someone who has reached their target range and weight to transition from the weekly to a monthly and really keep their weight sustained, possibly to continue further downward. But really, our thought would be the most likely use would be in the maintenance setting.

是的。謝謝，亞歷克斯。對於每個月的養生法，我們認為它實際上更像是一種維持養生法，而不是減肥養生法。因此，對於已經達到目標範圍和體重的人來說，從每週一次過渡到每月一次，並真正保持體重不變，甚至可能繼續進一步下降，這將是一個選擇。但實際上，我們認為最有可能的用途是在維護環境中。

So just furthers the convenience aspect of the compound or the mechanism. I forgot, was there a second part to that question?

因此，只是進一步提高了化合物或機制的便利性。我忘了，這個問題還有第二部分嗎？

Yes. No, that makes sense. So you're kind of just looking like longer dosing intervals as kind of the main term mechanism for driving that difference between equilibrium versus stimulating continuous core deficit?

是的。不，這是有道理的。所以你認為較長的給藥間隔是驅動平衡與刺激持續核心赤字之間差異的主要機制？

Yes. It's kind of a little bit of both. You're re-equilibrating maybe at a lower caloric intake, that's what the hope would be anyway.

是的。兩者兼而有之。你可能會以較低的熱量攝取來重新平衡，無論如何這就是希望。

Okay. That makes sense. Perfect. And then my second question is in regards to the amylin asset. So when you look across the various investigational therapies with this mechanism, most companies seem to be gravitating towards that calcitonin component that you mentioned earlier.

好的。這是有道理的。完美的。我的第二個問題是關於胰淀素資產的。因此，當您查看具有這種機制的各種研究療法時，大多數公司似乎都傾向於您之前提到的降鈣素成分。

So we're just curious about your views on calcitonin. And do you think there's an optimal ratio in terms of agonism. And if the agonism is balanced. And then also, we're wondering how work with VK2735, which is also (inaudible) agonism bias for the M1 program.

所以我們只是好奇您對降鈣素的看法。您認為在激動方面是否有最佳比例？如果激動是平衡的。然後，我們也想知道如何與 VK2735 一起工作，這也是 M1 程序的（聽不清楚）激動偏見。

Yes. So historically, I think the first compound was very heavily active on the amylin receptor and less so on the calcitonin receptor pramlintide was that compound. And more recently, the most programs are targeting both. I don't know if that's intentional, or it's just very difficult to tease away along from calcitonin. We have worked on compounds that target both and it seems like the ones that have more of a balance on both receptors just show a slightly better weight loss profile than ones that skew one way or another.

是的。因此，從歷史上看，我認為第一種化合物對胰島澱粉樣多肽受體非常活躍，而對降鈣素受體普蘭林肽的活性較低。最近，大多數計劃都針對這兩者。我不知道這是故意的，還是很難擺脫降鈣素。我們已經研究了針對這兩種受體的化合物，似乎那些在兩種受體上都具有更多平衡的化合物比那些偏向某種方式的化合物顯示出稍微更好的減肥效果。

And so that's what has led us to the more balanced mechanism. But I don't know that it's really well understood, at least it isn't by me, what is the ideal ratio. It just seems like the closer you get to one, the better the profile seems to look overall.

這就是導致我們建立更加平衡機制的原因。但我不知道它是否真的很好理解，至少我不是這麼理解，理想的比例是多少。看起來你越接近一個，整體輪廓看起來就越好。

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

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

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

再次感謝您對 Viking Therapeutics 的參與和持續支持。我們期待在未來幾個月內再次為您提供最新消息。謝謝。

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。