Viking Therapeutics Inc (VKTX) 2023 Q3 法說會逐字稿

Welcome to the Viking Therapeutics Third Quarter 2023 Financial Results Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded today, October 25, 2023. I would now like to turn the conference over to Viking's Manager of Investor Relations, Stephanie Diaz. Please go ahead, Stephanie.

歡迎參加 Viking Therapeutics 2023 年第三季財務業績電話會議。 （操作員說明）謹此提醒，本次電話會議將於今天（2023 年 10 月 25 日）進行錄製。我現在將會議轉交給 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. Before we begin, I would like to caution that comments made during this conference call today, October 25, 2023, will contain forward-looking statements under the Safe Harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including statements about Viking's expectations regarding its development activities, 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.

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。在我們開始之前，我想提醒大家，在今天（2023 年10 月25 日）的電話會議上發表的評論將包含根據1995 年美國私人證券訴訟改革法案的安全港條款做出的前瞻性陳述，包括有關Viking 預期的陳述關於其開發活動、時間表和里程碑。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. I will 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 dialed in by phone or listening on the webcast. Today, we'll review our financial results for the third quarter and first nine months of 2023, and provide an update on recent progress with our clinical programs and operations.

謝謝斯蒂芬妮，祝所有通過電話撥入或收聽網絡廣播的人下午好。今天，我們將回顧 2023 年第三季和前 9 個月的財務業績，並提供臨床專案和營運的最新進展。

During the third quarter, Viking continued to build on the momentum established during the first half of the year. As a reminder, during the first six months of 2023, the company announced positive clinical data from our phase one trial evaluating VK2735, a dual GLP-1 and GIP receptor agonist, for the potential treatment of obesity, and from our Phase 2b VOYAGE Study, evaluating VK2809 in patients with biopsy-confirmed nonalcoholic steatohepatitis and fibrosis.

第三季度，維京繼續延續上半年的勢頭。提醒一下，在2023 年前六個月，該公司宣布了我們評估VK2735（一種GLP-1 和GIP 受體激動劑）對肥胖的潛在治療作用的一期試驗以及我們的2b 期VOYAGE 研究的積極臨床數據，評估 VK2809 在活檢確診的非酒精性脂肪性肝炎和纖維化患者中的作用。

Also, during the first six months, the company initiated the Phase 1 trial to evaluate a novel oral formulation of VK2735. Finally, the company closed a successful public offering of common stock, raising gross proceeds of approximately $288 million that we plan to use for the continued advancement of our pipeline programs through key clinical milestones. Building on these achievements and following the positive results from our phase one trial of VK2735, during the third quarter, the company advanced this program into Phase 2 development with the initiation of the venture study to evaluate the safety and efficacy of VK2735 in patients with obesity.

此外，在前六個月內，該公司啟動了第一階段試驗，以評估 VK2735 的新型口服製劑。最後，該公司成功完成了普通股公開發行，籌集了約 2.88 億美元的總收益，我們計劃將其用於透過關鍵的臨床里程碑繼續推進我們的管道項目。在這些成就的基礎上，並繼 VK2735 一期試驗取得積極成果後，公司在第三季度將該項目推進到二期開發，啟動了風險研究，以評估 VK2735 對肥胖患者的安全性和有效性。

We recently announced that interest in this trial exceeded our expectations, allowing us to upsize the study and complete enrollment more quickly than expected. I'll provide further details on our operations and development activities after we review our financial results for the third quarter and first nine months of 2023. For that, I'll turn the call over to Greg Zante, Viking's Chief Financial Officer.

我們最近宣布，對該試驗的興趣超出了我們的預期，使我們能夠擴大研究規模並比預期更快地完成入組。在我們審查 2023 年第三季和前 9 個月的財務表現後，我將提供有關我們營運和開發活動的更多詳細資訊。為此，我將電話轉給 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 today. I'll now go over our results for the third quarter and nine months ended September 30, 2023, beginning with the results for the quarter.

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，我們預計今天將提交該表格。我現在將回顧我們第三季和截至 2023 年 9 月 30 日的九個月的業績，從本季的業績開始。

Our research and development expenses for the three months ended September 30, 2023 were $18.4 million, compared to $12 million for the same period in 2022. The increase was primarily due to increased expenses related to preclinical studies, clinical studies, stock-based compensation, salaries and benefits, and third-party consultants, partially offset by decreased expenses related to manufacturing for our drug candidates.

截至 2023 年 9 月 30 日的三個月，我們的研發費用為 1,840 萬美元，而 2022 年同期為 1,200 萬美元。這一增長主要是由於與臨床前研究、臨床研究、股票補償、工資和福利以及第三方顧問，部分被候選藥物生產相關費用的減少所抵銷。

Our general and administrative expenses for the three months ended September 30, 2023 were $8.9 million, compared to $4.2 million for the same period in 2022. The increase was primarily due to increased expenses related to legal and patent services, stock-based compensation, third-party consultants, and salaries and benefits.

截至 2023 年 9 月 30 日的三個月，我們的一般和管理費用為 890 萬美元，而 2022 年同期為 420 萬美元。這一增長主要是由於與法律和專利服務、股票薪酬、第三-當事人顧問、薪資和福利。

For the three months ended September 30, 2023, Viking reported a net loss of $22.5 million, or $0.23 per share, compared to a net loss of $15.8 million, or $0.21 per share in the corresponding period in 2022. The increase in net loss for the three months ended September 30, 2023 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 2022.

截至 2023 年 9 月 30 日的三個月，Viking 淨虧損為 2,250 萬美元，即每股 0.23 美元，而 2022 年同期淨虧損為 1,580 萬美元，即每股 0.21 美元。截至2023年9月30日的三個月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2022年同期相比的增加所抵消。

I'll now go over our results for the nine months ended September 30, 2023. Our research and development expenses for the nine months ended September 30, 2023 were $43.3 million, compared to $38.1 million for the same period in 2022. The increase was primarily due to increased expenses related to preclinical studies, stock-based compensation, salaries and benefits, manufacturing for our drug candidates, regulatory service costs and third party consultants partially offset by decreased expenses related to clinical studies.

現在，我將回顧截至2023 年9 月30 日止九個月的業績。截至2023 年9 月30 日止九個月，我們的研發費用為4,330 萬美元，而2022 年同期為3,810 萬美元。增幅為主要是由於與臨床前研究、股票薪酬、工資和福利、候選藥物製造、監管服務成本和第三方顧問相關的費用增加，但部分被臨床研究相關費用的減少所抵消。

Our general and administrative expenses for the nine months ended September 30, 2023 were $28.2 million, compared to $12 million for the same period in 2022. The increase was primarily due to increased expenses related to legal and patent services, stock-based compensation, salaries and benefits, and third party consultants.

截至2023 年9 月30 日的九個月，我們的一般和管理費用為2820 萬美元，而2022 年同期為1200 萬美元。這一增長主要是由於與法律和專利服務、股票薪酬、工資相關的費用增加和福利以及第三方顧問。

For the nine months ended September 30, 2023, Viking reported a net loss of $61.3 million or $0.66 per share, compared to a net loss of $49.3 million or $0.64 per share in the corresponding period in 2022. The increase in net loss during the period 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 2022.

截至2023年9月30日的九個月，維京報告的淨虧損為6,130萬美元，即每股0.66美元，而2022年同期的淨虧損為4,930萬美元，即每股0.64美元。 期內淨虧損增加主要是由於與 2022 年同期相比，先前提到的研發費用以及一般和管理費用的增加被利息收入的增加部分抵消。

Turning to the balance sheet, at September 30 2023, Viking held cash, cash equivalents and short term investments of $376 million, compared to $155 million as of December 31, 2022. This concludes my financial review, and I'll now turn the call back over to Brian.

轉向資產負債表，截至2023 年9 月30 日，Viking 持有現金、現金等價物和短期投資為3.76 億美元，而截至2022 年12 月31 日為1.55 億美元。我的財務審查到此結束，現在我將轉交電話回到布萊恩。

Thanks, Greg. I'll begin today with an update on our VK2735 program, which is the newest clinical stage compound at the company. VK2735 is a dual agonist of the Glucagon-Like Peptide 1 or GLP-1 receptor and the Glucose-Dependent Insulinotropic Polypeptide or GIP Receptor that is being evaluated for the treatment of obesity.

謝謝，格雷格。今天我將首先介紹我們的 VK2735 計畫的最新情況，這是該公司最新的臨床階段化合物。 VK2735 是胰高血糖素樣勝肽 1 或 GLP-1 受體和葡萄糖依賴性促胰島素多肽或 GIP 受體的雙重激動劑，正在評估其治療肥胖的作用。

Earlier this year, we announced positive results from a Phase 1 single ascending dose and multiple ascending dose study of VK2735. The study was designed to evaluate this compounds preliminary safety, tolerability and pharmacokinetic profile as well as its potential impact on exploratory metabolic measures including body weight and liver fat.

今年早些時候，我們宣布了 VK2735 的 1 期單次劑量遞增和多次劑量遞增研究的積極結果。該研究旨在評估該化合物的初步安全性、耐受性和藥物動力學特徵及其對探索性代謝指標（包括體重和肝臟脂肪）的潛在影響。

The single ascending dose portion of the study, which enrolled healthy men and women demonstrated that single doses of VK2735 were safe and well tolerated and displayed favorable pharmacokinetics. Following single subcutaneous doses VK2735 demonstrated the half-life of approximately 170 to 250 hours and excellent therapeutic exposures. The multiple ascending dose portion of this study enrolled healthy men and women with a minimum body mass index of 30 kilograms per meter squared. These subjects received VK2735 once weekly for 28 days.

研究的單劑量遞增部分招募了健康男性和女性，證明單劑量 VK2735 是安全的、耐受性良好，並顯示出良好的藥物動力學。單次皮下注射後，VK2735 表現出約 170 至 250 小時的半衰期和出色的治療暴露。本研究的多劑量遞增部分招募了體重指數最低為每平方公尺 30 公斤的健康男性和女性。這些受試者每週接受一次 VK2735，持續 28 天。

In this portion of the study VK2735, demonstrating a encouraging safety and tolerability and positive signs of clinical activity. All cohorts receiving VK2735 demonstrated reductions in mean body weight from baseline ranging up to 7.8%. Cohorts receiving VK2735 also demonstrated reductions in mean body weight relative to placebo, ranging up to 6%. Statistically significant differences in body weight compared to placebo were also maintained or improved at the day 43 follow up time point 21 days after the last dose of VK2735 was administered.

在這部分研究中，VK2735 表現出令人鼓舞的安全性和耐受性以及臨床活性的積極跡象。所有接受 VK2735 治療的族群均顯示平均體重較基線降低高達 7.8%。與安慰劑相比，接受 VK2735 治療的族群的平均體重也降低了 6%。在給予最後一劑 VK2735 後 21 天後的第 43 天追蹤時間點，與安慰劑相比，體重的統計學顯著差異也維持或改善。

In this study, the VK2735 also demonstrated encouraging safety and tolerability with 98% of observed adverse events reported as mild or moderate, and 99% of gastrointestinal related adverse events reported as mild or moderate. These results were featured earlier this month in an oral presentation at obesity week, the annual meeting of the Obesity Society. The presentation highlighted the prior safety tolerability and weight loss findings, as well as new data demonstrating VK2735s impact on liver fat and plasma lipids.

在這項研究中，VK2735 也表現出令人鼓舞的安全性和耐受性，98% 的觀察到的不良事件報告為輕度或中度，99% 的胃腸道相關不良事件報告為輕度或中度。這些結果在本月稍早肥胖協會年會「肥胖週」上的口頭報告中得到了重點報導。演講強調了先前的安全耐受性和減肥研究結果，以及證明 VK2735 對肝臟脂肪和血漿脂質影響的新數據。

Notably, after four weekly doses of VK2735 subjects in the Phase 1 trial reported liver fat reductions of up to 47% from baseline. Among subjects with non-alcoholic fatty liver disease, placebo adjusted reductions in liver fat reached approximately 59%. Though the sample size was limited, these results may indicate VK2735s potential benefit in patients with various forms of fatty liver disease. The obesity week presentation also highlighted VK2735s effect on plasma lipids. Despite normal baseline plasma lipid levels among these healthy volunteers, treatment with VK2735 produced encouraging reductions from baseline and total cholesterol of up to 21% and reductions in LDL cholesterol of upto 23%. In addition, plasma levels of apolipoprotein B were reduced by up to 21%.

值得注意的是，在第 1 期試驗中，每週服用 VK2735 4 次後，受試者報告肝臟脂肪較基線減少高達 47%。在非酒精性脂肪肝疾病的受試者中，安慰劑調整後的肝臟脂肪減少量達到約 59%。儘管樣本量有限，但這些結果可能表明 VK2735 對患有各種形式的脂肪肝疾病的患者俱有潛在的益處。肥胖週演講也強調了 VK2735 對血漿脂質的影響。儘管這些健康志願者的基線血脂水平正常，但使用 VK2735 治療後，總膽固醇較基線降低了 21%，LDL 膽固醇降低了 23%，令人鼓舞。此外，載脂蛋白 B 的血漿濃度降低了 21%。

Following the encouraging results from our Phase 1 study, during the third quarter Viking initiated the Phase 2 VENTURE trial to evaluate VK2735 in patients with obesity. The VENTURE trial is a randomized, double blind placebo controlled multicentre study, that is evaluating the safety tolerability, pharmacokinetics and weight loss efficacy of VK2735, administered subcutaneously once weekly for 13 weeks.

在我們的 1 期研究取得令人鼓舞的結果後，Viking 在第三季度啟動了 2 期 VENTURE 試驗，以評估肥胖患者的 VK2735。 VENTURE試驗是一項隨機、雙盲安慰劑對照多中心研究，旨在評估VK2735的安全耐受性、藥物動力學和減肥功效，每週皮下注射一次，持續13週。

This trial was designed to enroll approximately 125 adults with obesity, or adults who are overweight with at least one weight related comorbid condition. The trial will evaluate VK2735 doses of up to 15 milligrams compared to the 10 milligram top dose evaluated in the prior Phase 1 multiple ascending dose study. The primary endpoint of the study will assess the percent change in body weight from baseline to week-13 among patients treated with VK2735 as compared to placebo. Secondary and exploratory endpoints will evaluate a range of additional safety and efficacy measures.

該試驗旨在招募約 125 名患有肥胖症的成年人，或患有至少一種體重相關合併症的超重成年人。該試驗將評估高達 15 毫克的 VK2735 劑量，而先前的 1 期多次遞增劑量研究中評估的最高劑量為 10 毫克。研究的主要終點將評估接受 VK2735 治療的患者與安慰劑相比，從基線到第 13 週的體重變化百分比。次要和探索性終點將評估一系列額外的安全性和有效性措施。

Earlier this week, we announced that the VENTURE study is now fully enrolled. In addition, due to heightened clinician and patient interest, we announced that the trials enrollment size has been increased to 176 patients from the original target at 125 patients. We expect to report the top line results from this study in the first half of 2024.

本週早些時候，我們宣布 VENTURE 研究現已全部入組。此外，由於臨床醫生和患者興趣的提高，我們宣布試驗入組規模已從最初的 125 名患者目標增加到 176 名患者。我們預計在 2024 年上半年報告這項研究的主要結果。

In addition to the subcutaneous formulation of VK2735 under evaluation in the VENTURE study, we are also pursuing an oral formulation of this compound. Earlier this year, we announced the initiation of a Phase 1 clinical study to evaluate a novel tablet formulation of VK2735. This study is an extension of the Phase 1 single ascending dose and multiple same dose study discussed earlier. The oral portion of the study is a randomized, double blind placebo controlled study in healthy volunteers who have a minimum body mass index of 30 kilograms per meter squared. Subjects in this portion of the study will receive once daily oral doses of VK2735 for 28 days. The primary objective of the study is to evaluate the safety, tolerability and pharmacokinetics of VK2735 following 28 days of oral dosing. Exploratory endpoints include changes in body weight and other pharmacodynamic markers. Enrollment in this study is continuing and we expect to report the results in the first quarter of 2024.

除了 VENTURE 研究中評估的 VK2735 皮下製劑外，我們也正在研究該化合物的口服製劑。今年早些時候，我們宣布啟動一項 1 期臨床研究，以評估 VK2735 的新型片劑配方。這項研究是先前討論的第一階段單次劑量遞增和多次相同劑量研究的延伸。研究的口服部分是一項隨機、雙盲安慰劑對照研究，受試者為健康志願者，這些志願者的最低體重指數為每平方公尺 30 公斤。這部分研究的受試者將每天口服一次 VK2735，持續 28 天。研究的主要目的是評估 VK2735 口服給藥 28 天後的安全性、耐受性和藥物動力學。探索性終點包括體重和其他藥效學標記的變化。這項研究的招募工作仍在繼續，我們預計將在 2024 年第一季報告結果。

I'll now provide an update on our most advanced compounds VK2809 for the treatment of NASH and fibrosis. VK2809 is an orally available small molecule agonist of the thyroid hormone receptor that is selected for liver tissue as well as the beta isoform of the receptor. Earlier this year, we announced positive or top line results from the ongoing Phase 2b VOYAGE study evaluating VK2809 in patients with biopsy-confirmed NASH and fibrosis. The study successfully achieved its primary endpoint, with patients receiving VK2809 experiencing 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 as assessed by magnetic resonance imaging, proton density fat fraction ranged from 38% to 55% among patients receiving VK2809.

我現在將提供有關我們用於治療 NASH 和纖維化的最先進化合物 VK2809 的最新資訊。 VK2809 是一種口服的甲狀腺激素受體小分子激動劑，選擇用於肝組織以及受體的 β 亞型。今年早些時候，我們宣布了正在進行的 2b 期 VOYAGE 研究的陽性或頂線結果，該研究評估了 VK2809 在活檢確診的 NASH 和纖維化患者中的作用。該研究成功實現了其主要終點，與安慰劑相比，接受 VK2809 治療的患者的肝臟脂肪含量從基線到第 12 週出現了統計上顯著的降低。透過磁振造影評估，接受 VK2809 治療的患者肝臟脂肪相對於基線的中位數相對變化、質子密度脂肪分數範圍為 38% 至 55%。

Importantly, up to 85% of patients receiving VK2809 experienced at least a 30% relative reduction in liver fat content. This level of efficacy is associated with greater likelihood of histologic improvement in NASH.

重要的是，在接受 VK2809 治療的患者中，高達 85% 的患者肝臟脂肪含量相對減少了至少 30%。這種療效水準與 NASH 組織學改善的可能性更大相關。

Additionally, VK2809-treated patients demonstrated statistically significant reductions in LDL cholesterol, triglycerides, and atherogenic proteins, all of which have been correlated with increased cardiovascular risk. These data indicate that VK2809 has the potential to provide longer term cardio-protective benefits.

此外，接受 VK2809 治療的患者的 LDL 膽固醇、三酸甘油酯和致動脈粥樣硬化蛋白具有統計學意義的顯著降低，所有這些都與心血管風險增加有關。這些數據表明 VK2809 有潛力提供長期的心臟保護作用。

The VOYAGE data also reinforced VK2809's encouraging safety and tolerability profile. 94% of treatment related adverse events among patients treated with VK2809 were reported as mild or moderate. Discontinuations due to adverse events were low and balanced among placebo and treatment arms. Consistent with prior studies, VK2809 demonstrated excellent gastrointestinal tolerability in this study. Rates of nausea, diarrhea, stool frequency, and vomiting similar among VK2809-treated patients compared to placebo.

VOYAGE 數據也強化了 VK2809 令人鼓舞的安全性和耐受性概況。據報道，接受 VK2809 治療的患者中 94% 的治療相關不良事件為輕度或中度。因不良事件而停藥的比例較低，安慰劑組和治療組之間保持平衡。與先前的研究一致，VK2809 在本研究中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。

The findings from both the Phase 2b VOYAGE study, as well as a previous Phase 2a NAFLD study are consistent with multiple prior studies that have demonstrated VK2809s lipid lowering properties, as well as its safety, tolerability and significant liver fat reduction. It is our belief that these features combined serve to establish VK2809 as a best-in-class therapeutic for the treatment of NASH.

2b 期 VOYAGE 研究以及先前的 2a 期 NAFLD 研究的結果與多項先前的研究一致，這些研究證明了 VK2809 的降脂特性及其安全性、耐受性和顯著的肝臟脂肪減少。我們相信，這些特性的結合有助於使 VK2809 成為治療 NASH 的最佳療法。

In the third quarter, the VOYAGE study continued and we expect to report data evaluating histologic changes assessed by hepatic biopsy after 52 weeks of treatment, in the first half of 2024. I will now review progress with our third clinical candidate VK0214 which is currently being evaluated in a Phase 1b trial in patients with X-linked adrenoleukodystrophy, or X-ALD.

第三季度，VOYAGE 研究繼續進行，我們預計在2024 年上半年報告治療52 週後通過肝臟活檢評估的組織學變化的數據。我現在將回顧我們的第三個臨床候選藥物VK0214 的進展情況，該目前藥物正在研究中在 X 連鎖腎上腺腦白質營養不良 (X-ALD) 患者的 1b 期試驗中進行了評估。

Like VK2809, VK0214 is an orally available small molecule thyroid hormone receptor beta agonist X-ALD is a rare and debilitating metabolic disorder that is caused by genetic mutations that disable the function of a Peroxisomal 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.

與VK2809 一樣，VK0214 是一種口服小分子甲狀腺激素受體β 激動劑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。結果，患者無法有效代謝極長鏈脂肪酸。這些化合物的累積被認為有助於 X-ALD 的發生和進展。

In a prior Phase 1 study in healthy subjects VK0214 demonstrated dose dependent exposures, no evidence of accumulation and the 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.

在先前對健康受試者進行的 1 期研究中，VK0214 表現出劑量依賴性暴露，沒有蓄積證據，且半衰期與預期每日一次給藥一致。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。VK0214 也表現出令人鼓舞的安全性和耐受性，沒有報告嚴重的不良事件，也沒有觀察到胃腸道副作用、生命徵象的治療或劑量相關訊號。或心血管措施。

Viking is currently enrolling a Phase 1b study evaluating VK0214 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 multicenter study in adult male patients with AMN. The primary objectives of the study are to evaluate the safety, tolerability and pharmacokinetics of VK0214 administered orally once daily for 28 days. The study also includes an exploratory assessment of changes in plasma levels very long chain fatty acids. This study continues to enroll, and we expect to complete enrollment by year-end.

Viking 目前正在進行一項 1b 期研究，評估 VK0214 對腎上腺脊髓神經病變或 AMN（X-ALD 形式，這是該疾病最常見的形式）患者的療效。該試驗是一項針對 AMN 成年男性患者的隨機、雙盲、安慰劑對照多中心研究。研究的主要目的是評估 VK0214 的安全性、耐受性和藥物動力學，每天口服一次，持續 28 天。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。這項研究仍在繼續招募，我們預計在年底前完成招募。

In conclusion, the first nine months of the year have been extraordinarily busy at Viking. Our newest program, evaluating VK2735 for the treatment of obesity was announced less than two years ago, and the program has matured quickly in 2023. During the first nine months of the year, we reported the results of the first Phase 1 trial of VK2735, which demonstrated encouraging safety and tolerability and exciting early signals of efficacy. We also initiated the complimentary Phase 1 trial evaluating a novel oral formulation of VK2735, which we believe may expand the market opportunity for this therapeutic.

總之，維京今年前九個月異常忙碌。我們最新的評估VK2735治療肥胖的計畫宣布不到兩年，該計畫在2023年迅速成熟。今年前九個月，我們報告了VK2735第一個1期試驗的結果，證明了令人鼓舞的安全性和耐受性以及令人興奮的早期療效訊號。我們還啟動了免費的 1 期試驗，評估 VK2735 的新型口服製劑，我們相信這可能會擴大這種療法的市場機會。

In the third quarter, we initiated the VENTURE Phase 2 trial to evaluate VK2735s longer term clinical benefits. We are very excited with the progress we've made with this program during 2023. And we look forward to reporting additional data for both the subcutaneous and oral formulations in the coming quarters. With respect to VK2809, the top line data from the VOYAGE study announced earlier this year, once again demonstrated best-in-class data from this program. The results reaffirmed VK2809's ability to drive significant reductions in liver fat, along with potentially cardioprotective benefits through robust reductions in plasma lipids.

第三季度，我們啟動了 VENTURE 2 期試驗，以評估 VK2735 的長期臨床效益。我們對該計劃在 2023 年取得的進展感到非常興奮。我們期待在未來幾季報告皮下和口服製劑的更多數據。關於 VK2809，今年稍早公佈的 VOYAGE 研究的頂線數據再次證明了該計畫的最佳數據。結果再次證實了 VK2809 能夠顯著降低肝臟脂肪，並透過大幅降低血漿脂質具有潛在的心臟保護作用。

The VOYAGE study is continuing, and we expect to report data on histologic changes assessed by hepatic biopsy after 52-weeks of treatment in the first half of 2024. And with respect to our third clinical program VK0214 the Phase 1b study evaluating VK0214 in patients with adrenomyeloneuropathy continues, and we anticipate completing enrollment by year-end.

VOYAGE 研究仍在繼續，我們預計在2024 年上半年報告52 週治療後通過肝臟活檢評估的組織學變化數據。關於我們的第三個臨床項目VK0214，該1b 期研究評估了VK0214 在患有以下疾病的患者中的作用：腎上腺脊髓神經病變仍在繼續，我們預計在年底前完成招募。

Importantly, as we aggressively advance our pipeline, we continue to carefully manage our finances and maintain a strong balance sheet of approximately $376 million, which we believe extends our operating runway beyond the value creating milestones ahead for each of our programs. This concludes our prepared comments for today. Thanks very much for joining us, and we'll now open the call for questions. Operator?

重要的是，隨著我們積極推進我們的產品線，我們將繼續謹慎管理我們的財務並維持約3.76 億美元的強勁資產負債表，我們相信這將擴大我們的營運跑道，超越為我們每個項目創造里程碑的價值。我們今天準備的評論到此結束。非常感謝您加入我們，我們現在開始提問。操作員？

(Operator Instructions) Our first question comes from Joon Lee of Truist Securities. Please go ahead.

（操作員指示）我們的第一個問題來自 Truist Securities 的 Joon Lee。請繼續。

Hey, congrats on the progress and thanks for taking our questions. For the VK2735, based on the completion of Phase 2 VENTURE trial enrollment disclosed earlier this week, we'd expect a top line from the 13-week study to come sometime in the February or March time frame. So, first quarter of next year. Any reason why we shouldn't expect data in first quarter of 24? And I have a quick follow-up.

嘿，恭喜您取得的進展，並感謝您提出我們的問題。對於 VK2735，根據本週早些時候披露的 2 期 VENTURE 試驗註冊完成情況，我們預計為期 13 週的研究的頂線將在 2 月或 3 月的某個時間出現。那麼，明年第一季。為什麼我們不應該期待 24 日第一季的數據？我有一個快速的跟進。

Hey, Joon, thanks. We're guiding really to the first half. Hard to put a more precise date on it than that because you never know if there are extra things to clean up in the database or things like that. Your timeline doesn't seem crazy, but I would be cautious to guide too detailed right now. We just completed enrollment.

嘿，瓊，謝謝。我們確實在引導上半場。很難給出比這更精確的日期，因為你永遠不知道資料庫中是否有額外的東西需要清理或類似的東西。你的時間表看起來並不瘋狂，但我現在會謹慎指導太詳細。我們剛剛完成註冊。

Yes. And congrats on the enthusiasm that met the over enrollment. And, on the Oral VK2735, can you elaborate on the reasons why it may be delayed to first quarter of next year? Is that due to an addition in possibly another cohort or those? Or just wondering what the delay could be due to? Thank you.

是的。並對超額報名的熱情表示祝賀。還有，關於Oral VK2735，您能詳細說明一下可能推遲到明年第一季的原因嗎？這是由於可能是另一個隊列或其他隊列的增加造成的嗎？或者只是想知道延遲可能是由於什麼原因造成的？謝謝。

Yes, thanks, Joon. No it's really just going more slowly than we'd like. Nothing more than that. We haven't reached the point. The protocol is flexible in that we can add additional cohorts, but we're not to the point of making any of those decisions at this point.

是的，謝謝，瓊。不，它只是進展得比我們希望的要慢。僅此而已。我們還沒有達到目的。該協議很靈活，因為我們可以添加額外的群組，但我們目前還沒有到做出任何這些決定的地步。

Our next question comes from Steve Seedhouse from Raymond James. Please go ahead.

我們的下一個問題來自 Raymond James 的 Steve Seedhouse。請繼續。

On the Oral 2735 study, I just wanted to ask if you have a sense of whether the pharmacology of the oral formulation is really translating clinically as you'd expect and if the relative potency versus the injectable formulation is sort of holding up. Can you comment on your updated or current conviction there?

在 Oral 2735 研究中，我只是想問您是否了解口服製劑的藥理學是否真的如您所期望的那樣在臨床上轉化，以及與注射製劑相比的相對效力是否保持不變。您能評論一下您更新的或當前的信念嗎？

Well we think, thanks Steve. We think the mechanism should hold if the drug is well absorbed and we get good exposures. We're blinded to the study right now. So it's just ongoing. We don't have any further comment really on efficacy or tolerability or any of those metrics just yet.

好吧，我們認為，謝謝史蒂夫。我們認為，如果藥物吸收良好並且我們獲得良好的暴露，該機制應該成立。我們現在對這項研究視而不見。所以它還在繼續。我們還沒有對功效或耐受性或任何這些指標進行任何進一步的評論。

Okay. Thanks for that, Brian. And just following up on the progress of the study, can you comment just generally on sort of where you are relative to the planned overall number of cohorts, like where you are in terms of dose levels? Has your thinking evolved at all? And specifically, obviously, the VENTURE Study enrolling the way it did, does that sort of change your urgency or your strategy with how you're executing this Phase 1 Oral study?

好的。謝謝你，布萊恩。就追蹤研究進展而言，您能否概括性地評論一下您相對於計劃的隊列總數的情況，例如您在劑量水平方面的情況？你的思想有進化嗎？具體來說，顯然，VENTURE 研究以它的方式進行招募，這是否會改變您執行第一階段口頭研究的緊迫性或策略？

No. It's a good question. No. The VENTURE Study enrolled really quickly, a really high interest and enthusiasm there. But it's a different study. It's a parallel cohort study and multi-center as opposed to the Phase 1 where it's a single site and it's a sequential cohort type of study. And in that type of a study, if, for example, the cohorts are not completely filled on a specific day and you have to have a patient or subject come in in staggered timeframes, it just delays the entire execution of the study. And that's really the reason for the delay there. It's just slower to move forward than we'd like. VENTURE, I think, is moving along really well.

不，這是一個好問題。不。VENTURE 研究的註冊速度非常快，人們的興趣和熱情非常高。但這是一項不同的研究。這是一項平行隊列研究，是多中心的，而不是第一階段，它是一個單一站點，並且是一個連續隊列類型的研究。在這種類型的研究中，例如，如果隊列在特定的一天沒有完全填滿，並且您必須讓患者或受試者在交錯的時間範圍內進入，那麼它只會延遲研究的整個執行。這確實是延誤的原因。只是前進的速度比我們希望的要慢。我認為，VENTURE 進展得非常順利。

Got it. And just lastly, I mean, obviously this space is hot right now and everyone is aware of these types of drugs. So I guess it's not totally shocking that the trial wouldn't enroll so fast. But there's also a lot of competing studies and commercially available products, of course. So anything you wanted to expand on just in terms of what you learned in the past six or seven weeks, just how that exceeded expectations so much? And is there anything specific you would call out? Or is it just what I noted, the general awareness of the mechanism?

知道了。最後，我的意思是，顯然這個領域現在很熱門，每個人都知道這些類型的藥物。所以我想試驗註冊得這麼快並不完全令人震驚。當然，還有很多競爭研究和商業產品。那麼，您想要擴展的內容只是您在過去六到七週內學到的東西，那麼它是如何超越預期的呢？有什麼具體要說的嗎？或者只是我所說的，對機制的普遍認識？

Yes, no, thanks. It's a great point. And we were surprised with the enthusiasm from the sites and everybody, all the investigators, had more people available than we could enroll. I think it's partly due to the extensive media coverage of weight loss drugs today. And I'm sure some contribution is there from the shortages that we see from semaglutide and Tirzepatide supplies. So I think both of those sort of combined here, that hyper-awareness and the commercial shortages.

是的，不，謝謝。這是一個很好的觀點。我們對網站的熱情感到驚訝，每個人，所有的調查人員，都有比我們能報名的更多的人。我認為這部分是由於當今媒體對減肥藥物的廣泛報導。我確信我們看到的索馬魯肽和替澤帕肽供應短缺有一定的貢獻。所以我認為這兩個因素在這裡結合在一起，即過度意識和商業短缺。

Is it too early? Because it's an experimental product. Do you have a sense that the investigators or even the patients just don't really distinguish between the drugs? In other words, if this is as big of a market as we all suspect, like there's going to be plenty of room for a lot of different players and that leaves room for you guys of course. Because it just seems like that would be implied by the speed with which you enrolled an experimental product.

是不是太早了？因為它是一個實驗產品。您是否覺得研究人員甚至患者並沒有真正區分這些藥物？換句話說，如果這是一個像我們所有人都懷疑的那樣大的市場，那麼就會有足夠的空間容納許多不同的參與者，當然也為你們留下了空間。因為這似乎是由您註冊實驗產品的速度所暗示的。

Yes, I think the investigators are aware of the differences in mechanisms certainly. On the patient side, I'm not so sure that awareness is there. There is a general awareness of GLP-1 agonists being attractive weight loss agents. And this drug has GLP in the part of the mechanism description. So to that extent, I'm sure it excited some candidate patients. But I don't think the patients necessarily view a dual as different from a single at this point. I think over time that will evolve as we get more data from the duals versus the singles. But today I just think it's sort of a high-level awareness in general from media coverage.

是的，我認為研究人員肯定意識到機制上的差異。在患者方面，我不太確定患者是否有意識。人們普遍認識到 GLP-1 激動劑是有吸引力的減肥藥。而這個藥在機制描述的部分有GLP。因此，從這個意義上說，我確信它讓一些候選患者興奮不已。但我不認為患者在這一點上一定認為雙重與單一不同。我認為隨著時間的推移，隨著我們從雙打和單打中獲得更多數據，這種情況將會改變。但今天我認為這是媒體報道中普遍存在的一種高層意識。

The next question comes from Jay Olson of Oppenheimer. Please go ahead.

下一個問題來自奧本海默的傑伊·奧爾森。請繼續。

Maybe to shift gears over to NASH for a moment. Can you share any thoughts on the failure of Akero's FGF21 drug and F4 NASH patients and talk about it? If you would consider studying cirrhotic NASH patients similar to the way Madrigal is doing with an outcome study?

也許暫時轉向 NASH。您能分享一下Akero的FGF21藥物失敗和F4 NASH患者的想法並談談嗎？您是否會考慮像 Madrigal 所做的結果研究那樣研究肝硬化 NASH 患者？

Hi, Jay. Yes it's a good question. And I'm not super close to the FGF21 mechanism. So I'm probably not the best person to ask there. But our understanding has always been that the F4 patient is just different from the F3 and earlier. They're just in a sicker state. The liver is far more advanced in disease and it's just different. We've seen failures in that indication before. Maybe if it was a longer study, there would have been a higher probability of success. But I don't know. That's just a speculative comment.

嗨，傑伊。是的，這是一個好問題。我對 FGF21 機制也不是很了解。所以我可能不是在那裡提問的最佳人選。但我們一直認為 F4 患者只是與 F3 及更早患者不同。他們只是處於病情較重的狀態。肝臟的疾病要嚴重得多，而且情況有所不同。我們之前已經看過該指示的失敗。也許如果研究時間更長，成功的可能性就會更高。但我不知道。這只是一個推測性的評論。

We will have to look at our biopsy data to drive any further decisions on going forward in cirrhotics versus just non-cirrhotics. But we don't have the data right now to support that decision.

我們將不得不查看我們的活檢數據，以推動肝硬化與非肝硬化的進一步決策。但我們現在沒有數據來支持這個決定。

Okay. All right. Sounds reasonable. And then congrats on getting the late breaker at AASLD for VK2809. Anything you'd like to highlight for investors to look out for in that presentation?

好的。好的。聽起來很有道理。然後恭喜您在 AASLD 獲得 VK2809 的後期突破者。您想在演講中向投資者強調什麼？

Yes, thanks, Jay. Well, we will be looking at some subsets. Diabetics versus non-diabetics because the prior 12-week study didn't have diabetics in that study. We'll also report data on effect sizes in F2 versus F3 to see if there is any differential efficacy as patients are more advanced in disease. Those sorts of things would be the incremental data around the presentation.

是的，謝謝，傑伊。好吧，我們將研究一些子集。糖尿病患者與非糖尿病患者，因為先前為期 12 週的研究中沒有糖尿病患者。我們也將報告 F2 與 F3 中效應大小的數據，以了解隨著患者病情進展是否存在任何差異療效。這些東西將是圍繞演示的增量數據。

The next question comes from Annabel Samimy with Stifel. Please go ahead.

下一個問題來自 Annabel Samimi 和 Stifel。請繼續。

Hi. I wanted to just pull back and look a little bit more big picture. So given the naturally higher potency of the dual agonists and the competitive profile of the injectable, which I think compares very favorably to others, and also the recent benchmarks set by other oral GLPs, I guess, have you reset your expectations around what we might see for the Phase 1? I guess they were relatively modest based on what we're seeing in some of the new benchmarks that are being set. So can you put some context around this? And are your more modest expectations possibly related to like a molecule-size question for dual agonists versus single agonists that could impact bioavailability? Thanks.

你好。我想退一步，看看更宏觀的情況。因此，考慮到雙激動劑天然較高的效力和注射劑的競爭特徵（我認為與其他藥物相比非常有利），以及其他口服 GLP 設定的最近基準，我想，您是否重新調整了我們的期望看到第一階段了嗎？根據我們在一些正在製定的新基準中看到的情況，我認為它們相對溫和。那麼您能提供一些背景資訊嗎？您更溫和的期望是否可能與雙激動劑與單一激動劑的分子大小問題有關，這可能會影響生物利用度？謝謝。

Thanks, Annabel. So we think that the dual mechanism is a really competitive mechanism. I think over time, the addition of a second agonist mechanism should allow the efficacy to exceed a monoagonist. Whether or not that's evident to 28 days, I mean, I don't know. We're still looking for if we see something in the 1% to 2% in excess of placebo, that would probably, and good tolerability and safety, that would probably be sufficient to move it forward into phase 2.

謝謝，安娜貝爾。所以我們認為雙軌制是一個真正的競爭機制。我認為隨著時間的推移，添加第二種激動劑機制應該會讓功效超過單一激動劑。我的意思是，我不知道這在28天內是否明顯。我們仍在尋找是否能看到比安慰劑多 1% 到 2% 的東西，這可能會，並且良好的耐受性和安全性，這可能足以將其推進到第 2 階段。

But I think it's important to keep in mind these are 28-day PK safety and tolerability studies, and they're being compared in ways that are almost like phase 3 registration studies. And there's a reason you don't treat obesity in 28 days. It takes years to develop, and it takes longer than 28 days to really effectively treat. Registration studies have to be at least 52 weeks. So I understand all the comparisons, but we're not too worried about our mechanism being non-competitive.

但我認為重要的是要記住這些是 28 天的 PK 安全性和耐受性研究，而且它們的比較方式幾乎類似於第 3 階段註冊研究。 28天內不治療肥胖是有原因的。它需要數年的時間才能形成，並且需要超過28天才能真正有效地治療。註冊研究必須至少持續 52 週。所以我理解所有的比較，但我們不太擔心我們的機制不具競爭性。

Yes, I'm not worried about the non-competitiveness of the mechanism. I think the dual agonists are pretty strong. I'm just wondering if you had any reservations about getting a larger molecule into an oral formulation, if that is one of the reasons for your more cautious or conservative expectations.

是的，我並不擔心機制的非競爭性。我認為雙重激動劑非常強大。我只是想知道您是否對將較大分子納入口服製劑有任何保留，這是否是您更加謹慎或保守期望的原因之一。

No, no. It's just generally the exposure levels from oral peptides are lower than sub-Q. So that would tend to lead to a lower level of efficacy long-term. And that's kind of what we've seen in other settings as well. But over 28 days, I think we're just looking for a signal of are the exposures there? Are we seeing some weight loss? And is the tolerability acceptable?

不，不。一般而言，口服勝肽的暴露量低於 sub-Q。因此，這往往會導致長期療效水平較低。這也是我們在其他環境中看到的情況。但在過去 28 天裡，我認為我們只是在尋找是否有風險暴露的訊號？我們看到體重減輕了嗎？耐受性是否可以接受？

Okay, fair enough. And then on NASH, I guess, what are your thoughts on the impact of some of these anti-obesity products on NASH? Is it more of a growth impactor for the market, or will it potentially eat into the opportunity? I mean, we're recognizing that the market is large and very heterogeneous, but some KOLs have cited meaningful reductions in the market. Just want to hear your thoughts on that, even with your own compound that's shown, 2735 has shown also liver fat content reductions for NAFLD patients. So I'm just trying to think about how you're considering the impact on the market.

好吧，很公平。然後關於 NASH，我想，您對其中一些抗肥胖產品對 NASH 的影響有何看法？它更多的是對市場成長的影響，還是可能會蠶食這個機會？我的意思是，我們認識到市場很大而且非常多樣化，但一些 KOL 提到了市場的有意義的減少。只是想聽聽您對此的想法，即使使用您自己的化合物，2735 也顯示出 NAFLD 患者肝臟脂肪含量的降低。所以我只是想想想你們如何考慮對市場的影響。

Yes, it's a really heterogeneous market. You have diabetics and non-diabetics, obese patients and non-obese patients. You have patients who have heavy fibrosis and not a lot of liver fat, and you have patients with a lot of liver fat and fibrosis. So it leads to the possibility of multiple combination therapies. I do think that expanding use of GLP-1s might lead to that being looked at as more of a sort of backbone type of therapy, but I don't think that precludes an opportunity for more directed drugs that are really targeting the liver and address specific features of NASH, where the single and dual agonists and triple agonists don't necessarily do that directly. So I think maybe the increase in awareness from using more GLP-1s in NASH in patients with NAFLD could help actually some of the more directed agents in that some patients who might not respond as well on liver histology might see earlier use of a combination agent with a GLP-1 or other dual agonists.

是的，這是一個非常多元化的市場。有糖尿病患者和非糖尿病患者、肥胖患者和非肥胖患者。有些患者患有嚴重纖維化但肝臟脂肪不多，有些患者則患有大量肝臟脂肪和纖維化。因此它帶來了多種聯合療法的可能性。我確實認為擴大 GLP-1 的使用可能會導致它被視為一種主要的治療方法，但我不認為這排除了開發真正針對肝臟並解決問題的更有針對性的藥物的機會。NASH 的具體特徵，其中單激動劑、雙激動劑和三種激動劑不一定直接起作用。因此，我認為，也許透過在NAFLD 患者的NASH 中使用更多GLP-1 來提高認識，實際上可以幫助一些更有針對性的藥物，因為一些可能對肝臟組織學反應不佳的患者可能會更早期使用合併藥物與 GLP-1 或其他雙重激動劑一起使用。

Okay, got it. And then one last question if I may. Could you remind us what your patent situation is with both products?

好，知道了。如果可以的話，還有最後一個問題。您能否提醒我們這兩種產品的專利狀況如何？

Well, with the dual agonists, the IP estate was run beyond 2040. With the VK2809, the thyroid beta agonist, we have multiple patents in the 2037 to I think 2043 range now. The composition of matter for that compound would expire in the mid-2030 time frame. I think it's May 2030 with a five-year extension on it. But we have at least five additional patents that begin to expire 2037 out to 2043, I believe, for this one.

嗯，有了雙激動劑，智慧財產權財產可以持續到 2040 年以後。有了 VK2809（甲狀腺 β 激動劑），我們現在在 2037 年到 2043 年範圍內擁有多項專利。該化合物的物質成分將在 2030 年中期到期。我認為是 2030 年 5 月，還有五年的延期。但我相信，對於這項專利，我們至少還有五項額外專利，將於 2037 年至 2043 年到期。

Our next question comes from Joe Pantginis from HC Wainwright. Please go ahead.

我們的下一個問題來自 HC Wainwright 的 Joe Pantginis。請繼續。

Brian, I want to latch on to your comment about the hyperawareness around the GLPs. And specifically, look, there's a growing notion here about the "Emerging AE profile" of these drugs as they're used for longer periods of time. I mean, no need to quote a lot of the studies or what have you. So I guess, can you take a moment to add a little more color or emphasis why you believe 2735 has a better AE profile? Obviously, it appears like it's coming out right now in the studies and what you've disclosed. But anything you can really emphasize, I think, would be helpful for us, as well as similar to an earlier question, as this field evolves, has it changed any of your thinking with regard to how your own development plans might progress?

Brian，我想了解您關於 GLP 的過度意識的評論。具體來說，隨著這些藥物使用時間的延長，人們越來越意識到這些藥物的「新興不良事件特徵」。我的意思是，不需要引用很多研究或你擁有的東西。所以我想，您能花點時間添加更多顏色或強調為什麼您認為 2735 具有更好的 AE 設定檔嗎？顯然，它似乎正在研究和您所披露的內容中出現。但我認為，你真正能強調的任何事情都會對我們有所幫助，就像之前的問題一樣，隨著這個領域的發展，它是否改變了你對自己的發展計劃如何進展的想法？

Yes thanks, Joe. I think what we've seen in the Phase 1 experience with VK2735 is really encouraging on AEs. AEs, for the most part were mild to moderate. Tolerability was really outstanding. We didn't really see a dose dependency in some of the AEs. The highest dose cohort actually looked a lot like the lowest dose cohort when it came to the GI tolerability side effects like nausea and vomiting. And it's a small data set, so it's hard to talk too much definitively. But there is some evidence that when GIP is activated, there is an offset to the GLP-1 induced nausea, and that might allow better tolerability with the dual agonist where GIP is part of the mechanism.

是的，謝謝，喬。我認為我們在 VK2735 的第一階段經驗中所看到的 AE 確實令人鼓舞。 AE 大部分為輕度至中度。耐受性確實非常出色。我們並沒有真正看到某些不良事件有劑量依賴性。當涉及噁心和嘔吐等胃腸道耐受性副作用時，最高劑量組實際上看起來很像最低劑量組。而且這是一個很小的數據集，因此很難明確地談論太多。但有一些證據表明，當 GIP 被激活時，GLP-1 引起的噁心會得到抵消，這可能會提高雙激動劑的耐受性，其中 GIP 是該機制的一部分。

Really early in our data set to say that, but if that is true, then the dual agonist should separate on tolerability over time relative to simply a high dose GLP-1 monoagonist. But really early to make those sorts of comments right now.

在我們的資料集中確實很早就說過了，但如果這是真的，那麼相對於簡單的高劑量GLP-1 單激動劑，雙激動劑隨著時間的推移在耐受性上應該是分開的。但現在發表這類評論還為時過早。

Any views on development plans? Have there been any alterations in your mind based on how the field has been evolving?

對發展計畫有何看法？根據該領域的發展，您的想法是否發生了任何變化？

No, no. We're full steam ahead on both. The oral program is a little more slow than we'd like, but it's pedal to the metal on both programs right now. No changes to our plans.

不，不。我們在這兩方面都全力以赴。口頭節目比我們想要的要慢一點，但現在兩個節目都在全力以赴。我們的計劃沒有改變。

The next question comes from Andy Hsieh of William Blair. Please go ahead.

下一個問題來自威廉布萊爾的安迪謝。請繼續。

So, looking at the obesity week presentation, I'm just curious if you have thoughts regarding baseline characteristics, especially for age. Looking at the average age, 29 for placebo, 42 for the highest dose. Does that favor placebo and underestimate the effect size of 27, 35? We've seen some imbalances in age across, several obesity studies.

因此，看看肥胖週的介紹，我很好奇您是否對基線特徵（尤其是年齡）有什麼想法。從平均年齡來看，安慰劑組為 29 歲，最高劑量組為 42 歲。這是否有利於安慰劑並低估了 27、35 的效果量？我們在多項肥胖研究中發現了一些年齡不平衡的情況。

Yes, I don't know if that's – there were some imbalances in age and also in weight, and then some of the cohorts had more men than women and more women than men, and it was really hard to discern any differences based on any of those metrics. But I think, we'll be able to make a better call on that after the Phase 2 study. It's a good question, though.

是的，我不知道這是否是——年齡和體重上存在一些不平衡，然後有些隊列中男性多於女性，女性多於男性，這真的很難根據這些指標來辨別任何差異。但我認為，在第二階段研究之後，我們將能夠對此做出更好的決定。不過，這是個好問題。

Yes, okay. Great. So related to that, just curious about, expectations or how you frame expectations for liver fat reduction for the VENTURE study that we'll read out in the first half.

是的，好的。偉大的。與此相關的是，只是好奇，期望或如何為我們將在上半場宣讀的 VENTURE 研究制定肝臟脂肪減少的期望。

Well, with VENTURE, we're looking more at body weight and not at liver fat, so we're just looking at body weight changes. We're not doing the MRI in the VENTURE trial. We did see really attractive reductions, although the numbers were small in the Phase 1 study, but nearly 60% relative reduction in liver fat after four doses. That was really impressive, a bit higher than we expected in just four doses, but we're not doing the MRI in the VENTURE study.

嗯，對於 VENTURE，我們更關注體重而不是肝臟脂肪，所以我們只關注體重變化。我們不會在 VENTURE 試驗中進行 MRI。我們確實看到了非常有吸引力的減少，儘管第一階段研究中的數字很小，但四次給藥後肝臟脂肪相對減少了近 60%。這確實令人印象深刻，僅四劑劑量就比我們預期的要高一些，但我們在 VENTURE 研究中沒有進行 MRI。

Got it, okay. And maybe lastly for manufacturing, obviously there's a lot of press and attention related to the drug class. I'm just curious, you can comment on 2735's CMC where it is, capacity for either like a Phase 2b or Phase 3 study?

明白了，好吧。也許最後對於製造來說，顯然有很多與藥物類別相關的媒體和關注。我只是好奇，您可以評論一下 2735 的 CMC 在哪裡，是否有能力進行 2b 期或 3 期研究？

Yes thanks, it's a great question and an area we're spending a lot of time on. We don't foresee any capacity constraints near term. If we were to be launching the drug next year, that would be different because the demands would be much higher, but for the clinical supplies, absolutely no problem we foresee today. We are looking more now than I think we probably would otherwise have looked at scalability and various approaches to enhance yields and shorten timelines for large scale syntheses. And I think we're a place where we have several options available to us. And I don't think by the time this compound would be available commercially, I don't think supply constraints would be the challenge that they are today.

是的，謝謝，這是一個很好的問題，也是我們花費大量時間的領域。我們預計近期不會有任何產能限制。如果我們明年推出這種藥物，情況會有所不同，因為需求會更高，但對於臨床供應來說，我們今天預見的絕對沒有問題。我們現在關注的東西比我想像的要多，否則我們可能會關注可擴展性和各種提高產量並縮短大規模合成時間的方法。我認為我們有多種選擇。我不認為當這種化合物投入商業使用時，供應限制不會成為今天所面臨的挑戰。

The next question comes from Thomas Smith of Leerink Partners. Please go ahead.

下一個問題來自 Leerink Partners 的托馬斯史密斯。請繼續。

Just on 2735, I think you've generated quite a bit of preclinical data now for the oral form of this compound. I was wondering if there's any plans or opportunities for you to present some of these preclinical data in the near term, maybe before we get the Phase 1 data that's now expected in Q1.

就在 2735，我認為您現在已經為該化合物的口服形式產生了大量臨床前數據。我想知道您是否有任何計劃或機會在短期內（也許在我們獲得目前預計在第一季度獲得的第一階段數據之前）提供一些臨床前數據。

Yes thanks, Tom. We've been pretty quiet about the data from the oral formulation. And so we don't have any plans at this point to present data between now, animal data between now and the Phase 1 readout in the first quarter.

是的，謝謝，湯姆。我們對口服製劑的數據一直保持沉默。因此，我們目前沒有任何計劃提供從現在到第一季第一階段讀數之間的動物數據。

Okay, got it. And another question on 2735. I know you just showed some strong liver fat reduction data at obesity week. Can you just remind us Brian, how you're thinking about 2735 potential in NASH? And I guess whether you're considering generating any of your own data there with 2735, either alone or in combination with 2809?

好，知道了。還有一個關於2735的問題。我知道你剛剛在肥胖週上展示了一些強有力的肝臟脂肪減少數據。 Brian，您能否提醒我們，您如何看待 2735 在 NASH 中的潛力？我猜您是否正在考慮使用 2735 單獨生成您自己的數據，或與 2809 一起生成數據？

Yes well, we did the MRIs here and we didn't have a baseline requirement for an MRI in the Phase 1 study, but we did it just to see if there was some impact. We know with the GLP-1s, I think we can see 30 some percent reductions. And so we had hoped with the GIP and GLP-1 dual agonists that you'd see something in that neighborhood. And we did see that and better. But so it was kind of a sort of proof-of-concept there. We don't have any plan today to move into NASH. It was just something that we wanted to know how does it compare to a mono agonist.

是的，我們在這裡做了 MRI，在第一階段研究中我們沒有 MRI 的基線要求，但我們這樣做只是為了看看是否有一些影響。我們知道，透過 GLP-1，我認為我們可以看到 30% 左右的減少。因此，我們希望透過 GIP 和 GLP-1 雙重激動劑，您能在附近看到一些東西。我們確實看到了這一點，而且做得更好。但這是一種概念驗證。我們今天沒有任何進入 NASH 的計劃。我們只是想知道它與單受體激動劑相比如何。

And I think it compares favorably to the mono agonist that we've seen. And I think it also, even though the timeline's a lot shorter it compares favorably to the triple agonist data that are out there, the much longer time treatment window with that compound. But I think we feel good about what we've seen so far.

我認為它比我們見過的單激動劑更有利。我也認為，儘管時間線短得多，但與現有的三重激動劑數據相比，該化合物的治療時間窗口要長得多。但我認為我們對迄今為止所看到的情況感覺良好。

(Operator Instructions) Our next question comes from Yale Jen of Laidlaw & Company. Please go ahead.

（操作員說明）我們的下一個問題來自 Laidlaw & Company 的 Yale Jen。請繼續。

Again, on the obesity week data, just curious that if the VENTURE data also looks good, does the obesity, I'm sorry, the obesity week data in the plasma lipid as well as in the statin lipid, would impact on your potential future, let's say Phase 3 study in terms of selecting more sub-cohort of the obesity patients or that's not necessarily into consideration?

再一次，關於肥胖週數據，只是好奇，如果 VENTURE 數據看起來也不錯，那麼肥胖是否會影響您潛在的未來，對不起，肥胖週血脂和他汀類脂質中的數據，假設第三階段研究是為了選擇更多的肥胖患者子隊列，或不一定要考慮這一點？

Not in consideration at this point. I think the plasma lipid effects were really interesting in that they might allow you to reduce the dose of a statin or something like that. So that was a really neat finding. And it was kind of across the board there. We saw a nice reductions in plasma lipids. But for now, the VENTURE Study will be a pure obesity study. It is a pure obesity study. And we anticipate the subsequent studies to really focus on obesity and not any subsets at this point.

目前暫不考慮。我認為血漿脂質效應非常有趣，因為它們可能允許您減少他汀類藥物或類似藥物的劑量。所以這是一個非常巧妙的發現。那裡的情況是全面的。我們看到血漿脂質明顯降低。但目前，VENTURE 研究將是一項純粹的肥胖研究。這是一項純粹的肥胖研究。我們預計後續研究將真正關注肥胖，而不是目前的任何子集。

Okay, great. Just one more question here. In terms again, in 2735, first of all do you guys have any specific injectors used in the study? And how do you see that in the future that at least currently there's some shortage issues? What's your thoughts?

好的，太好了。這裡還有一個問題。再說一遍，2735，首先你們研究中有沒有使用什麼特定的注射器？您如何看待未來至少目前存在的一些短缺問題？你有什麼想法？

Yes, yes. Fortunately, we have some time to work through that. And we are looking at sort of the early models of injectors. This trial is a vial and syringe trial where people are dosed in the clinic. But the next studies we would anticipate to use some form of an auto-injector.

是的是的。幸運的是，我們有一些時間來解決這個問題。我們正在研究早期的噴射器模型。該試驗是小瓶子和注射器試驗，人們在診所接受給藥。但接下來的研究我們預計會使用某種形式的自動注射器。

Okay, great. And congrats on all the progress and look forward to readout early next year.

好的，太好了。恭喜所有進展，並期待明年初的宣讀。

Our next question comes from Justin Zelin of BTIG. Please go ahead.

我們的下一個問題來自 BTIG 的 Justin Zelin。請繼續。

Hey, Brian. Congrats on the progress here. Just wanted to ask you've seen promising data from both 2809 and 2735. Just wanted to hear your current thoughts on a potential study using both agents in the treatment of NASH. And then just a quick follow-up.

嘿，布萊恩。恭喜這裡的進展。只是想問您是否看到了 2809 和 2735 的有希望的數據。只是想聽聽您目前對使用這兩種藥物治療 NASH 的潛在研究的想法。然後進行快速跟進。

Yes thanks, Justin. We spent a lot of time on that thinking about how these could be combined. They're different formulations. And so the up-front formulation work is a little more extensive if we were to pursue a combination agent. And then the other requirements on tox is also, it's just different with two unapproved agents. So more extensive on that front as well. So I think it's a really potentially high-value combination. But we don't have anything to say further about it right now. I think it could be very useful though in the future.

是的，謝謝，賈斯汀。我們花了很多時間思考如何將這些結合起來。它們是不同的配方。因此，如果我們要尋求一種組合劑，前期的配製工作會更加廣泛。然後對tox的其他要求也是，只是與兩個未經批准的代理人不同。在這方面也更加廣泛。所以我認為這是一個真正具有潛在高價值的組合。但我們現在對此無話可說。我認為它在未來可能非常有用。

Right. That makes sense to me. And then you're developing both an oral and an injectable. Maybe just to hear your current thoughts on how that market might evolve. Obviously with multiple modalities, do you think patients might start in an injectable and then move to an oral for maintenance?

正確的。這對我來說很有意義。然後你正在開發口服劑和注射劑。也許只是想聽聽您目前對該市場如何發展的想法。顯然，對於多種治療方式，您認為患者可能會從注射開始，然後轉向口服維持治療嗎？

Yes. We view them as different products, really. The option you mentioned where somebody maybe doesn't want to start with an injectable because they feel like it's a little more intensive or intrusive, whatever starting with an oral and seeing some weight loss might lower the resistance to start using injectable. So that's one option. The other would be the flip side where someone who's lost a lot of weight on an injectable might want to transition to an oral and so for more of a maintenance, longer-term usage. That's another great opportunity.

是的。我們確實將它們視為不同的產品。在您提到的選項中，有人可能不想從注射劑開始，因為他們覺得注射劑有點強度或侵入性，無論從口服開始並看到一些體重減輕可能會降低開始使用注射劑的阻力。所以這是一種選擇。另一方面是透過注射劑減肥的人可能想過渡到口服劑，以便更多地維持、長期使用。這又是一個絕佳的機會。

And then the other big bucket we think about is, temporary use. Somebody wants to lose some weight for summer or an upcoming event or something like that. I think there would be a great opportunity there. So the oral does not need the same efficacy as the sub-Q because the uses will likely be different. So I think they're nicely complementary products and have completely complementary areas of application.

然後我們考慮的另一個大桶是臨時使用。有人想為夏天或即將到來的活動或類似的事情減肥。我認為那裡會有一個很好的機會。因此，口服不需要與 sub-Q 具有相同的功效，因為用途可能會有所不同。所以我認為它們是很好的互補產品，並且具有完全互補的應用領域。

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

我們的問答環節到此結束。現在我想將會議轉回斯蒂芬妮·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. Have a good afternoon.

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。祝你下午好。

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。