Neumora Therapeutics Inc (NMRA) 2025 Q2 法說會逐字稿

Ladies and gentlemen, thank you for standing by. This is RG, your conference operator today. (Operator Instructions) Please be advised that today's conference is being recorded.

女士們、先生們，感謝你們的耐心等待。這裡是RG，您今天的會議接線生。（操作人員指示）請注意，今天的會議正在錄音。

I would like now to turn the conference over to Helen Rubinstein, Vice President of Investor Relations and Communications. Please go ahead.

現在我將把會議交給投資者關係和傳播副總裁海倫·魯賓斯坦。請繼續。

Good afternoon, and thank you for joining Neumora Therapeutics second quarter 2025 financial results conference call. Before we begin, I encourage everyone to go to the Investors & Media section of our website at neumoratx.com, where you can find the press release related to today's call.

下午好，感謝各位參加 Neumora Therapeutics 2025 年第二季財務業績電話會議。在會議開始之前，我鼓勵大家造訪我們網站 neumoratx.com 的「投資者與媒體」版塊，在那裡您可以找到與今天電話會議相關的新聞稿。

With me today from Neumora are Chief Executive Officer, Paul Berns; President, Joshua Pinto; Chief Operating and Development Officer, Bill Aurora, Chief Scientific Officer, Nick Brandon; and Chief Financial Officer, Michael Milligan.

今天與我一同出席的來自 Neumora 的有：首席執行官 Paul Berns；總裁 Joshua Pinto；首席營運和發展官 Bill Aurora；首席科學官 Nick Brandon；以及首席財務官 Michael Milligan。

I'd like to point out that we will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and our actual results may differ materially. Please review the risk factors discussed in today's press release and in our SEC filings for additional details. With that, I'll now turn the call over to Paul.

我想指出，我們將發表一些前瞻性聲明，這些聲明是基於我們目前的預期和信念。這些聲明存在一定的風險和不確定性，我們的實際結果可能與這些聲明有重大差異。請查看今天新聞稿和我們提交給美國證券交易委員會的文件中討論的風險因素，以了解更多詳情。接下來，我將把電話交給保羅。

Thanks, Helen. Good afternoon, everyone, and thank you for joining us. At Neumora, we are on a mission to address the largest population health challenges of our generation and to do so at scale. To achieve that goal, we know that we need to generate better medicines, therapies that enable better outcomes that meaningfully improve the treatment of prevalent diseases and ultimately that positively impact quality of life for patients and their families.

謝謝你，海倫。各位下午好，感謝各位的參與。在紐莫拉，我們的使命是應對我們這一代面臨的最大人口健康挑戰，並大規模地解決這些問題。為了實現這一目標，我們知道我們需要研發更好的藥物和療法，從而帶來更好的治療效果，切實改善常見疾病的治療，並最終對患者及其家人的生活品質產生積極影響。

With that aim in mind, we built an industry-leading pipeline targeting some of the most prevalent and burdensome brain diseases. Our approach is centered on advancing programs with best-in-class pharmacology, targeting novel mechanisms of action with the potential to improve upon the current standard of care for hundreds of millions of people. We are proud to be making important progress towards that goal.

為了實現這一目標，我們建立了業界領先的研發管線，目標是一些最普遍、最棘手的腦部疾病。我們的方法以推進採用一流藥理學的方案為中心，針對新的作用機制，力求改善數億人的當前治療標準。我們很自豪能在實現這一目標的道路上取得重要進展。

Today, we announced that we prioritized obesity as the lead indication for NMRA-215, our highly brain-penetrant NLRP3 inhibitor. An increasing body of evidence supports the need for the role of centrally-acting drugs to drive weight loss in obesity, and NLRP3 inhibition in particular has shown promise across multiple studies.

今天，我們宣布將肥胖症作為 NMRA-215（一種具有高度腦滲透性的 NLRP3 抑制劑）的主要適應症。越來越多的證據表明，中樞作用藥物在肥胖症減肥中發揮重要作用，而 NLRP3 抑制劑尤其在多項研究中顯示出良好的效果。

Importantly, recent data suggest that molecules with high CNS penetration and activity are required for efficacy with this target. Currently, obesity and overweight affects more than 2.5 billion people globally. And by 2035, that number is expected to increase to up to 4 billion people. The need here is immense. Obesity is associated with significant negative outcomes and lower quality of life, and there is room to improve upon the efficacy and tolerability of the current generation of incretin therapies.

重要的是，最近的數據表明，對於該靶點，需要具有高中樞神經系統滲透性和活性的分子才能發揮療效。目前，全球有超過25億人受到肥胖和超重的影響。預計到 2035 年，這一數字將增加至 40 億人。這裡的需求非常巨大。肥胖與嚴重的負面後果和較低的生活品質有關，目前一代腸促胰島素療法的療效和耐受性還有提升空間。

In fact, up to a third of patients are non responders to current therapies, and do not experience clinically meaningful weight loss. Additionally, patients experience numerous on-target GI adverse effects, and weight regain is common after patients stop taking these drugs.

事實上，高達三分之一的患者對目前的療法沒有反應，也沒有經歷具有臨床意義的體重減輕。此外，患者還會出現許多針對胃腸道的不良反應，患者停止服用這些藥物後體重反彈也很常見。

These challenges are highlighted by the real-world use data on GLP-1. A recent real-world study found that 68% of people taking a GLP-1 for obesity discontinued use of their medication within one year. And research from the Blue Cross Blue Shield Association found that 58% of patients discontinued use before reaching a clinically meaningful health benefit.

GLP-1 的實際使用數據凸顯了這些挑戰。最近一項真實世界研究發現，68% 服用 GLP-1 治療肥胖症的人在一年內停止使用該藥物。藍十字藍盾協會的研究發現，58% 的患者在達到臨床意義的健康益處之前就停止了使用。

We believe that NLRP3 inhibition may offer an efficacious, well-tolerated treatment option for obesity, potentially as a monotherapy in combination with GLP-1 medications or the maintenance treatment option. Our deep expertise in neuroscience and specifically in developing highly brain-penetrant chemistry makes Neumora uniquely positioned to bring a potential new mechanism to this large and growing public health challenge.

我們認為，NLRP3 抑制劑可能為肥胖症提供一種有效且耐受性良好的治療選擇，可以作為單一療法與 GLP-1 藥物聯合使用，或作為維持治療方案。我們在神經科學領域，尤其是在開發高腦滲透性化學物質方面擁有深厚的專業知識，這使得 Neumora 能夠為應對這一日益嚴峻的公共衛生挑戰帶來潛在的新機制。

The breadth of our pipeline and its potential impact is immense, and we are in a strong position to translate that science into real-world therapeutic breakthroughs. We expect to have up to six clinical data readouts in patients over the next 18 months, and I'm excited to continue to build on this momentum.

我們的研發管線範圍廣泛，潛在影響巨大，我們有能力將這些科學成果轉化為現實世界的治療突破。我們預計在接下來的 18 個月內將有多達 6 例臨床數據公佈結果，我很高興能夠繼續保持這一勢頭。

I will now turn the call over to Josh Pinto, President of Neumora to review our pipeline updates. Josh?

現在我將把電話轉交給 Neumora 總裁 Josh Pinto，讓他介紹我們的管道最新進展。喬希？

Thanks, Paul. We continue to make important progress across our pipeline, which is a direct reflection of our highly productive team, differentiated approach to neuroscience drug development and rigorous prioritization of our pipeline.

謝謝你，保羅。我們的研發管線持續取得重要進展，這直接反映了我們高效的團隊、差異化的神經科學藥物研發方法以及對研發管線的嚴格優先排序。

With the initiation of our Phase I study of NMRA-861, we now have three clinical stage assets advancing through development, each with near-term catalysts on the horizon including data from our Phase I-b study of NMRA-511 in Alzheimer's disease agitation, which is expected around year-end.

隨著 NMRA-861 的 I 期研究啟動，我們現在有三個處於臨床階段的資產正在推進開發，每個資產都有近期催化劑即將到來，包括 NMRA-511 在阿茲海默症躁動方面的 I-b 期研究數據，預計將在年底左右公佈。

Top line data from the optimized Phase III KOASTAL program with navacaprant in major depressive disorder with the first top line data expected in the first quarter of 2026. And Phase I SAD, MAD data for our recently announced M4 PAM, NMRA-861 which is anticipated in the first quarter of 2026.

針對重度憂鬱症的navacaprant優化後的III期KOASTAL計畫的主要數據預計將於2026年第一季公佈。我們最近宣布的 M4 PAM NMRA-861 的 I 期 SAD、MAD 數據預計將於 2026 年第一季公佈。

Additionally, we expect to bring another M4 PAM and NMRA-898 into the clinic in 2025. And we are currently running a preclinical diet-induced obesity, or DIO model with NMRA-215 in mouse, a model that we believe is highly translatable to the clinical setting.

此外，我們預計將於 2025 年將另一種 M4 PAM 和 NMRA-898 引入臨床。我們目前正在使用 NMRA-215 在小鼠進行臨床前飲食誘導肥胖 (DIO) 模型研究，我們認為該模型具有很高的臨床轉換價值。

We are excited to provide more details on the DIO data this fall, which we believe has the potential to be highly compelling. Looking forward, we expect to initiate clinical studies with NMRA-215 in the first quarter of 2026. As we continue to prioritize our pipeline, we are focused on allocating resources to the programs we believe will make the biggest difference for patients. Given that focus, we will not be advancing our NMDA program here.

我們很高興能在今年秋季提供更多關於DIO數據的細節，我們相信這些數據可能會非常引人注目。展望未來，我們預計將於 2026 年第一季啟動 NMRA-215 的臨床研究。在繼續推進研發管線的同時，我們將重點放在那些我們認為能夠為患者帶來最大益處的項目上，並為此分配資源。有鑑於此，我們將不會在這裡推進我們的 NMDA 計畫。

As you've heard, we have a wealth of opportunities at Neumora and are entering a catalyst-rich period. With that in mind, we plan to host an R&D event in the fourth quarter of this year to discuss our programs in more detail. Each of our programs targets a substantial unmet need and represents a meaningful market opportunity.

正如你所聽到的，Neumora 擁有大量的機會，並且正進入一個充滿催化劑的時期。考慮到這一點，我們計劃在今年第四季舉辦一次研發活動，更詳細地討論我們的專案。我們的每個專案都針對尚未滿足的重大需求，並代表著重要的市場機會。

Our development strategy has multiple pathways for success and the potential to deliver multiple breakthrough and blockbuster therapy to patients in need of better treatment options. And we look forward to sharing more detail later this year.

我們的研發策略擁有多個成功途徑，並有可能為需要更好治療方案的患者提供多種突破性、重磅療法。我們期待在今年稍後分享更多細節。

With that overview, I will now turn the call over to Bill to provide an overview of our clinical programs. Bill?

有了以上概述，我現在將把電話交給比爾，讓他概述我們的臨床項目。帳單？

Thanks, Josh. We designed our clinical programs to target mechanisms of action that we believe have the potential to fundamentally change how the diseases are treated. Our approach is grounded in strong scientific rationale and a commitment to improving patient outcomes. This is clearly seen in our newly initiated Phase I study of NMRA-861.

謝謝你，喬希。我們設計的臨床計畫旨在針對我們認為有可能從根本上改變疾病治療方式的作用機制。我們的方法以強有力的科學基礎和改善病患療效的承諾為基礎。這一點在我們新啟動的 NMRA-861 I 期研究中得到了充分體現。

NMRA-861 is a highly potent and selective M4 Positive Allosteric Modulator, or PAM, which we believe offers best-in-class pharmacology. Schizophrenia is a complex disorder and the effectiveness of current treatments is often limited by suboptimal efficacy, side effects and high rates of non-adherence. We believe M4 PAM represent a promising new class with the potential to deliver a more favorable therapeutic profile, including efficacy, improved tolerability and once-daily dosing.

NMRA-861 是一種高效且選擇性極強的 M4 正變構調節劑 (PAM)，我們相信它具有一流的藥理特性。精神分裂症是一種複雜的疾病，目前治療的有效性常常受到療效不佳、副作用和高依從性等因素的限制。我們認為 M4 PAM 代表了一種很有前途的新類別，具有提供更有利的治療特性的潛力，包括療效、更好的耐受性和每日一次給藥。

NMRA-861 demonstrated robust activity in preclinical efficacy models and was also well tolerated in preclinical safety studies with no convulsions observed in rabbits, dogs or rats. NMRA-861 is currently being evaluated in a Phase I single ascending dose and multiple ascending dose study in healthy adult participants and adults with stable schizophrenia.

NMRA-861 在臨床前療效模型中表現出強大的活性，並且在臨床前安全性研究中也具有良好的耐受性，在兔子、狗或大鼠中均未觀察到驚厥。NMRA-861 目前正在健康成年受試者和患有穩定型精神分裂症的成年人中進行 I 期單次遞增劑量和多次遞增劑量研究的評估。

We look forward to reporting data from that study including safety and tolerability, human pharmacokinetic data confirming the potential for once-daily dosing and central nervous system penetration in the first quarter of 2026.

我們期待在 2026 年第一季公佈該研究的數據，包括安全性和耐受性、人體藥物動力學數據，以證實每日一次給藥的潛力以及中樞神經系統滲透性。

Additionally, we expect to bring another PAM into the clinic this year as we continue to advance our broader M4 franchise. We also have upcoming clinical milestones for navacaprant and NMRA-511. Enrollment is ongoing in the KOASTAL program, and we continue to expect top line data from KOASTAL-3 in the first quarter of 2026 and KOASTAL-2 in the second quarter of 2026.

此外，隨著我們不斷推進更廣泛的 M4 產品線，我們預計今年將另一款 PAM 產品引入臨床。我們還有 navacaprant 和 NMRA-511 即將的臨床里程碑。KOASTAL 計畫的招生工作仍在進行中，我們繼續預計 KOASTAL-3 將於 2026 年第一季公佈其主要數據，KOASTAL-2 將於 2026 年第二季公佈其主要數據。

Additionally, we expect top line results from our Phase Ib signal-seeking study of NMRA-511 in Alzheimer's disease education around the end of this year. We have made meaningful progress across our robust and growing pipeline with multiple programs advancing towards near-term clinical milestones. With our robust pipeline and R&D efforts, we believe we are poised to bring forward novel therapeutics and deliver transformative treatments to millions of patients around the world.

此外，我們預計今年年底左右將公佈 NMRA-511 在阿茲海默症教育方面的 Ib 期訊號探索研究的主要結果。我們強大的研發管線取得了實質進展，多個計畫正朝著近期臨床里程碑邁進。憑藉我們強大的產品線和研發實力，我們相信我們能夠推出創新療法，為全球數百萬名患者帶來變革性的治療方案。

With that, I'll now turn the call over to Mike for a review of the financials. Mike?

接下來，我將把電話交給麥克，讓他來審核財務狀況。麥克風？

Thanks, Bill, and good afternoon, everyone. Our financial results for the second quarter of 2025 are detailed in the press release that we issued this morning. I'd like to take a moment to provide some context and highlight a few key points.

謝謝你，比爾，大家下午好。我們今天早上發布的新聞稿中詳細列出了 2025 年第二季的財務表現。我想花點時間提供一些背景信息，並強調幾個關鍵點。

We ended the quarter with $217.6 million in cash, cash equivalents and marketable securities as of June 30, 2025. We anticipate our cash runway to support operations into 2027 well beyond all of our upcoming clinical milestones. Our total net loss for the second quarter was $52.7 million, compared to $58.7 million for the same period in 2024. This decrease was primarily due to a reduction in stock-based compensation and personnel-related expense and a reduction in clinical trial costs.

截至 2025 年 6 月 30 日，我們本季末持有現金、現金等價物及有價證券共 2.176 億美元。我們預計，我們的現金儲備足以支援營運到 2027 年，遠遠超過我們所有即將實現的臨床里程碑。第二季淨虧損總額為 5,270 萬美元，而 2024 年同期淨虧損總額為 5,870 萬美元。這一下降主要是由於股票選擇權激勵和人事相關費用的減少以及臨床試驗成本的降低。

With that, I'll now hand the call over to Helen to manage Q&A with the operator. Helen?

接下來，我將把電話交給海倫，由她負責與接線生進行問答環節。海倫？

Thanks, Mike. Before I turn it over to the operator, I'll ask that you limit yourself to one question. If you have additional question, please feel free to return to the queue. Now I'll turn it over to the operator to handle Q&A. Operator?

謝謝你，麥克。在把電話交給接線員之前，請您只提一個問題。如果您還有其他問題，請隨時返回佇列。現在我將把問答環節交給接線員。操作員？

(Operator Instructions) Your first question comes from the line of Brian Abrahams of RBC Capital Markets.

（操作員說明）您的第一個問題來自 RBC Capital Markets 的 Brian Abrahams。

This is Joe on for Brian. Can you talk about the preclinical study design in obesity, the type of diet, whether if you're looking to combine GLP-1s and whether -- what sort of comparator arms you're looking to implement in the study? Are there any certain aspect of weight loss that you're looking to demonstrate such as better quality weight loss or maintenance of weight loss post the GLP-1 withdrawal?

這裡是喬替布萊恩報道。您能否談談肥胖症的臨床前研究設計、飲食類型、是否考慮合併使用 GLP-1 以及—您打算在研究中實施哪些類型的對照組？您希望證明減肥的某些特定方面，例如更高品質的減肥或在停用 GLP-1 後維持減肥效果？

Thanks, Joe. This is Josh here. I'll take that question. For our program, NMRA-215, which is our NLRP3 inhibitor that we're moving forward, and we've announced that we prioritize in obesity. The next step, as you've highlighted, will be to run a diet-induced obesity study in mouse.

謝謝你，喬。我是喬許。我來回答這個問題。對於我們的項目，NMRA-215 是我們正在推進的 NLRP3 抑制劑，我們已經宣布我們將優先用於治療肥胖症。正如您所強調的，下一步將是對小鼠進行飲食誘導肥胖研究。

Part of the reason we're so excited about this study is we know that this model really translates between the animal setting and the human setting. We think it will give us a prediction in terms of how this molecule could ultimately perform in a clinical trial setting.

我們對這項研究感到如此興奮的部分原因是，我們知道這種模型確實可以在動物環境和人類環境之間轉換。我們認為這將使我們能夠預測該分子在臨床試驗環境中的最終表現。

In this study, we are going to look to run a set of studies. And across them, there's really going to be three key goals. First, we're going to assess the potential of NMRA-215 as a monotherapy treatment for obesity. And in this, it will just be an NMRA-215 dose in the mice. We really think that this could provide a value proposition as you relate to what's out there today in terms of the GLP-1 as well as the GLP therapies.

在本研究中，我們將進行一系列研究。而貫穿其中，實際上將有三個關鍵目標。首先，我們將評估 NMRA-215 作為肥胖單一療法的潛力。而在這個實驗中，小鼠體內只會注射 NMRA-215 劑量。我們真心認為，就目前市面上的 GLP-1 和 GLP 療法而言，這可以提供一個有價值的主張。

We think that this molecule could offer the potential for incretin-like weight loss with better tolerability, convenience as a small molecule, which can also result in a lower cost of goods as well.

我們認為這種分子具有類似腸促胰島素的減肥潛力，且耐受性更好，作為小分子使用更方便，這也有助於降低產品成本。

And so from a monotherapy perspective, we absolutely will be looking to show benefit there. We'll also be testing the product in combination as an add-on to a GLP-1 product. In this particular model, we will use semaglutide. It is known to be the standard GLP-1 used in the mouse DIO model. And so we will look at 215 as an add-on to stem up in this study.

因此，從單一療法的角度來看，我們絕對會努力證明其療效。我們也將測試該產品與 GLP-1 產品合併使用時的附加效果。在這個特定模型中，我們將使用索馬魯肽。已知它是小鼠 DIO 模型中使用的標準 GLP-1。因此，我們將 215 作為本研究中的一個附加項來考慮。

And ultimately to see can we with 215 reduce the level of sema that is given and ultimately increase the weight loss and the tolerability. As we know in this population, there's been a range of studies out there but we've seen anywhere from 60% to 70% of people taking the GLP-1s right now do not respond or ultimately discontinued due to lack of maximum weight loss. So we think that there's absolutely room to add big therapeutics on top of this.

最終目的是看看我們能否透過 215 來降低所給予的血清素水平，並最終增加減肥效果和耐受性。我們知道，在這個人群中已經有很多研究，但我們發現，目前服用 GLP-1 的人中有 60% 到 70% 沒有反應，或者最終因為沒有達到最大減肥效果而停止服用。所以我們認為，在此基礎上，絕對還有空間增加大型治療藥物。

And then finally, one of the key questions is just the long-term durability of the existing therapy that we will be looking to test NMRA-215 as a maintenance treatment. And so you can think about this paradigm, Joe, as dosing both 215 and semaglutide combination to reach a level of weight loss and then removing the semaglutide dose ultimately to demonstrate that NMRA-215 can maintain the weight loss over a long-term period.

最後，關鍵問題之一是現有療法的長期持久性，我們將測試 NMRA-215 作為維持治療的效果。所以你可以把這個範式理解為，喬，同時使用 215 和索馬魯肽組合來達到一定的減肥效果，然後最終停止使用索馬魯肽，以證明 NMRA-215 可以長期維持減肥效果。

And what this could really provide the market is a long-term cost effective and tolerable option beyond the GLP-1 therapy today. So we're really excited to bring this program forward, Joe and really looking forward to providing the data from our DIO models as we move through the rest of 2025.

而這真正能為市場帶來的，是除目前 GLP-1 療法之外，一種長期、經濟有效且耐受性良好的選擇。所以，喬，我們非常高興能夠推進這個項目，也非常期待在 2025 年剩餘的時間裡提供我們 DIO 模型的數據。

Paul Matteis of Stifel.

史蒂費爾的保羅·馬泰斯。

This is Matthew on for Paul. My question is on 861. Could you perhaps provide more description on what gives you confidence that this would be safer than the 266 molecule, which was also from the Vanderbilt deal?

這是馬太替保羅說的話。我的問題是關於861號的。您能否詳細說明一下，是什麼讓您確信這種分子比同樣來自范德比爾特交易的 266 分子更安全？

Yes, absolutely. So Joe, this is Josh here. I'll take the question first, and then I'll pass it over to Nick to provide some specifics. I think, Joe, one of the things to really remember about our M4 franchise is that all of our compounds are structurally distinct. And so as we think about the convulsions that happened with 266, 861 and 898, which is our third M4 PAM that we announced today are all structurally distinct from one another.

是的，絕對的。喬，這位是喬許。我先回答這個問題，然後交給尼克提供一些具體細節。我認為，喬，關於我們的 M4 系列產品，真正需要記住的一點是，我們所有的化合物在結構上都是不同的。因此，當我們思考 266、861 和 898 所發生的劇烈波動時，我們今天宣布的第三款 M4 PAM 都是彼此結構不同的產品。

But Nick, maybe you can provide some added detail just on what gives us confidence on the safety of 861 as it relates to what we saw in 266, here.

但尼克，或許你可以提供一些細節，說明是什麼讓我們對 861 的安全性有信心，因為它與我們在 266 中看到的情況有關。

Yes. Thanks, Josh. It's Nick here. Matthew, good question. So just stepping back, if you remember with 266, we had unfortunate and unexpected convulsions in rabbit.

是的。謝謝你，喬希。我是尼克。馬修，問得好。所以，讓我們回顧一下，如果你還記得 266 號兔子，我們當時遇到了不幸且意想不到的抽搐。

And really, as we brought these structurally distinct compound forward, that was really the main barrier for us to achieve. When you look at the basic pharmacology, have a look at our current corporate debt, the molecules are really good in -- 898. Critically, we've taken both those compounds into rabbit. We pushed doses and exposures which have exceeded where we saw convulsions of 266.

事實上，當我們提出這些結構不同的化合物時，這才是我們實現目標的主要障礙。當你研究基礎藥理學，看看我們目前的公司債務，這些分子在——898中真的很好。關鍵是，我們已經將這兩種化合物都引入了兔子體內。我們加大了劑量和暴露量，超過了我們觀察到 266 例抽搐的劑量。

So moving forward, we've truly derisked the 266 with both of these molecules. So we feel like we're in a really good now -- good position out to push both these forward. And obviously, very excited as we announced, we've started our Phase I study with 861 and more news to follow on 899.

因此，展望未來，我們已經利用這兩種分子真正降低了 266 的風險。所以，我們感覺我們現在處於一個非常好的位置——一個能夠推動這兩項事業向前發展的良好位置。顯然，我們非常激動地宣布，我們已經開始了 861 的 I 期研究，關於 899 的更多消息也將陸續公佈。

Yatin Suneja, Guggenheim.

Yatin Suneja，古根漢美術館。

Exciting announcements today. Maybe just a couple on the KOASTAL program first, if I may. Any color on screen failure rate you can provide on the two studies or any parameters that might give you confidence that the site quality is good here. And then if you can also comment on the male to female ratio that you might be targeting or you might have enrolled so far. And then just a quick one on the 511.

今天有一些令人興奮的消息要宣布。如果可以的話，我想先在 KOASTAL 節目中介紹幾個人。請提供這兩項研究中任何關於螢幕故障率的顏色數據，或任何能讓您確信該網站品質良好的參數。此外，如果您還能就您目前的目標男女比例或您迄今為止招收的男女比例發表一些看法就更好了。然後簡單介紹一下511號公車。

Obviously, those data are going to come relatively soon. So if you can maybe help us set expectation what we should be expecting and what would be considered good for you to move forward?

顯然，這些數據很快就會公佈。所以，如果您能幫助我們設定預期，告訴我們應該期待什麼，以及對您來說，怎樣的進展才算好，那就太好了？

Yatin, this is Bill. Good to speak with you again. We are really pleased with some of the benefits we're seeing from the measures we put into place with KOASTAL-2 and 3. As you'll recall, we took three steps when we paused the KOASTAL-1 study. Number one, we enhance the medical monitoring.

亞廷，我是比爾。很高興再次與您交談。我們對透過 KOASTAL-2 和 3 實施的措施所取得的一些成果感到非常滿意。您應該還記得，我們​​在暫停 KOASTAL-1 研究時採取了三個步驟。第一，我們加強醫療監測。

Second, we added in verified clinical trials. And third, we reduced the overall number of sites that we're participating to focus on those that have more experience in. So the first of these steps, which is enhancing the medical monitoring included partnering with MGH, SAFR Group, CTNI. And we are seeing that, that independent verification of the diagnosis is helping to ensure that appropriate patients are being randomized.

其次，我們加入了經過驗證的臨床試驗。第三，我們減少了參與的網站總數，以便專注於那些我們更有經驗的網站。因此，這些步驟中的第一步，即加強醫療監測，包括與 MGH、SAFR 集團、CTNI 合作。我們看到，對診斷進行獨立驗證有助於確保合適的患者被隨機分組。

The VCT approach or verified clinical trials is a screening database that's helped us to ensure that the subject is being considered for the study aren't enrolled at a different site or in a trial that would serve its exclusionary, for example, in a TRD study. So that is also providing some added benefits. So we're pleased with what we are seeing with the measures we've put into place and the trial is progressing in that regard.

VCT 方法或已驗證的臨床試驗是一個篩選資料庫，它幫助我們確保正在考慮參與研究的受試者沒有在其他地點或試驗中被納入，從而導致其被排除在外，例如，在 TRD 研究中。所以這也帶來了一些額外的好處。因此，我們對已採取的措施所取得的成效感到滿意，試驗在這方面正在取得進展。

With respect to male to female ratio, I'll just simply state that we are seeing more females already enrolled relative to males in KOASTAL-2 and 3. I won't get into specifics today, but we are pleased to see that, that is, in fact, more consistent with the prevalence of MDD and historically, what's been enrolled with sex distribution across the studies.

關於男女比例，我只想簡單地說，在 KOASTAL-2 和 3 中，我們已經看到女性的入學人數比男性多。今天我不打算深入探討具體細節，但我們很高興地看到，這實際上與 MDD 的盛行率以及歷史上納入研究的性別分佈情況更加一致。

Lastly with 511, as you'll recall, this is a signal-seeking study that is not powered to demonstrate statistical significance between active and placebo. Part A of the Phase Ib study was designed to evaluate the safety, tolerability and the PK in healthy elderly participants. We completed Part A in 2024 and NMRA-511 was well tolerated in those participants. We've subsequently moved on to Part B and expect to have results towards the end of this year. Part B is designed to evaluate the safety, tolerability, efficacy in people with AD agitation.

最後，關於 511，您可能還記得，這是一項訊號探索研究，其統計效力不足以證明活性藥物和安慰劑之間存在統計意義。Ib 期研究的 A 部分旨在評估健康老年參與者的安全性、耐受性和藥物動力學。我們在 2024 年完成了 A 部分，NMRA-511 在這些參與者中耐受性良好。我們隨後進入了B部分，預計在今年年底前得出結果。B 部分旨在評估該藥物對患有 AD 躁動症患者的安全性、耐受性和有效性。

The primary endpoint is the change from baseline to week eight on CMAI although the study is not powered to show statistical significance, we believe the data will help us better understand the drug's effect in AD agitation, including the domains of agitation that it affects and then we'll proceed with further steps around clinical development based on what we learned.

主要終點是 CMAI 治療第八週與基線相比的變化，儘管研究的統計效力不足以顯示統計學意義，但我們相信這些數據將幫助我們更好地了解該藥物對 AD 躁動的影響，包括它所影響的躁動領域，然後我們將根據我們所了解到的情況，繼續推進臨床開發方面的後續步驟。

Douglas Tsao, H.C. Wainwright.

道格拉斯·曹，H.C. 溫賴特。

I'm just curious in terms of 215 and your thoughts in terms of development in obesity. Obviously, this is a very competitive space. And once you get past the preclinical stage and even Phase I things start to become more expensive in terms of the studies.

我只是對 215 這個數字感到好奇，以及您對肥胖症發展的看法。顯然，這是一個競爭非常激烈的領域。一旦過了臨床前階段，甚至進入 I 期臨床試驗，研究成本就會開始增加。

And obviously, as a sort of CNS-focused company, sort of obesity is maybe a little bit out of your sort of primary focus. I'm just curious, is this something that you would want to take to a certain stage of development and accrue a certain amount of clinical data before potentially finding a partnership?

顯然，作為一家專注於中樞神經系統的公司，肥胖症可能不太符合你們的主要關注點。我只是好奇，在尋找合作夥伴之前，您是否希望將這項研究推進到一定的發展階段並累積一定數量的臨床數據？

Yes. Doug, this is Josh, and thanks for the question. I think in terms of how we view the obesity indication for us at Neumora, we're really committed to following the science as we advance our pipeline. And there's been this increasing body of evidence that really supports the role of centrally-acting drugs for treating obesity. We've even seen it with some of the GLP-1 therapies. It's clear that some of the appetite suppression is working through central mechanisms.

是的。道格，我是喬什，謝謝你的提問。我認為，就 Neumora 公司如何看待肥胖症這種適應症而言，我們真正致力於在推進產品研發的過程中遵循科學。越來越多的證據表明，中樞作用藥物在治療肥胖症方面發揮重要作用。我們甚至在一些 GLP-1 療法中也看到了這種情況。很明顯，部分食慾抑制是透過中樞機制來實現的。

And what we think NLRP3 offers is really a distinct approach for the treatment of patients with obesity different than the incretins or some of the other mechanisms that are in clinical development. And we've seen that through multiple sponsors having generated preclinical data in the DIO model, supporting the role for NLRP3 inhibition in obesity.

我們認為 NLRP3 為治療肥胖症患者提供了一種獨特的方法，這與腸促胰素或其他一些正在臨床開發的機制不同。我們已經看到，多個贊助商在 DIO 模型中產生了臨床前數據，支持 NLRP3 抑制在肥胖症中的作用。

And so as we looked at this opportunity, we really felt like this fit within the scope of what Neumora was set up to do, which is tackle a large population of health challenges at scale that require expertise in developing chemistry that can act centrally. And that's what we've done. And I think you've seen through some of the data we put out today, Doug, that we absolutely believe we have the best-in-class NLRP3 inhibitor in terms of CNS penetration.

因此，當我們審視這個機會時，我們真的覺得這符合 Neumora 的宗旨，即大規模地應對大量健康挑戰，這需要開發能夠發揮核心作用的化學方面的專業知識。我們就是這麼做的。道格，我想你已經從我們今天公佈的一些數據中看到了，我們絕對相信，就中樞神經系統滲透性而言，我們擁有同類最佳的 NLRP3 抑制劑。

From a development perspective, we're not going to comment right now in terms of whether we're going to partner and, or move the program forward on our own at various stages. What I can say is that progression of NMRA-215 through the DIO model and into Phase I is contemplated in our spend that's associated with cash runway into 2027.

從發展角度來看，我們現在不會評論是否會與其他機構合作，或在不同階段獨立推進該專案。我可以說的是，NMRA-215 透過 DIO 模型進入第一階段的進程，已經納入了我們與 2027 年現金流相關的支出計劃中。

And so it is currently in our operating plan to move forward under our own. And so Doug, we're really excited about this announcement today and really looking forward to kind of what's going to -- what we're going to bring forward over the rest of this year in terms of some of the preclinical data for NMRA-215 and obesity.

因此，目前我們的營運計劃是自主推進。所以道格，我們對今天的公告感到非常興奮，並且非常期待今年餘下時間裡我們將要公佈的關於 NMRA-215 和肥胖症的一些臨床前數據。

Myles Minter, William Blair.

邁爾斯·明特，威廉·布萊爾。

The first one is on 215. One of your peers that you listed as a molecule on Slide 28 in your presentation, did have a diet-induced obesity model showing 15% body weight decrease as a monotherapy. Just curious as your comment that efficacy is related to increasing brain exposure and your greater than twofold that compound according to your data. Are you expecting efficacy in that preclinical model to be greater than 15% weight loss in a monotherapy setting? That's the first question.

第一個在215號。你在簡報第 28 頁投影片中列出的一位同行的分子，確實有一個飲食誘導肥胖模型，顯示作為單一療法可使體重減少 15%。我只是好奇，因為你提到療效與增加大腦暴露量有關，而根據你的數據，這種化合物的濃度是其兩倍以上。您是否預期在單藥治療的情況下，該臨床前模型中的治療效能達到超過 15% 的體重減輕？這是第一個問題。

Second question is, has your confidence in KOASTAL-2 or 3 changed at all since we've seen the VENTURA 1 and 2 trial data at ACNP believe those showed a 0.9 point and 0.5 point improvement versus placebo on the MADRS, respectively. So just wondering whether views have changed since you've actually seen that data.

第二個問題是，自從我們在 ACNP 上看到 VENTURA 1 和 2 的試驗數據以來，您對 KOASTAL-2 或 3 的信心是否有所改變？我們認為這些數據分別顯示，與安慰劑相比，MADRS 評分提高了 0.9 分和 0.5 分。所以我想知道，自從你實際看到這些數據以來，你的觀點是否有所改變。

Myles, this is Josh. In terms of 215, we've obviously looked at the weight loss that has been generated by competitors across the DIO model quite substantially. I think as you look at the weight loss that's been achieved by the NLRP3 inhibitor to date, I think it's showing in general, about 10% to 15% weight losses of monotherapy.

邁爾斯，這是喬希。就 215 而言，我們顯然已經相當詳細地研究了競爭對手在 DIO 模式下所取得的減重成果。我認為，從 NLRP3 抑制劑迄今所獲得的減肥效果來看，總體而言，單藥治療可使體重減輕約 10% 至 15%。

From our perspective, that is quite compelling weight loss, particularly as we think about the translation from mouse models to humans. If you look at it in comparison, semaglutide, which is a very well-known molecule that's typically used as a controlled GLP-1 in these studies tends to generate in and around 20% weight loss.

從我們的角度來看，這是一個非常顯著的減肥效果，尤其是在考慮到從小鼠模型到人類的轉化時。相較之下，索瑪魯肽是一種非常知名的分子，通常在這些研究中用作受控的 GLP-1，它往往能產生約 20% 的體重減輕。

And so -- as we sit here today, I'm not going to provide a specific numerical guide in terms of what we would expect for NMRA-215 in the DIO model, but we absolutely think that the potential of these molecules is based on their activity centrally. And so we believe based on the data that we put out today showing that NMRA-215 has best-in-class brand exposure that we have a chance to show some really compelling data within the DIO model.

因此——就我們今天在這裡的情況而言，我不會就 NMRA-215 在 DIO 模型中的預期提供具體的數值指導，但我們絕對認為這些分子的潛力取決於它們在中心的活性。因此，我們相信，根據我們今天公佈的數據，NMRA-215 擁有同類最佳的品牌曝光度，我們有機會在 DIO 模型中展示一些真正引人注目的數據。

In terms of your second question on confidence around K2 or K3 post ACNP, I don't think our confidence or conviction of the study has really changed since we announced the changes that we're making to the study in the March time frame. And maybe I'll turn it over to Bill right now just to comment on how some of those changes have really come into play in what we're seeing out of it.

關於您提出的第二個問題，即 ACNP 之後 K2 或 K3 的信心，我認為自從我們在 3 月宣布對研究進行更改以來，我們對這項研究的信心或信念並沒有真正改變。也許我現在應該把麥克風交給比爾，讓他談談這些變化是如何真正影響我們目前所看到的局面的。

This is Bill. As you'll recall, navacaprant is far more selective for kappa over mu opioid receptors. So there's a difference in pharmacology between navacaprant and aticaprant. And then of course, our is a monotherapy development program in contrast to the adjunctive setting.

這是比爾。你應該還記得，納伐卡普蘭對 kappa 鴉片受體的選擇性遠高於對 mu 鴉片受體的選擇性。所以，納伐卡普蘭和阿替卡普蘭在藥理學上是有差別的。當然，我們的是單一療法開發項目，這與輔助療法有所不同。

And so with those fundamental differences between the molecules and the program we remain confident in our program, especially we've taken post K1 also are proving to be quite helpful with enhancing the medical monitoring and the application of the verified clinical trials database as well as having going through the sites that are most experienced in MDD and having stopped those sites that have just less experience. And so things are progressing for plan, and we're on track for K3 in the first quarter and K2 in the second quarter of next year.

因此，儘管分子和方案之間存在這些根本差異，但我們仍然對我們的方案充滿信心，特別是我們採取的 K1 後措施也證明對加強醫療監測和應用已驗證的臨床試驗數據庫非常有幫助，此外，我們還與在 MDD 方面最有經驗的機構合作，並停止了那些經驗較少的機構。因此，各項工作都在按計劃進行，我們預計在明年第一季推出 K3，第二季推出 K2。

(Operator Instructions)

（操作說明）

Ami Fadia, Needham.

阿米法迪亞，尼德姆。

Apologies if this is already asked. My question is regarding the 861 molecule. You mentioned earlier that it's obviously different from your earlier M4 PAM but could you give us any color on any preclinical work that you may have done that gives you confidence around the safety profile?

如果這個問題之前已經有人問過，請見諒。我的問題與861分子有關。您之前提到過，它顯然與您之前的 M4 PAM 不同，但您能否詳細介紹一下您可能進行過的任何臨床前研究，這些研究讓您對安全性有信心？

Thanks, Ami, this is Josh. What I'll start off by mentioning is that just a reminder, all of our M4 PAMs are structurally distinct from one another, including 266, 861 and 898. But I'll turn this over to Nick right now to provide some more specifics on your question on 861 safety profile.

謝謝Ami，我是Josh。首先我要提醒大家的是，我們所有的 M4 PAM 在結構上都是彼此不同的，包括 266、861 和 898。但我現在就把這個問題交給 Nick，請他就你提出的關於 861 安全特性的問題提供一些更具體的說明。

Ami, Nick. I think the critical preclinical information we have is what we did in vivo in the rabbit. As you recall, it was unexpected in the rabbit which was on clinical hold with that molecule. We've done a lot of work in the last 12 months with 861 and 898 in the rabbit where we've taken and we've dosed those compounds and achieved exposures, which surpassed where we were with 266 and we've not seen any evidence of any convulsion.

阿米，尼克。我認為我們掌握的關鍵臨床前資訊是我們在兔子身上進行的體內實驗。你應該還記得，在當時因該分子而暫停臨床試驗的兔子身上，出現這種情況是意料之外的。在過去的 12 個月裡，我們對兔子進行了大量的研究，使用了 861 和 898 這兩種化合物，並進行了給藥，達到了比 266 更高的暴露水平，而且我們沒有看到任何抽搐的跡象。

We feel very confident we have derisked both molecules as we move forward alongside the really encouraging overall pharmacological profile and other data we have, we're really encouraged about moving both of them forward. And as I mentioned earlier, really excited about having 861 back in Phase I clinical development.

我們非常有信心，隨著我們推進這兩個分子，我們已經降低了它們的風險。結合我們非常令人鼓舞的整體藥理特性和其他數據，我們對推進這兩個分子的研發感到非常振奮。正如我之前提到的，我非常高興 861 重新進入 I 期臨床開發階段。

(inaudible) of JPMorgan.

（聽不清楚）摩根大通。

This is Miriam on for Tess. What synergies do you see between your existing neuro-focused pipeline and obesity? And along these lines, how did you come about deciding that this is the right next indication for Neumora? And can you help us reconcile what your cash runway does and does not include in terms of R&D initiatives?

這裡是Miriam，為您報道Tess。您認為您現有的以神經科學為重點的產品線與肥胖症之間有哪些綜效？那麼，您是如何決定這是 Neumora 的下一個合適適應症的呢？您能否幫我們核算一下，您的現金儲備哪些用於研發項目，哪些不用於研發項目？

Great. this is Josh, and I'll take the question. I think as I mentioned previously, we were looking at indications to take 215 into -- we are really committed as I highlighted before, to following the science -- and the growing body of evidence highlighting that the drugs that are being developed and brought forward to treat obesity really are working through central mechanisms.

好的，我是喬什，我來回答這個問題。我認為正如我之前提到的，我們正在研究將 215 納入研究的跡象——正如我之前強調的，我們真正致力於遵循科學——以及越來越多的證據表明，正在開發和推出的用於治療肥胖症的藥物確實是通過中樞機制發揮作用的。

And so we feel like obesity is an indication that fits squarely within our mandate of bringing novel mechanisms and novel approaches forward to patients suffering from a range of large population health disorders that are driven through central mechanism.

因此，我們認為肥胖症完全符合我們的使命，為患有由中樞機制驅動的各種大型人群健康疾病的患者帶來新的機制和新的方法。

And so we really feel like NMRA-215 into obesity is an opportunity for us to develop a new therapeutic that we believe could be best-in-class for that area. So we think there are a lot of synergies in terms of the team's expertise in designing and developing molecules that are highly brain penetrant, as really the critical step to unlock the potential of this class and target.

因此，我們真的覺得 NMRA-215 在肥胖症領域為我們提供了一個機會，讓我們開發出一種新的療法，我們相信這種療法可能是該領域最好的。因此，我們認為，該團隊在設計和開發具有高度腦滲透性的分子方面的專業知識有很多協同效應，因為這對於釋放此類藥物和目標的潛力至關重要。

In terms of cash runway and what's included, what I will highlight is that we have a strong cash balance as we sit here today. Mike highlighted about $217 million on the balance sheet as we ended the second quarter. This gives us runway into 2027. That fully funds all of our critical programs where we provided public guidance through the clinical stage case.

就現金儲備和資金組成而言，我要強調的是，目前我們擁有充足的現金餘額。麥克指出，在第二季末，資產負債表上的金額約為 2.17 億美元。這讓我們有時間撐到2027年。這筆資金足以支持我們所有關鍵項目，我們在臨床階段為公眾提供指導。

And so we think that with each of the foremost advanced programs, we will be able to deliver meaningful clinical milestones for each of them within the current cash runway period. So we're really excited about what we have moving forward and, frankly, the opportunity we have to bring forward six potential clinical catalysts in patients over the next 18 months.

因此我們認為，憑藉每個最先進的項目，我們都能夠在目前的資金支持期內實現每個項目有意義的臨床里程碑。因此，我們對未來的發展感到非常興奮，坦白說，我們有機會在未來 18 個月內為患者帶來六個潛在的臨床催化劑。

That ends our Q&A session, and we appreciate your participation. I will now turn the call back over to Paul Berns, Chief Executive Officer, for closing remarks. Please go ahead.

問答環節到此結束，感謝各位的參與。現在我將把電話轉回給執行長保羅·伯恩斯，請他作總結發言。請繼續。

Thanks, operator, and thank you again to everyone for joining us this afternoon. So as you can see, this is an exciting time at Neumora with up to six distinct catalysts anticipated over the next 18 months, each serving as a critical inflection point with the potential to create significant value across our portfolio. These include preclinical data with NMRA-215 in obesity and the initiation of clinical studies with this program.

謝謝接線員，也再次感謝今天下午各位的參與。因此，正如您所看到的，對於 Neumora 而言，這是一個激動人心的時刻，預計未來 18 個月內將有多達六個不同的催化劑，每一個都將成為一個關鍵的轉折點，有可能為我們的投資組合創造巨大的價值。其中包括 NMRA-215 在肥胖症的臨床前數據以及該計畫的臨床研究啟動。

Initial clinical data from NMRA-861 in schizophrenia, the Phase Ib data in Alzheimer's disease agitation and Phase III data from navacaprant in the KOASTAL program. We are well positioned to achieve all upcoming milestones, which reflect the strength of our pipeline and caliber of our execution.

NMRA-861 在精神分裂症的初步臨床數據、阿茲海默症躁動的 Ib 期數據以及 KOASTAL 計畫中 navacaprant 的 III 期數據。我們已做好充分準備，實現所有即將到來的里程碑，這反映了我們強大的研發實力和卓越的執行能力。

But most importantly, it reflects our commitment to the millions of people who are in need of better treatment options. We are working with urgency to bring forward the next generation of novel therapies and ultimately redefine drug development in neuroscience. So thank you again for your continued support, and that concludes our call this afternoon.

但最重要的是，它體現了我們對數百萬需要更好治療方案的人的承諾。我們正爭分奪秒地推動下一代新型療法的研發，並最終重新定義神經科學領域的藥物開發。再次感謝各位一直以來的支持，我們今天下午的通話就到此結束了。

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝各位的參與。您現在可以斷開連線了。