BioXcel Therapeutics Inc (BTAI) 2022 Q2 法說會逐字稿

Good morning, and welcome to the BioXcel Therapeutics Second Quarter 2022 Financial Results Conference Call. (Operator Instructions)

早上好，歡迎來到 BioXcel Therapeutics 2022 年第二季度財務業績電話會議。 （操作員說明）

Just to remind everyone, certain matters discussed in today's conference call and/or answers that may be given to questions asked are forward-looking statements that are subject to risks and uncertainties related to future events and/or the future financial or business performance of the company. Actual results could differ materially from those anticipated in these forward-looking statements. Risk factors that may affect future results are detailed in the company's quarterly report on Form 10-Q for the quarter ended March 31, 2021, which can be found at www.bioxceltherapeutics.com or on www.sec.gov, which will be updated in its quarterly report on Form 10-Q for the quarter ended June 30, 2022.

提醒大家，今天電話會議中討論的某些事項和/或可能對所提問題的回答是前瞻性陳述，受與未來事件和/或未來財務或業務表現相關的風險和不確定性的影響公司。實際結果可能與這些前瞻性陳述中預期的結果存在重大差異。可能影響未來業績的風險因素詳見公司截至 2021 年 3 月 31 日止季度的 10-Q 表季度報告，可在 www.bioxceltherapeutics.com 或 www.sec.gov 上找到，該報告將進行更新在截至 2022 年 6 月 30 日的季度的 10-Q 表季度報告中。

As a reminder, today's conference is being recording. Joining us on today's call are Dr. Vimal Mehta, Chief Executive Officer; Richard Steinhart, Chief Financial Officer; Matt Wiley, Chief Commercial Officer; Dr. Rob Risinger, Chief Medical Officer of Neuroscience; Dr. Frank Yocca, Chief Scientific Officer; and Dr. Vince O'Neill, Chief Medical Officer of Oncology. It is now my pleasure to turn the call over to Dr. Mehta, the CEO of BioXcel Therapeutics. Please go ahead.

提醒一下，今天的會議正在錄製中。與我們一起參加今天電話會議的還有首席執行官 Vimal Mehta 博士；理查德·斯坦哈特，首席財務官；首席商務官 Matt Wiley；神經科學首席醫療官 Rob Risinger 博士；首席科學官 Frank Yocca 博士；和腫瘤科首席醫學官 Vince O'Neill 博士。現在我很高興將電話轉給 BioXcel Therapeutics 的首席執行官 Mehta 博士。請繼續。

Thank you, operator. Welcome, everyone, and thank you for joining our call today to discuss BioXcel Therapeutics' financial performance and business highlights for the second quarter of 2022. It has been a busy but rewarding few months, and we have been -- we have many exciting updates to review this morning. As you know, we are a biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology. You have heard me discuss our 5-year vision to become the premier AI-driven neuroscience company, and our progress from this past quarter across all parts of our business continues to bring us closer to this ambitious goal.

謝謝你，運營商。歡迎大家，並感謝您今天加入我們的電話會議，討論 BioXcel Therapeutics 2022 年第二季度的財務業績和業務亮點。這幾個月雖然忙碌但收穫頗豐，而且我們一直——我們有許多令人興奮的更新今天早上複習。如您所知，我們是一家生物製藥公司，利用人工智能方法開發神經科學和免疫腫瘤學領域的變革性藥物。您已經聽到我討論了我們成為首屈一指的 AI 驅動的神經科學公司的 5 年願景，而我們從上個季度在我們業務的所有部分取得的進展繼續使我們更接近這個雄心勃勃的目標。

Let me begin by highlighting our notable achievements across the organization. We have laid the foundation for a successful entry into the market for IGALMI, our FDA-approved acute treatment for mild, moderate or severe agitation associated with bipolar 1 or 2 disorder or schizophrenia in adults. Our sales team has been in the field for over 2 months, and key commercial activities are in full swing to create awareness and drive eventual adoption. With trade launch in early July, our priority remains delivering this new treatment option to hospital systems, healthcare professionals and patients. Our Chief Commercial Officer, Matt Wiley, will discuss commercial progress and early feedback from the field in more detail shortly.

首先讓我強調一下我們在整個組織中取得的顯著成就。我們為 IGALMI 的成功進入市場奠定了基礎，IGALMI 是我們 FDA 批准的急性治療藥物，用於治療與雙相 1 型或 2 型障礙或成人精神分裂症相關的輕度、中度或重度激越。我們的銷售團隊已經在該領域工作了 2 個多月，關鍵的商業活動正在如火如荼地進行，以提高知名度並推動最終採用。隨著 7 月初的交易啟動，我們的首要任務仍然是為醫院系統、醫療保健專業人員和患者提供這種新的治療選擇。我們的首席商務官 Matt Wiley 將在短期內更詳細地討論商業進展和來自該領域的早期反饋。

While IGALMI trade launch marked an important milestone for the 501 program, we continue our heavy focus on our 3-pillar portfolio expansion strategy for the franchise. Let me summarize our progress since last quarter. Following a successful Type B meeting with the FDA, we have further executed our strategy for our first strategic pillar, which is broadening the medical settings where 501 can be offered. On this front, I'm excited to announce our SERENITY III trial for at-home use. This pivotal double-blinded, placebo-controlled single study is designed to evaluate BXCL501 60-microgram dose for agitation associated with bipolar 1 or 2 disorders and schizophrenia, and will consist of 2 parts.

雖然 IGALMI 貿易的推出標誌著 501 計劃的一個重要里程碑，但我們繼續重點關注特許經營的三支柱投資組合擴張戰略。讓我總結一下自上個季度以來我們的進展。在與 FDA 成功舉行 B 類會議之後，我們進一步執行了我們的第一個戰略支柱戰略，即擴大可以提供 501 的醫療環境。在這方面，我很高興地宣布我們的 SERENITY III 居家試用版。這項關鍵的雙盲、安慰劑對照的單一研究旨在評估 BXCL501 60 微克劑量對與 1 種或 2 種雙相情感障礙和精神分裂症相關的激越的療效，將由兩部分組成。

The first part is similar to our SERENITY I and II trials, which were the basis for our IGALMI approval earlier this year, and is designed to assess efficacy and safety in acutely agitated bipolar and schizophrenia patients in an institutional setting. Like SERENITY I and II, SERENITY III primary efficacy endpoint is a change from baseline in PEC total score at 2 hours compared to placebo. The second part of SERENITY III is designed to assess safety compared to placebo when self-administered at home. We believe SERENITY III may be de-risked for the following reasons. First, it will utilize many of the same investigators and clinical sites as SERENITY 1 and 2. Second, we have already observed dose-dependent responses in our Phase I/IIb study for 60-, 80-, 120- and 180-microgram doses.

第一部分類似於我們的 SERENITY I 和 II 試驗，它們是我們今年早些時候獲得 IGALMI 批准的基礎，旨在評估機構環境中急性激越雙相情感障礙和精神分裂症患者的療效和安全性。與 SERENITY I 和 II 一樣，SERENITY III 的主要療效終點是與安慰劑相比，2 小時時 PEC 總分相對於基線的變化。 SERENITY III 的第二部分旨在評估在家中自行給藥時與安慰劑相比的安全性。我們認為 SERENITY III 可能因以下原因而被去風險化。首先，它將使用許多與 SERENITY 1 和 2 相同的研究人員和臨床地點。其次，我們已經在 I/IIb 期研究中觀察到 60、80、120 和 180 微克劑量的劑量依賴性反應.

Recent market results show a significant number of newly identified unclaimed and untreated episodes in bipolar patients in the at-home setting. This is additive to the claims data research showing that 1/3 of the 25 million bipolar and schizophrenia agitation-related episodes occur outside the institutional setting. Coupled together, this is a clearly defined medical need and large market opportunity in which we have already demonstrated the efficacy and safety of IGALMI. Additionally, the experience which psychiatrists will gain in the institutions with the current commercial effort will help build a strong bridge to eventual community use, if approved. We expect to initiate SERENITY III in the second half of 2022.

最近的市場結果顯示，在家庭環境中，雙相情感障礙患者中有大量新發現的無人認領和未經治療的發作。這是對索賠數據研究的補充，表明 2500 萬雙相情感障礙和精神分裂症激越相關發作中有 1/3 發生在機構環境之外。結合在一起，這是一個明確定義的醫療需求和巨大的市場機會，我們已經在其中證明了 IGALMI 的有效性和安全性。此外，如果獲得批准，精神病醫生將通過當前的商業努力在機構中獲得的經驗將有助於為最終的社區使用架起一座堅固的橋樑。我們預計在 2022 年下半年啟動 SERENITY III。

Next, as part of our indication expansion strategy, we have made strides in our clinical development programs for 501. Our TRANQUILITY program for the acute treatment of agitation in patients with Alzheimer's disease is advancing well. Our TRANQUILITY 2 pivotal trial is enrolling, with top-line data now expected in the first half of 2023, and we still anticipate initiating enrollment in the second half of this year for TRANQUILITY 3, our second pivotal trial in the program. With the recent approval of IGALMI and a strong initial label, we believe the TRANQUILITY program has been significantly de-risked.

接下來，作為我們適應症擴展戰略的一部分，我們在 501 的臨床開發計劃中取得了長足進步。我們針對阿爾茨海默病患者激越的急性治療 TRANQUILITY 計劃進展順利。我們的 TRANQUILITY 2 關鍵試驗正在招募中，現在預計將在 2023 年上半年獲得一線數據，我們仍然預計將在今年下半年開始招募 TRANQUILITY 3，這是我們在該計劃中的第二個關鍵試驗。隨著 IGALMI 最近的批准和強大的初始標籤，我們相信 TRANQUILITY 計劃已經大大降低了風險。

Additionally, the positive efficacy, safety and tolerability data generated to date, along with breakthrough therapy designation from the FDA, provides us continued confidence in the pivotal TRANQUILITY program. We look forward to progressing 501 towards a supplemental NDA for agitation in patients with Alzheimer's. Alzheimer's disease-related agitation remains a clinical area of significant and growing unmet need, with an estimated 100 million episodes per year in the U.S. and no FDA-approved therapies. We are excited by the potential of 501 to play a key role in providing a much-sought-after solution for Alzheimer's-associated agitation.

此外，迄今為止產生的積極療效、安全性和耐受性數據，以及 FDA 的突破性治療指定，使我們對關鍵的 TRANQUILITY 計劃充滿信心。我們期待將 501 推進到針對阿爾茨海默氏症患者激越的補充 NDA。與阿爾茨海默氏病相關的躁動仍然是一個重要且不斷增長的未滿足需求的臨床領域，在美國估計每年有 1 億次發作，並且沒有 FDA 批准的治療方法。我們很高興 501 有潛力在為阿爾茨海默氏症相關的躁動提供備受追捧的解決方案方面發揮關鍵作用。

Further to our indication expansion strategy, we are investigating the potential utility of 501 as an adjunctive treatment in major depressive disorder. Our Phase I multiple ascending dose trial in healthy volunteers is progressing well, with our 30- and 60-microgram dose cohorts complete. This double-blinded, placebo-controlled study includes multiple cohorts, each consisting of 18 volunteers. The 80-microgram dose escalation portion of the trial is currently underway.

除了我們的適應症擴展策略，我們正在研究 501 作為重度抑鬱症輔助治療的潛在效用。我們在健康志願者中進行的 I 期多次遞增劑量試驗進展順利，我們的 30 微克和 60 微克劑量隊列已經完成。這項雙盲、安慰劑對照研究包括多個隊列，每個隊列由 18 名志願者組成。該試驗的 80 微克劑量遞增部分目前正在進行中。

Data readout for this daily dosing study is expected in the first half of 2023 and will inform our dose selection for a future proof-of-concept depression study. Over 300 million antidepression prescriptions are filled annually in the U.S. and current treatments are limited by slow onset of action and incomplete responses. More broadly, the 60-microgram dose daily dosing over 7 days in healthy volunteers is quite encouraging and supportive for our leading programs for at-home use.

這項每日劑量研究的數據預計將於 2023 年上半年讀出，並將為我們未來抑鬱症概念驗證研究的劑量選擇提供信息。美國每年開出超過 3 億份抗抑鬱藥處方，目前的治療受到起效緩慢和反應不完全的限制。更廣泛地說，健康志願者在 7 天內每天服用 60 微克的劑量非常鼓舞人心，並支持我們領先的居家使用計劃。

Moving on to the third and final pillar for our 501 expansion strategy, growing geographic footprint, given the significant near-term U.S. market opportunities the company has available by developing 501 for bipolar 1 and 2 and schizophrenia patients in the home setting and as an adjunctive treatment for MDD, we have made the strategic choice to prioritize resources to execute on U.S. strategy over ex U.S. As a result, we have chosen not to file an MAA at this time. We fully intend to pursue a well-timed geographic expansion at the most appropriate and opportune time.

繼續我們 501 擴張戰略的第三個也是最後一個支柱，即不斷擴大的地理足跡，考慮到公司通過在家庭環境中為雙相情感障礙 1 和 2 以及精神分裂症患者開發 501 以及作為輔助藥物，可以獲得重大的近期美國市場機會對於 MDD 的治療，我們做出了戰略選擇，優先考慮資源以執行美國戰略而不是前美國。因此，我們選擇此時不提交 MAA。我們完全打算在最合適和最合適的時間進行適時的地域擴張。

Moving beyond 501, we are leveraging our proven AI technology to build out a sustainable R&D pipeline. As part of our effort to build out our neuroscience franchise, we continue to advance formulation work for BXCL502, which demonstrates a novel and differentiated mechanism of action for the chronic treatment of agitation related to dementia and other neuropsychiatric conditions.

超越 501，我們正在利用我們成熟的 AI 技術來構建可持續的研發管道。作為我們建立神經科學專營權的努力的一部分，我們繼續推進 BXCL502 的配方工作，它展示了一種用於長期治療與癡呆症和其他神經精神疾病相關的躁動的新穎且差異化的作用機制。

Shifting to our oncology franchise, we have established OnkosXcel, a fully operational focused subsidiary to provide maximum strategic and financial flexibility and position us for sustained expansion and optimization of the franchise. We are actively seeking strategic options, including third-party investments, to advance OnkosXcel and ultimately unlock significant value for our immuno-oncology franchise. Under OnkosXcel, we are advancing the clinical development of BXCL701, our leading immuno-oncology clinical candidate being developed for the treatment of aggressive forms of prostate cancer.

轉向我們的腫瘤專營權，我們建立了 OnkosXcel，這是一家專注於全面運營的子公司，以提供最大的戰略和財務靈活性，並使我們能夠持續擴展和優化專營權。我們正在積極尋求戰略選擇，包括第三方投資，以推進 OnkosXcel 並最終為我們的免疫腫瘤專營權釋放巨大價值。在 OnkosXcel 的領導下，我們正在推進 BXCL701 的臨床開發，這是我們領先的免疫腫瘤學臨床候選藥物，正在開髮用於治療侵襲性前列腺癌。

This includes progress on our metastatic castrate-resistant prostate cancer Phase II trial of BX - of 701 plus KEYTRUDA combination therapy in patients with either small cell neuroendocrine carcinoma or adenocarcinoma phenotype. Patient enrollment is in the SCLC or it is expected to be completed in the second half of this year. In addition, enrollment is advancing for our adenocarcinoma randomized trial expansion, evaluating 701 monotherapy versus 701 KEYTRUDA combination therapy. We look forward to providing additional updates on our plan to maximize shareholder value to our oncology subsidiary later this year.

這包括我們的 BX 轉移性去勢抵抗性前列腺癌 II 期試驗的進展 - 701 加 KEYTRUDA 聯合治療小細胞神經內分泌癌或腺癌表型患者。患者入組正在SCLC或預計在今年下半年完成。此外，我們的腺癌隨機試驗擴展招募正在推進，評估 701 單一療法與 701 KEYTRUDA 聯合療法。我們期待在今年晚些時候為我們的腫瘤子公司提供最大化股東價值計劃的更多更新。

On the corporate front, we have welcomed industry veteran Michael Miller to our Board of Directors and the BioXcel family. We are very pleased to have his strategic leadership and commercial growth experience available during this exciting time for BioXcel.

在企業方面，我們歡迎行業資深人士 Michael Miller 加入我們的董事會和 BioXcel 家族。我們很高興在 BioXcel 的這個激動人心的時刻獲得他的戰略領導和商業增長經驗。

Lastly, we continue to fortify our intellectual property, with 2 new patents related to IGALMI's film formulations containing dexmedetomidine and methods of treating agitation using the films.

最後，我們繼續鞏固我們的知識產權，獲得了 2 項與 IGALMI 含有右美托咪定的薄膜配方和使用薄膜治療躁動的方法相關的新專利。

In summary, we have made great progress across all aspects of our business this quarter and are continuing our work to transform the agitation treatment landscape and other neuropsychiatric conditions. We have many exciting catalysts on the horizon and look forward to continuing our journey towards becoming the leading AI-enabled neuroscience company.

總而言之，本季度我們在業務的各個方面都取得了長足進步，並將繼續努力改變躁動治療領域和其他神經精神疾病。我們在地平線上有許多令人興奮的催化劑，並期待繼續我們的旅程，成為領先的人工智能神經科學公司。

Now I would like to turn the call over to Matt Wiley, who will give an update on the IGALMI launch. Matt?

現在我想把電話轉給 Matt Wiley，他將提供 IGALMI 發布的最新信息。馬特？

Thank you, Vimal, and good morning, everyone. I'm pleased to report our progress on 3 fronts this morning: our early market access momentum, key learnings from our initial field force efforts and our commercial strategy and execution.

謝謝你，Vimal，大家早上好。今天上午，我很高興地報告我們在 3 個方面取得的進展：我們早期的市場准入勢頭、從我們最初的現場工作中獲得的重要經驗，以及我們的商業戰略和執行。

The market access activities are progressing very well and are on schedule. While the contracting time frame with group purchasing organizations, or GPOs, can take 6 to 9 months on average, we have been encouraged by our early engagement. There are 3 national GPOs that represent over 90% of beds in our 1,700 targeted hospitals, and we are in various stages of discussions and negotiations with each. We expect to finalize the contracting process over the next few months, and we'll share our progress with you when these relationships are complete. In addition to national GPOs, we've engaged with integrated delivery network hospitals, or IDNs, to drive further downstream adoption of IGALMI. We have also executed a CMS contract and completed the federal supply schedule submission to unlock access to state and VA hospitals respectively.

市場准入活動進展順利，如期進行。雖然與團購組織 (GPO) 簽訂合同的時間框架平均需要 6 到 9 個月，但我們對早期參與感到鼓舞。有 3 個國家 GPO 占我們 1,700 家目標醫院中超過 90% 的床位，我們正在與每個 GPO 進行不同階段的討論和談判。我們希望在接下來的幾個月內完成合同流程，並在這些關係完成後與您分享我們的進展。除了國家 GPO 之外，我們還與綜合交付網絡醫院 (IDN) 合作，以推動 IGALMI 在下游的進一步採用。我們還執行了 CMS 合同並完成了聯邦供應計劃提交，以分別解鎖對州和 VA 醫院的訪問。

We have completed the first phase of our commercial build-out and deployment of our sales personnel in the highest-priority targets. To date, our field force has successfully engaged a majority of their target hospitals and has made progress in P&T formulary review discussions. Multiple hospital systems and IDNs have indicated their interest for the product and expressed an intent to review. As the P&T committees review IGALMI in their scheduled meetings during the second half of this year, we will provide an update with more specific metrics. We've learned a lot since the field launch 10 weeks ago.

我們已經完成了第一階段的商業擴建和銷售人員在最優先目標中的部署。迄今為止，我們的現場工作人員已成功與大多數目標醫院接洽，並在 P&T 處方審查討論方面取得了進展。多個醫院系統和 IDN 已表示對該產品感興趣，並表示有意審查。隨著 P&T 委員會在今年下半年的預定會議上審查 IGALMI，我們將提供更具體指標的更新。自 10 週前現場啟動以來，我們學到了很多東西。

The early response to our awareness activity, sales messaging and IGALMI concept, for which there is no commercial precedent, has been starkly positive and has revealed tremendous opportunity within the bipolar and schizophrenia agitation markets. Through discussions with stakeholders and target hospitals, our understanding of the value proposition of IGALMI continues to strengthen. The challenges surrounding the administration of intramuscular injections is a market dynamic that is becoming increasingly worrisome to institutional stakeholders and one which creates a market environment favorable to IGALMI. The use of physical restraint is often required to inject agitated patients and can increase both the expenses and safety risk to staff.

對我們的宣傳活動、銷售信息和 IGALMI 概念的早期反應是非常積極的，這在這方面沒有商業先例，並揭示了雙相情感障礙和精神分裂症激越市場的巨大機會。通過與利益相關者和目標醫院的討論，我們對 IGALMI 價值主張的理解不斷加強。圍繞肌內註射管理的挑戰是一種市場動態，它正變得越來越令機構利益相關者擔憂，並且創造了有利於 IGALMI 的市場環境。給情緒激動的患者註射時通常需要使用身體約束，這會增加費用和工作人員的安全風險。

Physical restraint can be costly and resource-intensive for hospitals at approximately $1,500 per patient, which typically surpasses the reimbursement. Consequently, a novel treatment option like IGALMI may offer an effective solution to address these issues while potentially limiting associated expenses. Furthermore, agitated patient outburst may result in patient, caregiver and staff injuries, which leads to lost work time, transfers, lawsuits and generally unsafe work environments. COVID-driven staffing pressures still exist at many of these places of care. As institutions look for ways to decrease the use of restraints and reduce injury to staff, we are observing a desire to increase the use of oral less-invasive medications for managing agitation consistent with consensus guidelines.

身體約束對於醫院來說可能是昂貴且資源密集型的，每位患者的費用約為 1,500 美元，通常超過報銷額。因此，像 IGALMI 這樣的新型治療方案可能會提供一種有效的解決方案來解決這些問題，同時可能會限制相關費用。此外，激動的患者爆發可能導致患者、護理人員和工作人員受傷，從而導致工作時間損失、轉移、訴訟和普遍不安全的工作環境。許多這些護理場所仍然存在 COVID 驅動的人員配置壓力。隨著機構尋找減少約束使用和減少員工傷害的方法，我們觀察到希望增加口服微創藥物的使用來管理與共識指南一致的躁動。

Turning now to marketing, we are deploying tactics to support the sales efforts and amplify the awareness of IGALMI. To educate healthcare providers on the core benefits of IGALMI, we have recently deployed our promotional speaker peer-to-peer program. These programs will ramp up significantly over the next 2 quarters to drive interest, formulary adoption and demand. The team has also successfully launched our IGALMI now available digital campaign, which has achieved over 100,000 visits to our HCP website and garnered meaningful engagement with the content in just a short period of time. Based on the positive market response to IGALMI, significant process with market access and increasingly favorable market dynamics, we are excited to begin our second phase of personal promotion and fully deploy our sales team across 70 territories over the next several months. This puts us in a strong position to take full advantage of the opportunity to treat volumes of patients.

現在轉向營銷，我們正在部署策略來支持銷售工作並擴大 IGALMI 的知名度。為了讓醫療保健提供者了解 IGALMI 的核心優勢，我們最近部署了我們的宣傳演講者點對點計劃。這些計劃將在接下來的兩個季度內顯著增加，以推動興趣、處方採用和需求。該團隊還成功推出了我們的 IGALMI now available digital campaign，我們的 HCP 網站的訪問量已超過 100,000 次，並在短時間內獲得了對內容的有意義的參與。基於對 IGALMI 的積極市場反應、重要的市場准入流程和日益有利的市場動態，我們很高興開始第二階段的個人推廣，並在未來幾個月內在 70 個地區全面部署我們的銷售團隊。這使我們處於有利地位，可以充分利用這個機會治療大量患者。

Now I'll turn the call over to Richard, who will give a financial update. Rich?

現在我將電話轉給理查德，他將提供財務更新。富有的？

Thank you, Matt. I will now review our second quarter 2022 financial results. Research and development expenses were $17.9 million for the second quarter of 2022 compared to $13.9 million for the same period in 2021. The increase in R&D expenses were primarily attributable to clinical costs related to the company's TRANQUILITY program. Selling, general and administrative expenses were $18.4 million for the second quarter of 2022 compared to $14.1 million for the same period in 2021. The increase in SG&A expenses were primarily due to personnel and costs related to the launch of IGALMI in the U.S.

謝謝你，馬特。我現在將回顧我們 2022 年第二季度的財務業績。 2022年第二季度的研發費用為1790萬美元，而2021年同期為1390萬美元。研發費用的增加主要歸因於與公司 TRANQUILITY 項目相關的臨床費用。 2022 年第二季度的銷售、一般和管理費用為 1840 萬美元，而 2021 年同期為 1410 萬美元。SG&A 費用的增加主要是由於與在美國推出 IGALMI 相關的人員和成本。

BioXcel Therapeutics reported a net loss of $37.7 million for the second quarter of 2022 compared to a net loss of $27.6 million in the same period in 2021. Cash burn for the quarter was approximately $33 million, which includes approximately $700,000 in inventory costs and $3.6 million in prepaid clinical trial fees. As of June 30, 2022, cash and cash equivalents totaled approximately $233.5 million. This excludes $30 million of contributions from the $260 million strategic financing announced in April. To date, the company has met the milestones and received $100 million from that agreement.

BioXcel Therapeutics 報告稱，2022 年第二季度淨虧損 3770 萬美元，而 2021 年同期淨虧損 2760 萬美元。本季度現金消耗約為 3300 萬美元，其中包括約 70 萬美元的庫存成本和 360 萬美元在預付的臨床試驗費用中。截至2022年6月30日，現金及現金等價物總額約為2.335億美元。這不包括 4 月份宣布的 2.6 億美元戰略融資中的 3000 萬美元捐款。迄今為止，該公司已達到里程碑，並從該協議中獲得了 1 億美元。

Now I'd like to turn the call back to Vimal.

現在我想把電話轉回 Vimal。

Thank you, Richard. We would now like to open the call for questions. Operator?

謝謝你，理查德。我們現在想開始提問。操作員？

Our first question is coming from the line of Greg Harrison with Bank of America.

我們的第一個問題來自美國銀行的 Greg Harrison。

Maybe, to start out, could you provide some more color on the ex U.S. strategy? Maybe just talk a little bit about the drivers behind the decision and how you would characterize the discussions that you've had with potential partners.

也許，首先，你能為前美國戰略提供更多色彩嗎？也許只是談談這個決定背後的驅動因素，以及你將如何描述你與潛在合作夥伴進行的討論。

Regarding the ex U.S. strategy, it has been evolving, considering that our program is evolving really fast. And U.S. opportunity is so attractive in the short run with our recent announcement of the SERENITY III program, where our drug is already approved -- IGALMI. It can go to the home setting. Alzheimer's program is progressing, and we will be ready to file an sNDA in that program after completion of 2 pivotal trials. So opportunity in the U.S. is really large. In addition, we are pursuing MDD. It's a strategic choice on resource deployment.

關於前美國戰略，考慮到我們的計劃發展得非常快，它一直在發展。美國的機會在短期內非常有吸引力，因為我們最近宣布了 SERENITY III 計劃，我們的藥物已經在該計劃中獲得批准—— IGALMI 。它可以轉到家庭設置。阿爾茨海默氏症項目正在進行中，我們將準備在完成 2 項關鍵試驗後提交該項目的 sNDA。所以美國的機會真的很大。此外，我們正在追求MDD。這是資源配置上的戰略選擇。

Shall we focus on U.S. or continue to focus both in U.S. and outside U.S.? So once we have captured opportunity in U.S., then we will start deployment of strategy outside -- ex-U.S. And our goal will be to look for a partner who can cover multiple geographies, rather than originally we were thinking or just, like, looking for a single partner in Europe. Now Japan is a very attractive market, considering the Alzheimer's-related agitation, and we have very strong IP position. So we are making strategic choices just from a resource deployment perspective. Otherwise, opportunity is very attractive outside U.S. in addition to U.S.

我們應該專注於美國還是繼續關注美國和美國以外的國家？因此，一旦我們在美國抓住了機會，我們就會開始在美國之外部署戰略。我們的目標是尋找一個可以覆蓋多個地區的合作夥伴，而不是我們最初的想法，或者只是在歐洲尋找一個單一的合作夥伴。現在日本是一個非常有吸引力的市場，考慮到阿爾茨海默氏症相關的躁動，我們擁有非常強大的知識產權地位。所以我們只是從資源部署的角度來做戰略選擇。否則，除了美國之外，美國以外的機會也非常有吸引力。

Okay. That makes sense. And then maybe just one more -- maybe an update on the IGALMI launch. Have you seen any early adopters in the month or so since trade launch, and if not, when would you expect the first to start to come on board?

好的。這就說得通了。然後可能只是一個 - 可能是 IGALMI 發布的更新。自交易推出以來的一個月左右，您是否看到過任何早期採用者？如果沒有，您預計什麼時候第一批開始加入？

Well, the process, Greg -- first of all, thanks for the question. The process takes 6 to 12 months on average to just get the formulary approval in the hospitals, and so driving adoption typically happens after that process has been completed. So the steps that we're taking now, that we've been taking over the last 10 weeks, is to drive interest, identify P&T stakeholders and begin the process to get formulary adoption in those hospitals. Once that happens, we'll see swifter uptake, but this is how typical hospital launches proceed. It's an operational fact, and we're just working within that set of facts.

那麼，過程，格雷格——首先，感謝你提出這個問題。該過程平均需要 6 到 12 個月才能在醫院獲得處方批准，因此推動採用通常發生在該過程完成之後。因此，我們現在正在採取的步驟，我們在過去 10 週內一直在採取的步驟，是為了提高興趣，確定 P&T 利益相關者，並開始在這些醫院採用處方集的過程。一旦發生這種情況，我們將看到更快的吸收，但這就是典型醫院啟動的過程。這是一個可操作的事實，我們只是在這組事實範圍內工作。

Our next question is coming from the line of Robyn Karnauskas with Truist Securities.

我們的下一個問題來自 Robyn Karnauskas 與 Truist Securities 的合作。

So on SERENITY III, why just 60 milligrams? Can you repeat dose? And what percentage of the population might that exclude that would need a higher dose? That's my first question, and then I have a follow-up.

那麼在 SERENITY III 上，為什麼只有 60 毫克？你能重複劑量嗎？排除需要更高劑量的人群的百分比是多少？這是我的第一個問題，然後我有一個跟進。

That's a great question, Robyn. 60 microgram, as you know, in our previous dose escalation study, we saw that 60, 80, 120, 180 -- they were all effective. We're starting with 60 because that's a dose, like, most relevant in an outpatient setting, and I will have Rob outline why we chose the 60-microgram dose. Rob?

這是一個很好的問題，羅賓。 60 微克，如你所知，在我們之前的劑量遞增研究中，我們看到 60、80、120、180——它們都是有效的。我們從 60 開始，因為這是一個劑量，就像，在門診環境中最相關，我將讓 Rob 概述為什麼我們選擇 60 微克劑量。搶？

Sure. So we chose the 60, as Vimal pointed out, because we actually have data on 60 micrograms from our dose-ranging study in schizophrenia. It separated from placebo at 2 hours. It has a large proportion of patients who respond to 60, so the number that might, let's say, need another dose is very small. So the trial is designed -- it's a frankly very slick design. We're demonstrating the efficacy in almost an identical population. It will be a combination of schizophrenia and bipolar disorder. It will be done at the very same sites that completed SERENITY I and II. So we expect identical results in terms of an improvement from baseline in the PEC total score at 2 hours, and then we're testing it for safety purposes at home, which we've received agreement from the FDA that this is a pivotal trial and will allow us to expand the label for this same indication, if you will -- agitation associated with schizophrenia or bipolar disorder -- but at-home use.

當然。所以我們選擇了 60，正如 Vimal 指出的那樣，因為我們實際上有來自精神分裂症劑量範圍研究的 60 微克數據。它在 2 小時時與安慰劑分離。它有很大一部分患者對 60 次有反應，所以比方說，可能需要另一劑的人數非常少。所以這個試驗是經過設計的——坦率地說，這是一個非常巧妙的設計。我們在幾乎相同的人群中展示了療效。這將是精神分裂症和躁鬱症的結合。它將在完成 SERENITY I 和 II 的同一地點完成。因此，我們期望在 2 小時後 PEC 總分相對於基線的改善方面得到相同的結果，然後我們出於安全目的在家中對其進行測試，我們已獲得 FDA 的同意，這是一項關鍵試驗，並且將允許我們擴展相同適應症的標籤，如果你願意——與精神分裂症或雙相情感障礙相關的躁動——但在家使用。

And so, just to be clear, can you repeat dose? And is the first portion just in the hospital and then the second portion's at home, or is it all at home and just the second portion is more for safety?

所以，為了清楚起見，你能重複劑量嗎？是第一部分在醫院，然後第二部分在家裡，還是全部在家裡，只有第二部分更安全？

The first portion is identical to what we've done in SERENITY I and II. It will be acutely agitated patients who present in an acutely agitated state. We will be able to demonstrate the 60-microgram dose is efficacious, and then the second portion of the study is testing the safety at home.

第一部分與我們在 SERENITY I 和 II 中所做的相同。會出現急性激越狀態的急性激越患者。我們將能夠證明 60 微克的劑量是有效的，然後研究的第二部分是在家中測試安全性。

So the first portion is in a hospital setting, just to be clear.

所以第一部分是在醫院環境中，只是為了清楚。

Yes.

是的。

Just to be clear.

只是為了清楚。

And there is -- I mean, there is a reason for it, because we are using PEC score, and it's a lot more convenient to have a PEC core rated by some experts rather than in a home setting. And that's why the reason to split the 2 phases.

還有——我的意思是，這是有原因的，因為我們使用的是 PEC 分數，而且讓一些專家對 PEC 核心進行評級比在家中進行評級要方便得多。這就是拆分兩個階段的原因。

It bridges the PEC score with what we've already demonstrated.

它將 PEC 分數與我們已經展示的內容聯繫起來。

That makes sense. And then the second question I had was regarding the impact of the healthcare reform Bill. I mean, obviously, if you sell this drug significantly in Alzheimer's, it's a rather large Medicare population and, like, 9 years after launch, you could be outside of that small biotech exclusion criteria, putting you within the 50 top drugs in Medicare. Have you thought about how we should think about -- I guess the first question would be, what is your estimated split for Alzheimer's for Medicare in the United States? And have you thought about how we should model that, given that that's now going to look like it's going to be in law?

這就說得通了。然後我的第二個問題是關於醫療改革法案的影響。我的意思是，很明顯，如果你在阿爾茨海默氏症中大量銷售這種藥物，它是一個相當大的 Medicare 人群，並且在推出 9 年後，你可能會超出那個小的生物技術排除標準，使你進入 Medicare 的 50 種頂級藥物。你有沒有想過我們應該如何思考——我想第一個問題是，你對美國醫療保險的阿爾茨海默氏症的估計分配是多少？你有沒有想過我們應該如何建模，鑑於現在看起來它將成為法律？

So the Med D provision in the draft Bill is really focused in on those drugs that are already costing CMS billions of dollars. So that's where the negotiations are going to happen first. We - so, to answer your question, the Medicare portion of Alzheimer's opportunity is roughly 1/3 of the total opportunity that we've seen in our modeling. And we would expect that we would address these potential issues down the line as we're thinking about, for instance, pricing flexibility that we've communicated in the past and how we want to approach this particular market. The fact is we've got a long way to go to get to FDA approval, and thinking downstream about a Bill that has not yet been ratified is a little premature.

因此，法案草案中的 Med D 條款真正關注的是那些已經讓 CMS 花費數十億美元的藥物。所以這就是談判將首先發生的地方。我們 - 所以，為了回答你的問題，阿爾茨海默氏症機會的醫療保險部分大約占我們在模型中看到的總機會的 1/3。我們希望在我們考慮時解決這些潛在問題，例如，我們過去曾溝通過的定價靈活性以及我們希望如何進入這個特定市場。事實上，要獲得 FDA 的批准，我們還有很長的路要走，下游考慮一項尚未批准的法案還為時過早。

Our next question is coming from the line of Sumant Kulkarni with Canaccord.

我們的下一個問題來自 Sumant Kulkarni 與 Canaccord 的合作。

I have a couple. The first one is on SERENITY III. On the safety aspect, what exactly do you plan to collect in terms of metrics for the at-home use component?

我有一對。第一個是關於 SERENITY III。在安全方面，您究竟計劃收集哪些家庭使用組件的指標？

The metrics for adverse events, for example, would be collected as you collect adverse events in any trial. The patients will be collecting adverse events at the time of dosing. There will be a reliable informant, we'll say. It may be a caregiver, it may be a spouse, may be a family member. A son, daughter, whomever will be there to also report adverse events, and they'll report these to the investigators. So the adverse events are collected identically to how you might study adverse events in other trials as an outpatient. A patient comes into the office and says, 'This is what happens. This is how I felt', and the investigator records that.

例如，將在收集任何試驗中的不良事件時收集不良事件的指標。患者將在給藥時收集不良事件。會有一個可靠的線人，我們會說。可能是照顧者，可能是配偶，可能是家人。一個兒子，一個女兒，無論誰都會在那里報告不良事件，他們會將這些報告給調查人員。因此，不良事件的收集方式與您作為門診患者在其他試驗中研究不良事件的方式相同。一個病人走進辦公室說，‘這就是發生的事情。這就是我的感受”，調查員記錄了這一點。

And then my follow-up is, given that the label currently does not restrict use of IGALMI to a specific setting, is there anything that precludes a position from sending a patient home with the film today as things stand?

然後我的後續行動是，鑑於標籤目前沒有將 IGALMI 的使用限制在特定的環境中，是否有任何事情可以阻止今天的情況將患者與電影一起送回家？

Sumant, that's a great question. As you said, label focus is on under the supervision. So wherever there is a supervision available, IGALMI, we believe, can be used. We're just focusing in the hospital setting because 2/3 of the patients, out of 25 million episode, comes to the hospital market. It's a very well-defined and focused approach. How physicians will use it once they develop experience, all of that will unfold in the next 6 to 12 months.

蘇曼特，這是一個很好的問題。正如您所說，標籤重點是在監督下。因此，只要有可用的監督，我們相信就可以使用 IGALMI。我們只關注醫院環境，因為在 2500 萬患者中，有 2/3 的患者來到醫院市場。這是一種定義明確且重點突出的方法。一旦他們積累了經驗，醫生將如何使用它，所有這些都將在未來 6 到 12 個月內展開。

Our next question is coming from the line of Kambiz Yazdi with Jefferies.

我們的下一個問題來自 Kambiz Yazdi 與 Jefferies 的合作。

What's the significance of in-home use for SERENITY III? Do you anticipate that freeing the outpatient completely as a second indication? Regarding clinical meaningfulness in Alzheimer's agitation and psychosis, was there -- what gives you confidence in your endpoint and interpretation as clinically meaningful? And then for - lastly, for your MDD trial, what are the drivers for dose selection in that trial?

SERENITY III 在家中使用的意義何在？您是否預計將完全釋放門診病人作為第二個適應症？關於阿爾茨海默氏症激越症和精神病的臨床意義，是什麼讓您對您的終點和解釋具有臨床意義充滿信心？然後 - 最後，對於您的 MDD 試驗，該試驗中劑量選擇的驅動因素是什麼？

I will pass it on to Rob to answer both the TRANQUILITY program as well as then followed up with MDD.

我會將它傳遞給 Rob 來回答 TRANQUILITY 程序以及隨後的 MDD。

Sure. So, let me be clear, it's the same indication in SERENITY III. This is acute agitation episodes associated with schizophrenia or bipolar disorder, and so we believe that using IGALMI for episodes that aren't just in the hospital or just directly in front of a healthcare provider, but enabling the patient to take this when they're agitated at home, could potentially even prevent the patient from requiring hospitalization or going to the emergency room or running to a clinic. So it's exactly the same indication, but there's tremendous value to the patient and the people around the patient to sort of prevent an escalation from occurring.

當然。所以，讓我明確一點，這與 SERENITY III 中的指示相同。這是與精神分裂症或雙相情感障礙相關的急性激越發作，因此我們認為，使用 IGALMI 治療不僅僅是在醫院或直接在醫療保健提供者面前的發作，而是讓患者在他們在家裡焦躁不安，甚至可能會阻止患者需要住院或去急診室或跑到診所。所以它是完全相同的適應症，但對患者和患者周圍的人來說，防止升級的發生具有巨大的價值。

And then the second piece is that why patients end up in the emergency room, because agitation is a spectrum -- mild, moderate and severe. It escalates. So if you are preventing the agitation when it's in early stages or mild stages at home, it's very different than these patients will not need to go to the emergency room. So I think it's the dynamics between the institution -- the reason patients end up there, because they don't have a choice or no treatment options at home. So that's why they end up, 2/3 of the patient, in institution. And if IGALMI is available and when their PEC scores are lower compared to when they end up in the emergency room, you could treat these patients with the dose we have selected.

然後第二部分是為什麼患者最終會進入急診室，因為躁動是一個範圍——輕度、中度和重度。它升級了。因此，如果您在家裡阻止處於早期或輕度階段的躁動，這與這些患者不需要去急診室有很大不同。所以我認為這是機構之間的動態——患者最終到那裡的原因，因為他們在家裡別無選擇或沒有治療選擇。所以這就是為什麼他們 2/3 的患者最終會進入機構。如果 IGALMI 可用並且當他們的 PEC 分數低於他們最終進入急診室時的分數時，您可以用我們選擇的劑量治療這些患者。

So, with respect to the major depression and dose selection, we are testing the tolerability and, of course, safety of escalating doses, both escalating individual doses and dosing at more than once a day -- for example, dividing doses. A morning and an evening dose, for example. And so the tolerability is really important prior to testing this in a proof-of-concept study for depression. So those are the sort of very simple biomarkers that would enable us to select the dose. How well is it tolerated? Are there any safety issues? And thus far, we continue to escalate patients.

因此，關於重度抑鬱症和劑量選擇，我們正在測試耐受性，當然還有增加劑量的安全性，包括增加個人劑量和每天多次給藥——例如，分次給藥。例如，早上和晚上的劑量。因此，在抑鬱症的概念驗證研究中對此進行測試之前，耐受性非常重要。因此，這些是使我們能夠選擇劑量的非常簡單的生物標誌物。它的耐受性如何？有沒有安全問題？到目前為止，我們繼續升級患者。

We'll move on to our next question, which is coming from the line of Yatin Suneja with Guggenheim.

我們將繼續討論下一個問題，該問題來自 Yatin Suneja 與 Guggenheim 的合作。

This is Eddie on for Yatin. For the at-home expansion program in SERENITY III, in part 1, what would be a reason why a patient wouldn't proceed to at-home dosing? Does the company, or experts you've spoken to, or regulators, have some safety bar for what would need to happen to ensure a patient can safely move to at-home administration? And then would there be a limit to the number of doses a patient can take in part 2? And then, for the MDD program, given the rapid onset of action you saw for agitation, do you expect to see a rapid onset of antidepressant efficacy, and what are the earliest time points you're looking for efficacy in those studies?

這是亞丁的艾迪。對於第 1 部分中 SERENITY III 中的家庭擴展計劃，患者不繼續進行家庭給藥的原因是什麼？公司、您與之交談過的專家或監管機構是否有一些安全措施來確保患者可以安全地轉移到家庭管理？那麼患者在第 2 部分中可以服用的劑量數量是否有限制？然後，對於 MDD 計劃，鑑於您看到的快速起效的激動，您是否期望看到快速起效的抗抑鬱藥效，以及您在這些研究中尋找療效的最早時間點是什麼時候？

So the patients in SERENITY III, in the first portion, will be dosed with either placebo or the 60-microgram dose. Those patients are independent of the patients in part 2. Part 2 is testing the dose at home. It's not a gateway. So I realize that your question implies that you think a patient's going to start with part 1 and continue to use it at home. That's not what we're doing. The first part of the trial is patients who are acutely agitated, they present with agitation, and we're treating it with the 60-microgram dose. So we'll have very accurate bead, if you will, on efficacy as well as safety in a tightly controlled situation where everything can be monitored, just as if you were in the emergency room.

因此，在第一部分中，SERENITY III 中的患者將服用安慰劑或 60 微克劑量。這些患者獨立於第 2 部分中的患者。第 2 部分是在家中測試劑量。它不是網關。所以我意識到你的問題暗示你認為患者將從第 1 部分開始並繼續在家中使用它。那不是我們正在做的。試驗的第一部分是急性激越的患者，他們表現為激越，我們正在用 60 微克的劑量對其進行治療。所以我們會有非常準確的珠子，如果你願意的話，在一個嚴格控制的情況下，一切都可以被監控，就像你在急診室一樣，在有效性和安全性方面。

The second part of the study is entirely at home in a whole different set of patients. So again, we will have enough data. The FDA has said that they will consider this a pivotal trial for the indication at home.

該研究的第二部分完全是在家裡對一組不同的患者進行的。同樣，我們將有足夠的數據。 FDA 表示，他們將認為這是該適應症在國內的關鍵試驗。

So there were no safety concerns or any reasons that we could not do the first portion in the at-home setting. As I mentioned previously, it's all about having the robustness of the data and using the scale that we have used in SERENITY I and II pack, and we were able to use this and at the same time demonstrate the safety at home so that it can become a package to -- for label expansion or for another sNDA.

因此，沒有任何安全問題或任何原因我們無法在家中進行第一部分。正如我之前提到的，這一切都是關於數據的穩健性和使用我們在 SERENITY I 和 II 包中使用的規模，我們能夠使用它，同時證明在家裡的安全性，以便它可以成為一個包裹——用於標籤擴展或另一個 sNDA。

And then on (technical difficulty) efficacy?

然後在（技術難度）功效上？

Sorry, say that again, please?

對不起，再說一遍好嗎？

The MDD study, if you could talk about what earliest time points you're going to look at for anti-depressive efficacy and whether that would be similar to what you'd see for agitation.

MDD 研究，如果你能談談你將要研究的最早時間點的抗抑鬱功效，以及這是否與你所看到的激越相似。

In MDD, we're not looking at 1 or 2 hours. We're looking at days and weeks. Efficacy in MDD, we expect to see very early, but remains to be seen. We'll be likely testing this within the first week, second week, et cetera, and we're not just looking at the acceleration of antidepressant response. We're also looking at the proportion of patients who improve. We know that SSRIs are not the be-all and end-all, for example. Antidepressants don't work for everyone. Maybe they work for a large proportion, greater than 50%, but we'd like to greatly improve that. So we're looking at both acceleration and responders or response overall when treated with BXCL501.

在 MDD 中，我們不看 1 或 2 小時。我們正在尋找幾天和幾週。 MDD 的療效，我們預計很早就可以看到，但仍有待觀察。我們可能會在第一周、第二周等時間內對此進行測試，而且我們不僅僅關注抗抑鬱反應的加速。我們也在研究病情好轉的患者比例。例如，我們知道 SSRIs 並不是萬能的。抗抑鬱藥並非對所有人都有效。也許他們的工作比例很大，超過 50%，但我們希望大大提高這一點。因此，當用 BXCL501 處理時，我們正在研究加速和響應者或整體響應。

And this study is going to have 4 weeks or something like that, right? Treatment of...

這項研究將持續 4 週左右，對嗎？治療...

Daily dosing over a period of 4 weeks.

在 4 週的時間內每天給藥。

We'll move on to our next question, which is coming from the line of Colin Bristow with UBS.

我們將繼續討論下一個問題，該問題來自 Colin Bristow 與 UBS 的合作。

I guess, as we think about subsequent quarters where you're going to report revenue, can you just give us any details around how revenue will be recognized? Is it when order made? Is it when it's shipped? Is it when it's received? So that's question one.

我想，當我們考慮您將報告收入的後續季度時，您能否向我們提供有關如何確認收入的任何詳細信息？是下單的時候嗎？是發貨的時候嗎？是收到的時候嗎？這是第一個問題。

Question two. Sorry if I've missed this, but it looks like TRANQUILITY 2 timing slipped a little from end of this year to first half of next. Just curious what's the rationale behind this.

問題二。抱歉，如果我錯過了這一點，但看起來 TRANQUILITY 2 的時間從今年年底到明年上半年略有下滑。只是好奇這背後的理由是什麼。

And then, third, you -- any details or anything further you can give us on the other assets you're moving into the clinic?

然後，第三，你——關於你要搬進診所的其他資產，你能給我們提供任何細節或任何進一步的信息嗎？

On the sales, we're going to recognize sales when it's sold to the final customer, so the hospital. That's when we actually recognize sales.

在銷售方面，我們將在銷售給最終客戶（即醫院）時確認銷售。那是我們真正認識到銷售的時候。

And regarding the TRANQUILITY program, we are conducting this trial in ALF where the early patients reside and in residential setting. And we have observed COVID disruption sometimes in these sites, and that restricts access for CRO to go into the elderly center, and we don't know what could happen in the next several months, in the fall, with the COVID. So we are just being cautious in providing a guidance that there could be a slip on the data readout because of those reasons.

關於 TRANQUILITY 計劃，我們正在 ALF 早期患者居住的地方和住宅環境中進行這項試驗。我們有時會在這些站點觀察到 COVID 中斷，這限制了 CRO 進入老年中心，我們不知道在接下來的幾個月裡，在秋天，COVID 會發生什麼。因此，我們只是謹慎地提供指導，即由於這些原因，數據讀數可能會出現下滑。

In terms of operational aspect, we are not seeing any issues in terms of number of patients that are there. These are entirely patients. They are frail, so you do get a little bit more screen failure than you will get it in the SERENITY trial, because those are younger patients. So I would say those are the reasons. Nothing very specific, except COVID-related delay or you can get more screen failures because these patients are frail and they may have some other associated medical complications, and they can get excluded.

在運營方面，我們沒有看到患者數量方面的任何問題。這些完全是病人。他們很虛弱，所以你確實會比在 SERENITY 試驗中遇到更多的篩選失敗，因為那些是年輕的患者。所以我想說這些就是原因。沒有什麼特別具體的，除了與 COVID 相關的延遲，否則您可能會遇到更多的篩查失敗，因為這些患者身體虛弱，他們可能有其他一些相關的醫療並發症，他們可能會被排除在外。

Okay. Great.

好的。偉大的。

And you had the third question. Was it related to MDD or our -- I just want to clarify.

你有第三個問題。它與 MDD 或我們的相關嗎？我只是想澄清一下。

Just in terms of the -- when do we get more information on your other assets that are somewhat under -- moving stealthily forward?

就——我們什麼時候能得到更多關於你的其他資產的更多信息——悄悄地向前推進？

Sure. So that asset is now going through the formulation. We expect that work to complete, and then once we have done all the, like, preclinical work stuff and we are ready to take to the clinic, we will disclose what that asset is, which indications we are choosing. Initially, we have mentioned that, like, one of the indication where it fits in very well is chronic agitation in -- treatment of chronic agitation in dementia. But we continue to explore additional options where the mechanism will fit in, and we will lay out the plan in 2023.

當然。因此，該資產現在正在製定中。我們希望這項工作能夠完成，然後一旦我們完成了所有臨床前工作，我們準備好去診所，我們將披露該資產是什麼，我們正在選擇哪些適應症。最初，我們已經提到，它非常適合的適應症之一是慢性躁動——治療癡呆症的慢性躁動。但我們會繼續探索適合該機制的其他選項，我們將在 2023 年制定計劃。

Our next question is coming from the line of Graig Suvannavejh with Mizuho.

我們的下一個問題來自 Graig Suvannavejh 與 Mizuho 的對話。

This is [Richard Wynne] for Graig Suvannavejh, who sends his best, and it's great to be back on the name. So my first question goes on to SERENITY III plans. How large do you expect the study to be, with the goal of enrolling how many patients, and by when do you expect enrollment to end? And my second part of that is, what do you think is the incremental increase to revenue since 1/3 of episodes occur outside of institutional settings? Can we assume a 30% increase to peak revenues, or what would the company think?

這是 Graig Suvannavejh 的 [Richard Wynne]，他發揮了自己的最佳水平，很高興回到這個名字。所以我的第一個問題是關於 SERENITY III 計劃。您預計該研究的規模有多大，目標是招募多少患者，您預計招募何時結束？我的第二部分是，由於 1/3 的事件發生在機構環境之外，您認為收入的增量增長是多少？我們可以假設增加 30% 以達到峰值收入，或者公司會怎麼想？

First question, I will pass it on to Rob, so he can outline. He's agreeing on number of patients and everything, but we expect this trial to be pretty short. Just to remind everyone, our both trials, SERENITY I and II, had 750 patients, 375 each, and 3-arm study. There, we were testing 2 doses and a placebo, and we completed the enrollment in about 5 months or so. So these are very fast trial in terms of the timing, and in terms of the number of patients, I will pass it on to Rob because he is currently doing powering studies to make sure we power the study. Rob?

第一個問題，我會轉給 Rob，讓他勾勒出輪廓。他同意患者數量和所有內容，但我們預計該試驗會很短。提醒大家，我們的兩項試驗，SERENITY I 和 II，都有 750 名患者，每組 375 名，並且是 3 組研究。在那裡，我們測試了 2 個劑量和一個安慰劑，我們在大約 5 個月左右的時間內完成了招募。因此，就時間和患者數量而言，這些試驗非常快，我會將其傳遞給 Rob，因為他目前正在進行有力的研究，以確保我們為研究提供動力。搶？

Yes. So each portion of the study -- the first and second half -- will be well under the, I believe it was, 350 patients in SERENITY I, 350 in SERENITY II. So, because they're independent patients, there are essentially, in a way, independent studies. We know that these will enroll relatively quickly. In addition, this -- there's no exclusion. So, unlike SERENITY I and II -- SERENITY I was patients with schizophrenia, SERENITY II was patients with bipolar disorders -- we're mixing that.

是的。因此，研究的每一部分——上半場和下半場——都將遠遠低於 SERENITY I 的 350 名患者，SERENITY II 的 350 名患者。因此，因為他們是獨立的患者，所以在某種程度上基本上是獨立的研究。我們知道這些將相對較快地註冊。此外，這 - 沒有排除。因此，與 SERENITY I 和 II 不同——SERENITY I 是精神分裂症患者，SERENITY II 是雙相情感障礙患者——我們將它們混合在一起。

And the FDA has agreed that we can test this in both patients with schizophrenia and bipolar disorder at the same time in the same study, because our effects are similar. Humans are humans, regardless of what the underlying illness is, and thus we expect an even faster enrollment. We don't anticipate any problems with recruitment for this. Agitation is relatively common, and we were able to enroll both the SERENITY I and II very rapidly, even in the midst of the kind of the major part of the COVID pandemic.

FDA 同意我們可以在同一研究中同時對精神分裂症和雙相情感障礙患者進行測試，因為我們的效果相似。人就是人，不管潛在的疾病是什麼，因此我們期待更快的入組。我們預計這方面的招聘不會有任何問題。躁動相對普遍，我們能夠非常迅速地註冊 SERENITY I 和 II，即使是在 COVID 大流行的主要階段。

So, Richard, we will provide a guidance once we roll out the plan -- pivotal plan, then when the data readout is expected. But it will certainly be in 2023, and we'll provide more granular guidance on first half or second half.

因此，理查德，一旦我們推出計劃 - 關鍵計劃，我們將提供指導，然後在預期數據讀出時提供指導。但肯定會在 2023 年，我們將在上半年或下半年提供更精細的指導。

Just to take your question on revenues for the community setting, so the math that you're calculating here is correct in that there are roughly 1/3 of the agitation episodes in the community setting. But one of the things that we've learned in recent market research is that, specifically in the bipolar population, which represents the majority of agitation, we see approximately 10 additional episodes that are not captured in the claims data. So this is roughly a 60% increase in what we previously thought the community setting opportunity was. These episodes were not seen in the schizophrenia patients as typically, when they're compliant with their antipsychotics, it would suppress the agitation episode, so it made sense. It was identical to what we saw in claims. But in bipolar, those 10, what I'll call, shadow episodes are being managed through meditation, exercise, illicit drug use, alcohol. We believe that those are opportunities for 501, should we get the approval for that indication.

只是回答你關於社區環境收入的問題，所以你在這裡計算的數學是正確的，因為社區環境中大約有 1/3 的激動事件。但我們在最近的市場研究中了解到的一件事是，特別是在代表大多數躁動的躁鬱症人群中，我們看到大約 10 次未在索賠數據中捕獲的事件。因此，這比我們之前認為的社區設置機會增加了大約 60%。這些發作在精神分裂症患者身上並不常見，當他們服從抗精神病藥物時，會抑制激越發作，所以這是有道理的。它與我們在索賠中看到的相同。但在躁鬱症患者中，這 10 個，我稱之為影子發作，是通過冥想、鍛煉、非法吸毒、酗酒來控制的。我們認為，如果我們獲得該適應症的批准，這些都是 501 的機會。

So then -- and you also mentioned that IGALMI exceeded expectations in their value proposition. What do you think the uptake curve should look like for IGALMI, then? Are you comfortable with where consensus is currently, or do you see that shifting?

那麼——你還提到 IGALMI 在他們的價值主張中超出了預期。那麼，您認為 IGALMI 的吸收曲線應該是什麼樣的？您對目前的共識是否滿意，或者您是否看到這種變化？

So there's a -- as I said, there's an operational or mechanical process to unlock the value and uptake in hospitals, and we still have to deal with that process. However, the early signs have been very encouraging. The interest in the drug is very encouraging, and we see things moving in a very positive direction. So I wouldn't see that impacting the uptake curves near term, just because of the mechanics of getting drug on formulary and unlocking the potential for demand. But once that's behind us, I see a big opportunity in helping a lot of patients.

所以有一個 - 正如我所說，有一個操作或機械過程來釋放醫院的價值和吸收，我們仍然必須處理這個過程。然而，早期跡象非常令人鼓舞。對該藥物的興趣非常鼓舞人心，我們看到事情正朝著非常積極的方向發展。因此，我認為這不會影響短期內的吸收曲線，只是因為將藥物納入處方集並釋放需求潛力的機制。但是一旦我們過去了，我就會看到幫助很多病人的巨大機會。

And we continue to see a lot of face-to-face meeting. Our sales teams are getting a lot of face-to-face time, despite the COVID or any other reason, and they're getting very positive feedback, as Matt said. So it's all very encouraging. In fact, whatever we were thinking this drug potential will be, now, being in the marketplace for 10 weeks, we are even more excited about it.

我們繼續看到很多面對面的會議。正如馬特所說，儘管有 COVID 或任何其他原因，我們的銷售團隊仍有很多面對面的時間，並且他們得到了非常積極的反饋。所以這一切都非常令人鼓舞。事實上，無論我們當時認為這種藥物的潛力如何，現在，在市場上銷售 10 週後，我們對此更加興奮。

The next question is coming from the line of Ram Selvaraju with H.C. Wainwright.

下一個問題來自 Ram Selvaraju 和 H.C.溫賴特。

Just (technical difficulty) I wanted to ask if you could (technical difficulty) some additional information regarding the regulatory process for the indication for the (technical difficulty) IGALMI within the context of what you are trying to capture with SERENITY III. So if SERENITY III proves to be positive, what we should be thinking about with respect to a regulatory (technical difficulty) period. And also, if you could comment on any intent on your side with respect to doing any exploratory clinical work in generalized anxiety disorder, if any?

只是（技術困難）我想問你是否可以（技術困難）在你試圖用 SERENITY III 捕獲的內容的背景下，關於（技術困難）IGALMI 適應症的監管過程的一些額外信息。因此，如果 SERENITY III 被證明是積極的，我們應該考慮監管（技術困難）期的內容。而且，如果有的話，您是否可以評論您在廣泛性焦慮症方面進行任何探索性臨床工作的意圖？

So, Ram, we would expect, once the trial is complete, to be able to put together a package for a supplemental NDA application very rapidly -- within a few months. And the review timeline will depend on the FDA, of course. We could request, for example, fast track, on the basis of several findings which we fully anticipate should have robust efficacy and similar or even better safety than what we have been approved with 120- and 180-microgram doses. And so that regulatory process we can certainly outline in a future discussion, but we really need to get this data. We believe we'll have the data relatively quickly, because we're enrolling all comers, if you will, with schizophrenia and bipolar disorder, and then we can provide more clarity and an update in the future.

所以，Ram，我們希望，一旦試驗完成，能夠在幾個月內非常迅速地為補充 NDA 申請組裝一個包。當然，審查時間表將取決於 FDA。例如，我們可以根據我們完全預期的幾項研究結果申請快速通道，這些研究結果應該具有強大的療效和與我們已經批准的 120 和 180 微克劑量相似甚至更好的安全性。因此，我們當然可以在未來的討論中概述監管過程，但我們確實需要獲得這些數據。我們相信我們會相對較快地獲得數據，因為我們正在招募所有患有精神分裂症和躁鬱症的人，然後我們可以在未來提供更清晰的信息和更新。

With regard to additional indications such as generalized anxiety disorder, we are planning studies to look at a variety of potential indications, if you will, putting our toes in the water for indications like generalized anxiety disorder. We could look at any anxiety disorder -- panic, PTSD, acute stress disorder, might even look at developmental disorders. We've had a lot of discussions with, in fact, investors who have said, 'Well, why aren't you studying this in autism?', for example. And so we have plans to do basket studies.

關於廣泛性焦慮症等其他適應症，我們正計劃研究各種潛在適應症，如果您願意，可以將我們的腳趾放在水中以尋找廣泛性焦慮症等適應症。我們可以研究任何焦慮症——恐慌症、創傷後應激障礙、急性應激障礙，甚至可以研究發育障礙。事實上，我們已經與投資者進行了很多討論，他們說，'好吧，你為什麼不研究自閉症？'，例如。因此，我們計劃進行籃子研究。

These are studies where we take small numbers of patients and -- sort of preliminary. They tend to be open-label studies, and you just determine if there's a signal or not. They're cheap, they're fast, and they are a way for us to give a certain directionality to the next steps in development. But let me point out that our focus has been, and continues to be, primarily on the expansion to at-home use to demonstrate utility, efficacy and safety in Alzheimer's disease and agitation associated with Alzheimer's and major depressive disorder. These will be the next, if you will, for IGALMI.

這些是我們接受少量患者的研究——有點初步。它們往往是開放標籤研究，您只需確定是否有信號。它們很便宜，速度很快，而且它們是我們為下一步開發提供一定方向性的一種方式。但我要指出，我們的重點一直是，並將繼續主要是擴大家庭使用，以證明其在阿爾茨海默氏病以及與阿爾茨海默氏症和重度抑鬱症相關的躁動症中的實用性、有效性和安全性。如果您願意，這些將是 IGALMI 的下一個。

Our next question is coming from the line of Corinne Jenkins with Goldman Sachs.

我們的下一個問題來自 Corinne Jenkins 與高盛的合作。

How should we think about your pricing strategy for potential indication expansion to include as-needed or chronic dosing of IGALMI?

我們應該如何考慮您的潛在適應症擴展定價策略，以包括 IGALMI 的按需或長期給藥？

Yes, so as we think of further downstream indications, we continue to have flexibility in how we might think about pricing in those settings. We haven't made any determinations yet. We'll still continue to monitor the market per the previous question around legislation and things of that nature. We'll watch the market dynamics closely, and we'll make a decision on pricing to best fit the markets that we're going into. Suffice to say that we have a very smart pricing strategy now in the institutional setting, and that may actually fit future downstream indications. So we'll continue to monitor and make that decision as -- if -- should we get approval for those indications and at the time that we enter those markets.

是的，所以當我們考慮進一步的下游跡象時，我們在如何考慮這些環境中的定價方面繼續具有靈活性。我們還沒有做出任何決定。我們仍將根據先前關於立法和類似性質的問題繼續監測市場。我們將密切關注市場動態，並做出最適合我們即將進入的市場的定價決定。可以說我們現在在機構環境中有一個非常聰明的定價策略，這實際上可能適合未來的下游指標。因此，我們將繼續監控並做出該決定——就好像——我們是否應該獲得這些適應症的批准，以及我們進入這些市場的時間。

And could you also please confirm how many doses of IGALMI are you expecting patients to receive in part 2 of the SERENITY III trial, and for how long will you be evaluating the patients?

您能否確認您希望患者在 SERENITY III 試驗的第 2 部分中接受多少劑量的 IGALMI，以及您將對患者進行多長時間的評估？

Patients will be using the BXCL501 at home when they have an episode of acute agitation. And so we're giving the film and monitoring them over a period of months so that we pick up the frequency and what happens when they use the film. Patients -- because it's placebo-controlled, patients are able to take, if you will, a rescue medication that will be very much an individual thing. Patients do take additional medications at home to attempt to treat their acute anxiety. They obviously also take alcohol or marijuana, try meditation -- there's a lot of things that they take. But principally we're testing the effect of a single dose of BXCL501 in that 60-microgram dose. And there is a possibility for an additional dose, but that will have to be up to the patient as to whether or not they're feeling something from the initial dose and calming.

當患者出現急性激越時，他們將在家中使用 BXCL501。所以我們在幾個月的時間裡給他們放電影並監控他們，這樣我們就能了解頻率以及他們使用電影時會發生什麼。患者——因為它是安慰劑對照的，如果你願意的話，患者能夠服用一種救援藥物，這將是非常個人化的事情。患者確實會在家中服用額外的藥物來嘗試治療他們的急性焦慮症。他們顯然也吸食酒精或大麻，嘗試冥想——他們吸食了很多東西。但主要是我們正在測試單劑量 BXCL501 在 60 微克劑量中的作用。並且有可能增加劑量，但這必須取決於患者是否從初始劑量和鎮靜中感覺到什麼。

It appears we have no additional questions at this time, so I'd like to pass the floor back over to Dr. Mehta for any additional concluding remarks.

看來我們此時沒有其他問題了，所以我想將發言權轉回給 Mehta 博士，讓他發表任何其他總結性意見。

Thank you, everyone, for joining us today. We look forward to connecting with many of you in the coming weeks, including at the Canaccord Growth Conference, where Matt and I will be hosting meetings and participating in a fireside chat. Have a great day.

謝謝大家今天加入我們。我們期待在接下來的幾週內與你們中的許多人建立聯繫，包括在 Canaccord 增長會議上，馬特和我將在會上主持會議並參加爐邊談話。祝你有美好的一天。

Ladies and gentlemen, this does conclude today's teleconference and webcast. Once again, we thank you for your participation, and you may disconnect your lines at this time.

女士們，先生們，今天的電話會議和網絡廣播到此結束。再次感謝您的參與，此時您可以斷開您的線路。