Myocardial Ischemia

大会由扬州市人民政府主办，同写意专业策划，以“打造生物医药新质生产力”为主题，邀请众多行业领袖和先锋人物一起取势明道，就如何打造中国医药新质生产力，面向未来创新药如何立项，资本寒冬下的创新药BD与出海，GLP-1&小核酸药物以及抗体药的质量与生产四大主题展开深度研讨，为行业发展提供方向性指引。自从semaglutide脱颖而出成为2023年最受关注的药物以来，譬如北辰的诺和诺德似乎紧迫感与日俱增，在不断深耕糖尿病和肥胖症的同时，也在未雨绸缪地向多个领域进行了开拓，心血管疾病就是诺和诺德非常看重的开发方向。1未雨绸缪诺和诺德11亿美元下注近日，欧洲市值排名第一的诺和诺德宣布将以11亿美元收购德国公司Cardior Pharmaceuticals的消息，后者的管线资产为诺和诺德的心脏代谢药物管道提供了新的源头活水。Cardior专注于靶向RNA，解决心脏病的根本原因。其主要候选药物CDR132L正处于2期开发阶段，用于治疗心力衰竭。诺和诺德没有透露为Cardior预付了多少费用，也没有透露具体金额支付和未来实现的里程碑的关联。这笔交易预计将于今年第二季度完成。其实，无所不能的semaglutide在心血管疾病领域的临床研究已经取得了可观的进展，Wegovy在一项试验中表明它可以降低心脏病发作和中风的风险，这个发现直接促使了FDA在今年3月扩大了Wegovy的标签范围，强调其对心脏的益处。有了这一额外的背书，那些之前冷眼旁观表示无法承保肥胖药物的医疗保险机构纷纷改弦更张。他们表示，如果医生开具的Wegovy处方是用于预防心脏问题，那么他们将覆盖Wegovy的费用。尽管semaglutide有可能在心血管疾病中突出重围，但诺和诺德似乎打算利用集团军的优势攫取市场更大的份额，从Cardior收购的交易中就能明显揣摩出他们的这个意图。Cardior的主要管线资产CDR132L与诺和诺德的semaglutide不仅在分子模态上不同，在作用机制和可能面对的患者全体也有很大的区别。CDR132L是一种寡核苷酸候选药，靶向miRNA132(miR-132)，通过抑制该RNA阻止并逆转有害心脏重塑的发展。有害心脏重塑指心脏在受到损伤或受到负荷过度的情况下发生的异常结构和功能改变，包括心肌肥厚、心肌纤维化、心室扩张和心肌功能下降等，这些改变可能导致心力衰竭和心律失常等严重并发症。针对有害心脏重塑的干预措施具有重要的临床意义，可以帮助延缓疾病的进展并改善患者的预后。CDR132L选择性阻断异常的miR-132水平，逆转细胞病理学并恢复心肌细胞的正常功能，改善心力衰竭患者的心脏收缩和舒张功能。CDR132L是一种高度稳定的水溶性寡核苷酸，专为肠胃外或皮下应用而配制。目前CDR132L正在HF-REVERT 2期临床研究中进行评估，针对曾患过心脏病的心力衰竭患者进行测试，有可能延长患者的生命并提高他们的生活质量。诺和诺德在接手Cardior之后，计划针对慢性心力衰竭和心脏肥大（心脏肥厚和硬化）患者开展另一项2期研究。值得注意的是，诺和诺德最近似乎着迷于RNA为靶标的疗法开发。在收购Cardior的寡核苷酸RNA抑制剂之前，他们还在马萨诸塞州列克星敦开设了一个大型研究中心，专注于RNA干扰疗法，其目标之一是开发出比semaglutide使用频率更低的肥胖症和糖尿病药物。2为何诺和诺德拿下CDR132L？诺和诺德为何对反义寡核苷酸下重注？从CDR132L的作用机理谈起，以下几张图片可形象化说明其作用机理。众所周知，心脏的功能依靠健康心肌的作用实现。在心脏应激情况下，例如心脏病发作，一些心肌细胞死亡，其余的心肌细胞经过重塑过程，承担起额外的心脏工作负荷。心肌细胞因此显著地改变了它们的结构，变得更加粗大和僵化，心肌也会出现纤维化过程。图1 心肌纤维化图片来源：Cardior PharmaceuticalsmicroRNA（miRNA）是一类短小的非编码RNA分子，通常由约20到25个核苷酸组成。miRNA主要通过与靶标mRNA的结合调节基因的表达。它们在细胞中发挥重要的调控作用，参与调节许多生物学过程，包括细胞增殖、分化、凋亡、代谢和发育等。miRNA通过促进mRNA的降解或抑制翻译过程，影响靶基因的表达水平，并下调蛋白形成。在许多疾病中，miRNA都被发现异常表达，是疾病发展的关键调控因子，因此对miRNA进行研究可以为疾病的诊断、治疗和预防提供重要的线索。miR-132是microRNA的一种，是短小的非编码RNA分子。miR-132的几个靶标与神经发育的介质、突触传递、炎症和血管生成相关。miR-132在各种心脏应激时过度激活，会引发心脏组织的不良重塑，从而导致心力衰竭的发生和进展。抑制miR-132是预防肥厚性心脏病心力衰竭进展的有效策略。CDR132L是首个针对miR-132的合成反义寡核苷酸抑制剂，具有高度水溶性和稳定性。通过其与靶标miR-132的结合，阻止和逆转有害心脏重塑的发展。CDR132L可以实现逐渐逆转病理调剂信号通路，减少病理性肥大心肌细胞生长、心脏纤维化、毛细血管稀疏，并最终改善心脏的收缩和舒张功能。HF-REVERT（NCT05350969，2期、多中心、随机、平行、3臂、安慰剂对照研究，评估CDR132L对心肌梗死后左心室射血分数减低患者的疗效和安全性）评估CDR132L在急性心肌梗死后心力衰竭患者（n=280）中的疗效和安全性，比较5和10 mg/kg CDR132L的效果，以每隔28天单次静脉注射三剂，与标准治疗联合应用。研究包括为期6个月的双盲治疗期，主要终点为左心室舒张末期容积指数和相关的次要终点，随后是为期6个月的开放标签观察期。图2 CDR132L 2期临床研究HF-REVERT的设计。图片来源：Eur J Heart FailHF-REVERT的主要临床终点将在2024年9月读数，整体2期研究预计在2025年3月11日完成。随着减肥药日益内卷，欧洲市值排名第一的诺和诺德也开始致力于多个领域新药研发，相信很快将有好消息传来。参考文献：1.Joseph,A.Novo Nordisk to acquire heart disease-focused Cardior Pharmaceuticals in deal worth$1.1 billion.STAT.25.03.2024.2.Batkai,S.et al.CDR132L improves systolic and diastolic function in a large animal model of chronic heart failure.Eur Heart J.2021 Jan 7;42(2):192-201.doi:10.1093/eurheartj/ehaa791.3.Bauersachs,J.et al.Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction:Rationale and design of the HF-REVERT trial.Eur J Heart Fail.2024 Jan 25.doi:10.1002/ejhf.3139.4.Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction(HF-REVERT).Clinicaltrials.gov.19.03.2024.5.Cardior Pharmaceuticals website:https://cardior.de/our-approach/更多优质内容，欢迎关注↓↓↓

古语云：“穷则变，变则通，通则久”。医药行业在行政监管与市场竞争的双重压力下，面临战略抉择。中药企业正是期望通过转型实现“换挡提速”，其中不乏片仔癀、云南白药等龙头，积极研发创新药的天士力、众生药业、以岭药业等。01云南白药、片仔癀，中药龙头“换挡提速”片仔癀、云南白药，A股总市值排名前2的中药龙头企业。其中，片仔癀以超1400亿元的市值取得断层式第一。2023年度，片仔癀交出了靓丽的成绩单：总营收首次超过100亿元，同比增长15.24%，归母净利润实现近28亿元，同比增长13%。2024年一季度，市场呈现出旺销态势，业绩延续增长，预计实现归母净利润同比增长不低于25%。片仔癀的主要业务板块，包括医药制造业、医药流通业及化妆品业等。其中，医药制造业是公司第一大业务板块，占据公司收入的“半壁江山”：以“片仔癀”为主产品，同时持续做大做强安宫牛黄丸等系列产品，涵盖了肝病用药、感冒用药、皮肤科用药等多个领域。片仔癀业绩靓丽，得益于控股子公司业绩指标再度跃升。2023年上半年，控股子公司合并营业收入、利润总额均达两位数增长，特别是龙晖药业的安宫牛黄丸销售创历史新高。化妆品业务是片仔癀打造的第二增长曲线，拥有“片仔癀”及“皇后”等多个品牌，2017-2021年实现快速增长，近两年却出现业绩“失速”，2021年、2022年、2023年前三季度分别实现收入8.41亿元、6.34亿元、4.31亿元，占公司总收入比例为10.49%、7.30%、5.67%。对此，片仔癀计划一边通过专业团队、渠道优化、黄金单品、品牌建设、科研投入五大行动赋能化妆品渠道增长，一边将化妆品板块分拆上市，目前正在梳理IPO尽职调查问题，推进股份制改造流程。片仔癀化妆品公司营收及增速（单位：百万元）资料来源：公司公告、招商证券相较于片仔癀，云南白药的营收规模更大：凭借生产经营核心底座（药品、健康品、中药资源、省医药四大事业部），2022年、2023年前三季度分别实现总营收约365亿元、297亿元。目前，云南白药的业务布局涉及天然药物、中药材饮片、特色药、医疗器械、健康日化产品、保健食品等多个领域，实现了从传统中药制造企业向现代化大健康企业的转型。例如，药品事业部以云南白药主系列产品为主，同时涵盖伤风感冒、心脑血管等领域其他品牌中药；健康品事业部以牙膏品类为业务核心，开拓口腔护理、养元青防脱洗护新品类；中药资源事业部打造包括品牌药材等B端产品、保健食品族等C端产品。如今，云南白药还进军了百亿级核药赛道。2022年9月，云南白药以2000万元拿下了北京大学第一医院、北京市肿瘤防治研究所合作研发的前列腺特异性膜抗原（PSMA）靶向核药相关专利。今年2月，全资子公司云核医药靶向PSMA的诊断核药INR101注射液获NMPA批准开展临床试验。近年来，核药赛道投融资火热，并购和BD交易也频频发生，已经成为药企的兵家必争之地，其中不乏诺华、拜耳、礼来等MNC巨头、老牌核药龙头东诚药业、“后起之秀”先通医药，以及远大医药、恒瑞医药等进军的传统药企。02以岭、康缘、众生，积极转型创新药除拓展化妆品业务、转型大健康公司外，更多中药企业选择研发创新药，包括中药创新药、化学药和生物药等。例如，以岭药业布局了丰富的1.1类中药创新药管线，在研立项品种涵盖呼吸、消化、心血管系统等疾病，目前已有5款处于临床III期及申报上市阶段，针对包括糖尿病视网膜病变、过敏性鼻炎和类风湿性关节炎等适应症。以岭药业在研项目情况图片来源：2023年半年报在开展创新中药研发的同时，以岭药业也积极布局化生药业务和健康产业。其中，化生药板块采取“转移加工切入—仿制药国际国内双注册—专利新药研发生产销售”齐步走的发展战略。截至2023年半年报，以岭药业已有4个1类创新药品种进入临床阶段，其中治疗术后疼痛的苯胺洛芬注射液已完成临床III期，即将申报NDA；另外3个管线针对的适应症，包括实体瘤、缺血性脑卒中和子宫肌瘤等。康缘药业也是国内中药创新药领域龙头之一，为了实现研发创新转型、寻求新的增长点，制定了“一体两翼”研发策略，即以现代中药为主体，化药、生物药协同发展。其中，已有12个创新中药管线处于临床II期、III期及NDA阶段，主要以妇科中成药成熟度最高。在化生药方面，康缘药业杀入了多个市场潜力巨大的赛道，其中已有5款化药1类项目进入临床试验，包括治疗阿尔茨海默症的DC20、WXSH0493片（高尿酸血症）、DC042（前列腺增生）、KY0135片（胰腺癌）、KY1702胶囊（脑瘤）；在生物药领域主打的CD38单抗KYS202002A注射液已获批3个临床，针对多发性骨髓瘤、系统性红斑狼疮，并在中美两国开展临床试验。众生药业的主要收入来自中成药销售，2023年上半年占据54.53%的收入比例，其次为化学药销售，占比36.4%，中药材及中药饮片销售占比为7.14%。在创新药的布局上，众生药业主要聚焦代谢、呼吸和肿瘤等疾病领域，目前已有7个处于临床试验阶段，1个已获批上市（来瑞特韦片，研发代号：RAY1216），来瑞特韦片是中国首个3CL单药抗新冠病毒感染口服药。众生药业在研管线图片来源：2023年半年报从进度上看，小分子RNA聚合酶抑制剂ZSP1273（昂拉地韦片）已完成治疗成人单纯性流感的III期临床试验顶线数据初步统计分析结果；治疗非酒精性脂肪性肝炎（NASH）/代谢功能障碍相关脂肪性肝炎（MASH）的一类创新药ZSP1601已完成Ib/IIa期临床研究，达到主要研究终点；长效GLP-1类创新结构多肽药物RAY1225注射液（RAY002），在临床前研究中，药代特性显著优于同靶点化合物，目前正在开展I期临床。此外，布局创新中药研发的中药企业，还有步长制药、方盛制药、健民集团等。0397款在研管线，天士力能否“逆天改命”？在众多中药企业中，积极投入研发、大刀阔斧向创新转型的，除康缘药业、以岭药业外，还有天士力、华润三九、济川药业等。以天士力为例，2021年、2022年、2023年前三季度的研发费用分别为5.8亿元、8.44亿元、5.58亿元。中药企业研发投入金额对比（单位：亿元）资料来源：Wind、招商证券在研发策略上，天士力与康缘药业一样，都是利用现代中药、生物药、化学药协同发展优势进行创新药物的战略布局。不同之处在于，天士力的疾病领域更为聚焦，主要为中国市场容量最大、发展最快的心脑血管、消化代谢、肿瘤领域，而且创新药管线数量极为丰富，目前已拥有97款在研产品，其中包括41款1类创新药，并有39款已进入临床试验阶段，25款已处于临床II、III期研究阶段。如此丰富的在研管线，不知能否让天士力实现“逆天改命”，重回高光时刻？从疾病领域看，心脑血管领域是天士力的主要收入来源，多年收入占比保持在60%左右，主要凭借核心产品复方丹参滴丸形成心脑血管品牌优势。目前，天士力已在这一领域布局18款产品，覆盖心衰、心梗、脑卒中和冠心病等适应症。在消化代谢领域，天士力主要聚焦糖尿病及并发症的治疗，共布局18款在研项目；在肿瘤领域，主要围绕肿瘤免疫治疗和肿瘤靶向治疗进行精准布局，拥有20个在研项目，涉及PARP抑制剂、新一代Wee1抑制剂、靶向EGFR单抗、PD-L1/VEGF双抗、靶向叶酸受体α的第三代ADC药物等。另外，在中枢神经领域及呼吸系统，天士力采取自主研发并行产品引进的研发策略，针对抑郁、失眠、帕金森等疾病领域。按药物类型看，天士力在生物药领域布局了12款产品，其中普佑克适应症从急性ST段抬高型心肌梗死（心梗）治疗拓展至急性缺血性脑卒中（脑梗）治疗，已处于III期验证性试验；在化学药领域布局了57款化学药产品，涵盖创仿结合研发管线。天士力生物药研发管线（部分）资料来源：公司年报，安信证券研究中心04结语总体来看，中药企业都在“求变”，创新药或许是个好的转变方向。然而，创新药研发之路道阻且长，不仅需要投入大量的人力、物力和财力，更面临着技术难度高、市场风险大、政策环境复杂等多重挑战。中药企业能否在激烈的市场竞争中占据有利地位，需要更加关注市场需求的变化，并灵活调整管线研发战略，尤其得实现研发成果的商业化变现。参考资料1.各家公司的财报、公告、官网2.招商证券、安信证券研报

Company to host conference call at 4:30 PM EDT today, Thursday, March 28, 2024SEATTLE and VANCOUVER, British Columbia, March 28, 2024 (GLOBE NEWSWIRE) -- Achieve Life Sciences, Inc. (NASDAQ: ACHV), a late-stage pharmaceutical company committed to the global development and commercialization of cytisinicline for smoking cessation and nicotine dependence, today announced fourth quarter and year-end 2023 financial results and provided an update on the cytisinicline development program. Recent Highlights Announced Company reached agreement with the U.S. Food and Drug Administration (FDA) on long-term cytisinicline exposure requirements to support a New Drug Application (NDA) submissionCompleted an equity financing of up to $124.2 million that included initial upfront gross proceeds of $60.0 million, prior to deducting placement agent fees and estimated offering expenses, and up to an additional approximately $64.2 million of gross proceeds upon exercise of milestone-driven warrantsPresented data from Phase 3 ORCA-2 and ORCA-3 trials, and Phase 2 ORCA-V1 trial at Society for Research on Nicotine and Tobacco (SRNT) John Bencich, Achieve’s Chief Executive Officer, commented, “2023 marked a significant turning point for Achieve as we accomplished several key milestones, such as repeating successful efficacy and safety outcomes in the second Phase 3 ORCA-3 trial for smoking cessation, positive data from the Phase 2 ORCA-V1 trial for vaping, and significant progress in our discussions with the FDA to further our goal of bringing cytisinicline forward to aid the millions of individuals who are seeking treatment for nicotine dependence. We are appreciative of the strong support and confidence from our stakeholders, including new investors who participated in the recent financing and smoking cessation opinion leaders who share in our enthusiasm for cytisinicline’s potential.” FDA Agreement on NDA Submission Requirement Achieve and the FDA have reached agreement that a single, open-label study evaluating for long-term safety exposure of cytisinicline will be sufficient to complete the requirement and enable an NDA submission anticipated in the first half of 2025. Achieve plans to initiate the “ORCA-OL” open-label exposure trial in the second quarter of 2024, which will include investigators and sites who have participated in the ORCA clinical trial program (ORCA-2, ORCA-3, and ORCA-V1 studies). Completed Registered Direct Offering and Concurrent Private Placement The Company completed an equity financing of up to $124.2 million that included initial upfront gross proceeds of $60.0 million, prior to deducting placement agent fees and estimated offering expenses, and up to an additional approximately $64.2 million gross proceeds upon exercise of milestone-driven warrants. Achieve expects proceeds from the registered direct offering and concurrent private placement, assuming the exercise of all of the milestone-driven warrants, will be sufficient to fund its development of cytisinicline into 2026 and through potential FDA approval. ORCA-2, ORCA-3 and ORCA-V1 Data Presented at Annual SRNT ConferenceDuring the Annual Society for Research on Nicotine and Tobacco conference in March, the Company had three cytisinicline clinical data abstracts selected for podium presentation. The selected abstracts covered data from the Phase 3 ORCA-2 and ORCA-3 trials, alongside the Phase 2 ORCA-V1 trial, and presented compelling evidence on the potential efficacy and safety of cytisinicline for smoking and vaping cessation. Results presented from the Phase 3 participant surveys, showed that 69% of survey respondents who received cytisinicline reported quitting smoking completely. For those on treatment that did not achieve full smoking abstinence, 22% reported a reduction of their smoking by over half. Nearly all participants who quit smoking attributed their success to cytisinicline and cited fewer cravings and tolerable side effects as the main reasons. Additionally, 97% reported they would recommend cytisinicline to others. The ORCA-3 trial further validated these survey results, demonstrating higher smoking abstinence rates with cytisinicline compared to placebo, without increased relapse risk after transitioning to placebo. Furthermore, the ORCA-V1 trial explored cytisinicline's potential in vaping cessation among 160 e-cigarette users, showing a significant increase in abstinence rates compared to placebo, with minimal side effects. Financial ResultsAs of December 31, 2023, the Company’s cash, cash equivalents, and restricted cash was $15.6 million. After giving effect to the February 2024 equity financing the Company’s pro forma cash, cash equivalents, and restricted cash as of December 31, 2023, would have been $71.8 million. Total operating expenses for the fourth quarter and year ended December 31, 2023 were $4.4 million and $27.3 million, respectively. Total net loss for the fourth quarter and year ended December 31, 2023 was $5.5 million and $29.8 million, respectively. As of March 28, 2024, Achieve had 34,251,911 shares outstanding. Conference Call DetailsAchieve will host a conference call at 4:30 PM EDT Thursday, March 28, 2024. To access the webcast, log on to the investor relations page of the Achieve website and use the following link 4Q23 Earnings Webcast. Alternatively, access to the live conference call is available by dialing (877) 269-7756 (U.S. & Canada) or (201) 689-7817 (International) and referencing conference ID 13744140. A webcast replay will be available approximately two hours after the call and will be archived on the website for 90 days. About Achieve and Cytisinicline Achieve’s focus is to address the global smoking health and nicotine addiction epidemic through the development and commercialization of cytisinicline. There are an estimated 28 million adults in the United States alone who smoke combustible cigarettes.1 Tobacco use is currently the leading cause of preventable death that is responsible for more than eight million deaths worldwide and nearly half a million deaths in the United States annually.2,3 More than 87% of lung cancer deaths, 61% of all pulmonary disease deaths, and 32% of all deaths from coronary heart disease are attributable to smoking and exposure to secondhand smoke.3 In addition, there are over 11 million adults in the United States who use e-cigarettes, also known as vaping.3  In 2023, approximately 2.1 million middle and high school students in the United States reported using e-cigarettes.4 Currently, there are no FDA-approved treatments indicated specifically as an aid to nicotine e-cigarette cessation.  Cytisinicline is a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor. It is believed to aid in treating nicotine addiction for smoking and e-cigarette cessation by interacting with nicotine receptors in the brain, reducing the severity of withdrawal symptoms, and reducing the reward and satisfaction associated with nicotine products. Cytisinicline is an investigational product candidate being developed for the treatment of nicotine addiction and has not been approved by the Food and Drug Administration for any indication in the United States. For more information on cytisinicline and Achieve visit www.achievelifesciences.com. Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the timing and nature of cytisinicline clinical development and regulatory review and approval, data results and commercialization activities, the anticipated proceeds from outstanding milestone-driven warrants, the sufficiency of Achieve’s capital resources to fund the development of cytisinicline through potential FDA approval, the the potential market size for cytisinicline, the potential benefits, efficacy, safety and tolerability of cytisinicline, the ability to discover and develop new uses for cytisinicline, including but not limited to as an e-cigarette cessation product, and the development and effectiveness of new treatments. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Achieve may not actually achieve its plans or product development goals in a timely manner, if at all, or otherwise carry out its intentions or meet its expectations or projections disclosed in these forward-looking statements. These statements are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including, among others, the risk that cytisinicline may not demonstrate the hypothesized or expected benefits; the risk that Achieve may not be able to obtain additional financing to fund the development of cytisinicline; the risk that cytisinicline will not receive regulatory approval or be successfully commercialized; the risk that new developments in the smoking cessation landscape require changes in business strategy or clinical development plans; the risk that Achieve’s intellectual property may not be adequately protected; general business and economic conditions; risks related to the impact on our business of macroeconomic conditions, including inflation, rising interest rates, instability in the global banking sector, and public health crises, such as the COVID-19 pandemic and the other factors described in the risk factors set forth in Achieve’s filings with the Securities and Exchange Commission from time to time, including Achieve’s Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q. Achieve undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable. Investor Relations ContactNicole Jonesachv@cg.capital(404) 736-3838 Media ContactGlenn SilverGlenn.Silver@Finnpartners.com(646) 871-8485 References1Cornelius ME, Loretan CG, Jamal A, et al. Tobacco Product Use Among Adults – United States, 2021. MMWR Morb Mortal Wkly Rep 2023;72:475–483.2World Health Organization. WHO Report on the Global Tobacco Epidemic, 2019. Geneva: World Health Organization, 2017.3U.S. Department of Health and Human Services. The Health Consequences of Smoking – 50 Years of Progress. A Report of the Surgeon General, 2014.4Birdsey J, Cornelius M, Jamal A, et al. Tobacco Product Use Among U.S. Middle and High School Students — National Youth Tobacco Survey, 2023. MMWR Morb Mortal Wkly Rep 2023;72:1173–1182. Consolidated Statements of Loss(In thousands, except per share and share data) Three months ended December 31, Twelve months ended December 31, 2023 2022 2023 2022 Operating expenses: Research and development 2,114 8,614 15,814 30,078 General and administrative 2,272 2,248 11,436 10,722 Total operating expenses 4,386 10,862 27,250 40,800 Loss from operations (4,386) (10,862) (27,250) (40,800)Other income (expense) (1,090) (370) (2,565) (1,550)Net loss$(5,476) $(11,232) $(29,815) $(42,350) Basic and diluted net loss per share$(0.26) $(0.83) $(1.50) $(4.00) Weighted average number of basic and diluted common shares 21,165,760 13,536,944 19,827,354 10,593,034 Consolidated Balance Sheets(In thousands) December 31, December 31, 2023 2022 Assets: Cash and cash equivalents $15,546 $24,771 Prepaid expenses and other current assets 1,436 2,559 Other assets and restricted cash 92 66 Right-of-use assets 66 123 License agreement 1,197 1,418 Goodwill 1,034 1,034 Total assets $19,371 $29,971 Liabilities and stockholders' equity: Accounts payable and accrued liabilities $4,088 $5,470 Current portion of long-term obligations 63 58 Convertible debt 16,662 16,071 Long-term obligations 6 69 Stockholders' equity (1,448) 8,303 Total liabilities and stockholders' equity $19,371 $29,971