Skye Bioscience Inc (SKYE) 2025 Q2 法說會逐字稿

Ladies and gentlemen, thank you for standing by. My name is Joel, and I will be your conference operator today. At this time, I would like to welcome everyone to the Skye Bioscience second-quarter 2025 financial results and business update call. (Operator Instructions) I would now like to turn the conference over to Bernie Hertel, Head of Investor Relations. Please go ahead.

女士們、先生們，感謝你們的支持。我叫喬爾，今天我將擔任你們的會議主持人。現在，我歡迎大家參加 Skye Bioscience 2025 年第二季財務業績和業務更新電話會議。（操作員指示）現在，我想將會議交給投資者關係主管 Bernie Hertel。請繼續。

Hello, and thank you all for participating in today's call. Before we begin, I'd like to caution that comments made during this conference call will contain forward-looking statements under the safe harbor provisions of the US Private Securities Litigation Reform Act of 1995, including statements about Skye's expectations regarding its development activities, time lines and milestones.

大家好，感謝大家參加今天的電話會議。在我們開始之前，我想提醒一下，本次電話會議期間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的前瞻性陳述，包括有關 Skye 對其開發活動、時間表和里程碑的期望的陳述。

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.

前瞻性陳述受風險和不確定性的影響，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 statements made today. I encourage you to review all the company's filings with the Securities and Exchange Commission concerning these and other matters.

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

I'll now turn the call over to Punit Dhillon, Skye's President and CEO.

現在我將把電話轉給 Skye 總裁兼執行長 Punit Dhillon。

Good afternoon, everyone. Today, we have most of our executive team participating in our financial results and operations update through prepared comments, or they're available to address questions during the Q&A.

大家下午好。今天，我們的大多數執行團隊成員都透過準備好的評論參與了我們的財務表現和營運更新，或者他們可以在問答環節回答問題。

As we often say, we've managed the course with discipline, and we're now approaching the point where preparation becomes proof. This quarter marks a notable prelude to our reporting of our Phase 2a data for nimacimab, Skye's differentiated peripheral CB1 inhibitor in terms of execution as well as the clarity arising from the convergence of key activities, including the progress of our Phase 2a study, understanding of the mechanism of nimacimab, and planning for next steps relating to our clinical development thesis. On today's call, we'll walk through the progress we've made, the data that we've generated and the path we're charting forward.

正如我們常說的那樣，我們已經按照紀律管理了課程，現在我們正接近準備成為證明的階段。本季標誌著我們報告 nimacimab 的 2a 期數據的重要前奏，nimacimab 是 Skye 在執行方面具有差異化的外周 CB1 抑製劑，同時也標誌著關鍵活動融合所帶來的清晰度，包括我們 2a 期研究的進展、對 nimacimab 機制的理解，以及與我們的臨床開發論文相關的下一步計劃。在今天的電話會議上，我們將介紹我們所取得的進展、我們產生的數據以及我們未來規劃的道路。

We'll cover three key areas: one, clinical progress, where we stand on our Phase 2a program and the top line timing; two, R&D foundation, how we believe our antibody approach to CB1 inhibition is mechanistically distinct and supported by reproducible preclinical data; and three, where nimacimab fits, positioning our asset within the evolving obesity treatment landscape, including gaps we believe are overlooked and not readily fulfillable with other mechanisms. Let's begin with the clinical progress.

我們將涵蓋三個關鍵領域：第一，臨床進展，我們在第 2a 階段計劃中的立場和頂線時間安排；第二，研發基礎，我們認為我們的 CB1 抑制抗體方法在機制上有何不同，並得到可重複的臨床前數據的支持；第三，nimacimab 的適用範圍，將我們的資產定位在不斷發展的臨床前數據的支持；第三，nimacimab 的適用範圍，將我們的資產定位在不斷發展的臨床前數據的支持；第三，nimacimab 的適用範圍，將我們的資產定位在不斷發展的臨床前數據的差距以及其他差距。讓我們從臨床進展開始。

The Phase 2a CBeyond is advancing as planned, on budget and ahead of schedule. Enrollment was completed in February, ahead of schedule and the 26-week visit for the last patient is projected to occur very shortly. The 26-week extension study is also now underway with both the monotherapy and combination arms enrolling.

CBeyond 第 2a 階段正在按計劃、按預算並提前推進。患者入組工作已於二月提前完成，預計最後一位患者的 26 週追蹤也將很快進行。目前，為期 26 週的延長研究也正在進行中，單一療法和聯合療法組均在招募患者。

Approximately, 50% of the patients from the original study are eligible for enrollment, and we're optimistic that a majority of the eligible patients will choose to participate in the extension study. The Data Safety Monitoring Committee has now reviewed the study 4 times and issued no recommendations for changes.

原始研究中約 50% 的患者符合入組條件，我們樂觀地認為大多數符合條件的患者將選擇參加擴展研究。資料安全監測委員會目前已對該研究進行了四次審查，並未提出任何修改建議。

This has been an effectively managed program from time line management and data capture on various endpoints to regulatory coordination from the initial IND to the recent protocol updates to facilitate the 26-week extension. We look forward to completing treatment of our final enrolled patient for this first segment of CBeyond and then stepping into the data analysis. We remain on track to deliver top line results by late Q3, early Q4.

這是一個有效管理的計劃，從時間軸管理和各個端點的數據捕獲到從初始 IND 到最近的協議更新的監管協調，以促進 26 週的延長。我們期待完成 CBeyond 第一階段的最後一位入組患者的治療，然後進入數據分析階段。我們仍有望在第三季末和第四季初公佈營收業績。

Next, let's discuss R&D. As a reminder, nimacimab is a fully humanized, peripherally restricted CB1 antibody designed to target a well-established metabolic pathway, but to do so without the central toxicity that has historically limited CB1 inhibitors.

接下來我們來討論一下研發。需要提醒的是，nimacimab 是一種完全人源化、週邊限制的 CB1 抗體，旨在針對已建立的代謝途徑，但沒有歷史上限制 CB1 抑制劑的中樞毒性。

We differentiate from non-antibody CB1 inhibitors in two fundamental ways: one, from a distribution standpoint; and two, mechanism, both advantages that support a broader therapeutic window and target engagement in the periphery. Let's focus in on peripheral restriction. Nimacimab shows negligible brain penetration across many different species.

我們從兩個基本面向將其與非抗體 CB1 抑制劑區分開來：一是從分佈的角度；二是從機制的角度，這兩種優勢都支持更廣泛的治療窗口和針對外圍的目標參與。讓我們集中討論外圍限制。Nimacimab 在許多不同物種中顯示出微不足道的腦滲透性。

It's confirmed through PET imaging, cerebral spinal fluid analysis and postmortem tissue assessments. Even at high and repeated doses, the molecule remains peripherally compartmentalized. Next, let's talk about mechanism, allosteric noncompetitive inhibition. Nimacimab binds at the allosteric site of CB1, retaining potency even in the presence of elevated endocannabinoids, which is commonly associated with the obese state.

透過 PET 影像、腦脊髓液分析和屍檢組織評估證實了這一點。即使劑量高且重複，該分子仍保持在周邊區域內。接下來我們來談談機制，變構非競爭性抑制。Nimacimab 與 CB1 的變構位點結合，即使在內源性大麻素升高的情況下仍能保持效力，而內源性大麻素升高通常與肥胖狀態有關。

This is in contrast to small molecules that bind to the orthosteric site of the CB1 receptor, which may face increasing competition to bind to the receptor and can lose efficacy in the presence of high concentration of endocannabinoids.

這與結合 CB1 受體正位點的小分子形成對比，後者可能面臨越來越激烈的與受體結合的競爭，並且在高濃度內源性大麻素存在的情況下可能失去功效。

We've evaluated this molecule through multiple preclinical studies using our human CB1 knock-in DIO mouse model. Based on these DIO mouse studies, we believe there are at least four distinct yet converging mechanisms that define nimacimab's action and form our platform's scientific core.

我們使用人類 CB1 敲入 DIO 小鼠模型透過多項臨床前研究評估了該分子。根據這些 DIO 小鼠研究，我們認為至少有四種不同但又趨同的機制可以定義 nimacimab 的作用並構成我們平台的科學核心。

One, caloric restriction via peripheral hormonal coordination. Nimacimab reduces food intake by acting on adipose and gastrointestinal tissues to modulate appetite regulating hormones such as GLP-1, leptin and resistin. This enables a peripherally-mediated reduction in central appetite signaling without requiring brain exposure.

一、透過外周激素協調來限制熱量。Nimacimab 透過作用於脂肪和胃腸組織來調節食慾調節荷爾蒙（如 GLP-1、瘦素和抵抗素）來減少食物攝取。這使得周邊介導的中樞食慾訊號減少，而無需大腦暴露。

Two, improvement and restoration of glycemic control. We see consistent improvements in fasting glucose and insulin with significant improvements in glucose tolerance in DIO models, supporting nimacimab's relevance for patients with prediabetes or insulin resistance.

二、改善及恢復血糖控制。我們看到空腹血糖和胰島素持續改善，DIO 模型中的葡萄糖耐受性顯著改善，支持 nimacimab 與糖尿病前期或胰島素抗性患者的相關性。

Three, enhancement of lipid metabolism. Nimacimab reduces steatosis and circulating cholesterol levels, a direct benefit for patients with obesity-linked metabolic comorbidities like NAFLD or dyslipidemia. Four, reduction of obesity-induced inflammation.

三、增強脂質代謝。Nimacimab 可降低脂肪變性和循環膽固醇水平，這對患有 NAFLD 或血脂異常等肥胖相關代謝合併症的患者有直接益處。四、減少肥胖引起的發炎。

Nimacimab reduces the level of key serum inflammatory mediators and macrophage infiltration in liver and adipose tissue, pointing to a disease-modifying role of nimacimab related to comorbidities of obesity. These effects seen in our DIO models are robust, reproducible and mechanistically distinct from, though complementary to, incretin-based agents. That gives us potential optionality across monotherapy, combination and maintenance strategies.

Nimacimab 降低了關鍵血清發炎介質的水平以及肝臟和脂肪組織中的巨噬細胞浸潤，顯示 Nimacimab 具有與肥胖合併症相關的疾病修飾作用。在我們的 DIO 模型中看到的這些效果是強大的、可重複的，並且在機制上與基於腸促胰島素的藥物不同，儘管是互補的。這為我們提供了單一療法、合併療法和維持策略的潛在選擇。

Okay. Let's dive into that last point and touch on the new preclinical data that was shared today. To test how nimacimab could perform in real-world settings, we recently conducted a preclinical DIO study asking three key questions: one, can nimacimab enhance the efficacy of a suboptimal dose of tirzepatide?

好的。讓我們深入探討最後一點，並談談今天分享的新臨床前數據。為了測試 nimacimab 在現實環境中的表現，我們最近進行了一項臨床前 DIO 研究，提出了三個關鍵問題：第一，nimacimab 能否增強次優劑量 tirzepatide 的療效？

This is highlighted by the yellow part of the study schematic. Two, does nimacimab offer a more durable weight loss profile post treatment? This is highlighted by comparing the yellow to the blue part of the study schematic. And three, can nimacimab act as a maintenance or rescue therapy after incretin discontinuation?

研究示意圖中的黃色部分突顯了這一點。二、尼瑪昔單抗治療後是否能帶來更持久的減肥效果？透過比較研究示意圖中的黃色部分和藍色部分，可以突出顯示這一點。第三，尼瑪昔單抗能否作為停用腸促胰島素後的維持治療或搶救治療？

This is comparing the yellow to the pink color as a clear control. Here's what we found. First, the combination efficacy. The preclinical DIO study findings demonstrated that at day 25, the combination of nimacimab and a suboptimal tirzepatide dose of three nanomoles per kilogram daily yielded 44% vehicle-adjusted weight loss. The combination outperformed either agent alone with nimacimab demonstrating 21.5% vehicle-adjusted weight loss and tirzepatide demonstrating 29.7% vehicle-adjusted weight loss.

這是將黃色與粉紅色進行比較，作為清晰的對照。以下是我們的發現。一是聯合療效。臨床前 DIO 研究結果表明，在第 25 天，nimacimab 與次優劑量（每日每公斤 3 納摩爾）的 tirzepatide 聯合使用可實現 44% 的載體調整體重減輕。此組合療法的效果優於單獨使用任何一種藥物，其中尼馬西單抗顯示載體調整後的體重減輕 21.5%，而替澤帕肽顯示載體調整後的體重減輕 29.7%。

The combination efficacy also exceeded an optimal dose of tirzepatide of 10 nanomoles per kilogram daily, which resulted in 38.9% vehicle-adjusted weight loss. This highlights a meaningful opportunity to develop combination strategies that achieve greater efficacy at lower doses, potentially improving tolerability, reducing cost, and expanding treatment accessibility.

合併用藥的療效也超過了每日每公斤10奈摩爾的tirzepatide最佳劑量，導致載體調整後的體重減輕38.9%。這凸顯了一個有意義的機會，即開發聯合策略，以較低的劑量實現更高的療效，從而有可能提高耐受性、降低成本並擴大治療的可及性。

Now point number two, nimacimab demonstrated durable posttreatment weight loss compared to incretin therapy after the therapy stopped. In comparison of nimacimab and tirzepatide following cessation of treatment in the preclinical DIO mouse model, nimacimab demonstrated superior durability of weight loss. Specifically, the low-dose tirzepatide group regained most of their original weight back eight days after coming off therapy, regaining 29.7% of weight by day 24 post treatment.

第二點，與腸促胰島素治療相比，尼馬昔單抗在治療停止後表現出持久的減重效果。在臨床前 DIO 小鼠模型中，停止治療後，nimacimab 與 tirzepatide 進行比較，nimacimab 表現出更優異的減肥持久性。具體來說，低劑量 tirzepatide 組在停止治療八天後恢復了大部分原來的體重，治療後第 24 天恢復了 29.7% 的體重。

In comparison, the nimacimab treated group maintained their post-treatment weight for approximately 20 days, regaining only 7.4% by day 24. This rebound effect has been well documented in animal models and clinical data and represents a major issue for patients who come off incretin-based therapies.

相較之下，尼馬西單抗治療組在治療後體重維持了約 20 天，到第 24 天僅恢復了 7.4%。這種反彈效應已在動物模型和臨床數據中得到充分證實，並且對於停止使用腸促胰島素治療的患者來說是一個主要問題。

Nimacimab's durability after cessation of therapy represents a potentially clinically beneficial and distinct outcome relative to incretin-based therapies. Let's move to the third point and now add back nimacimab. Here, we're looking at maintenance of weight loss using nimacimab alone post incretin treatment.

與基於腸促胰島素的療法相比，Nimacimab 在停止治療後的持久性代表了潛在的臨床益處和獨特的結果。讓我們轉到第三點，現在重新加入尼瑪昔單抗。在這裡，我們正在研究在腸促胰島素治療後單獨使用尼馬昔單抗來維持減重效果。

When nimacimab alone was used after an initial tirzepatide or combination treatment in the preclinical DIO mouse model, it greatly reduced rebound weight gain in these bottom three groups of mice, the suboptimal TRZ and nima combo in purple, the optimal TRZ dose in red, and the one we're going to zoom into is the suboptimal TRZ following nimacimab, which is in pink.

在臨床前 DIO 小鼠模型中，在初始 tirzepatide 或聯合治療後單獨使用 nimacimab 時，它大大減少了下面三組小鼠的反彈性體重增加，紫色表示次優 TRZ 和 nima 組合，紅色表示最佳 TRZ 劑量，而我們要放大的是 nimacimab 之後的次優 TRZ，即粉紅色。

The key takeaway, no matter which of these line graphs you're looking at, is that the data show nimacimab reinforcing its potential role as a post-incretin weight loss maintenance therapy. And specifically, when nimacimab was added following treatment with low-dose tirzepatide, the pink line, nimacimab reduced rebound weight gain from 29.7% to 12.8%.

無論您查看哪張折線圖，關鍵的一點是，數據顯示尼馬昔單抗強化了其作為腸促胰島素治療後減肥維持療法的潛在作用。具體來說，當在低劑量 tirzepatide 治療後添加 nimacimab（粉紅線）時，nimacimab 將反彈體重增加從 29.7% 降低到 12.8%。

Taken together, these data suggest nimacimab has utility across a broad continuum of care, not just initiating weight loss, but also sustaining it. This continues to strengthen our thesis and bring us to the real-world setting and answering where nimacimab fits and understanding the real-world therapeutic gap.

綜合起來，這些數據表明尼瑪昔單抗在廣泛的護理過程中具有實用性，不僅可以啟動減肥，還可以維持減肥效果。這進一步強化了我們的論點，並將我們帶入現實世界，回答尼瑪昔單抗的適用範圍並了解現實世界的治療差距。

Again, we're not trying to displace GLP-1s. We believe they are foundational and they're backbone, but they also have well-recognized limitations. 58% of patients discontinue before 12 weeks, 80% by year two, up to 40% of weight loss can come from lean mass, and GI side effects remain a major driver of treatment discontinuation and patient dissatisfaction.

再次強調，我們並不是想取代 GLP-1。我們相信它們是基礎和支柱，但它們也具有眾所周知的限制。 58% 的患者在 12 週之前停藥，80% 的患者在第二年之前停藥，高達 40% 的體重減輕可能來自瘦體重，而胃腸道副作用仍然是治療停止和患者不滿的主要原因。

This ultimately creates a significant therapeutic gap and one that nimacimab is designed to address. There's three market opportunities: one, as a monotherapy for patients who can't tolerate or don't respond to incretin therapeutics; two, as a combination partner to amplify efficacy or reduce incretin dose burden; and three, as a maintenance therapy to sustain weight loss after a desired weight is achieved with better tolerability.

這最終造成了巨大的治療差距，而 nimacimab 正是旨在解決這個問題。有三個市場機會：第一，作為無法耐受或對腸促胰島素療法沒有反應的患者的單一療法；第二，作為組合療法來增強療效或減少腸促胰島素的劑量負擔；第三，作為維持療法，在達到理想體重後維持減肥效果，並且耐受性更好。

As developers are racing to optimize potency, dosing and formulation, the field is now bumping up against a real-world ceiling, tolerability. And despite their clinical efficacy, incretin-based drugs are facing significant discontinuation rates, up to 50% within the first year and nausea is the most frequently cited reason.

隨著開發人員競相優化效力、劑量和配方，該領域現在正遭遇現實世界的上限——耐受性。儘管具有臨床療效，但腸促胰島素類藥物的停藥率很高，第一年內停藥率高達 50%，最常見的原因是噁心。

As illustrated here, many of the late-stage programs cluster in the high nausea, high dropout zone, trading gastrointestinal burden for marginal weight loss gains. This has created a therapeutic paradox. There are actually stronger agents, but they have a weaker persistence.

如這裡所示，許多後期項目都集中在高噁心、高退出率區域，以胃腸道負擔換取邊際減肥收益。這造成了治療悖論。實際上存在更強的特工，但它們的持久性較弱。

We believe that this is not just a side effect problem. We believe it's a structural vulnerability in the current obesity treatment paradigm, and it's leaving a growing population of patients without sustainable options. That's where nimacimab comes in.

我們相信這不僅僅是一個副作用問題。我們認為這是當前肥胖症治療模式的結構性弱點，它導致越來越多的患者沒有可持續的選擇。這就是尼瑪昔單抗的用武之地。

Rather than replicate what's already been done, nimacimab is designed to potentially expand the therapeutic options in obesity treatment, not only as a well-tolerated and effective monotherapy, but as a differentiated and essential combination where the current incretin saturated market does not provide such options. Its mechanism offers alignment to GLP-1s, unlocking the combination potential without compounding the GI burden.

nimacimab 並非重複已有成果，而是旨在潛在地擴展肥胖症治療的治療選擇，它不僅是一種耐受性良好且有效的單一療法，而且是一種差異化且必不可少的組合療法，而目前腸促胰島素飽和市場並未提供此類選擇。其機制與 GLP-1 一致，釋放了組合潛力，而不會增加胃腸道負擔。

This positions nimacimab to potentially meet the needs of patients who discontinue using the drug due to side effects, who fail to sustain weight loss or who require multi-pathway intervention for broader metabolic impact. For us at Skye, the opportunity is clear.

這使得尼馬昔單抗有可能滿足那些因副作用而停止使用該藥物、無法維持減肥效果或需要多途徑幹預以獲得更廣泛代謝影響的患者的需求。對我們 Skye 來說，機會是顯而易見的。

Nimacimab is not just an alternative. We believe it's a next-generation backbone candidate for durable, combinable and more accessible obesity care, and it's a platform that can potentially extend beyond monotherapy to life cycle expansion across lines of therapy and patient segments that are currently underserved by today's options. And this is a key area to zoom in on, and we've been working on how best to frame it within the broader obesity treatment landscape.

Nimacimab 不僅僅是一種替代品。我們相信它是持久、可組合且更易於獲得的肥胖症護理的下一代骨幹候選藥物，並且它是一個可以超越單一療法延伸到跨療法系列和目前治療方案尚未充分服務的患者群體的生命週期擴展的平台。這是一個需要重點關注的關鍵領域，我們一直在研究如何在更廣泛的肥胖治療領域中最好地建構它。

We believe we're entering the fourth wave of obesity pharmacotherapy, a new phase that's driven by scientific innovation still, but needs to address real-world complexity in patient care. The FDA has now approved six drugs for long-term obesity treatment, each marking a step forward in the standard-of-care, from short-term stimulants to safer agents like Orlistat to the rise of GLP-1-based therapies such as semaglutide and tirzepatide, which have brought us closer to disease resolution, but a new chapter is unfolding.

我們相信，我們正在進入肥胖藥物治療的第四波浪潮，這是一個仍然由科學創新驅動的新階段，但需要解決患者護理中的現實複雜性。美國食品藥物管理局 (FDA) 目前已批准六種用於長期肥胖治療的藥物，每一種都標誌著標準治療的進步，從短期興奮劑到奧利司他等更安全的藥物，再到基於 GLP-1 的療法（如司美格魯肽和替澤帕肽），這些藥物使我們更接近疾病的治愈，但新的篇章正在展開。

Today's obesity market is evolving beyond the singular goal of caloric restriction. The next generation of anti-obesity medications such as the peripheral approach is being shaped by the need for broader metabolic impact, targeting pathways related to insulin sensitivity, lipid regulation, inflammation, and central reward signaling. This reflects a shift from weight loss alone to true disease modification, sustainable weight loss, and even addressing the other related comorbidities.

當今的肥胖市場正在不斷發展，不再僅限於限制熱量這一單一目標。下一代抗肥胖藥物（例如周邊方法）正受到更廣泛的代謝影響的需求的影響，針對與胰島素敏感性、脂質調節、發炎和中樞獎勵訊號相關的途徑。這反映了從單純的減肥到真正的疾病改變、可持續的減肥，甚至解決其他相關合併症的轉變。

With the top line data ahead, we're preparing to potentially demonstrate how nimacimab delivers on the core needs of the evolving obesity treatment paradigm that, in our opinion, fit the definition of the fourth wave by improving quality and durability of weight loss through alternative metabolic pathways, better tolerability, and strategic combinability.

憑藉未來的頂線數據，我們準備展示 nimacimab 如何滿足不斷發展的肥胖治療模式的核心需求，我們認為，該模式符合第四波的定義，即透過替代代謝途徑、更好的耐受性和戰略組合性來提高減肥的品質和持久性。

Thank you, again, for listening to our update, and I'll wrap by emphasizing that the next 90 days will be busy, and Kate's going to walk you through a few of our upcoming milestones in her remarks. Overall, for us, finishing Q2 and heading into Q3 isn't just a checkpoint. It's a culmination of disciplined execution, scientific clarity and focused investment in a differentiated mechanism.

再次感謝您收聽我們的最新消息，最後我想強調的是，接下來的 90 天將會很忙碌，凱特將在她的演講中向您介紹我們即將實現的一些里程碑。總的來說，對我們來說，完成 Q2 並進入 Q3 不僅僅是一個檢查點。它是嚴謹的執行、科學的清晰度和差異化機制的重點投資的頂峰。

We appreciate your continued support, and now I'll turn the call to Kate, our CFO.

我們感謝您一直以來的支持，現在我將把電話轉給我們的財務長凱特。

Thanks, Punit. After the market closed today, we issued a press release and filed Skye's Form 10-Q with the Securities and Exchange Commission, outlining our quarterly financial results. We encourage you to reference our filings for the details of our financials and the risk factors described therein. I will now provide a brief overview of key financial results for the second quarter ended June 30, 2025. We ended the second quarter with cash and cash equivalents and short-term investments totaling $48.6 million.

謝謝，Punit。今天收盤後，我們發布了一份新聞稿，並向美國證券交易委員會提交了 Skye 的 10-Q 表格，概述了我們的季度財務表現。我們鼓勵您參考我們的文件，以了解我們的財務詳情和其中所述的風險因素。我現在將簡要概述截至 2025 年 6 月 30 日的第二季主要財務業績。截至第二季末，我們的現金、現金等價物及短期投資總額為 4,860 萬美元。

Our cash flow guidance remains intact, with the expectation that our current capital is projected to fund operations and key clinical milestones through at least Q1 2027. This includes the completion of our Phase 2a study for nimacimab and certain Phase 2b manufacturing and preparatory clinical activities, including the initial manufacturing runs needed to start the Phase 2b dose-ranging study and clinical feasibility activities.

我們的現金流指導保持不變，預計我們目前的資本將至少為 2027 年第一季的營運和關鍵臨床里程碑提供資金。這包括完成我們對 nimacimab 的 2a 期研究和某些 2b 期製造和準備臨床活動，包括啟動 2b 期劑量範圍研究和臨床可行性活動所需的初始製造運行。

In addition, our runway also includes a modest discovery research and development budget and the formulation and development work expected to support later-stage studies for nimacimab. Research and development expenses for the three months ended June 30, 2025, were $14.3 million as compared to $4.1 million for the same period in 2024.

此外，我們的資金還包括適度的發現研究和開發預算以及預計將支持尼馬昔單抗後期研究的配方和開發工作。截至 2025 年 6 月 30 日的三個月的研發費用為 1,430 萬美元，而 2024 年同期為 410 萬美元。

The increase was primarily due to contract manufacturing, clinical trial costs associated with our clinical study for nimacimab, discovery, research, and development expenses and salaries and stock-based compensation expense.

成長主要歸因於合約製造、與我們對尼馬昔單抗的臨床研究相關的臨床試驗成本、發現、研究和開發費用以及工資和股票薪酬費用。

General and administrative expenses for the three months ended June 30, 2025, were $3.9 million as compared to $4.3 million for the same period in 2024. The decrease was primarily related to decreases in general business expenses and legal and professional fees, offset by increases in salaries and stock-based compensation expenses, consulting and advisory fees, along with investor relation costs.

截至 2025 年 6 月 30 日的三個月的一般及行政費用為 390 萬美元，而 2024 年同期為 430 萬美元。下降主要與一般業務費用和法律及專業費用的減少有關，但被工資和股票薪酬費用、諮詢和顧問費用以及投資者關係成本的增加所抵消。

Our net loss for the three months ended June 30, 2025, totaled $17.6 million, including noncash share-based compensation expense of $4.2 million. This compared to $7.9 million for the same period in 2024 with noncash share-based compensation expense of $4.3 million. In Q2, we maintained our track record of execution, hitting clinical milestones while managing capital with precision.

截至 2025 年 6 月 30 日的三個月，我們的淨虧損總計 1,760 萬美元，其中包括 420 萬美元的非現金股權激勵費用。相較之下，2024 年同期為 790 萬美元，非現金股權激勵費用為 430 萬美元。在第二季度，我們保持了執行記錄，實現了臨床里程碑，同時精確管理了資本。

We continued to build internal cadence and operational rigor, including the strategic expansion of our team to 20 employees. We made key hires in regulatory affairs, quality, clinical operations and CMC. Notably, we welcomed a Vice President of CMC to directly support our advancing development activities.

我們繼續建立內部節奏和營運嚴謹性，包括將我們的團隊策略性地擴展到 20 名員工。我們在監管事務、品質、臨床營運和 CMC 方面進行了關鍵招聘。值得注意的是，我們歡迎 CMC 副總裁直接支持我們推動開發活動。

This deliberate scaling is intended to allow us to minimize downtime between clinical trials and stay positioned to move quickly following upcoming data readouts. As we enter the second half of 2025, we remain focused on disciplined execution and are well positioned to advance nimacimab through its next development phase.

這種刻意的擴展旨在讓我們最大限度地減少臨床試驗之間的停機時間，並能夠在即將獲得的數據讀數後快速採取行動。進入 2025 年下半年，我們將繼續專注於嚴格執行，並做好充分準備推動 nimacimab 進入下一開發階段。

We are entering what is arguably the most crucial execution period in Skye's history. To outline what you can expect in the coming months: on September 4, we will host a KOL event at Nasdaq, which will be webcast live focused on the mechanism, CBeyond Phase 2a clinical data expectations and market positioning.

我們正進入 Skye 史上最關鍵的執行時期。概述一下未來幾個月您可以期待的事情：9 月 4 日，我們將在納斯達克舉辦一場 KOL 活動，該活動將透過網路直播，重點關注機制、CBeyond 第 2a 階段臨床數據預期和市場定位。

In addition, in the fall, we are participating in multiple investor conferences where we look forward to engaging directly with many of you. Finally, ahead of our top line data, we are presenting the Phase 1 SAD/MAD NAFLD data at EASD on September 19, reinforcing hepatic and metabolic benefits. In late Q3, early Q4, we expect our top line clinical readout from CBeyond.

此外，秋季我們將參加多個投資者會議，並期待與你們中的許多人直接接觸。最後，在我們的頂線數據之前，我們將於 9 月 19 日在 EASD 上展示第一階段 SAD/MAD NAFLD 數據，以強化肝臟和代謝益處。我們預計在第三季末和第四季初，CBeyond 將提供頂線臨床讀數。

As we have previously stated, this will be data from both the monotherapy and combo arms with placebo-adjusted weight loss, safety, body composition and mechanistic biomarkers. With the top line data in hand in Q4, we expect to finalize the Phase 2b protocol, further advance CMC, initiate regulatory engagement and external planning for next phase studies. This concludes our prepared comments for today.

正如我們之前所說，這將是來自單一療法和組合療法的數據，並帶有安慰劑調整的體重減輕、安全性、身體組成和機械生物標記。憑藉第四季度獲得的頂線數據，我們預計將完成第 2b 階段協議，進一步推進 CMC，啟動監管參與和下一階段研究的外部規劃。我們今天的準備評論到此結束。

Thank you very much for joining us, and we'll now open the call for questions from our covering sell-side analysts. Operator, over to you.

非常感謝您加入我們，現在我們將開始接受賣方分析師的問題。接線員，交給你了。

(Operator Instructions) Edward Tenthoff, Piper Sandler.

（操作員指示）Edward Tenthoff，Piper Sandler。

Great, thank you very much and thanks for the update getting excited for data. I had just a little bit of a housekeeping question, but with a specific angle on it. So R&D was higher. I saw that you've made some progress on the manufacturing lines. Did that account for a big part of it?

太好了，非常感謝，也感謝您對數據的更新。我只是想從特定角度問一些日常問題。因此研發費用更高。我看到你們在生產線上取得了一些進展。這佔了很大一部分嗎？

And in the press release you mentioned this Arecor, and a potentially higher concentration nimacimab formulation. Can you tell us a little bit about what the goal is from that, and when you may be able to use that higher concentration nimacimab? Thanks.

在新聞稿中您提到了 Arecor 和可能濃度較高的 nimacimab 製劑。您能否告訴我們您的目標是什麼，以及何時可以使用更高濃度的尼馬西單抗？謝謝。

Hey Ted, thanks for joining the call. I'll take the first -- this is Punit here. I'll take the first -- or I'll let Kate take the financial questions relating to R&D. I can jump in and just explain the Arecor relationship. So at the moment, we have a concentration of 200 mgs per 2 ml or 100 mg per ml is our current concentration, and that's what we're using in the clinic.

嘿，泰德，感謝您參加電話會議。我先說第一個——我是 Punit。我將回答第一個問題——或者我將讓凱特回答與研發有關的財務問題。我可以直接解釋一下 Arecor 的關係。因此，目前我們的濃度為每 2 毫升 200 毫克或每毫升 100 毫克，這也是我們在臨床上使用的濃度。

Our goal here from a target product profile is to increase that concentration to allow for a longer dosing period or less frequent dosing. And ideally, it would mean even considering 200 mg per ml. So we're basically looking to increase our concentration to go higher than 100 mg per ml and Arecor is supporting that effort. And just so we are clear about that, that's a separate kind of R&D track. It doesn't interfere with our clinical development strategy.

從目標產品概況來看，我們的目標是提高濃度，以延長給藥時間或減少給藥頻率。理想情況下，這甚至意味著考慮每毫升 200 毫克。因此，我們基本上希望將濃度提高到每毫升 100 毫克以上，而 Arecor 也支持這項努力。我們要清楚，這是一種單獨的研發軌道。它不會幹擾我們的臨床發展策略。

So as you know, our clinical development strategy and CMC efforts continue on track to support the advancement of nimacimab. But as we consider additional life cycle management, that's where we are looking for ways that we can improve concentration.

因此，如您所知，我們的臨床開發策略和 CMC 工作將繼續順利推進，以支持 nimacimab 的進步。但當我們考慮額外的生命週期管理時，我們正在尋找可以提高注意力的方法。

Kate, do you want to answer the financial piece?

凱特，你想回答財務問題嗎？

Kate is probably on mute. And the question really is just with the step-up in R&D to $14 million in the second quarter, was that largely due to this manufacturing line or more clinical trial expense? Thanks.

凱特可能處於靜音狀態。真正的問題是，第二季研發費用增加到 1,400 萬美元，這主要是由於這條生產線還是更多的臨床試驗費用？謝謝。

Yeah, sure. So there was approximately $9.1 million that we spent during the six months ended on contract manufacturing costs, and that related primarily to the Phase 2a resupply for the extension study and the supply for the Phase 2b trial as well.

是的，當然。因此，在截至 2019 年的六個月內，我們在合約製造成本上花費了大約 910 萬美元，這主要與擴展研究的第 2a 階段補給以及第 2b 階段試驗的供應有關。

Great, thanks. Excited for more data and seeing you this fall.

太好了，謝謝。很高興能獲得更多數據並在今年秋天見到您。

Thanks, Ed.

謝謝，艾德。

(Operator Instructions) Jay Olson, Oppenheimer.

（操作員指示）傑伊·奧爾森，奧本海默。

Oh, hey guys, this is Matt on for Jay. Congrats on all the progress. So as we near CBeyond data, just curious, I guess, what you're thinking for nimacimab's weight loss efficacy potential at week 26. Should we expect to see something around 8% or if it's slightly below that, would the range of around 5% to 8% be potentially compelling? And then I guess, additionally, beyond weight loss and obviously, safety, what other key metrics will you be paying attention to? And what biomarkers do you believe could be informative as well? Really appreciate it.

哦，嘿，大家好，我是馬特，代替傑伊。祝賀你取得的所有進展。因此，當我們接近 CBeyond 數據時，我只是好奇，您對 nimacimab 在第 26 週的減肥功效潛力有何看法。我們是否應該預期看到 8% 左右的成長率，或者如果略低於這個數字，那麼 5% 到 8% 左右的成長率是否具有潛在的吸引力？然後我想，此外，除了減肥和顯然的安全性之外，您還會關注哪些其他關鍵指標？您認為哪些生物標記也能提供資訊？真的很感激。

Hey Matt, thanks for joining and taking the call on behalf of Jay. Yes, so we are looking at Phase 2, the CBeyond trial, the Phase 2a really as a proof of mechanism study. It was originally designed to detect an 8% placebo-adjusted difference in weight loss with 80% power over 26 weeks.

嘿，馬特，感謝您代表傑伊參加並接聽電話。是的，所以我們正在研究第 2 階段，即 CBeyond 試驗，第 2a 階段實際上作為機制研究的證明。它最初的設計目的是檢測 26 週內安慰劑調整後體重減輕的 8% 差異，效力為 80%。

So our goal here is to demonstrate a really clear clinically meaningful weight loss separation from placebo. And as you alluded to, we believe that if we're seeing 5% to 8% range placebo adjusted, that's really a strong signal of biological activity of nimacimab.

因此，我們的目標是證明與安慰劑相比，減肥效果具有真正明顯的臨床意義。正如您所提到的，我們相信，如果我們看到安慰劑調整範圍在 5% 到 8% 之間，那麼這確實是 nimacimab 生物活性的強烈信號。

Importantly, the study was not powered really to detect a smaller difference with any statistical significance. So that's an intentional component because otherwise we would have required a way larger study. So the objective here is to validate the mechanism, establish a really strong safety and tolerability profile, and really proceed to a definitive dose-ranging study to identify the optimal dose and then the ultimate regimen for nimacimab in a Phase 3 setting.

重要的是，這項研究實際上並沒有能力檢測出具有統計意義的較小差異。所以這是一個有意為之的組成部分，因為否則我們將需要進行更大規模的研究。因此，這裡的目標是驗證機制，建立真正強大的安全性和耐受性概況，並真正進行明確的劑量範圍研究，以確定最佳劑量，然後確定 3 期環境中 nimacimab 的最終方案。

And our goal here is to deliver obviously consistent weight loss, improve GI tolerability profile. I think we alluded to that today in terms of where there's a lot of white space in the market, and that's where we feel we have really the upper hand.

我們的目標是實現明顯持續的減肥效果，改善胃腸道耐受性。我認為我們今天提到了這一點，即市場上存在大量空白，而我們認為我們在這方面確實佔了上風。

And obviously, a clear safety signal without any neuropsychiatric side effects. So all of those three parameters, we would consider CBeyond a success, and it really puts a strong foundation to move forward with Phase 2b for us.

顯然，這是一個明確的安全訊號，沒有任何神經精神副作用。因此，就這三個參數而言，我們認為 CBeyond 是成功的，它為我們推進第 2b 階段奠定了堅實的基礎。

Okay. Got it. That makes sense to me. Really appreciate it. And just a quick follow-up. If you have any expectations on the potential discontinuation rate within 26 weeks and also how, based on your expectations, you believe that could translate into an advantage versus GLP-1s in the real-world setting? And also just to clarify, as you previously said you expect about 50% of patients from the original study to be eligible for the extension study. If you could just walk us through your thinking there, that would be great. Thank you so much again.

好的。知道了。我覺得很有道理。真的很感激。這只是一次快速的跟進。您對 26 週內的潛在停藥率有何預期？此外，根據您的預期，您認為這在現實環境中如何轉化為相對於 GLP-1 的優勢？另外需要澄清的是，正如您之前所說，您預計原始研究中約 50% 的患者有資格參加擴展研究。如果您能向我們介紹您的想法，那就太好了。再次感謝您。

Yeah. So Dr. Arora, you can take the 50% approximate on the extension study. Let me walk you through the other pieces of your question. So in terms of discontinuation, we're expecting the similar trends we're seeing in most obesity studies.

是的。因此，Arora 博士，您可以在擴展研究中取 50% 的近似值。讓我帶您了解問題的其他部分。因此，就停藥而言，我們預期會出現與大多數肥胖研究類似的趨勢。

Now keep in mind, in the last two years, I think overall across all obesity studies, we've seen probably about 25% to 30% discontinuation. And I don't think that's a factor of always the drugs. It's also a factor of a very competitive landscape and the accessibility of just commercial drugs and access to new modalities. And a lot of patients are looking for that access. So we haven't seen any unusual trend in terms of discontinuation in our study and definitely not seeing anything related to safety.

現在請記住，在過去兩年中，我認為總體而言，在所有肥胖研究中，我們可能會看到約 25% 至 30% 的停藥率。我不認為這總是藥物的因素。這也是競爭激烈的市場環境以及商業藥品和新治療方式的可近性的因素。很多患者都在尋求這種治療途徑。因此，我們在研究中沒有發現任何停藥方面的異常趨勢，而且肯定沒有發現任何與安全相關的趨勢。

But in terms of the real-world situation, as I alluded to in the presentation, there's a really large opportunity here where we're seeing 50% of patients not continuing incretin therapy after a year, right? And that's where this maintenance data really showcases. And here, we can essentially capture those patients and continue on with drug and allowing patients to have that long-term sustainable weight loss.

但就現實世界的情況而言，正如我在演講中提到的那樣，這裡有一個巨大的機會，我們看到 50% 的患者在一年後不再繼續接受腸促胰島素治療，對嗎？這就是維護數據真正展示的地方。在這裡，我們基本上可以捕捉到這些患者並繼續用藥，讓患者實現長期可持續的減肥。

So I think there's a really clear market opportunity there where nimacimab's not really competing for that initial weight loss that incretins do, but it's designed to really lock in those losses that once the incretin therapies do their work, then we can see that there's an application there in a really large market.

因此，我認為這裡有一個非常明顯的市場機會，nimacimab 並不是真正地與腸促胰島素競爭最初的減肥效果，而是真正地鎖定這些減肥效果，一旦腸促胰島素療法發揮作用，我們就可以看到它在一個非常大的市場中有一個應用。

And obviously, there's still an opportunity there in the monotherapy setting, too, because there's patients that don't respond. I hope I answered those two questions. I'll turn it over to Dr. Arora to just talk about extension study and those expectations.

顯然，單一療法也仍然存在機會，因為有些患者對單一療法沒有反應。我希望我回答了這兩個問題。我將把主題交給 Arora 博士，讓他談談延伸研究和這些期望。

Yeah. So thank you. The extension study enrollment has started. I think I'll just start with the good news. We've been enrolling for the last month or so patients in the combination arms, and we are also now enrolling patients in monotherapy.

是的。所以謝謝你。延伸學習招生已經開始。我想我先從好消息開始。大約一個月前，我們一直在招募聯合治療組的患者，現在也正在招募單一療法的患者。

Just between the logistics of starting the extension and allowing patients to roll in. As you know, we didn't initially plan for an extension, but we've been able to execute on it. Between that and the natural early terminations that you get in an obesity study, we still believe that about approximately 50% of our original patient target will be eligible to roll over into extension.

這只是在開始擴建和允許患者入院的後勤工作之間。如您所知，我們最初並沒有計劃延期，但我們已經能夠執行了。在這和肥胖研究中自然提前終止的情況之間，我們仍然相信，大約 50% 的原始患者目標將有資格延續到延期。

And it's just started. So I can't give you any precise numbers. But just based on the enthusiasm at the sites and from what we hear, we are very optimistic that a majority of these patients are going to roll over because we see a lot of interest in it.

而這一切才剛開始。所以我無法給你任何精確的數字。但僅根據現場的熱情和我們所聽到的消息，我們非常樂觀地認為大多數患者都會接受翻身治療，因為我們看到很多人對此感興趣。

Okay, got it. That all makes sense. I really appreciate the questions again. Thank you so much.

好的，明白了。這一切都是有道理的。我非常感謝你再次提出的問題。太感謝了。

Thanks man.

謝謝老兄。

(Operator Instructions) Jonathan Wolleben, Citizens.

（操作員說明）Jonathan Wolleben，公民。

Hey, thanks for the update and taking the questions. Punit, you laid out a nice optionality between maintenance, monotherapy combo. How do you think about what we'll see in CBeyond, and how that might guide development and the different utility in those three different modalities for nimacimab?

嘿，感謝您的更新和回答問題。Punit，您在維護和單一療法組合之間提供了很好的選擇。您如何看待我們將在 CBeyond 中看到什麼，以及這將如何指導 nimacimab 在這三種不同模式下的開發和不同效用？

Yeah. So it's a great question. Thanks, Jon. Look, I think there's a significant opportunity for a broader maintenance franchise really taking place, and that's probably really underappreciated in the market because, let's face it, we're dealing with a very rapidly moving market. And just this week, we've seen some highlights from other obesity drug developers and everyone is adjusting to what -- where does everything shake out.

是的。這是一個很好的問題。謝謝，喬恩。瞧，我認為更廣泛的維護特許經營確實存在重大機遇，但這在市場上可能被低估了，因為，讓我們面對現實吧，我們正在應對一個快速變化的市場。就在本週，我們看到了其他減肥藥物開發商的一些亮點，每個人都在適應一切將如何發展。

I think that there's a clear opportunity for nimacimab in all three settings. In the monotherapy, we've quoted about 10% to 15% of patients, based on our primary research, that don't respond to GLP-1 therapy. So there's a pretty large capture rate of those patients.

我認為尼瑪昔單抗在這三種情況下都有明顯的機會。在單一療法中，根據我們的主要研究，我們發現約有 10% 至 15% 的患者對 GLP-1 療法沒有反應。因此這些患者的捕獲率相當高。

In the maintenance setting, we've pointed to some really important stats there, about 50% discontinuing after one year, 80% discontinuing after two years. So there's really a clear need for a drug that can capture that patient population with minimal GI side effects, and we're not expecting to add on to any of the tolerability concerns that we're seeing with incretins.

在維護設定中，我們指出了一些非常重要的統計數據，大約 50% 在一年後停止，80% 在兩年後停止。因此，我們確實需要一種能夠適應該患者群體且胃腸道副作用最小的藥物，並且我們不希望增加腸促胰島素所引起的任何耐受性問題。

And then the third opportunity is in terms of combination, I think that's really going to come down to evidence-based data. So far, this data that we pointed to today really is another important development because now we've shown with a suboptimal dose of tirzepatide in combination with nimacimab that we actually get a deeper weight loss.

第三個機會是組合方面，我認為這實際上取決於基於證據的數據。到目前為止，我們今天指出的這些數據確實是另一個重要的進展，因為現在我們已經證明，使用次優劑量的 tirzepatide 與 nimacimab 聯合使用，我們實際上可以獲得更深層次的減肥效果。

So apply that to the real world, then we expect that a patient may be able to take a more tolerable dose of an incretin therapy, and we can make up that delta in terms of weight loss with another modality. And it really points to a separation of the different biology here and pathway that CB1 is acting on versus GLP-1. Tu has been doing a lot of the market access research. So I want to give him a few minutes here to just maybe elaborate on anything I've said.

因此，將其應用到現實世界中，我們預計患者可能能夠接受更耐受劑量的腸促胰島素療法，並且我們可以透過另一種方式彌補減肥方面的差距。它確實指出了 CB1 與 GLP-1 作用的不同生物學和途徑的分離。Tu 一直在做大量的市場准入研究。所以我想給他幾分鐘時間來詳細解釋我所說的一切。

Yeah. No, I think -- thanks, Punit. I think you've hit all the highlights. I think what's important is when we speak to KOLs, they make it pretty clear that they are very excited at the prospects of new modalities that are beyond just incretins.

是的。不，我想——謝謝，Punit。我認為你已經了解了所有要點。我認為重要的是，當我們與 KOL 交談時，他們明確表示，他們對超越腸促胰島素的新模式的前景感到非常興奮。

I think they want the option to be able to provide their patients with additional mechanisms of action that may be more tolerable, may provide different benefit and may provide different options for patients that may not need to lose significant amounts of weight, but may need to manage other areas of their health.

我認為他們希望能夠為患者提供額外的作用機制，這些機制可能更容易忍受，可能提供不同的益處，並可能為不需要大量減肥但需要管理其他健康領域的患者提供不同的選擇。

So these are important things that I think the market needs to understand and is beginning to understand that weight loss as a bottom line number is no longer going to be the most important endpoint as these new drugs, new therapies, in particular, these non-incretin drugs new data is coming to the fore and that these other complementary mechanisms and other endpoints are going to be important.

因此，我認為市場需要了解這些重要的事情，並且開始了解，隨著這些新藥、新療法，特別是這些非腸促胰島素藥物的新數據的出現，減肥作為底線數字不再是最重要的終點，這些其他補充機制和其他終點將變得重要。

Yeah, and just to add to that, looking at the oral rip on data today, I mean, there's still a clear opportunity here that orals are not necessarily going to save the day in a in a maintenance setting. They don't necessarily add any more substantial weight loss, but here we've now pointed to a completely different biology, a peripheral mechanism may be enhancing that weight loss.

是的，補充一點，從今天的口服藥物數據來看，我的意思是，這裡仍然存在一個明顯的機會，即口服藥物不一定能在維護環境中挽救局面。它們不一定會帶來更顯著的減肥效果，但我們現在指出了一種完全不同的生物學原理，即一種外圍機制可能會增強減肥效果。

So I think from a competitive positioning snapshot perspective there's clearly room from an efficacy standpoint we'll see what that data looks like in the clinical setting now. There's a maintenance franchise which we're starting to, I think, understand better and there's a really clear safety mode, right, with the peripheral exclusion on the neuropsychiatric side as well as the tolerability profile to date. So those three things I think really stand out from a competitive positioning perspective.

因此，我認為從競爭定位快照的角度來看，從功效的角度來看顯然還有空間，我們現在將看看這些數據在臨床環境中的情況。我認為，我們開始更好地理解維護特許經營權，並且有一個非常清晰的安全模式，對，包括神經精神方面的外圍排除以及迄今為止的耐受性概況。因此，我認為從競爭定位的角度來看，這三件事確實非常突出。

It's really helpful color guys. I appreciate it and looking forward to the event in September.

這對色彩愛好者來說真的很有幫助。我很感激並期待九月的活動。

Thanks, John.

謝謝，約翰。

(Operator Instructions) Kristin Kluska, Cantor Fitzgerald.

（操作員指示）克里斯汀·克魯斯卡 (Kristin Kluska)，領唱菲茨杰拉德 (Cantor Fitzgerald)。

Hi, this is Ayan on Kristin's line. Congrats on the progress here. First, regarding the independent board that oversees the trial for safety, could you just remind us what the protocol is here? What types of adverse events would they report?

大家好，我是 Kristin 的 Ayan。恭喜你在這裡的進展。首先，關於監督試驗安全的獨立委員會，您能否提醒我們這裡的協議是什麼？他們會報告哪些類型的不良事件？

And then second, I know you touched on this already, but I just wanted to get some clarification around the enrollment eligibility in the extension study and how about 50% of the patients from the original study made the cut?

其次，我知道您已經談到了這一點，但我只是想澄清一下擴展研究中的入組資格，以及原始研究中約 50% 的患者是如何入選的？

Sure. Thanks for joining today. And I'm going to let Dr. Arora, Chief Medical Officer, take both of those questions.

當然。感謝您今天的加入。我將讓首席醫療官阿羅拉博士來回答這兩個問題。

Yeah, thank you, Ayan. As far as the [CMC] is concerned, on a routine basis, they meet quarterly, and we actually provide them all of the data -- safety data of the study. So we give them the complete listing of all adverse events, all serious adverse events, and any AESIs that are reported. And they also have complete information on all of those patients, any narratives, all the labs.

是的，謝謝你，Ayan。就 [CMC] 而言，他們每季都會例行開會，我們實際上會向他們提供所有數據——研究的安全數據。因此，我們向他們提供了所有不良事件、所有嚴重不良事件以及任何報告的 AESI 的完整清單。他們也掌握所有這些病人的完整資訊、任何敘述、所有實驗室的資訊。

So actually, they have a complete store of unblinded information with which they work when they review the data for the study. They are in a position to come back and ask us for clarifications, to ask us if they want us to monitor anything, what they want to know about an individual patient. At this point, frankly, we've had four reviews completed.

因此，實際上，他們擁有完整的非盲點資訊庫，可以在審查研究數據時使用這些資訊。他們可以回來向我們尋求澄清，詢問我們是否希望我們監測任何事情，他們想了解有關個別患者的什麼資訊。坦白說，到目前為止，我們已經完成了四項審查。

The last one was on July 18. Barring some minor clarifications and some questions where they wanted to know about an individual patient and were curious about certain things, there really hasn't been anything too significant. And after each meeting, they have indicated that they are comfortable with the study continuing exactly as it is.

最後一次是在7月18日。除了一些小小的澄清和他們想了解個別病人並對某些事情感到好奇的問題外，實際上沒有什麼太重要的事情。每次會議結束後，他們都表示願意繼續進行目前的研究。

Thank you for that. And then the second question on just a clarification around the enrollment eligibility in the extension study.

謝謝你。第二個問題是關於延伸學習的入學資格的澄清。

Yes. So the enrollment eligibility, and we were talking about this earlier, so patients who complete their dosing for 26 weeks are eligible for enrollment into the extension study. So anyone who does not complete 26 weeks of dosing is not. But primarily, what's happened here is that because we designed the extension study somewhat belatedly after the original study was started, it's taken us a while to get it going, to get all the approvals to get all the sites set up. So we did lose a certain number of patients who would be otherwise eligible to roll over into the study.

是的。因此，我們之前討論過入學資格，完成 26 週服藥的患者有資格參加延長研究。因此，任何未完成 26 週服藥的人均不合格。但主要原因是，由於我們在原始研究開始後才設計擴展研究，所​​以我們花了一段時間才開始進行，獲得所有批准並建立所有站點。因此，我們確實失去了一定數量的原本有資格參與研究的患者。

So when we say 50%, it doesn't mean that 50% would not -- the remaining 50% would not necessarily have been eligible. A lot of those patients are not eligible simply because they had already completed the study before the time for rollover came.

因此，當我們說 50% 時，並不意味著 50% 沒有資格——剩下的 50% 不一定有資格。許多患者沒有資格，只是因為他們在延期之前已經完成了研究。

And, of course, there is a certain amount -- yes, there is a certain amount of dropouts as well, as you know, as we've been seeing them with all of these three studies and ours seem to be in line with what you see. When you combine those two things, what we are looking at now is that we think it will be about 50% -- about 50% are eligible.

當然，有一定數量的——是的，也有一定數量的輟學，正如你所知，我們在所有這三項研究中都看到了這一點，而我們的研究似乎與你所看到的一致。當你將這兩件事結合起來時，我們現在看到的是，我們認為大約有 50%——大約 50% 的人符合條件。

Got it. Thank you for that.

知道了。謝謝你。

Albert Lowe, Craig-Hallum.

阿爾伯特·洛，克雷格·哈勒姆。

Hi, thanks for taking my question. Just a quick one for me. I know the original study design had this 13-week follow-up period to track for durability of weight loss. And I was wondering if the follow-up period after the extension study still has this follow-up period to look for durability and rebound weight gain? And in either case, when might we see data from either portion of CBeyond?

你好，謝謝你回答我的問題。對我來說只是一個快速的步驟。我知道最初的研究設計有 13 週的追蹤期來追蹤減肥的持久性。我想知道延長研究後的追蹤期是否仍有這個追蹤期來尋找耐久性和反彈體重增加？無論如何，我們何時可以看到 CBeyond 各部分的數據？

Hey Albert, thanks for joining the call today. Yeah, that's a great question. We're going to continue to have that 13-week follow-up, but that probably won't be available until the first half of 2026 in terms of that part of the data readout. So now with the extension, we will finish the 52 weeks and then all those patients will be tracked for a follow-up 13 weeks and then that data would be available. So that's more of a 2026 event now.

嘿，艾伯特，感謝您今天參加電話會議。是的，這是一個很好的問題。我們將繼續進行為期 13 週的跟踪，但就該部分數據讀數而言，可能要到 2026 年上半年才能獲得。因此，現在透過延長，我們將完成 52 週的治療，然後對所有患者進行 13 週的跟踪，然後就可以獲得這些數據了。所以現在這更像是 2026 年的事件。

Alright. Got it, thank you.

好吧。明白了，謝謝。

There are no further questions at this time. This concludes today's conference call. We thank you for your participation. You may now disconnect.

目前沒有其他問題。今天的電話會議到此結束。我們感謝您的參與。您現在可以斷開連線。