Phase 2 trial to assess impact of peripherally-acting CB1 inhibitor on weight loss and metabolic biomarkers related to co-morbid obesity and chronic kidney disease

评估外周作用CB1抑制剂对体重减轻和与合并症肥胖和慢性肾脏疾病相关的代谢生物标志物的影响的2期试验

San Francisco, California--(Newsfile Corp. - January 9, 2024) - Skye Bioscience, Inc. (OTCQB: SKYE) ('Skye' or the 'Company'), a pharmaceutical company developing drugs targeting the endocannabinoid system, has received clearance of its Investigational New Drug ('IND') application with the U.S. Food and Drug Administration ('FDA') to initiate a Phase 2 clinical trial of nimacimab in patients with obesity and chronic kidney disease.

加利福尼亚州旧金山-（新闻文件公司-2024年1月9日）-Skye Bioscience，Inc.（OTCQB:Skye）（“Skye”或“公司”），一家开发针对内源性大麻素系统的药物的制药公司，已获得美国食品和药物管理局（FDA）批准其研究性新药（“IND”）申请，以启动尼莫单抗在肥胖和慢性肾病患者中的2期临床试验。

Skye plans to initiate the Phase 2 trial in mid-2024..

Skye计划在2024年年中启动第二阶段试验。。

Nimacimab is a negative allosteric-modulating antibody targeting the cannabinoid 1 receptor ('CB1'), which has been implicated as an important target in cardiometabolic diseases including obesity and renal complications. The high correlation of these comorbid conditions, with 80% of patients with kidney disease being obese and 30% of obese patients having kidney disease, represents an opportunity for a mechanism that can affect their common underlying disease processes..

尼莫单抗是一种靶向大麻素1受体（“CB1”）的负变构调节抗体，已被认为是包括肥胖和肾脏并发症在内的心脏代谢疾病的重要靶标。这些合并症的高度相关性，80%的肾脏疾病患者肥胖，30%的肥胖患者患有肾脏疾病，代表了一种可能影响其常见潜在疾病过程的机制的机会。。

Nimacimab was observed to have very limited accumulation in the CNS in pre-clinical studies, a safety issue in earlier generations of CB1 inhibitors. Safety and tolerability assessments from the completed Phase 1b study of nimacimab in non-alcoholic fatty liver disease ('NAFLD') patients with diabetes or prediabetes demonstrated no serious adverse events, no early terminations of treatment due to adverse events, and no adverse events of concern occurring in a dose-dependent manner.

在临床前研究中，观察到尼莫单抗在中枢神经系统中的积累非常有限，这是早期CB1抑制剂的安全性问题。尼莫单抗在非酒精性脂肪性肝病（NAFLD）糖尿病或糖尿病前期患者中完成的1b期研究的安全性和耐受性评估显示，没有严重的不良事件，没有因不良事件而提前终止治疗，也没有以剂量依赖的方式发生不良事件。

Encouraging trends were observed in exploratory biomarkers including cholesterol, liver enzymes and liver function in patients receiving nimacimab versus placebo after the four-week dosing period. Moreover, pharmacokinetic assessment of nimacimab highlighted a half-life of approximately three weeks, potentially allowing for monthly dosing, which would offer a competitive advantage over once-a-week subcutaneous dosing of current peptidic GLP-1 receptor agonists..

在四周给药期后，接受尼莫单抗与安慰剂治疗的患者的探索性生物标志物（包括胆固醇，肝酶和肝功能）出现了令人鼓舞的趋势。此外，尼莫单抗的药代动力学评估强调了大约三周的半衰期，可能允许每月给药，这将比当前肽GLP-1受体激动剂每周一次皮下给药具有竞争优势。。

Additionally, third-party research has strongly indicated the role of CB1 inhibition in modifying insulin and leptin sensitivity, preserving lean mass, and ultimately augmenting durability of weight loss. With nimacimab's differentiated characteristics, this novel molecule may provide an important alternative as a single or combination therapy targeting obesity and other metabolic, inflammatory and fibrotic conditions..

此外，第三方研究强烈表明CB1抑制在改变胰岛素和瘦素敏感性，保持瘦体重以及最终增强减肥持久性方面的作用。由于尼莫单抗的分化特征，这种新型分子可能作为针对肥胖和其他代谢，炎症和纤维化疾病的单一或联合疗法提供重要的替代方案。。

'We believe that the encouraging safety profile of nimacimab from preclinical and clinical studies exceeds that of small molecule CB1 inhibitors and that this class of drug offers the potential to treat a range of metabolic conditions,' said Tu Diep, Chief Development Officer of Skye. 'We look forward to evaluating multiple meaningful clinical endpoints in the Phase 2 trial, including weight loss, changes in albuminuria related to kidney function, and other biomarkers, in order to guide the future development of nimacimab.'.

Skye首席开发官Tu Diep说：“我们认为，临床前和临床研究中尼莫单抗令人鼓舞的安全性超过了小分子CB1抑制剂，这类药物具有治疗一系列代谢疾病的潜力。”我们期待着在2期试验中评估多个有意义的临床终点，包括体重减轻，与肾功能相关的蛋白尿变化以及其他生物标志物，以指导尼莫单抗的未来发展。”。

'With the growth of GLP-1 agonists we are also seeing large pharmaceutical companies acquiring drugs with complementary mechanisms of action to treat obesity,' said Punit Dhillon, CEO and Chair of Skye. 'We see peripheral CB1 inhibition playing a strong role in future combination therapies and are advancing nimacimab as a key possible component of such combinations.'.

Skye首席执行官兼主席Punit Dhillon说：“随着GLP-1激动剂的增长，我们也看到大型制药公司正在收购具有互补作用机制的药物来治疗肥胖症。”我们看到外周CB1抑制在未来的联合治疗中发挥着重要作用，并且正在将尼莫单抗作为这种组合的关键可能组成部分。

About the Endocannabinoid System and Peripheral CB1 Inhibition for Weight Loss

关于内源性大麻素系统和外周CB1抑制减肥

The endocannabinoid system ('ECS') has emerged as one of the most relevant regulators of energy balance. The ECS acts through two cannabinoid receptors: types 1 and 2 (CB1 and CB2). CB1 is widely expressed in the CNS and brain but is also expressed in peripheral tissues such as adipose tissue, skeletal muscle, and in the liver, kidney, gut, and pancreas.

内源性大麻素系统（“ECS”）已成为能量平衡最相关的调节剂之一。EC通过两种大麻素受体起作用：1型和2型（CB1和CB2）。CB1在中枢神经系统和大脑中广泛表达，但也在脂肪组织，骨骼肌等外周组织以及肝脏，肾脏，肠道和胰腺中表达。

In obese states, CB1 agonists such as anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG), the body's naturally-produced endocannabinoids, are increased and may exert unfavorable effects on insulin-sensitive tissues. Peripheral inhibition of CB1 has been shown to cause a reduction in food intake and sustained weight loss through multiple mechanisms, including increasing incretin expression in the gut and reducing ghrelin expression.

在肥胖状态下，CB1激动剂如anandamide（AEA）和2-花生四烯酸甘油（2-AG）（人体天然产生的内源性大麻素）会增加，并可能对胰岛素敏感组织产生不利影响。已显示CB1的外周抑制通过多种机制导致食物摄入减少和持续体重减轻，包括增加肠道中的肠促胰岛素表达和减少生长素释放肽表达。

The ECS also contributes to the control of lipid and glucose metabolism, and it is well established that blockade of CB1 receptors enhances insulin sensitivity in both humans and rodents..

ECS还有助于控制脂质和葡萄糖代谢，并且众所周知，阻断CB1受体可增强人和啮齿动物的胰岛素敏感性。。

Clinically, early development of small molecule drugs that blocked CB1 appeared encouraging with the approval of rimonabant (Sanofi) in Europe for weight loss and obesity. However, it was soon removed from the market because of side effects related to the high exposure of the drug to the CNS and brain, which resulted in safety issues such as depression, anxiety and suicidal ideation.

临床上，随着利莫那班（赛诺菲）在欧洲获得减肥和肥胖的批准，阻断CB1的小分子药物的早期开发似乎令人鼓舞。然而，由于该药物与中枢神经系统和大脑的高暴露有关的副作用，它很快被从市场上删除，这导致了抑郁，焦虑和自杀念头等安全问题。

A new class of drugs are now designed to only target CB1 in the periphery, while avoiding the CNS..

现在设计了一类新的药物，只针对外围的CB1，同时避免中枢神经系统。。

About Nimacimab

关于尼莫昔单抗

Nimacimab is a first-in-class humanized monoclonal antibody that acts as a negative allosteric modulator to inhibit CB1 signaling in the periphery. Inhibition of CB1 has shown anti-fibrotic, anti-inflammatory, and metabolic mechanisms of action with potential to address a broad range of diseases with notable unmet medical needs such as obesity, chronic kidney disease, and non-alcoholic steatohepatitis (NASH)..

尼莫单抗是一流的人源化单克隆抗体，可作为负变构调节剂抑制外周CB1信号传导。CB1的抑制已显示出抗纤维化，抗炎和代谢的作用机制，有可能解决广泛的疾病，这些疾病具有明显未满足的医疗需求，例如肥胖，慢性肾病和非酒精性脂肪性肝炎（NASH）。。

Preclinical studies over 26 weeks showed that nimacimab has very limited accumulation in the brain.

超过26周的临床前研究表明，尼莫单抗在大脑中的积累非常有限。

The safety and tolerability assessments from the completed Phase 1b study of nimacimab in non-alcoholic fatty liver disease ('NAFLD') patients with diabetes or prediabetes demonstrated no serious adverse events, no early terminations of treatment due to adverse events, and no adverse events of concern occurring in a dose-dependent manner.

尼莫单抗在糖尿病或糖尿病前期非酒精性脂肪肝病（NAFLD）患者中完成的1b期研究的安全性和耐受性评估显示，没有严重的不良事件，没有因不良事件而提前终止治疗，也没有以剂量依赖的方式发生不良事件。

The most frequently reported treatment-emergent adverse events (>5% of subjects) in the pooled nimacimab and placebo groups were diarrhea, headache, dizziness (9.5 vs. 5.0%), upper respiratory tract infection, nausea and vomiting. Encouraging trends were observed in exploratory biomarkers of cholesterol, liver enzymes and liver function in patients receiving nimacimab versus placebo after the three-week dosing period..

尼莫单抗和安慰剂组中最常报告的治疗紧急不良事件（>5%的受试者）是腹泻，头痛，头晕（9.5比5.0%），上呼吸道感染，恶心和呕吐。在三周给药期后，接受尼莫单抗与安慰剂治疗的患者的胆固醇，肝酶和肝功能的探索性生物标志物出现了令人鼓舞的趋势。。

The promising PK data of approximately 21 days from the Phase 1 study suggests that nimacimab can be dosed once-a-month subcutaneously, which would potentially offer a competitive advantage over once-a-week subcutaneous dosing of current peptidic GLP-1 receptor agonists or even orally dosed GLP-1 receptor agonists due to their less desirable tolerability profile..

第一阶段研究大约21天的有希望的PK数据表明，尼莫单抗可以每月皮下给药一次，这可能比目前每周皮下给药一次的肽GLP-1受体激动剂甚至口服GLP-1受体激动剂具有竞争优势，因为它们的耐受性较差。。

About Skye Bioscience

关于Skye Bioscience

Skye is focused on unlocking the pharmaceutical potential of the endocannabinoid system to treat diseases with inflammatory, fibrotic, and metabolic processes. Backed by leading life science venture investors, Skye's strategy leverages biologic targets with substantial human proof of mechanism for the development of first-in-class therapeutics with significant clinical and commercial differentiation.

Skye专注于释放内源性大麻素系统治疗炎症，纤维化和代谢过程疾病的药物潜力。在领先的生命科学风险投资者的支持下，Skye的战略利用具有大量人类证据机制的生物靶标，开发具有显着临床和商业差异的一流疗法。

Nimacimab, a negative allosteric modulating antibody that inhibits peripheral CB1, showed a favorable safety and tolerability profile in a Phase 1 study. Skye plans to start a Phase 2 study in obesity and chronic kidney disease for nimacimab in mid-2024. SBI-100 Ophthalmic Emulsion, a CB1 agonist, is currently being studied in a Phase 2 study of patients with glaucoma and ocular hypertension.

尼莫单抗是一种抑制外周CB1的负变构调节抗体，在1期研究中显示出良好的安全性和耐受性。Skye计划在2024年年中开始一项针对尼莫单抗的肥胖和慢性肾脏疾病的2期研究。SBI-100眼用乳剂是一种CB1激动剂，目前正在青光眼和高眼压患者的2期研究中进行研究。

For more information, please visit: https://www.skyebioscience.com..

有关更多信息，请访问：https://www.skyebioscience.com..

CONTACT

联系人

Investor Relations

投资者关系

ir@skyebioscience.com

ir@skyebioscience.com

(858) 410-0266

(858) 410-0266

LifeSci Advisors, Mike Moyer

LifeSci顾问，Mike Moyer

mmoyer@lifesciadvisors.com

mmoyer@lifesciadvisors.com

617-308-4306

617-308-4306

FORWARD-LOOKING STATEMENTS

前瞻性声明

This press release contains forward-looking statements, including statements regarding our product development, business strategy, timing of clinical trials and commercialization of cannabinoid-derived therapeutics. Such statements and other statements in this press release that are not descriptions of historical facts are forward-looking statements that are based on management's current expectations and assumptions and are subject to risks and uncertainties.

本新闻稿包含前瞻性声明，包括关于我们的产品开发，业务战略，临床试验时间和大麻素衍生疗法商业化的声明。本新闻稿中不属于历史事实描述的此类声明和其他声明是基于管理层当前预期和假设的前瞻性声明，具有风险和不确定性。

If such risks or uncertainties materialize or such assumptions prove incorrect, our business, operating results, financial condition, and stock price could be materially negatively affected. In some cases, forward-looking statements can be identified by terminology including 'anticipated,' 'plans,' 'goal,' 'focus,' 'aims,' 'intends,' 'believes,' 'can,' 'could,' 'challenge,' 'predictable,' 'will,' 'would,' 'may' or the negative of these terms or other comparable terminology.

如果出现此类风险或不确定性或此类假设不正确，我们的业务、经营成果、财务状况和股价可能会受到重大负面影响。在某些情况下，前瞻性陈述可以通过术语来识别，包括“预期”，“计划”，“目标”，“重点”，“目标”，“意图”，“信念”，“可以”，“可能”，“挑战”，“可预测”，“意志”，“将会”，“可能”或这些术语或其他类似术语的负面影响。

We operate in a rapidly changing environment and new risks emerge from time to time. As a result, it is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements the Company may make.

我们在快速变化的环境中运营，新的风险不时出现。因此，我们的管理层不可能预测所有风险，也不可能评估所有因素对我们业务的影响，也不可能评估任何因素或因素组合可能导致实际结果与公司可能做出的任何前瞻性声明中所包含的结果产生重大差异的程度。

Risks and uncertainties that may cause actual results to differ materially include, among others, our capital resources, uncertainty regarding the results of future testing and development efforts and other risks that are described in the Risk Factors section of Skye's most recent annual or quarterly report filed with the Securities and Exchange Commission.

可能导致实际结果产生重大差异的风险和不确定性包括我们的资本资源、未来测试和开发工作结果的不确定性以及Skye提交给证券交易委员会的最新年度或季度报告中风险因素部分描述的其他风险。

Except as expressly required by law, Skye disclaims any intent or obligation to update these f.

除非法律明确要求，否则Skye不承担更新这些f的任何意图或义务。

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/193647

要查看此新闻稿的源版本，请访问https://www.newsfilecorp.com/release/193647