Cannabinol

关于大麻和大麻素受体历史上大麻是一种药品，由大麻属植物制成，其主要的成分为四氢大麻酚（Tetrahydrocannabinol, THC）和大麻二酚 (Cannabidiol，CBD)。大麻素是从大麻里发现的一组萜酚类化合物，也自然地存在于动物神经和免疫系统里。1980年代，人们发现了两种对大麻素有特异反应的 G 蛋白偶联受体，分别是大麻素受体 1（CB1）和大麻素受体 2（CB2）。大麻素受体和内源性大麻素不仅参与调节中枢和外周神经系统的许多生理功能，还参与调节人体许多外周部位的生理功能：内分泌系统、免疫系统、胃肠道、心血管系统和生殖系统。CB1 受体虽然主要存在于大脑，但在脾脏、肺、胸腺、心脏和血管中也有表达。在中枢神经系统中，它们在杏仁核、海马、皮层、基底节和小脑中神经元的轴突和突触前末梢的表达量最高。它们与 GABA 能（抑制性）和谷氨酸能（兴奋性）神经元密切相关，介导抑制性和兴奋性神经递质的持续释放。CB2 受体在脑外（如脾脏、扁桃体、骨髓、胰腺、外周血白细胞）和脑内（星形胶质细胞和小胶质细胞）具有免疫功能的组织中最为丰富。它们具有调节免疫细胞迁移和细胞因子释放的功能，还在心血管和呼吸系统、骨骼、胃肠道、肝脏和生殖系统中发挥作用。大麻素根据其来源可分为 3 类：内源性大麻素、植物性大麻素和合成大麻素。内源性大麻素是人体内产生的化学物质，与某些植物大麻素一样附着在相同的受体(CB1 和CB2）。内源性大麻素化学物质有助于维持健康身体的平衡与和谐。研究最为广泛的两种内源性大麻素，即 Anandamide 和 2-AG，以及负责内源性大麻素代谢的酶，构成了内源性大麻素系统。 Anandamide 和 2-AG 以及其他植物大麻素的分子靶标不仅仅是 CB1 和 CB2，还有 TRPR 和 GPR55。内源性大麻素的一个主要特点是其前体存在于脂膜中，可通过一到两个快速酶解步骤合成，并释放到细胞外空间。 植物性大麻素是从大麻植物中发现和提取的化学物质。大麻植物含有 100 多种已知的植物大麻素，通常植物大麻素在雌株未播种的花蕾中含量最高。THC 和 CBD 是研究最广泛的植物大麻素。目前只有一种植物大麻素产品获得了美国 FDA 的批准，即 CBD 口服液，该产品被批准用于治疗与罕见癫痫相关的癫痫发作。 非 FDA 批准的 "医用大麻 "没有科学定义，但一般认为它是一种含有大麻植物中植物大麻素的产品，旨在缓解疾病症状。合成大麻素是在实验室中模仿植物大麻素制成的化学物质。美国 FDA 批准了 3 种合成大麻素产品，这些产品模仿植物大麻素 THC。合成大麻素可能比大麻提取的四氢大麻酚更有效。美国 FDA 批准的合成四氢大麻酚制剂 Nabilone (大麻隆) 和  Dronabinol(屈大麻酚) 适用于治疗与癌症化疗有关的恶心和呕吐；Dronabinol还适用于治疗与艾滋病患者体重减轻有关的厌食症。大麻素受体配体从结构上可分为五大化学类：经典类、非经典类、氨基烷基吲哚类、二十烷类和类肽化合物。经典类包含二苯并呋喃衍生物，其中最著名的是Δ9-THC 和 HU-210，后者是Δ8-THC 的合成类似物。非经典类包括缺少吡喃环的Δ9-THC 双环和三环类似物，如 (-)-CP 55,940 等。氨基烷基吲哚类（以 (+)-WIN 55,212-2 为代表）和二十烷类（由内源性大麻素组成）的结构与经典和非经典大麻素受体激动剂截然不同，彼此也有区别。类肽化合物包括内源性 Hemopressin、其衍生物 RVD-Hpα 和 VD-Hpα 以及新型 Pep19 都被证明具有大麻素受体配体的功能。新药研发简报根据智慧芽新药情报库统计，全球靶向大麻素受体 ( CB1 和 CB2 ) 的药物研发管线合计 256 例，其中约 119 个 (46%) 管线处于非在研阶段，74 个 (29%) 管线处于临床前研究阶段。5 款药物已获批上市 (Cannabidiol/Dronabinol大麻二酚/四氢大麻酚 和 Rimonabant) ，6款药物处于临床2/3期或3期研究阶段，23款药物处于临床2期。除开发具有亚型选择性的 CB1 或 CB2 治疗性药物外，部分药物研发工作聚焦开发非选择性的 CB1/CB2 药物分子以及 CB1/2 与 5-HT1A、NMDA 受体等的多特异性药物。靶向 CB1 和 CB2 受体的临床适应症及药物研发机会包括：神经系统疾病治疗（如神经痛、癫痫、帕金森病等）、代谢性疾病（如肥胖、2型糖尿病、非酒精性脂肪性肝炎等）、疼痛管理（疼痛和神经痛）、免疫系统调节（如类风湿性关节炎、炎症性肠病等）、抗癌治疗和药物成瘾和心理健康等。针对 CB1 和 CB2 受体的新型药物可能包括激动剂、拮抗剂、部分激动剂、偏向性激动剂、别构调控剂等，以更精确地调节大麻素系统的活性，减少副作用。Cannabidiol/Dronabinol（大麻二酚/四氢大麻酚）是由 GW Pharmaceuticals 公司原研开发的一款治疗入睡和睡眠障碍的药物，2022 年首次在德国获批上市。Cannabidiol 是一种存在于大麻中的活性大麻素，可从大麻或非大麻植物中提取，可用于治疗与 Lennox-Gastaut 综合征或 Dravet syndrome 综合征相关的癫痫发作，以及缓解中度至重度神经性疼痛或其他疼痛症状。尽管目前正在研究其确切的医学影响，Cannabidiol 已显示出镇痛、抗惊厥、肌肉松弛、抗焦虑、抗精神病的前景，并显示出神经保护、抗炎和抗氧化活性等。Dronabinol是一种合成的 Δ9-四氢大麻酚（Δ⁹-THC），通过对 CB1 和 CB2 受体产生微弱的部分激动活性来发挥其作用，从而产生众所周知的吸食大麻的效果，如增加食欲、减轻疼痛以及改变情绪和认知过程。它已被不同国家和地区被批准用于治疗艾滋病患者因体重减轻而引起的厌食症，以及治疗因癌症化疗而引起的恶心和呕吐，这些患者对常规止吐药治疗无效。GW Pharmaceuticals 建立了世界领先的大麻素科学平台，以开发深层次、创新性的早期和晚期大麻素候选产品管线，以及高度专业化的种植和制造技术。GW 也是全球率先开发出了世界上第一种从大麻植物中提取的处方药并实现了商业化。与未经 FDA 批准的 Cannabidiol 产品或大麻衍生产品不同，GW 获得监管机构批准的产品组合可确保所生产的每一种产品的安全性和疗效都经过临床试验的全面评估、独立的同行评审、监管机构的批准，并始终如一地进行生产，以确保达到最高质量标准。2021年，JAZZ 公司耗资72亿美元将 GW Pharmaceuticals 公司收入麾下。Rimonabant 是由 Sanofi-Aventis 公司原研开发、生产和销售的一种厌食抗肥胖药物。它是大麻素受体 CB1 的反向激动剂，其主要作用途径是降低食欲。Rimonabant 是全球首个获准使用的选择性 CB1 受体阻断剂，2006 年首次获批上市后已在包括欧盟、墨西哥和巴西在内的 38 个国家获得批准。但该药在美国 FDA 的上市申请被驳回，这一决定是因为它可能会增加自杀念头和抑郁情绪。早期的临床观察发现，大麻会刺激食欲，这表明内源性大麻素系统参与了能量平衡的控制。Rimonabant 是第一种上市的 CB1 受体拮抗剂，被开发为抗肥胖药，通过阻断中枢大麻素活性可能会减少食物摄入量。2005-2006年前后，Sanofi-Aventis 及临床研究团队分别在《柳叶刀》(2篇)和《新英格兰医学杂志》撰文，介绍了Rimonabant 对超重患者减轻体重和心血管风险因素的影响、超重血脂异常患者代谢风险因素的影响以及对超重或肥胖 2 型糖尿病患者的疗效和耐受性。结果表明，对于二甲双胍或磺脲类药物控制不佳的超重或肥胖 2 型糖尿病患者来说，20 mg/天的Rimonabant 与饮食和运动相结合，可以减轻体重，改善 HbA1c 以及一系列心血管和代谢风险因素，具有临床意义。然而，对所有已发表的随机对照试验进行的一项元分析 (meta-analysis) 结果表明，每天服用 20 mg 的Rimonabant会增加精神不良事件（抑郁性情绪障碍和焦虑）的风险。Rimonabant引起的不良事件明显多于安慰剂，严重不良事件是安慰剂的 1.4 倍。服用Rimonabant的患者因抑郁情绪障碍而中断治疗的可能性是服用安慰剂患者的 2.5 倍。美国 FDA 对四项主要试验以及未发表的试验进行了分析，发现服用Rimonabant（20 mg/天）比服用安慰剂更容易出现精神方面的不良反应。此外，据报道有两名服用Rimonabant的患者死于自杀。美国从未批准该药物用于治疗肥胖症。此后，欧洲监管当局取消了Rimonabant的上市许可。Taranabant 是一款由 Merck 公司原研开发的一款 CB 受体小分子类反向激动剂。据悉，Taranabant 对超重病人的临床3期研究数据表现出与Rimonabant 相似的减重效果，但由于潜在的副作用等原因，Merck 公司终止了对 Taranabant 的临床开发。此后，多项与CB1 拮抗剂相关的临床在研项目受此影响而宣告终止，包括阿斯利康、辉瑞、BMS、AbbVie 等跨国大药企。明知前路艰险，但依然有勇士无畏前行。INV-202 是一款由 Inversago Pharma 公司开发的一款 CB1 拮抗剂。前车之鉴，Inversago Pharma 公司开发的第二代 CB1 受体拮抗剂拮抗剂旨在降低分子对血脑屏障的通透效率，将药物分子限定在中枢神经系统之外的外周系统。根据23年更新的一份临床1b期研究报告，INV-202的耐受性良好，没有出现严重或严重的治疗突发不良事件；最常见的不良事件与已知的 CB1 受体阻断对胃肠道的影响有关。INV-202 显著降低了3.5公斤的平均体重，同时还显著降低了腰围和体重指数。今年8月诺和诺德公司和 Inversago Pharma 宣布，诺和诺德已同意在达到某些开发和商业里程碑的情况下，以最高 10.75 亿美元的现金收购 Inversago。另一位长期致力于 CB 受体系统药物开发的公司 Corbus Pharmaceuticals 公司宣布，公司正在致力于开发第二代 CB1 受体拮抗剂 CRB-913，该项目目前处于临床申报阶段。根据公司11月更新的临床前研究数据表明，CRB-913 进入大脑的比例很低，而减肥效果显著。临床前的减肥数据，如此振奋人心。加之近几年肥胖市场的大热，Corbus 公司对CB1 受体相关管线的调整思路非常明显。Ajulemic acid (Lenabasum) 是由美国 Corbus Pharmaceuticals 公司原研开发的另一款 CB2 受体激动剂和 IL-1β 抑制剂，目前处于临床3期阶段。早期的临床研究结果表明，Ajulemic acid 对慢性神经病理性疼痛患者有止痛作用，但没有临床相关的精神或身体副作用。目前，该药的正在围绕盘状红斑狼疮、皮肌炎、系统性硬皮病、囊性纤维化、系统性红斑狼疮等皮肤疾病进行临床研究。(但该项目在近期的公司管线汇报中并未提及。)CardiolRx (Cannabidiol) 是一款由 Cardiol Therapeutics 公司原研开发的一款 CB1/CB2 反向激动剂。在研临床适应症为心血管疾病、心包炎、心肌炎和心脏衰竭。CB1/CB2 新药开发策略尽管 CB1/CB2 具有广泛的治疗潜力，但候选药物的开发却受到不良反应、快速耐受性发展和滥用可能性的阻碍。有人提出，配体是否可通过产生偏向性信号转导，作为一种新药开发策略，将 CB1/CB2 受体的治疗效果和不良反应区分开来。但由于缺乏强偏性激动剂，人们对 CB1 受体的偏性信号转导了解甚少。研究人员对经典大麻素激动剂和异构配体的偏向信号转导特征进行调查研究，寻找 CB1 受体偏向信号转导在不同病理状态下的潜在治疗优势。CP55940 是一款由辉瑞公司 1974 年原研开发的一种合成大麻素。它可模拟天然四氢大麻酚的效果，作为 CB1/CB2 激动剂发挥作用。据报道，CP55940 的药效是 Δ9-THC 的 45 倍，能被Rimonabant完全拮抗，被用作研究内源性大麻素系统的研究工具，但从未进行临床研究或在市场上销售。一篇发表于《分子药理学杂志》的研究 (DOI: 10.1124/mol.115.101980) 表明，在 CB1 受体下游的多条信号通路中，激动剂 THC 和 CP55940 显示出偏向于 β-arrestin1 的信号转导，而内源性大麻素 2-AG 和 AEA 显示出偏向于 Gαi/o 的信号转导。研究人员认为，加强基于 Gαi/o 的内源性大麻素信号转导可能对亨廷顿病有治疗作用。与此相反，偏向于 β-arrestin1 信号通路的药物可能对 CB1 受体下游的治疗性信号转导有害，尤其是在 CB1 受体水平已经降低的亨廷顿病患者中。ORG27569 是一款靶向 CB1 受体的别构调控剂。据报道，ORG27569 是一种偏向于 CB1 受体的 β-arrestin1 信号通路的配体，在 G 蛋白信号传导方面起着负向别构激动剂的作用，而在 β-arrestin1 介导的 pERK1/2 信号传导方面起着正向别构激动剂的作用。 一篇近期由浙江大学张岩教授及合作者发表于《细胞》(DOI: 10.1016/j.cell.2023.11.017) 杂志的研究成果，弥补了结构生物学领域对于 CB1 受体如何偶联到下游 β-arrestin 信号蛋白的知识空缺。通过对比处于拮抗剂结合的非激活态、激动剂-受体-Gi 蛋白结合的激活态和激动剂-受体-β-arrestin1 态的细微结构差异。研究人员似乎对 CB1 受体下游偏向性激动找到了一些线索，这可能为设计更安全的镇痛和抗焦虑药物提供了结构基础。以上文章来源于GPCR drug diacovery，作者段思研       本文仅作信息交流之目的，文中观点不代表相关疾病治疗立场，也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

Closed calendar year 2022 with strong cash position of $11.5 millionApproaches completion of enrollment for Ph 2 clinical trial in EBAdvances research using rare cannabinoids in treating glaucoma and neurodegenerative diseases such as Alzheimer’s, Huntington’s and Parkinson’s VANCOUVER, British Columbia, Feb. 17, 2023 (GLOBE NEWSWIRE) -- InMed Pharmaceuticals Inc. (“InMed” or the “Company”) (Nasdaq: INM), a leader in the pharmaceutical research, development and manufacturing of rare cannabinoids and cannabinoid analogs, today announced financial results for the second quarter of fiscal year 2023 which ended December 31, 2022. The Company’s full financial statements and related MD&A for the second quarter ended December 31, 2022, are available at www.inmedpharma.com, www.sedar.com and at www.sec.gov. “This period was another strong operational quarter for the Company as we advanced our pharmaceutical programs, including the launch of INM-900 series compounds for the evaluation of neurodegenerative diseases. We are currently approaching the end of enrollment in our Ph 2 clinical trial in Epidermolysis Bullosa (“EB”). As we move into calendar 2023, we have a strong pipeline of programs at various stages of development,” said Eric A. Adams, President and CEO of InMed. “Fiscal Q2 saw significant cost savings across the different business segments resulting in a reduced cash burn. In addition, our strong cash position of over $11 million enables us to pursue several material milestones throughout calendar 2023.” Business update Pharmaceutical Development Programs INM-755 – Phase 2 Clinical Trial in EBTo date, the Ph 2 clinical trial has enrolled 17 patients of its targeted 20 patients. Several additional prospective patients have been identified for screening at the clinical sites and enrollment is expected to complete at the end of March 2023, with initial read out expected in early calendar 3Q 2023. INM-088 – Glaucoma ProgramThe Company continues to conduct the required IND enabling preclinical testing and has planned GLP toxicology studies in mid-2023. Human clinical trials remain on track to commence in calendar 2024. INM-900 – Neurodegenerative Diseases ProgramTwo cannabinoid analogs are being assessed in in vivo models of neurodegenerative diseases and the Company expects these studies to be completed and a candidate selected for further development in calendar 2Q 2023. Our research demonstrated the neuroprotective effects of specific cannabinoid analogs and their potential to improve neuronal function. BayMedica Commercial Business BayMedica continues to be a leading producer of cannabichromene (CBC) with increased revenue in the last two quarters, including a 46% quarter over quarter increase in fiscal 2Q 2023. Management continues to evaluate strategic options and long-term supply agreements for this business segment. Financing Activities and Results of Operations (expressed in US Dollars):On November 21, 2022, the Company closed a private placement of its common shares and issued an aggregate of 1,818,185 common shares (or pre-funded warrants in lieu of), for gross proceeds of approximately $6 million. For the six months ended December 31, 2022, the Company recorded a net loss of $5.6 million, or $3.54 per share, compared with a net loss of $7.3 million, or $14.03 per share, for the six months ended December 31, 2021. Research and development and patents expenses were $2.2 million for the six months ended December 31, 2022, compared with $4.0 million for the six months ended December 31, 2021. The decrease in research and development and patents expenses was primarily due to decreased expenditures related to the transition from capital intensive GLP toxicology into relatively less capital intensive clinical trials. The Company incurred general and administrative expenses of $3.0 million for the six months ended December 31, 2022, compared with $3.2 million for the six months ended December 31, 2021. The decrease was due to lower personnel expenses, insurance fees, investor relation expenses, accounting fees and stock-based compensation expenses, and was partially offset by higher consulting fees and BayMedica operating costs. Revenues increased by $0.5 million to $0.8 million in our BayMedica segment, or 198%, for the six months ended December 31, 2022, compared to the six months ended December 31, 2021. The increase in sales results from expanded marketing efforts to sell inventory on-hand and the Company acquired BayMedica on October 13, 2021, so the six months ended December 31, 2021 results were approximately 2 and a half months. At December 31, 2022, the Company's total issued and outstanding shares were 1,589,992. Subsequent to quarter end, 1,738,204 pre-funded warrants were exercised. As of the date of these filings, the issued and outstanding shares are 3,328,196. During the three and six months ending December 31, 2022, the weighted average number of common shares was 2,300,526 and 1,583,073, which is used for the calculation of loss per share for the respective interim periods. At December 31, 2022, the Company’s cash, cash equivalents and short-term investments were $11.5 million, which compares to $6.2 million at June 30, 2022. The increase in cash, cash equivalents and short-term investments during the six months to December 31, 2022, was primarily the result of both the September 13, 2022 and November 21, 2022 private placements partially offset by cash outflows from operating activities. With the completion of recent financings and depending on how we prioritize investment into our various development activities, InMed has a projected cash runway to the end of calendar 2023, allowing the Company to pursue certain material milestones over the coming year which we believe will increase shareholder value. Table 1: Condensed Consolidated Interim Balance Sheets: InMed Pharmaceuticals Inc. CONDENSED CONSOLIDATED INTERIM BALANCE SHEETS (unaudited) As at December 31, 2022 and June 30, 2022 Expressed in U.S. Dollars December 31, June 30, 2022 2022 ASSETS$$Current Cash and cash equivalents11,452,578 6,176,866 Short-term investments43,053 44,804 Accounts receivable, net81,647 88,027 Inventories1,613,506 2,490,854 Prepaids and other current assets826,931 797,225 Total current assets14,017,715 9,597,776 Non-Current Property, equipment and ROU assets, net703,922 904,252 Intangible assets, net2,026,929 2,108,915 Other assets171,130 176,637 Total Assets16,919,696 12,787,580 LIABILITIES AND SHAREHOLDERS' EQUITY Current Accounts payable and accrued liabilities1,970,265 2,415,265 Current portion of lease obligations414,307 404,276 Deferred rent16,171 - Acquisition consideration payable- 500,000 Total current liabilities2,400,743 3,319,541 Non-current Lease obligations, net of current portion183,902 389,498 Total Liabilities2,584,645 3,709,039 Shareholders' Equity Common shares, no par value, unlimited authorized shares: 1,589,992 (June 30, 2022 - 650,667) issued and outstanding 74,862,424 70,718,461 Additional paid-in capital38,407,932 31,684,098 Accumulated deficit(99,063,874)(93,452,587) Accumulated other comprehensive income128,569 128,569 Total Shareholders' Equity14,335,051 9,078,541 Total Liabilities and Shareholders' Equity16,919,696 12,787,580 Table 2: Condensed Consolidated Interim Statements of Operations: InMed Pharmaceuticals Inc. CONDENSED CONSOLIDATED INTERIM STATEMENTS OF OPERATIONS (unaudited) For the three and six months ended December 31, 2022 and 2021 Expressed in U.S. Dollars Three Months EndedSix Months Ended December 31December 31 2022 2021 2022 2021 $ $ $ $ Sales469,783 265,092 790,571 265,092 Cost of sales338,620 153,537 573,654 153,537 Inventory write-down- - 576,772 - Gross profit (loss)131,163 111,555 (359,855)111,555 Operating Expenses Research and development and patents851,356 2,537,070 2,230,009 4,028,322 General and administrative1,464,879 1,836,786 3,025,356 3,209,653 Amortization and depreciation49,049 49,797 98,097 78,329 Total operating expenses2,365,284 4,423,653 5,353,462 7,316,304 Other Income (Expense) Interest and other income115,797 26,277 188,384 31,425 Foreign exchange gain (loss)20,237 3,007 (76,554)(81,105)Loss before income taxes(2,098,087)(4,282,814)(5,601,487)(7,254,429) Tax expense(3,000)- (9,800)- Net loss for the period(2,101,087)(4,282,814)(5,611,287)(7,254,429) Net loss per share for the period Basic and diluted(0.91)(7.73)(3.54)(14.03)Weighted average outstanding common shares Basic and diluted2,300,526 553,894 1,583,073 516,933 Table 3: Condensed Consolidated Interim Statements of Cash Flows: InMed Pharmaceuticals Inc. CONDENSED CONSOLIDATED INTERIM STATEMENTS OF CASH FLOWS (unaudited)For the six months ended December 31, 2022 and 2021 Expressed in U.S. Dollars 2022 2021 Cash provided by (used in):$ $ Operating Activities Net loss(5,611,287)(7,254,429)Items not requiring cash: Amortization and depreciation98,097 78,329 Share-based compensation187,318 325,921 Amortization of right-of-use assets197,767 126,080 Loss on disposal of assets- 11,355 Interest income received on short-term investments(418)- Unrealized foreign exchange loss2,167 1,038 Inventory write-down576,772 - Bad debts25,085 - Changes in operating assets and liabilities: Inventories300,576 (501,700) Prepaids and other currents assets(29,706)847,374 Other non-current assets5,507 6,030 Accounts receivable(18,705)(2,285) Accounts payable and accrued liabilities(508,871)296,437 Deferred rent16,171 3,248 Lease obligations(209,112)(125,123)Total cash used in operating activities(4,968,639)(6,187,725) Investing Activities Cash acquired from acquisition of BayMedica- 91,566 Payment of acquisition consideration payable(500,000)- Purchase of property and equipment- (35,555)Total cash (used in) provided by investing activities(500,000)56,011 Financing Activities Shares issued for cash12,000,262 12,000,001 Share issuance costs(1,255,911)(1,294,247) Repayment of debt- (232,202) Settlement of debt upon acquisition of subsidiary- (425,000)Total cash provided by financing activities10,744,351 10,048,552 Increase in cash during the period5,275,712 3,916,838 Cash and cash equivalents beginning of the period6,176,866 7,363,126 Cash and cash equivalents end of the period11,452,578 11,279,964 About InMed: InMed Pharmaceuticals is a global leader in the research, development and manufacturing of rare cannabinoids, including clinical and preclinical programs targeting the treatment of diseases with high unmet medical needs. We also have significant know-how in developing proprietary manufacturing approaches to produce cannabinoids for various market sectors. For more information, visit www.inmedpharma.com. Investor Contact: Colin ClancyVice President, Investor Relationsand Corporate CommunicationsT: +1.604.416.0999E: cclancy@inmedpharma.com Cautionary Note Regarding Forward-Looking Information: This news release contains "forward-looking information" and "forward-looking statements" (collectively, "forward-looking information") within the meaning of applicable securities laws. Forward-looking information is based on management's current expectations and beliefs and is subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Forward-looking information in this news release includes statements about: having a unique offering as the only company that has the breadth and depth in cannabinoid drug research, development and significant manufacturing know; several material milestones anticipated in the coming quarters; additional prospective patients have been identified for screening; advancing preclinical toxicology and having planned GLP studies planned for 2023 in advance of human clinical trials; being on track to begin the clinical trial in 2024; expecting in vivo studies to be completed and a candidate selected for further development in calendar 2Q 2023; BayMedica continuing to be a leading producer of CBC globally; having a strong pipeline of programs at various stages of development evaluating strategic options and long-term supply agreements for the BayMedica commercial segment; having projected cash runway to the end of calendar 2023, depending on how we prioritize our investment into various development activities; belief that hitting certain material milestones will increase shareholder value; all plans for our preclinical and clinical programs; being a global leader in the manufacturing and development of rare cannabinoids and delivering new treatment alternatives to patients that may benefit from cannabinoid-based pharmaceutical drugs. With respect to the forward-looking information contained in this news release, InMed has made numerous assumptions. While InMed considers these assumptions to be reasonable, these assumptions are inherently subject to significant business, economic, competitive, market and social uncertainties and contingencies. Additionally, there are known and unknown risk factors which could cause InMed's actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking information contained herein. A complete discussion of the risks and uncertainties facing InMed’s stand-alone business is disclosed in InMed’s Annual Report on Form 10-K and other filings with the Securities and Exchange Commission on www.sec.gov. All forward-looking information herein is qualified in its entirety by this cautionary statement, and InMed disclaims any obligation to revise or update any such forward-looking information or to publicly announce the result of any revisions to any of the forward-looking information contained herein to reflect future results, events or developments, except as required by law.