Veru Inc (VERU) 2025 Q2 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to Veru Inc.'s investor conference call. (Operator Instructions) Please note that this event is being recorded.

女士們、先生們，早安，歡迎參加 Veru Inc. 的投資者電話會議。（操作員指示）請注意，此事件正在被記錄。

I would now like to turn the conference call over to Mr. Sam Fisch, Veru Inc.'s Executive Director, Investor Relations and Corporate Communications. Please go ahead, sir.

現在，我想將電話會議交給 Veru Inc. 投資者關係和企業傳播執行董事 Sam Fisch 先生。先生，請繼續。

Statements made on this conference call may be forward-looking statements. Forward-looking statements may include, but are not necessarily limited to, statements of the company's plans, objectives, expectations, or intentions regarding its business, operations, regulatory interactions, finances and development, and product portfolio.

本次電話會議的陳述可能是前瞻性陳述。前瞻性陳述可能包括但不限於公司關於其業務、營運、監管互動、財務和發展以及產品組合的計劃、目標、期望或意圖的陳述。

Such forward-looking statements are subject to known and unknown risks and uncertainties, and our actual results may differ significantly from those projected, suggested, or included in any forward-looking statements. Risks that may cause actual results or developments to differ materially are contained in our 10-Q and 10-K SEC filings as well as in our press releases from time to time.

此類前瞻性陳述受已知和未知的風險和不確定性的影響，我們的實際結果可能與任何前瞻性陳述中預測、建議或包含的結果有重大差異。我們向美國證券交易委員會提交的 10-Q 和 10-K 文件以及我們不時發布的新聞稿中都包含可能導致實際結果或發展出現重大差異的風險。

I would now like to turn the conference call over to Dr. Mitchell Steiner, Veru Inc.'s Chairman, CEO and President.

現在，我想將電話會議交給 Veru Inc. 的董事長、執行長兼總裁 Mitchell Steiner 博士。

Good morning. With me on this morning's call are Dr. Gary Barnette, the Chief Scientific Officer; Michele Greco, Chief Financial Officer and Chief Administrative Officer; Michael Purvis, General Counsel and Executive Vice President of Corporate Strategy; and Sam Fisch, Executive Director of Investor Relations and Corporate Communications. Thank you for joining our Q2 fiscal year 2025 earnings call.

早安.參加今天早上電話會議的還有首席科學官加里·巴內特博士、首席財務官兼首席行政官米歇爾·格雷科、總法律顧問兼企業戰略執行副總裁邁克爾·珀維斯以及投資者關係和企業傳播執行總監薩姆·菲什。感謝您參加我們的 2025 財年第二季財報電話會議。

Veru is a late clinical stage biopharmaceutical company focused on developing novel medicines for the treatment of cardiometabolic and inflammatory diseases. Our drug development program consists of two clinical stage drug candidates, enobosarm and sabizabulin. Enobosarm, an oral selective androgen receptor modulator, SARM is being developed as a novel drug that makes GLP-1 receptor agonist weight reduction more tissue selective by preserving lean mass muscle, while causing greater fat loss in older patients who are overweight who have obesity.

Veru 是一家後期臨床階段生物製藥公司，專注於開發治療心臟代謝和發炎疾病的新型藥物。我們的藥物開發計劃包括兩種臨床階段候選藥物，enobosarm 和 sabizabulin。Enobosarm 是一種口服選擇性雄激素受體調節劑，SARM 正在開發一種新型藥物，透過保留瘦肌肉，使 GLP-1 受體激動劑減肥更具組織選擇性，同時使超重肥胖的老年患者減少更多脂肪。

Sabizabulin is an oral microtubule disruptor is being developed as a broad anti-inflammatory agent to reduce vascular plaque inflammation to slow the progression and promote the regression of atherosclerotic cardiovascular disease.

Sabizabulin 是一種口服微管破壞劑，正在開發一種廣泛的抗發炎劑，以減少血管斑塊炎症，減緩動脈粥狀硬化心血管疾病的進展並促進其消退。

This morning, we will focus our update only on our obesity program. As defined by FDA, obesity is a disease of excess body adiposity or fat. Therefore, the medical objective to treat obesity by weight reduction drug or drugs in combination should be to reduce excess body fat, not lean mass in order to improve the mobility and mortality associated with obesity.

今天早上，我們將只關注肥胖計劃的更新。根據FDA的定義，肥胖症是一種身體內脂肪過多或堆積過多的疾病。因此，透過減重藥物或合併藥物治療肥胖症的醫學目標應該是減少體內多餘的脂肪，而不是瘦體重，以改善與肥胖相關的活動能力和死亡率。

GLP-1 receptor agonists have been shown to produce significant weight loss in patients who are overweight, who have obesity. Unfortunately, the weight loss is tissue nonselective with the indiscriminate loss of both fat and lean mass. Of the total weight loss up to 50% of the total weight loss is attributable to lean mass. We must do a better job of getting rid of fat tissue only.

研究表明，GLP-1 受體激動劑可使超重和肥胖患者體重明顯減輕。不幸的是，體重減輕是組織非選擇性的，脂肪和瘦體重都會不加區別地減少。在整體體重減輕中，高達 50% 的減輕歸因於瘦體重。我們必須更好地去除脂肪組織。

Let's face it. No one wants to lose lean muscle mass. Most of this is common sense, but the beneficial consequences of increasing or maintaining muscle mass in an aging population are increased basal metabolism with sustainable weight management, better control of blood glucose, better joint health, better increased strength, increased balance, potential decreasing falls, increased bone mineral density, potential decreasing nontraumatic bone fractures, and increases in the possibility of maintaining independence in an older population.

讓我們面對現實吧。沒有人願意失去肌肉。其中大部分都是常識，但老年人增加或維持肌肉質量的有益後果是增加基礎代謝，可持續控制體重，更好地控制血糖，改善關節健康，增強力量，增強平衡，減少跌倒，增加骨礦物質密度，減少非創傷性骨折，並增加老年人保持獨立的可能性。

With that objective, we are developing enobosarm, which is an oral novel SARM, that has demonstrated in previous clinical studies improvements in body composition, with tissue selective increases in lean mass and decreases in fat mass, improvements in both muscle strength and physical function, no masculinizing effects in women and neutral prostate effects in men.

為了實現這一目標，我們正在開發 enobosarm，這是一種口服新型 SARM，在先前的臨床研究中已證明它可以改善身體成分，組織選擇性增加瘦體重並減少脂肪量，改善肌肉力量和身體機能，對女性沒有男性化作用，對男性前列腺沒有中性作用。

We conducted a Phase 2b multicenter, double-blind, placebo-controlled randomized dose-finding quality clinical study designed to evaluate the safety and efficacy of enobosarm 3 milligrams, enobosarm 6 milligrams, or placebo as a treatment to augment fat loss and prevent muscle loss in 168 older patients greater than equal to 60 years of age, receiving semaglutide, which is Wegovy weight -- for chronic weight management.

我們進行了一項 2b 期多中心、雙盲、安慰劑對照的隨機劑量探索質量臨床研究，旨在評估 enobosarm 3 毫克、enobosarm 6 毫克或安慰劑作為增強脂肪減少和防止肌肉減少的治療方法的安全性和有效性，適用於 168 名年齡大於 60 歲、接受司美格魯肽（Wegovy 體重 - 慢性體重等於 60 歲、接受司美格魯肽（Wegovy 體重）的老年患者。

The primary endpoint is percent change in baseline and total lean body mass and the key secondary endpoints are percent change in baseline and total body fat mass, total body weight and physical function as measured by Stair Climb Test at 16 weeks. After completing the efficacy dose assessment portion of the Phase 2b QUALITY clinical study, the patients continued into a Phase 2b extension maintenance trial where all patients have stopped treatment with semaglutide but continue to take placebo, enobosarm 3 milligrams, or enobosarm 6 milligrams in a blinded fashion for an additional 12 weeks.

主要終點是基線和總體瘦體重的百分比變化，關鍵次要終點是基線和整體脂肪質量、總體重和身體功能的百分比變化（透過 16 週的爬樓梯測試測量）。在完成 2b 期 QUALITY 臨床研究的療效劑量評估部分後，患者繼續進入 2b 期延長維持試驗，所有患者均停止使用司美格魯肽治療，但繼續以盲法服用安慰劑、enobosarm 3 毫克或 enobosarm 6 毫克，持續 12 週。

Phase 2b clinical trial will evaluate whether enobosarm can maintain muscle and prevent the fat regain that generally occurs after discontinuing of GLP receptor agonist. The purpose of the Phase 2b QUALITY clinical trial is to select the dose of enobosarm in combination with semaglutide, Wegovy that best preserves lean mass or muscle and physical function after 16 weeks of treatment to advance into a Phase 3 clinical program.

2b 期臨床試驗將評估 enobosarm 是否可以維持肌肉並防止停用 GLP 受體激動劑後通常發生的脂肪反彈。2b 期 QUALITY 臨床試驗的目的是選擇 enobosarm 與 semaglutide、Wegovy 聯合使用的劑量，以便在 16 週的治療後最好地保持瘦體重或肌肉和身體功能，從而進入 3 期臨床計劃。

The positive top-line results of the Phase 2b QUALITY clinical study demonstrated that enobosarm is a novel drug that when combined with the GLP-1 receptor agonist makes weight reduction more tissue selective for greater fat loss while preserving lean mass or muscle.

2b 期 QUALITY 臨床研究的積極頂線結果表明，enobosarm 是一種新型藥物，與 GLP-1 受體激動劑結合使用時，可以使減肥更具組織選擇性，從而實現更大的脂肪減少，同時保持瘦體重或肌肉。

Phase 2b QUALITY study is the first human study to report the effects of a muscle preservation drug candidate on body composition and physical function in older patients who are receiving a GLP-1 receptor agonist for weight reduction. The Phase 2b QUALITY clinical study met its primary endpoint with a statistically significant and clinically meaningful benefit of a 71% preservation of total lean body mass in all patients receiving enobosarm plus semaglutide versus placebo plus semaglutide at 16 weeks, and that p-value equals 0.002.

2b 期 QUALITY 研究是第一個報告肌肉保存候選藥物對接受 GLP-1 受體激動劑減肥的老年患者的身體組成和身體功能的影響的人體研究。2b 期 QUALITY 臨床研究達到了其主要終點，在 16 週時，所有接受 enobosarm 加 semaglutide 治療的患者與接受安慰劑加 semaglutide 治療的患者相比，總體瘦體重保留了 71%，具有統計學上顯著且有臨床意義的益處，並且 p 值等於 0.002 值。

Enobosarm 3-milligram plus semaglutide was the best dose with a greater than 99% mean relative reduction in the loss of lean mass and that p-value is less than 0.001, meaning almost the entire weight loss was fat mass. The enobosarm 6-milligram plus semaglutide dose preserved lean mass, but was not any better than the enobosarm 3-milligram plus semaglutide dose. This is not unexpected. This is similar to what we have seen in our previous multiple ascending dose clinical study. We believe that at a certain point, the targeted androgen receptor becomes oversaturated by drug.

Enobosarm 3 毫克加索美魯肽是最佳劑量，瘦體重損失平均相對減少量超過 99%，且 p 值小於 0.001，這意味著幾乎所有減掉的體重都是脂肪量。6 毫克依諾博司姆加司美格魯肽劑量可維持瘦體重，但不比 3 毫克依諾博司姆加司美格魯肽劑量更好。這並不出乎意料。這與我們先前在多次遞增劑量臨床研究中看到的情況類似。我們相信，在某個時刻，目標雄性激素受體會被藥物過度飽和。

As for the secondary clinical endpoints, enobosarm plus semaglutide treatment resulted in a dose-dependent greater loss of fat mass compared to placebo plus semaglutide with the enobosarm 6-milligram dose having a 46% greater relative loss of fat mass compared to placebo plus semaglutide group of 16 weeks, net p-value of 0.014.

至於次要臨床終點，與安慰劑加索馬魯肽相比，enobosarm 加索馬魯肽治療導致劑量依賴性的更大脂肪量損失，與 16 週的安慰劑加索馬魯肽組相比，enobosarm 6 毫克劑量的脂肪量相對損失高出 46%，淨 p 值為 0.014。

Although enobosarm plus semaglutide significantly preserved lean mass, the additional loss of fat mass caused by enobosarm treatment was able to replace that lean mass preserved to allow a similar net mean weight loss measured by DEXA with semaglutide at 16 weeks. Accordingly, with enobosarm treatment, the tissue composition of the total weight loss shifted to greater and more selective for fat loss.

儘管依諾博司姆合併索馬魯肽療法可顯著保留瘦體重，但依諾博司姆治療引起的額外脂肪量損失能夠取代保留的瘦體重，從而實現在 16 週時通過 DEXA 測量的與索馬魯肽相似的淨平均體重減輕。因此，透過enobosarm治療，整體重減輕的組織成分轉向更大且更有選擇性的脂肪減輕。

For the placebo semaglutide group, the median percentage of total body weight loss was 32% for lean mass and estimated fat loss was 68%. In contrast, in the all enobosarm plus semaglutide group, the total weight loss due to lean mass was only 9.4% and estimated fat loss was 90.6%. And in the enobosarm 3-milligram plus semaglutide group, it was 0.9% lean mass and 99.1% estimated fat loss. Therefore, enobosarm plus semaglutide improved changes in body composition, resulting in more selective and greater loss of fat compared to subjects receiving placebo plus semaglutide.

對於安慰劑司美格魯肽組，整體體重減輕的中位數百分比為瘦體重減輕 32%，估計脂肪減輕為 68%。相較之下，在所有依諾博賽姆加索美魯肽組中，由於瘦體重導致的總體體重減輕僅為 9.4%，而估計脂肪減輕為 90.6%。在 enobosarm 3 毫克加 semaglutide 組中，瘦體重減少了 0.9%，估計脂肪減少了 99.1%。因此，與接受安慰劑加司美格魯肽治療的受試者相比，enobosarm 加司美格魯肽改善了身體組成的變化，從而導致更有選擇性和更大的脂肪減少。

Now physical function was measured by the Stair Climb Test. Stair Climb Test is an activity of daily living as it measures muscle strength, balance and agility. Decline in performance measured by Stair Climb Test has been shown in older patients to predict a higher risk for mobility disabilities, gait difficulties, falls and bone fractures, hospitalizations, and mortality. A responder's analysis was conducted using a greater than 10% decline in stair climb power as a cutoff at 16 weeks. The greater than 10% decline in stair climb power at 16 weeks represents a seven- to eight-year loss of stair climb power function that occurs with aging, and this was documented by Van Roie in 2019.

現在透過爬樓梯測試來測量身體機能。爬樓梯測試是一項日常生活活動，它可以測量肌肉力量、平衡和敏捷性。研究表明，老年患者爬樓梯測試所測量的表現下降預示著行動障礙、步態困難、跌倒和骨折、住院和死亡的風險更高。以 16 週時爬樓梯能力下降超過 10% 作為截止值，對響應者進行了分析。16 週時爬樓梯能力下降超過 10% 代表著隨著年齡增長而發生的爬樓梯能力功能喪失 7 到 8 年，Van Roie 在 2019 年記錄了這一點。

In our study, the loss of lean mass matter, as 42.6% of patients on placebo plus semaglutide group had at least a 10% decline in stair climb power physical function in 16 weeks. Again, this is the first human study to demonstrate that older patients receiving GLP-1 receptor agonist for weight loss are at higher risk for accelerated loss of lean mass and with physical decline. The all enobosarm plus semaglutide group had statistically significant and clinically meaningful 54.4% relative reduction in the proportion of subjects with loss at least 10% stair climb power compared to placebo semaglutide group, and that p-value was 0.0049.

在我們的研究中，瘦體重的損失很重要，因為在 16 週內，安慰劑加司美魯肽組中 42.6% 的患者爬樓梯力量身體功能下降了至少 10%。再一次，這是第一個人體研究，證明接受 GLP-1 受體激動劑減肥的老年患者加速瘦體重損失和體力下降的風險更高。與安慰劑索馬魯肽組相比，全依諾博賽姆加索馬魯肽組爬樓梯能力下降至少 10% 的受試者比例相對減少了 54.4%，具有統計學意義和臨床意義，p 值為 0.0049。

In the enobosarm 3-milligram plus semaglutide group, there was a 62.4% relative reduction in the proportion of patients with at least a 10% decline in Stair Climb power from baseline versus placebo plus semaglutide group, that p-value was 0.0066. In the 6-milligram plus semaglutide group, there was a 46.2% relative reduction in the proportion of patients with at least a 10% decline in stair climb power from baseline versus placebo plus semaglutide group and the p-value is 0.0505.

在依諾博賽姆3毫克加索美魯肽組中，與安慰劑加索美魯肽組相比，爬樓梯能力較基線下降至少10%的患者比例相對減少了62.4%，p值為0.0066。在依諾博賽姆6毫克加索美魯肽組中，與安慰劑加索美魯肽組相比，爬樓梯能力較基線下降至少10%的患者比例相對減少了46.2%，p值為0.0505。

In conclusion, enobosarm treatment on average preserved lean mass and muscle, which translated into a reduction in the proportion of patients who had a clinically significant decline in Stair Climb physical function versus patients receiving semaglutide alone.

總之，enobosarm 治療平均保留了瘦體重和肌肉，與單獨接受 semaglutide 治療的患者相比，這意味著爬樓梯身體功能出現臨床顯著下降的患者比例有所減少。

In summary, enobosarm plus semaglutide improved changes in body composition, which resulted in more selective and greater loss of adiposity or fat mass while preserving lean mass and muscle and preserving physical function or stair climb power compared to patients receiving placebo or semaglutide alone.

綜上所述，與單獨接受安慰劑或索馬魯肽治療的患者相比，enobosarm 聯合索馬魯肽治療可改善身體組成的變化，從而更有選擇性地減少更多脂肪，同時保持瘦體重和肌肉，並保持身體機能或爬樓梯能力。

Enobosarm represents a novel drug that in combination with a GLP-1 receptor agonist containing therapy causes greater and more selective loss of fat mass, which is the goal for higher quality chronic weight management.

Enobosarm 是一種新型藥物，它與含有 GLP-1 受體激動劑的療法相結合，可以更大程度、更有選擇性地減少脂肪量，這是更高品質的慢性體重管理的目標。

Next, we will discuss several upcoming clinical and regulatory catalysts. Number one, results of the unblinded safety data for the Phase 2b QUALITY study are expected this quarter. Safety data for the Phase 2b QUALITY study remains blinded as the Phase 2 extension maintenance clinical study portion is still finishing up.

接下來，我們將討論幾個即將到來的臨床和監管催化劑。首先，預計第 2b 階段 QUALITY 研究的非盲安全資料結果將於本季公佈。由於第 2 階段擴展維持臨床研究部分仍在收尾，因此第 2b 階段品質研究​​的安全數據仍處於盲態。

It should be noted that the aggregate blinded safety data have not shown any significant differences compared to previous clinical studies of enobosarm and what is expected for GLP-1 receptor agonist. Further, the Independent Data Monitoring Committee met February 10, 2025, to evaluate the unblinded safety data. And they made the recommendation to continue the study as planned.

值得注意的是，與 enobosarm 的先前臨床研究和 GLP-1 受體激動劑的預期相比，整體盲法安全數據並未顯示出任何顯著差異。此外，獨立資料監測委員會於 2025 年 2 月 10 日召開會議，評估未盲安全資料。他們建議按計劃繼續進行研究。

Next catalyst is the Phase 2b extension maintenance study, efficacy and safety results are expected this quarter. As a reminder, after completing the efficacy dose finding portion of the Phase 2b quality clinical study, which evaluates the effects of enobosarm body composition during the active weight loss, participants continued into the Phase 2b trial -- Phase 2b extension trial where all patients stopped treatment with semaglutide, but continued taking placebo, enobosarm 3-milligrams, enobosarm 6-milligrams, monotherapy in a blinded fashion for 12 additional weeks.

下一個催化劑是第 2b 階段擴展維護研究，預計本季將公佈療效和安全性結果。提醒一下，在完成 2b 期品質臨床研究的療效劑量探索部分（該部分評估了主動減肥期間 enobosarm 身體組成的影響）後，參與者繼續進入 2b 期試驗 - 2b 期擴展試驗，所有患者均停止使用 semaglutide 治療，但繼續以盲法服用安慰劑、enobosarm 36 毫克單一療法 12 週。

The Phase 2b extension clinical trial, we'll evaluate whether enobosarm can maintain muscle and more importantly, prevent fat regain that generally occurs after discontinuing GLP-1 receptor agonist. The company plans to present the full clinical efficacy and safety datasets for the Phase 2b quality clinical study and the Phase 2b extension maintenance study in future scientific conferences and publications.

在第 2b 期擴展臨床試驗中，我們將評估 enobosarm 是否可以維持肌肉，更重要的是，防止停用 GLP-1 受體激動劑後通常發生的脂肪反彈。該公司計劃在未來的科學會議和出版物中展示 2b 期品質臨床研究和 2b 期擴展維持研究的完整臨床療效和安全性資料集。

The next catalyst is we expect regulatory clarity for the GLP-1 receptor agonist and enobosarm combination Phase 3 clinical program following an end of Phase 2 FDA meeting, which is anticipated in Q3 2025. As the Phase 2b QUALITY clinical study is a positive study, we plan to request an end of Phase 2 meeting with FDA.

下一個催化劑是，我們預計 GLP-1 受體激動劑和依諾博沙姆組合 3 期臨床計畫的監管將在第 2 階段 FDA 會議結束後變得清晰，預計會議將於 2025 年第三季舉行。由於第 2b 階段 QUALITY 臨床研究是一項積極的研究，我們計劃請求結束與 FDA 的第 2 階段會議。

During our previous pre-IND FDA meeting, FDA provided general comments about the regulatory path forward for enobosarm as a drug that improves body composition during chronic weight management, including input on Phase 3 clinical program design.

在我們先前的 IND 前 FDA 會議上，FDA 對 enobosarm 作為一種改善慢性體重管理期間身體組成的藥物的監管路徑提供了一般性評論，包括對 3 期臨床計劃設計的意見。

On the basis of this FDA input, we plan to propose a Phase 3 clinical program that is similar to the positive -- already positive Phase 2b QUALITY clinical trial. The proposed Phase 3 clinical trial design is a double-blind, placebo-controlled study in older patients greater than or equal to the age of 60, who have obesity or overweight and who are eligible for treatment with GLP-1 receptor agonist. The GLP receptor agonist may be either Wegovy with semaglutide and/or Zepbound, tirzepatide. Patients will be randomized to oral daily enobosarm or matching placebo. All subjects will start and receive the GLP-1 receptor agonist during the study.

根據 FDA 的意見，我們計劃提出一個與已經取得積極成果的 2b 期 QUALITY 臨床試驗類似的 3 期臨床計劃。建議的 3 期臨床試驗設計是一項雙盲、安慰劑對照研究，針對年齡大於或等於 60 歲、肥胖或超重且有資格接受 GLP-1 受體激動劑治療的老年患者。GLP 受體激動劑可以是 Wegovy 與 semaglutide 和/或 Zepbound、tirzepatide。患者將隨機分配每日口服 enobosarm 或匹配的安慰劑。所有受試者將在研究期間開始並接受 GLP-1 受體激動劑。

The proposed primary endpoint will be the effect of enobosarm on physical function measured by Stair Climb Test at 24 weeks. Proposed key secondary endpoints will be to assess the effect of enobosarm on total lean mass, total fat mass, HOMA-IR, which is insulin resistance, and hemoglobin A1c at 24 weeks.

建議的主要終點是 enobosarm 對 24 週時透過爬樓梯測試測量的身體功能的影響。提出的關鍵次要終點是評估 enobosarm 對 24 週時總瘦體重、總脂肪量、HOMA-IR（即胰島素抗性）和糖化血紅蛋白 A1c 的影響。

After the Phase 3 clinical trial ends at 24 weeks of treatment, the plan is to continue to measure total lean mass, total body weight, Stair Climb Test, total fat mass, bone mineral density, HOMA-IR, as I mentioned, is insulin resistance, and hemoglobin A1c for up to 68 weeks to capture the longer-term benefits of enobosarm improvements on body composition with greater loss of adiposity or fat, preservation of both lean, mass and bone for chronic weight management.

在 24 週治療結束後，計劃繼續測量總瘦體重、總體重、爬樓梯測試、總脂肪量、骨礦物質密度、HOMA-IR（正如我所提到的胰島素抵抗）和糖化血紅蛋白 A1c，持續長達 68 週，以捕捉 enobosarm 對身體體重成分改善的長期益處，即更大程度地減少從而減少或脂肪，骨骼體重、體重和正常體重。

Another catalyst is we have a novel modified release oral enobosarm formulation, which is on track to be available for the Phase 3 clinical studies and commercialization. Veru is currently developing a novel, patentable, modified release oral formulation for enobosarm.

另一個催化劑是我們有一種新型緩釋口服依諾博沙姆製劑，該製劑即將進入 3 期臨床研究和商業化階段。Veru 目前正在開發一種新型、可專利的改良釋放口服製劑 enobosarm。

The actual formulation, pharmacokinetic release profiles and method of manufacturing will be subject to future patents. If issued, the expiry for the new modified release oral enobosarm formulation patent is expected to be in 2045.

實際配方、藥物動力學釋放曲線和製造方法將受到未來專利的保護。如果獲得批准，新的緩釋口服依諾博沙姆製劑專利預計於 2045 年到期。

The new enobosarm formulation has completed animal trials and is anticipated to be in Phase 1 bioavailability clinical trials during the first half of calendar 2025. Again, the expectation is that this novel modified release oral enobosarm formulation will be available for Phase 3 clinical studies and for commercialization.

新的 enobosarm 配方已完成動物試驗，預計 2025 年上半年進行第一階段生物利用度臨床試驗。再次，我們期望這種新型緩釋口服依諾博沙姆製劑能夠用於第 3 期臨床研究並實現商業化。

Finally, we are focusing our Phase 3 clinical program on the older patient population that could benefit from weight reduction drug for chronic weight management because they're at higher risk for muscle weakness and falls because of age-related loss of muscle.

最後，我們將 3 期臨床計劃的重點放在老年患者群體上，他們可以從減肥藥物中受益，用於長期體重管理，因為他們因年齡相關的肌肉損失而面臨更高的肌肉無力和跌倒風險。

CDC prevalence is 41.5% among 47.4 million patients enrolled in Medicare Part D plans, up to 34.4% of patients over the age of 60 with obesity in the United States have sarcopenic obesity. Sarcopenic obese patients are patients who have obesity and low muscle mass at the same time and are potentially at the greatest risk for developing critically low muscle mass when taking a currently approved GLP-1 receptor agonist.

在參加聯邦醫療保險 D 部分計畫的 4,740 萬名患者中，CDC 盛行率為 41.5%，美國 60 歲以上肥胖患者中高達 34.4% 患有肌肉減少性肥胖。肌少性肥胖患者是指同時患有肥胖症和肌肉質量低下的患者，並且在服用目前批准的 GLP-1 受體激動劑時，發生肌肉質量極低的風險最高。

Now, although older patients represent a large market population alone, success in this population can be a segue into the combination of enobosarm and GLP-1 receptor agonist treatment in younger patients who have obesity as well as diabetic and the frailty populations.

現在，儘管老年患者本身就佔據著很大的市場人口，但在這一人群中的成功可以成為enobosarm和GLP-1受體激動劑聯合治療年輕肥胖患者以及糖尿病患者和體弱人群的延續。

I will now turn the call over to Michele Greco, our CFO/CAO, to discuss the financial highlights. Michele?

現在，我將把電話轉給我們的財務長/首席行政官 Michele Greco，討論財務亮點。米歇爾？

Thank you, Dr. Steiner. Let's review the results for the three months ended March 31, 2025. Research and development costs increased to $3.9 million from $3 million in the prior quarter. The increase is due to expenses related to the company's enobosarm Phase 2b QUALITY clinical study for higher quality weight loss.

謝謝你，施泰納醫師。讓我們回顧一下截至 2025 年 3 月 31 日的三個月的結果。研發成本從上一季的 300 萬美元增加至 390 萬美元。增加的原因是該公司為實現更高品質的減肥而進行的 enobosarm 第 2b 階段品質臨床研究的相關費用。

Selling, general and administrative expenses were $5.2 million compared to $5.9 million in the prior quarter. The decrease is primarily due to a decrease in share-based compensation. We recognized a gain on sale of ENTADFI assets of $974,000, while there was none in the prior quarter. The gain represents non-refundable consideration received related to promissory notes due to Veru.

銷售、一般及行政開支為 520 萬美元，而上一季為 590 萬美元。減少的主要原因是股權激勵減少。我們確認出售 ENTADFI 資產的收益為 974,000 美元，而上一季則沒有收益。此收益代表了與應付給 Veru 的本票相關的不可退還的對價。

The bottom-line result for continuing operations was a net loss of $7.9 million or $0.05 per diluted common share compared to a net loss of $8.7 million or $0.06 per diluted common share in the prior year's quarter.

持續經營的最終結果是淨虧損 790 萬美元或每股稀釋普通股 0.05 美元，而去年同期的淨虧損為 870 萬美元或每股稀釋普通股 0.06 美元。

Net loss from discontinued operations, net of taxes related to the FC2 Female Condom business, which was sold on December 30, 2024, was $49,000 or $0.00 per diluted common share compared to a net loss of $1.3 million or $0.01 per diluted common share in the prior quarter. The net loss from discontinued operations during the current quarter represents changes in an estimate made at the time of the FC2 business sale, while the net loss for the prior-year quarter represents the operations of the FC2 business during that period.

與 2024 年 12 月 30 日出售的 FC2 女用避孕套業務相關的非持續經營淨虧損（扣除稅款）為 49,000 美元或每股稀釋普通股 0.00 美元，而上一季的淨虧損為 130 萬美元或每股稀釋普通股 0.01 美元。本季非持續經營淨虧損代表出售 FC2 業務時估計的變化，而去年同期淨虧損代表該期間 FC2 業務的營運。

Now, turning to the results for the six months ended March 31, 2025. Research and development costs increased to $9.6 million from $4.6 million in the prior period. The increase is due to $6.4 million in expenses related to the company's enobosarm Phase 2b QUALITY clinical study for high-quality weight loss during the six months.

現在，讓我們來看看截至 2025 年 3 月 31 日的六個月的業績。研發成本從上一時期的 460 萬美元增加到 960 萬美元。增加的原因是，該公司在六個月內為實現高品質減肥而進行的 enobosarm 第 2b 階段 QUALITY 臨床研究的相關費用為 640 萬美元。

Selling, general, and administrative expenses were $10.4 million compared to $12.6 million in the prior period. The decrease is primarily due to a decrease in share-based compensation. We recognized a gain on sale of ENTADFI assets of $1.7 million compared to a gain of $918,000 in the prior period, which is based on nonrefundable consideration received related to promissory notes due to Veru.

銷售、一般及行政開支為 1,040 萬美元，而上一季為 1,260 萬美元。減少的主要原因是股權激勵減少。我們確認出售 ENTADFI 資產的收益為 170 萬美元，而上期收益為 918,000 美元，該收益基於與應付給 Veru 的本票相關的不可退還對價。

In conjunction with the sale of the FC2 Female Condom business, we recorded a gain on extinguishment of debt of $8.6 million related to the termination of the SWK Residual Royalty Agreement. This represents the difference between the change of control payment of $4.2 million and the net carrying amount of the extinguished debt of $12.8 million, which included an embedded derivative for the change of control provision at fair value of $4.7 million.

在出售 FC2 女用避孕套業務的同時，我們記錄了與終止 SWK 剩餘特許權使用費協議相關的 860 萬美元債務清償收益。這是控制權變更支付金額 420 萬美元與已清償債務淨帳面價值 1,280 萬美元之間的差額，其中包括公允價值為 470 萬美元的控制權變更準備金嵌入式衍生品。

The bottom-line result for continuing operations was a net loss of $9.6 million or $0.07 per diluted common share, compared to a net loss of $16.4 million or $0.13 per diluted common share in the prior period. Net loss from discontinued operations net of taxes related to the FC2 business was $7.2 million or $0.05 per diluted common share, including the $4.2 million loss on sale of the FC2 business compared to a net loss of $1.9 million or $0.02 per diluted common share in the prior period.

持續經營的最終結果是淨虧損 960 萬美元或每股稀釋普通股 0.07 美元，而上一期間的淨虧損為 1,640 萬美元或每股稀釋普通股 0.13 美元。與 FC2 業務相關的非持續營業淨虧損（扣除稅項）為 720 萬美元，即每股稀釋普通股 0.05 美元，其中包括出售 FC2 業務的 420 萬美元損失，而上一期間的淨虧損為 190 萬美元，即每股稀釋普通股 0.02 美元。

The increase in the net loss from discontinued operations of $5.3 million is due to the loss on the sale of the FC2 Female Condom business of $4.2 million and the increase in the loss from the change in fair value of derivative liabilities of $3.1 million, partially offset by a decrease in selling, general, and administrative expenses of $2.2 million.

終止營業淨虧損增加 530 萬美元，是由於出售 FC2 女用避孕套業務的損失 420 萬美元，以及衍生負債公允價值變動損失增加 310 萬美元，但被銷售、一般及管理費用減少 220 萬美元部分抵銷。

The purchase price for the sale of the FC2 business was $18 million in cash, subject to adjustments as set forth in the purchase agreement for the transaction. Net proceeds from the sale of the FC2 Female Condom business were approximately $16.3 million after selling costs and other purchase price adjustments, but before a change of control payment of $4.2 million owed to SWK pursuant to a Residual Royalty Agreement for a 2018 financing transaction.

FC2 業務的出售價格為 1,800 萬美元現金，但須依照交易購買協議中規定的條件進行調整。FC2 女用保險套業務出售的淨收益約為 1,630 萬美元，扣除銷售成本和其他購買價格調整後，但尚未支付根據 2018 年融資交易的剩餘特許權使用費協議欠 SWK 的 420 萬美元的控制權變更款項。

The loss on the sale of the FC2 Female Condom business is approximately $4.2 million, the difference between the estimated net proceeds of $16.3 million and the total carrying value of the FC2 business of $20.6 million. The sale of the FC2 Female Condom business represented a change in strategy, allowing the company to focus all its efforts exclusively on drug development.

FC2 女用避孕套業務出售的損失約為 420 萬美元，即預計淨收益 1,630 萬美元與 FC2 業務總帳面價值 2,060 萬美元之間的差額。FC2女用避孕套業務的出售代表著策略的轉變，使公司能夠將所有精力集中在藥物開發上。

Now, looking at the balance sheet. As of March 31, 2025, our cash, cash equivalents, and restricted cash balance was $20 million compared to $24.9 million as of September 30, 2024. The restricted cash balance as of March 31, 2025, was $354,000 related to the sale of the FC2 Female Condom business.

現在，看一下資產負債表。截至 2025 年 3 月 31 日，我們的現金、現金等價物及受限現金餘額為 2,000 萬美元，而截至 2024 年 9 月 30 日為 2,490 萬美元。截至 2025 年 3 月 31 日，受限現金餘額為 354,000 美元，與出售 FC2 女用避孕套業務有關。

Our net working capital was $15.8 million on March 31, 2025, compared to $23.4 million on September 30, 2024. The company is not profitable and has had negative cash flow from operations. We will need additional capital to support our drug development candidates. Based upon the company's current operating plan, our cash as of the issuance date of these financial statements is not sufficient for the company to fund operations for the next 12 months.

截至 2025 年 3 月 31 日，我們的淨營運資本為 1,580 萬美元，而 2024 年 9 月 30 日為 2,340 萬美元。該公司尚未獲利，經營現金流為負。我們需要額外的資金來支持我們的候選藥物開發。根據公司目前的經營計劃，截至這些財務報表發布之日，我們的現金不足以為公司未來 12 個月的營運提供資金。

However, we have sufficient capital to take the company into the fourth quarter of this calendar year, which is beyond the upcoming near-term catalysts, which include the unblind safety data for the Phase 2b QUALITY clinical trial, the top-line efficacy and safety data for the enobosarm Phase 2b extension maintenance study, the regulatory clarity from the FDA end of Phase 2 meeting for the enobosarm Phase 3 program, and the Phase 1 bioavailability data for the novel modified release oral enobosarm formulation.

然而，我們有足夠的資本將公司帶入今年第四季度，這超出了即將到來的近期催化劑，其中包括 2b 期 QUALITY 臨床試驗的非盲安全數據、enobosarm 2b 期擴展維持研究的頂線療效和安全性數據、FDA 在第 2 階段會議結束時對 enobosarm 3 期療效和安全性數據、FDA 在第 2 階段會議結束時對 enobosarm 3 期計劃的數據改進 1002 系統釋放第一次。

During the six months ended March 31, 2025, we used cash of $19.1 million for operating activities compared with $11.7 million used for operating activities in the prior period. We generated cash from investing activities of $18.4 million for the six months ended March 31, 2025, while we used $40,000 in investing activities in the prior period.

在截至 2025 年 3 月 31 日的六個月內，我們用於經營活動的現金為 1,910 萬美元，而上一期間用於經營活動的現金為 1,170 萬美元。截至 2025 年 3 月 31 日的六個月，我們從投資活動中獲得的現金為 1,840 萬美元，而上一期間我們在投資活動中使用了 40,000 美元。

The cash generated in the current year relates to proceeds from the sale of the FC2 Female Condom business of $16.3 million, proceeds of $1.7 million from the sale of the ENTADFI assets and proceeds of $393,000 from the sale of On Kinetics equity securities. We used cash in financing activities for the six months ended March 31, 2025, of $4.2 million related to the change of control payment pursuant to the Residual Royalty Agreement, which terminated in conjunction with the sale of the FC2 Female Condom business. In the prior period, we generated $36.8 million from financing activities.

本年度產生的現金包括出售 FC2 女用避孕套業務所得的 1,630 萬美元、出售 ENTADFI 資產所得的 170 萬美元以及出售 On Kinetics 股權證券所得的 393,000 美元。截至 2025 年 3 月 31 日的六個月內，我們在融資活動中使用了 420 萬美元的現金，與根據剩餘特許權使用費協議支付的控制權變更有關，該協議隨 FC2 女用避孕套業務的出售而終止。在上一期間，我們從融資活動中獲得了 3,680 萬美元的收入。

Now, I'd like to turn the call back to Dr. Steiner. Dr. Steiner?

現在，我想把電話轉回給施泰納醫生。斯坦納博士？

Thank you, Michele. And with that, I'll now open the call to questions. Operator?

謝謝你，米歇爾。現在，我開始回答問題。操作員？

(Operator Instructions) Dennis Ding, Jefferies.

（操作員指示） 丹尼斯丁，傑富瑞。

Good morning. This is Anthea on for Dennis. Could you talk a little bit more about how you're thinking about your cash balance and runway? Specifically, what options are you exploring to fund the Phase 3? And is there a potential to partner out the program?

早安.這是丹尼斯的安西婭。能否再多談談您對現金餘額和跑道的看法？具體來說，您正在探索哪些方案來資助第三階段？是否有可能與合作夥伴共同進行該計劃？

Yeah, thank you for the question. So hopefully, you heard loud and clear that we have enough cash to last us into the fourth quarter -- calendar quarter. That gives us plenty of time to get through these catalysts. Part of what we're trying to do is to get the full appreciation and value understood by investors and others based on the clinical data and other information that's coming out.

是的，謝謝你的提問。所以希望您能清楚地聽到，我們有足夠的現金來維持到第四季度——日曆季度。這給了我們充足的時間來克服這些催化劑。我們正在努力做的事情之一是讓投資者和其他人根據臨床數據和其他資訊充分了解其價值。

So very -- so as I mentioned -- so we're expecting this quarter to have the unblinded safety data for the Phase 2b QUALITY clinical study. The top-line efficacy and safety data for the enobosarm extension study will come out this quarter as well. Q3, we have regulatory clarity because that's when we'll have the meeting with the FDA on the Phase 3 program. Remember, that dictates how much money, how big the study is. So it's kind of premature to say how much cash we're going to need for the clinical study until we know exactly what the FDA agrees to. We have an idea. But again, we need to get clarity. And so that will help dictate how we're thinking and what to do.

正如我所提到的，我們預計本季將獲得第 2b 階段 QUALITY 臨床研究的非盲安全數據。Enobosarm 擴展研究的頂線療效和安全性數據也將於本季公佈。第三季度，我們對監管有了清晰的認識，因為那時我們將與 FDA 就第三階段計劃舉行會議。請記住，這決定了需要多少錢、研究規模有多大。因此，在我們確切知道 FDA 同意什麼之前，現在說我們需要多少現金進行臨床研究還為時過早。我們有一個想法。但再次強調，我們需要弄清楚。這將有助於決定我們如何思考以及做什麼。

And then we're expecting the Phase 1 bioavailability bridging data, if you will, for the novel modified release oral enobosarm formulation. So these are all value-generating opportunities.

然後，如果您願意的話，我們期待新型緩釋口服依諾博沙姆製劑的第一階段生物利用度橋接數據。所以這些都是創造價值的機會。

With that said, yes, I think the approach should be to go for non-dilutive funding and non-dilutive funding would be best from either a partnership type partnership or more from a large pharmaceutical company, of which we are in active discussions. And the reason we're in active discussions is because we have Phase 2b data that uniformly have we been told by key opinion leaders. We've been told by the Scientific Advisory Board. We've been told by every expert in the field that this is a game changer to be able to have a drug that will make a GLP-1 burn only fat that's unheard of. And so we are the first company to report on GLP-1 in combination with a muscle preservation drug that's an oral. And being an oral drug and being a non-peptide, being a small molecule has some very interesting potential.

話雖如此，是的，我認為方法應該是尋求非稀釋性融資，而非稀釋性融資最好來自合夥類型的合作夥伴關係或更多來自大型製藥公司，我們正在積極討論這一點。我們之所以積極討論，是因為我們擁有 2b 階段的數據，這些數據都是關鍵意見領袖一致告知我們的。科學顧問委員會已經告知我們。該領域的每一位專家都告訴我們，這是一種改變遊戲規則的藥物，可以讓 GLP-1 只燃燒脂肪，這是聞所未聞的。因此，我們是第一家報告 GLP-1 與口服肌肉保存藥物合併使用的公司。作為一種口服藥物、非勝肽類藥物和小分子藥物，它具有非常有趣的潛力。

And the way I see it, the future of weight loss and chronic weight management is going to be a journey in which you lose fat only and you hold on to lean. And furthermore, it's going to be an oral space. It's going to be an oral drug that you take for weight loss. It can be an oral drug you take for body composition and you can do -- and especially the small molecules, you can pair them together as a fixed combination.

在我看來，未來的減肥和長期體重管理將是一段只減掉脂肪並保持苗條的旅程。此外，它也將成為一個口語空間。這是一種用於減肥的口服藥物。它可以是一種口服藥物，用於調節身體結構，特別是小分子，你可以將它們配對在一起形成一個固定的組合。

This could be very, very interesting. This is where the field is going. So as we get more and more information, I think that will solidify clearly that we're ahead of the pack. I think the myostatin inhibitors, even if everything is equal, the IV or subcu, and that's what they're trying to move away from. So our strategy is to get the milestones behind us, to keep the discussions with the pharmaceutical companies going and to have more clarity on the Phase 3 program, and that will help us understand better how -- what's the best way to fund the Phase 3.

這可能非常非常有趣。這就是該領域的發展方向。因此，隨著我們獲得越來越多的信息，我認為這將清楚地鞏固我們領先的地位。我認為肌肉生長抑制素抑制劑，即使一切都相同，靜脈注射或皮下注射，也是他們試圖擺脫的。因此，我們的策略是完成里程碑，繼續與製藥公司進行討論，並更清楚地了解第三階段計劃，這將幫助我們更好地了解如何為第三階段提供資金的最佳方法。

Got it, thank you.

知道了，謝謝。

Gary Nachman, Raymond James.

蓋瑞納赫曼、雷蒙詹姆斯。

Thanks for all the updates. So Mitch, for the Phase 2b extension maintenance study, review what outcomes would be considered a success in terms of the magnitude of benefit on weight loss and muscle mass for enobosarm versus placebo after stopping the GLP-1. Does it need to be stat sig or just show a positive trend?

感謝所有的更新。因此，Mitch，對於 2b 期延長維持研究，回顧一下在停止使用 GLP-1 後，enobosarm 與安慰劑相比，在減肥和肌肉質量方面獲益的程度方面，什麼樣的結果才算成功。它需要是統計訊號還是僅顯示正面趨勢？

And then if you could just say if the data is imminent or if it will be later in the quarter, if you could narrow that at all? And then I have a follow-up.

然後，如果您能說一下數據是否即將公佈，或者是否會在本季稍後公佈，您是否可以縮小範圍？然後我有一個後續問題。

Okay, yeah. So okay, fair enough. So we're laughing, you want to know the exact timing of the date of release. And I'll see if I can give you some more clarity.

好的，是的。好吧，夠公平了。所以我們在笑，你想知道發布日期的確切時間。我會看看是否能給你更清晰的解釋。

So as you know, the study is powered on the Phase 2b QUALITY study, which is the formal first 168 patients, 16 weeks, lean body mass being the primary endpoint. So the way to think of the extension study is almost like a safety study. And what happens when you stop with GLP-1. So it will be more descriptive, but it's telling a real story about the working hypothesis that muscle is important. And so the idea -- so if you can consider it successful is we already know that we maintain lean mass with the enobosarm and we burn more fat mass going into it.

如您所知，研究以 2b 期品質研究為基礎，正式研究對象為前 168 名患者，為期 16 週，以瘦體重為主要終點。因此，擴展研究的思考方式幾乎就像安全性研究一樣。當你停止使用 GLP-1 時會發生什麼。因此它將更具描述性，但它講述了關於肌肉很重要這一工作假設的真實故事。所以這個想法——如果你認為它是成功的，那就是我們已經知道，使用 enobosarm 我們可以保持瘦體重，並且燃燒更多的脂肪。

And we also know that the placebo group, meaning semaglutide alone is acting just like you would expect semaglutide to act in other studies. So the step 1 study with semaglutide at 68 weeks, there was a 40% reduction in -- there was -- for the total weight loss, 40% was lean and 60% was fat. We saw 32% lean and 68% fat at 16 weeks. So the placebo group is acting just like we expect from the published New England Journal of Medicine article, step 1. So the expectation is that the placebo arm now without semaglutide and without enobosarm will act similarly, which we expect to see fat regain.

我們也知道，安慰劑組（即單獨使用司美格魯肽）的作用就像您預期司美格魯肽在其他研究中的作用一樣。因此，在第 1 期研究中，使用司美格魯肽治療 68 週後，整體體重減少了 40%，其中 40% 為瘦體重，60% 為脂肪體重。16 週後我們發現瘦肉佔 32%，脂肪佔 68%。因此，安慰劑組的表現正如我們在《新英格蘭醫學雜誌》發表的文章第 1 步中所預期的那樣。因此，我們預期現在不含司美格魯肽和依諾博賽姆的安慰劑組將發揮類似的作用，我們預計會看到脂肪重新增加。

Remember, fat is the enemy. We have to pause for a moment. When we deal with weight loss and obesity, it's all about what happens to fat through the process, meaning that if fat comes back and you get fat regain, that's bad. So fat regain is what we're trying to blunt and with fat regain comes weight gain. And then the question of muscle, we're going to -- I guess, because we're doing DEXA, we're going to have a better clear understanding what happens to muscle.

記住，脂肪是敵人。我們必須暫停一下。當我們處理減肥和肥胖問題時，關鍵在於脂肪在過程中發生的變化，這意味著如果脂肪再次出現並且你再次胖回來，那就糟糕了。因此，我們要嘗試抑制脂肪的反彈，而脂肪的反彈就會導致體重的增加。然後是關於肌肉的問題，我想，因為我們正在進行 DEXA 檢查，所以我們將更清楚地了解肌肉發生了什麼。

Now if muscle comes back in the placebo group and you have fat regain, muscle I'm not worried about. I'm happy if muscle comes back, muscle doesn't come back, that's fine. The key thing to focus on is what happens to fat regain. How about enobosarm? If you hold on to -- if you have enobosarm and muscle is not depleted, meaning that you're not getting two signals to the brain.

現在，如果安慰劑組的肌肉恢復了，而脂肪又恢復了，那麼我並不擔心肌肉。如果肌肉恢復了我就很高興，肌肉沒有恢復也沒關係。需要關注的關鍵問題是脂肪反彈的情況。埃諾博薩姆 (enobosarm) 怎麼樣？如果你堅持下去——如果你有enobosarm並且肌肉沒有耗盡，這意味著你沒有向大腦發送兩個信號。

One signal in the brain is you stop the GLP-1, you're told to eat and you have a muscle depletion, you're told to eat, you get a double eat. And so you overeat. But enobosarm shuts off one of those and the idea is that we will, again, focus on fat, blunt the fat regain. And I think the success would be if we can show that we blunted so much, in fact, it may actually cause additional fat loss. Think about that for a moment. So if we cause additional fat loss and don't cause regain, then enobosarm monotherapy could be a nice off-ramp for patients who are -- for patients who want to stop with GLP-1 for sort of reasons.

大腦中的一個訊號是你停止 GLP-1，你被告知要吃東西，但你的肌肉會消耗殆盡，你被告知要吃東西，但你會吃雙倍的食物。所以你吃太多。但是 enobosarm 關閉了其中之一，其想法是，我們將再次關注脂肪，減緩脂肪的反彈。我認為，如果我們能夠證明我們確實減輕了這麼多，那麼我們就成功了，事實上，它實際上可能會導致額外的脂肪減少。想一想。因此，如果我們能夠進一步減少脂肪，並且不會導致脂肪反彈，那麼對於因某種原因想要停止使用 GLP-1 的患者來說，enobosarm 單一療法可能是一個不錯的選擇。

Now to be very clear, the whole idea is to stay on GLP-1 to get the benefit. And unfortunately, 60% of patients at year one come off the GLP-1. And by year two, it's 80% for all kinds of reasons or one of the main reasons is they reached the weight loss that they're happy with and the problem they're having is they stop, they'll get all the fat back and they feel like they've lost it. So again, is to focus on the fat. And if we can show a blunted fat regain or further loss of fat in an extension of 12 weeks, that would be considered success.

現在要非常清楚的是，整個想法就是繼續使用 GLP-1 來獲得益處。不幸的是，第一年就有 60% 的患者停止服用 GLP-1。到第二年，由於各種原因，80% 的人都會放棄減肥，其中一個主要原因是他們達到了令自己滿意的減肥效果，而他們遇到的問題是，一旦停止減肥，脂肪就會全部反彈，他們感覺好像已經減掉了所有脂肪。所以再次強調，重點是脂肪。如果我們能夠證明在延長的 12 週內脂肪恢復速度減緩或脂肪進一步減少，那就算是成功了。

And the second question you asked, which is the timing, I will tell you the following. The safety data for the Phase 2b QUALITY study will come out first this quarter. And then shortly after that, we expect to see the Phase 2b extension maintenance data come out and the safety and the efficacy will come out together.

至於您問到的第二個問題，也就是時間問題，我來回答。第 2b 階段 QUALITY 研究的安全資料將於本季首次公佈。此後不久，我們預計將看到第 2b 階段擴展維護資料出來，安全性和有效性也將同時出來。

That's helpful. And then just in terms of the Phase 3 study, understanding that you still have to meet with FDA, what's your best guess on how big you think it will need to be? And are you leaning towards using the 3-milligram, 6-milligram, or both doses and also doing it just for older patients?

這很有幫助。那麼就第 3 階段研究而言，您了解到您仍需要與 FDA 會面，您認為研究需要多大規模最好能猜一下嗎？您是否傾向於使用 3 毫克、6 毫克或兩種劑量，並且僅對老年患者使用？

And then just quickly, any potential concerns with tariffs? So where is enobosarm sourced and manufactured, if you can comment on that thinking ahead, particularly for the modified formulation?

那麼，對於關稅，您有什麼潛在的擔憂嗎？那麼 enobosarm 的來源和製造地點在哪裡，您能否對此進行評論，特別是針對修改後的配方？

Yeah. Gary Barnette will now answer the question about tariffs because he's got a better handle on how we're making the formulation where it's sourced. But to answer your first question, the expectation is that the primary endpoint for the trial will be in older patients. We picked older patients because older patients have a different risk benefit. I think it's important because it's a call to action.

是的。加里·巴內特 (Gary Barnette) 現在將回答有關關稅的問題，因為他更了解我們如何在原料來源地制定配方。但要回答您的第一個問題，預計試驗的主要終點是老年患者。我們選擇年齡較大的患者是因為年齡較大的患者有不同的風險效益。我認為這很重要，因為它是一種行動呼籲。

And the risk benefit is that if patients have a decline in function, that actually means something. That means something in terms of balance, gait difficulties, mobility disability, falls and fractures, mortality. I mean, you can dip into an entire literature. So that tells you sets up nicely why physical function is important. With that said, the primary endpoint will be stair climb at 24 weeks.

而風險效益是，如果患者的功能下降，其實意味著一些事情。這對於平衡、步態困難、行動障礙、跌倒和骨折、死亡率都有一定意義。我的意思是，你可以深入研究整個文獻。這很好地告訴你了為什麼身體機能如此重要。話雖如此，主要終點將是 24 週時的爬樓梯能力。

If you do the power calculations, that ends up being about -- and back up. I don't know whether we use three or six yet. It feels like three, but we got to get the full dataset to see because three does a great job on lean, but six does a great job on fat, but three does a good job on fat too. So we're still debating that. But put that aside for a moment. There will be one dose. So one dose we'll take forward.

如果你進行功率計算，結果就會是——並支持。我還不知道我們是否使用三個或六個。感覺就像三，但我們必須獲得完整的數據集才能看到，因為三在瘦肉方面做得很好，但六在脂肪方面做得很好，但三在脂肪方面也做得很好。所以我們仍在討論這個問題。但先把這個放在一邊。將會有一劑。因此我們將採取一劑措施。

And so, it will be one dose versus semaglutide -- plus semaglutide and/or tirzepatide. We're thinking now we'll probably do both. Why? Because there's only two drugs on the market right now, GLP-1s that are commercial. And so it makes sense that we want to be used in combination with either one, we should probably have data on both of them and stratify the Phase 3 so that we prespecify that we're going to analyze the data with semaglutide group and tirzepatide group separately. And I think that will be very helpful.

因此，它將是一種劑量，而不是司美格魯肽——加上司美格魯肽和/或替澤帕肽。我們現在想我們可能會同時做這兩件事。為什麼？因為目前市面上只有兩種藥物，即商業化的 GLP-1。因此，我們希望與其中任何一種藥物結合使用是有道理的，我們應該同時擁有這兩種藥物的數據，並對第 3 階段進行分層，以便我們預先指定分別分析 semaglutide 組和 tirzepatide 組的數據。我認為這將會非常有幫助。

All the rest of the companies, even though there's 120 companies working on this on obesity products, right now, the tirzepatide and semaglutide are way ahead. And so by the time our Phase 3 is completed, those are still going to be the market leaders that we'll have to approach.

其餘所有公司，儘管目前有 120 家公司致力於肥胖症產品研發，但 tirzepatide 和 semaglutide 仍遙遙領先。因此，當我們的第三階段完成時，這些仍將是我們必須接近的市場領導者。

So with that said, we believe that the numbers will be something like 200 patients per arm. So a total of approximately 400 patients randomized for the Phase 3.

因此，我們相信每組患者的數量約為 200 名。因此，總共有大約 400 名患者隨機進入第 3 階段。

Gary Barnette, can you answer the question about tariffs and whether we have concerns about sourcing and that could potentially affect enobosarm price?

加里·巴內特，您能回答有關關稅的問題嗎？我們是否擔心採購問題，這可能會影響 enobosarm 的價格？

Yeah. At this point, we don't foresee anything significant. Obviously, there potentially could be something come up. But the cost of goods of enobosarm is relatively low. So we believe we'll be in good shape regarding tariffs.

是的。目前，我們還沒有預見任何重大事件。顯然，可能會發生一些事情。但enobosarm的商品成本相對較低。因此我們相信，關稅問題將會得到妥善解決。

Okay, great. Thanks a lot.

好的，太好了。多謝。

William Wood, B. Riley.

威廉·伍德，B.萊利。

Congratulations on a very nice quarter and very promising results, certainly looking ahead to those. Maybe just wanted to tease out a bit more on what you might have seen already on safety. Understanding it's blinded to-date, you did say that you haven't seen any significant differences compared to what you're expected or expecting based on the previous studies.

恭喜您取得了非常好的季度和非常有希望的成果，當然我們也對未來充滿期待。也許只是想進一步了解您可能已經了解的安全方面的情況。據我了解，迄今為止它是盲法的，您確實說過，與根據以前的研究所預期或期望的結果相比，您沒有看到任何顯著的差異。

So just to sort of help us out and set a bar, maybe you could provide some color on what your expectations are for the safety based on these prior studies and how we should be interpreting this in terms of just the general safety, but maybe specifically on these liver tests?

因此，為了幫助我們並設定一個標準，也許您可以根據這些先前的研究，提供一些關於您對安全性的期望，以及我們應該如何從一般安全性的角度來解釋這一點，但也許具體到這些肝臟測試？

Yeah. So I think maybe the best way to answer is to go head on with liver and because people are saying that SARMs have -- from the literature -- SARMs in general which the data comes from the recreational use of SARMs at doses 10 to 20 times higher. So if we're at 3-milligrams, they're giving dose of 30-milligrams, which is 10 times higher, up to 75-milligrams, which is up to 20 times higher. So go take an Advil and the next day, take 21 of them, see how you feel.

是的。所以我認為也許最好的回答方式是直接討論肝臟，因為人們說 SARM 具有——從文獻中——SARM 總體而言，其數據來自於以 10 到 20 倍劑量娛樂性使用 SARM。因此，如果我們的劑量是 3 毫克，他們給出的劑量是 30 毫克，高出 10 倍，最高可達 75 毫克，最高可達 20 倍。因此，去服用一片 Advil，第二天服用 21 片，看看感覺如何。

So the problem is that it's uncontrolled, don't know who's making it, it's made by Chinese and Indian companies. So even in that case, the real-world data looks pretty good in terms of liver safety compared to, for example, alkylated anabolic-androgens, which has also been abused in the past. I put abuse aside from our clinical studies, which we have a database of about 1,600 patients, we saw a rate of ALT increase of about 1.8% or something like that in the placebo group and about 3.4% or something like that in the enobosarm group. And that's like in 500 patients per group.

所以問題在於它不受控制，不知道是誰製造的，它是由中國和印度公司製造的。因此，即使在這種情況下，與過去也被濫用的烷基化合成代謝雄激素等相比，現實世界的數據在肝臟安全性方面看起來相當不錯。我將濫用情況排除在我們的臨床研究之外，我們擁有約 1,600 名患者的資料庫，我們發現安慰劑組的 ALT 增加率約為 1.8% 或類似水平，而 Enobosarm 組的 ALT 增加率約為 3.4% 或類似水平。也就是說每組有 500 位患者。

And what we see is very, very characteristic of what you see with the testosterone type product, not the alkylated testosterone that we have modified to make it oral and has been the problem. But if you take regular testosterone, we're probably more similar to that, where you see slight increases, mild increases in ALT in a few subjects, always goes down either on drug, mostly -- almost always on drug unless the patient stops the study for some reason, and it goes down to normal.

我們所看到的情況與睪固酮類產品非常相似，而不是我們改良後口服的烷基化睪固酮，而烷基化睪固酮一直是問題所在。但如果你定期服用睪固酮，我們可能會看到類似的情況，你會看到 ALT 輕微增加，少數受試者的 ALT 輕度增加，在服藥後總會下降，大多數情況下——幾乎總是在服藥後下降，除非患者因某種原因停止研究，然後降至正常水平。

We've never seen anything related to function, meaning bilirubin increases, alkaline phosphatase increases, procoagulation issues. So in other words, it's mild increases self-limiting comes back down and represents what's called adaptation of tolerance, which is a common mechanism of the liver handles some agents. The other thing about enobosarm is we're not a -- we don't fit the two rule looks at what dose -- technically called rule of 2, in which if your dose is over 100 milligrams, it raises concern. Our dose is 3 milligrams. We don't fit that rule.

我們從未見過任何與功能相關的情況，例如膽紅素增加、鹼性磷酸酶增加、促凝血問題。換句話說，它的輕度增加會自我限制並回落，代表所謂的耐受性適應，這是肝臟處理某些藥物的常見機制。關於依諾博沙姆的另一件事是，我們不符合——我們不符合考慮劑量的兩條規則——技術上稱為 2 條規則，其中如果你的劑量超過 100 毫克，就會引起關注。我們的劑量是3毫克。我們不符合該規則。

So from that standpoint, our expectation is that what we're seeing is what we've been seeing before, and it's acting the same way, mild increases comes back down mostly -- usually on drug. And so we're not expecting -- and it's tolerant adaptation. And it's not drug-induced liver injury by Hy's law, which is what people get into trouble with the drug development. We just have not seen that.

因此，從這個角度來看，我們預期看到的是我們以前也看到過的情況，而且其作用方式相同，輕微的增加大多會回落——通常依靠藥物。所以我們並不期待──這是一種寬容的適應。根據海氏定律，這不是藥物引起的肝損傷，而藥物引起的肝損傷正是人們在藥物研發上遇到的困擾。我們只是還沒看到這一點。

And so I want to set the bar that in the aggregate, it's not like we saw something in the aggregate and now we're going to separate it out, as we have to see anything in the aggregate that would be -- that consistent with drug-induced liver injury by Hy's law.

因此，我想設定一個標準，從總體上看，這並不是說我們在總體上看到了什麼，現在我們要把它分離出來，因為我們必須從總體上看到任何與 Hy 定律規定的藥物性肝損傷相一致的東西。

I mean, Gary Barnette, do you want to add to that?

我的意思是，蓋瑞巴內特，你想補充嗎？

Yeah. I think you summarized it correctly. And that's exactly what we've seen in previous studies. From a -- if you go away and expand out of liver, we don't see any significant serious adverse events, and we're not seeing that in this particular study either. So it's -- the safety in aggregate is consistent with the studies that we've conducted previously.

是的。我認為你總結得非常正確。這正是我們在先前的研究中所看到的。從某種程度上來說——如果你離開並擴散到肝臟之外，我們不會看到任何重大的嚴重不良事件，而且我們在這個特定的研究中也沒有看到這種情況。因此，整體安全性與我們先前進行的研究一致。

One of the interesting thing is that GLP-1s also affect ALT, but same way, elevations have come down with time. And so adaptation, tolerance approach and they're widely used, and that's true for tirzepatide and for semaglutide. So again, we're not seeing anything inconsistent with what we've seen before, which we've been saying. I think what will be different is when we provide the full safety data set, you'll see what's happening in each category, semaglutide alone versus semaglutide plus [3 milligrams] plus [6 milligrams]. Is that helpful?

有趣的是，GLP-1 也會影響 ALT，但同樣，升高會隨著時間的推移而下降。因此，適應性、耐受性方法被廣泛使用，對於 tirzepatide 和 semaglutide 來說都是如此。所以，我們再說一遍，我們沒有看到任何與我們之前所說的不一致的東西。我認為，當我們提供完整的安全資料集時，您將看到每個類別中發生的情況，單獨使用司美格魯肽與司美格魯肽加[3毫克]加[6毫克]。這樣有幫助嗎？

Very helpful. I appreciate that very extra detail there, Mitch. So just one more actually from us. It looks from everything sort of that you presented so far, the FDA has sort of provided two paths towards -- two shots on goal or two paths towards regulatory improvement. You can sort of go after functional improvements or potentially go after metabolic improvements.

非常有幫助。米奇，我很欣賞你提供的額外細節。實際上我們只剩下一個了。從您目前介紹的所有內容來看，FDA 似乎提供了兩條路徑——兩條達到目標的路徑或兩條改善監管的路徑。您可以追求功能改善或潛在地追求代謝改善。

It looks like you're sort of at least initially overwhelmingly targeting functional data, obviously, with your very nice positive stair climb also as your primary endpoint or in Phase 3. I was curious, though, to how you're seeing sort of the other path if you feel that, that would be open to enobosarm. Also, I don't think we've seen too much data on that. And so how do you see these two alternate paths towards regulatory improvement? And will we -- or what should we be expecting as far as sort of the metabolic tests from the Phase 2b QUALITY coming up here shortly?

看起來你至少在最初主要針對功能數據，顯然，你非常好的積極爬樓梯也是你的主要終點或在第 3 階段。不過，我很好奇，如果您覺得另一條路對 enobosarm 來說是開放的，那麼您是如何看待它的呢？此外，我認為我們還沒有看到太多關於這方面的數據。那麼您如何看待這兩條實現監管改進的替代途徑？那麼，對於即將進行的第 2b 階段質量代謝測試，我們該期待什麼呢？

Yeah. So let me just -- so let me take how I'm seeing it from a standpoint of path. So the first thing to say, let's talk about enobosarm for a second. So enobosarm has consistently shown lean body mass maintenance or improvement in other patient populations, and we've shown the same thing in this patient population. We've shown reductions in fat and other populations, older patients.

是的。所以讓我——讓我從路徑的角度來看待它。首先，我們來討論一下 enobosarm。因此，enobosarm 在其他患者群體中一直表現出維持或改善瘦體重的效果，我們在該患者群體中也表現出了同樣的效果。我們已經證明脂肪和其他人群、老年患者的減少。

Again, we've shown the same thing in this patient population. We have not seen the individual data with some of the metabolic parameters, but some of the metabolic parameters have looked for are LDL, insulin resistance, and HbA1c. We've seen in our previous studies, LDL is maintained or slightly lower, triglycerides go down. This with enobosarm in other populations. And we've also seen insulin resistance get better.

我們再次在該患者群體中證明了同樣的情況。我們還沒有看到一些代謝參數的單獨數據，但已經尋找的一些代謝參數是 LDL、胰島素抗性和 HbA1c。我們在先前的研究中看到，LDL 保持穩定或略低，三酸甘油酯下降。這與其他人群中的 enobosarm 相同。我們也發現胰島素阻抗有所改善。

So HOMA-IR got better. HbA1c, I'm not quite sure on that one. But my guess is it got better. Maybe Gary knows. In this study, we're measuring -- we're not measuring HOMA-IR in the Phase 2b, but we are measuring HbA1c and LDL. And so from a metabolic standpoint, we're going to be additive, I believe, to what you see with the GLP-1.

因此 HOMA-IR 變得更好了。HbA1c，我不太確定這一點。但我猜情況會好起來。也許加里知道。在這項研究中，我們正在測量——我們沒有在第 2b 階段測量 HOMA-IR，而是測量了 HbA1c 和 LDL。因此，從代謝的角度來看，我相信我們會對 GLP-1 的作用做出補充。

Now to take a step back and what we do differently, of course, is we have -- in addition to muscle mass being metabolic, we also have muscle mass being physical function. And that's been the hardest one for other drugs like myostatin inhibitors to show.

現在退一步來看，我們所做的不同之處當然是——除了肌肉質量與新陳代謝有關之外，我們還有肌肉質量與身體機能有關。而這對於其他藥物如肌肉生長抑制素抑制劑來說是最難證明的。

And so -- and part of that is because the androgen receptor is a time-tested receptor. We know -- all you have to do is look at the real-world literature, people -- they maintain muscle, they burn fat, they improve their performance.

所以 — — 部分原因是因為雄性激素受體是一種經過時間考驗的受體。我們知道——你所要做的就是看看現實世界的文獻，人們——他們保持肌肉，燃燒脂肪，提高他們的表現。

And so it is a performance drug. There's no question about it, but FDA is asking it to be a performance drug. They're asking you to show function. So by definition, it's not just what you see on DEXA, it's what you see by performance. And we've seen that, whereas the myostatin inhibitors in general have had a tough time. So I -- and we're oral. So that puts us in a good position.

所以它是一種性能藥物。毫無疑問，但 FDA 要求將其作為功能性藥物。他們要求你展示功能。因此，根據定義，它不僅僅是您在 DEXA 上看到的內容，更是您透過效能看到的內容。我們已經看到，肌肉生長抑制素抑制劑整體上一直處境艱難。所以我 — — 我們是口頭的。這讓我們處於有利地位。

Now, the pathway from a regulatory standpoint, you have to think of it a couple of ways. The FDA has put out a guidance in January 2025 that is very interesting because the debate in the field is what is the regulatory pathway. And what you heard from others is that if you showed a 5% greater weight reduction -- incremental weight reduction when you combine two drugs together, then that gets you over the hurdle.

現在，從監管的角度來看，你必須從幾個方面來考慮這個問題。FDA 於 2025 年 1 月發布了一份指南，這非常有趣，因為該領域的爭論在於監管途徑是什麼。而你從其他人那裡聽說的是，如果你在將兩種藥物結合在一起時體重減輕了 5%——體重逐漸減輕，那麼你就克服了障礙。

Based on everything I know, several meetings with the FDA, the FDA guidance itself and furthermore, workshops with the FDA, that's evolving. People are now understanding what the FDA meant was for the first time you have a drug for weight loss, 5% weight loss compared to placebo and standard of care or standard lifestyle changes is 5%.

根據我所了解的一切，與 FDA 的幾次會議、FDA 指南本身以及與 FDA 的研討會都在不斷發展。現在人們明白了 FDA 的意思，即首次使用減肥藥時，與安慰劑相比，體重減輕 5%，而標準護理或標準生活方式的改變則為 5%。

But once you're in and you have an approved drug, that's 10%, for example, weight loss and you put that in combination with a second drug and you come back with 15%. The agency doesn't know what that means. What did you do to make the patient better?

但一旦你進入該行業並獲得了一種核准的藥物，那麼減肥效果就會是 10%，如果你將這種藥物與第二種藥物結合使用，減肥效果就會達到 15%。該機構不知道這意味著什麼。您做了什麼讓病人好起來？

So the agency says you have to have a second test. And that second test is what did you do that's clinically meaningful. So the FDA says clinically meaningful means HbA1c gets better, insulin resistance gets better, LDL gets better, for example. Those are metabolic things that get better.

因此該機構表示你必須進行第二次測試。第二次測試具有臨床意義。因此，FDA 表示，臨床意義意味著例如 HbA1c 變好、胰島素抗性變好、LDL 變好。這些都是新陳代謝變得更好的事情。

In the case of our drug, the fact that we showed improvement in lean -- stabilized, the technical term, stabilized preserved lean mass, we can show function. If you show benefit in function, that's a benefit, clinically meaningful. But if you think about what the GLP-1 is doing, the GLP-1 treatment makes HbA1c better, makes insulin resistance better, makes LDL better. So the combination has to make better, better.

就我們的藥物而言，事實是，我們顯示出瘦肉質量的改善——穩定，技術術語，穩定保存的瘦肉質量，我們可以顯示功能。如果在功能上表現出益處，那就是益處，具有臨床意義。但如果你想想 GLP-1 的作用，GLP-1 治療可以改善 HbA1c，改善胰島素阻抗，改善 LDL。因此，組合必須更加完善。

Whereas in the situation with physical function, we just showed in our Phase 2b, the physical function is not better with GLP-1. The GLP-1 42.6% of older patients, in fact, have a 10% or greater decline in stair climb power. So we can make something worse better. That's interesting.

而在身體功能方面，我們剛剛在第 2b 階段表明，GLP-1 並沒有改善身體功能。事實上，42.6% 的老年患者使用 GLP-1 後，爬樓梯能力下降了 10% 或更多。所以我們可以讓更糟糕的事情變得更好。那很有意思。

Now pause for a moment, that means that the bar for -- is high and low. It's low for the first time you have a product that's by itself. It's high if you give it in combination because you're being asked to do more than just weight loss.

現在暫停一下，這意味著——的標準有高有低。第一次擁有單獨產品時，其價格很低。如果合併使用的話，效果會比較好，因為要求你做的不只是減肥。

The FDA also has said in their guidance that there's a body composition pathway for approval. And so body composition basically means fat and muscle and bone and that kind of stuff. They know there's a problem that with GLP-1s that you change body composition. And in fact, the FDA has purposely gone out of the way to define obesity as excess adiposity. So weight reduction drug has to be a drug that burns fat.

FDA 也在其指南中表示，有一個身體組成審批途徑。因此，身體組成基本上意味著脂肪、肌肉、骨骼等等。他們知道 GLP-1 會改變身體成分，這是一個問題。事實上，FDA 刻意將肥胖定義為過度脂肪。所以減肥藥一定是燃燒脂肪的藥物。

Fat is what you see at no point for losing lean. In fact, the FDA now mandates sponsors to do a DEXA or a MRI to quantify at least in the subpopulation, how much lean is lost and how much fat is lost because the whole goal is to show fat loss.

您在減肥過程中永遠看不到脂肪。事實上，FDA 現在要求贊助商進行 DEXA 或 MRI 檢查，以至少在亞群中量化損失了多少瘦肉和多少脂肪，因為整個目標是顯示脂肪減少。

So with that -- so in that same guidance, they say, however, if your drug is a body composition drug, like in our case, we're preserving lean, then that path is beyond the scope of the weight reduction guidance because you're now a body composition drug in combination with GLP-1 and come seek advice. Well, our pre-IND was that advice.

因此，在同一個指導中，他們說，但是，如果您的藥物是一種身體成分藥物，就像我們的情況一樣，我們要保持瘦身，那麼這種途徑就超出了減肥指導的範圍，因為您現在是一種與 GLP-1 結合的身體成分藥物，並來尋求建議。嗯，我們在 IND 之前就提出了這樣的建議。

So when we had the pre-IND meeting, the FDA made it very, very clear that in our case, we're fortunate because we do improve lean mass. The DEXA scan of lean mass by itself is cosmetic, okay? So holding on to lean mass is wonderful. But what does it mean? And again, it's performance, it's function. And so performance and function has to be measured somehow.

因此，當我們召開 IND 前會議時，FDA 非常明確地表示，就我們的情況而言，我們很幸運，因為我們確實增加了瘦體重。單獨進行 DEXA 瘦體重掃描是出於美觀的目的，對嗎？因此，保持瘦體重是很好的。但這意味著什麼？再說一次，這是性能，這是功能。因此必須以某種方式衡量性能和功能。

We did a Stair Climb Test. And so now we have in our Phase 2b, a great situation that if we replicate the Phase 2b in the Phase 3 setting, that's wonderful, then we win. So the primary endpoint is physical function by Stair Climb Test at 24 weeks, and we show that we can stop physical decline -- stop the decline in physical activity, physical function by stair climb, in patients on GLP-1, that's clinically meaningful on its own. So that is a very clear pathway forward with FDA, consistent with the guidance and consistent with what they told us in our meetings with FDA.

我們做了爬樓梯測試。所以現在我們處於第 2b 階段，如果我們在第 3 階段環境中複製第 2b 階段，那就太好了，那麼我們就贏了。因此，主要終點是 24 週時透過爬樓梯測試來評估身體機能，我們的結果表明，對於使用 GLP-1 的患者，我們可以阻止身體機能衰退——透過爬樓梯來阻止身體活動和身體機能的衰退，這本身就具有臨床意義。因此，這是一條與 FDA 合作的非常明確的前進道路，與指導方針一致，也與他們在我們與 FDA 會面時告訴我們的內容一致。

I appreciate the color. I'll hop back in the queue, but definitely on the lookout for the imminent data and congratulations again for a very nice quarter.

我很欣賞這個顏色。我會重新回到隊列中，但一定會關注即將發布的數據，並再次祝賀這個非常好的季度。

(Operator Instructions) Yi Chen, H.C. Wainwright.

（操作員指示）Yi Chen，H.C. Wainwright。

Good morning. Eduardo on for Yi. Just a quick question again on the Phase 3 trial. You mentioned adding tirzepatide. And I'm curious what your thoughts are there. There's some anecdotal evidence that tirzepatide skews a little bit more towards fat loss instead of lean mass. I'm curious how you're planning around that in your trial design potentially. If you're losing more -- less lean mass, right, you might need a little bit more patients in that group to power a difference. I'm curious how you're thinking about that in the trial design?

早安.愛德華多替換易建聯上場。再問一個關於第三階段試驗的簡單問題。您提到添加 tirzepatide。我很好奇您的想法是什麼。有一些軼事證據表明，tirzepatide 更傾向於減少脂肪而不是瘦體重。我很好奇您在試驗設計中是如何規劃這個問題的。如果您減掉的瘦體重更多，對吧，您可能需要該組中更多的患者來產生影響。我很好奇您在試驗設計中是如何考慮這個問題的？

Yeah. So we have -- yes, so if you go back and look at the data, you'll see the following. To my surprise, until I saw the data, tirzepatide loses about the same amount of muscle or lean mass as semaglutide. And the data comes from the step 1 study for semaglutide, where I think it's about 6.8 -- at 68 weeks, it was 6.8 kilograms of lean that's lost. And so remember, it's with the lean, not so much what the fat is, it's how much lean you're trying to preserve for function. And so 6.8.

是的。所以我們有——是的，所以如果你回頭去看看數據，你會看到以下內容。令我驚訝的是，直到我看到數據，tirzepatide 損失的肌肉或瘦體重與 semaglutide 損失的肌肉或瘦體重大致相同。數據來自司美格魯肽的第 1 期研究，我認為大約是 6.8——在 68 週時，減掉了 6.8 公斤的瘦體重。因此請記住，重要的不是脂肪有多少，而是您要保留多少瘦肉以維持身體功能。所以是 6.8。

And if you go back and look at the tirzepatide data and you have to look in the supplemental tables, I was able to find a number at 72 weeks. Remember, 72 weeks is because they have a different titration period, so it gets to 72 weeks. It was about 6.2 kilograms. So the difference between the lean mass loss is approximately a year plus is similar.

如果你回頭查看 tirzepatide 數據，並且查看補充表，我能夠在 72 週時找到一個數字。請記住，72 週是因為他們有不同的滴定期，所以達到 72 週。大約有6.2公斤。因此，瘦體重損失的差異大約是一年多的時間。

So I think that the functional issues tirzepatide is going to have to be pretty much similar to what we found with semaglutide. With that said, we're going to power the study based on those numbers and stratify the subjects based on whether on tirzepatide or semaglutide, so we don't mix apples with oranges, if that makes sense. I think the apples are going to look very much like oranges in the study. But to be curious, we'll keep them separate.

因此我認為 tirzepatide 的功能問題與我們在 semaglutide 中發現的問題非常相似。話雖如此，我們將根據這些數字來推動這項研究，並根據是否使用替澤帕肽或司美格魯肽對受試者進行分層，所以我們不會將蘋果和橘子混在一起，如果這說得通的話。我認為書房裡的蘋果看起來很像橘子。但出於好奇，我們會將它們分開。

Gary Barnette, do you want to add to that?

巴內特 (Gary Barnette)，你想補充嗎？

No, that's right. There will be a stratification on which -- and we'll make sure they're equal between the treatment groups. So that difference will wash out or will be accounted for in the randomization. And of course, the type of GLP-1 that they'll be on will also be one of our covariates in the ANOVA in the final statistical analysis.

不，沒錯。我們將進行分層—並確保各治療組之間的水平相同。因此，這種差異將會消失或在隨機化過程中被考慮。當然，他們所服用的 GLP-1 類型也將成為最終統計分析中變異數分析的協變數之一。

Leland Gershell, Oppenheimer.

利蘭·格謝爾，奧本海默。

Just wondering, Mitch, the industry has been investing a fair bit in the development of potential therapies for the side effect of the GLP-1s vis-à-vis the myostatin blockers and so forth. Wondering if the work you've done to look at the differences between ANOVO and perhaps those strategies, are there any concerns you may have that those may show any benefits that may supersede or be differentiated from ANOVO as we await the remaining data from the Phase 2?

只是想知道，米奇，業界一直在投入大量資金來開發針對 GLP-1 相對於肌肉生長抑制素阻斷劑等副作用的潛在療法。想知道您所做的工作是否研究了 ANOVO 與這些策略之間的差異，在我們等待第 2 階段的剩餘數據時，您是否擔心這些策略可能會顯示出任何可能取代或與 ANOVO 區分開來的優勢？

Great question. So let's -- I'll begin with what I think makes us different, and I'll end with what I think makes us different. What makes us different is we're oral and they're IV or subcu. And the whole space is moving -- even if all things are equal, things are moving in the direction of oral treatments for chronic weight management. And all the GLP-1 containing agents have a degree of lean mass loss.

好問題。那麼讓我們——我將以我認為我們之間的不同之處開始，並以我認為我們之間的不同之處結束。我們的不同之處在於，我們採用口服給藥，而他們採用靜脈注射或皮下注射。整個領域都在發展——即使所有條件相同，事情也在朝著口服治療慢性體重管理的方向發展。所有含有 GLP-1 的藥物都會造成一定程度的瘦體重流失。

Nobody is going to disagree that older patients are at risk because they have less muscle mass to begin with. And it's not a percent thing. 25% of a small amount of muscle is still a big amount. And so the older patients, even big pharma will tell you are the ones that most at risk that we need to keep an eye on.

沒有人會否認老年患者有患病風險，因為他們的肌肉質量本來就較低。這不是一個百分比的問題。少量肌肉的 25% 仍然是一個很大的數量。因此，甚至大型製藥公司都會告訴你，老年患者是最危險的族群，我們需要密切注意。

With that said, I think the myostatin inhibitors are going to have to overcome a problem in their development, which has been showing physical function benefits, and physical function benefits by objective measurements of muscle function.

話雖如此，我認為肌肉生長抑制素抑制劑必須克服其開發過程中的一個問題，即顯示出身體功能的益處，以及透過肌肉功能的客觀測量顯示出身體功能的益處。

Now, I'm not talking about six-minute walk test because six-minute walk test should get better if you lose weight because six-minute walk test is cardiovascular. That's why they use six-minute walk test, for example, for pulmonary artery, hypertension drugs, and that kind of stuff. But muscular dystrophy, for example, they use for muscle quality, they use stair climb and those kinds of tests.

現在，我不是說六分鐘步行測試，因為如果你減肥，六分鐘步行測試應該會變得更好，因為六分鐘步行測試是心血管測試。這就是為什麼他們使用六分鐘步行測試來檢查肺動脈、高血壓藥物以及諸如此類的東西。但是對於肌肉萎縮症，例如，他們使用爬樓梯和諸如此類的測試來檢查肌肉質量。

So I'm not -- I think the challenge is I think they're going to show a greater loss of fat. I think they're going to show a preservation of lean. But because lean doesn't translate necessarily to function, then they're going to have to make better, better, which means they're going to have to look at LDL, they're going to look at HbA1c, they have to look at insulin resistance, something metabolic.

所以我並不認為——我認為挑戰在於，我認為他們將會表現出更大的脂肪減少。我認為他們會保持精益。但因為瘦身不一定意味著健康，所以他們必須做得更好，這意味著他們必須專注於 LDL，專注於 HbA1c，並專注於胰島素阻抗等代謝因素。

I think that's a challenge because you can only make things better, better, so much better, meaning that if your LDL hit 70 with GLP-1 alone, then what's better than better. You're already in a better range. Same thing with HbA1c and same thing with insulin resistance. GLP-1s do a good job on their own.

我認為這是一個挑戰，因為你只能讓事情變得更好、更好、好得多，這意味著如果你的 LDL 僅通過 GLP-1 就達到 70，那麼還有什麼比更好更好的呢。你已經處於更好的範圍內了。HbA1c 和胰島素抗性也是同樣的情況。GLP-1 本身就能發揮良好的作用。

So what are you going to show? So I think it's a question mark. So I'm going to end with what I think makes us different again, and that is we're oral. And because we're oral, that doesn't matter what they show because a small molecule, it's oral that can be combined with the future of weight loss medicines, which is an oral agent that's not a peptide, it's a small molecule.

那你要展示什麼呢？所以我認為這是一個問號。所以，我想最後再說一下我認為我們的不同之處，那就是我們是口頭的。而且因為我們是口服的，所以它們顯示什麼並不重要，因為小分子是口服的，可以與未來的減肥藥物結合，這是一種口服藥物，不是勝肽，而是一種小分子。

And then you'll be able to produce -- mass produce the drug more cheaply, distribute it much better when you're not looking for cold storage and that kind of stuff, and get to a massive number of people that could benefit from a weight-loss drug that is now a drug that is taking 99% of the fat away and leaving lean alone. So it's a true weight loss drug, getting rid of the fat. That's the enemy.

然後你就能以更低的成本大規模生產這種藥物，在不需要冷藏和諸如此類的東西的情況下，可以更好地分銷它，並讓大量人受益於這種減肥藥，這種藥物現在能帶走 99% 的脂肪，而只留下瘦肉。所以它是一種真正的減肥藥，可以消除脂肪。那是敵人。

Ladies and gentlemen, this concludes our question-and-answer session. I would like to turn the conference back over to Dr. Mitchell Steiner for any closing remarks.

女士們、先生們，我們的問答環節到此結束。我想將會議交還給米切爾施泰納博士，請他做最後發言。

I appreciate everyone who joined us on today's call, and I look forward to updating all of you on our progress at our next investors call and stay tuned for the numerous catalysts that will be coming out over the short term. Thank you. Bye now.

我感謝參加今天電話會議的所有人，我期待在下次投資者電話會議上向大家通報我們的進展，並繼續關注短期內即將出現的眾多催化劑。謝謝。再見了。

The digital replay of the conference call will be available beginning approximately 12:00 PM Eastern Time today, May 8, by dialing 1877 344-7529 in the United States and 1412 317-0088 internationally. You will be prompted to enter the replay access code, which will be 768 2749. Please record your name and company when joining.

本次電話會議的數位回放將於今天（5 月 8 日）美國東部時間下午 12:00 左右開始提供，美國境內撥打 1877 344-7529 或國際撥打 1412 317-0088。系統將提示您輸入重播存取代碼，即 768 2749。加入時請記錄您的姓名和公司。

The conference call has now concluded. Thank you for attending today's discussion.

電話會議現已結束。感謝大家參加今天的討論。