DPP-9

点击“蓝字”关注我们 2024年联合国糖尿病日的主题为“糖尿病与幸福感”，呼吁除关注血糖之外还要致力于提升患者生活质量，这与当前“以患者为中心”的糖尿病治疗理念相一致。我国2型糖尿病（T2DM）人群数量庞大，其中新诊断患者占比超过半数。近日《柳叶刀》发布的最新全球糖尿病地图显示，我国成人糖尿病患者1.48亿，≥30岁的糖尿病患者中，7800万人尚未得到治疗[1]。 如何根据新诊断T2DM患者的临床特点和治疗需求来制定相应管理策略，从而提升整体幸福感？近年来，二肽基肽酶Ⅳ抑制剂（DPP-4i）如福格列汀等国产原研药屡获突破，其对于改善我国T2DM管理，尤其是在新诊断患者早期联合治疗中的价值如何？围绕以上热点问题，本刊对中山大学孙逸仙纪念医院严励教授进行了专访。 严励 教授 中山大学孙逸仙纪念医院 中山大学名医，二级教授，博士研究生导师 中山大学孙逸仙纪念医院内分泌内科主任 中华医学会内分泌学分会副主任委员，肥胖学组组长 中国医师协会内分泌科医师分会副会长 广东省糖尿病临床医学研究中心主任 国家临床医学研究中心广东分中心主任 广州市代谢性疾病重点实验室主任 广东省医师协会内分泌科医师分会第三届委员会主任委员 《国际糖尿病》 作为资深糖尿病专家，请您从疾病管理、药物治疗的角度谈谈如何帮助糖尿病患者提升幸福感？ 严励教授 近年来，糖尿病管理新理念强调“以患者为中心”，尊重和响应患者个人偏好、需求和价值观，并以此为基础来制定临床决策。这种新理念可更好地调动患者治疗的积极性，提升对糖尿病的认识，更好地改善血糖控制和临床结局，帮助患者提升幸福感。具体而言，可从以下几个方面入手： ①加强糖尿病教育：提高患者对糖尿病的认知程度，正确看待疾病，积极配合治疗。 ②整体情况评估：在确诊之后，应对患者病情、心理状况以及社会支持力度等进行整体评估，才能制定出真正适合患者的治疗方案。 ③个体化药物选择：应综合考虑药物因素（机制、特点、有效性、安全性、可及性等）与患者因素（病理生理特点、血糖水平、并发症情况、经济条件等），选择合适的药物方案。 ④确保方案实施：医生应和患者共同参与制定治疗方案，定期随访，及时发现问题并根据需要进行调整。 《国际糖尿病》 处于不同糖尿病病程的患者治疗需求不同，请您谈谈新诊断T2DM患者的临床特点有哪些？相应的管理策略又是什么？ 严励教授 我国糖尿病人群中新诊断患者占比较大，这个庞大的患者群有很多特点需引起临床关注，并给予针对性管理策略，主要包括： 对病情感到焦虑担忧：新诊断T2DM患者通常对糖尿病认知较差，确诊后心理负担重，医生应与患者充分沟通，加强糖尿病知识教育，打消患者的担忧顾虑，积极配合治疗。 不了解糖尿病管理知识：新诊断患者通常不知该如何配合医生去落实治疗方案，应从饮食运动、药物治疗、血糖监测等各个方面提升患者自我管理糖尿病的技能。 诊断较晚，血糖水平较高：我国新诊断患者一般确诊较晚，大多数患者的糖化血红蛋白（HbA1c）水平较高，需要采取有效措施以尽快控糖达标。 对全面检查不理解：一旦诊断T2DM，为了制定有针对性的治疗方案，应对患者进行全面评估，包括胰岛β细胞功能、并发症情况等。需向患者解释这些检查的必要性和重要性。 《国际糖尿病》 对于新诊断T2DM患者，您如何看待早期联合策略以及DPP-4i在早期联合中的应用价值和地位? 严励教授 近年来，T2DM治疗新理念主张对于新诊断患者采取早期联合降糖策略。早在2020年，ADA指南就基于DPP-4i的VERIFY研究将早期联合治疗的证据等级由“E”提升至“A”[2]。关于早期联合策略，可从以下三个方面来理解和阐述： 为何要早期联合降糖？T2DM病理生理机制复杂，且呈慢性进展性，单药治疗针对的病理生理机制有限，难以迅速达到或长期维持血糖达标。早期联合治疗有助于更好地覆盖多种病理异常，提高血糖达标率；而且，血糖控制具有“记忆效应”，早期良好的血糖控制对于后续血糖长期稳定控制以及并发症防治具有重要意义。 何时开始早期联合治疗？2022年ADA/EASD共识报告建议，对于确诊时HbA1c水平高于血糖控制目标值1.5%（通常为HbA1c>8.5%）的患者，推荐考虑起始联合治疗[3]。2023年ADA指南建议对于初始HbA1c≥7.5%的患者即可考虑以二甲双胍为基础的联合治疗[4]。 如何优化早期联合治疗？不同作用机制的降糖药物联合可实现机制互补，提升降糖疗效并减少副作用。二甲双胍作为降糖治疗的基础用药，其作用机制主要是减少肝糖输出、改善外周胰岛素敏感性；DPP-4i则通过延缓GLP-1降解来提高GLP-1水平，促进胰岛素分泌，同时还有β细胞保护作用。DPP-4i+二甲双胍可覆盖多种T2DM病理生理缺陷，增强降糖疗效，且不增加低血糖风险，已成为临床最常见的早期联合方案之一，得到多项循证研究的支持和证实[5]。尤其是亚洲T2DM患者通常发病年龄更为年轻，β细胞损害更早、更严重，DPP-4i+二甲双胍早期联合治疗可在相对长的病程中实现早期血糖控制，保护β细胞功能，有助于改善患者远期预后[5]。 《国际糖尿病》 近年来我国原研药不断崛起，福格列汀于2024年6月作为国产1类创新药获批国内上市。从Ⅲ期临床研究结果来看，福格列汀的表现如何？ 严励教授 我们科室有幸参与了福格列汀的两项Ⅲ期临床研究。其中，单药治疗研究共纳入458例经饮食和运动不能有效控制血糖的T2DM患者，以2:1:1比例随机接受福格列汀12 mg、阿格列汀25 mg、安慰剂每日一次治疗[6]；联合治疗研究共纳入408例经二甲双胍治疗不能有效控制血糖的T2DM患者，以2:1比例随机接受福格列汀12 mg联合二甲双胍、安慰剂联合二甲双胍每日一次治疗[7]。结果表明，福格列汀无论单药治疗或与二甲双胍联合治疗，均表现出良好的降糖疗效、安全性和依从性。主要结果包括： 有效降低HbA1c：福格列汀单药治疗24周，HbA1c自基线降低0.70%，优效于安慰剂，非劣效于阿格列汀。福格列汀联合二甲双胍可进一步降低HbA1c（-0.81%），优效于二甲双胍单药治疗（图1）。 图1. 福格列汀单药或联合二甲双胍治疗有效降低HbA1c HbA1c达标率较高：福格列汀单药治疗24周，HbA1c达标率（HbA1c<7%）非劣于阿格列汀（37.0% vs. 35.5%）；联用二甲双胍治疗，HbA1c达标率进一步提高（38.7%，图2）。 图2. 福格列汀单药或联合二甲双胍治疗HbA1c达标率较高 低血糖风险低：双盲治疗期（24周），福格列汀单药治疗T2DM患者低血糖发生率<1%，联合二甲双胍治疗时低血糖发生率<2%，不增加低血糖风险，且无论单药还是联合均无重度低血糖发生；延长治疗期（28周），福格列汀不增加低血糖发生率。 不影响体重：福格列汀几乎不影响患者体重，Ⅲ期试验中患者持续治疗52周体重变化不超过1 kg。 表现出更好的靶点安全性：福格列汀组未发生其他DPP-4i常见的咽炎、鼻咽炎以及感染等常见不良反应，且未发生严重不良反应。 《国际糖尿病》 请您展望一下未来国产原研药物的临床地位和应用前景如何？ 严励教授 我国人口基数大，糖尿病患病率仍在持续增加，满足糖尿病治疗需求不能仅依赖进口药，更需要国产药（包括仿制药和原研创新药）的强力支撑。作为临床医生，我非常欣喜地看到，近年来我国新药研发能力和速度明显提升，不断开发出更多国产新药投放市场，以更好地满足临床需求。 以DPP-4i为例，该类药物因降糖有效、安全且可及性良好而深受医生和患者欢迎，也成为备受青睐的国内药品研发热点。更高的DPP-4选择性可带来更高安全性，因DPP-8和DPP-9也是DPP家族成员，抑制DPP-8、DPP-9可能为导致药物产生体内毒性的重要原因。福格列汀对DPP-4具有高度选择性，在抑制DPP-4活性同时，避免与其他DPP家族交叉抑制，对DPP 8/9几乎无抑制，从而有效避免靶外作用[8]。福格列汀的成功研发，进一步优化了DPP-4i治疗选择，增强国人用药可选性，为医生提供全新治疗武器。更令人欣喜的是，福格列汀已于近日被成功纳入国家医保目录，这将大大提升其可负担性和可及性，更多T2DM患者将会从这种治疗中获益。 国家也非常重视和鼓励国内企业开展创新药的科研工作，并在药物审批等方面给予高度政策支持。我国创新药物研发前景广阔，也希望今后能不断开发出更多更好的国产原研药，帮助提升我国整体糖尿病防治水平。 参考文献 （上下滑动可查看） 1. NCD Risk Factor Collaboration (NCD-RisC). Lancet. 2024; 404(10467): 2077-2093. 2. ADA. Diabetes Care. 2020; 43(Suppl 1): S98-S110. 3. Davies MJ, et al. Diabetes Care. 2022; 45(11): 2753-2786. 4. ElSayed NA, et al. Diabetes Care. 2023; 46(Suppl 1): S140-S157. 5. 刘泽灏, 雷闽湘. 中华糖尿病杂志. 2024; 16(6): 723-728. 6. Xu M, et al. BMC Med. 2023; 21(1): 388. 7. 信立汀®说明书. 2024年6月28日. 8. Deacon CF. Diabetes Obes Metab. 2011; 13(1): 7-18. 声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。 最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！ （来源：《国际糖尿病》编辑部） 版权声明 版权属《国际糖尿病》所有。欢迎个人转发分享。其他任何媒体、网站未经授权，禁止转载。

Designation for BXCL701 in combination with a checkpoint inhibitor (CPI) for treatment of patients with metastatic SCNC with progression on chemotherapy and no evidence of microsatellite instability BXCL701 is an investigational, oral innate immune activator designed to inflame the tumor microenvironment and augment CPI activity Company to discuss registration path at upcoming meeting with FDA NEW HAVEN, Conn., Feb. 12, 2024 (GLOBE NEWSWIRE) --BioXcel Therapeutics, Inc. (Nasdaq: BTAI), a biopharmaceutical company utilizing artificial intelligence to develop transformative medicines in neuroscience and immuno-oncology, today announced that the U.S. Food and Drug Administration (FDA) has designated as a Fast Track development program the investigation of BXCL701 in combination with a CPI for the treatment of patients with metastatic small cell neuroendocrine prostate cancer (SCNC) with progression on chemotherapy and no evidence of microsatellite instability. The FDA grants Fast Track designation to facilitate the development and expedite the review of medicines to treat serious conditions, fill unmet medical needs, and bring promising medicines to patients more quickly. Therapies granted this designation are given the opportunity for more frequent interactions with the FDA, a rolling review, and potential eligibility for accelerated approval and priority review. “The FDA’s Fast Track designation for the investigation of BXCL701 in SCNC is an important recognition of our most advanced immuno-oncology asset and an acknowledgment of its potential to address the considerable unmet medical need in these patients. At the same time, it further validates the unique AI-based drug re-innovation approach that we used to discover this asset,” said Vimal Mehta, Ph.D., CEO of BioXcel Therapeutics. “BXCL701 has already demonstrated considerable potential in our clinical trials to date, and we plan to further define its development path while exploring strategic options for our OnkosXcel Therapeutics subsidiary.” SCNC, classified as a “cold” tumor, represents an underserved, growing patient population, with cases increasing due to earlier and more widespread use of androgen receptor inhibitors. In 2024, the American Cancer Society estimates that 299,0101 men will be diagnosed with prostate cancer in the United States, with approximately 20% expected to progress to the more aggressive metastatic castration-resistant form, including an estimated 11,960 patients expected to progress to SCNC2. “SCNC is characterized by poor prognosis and a low survival rate, and current treatment options are suboptimal,” said Vincent J. O’Neill, M.D., Executive Vice President, Chief of Product Development and Medical Officer of BioXcel Therapeutics. “We are encouraged by the potential of BXCL701, which has demonstrated clinical proof of concept in both SCNC and adenocarcinoma. Following the positive survival results from our Phase 2 trial that we reported at the end of last year, we look forward to further discussing the registration path at an upcoming meeting with the FDA.” About BXCL701 BXCL701 is an investigational, oral innate immune activator designed to initiate inflammation in the tumor microenvironment. Approved and experimental immunotherapies often fail to address cancers that appear “cold.” Therefore, BXCL701 is being evaluated to determine if it can render “cold” tumors “hot,” making them more detectable by the adaptive immune system and thereby facilitating the development of a strong anticancer immune response. OnkosXcel Therapeutics’ preclinical data support BXCL701’s potential synergy with both current checkpoint inhibitors and emerging immunotherapies directed to activate T-cells. BXCL701 is currently being developed as a potential therapy for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors. BXCL701 has received Orphan Drug Designation from the U.S. Food and Drug Administration in five indications: SCNC, acute myelogenous leukemia, pancreatic cancer, stage IIb to IV melanoma, and soft tissue sarcoma. An 800+-subject clinical database, with data collected by the Company and others, supports the ongoing development of BXCL701. About BioXcel Therapeutics, Inc. BioXcel Therapeutics, Inc. (Nasdaq: BTAI) is a biopharmaceutical company utilizing artificial intelligence to develop transformative medicines in neuroscience. Its wholly owned subsidiary, OnkosXcel Therapeutics, is focused on the development of medicines in immuno-oncology. The Company’s drug re-innovation approach leverages existing approved drugs and/or clinically validated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indications. For more information, please visit bioxceltherapeutics.com. Forward-Looking Statements This press release includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended (the “Securities Act”) and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). All statements contained in this press release other than statements of historical fact should be considered forward-looking statements, including, without limitation, the potential benefits from treatment with BXCL701 and from fast track designation, potential meeting with the FDA and strategic options for the OnkosXcel Therapeutics subsidiary. When used herein, words including “anticipate,” “believe,” “can,” “continue,” “could,” “designed,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements use these words or expressions. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon the Company’s current expectations and various assumptions. The Company believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. The Company may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, its dependence on the success and commercialization of IGALMI™, BXCL501, BXCL502 BXCL701 and BXCL702 and other product candidates; its lack of experience in marketing and selling drug products; the risk that IGALMI or the Company’s product candidates may not be accepted by physicians or the medical community in general; the failure of preliminary data from its clinical studies to predict final study results; failure of its early clinical studies or preclinical studies to predict future clinical studies; its ability to receive regulatory approval for its product candidates; its ability to enroll patients in its clinical trials; undesirable side effects caused by the Company’s product candidates; and its novel approach to the discovery and development of product candidates based on EvolverAI, as well as the other important factors discussed under the caption “Risk Factors” in its Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2023, as such factors may be updated from time to time in its other filings with the SEC, which are accessible on the SEC’s website at These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While the Company may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release. Contact Information Corporate BioXcel Therapeutics Erik Kopp 1.203.494.7062 ekopp@bioxceltherapeutics.com Investor Relations BioXcel Therapeutics Brennan Doyle 1.475.355.8462 bdoyle@bioxceltherapeutics.com Media Russo Partners David Schull T: 858-717-2310 David.schull@russopartnersllc.com Scott Stachowiak T: 646-942-5630 Scott.stachowiak@russopartnersllc.com Source: BioXcel Therapeutics, Inc. BT BIOXCEL THERAPEUTICS is a registered trademark of BioXcel Therapeutics, Inc. All other trademarks are the properties of their respective owners. Copyright © 2024, BioXcel Therapeutics, Inc. All rights reserved. References 1 American Cancer Society. Key Statistics for Prostate Cancer. Accessed February 8, 2024 's%20estimates,34%2C700%20deaths%20from%20prostate%20cancer 2. B.R. Alabi, S. Liu and T. Stoyanova, Current and emerging therapies for neuroendocrine prostate cancer, Pharmacology and Therapeutics (2022),

Median overall survival of 15.5 months with BXCL701 + KEYTRUDA® (pembrolizumab), compared to 9.6 months with checkpoint inhibitor monotherapy in late-line refractory patients in separate Phase 2 trial1 59% of studied patients alive at one year following treatment with BXCL701 + KEYTRUDA Median progression-free survival of 4.2 months with BXCL701 + KEYTRUDA compared to 2.1 months with checkpoint inhibitor monotherapy in late-line refractory patients in separate Phase 2 trial1 Company plans to determine program development path following end of Phase 2 meeting with FDA scheduled for December NEW HAVEN, Conn., Nov. 08, 2023 (GLOBE NEWSWIRE) -- BioXcel Therapeutics, Inc. (Nasdaq: BTAI), a biopharmaceutical company utilizing artificial intelligence to develop transformative medicines in neuroscience and immuno-oncology, today announced positive overall survival (OS) data from its Phase 2 trial of BXCL701, the Company's investigational oral innate immune activator, in combination with KEYTRUDA® (pembrolizumab) in patients with metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma phenotype, the most common form of the disease. As of a September 6, 2023 data cutoff, evaluable patients with adenocarcinoma (n=29) showed a median OS of 15.5 months (95% CI 9.6–NR), and a 12-month survival rate of 59%. “Patients with mCRPC who have failed androgen deprivation and taxane-based chemotherapy have few remaining treatment options and, unfortunately, KEYTRUDA to date has not shown additional benefit in this setting,” said Vincent J. O’Neill, M.D., Chief R&D Officer, OnkosXcel Therapeutics, a wholly owned subsidiary of BioXcel Therapeutics. “Therefore, we are highly encouraged by these combination data bearing in mind historical data with checkpoint inhibitor monotherapy. In addition, we now have a second positive dataset in a separate cold tumor histology, further increasing our belief that BXCL701 has the potential to inflame the tumor microenvironment of cold tumors, thereby sensitizing them to checkpoint inhibition. We believe the data warrant further evaluation of BXCL701 in this setting and look forward to determining the development path for this program following our end of Phase 2 meeting with the FDA scheduled for December.” In 2023 in the United States, there are expected to be an estimated 288,3002 new patients with prostate cancer, which is classified as a “cold” tumor. Of those, 20% are expected to advance to mCRPC, a form of advanced prostate cancer that is no longer responding to testosterone-lowering hormone treatments and has spread to other areas of the body such as the lymph nodes, bones, bladder, rectum, liver, or lungs. Approximately 80% of mCRPC cases are of the adenocarcinoma phenotype, which represent approximately 46,128 patients. In addition to the new OS data, the Company recently presented an update on response rate data from the Phase 2 adenocarcinoma cohort at the Prostate Cancer Foundation Annual Scientific Retreat. The Company reported a RECIST partial response rate of 28% with a median duration of response of 19 months. This is in contrast to a RECIST response rate of 5% with a median duration of response of 16.8 months from the KEYNOTE-199 trial of pembrolizumab monotherapy in a similar patient population. The Company’s Phase 2 trial is an open-label, multicenter study to evaluate the safety and efficacy of BXCL701 in combination with pembrolizumab in men with mCRPC of adenocarcinoma phenotype as well as in men with SCNC. Twenty-nine (29) evaluable adenocarcinoma patients received 0.3 mg of BXCL701 twice daily (BID) on days 1 through 14 of a 21-day cycle (0.2 mg BID the first week of Cycle 1) plus 200 mg of pembrolizumab administered intravenously on day 1 and every subsequent 21 days. The primary objective of the trial is a composite response rate defined as either objective response by RECIST 1.1 criteria and/or PSA50 and/or CTC count conversion. Secondary objectives include duration of response, progression-free survival, overall survival, and biomarker evaluation as measured by changes in circulating cytokines and correlation of outcome with baseline tumor characteristics. The Company is continuing to actively evaluate strategic options for OnkosXcel Therapeutics, including potential financing, strategic partnership, or M&A. About OnkosXcel Therapeutics, LLC and BXCL701 OnkosXcel Therapeutics, LLC is a wholly owned subsidiary of BioXcel Therapeutics, Inc., focused on developing transformative medicines in oncology utilizing artificial intelligence. The subsidiary was formed in 2022 to develop BXCL701. BXCL701 is an investigational, oral innate immune activator designed to initiate inflammation in the tumor microenvironment. Approved and experimental immunotherapies often fail to address cancers that appear “cold.” Therefore, BXCL701 is being evaluated to determine if it can render “cold” tumors “hot,” making them more detectable by the adaptive immune system and thereby facilitating the development of a strong anti-cancer immune response. OnkosXcel Therapeutics’ preclinical data support BXCL701’s potential synergy with both current checkpoint inhibitors and emerging immunotherapies directed to activate T-cells. BXCL701 is currently being developed as a potential therapy for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors. BXCL701 has received Orphan Drug Designation from the U.S. Food & Drug Administration in four indications: acute myelogenous leukemia, pancreatic cancer, stage IIb to IV melanoma, and soft tissue sarcoma. An 800+-subject clinical database, with data collected by the Company and others, supports the ongoing development of BXCL701. About BioXcel Therapeutics, Inc. BioXcel Therapeutics, Inc. (Nasdaq: BTAI) is a biopharmaceutical company utilizing artificial intelligence to develop transformative medicines in neuroscience and immuno-oncology. The Company’s drug re-innovation approach leverages existing approved drugs and/or clinically validated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indications. For more information, please visit bioxceltherapeutics.com. Forward-Looking Statements This press release includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended (the “Securities Act”) and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). All statements contained in this press release other than statements of historical fact should be considered forward-looking statements, including, without limitation, statements regarding: the Company’s expected timing of, trial design and data results from, future clinical trials of BXCL701 with pembrolizumab, potential benefits from treatment with BXCL701, the Company’s planned discussions with FDA, the future clinical development of BXCL701, the Company’s plans to evaluate strategic options for OnkosXcel Therapeutics and potential market size and opportunity for product candidates. The words “anticipate,” “believe,” “can,” “continue,” “could,” “designed,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements use these words or expressions. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward- looking. All forward-looking statements are based upon the Company’s current expectations and various assumptions. The Company believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. The Company may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, its limited operating history; its incurrence of significant losses; its need for substantial additional funding and ability to raise capital when needed; its ability to successfully negotiate amended terms under the financing agreements to be able to access funding and to obtain relief under financial covenants; its significant indebtedness and potential payment obligations related to such indebtedness and other contractual obligations; risks associated with the strategic reprioritization; its limited experience in drug discovery and drug development; risks related to the TRANQUILITY II Phase 3 trial and related audit; its dependence on the success and commercialization of IGALMI™, BXCL501, BXCL502 BXCL701 and BXCL702 and other product candidates; its lack of experience in marketing and selling drug products; the risk that IGALMI or the Company’s product candidates may not be accepted by physicians or the medical community in general; the failure of preliminary data from its clinical studies to predict final study results; failure of its early clinical studies or preclinical studies to predict future clinical studies; its ability to receive regulatory approval for its product candidates; its ability to enroll patients in its clinical trials; undesirable side effects caused by the Company’s product candidates; its novel approach to the discovery and development of product candidates based on EvolverAI; the significant influence of and dependence on BioXcel LLC; its exposure to patent infringement lawsuits; its reliance on third parties; its ability to comply with the extensive regulations applicable to it; impacts from data breaches or cyber-attacks, if any; impacts from the COVID-19 pandemic; risks associated with the increased scrutiny relating to environmental, social and governance (ESG) matters; its ability to commercialize its product candidates; and the other important factors discussed under the caption “Risk Factors” in its Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2023, which are accessible on the SEC’s website at . These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While the Company may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release. Contact Information Corporate BioXcel Therapeutics Erik Kopp 1.203.494.7062 ekopp@bioxceltherapeutics.com Investor Relations BioXcel Therapeutics Brennan Doyle 1.475.355.8462 bdoyle@bioxceltherapeutics.com Media Russo Partners David Schull T: 858-717-2310 David.schull@russopartnersllc.com Scott Stachowiak T: 646-942-5630 Scott.stachowiak@russopartnersllc.com Source: BioXcel Therapeutics, Inc. BT BIOXCEL THERAPEUTICS is a registered trademark of BioXcel Therapeutics, Inc. All other trademarks are the properties of their respective owners. Copyright © 2023, BioXcel Therapeutics, Inc. All rights reserved. 1. FOR ILLUSTRATIVE PURPOSES ONLY: Analysis based on results from Pembrolizumab KEYNOTE-199 study. Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Emmanuel S. Antonarakis et al. Journal of Clinical Oncology; published at ascopubs.org/journal/jco on November 27, 2019: DOI . Pembrolizumab is not an approved therapy for the treatment of any form of mCRPC, and no head-to-head clinical trial has been conducted evaluating BXCL701 against pembrolizumab or other candidates or products. Notable differences exist between the Company’s trial designs, conditions under study and subject characteristics as compared to the third-party results discussed above and caution should be exercised when comparing data across these studies. 2. American Cancer Society. Key Statistics for Prostate Cancer. Retrieved October 9, 2023. 's%20estimates,34%2C700%20deaths%20from%20prostate%20cancer