nimacimab (RYI-018) / Skye Biosci - LARVOL DELTA

Demonstrating the sufficiency of peripheral CB1 inhibition to promote weight loss using clinical pharmacokinetic (PK) and pharmacodynamic (PD) models (ECO 2025) - " We compared clinical PK profiles of rimonabant, monlunabant, and nimacimab using PK/PD modeling to analyze their target engagement and distribution in the brain and periphery. Our findings suggest that peripheral CB1 inhibition, rather than central CB1 inhibition, is sufficient to drive weight loss, minimizing the potential for neuropsychiatric AEs associated with central CB1 inhibition. This work supports further development of novel mAb-based CB1 inhibitors with superior peripheral restriction to promote weight loss with reduced centrally mediated neuropsychiatric effects which continues to be a hurdle for the less restricted small molecule inhibitors. Conflict of Interest: The author is a consultant for Skye Bioscience, a biopharmaceutical company developing therapies for obesity and metabolic diseases."

Clinical • PK/PD data • Genetic Disorders • Metabolic Disorders • Obesity • Psychiatry

Arecor partners with Skye Bioscience to improve formulation of obesity drug (Proactiveinvestors) - "Arecor Therapeutics PLC...has entered a development partnership with Skye Bioscience Inc...to create a more concentrated formulation of an experimental obesity treatment, as drugmakers vie for a share of the fast-growing weight-loss market...The Cambridge-based company will use its proprietary Arestat technology to reformulate nimacimab, a monoclonal antibody developed by Skye that targets the CB1 receptor...Under the agreement, Skye will cover the cost of the development work. It will also have the option to license the rights to the new formulation and associated intellectual property for further development and commercial use."

Licensing / partnership • Obesity

Nimacimab, a Peripherally Restricted CB1 Inhibitor, Promotes Metabolic Homeostasis in a Diet-Induced Obesity (DIO) Mouse Model as Demonstrated by Weight Loss, Restored Hormonal Regulation, and Reduced Inflammatory Biomarkers (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Preclinical • Metabolic Disorders • Obesity

Skye Bioscience Clinical Model Demonstrating Necessity of Peripheral CB1 Inhibition for Weight Loss Presented at European Congress on Obesity (Skye Bioscience Press Release) - "Skye Bioscience, Inc...presented a clinical pharmacokinetic ('PK') and pharmacodynamic ('PD') model that underscores the fundamental relationship between biodistribution and efficacy of CB1 inhibitors...Published clinical PK and potency data coupled with Phase 2 ('P2') and Phase 3 efficacy data from Novo Nordisk’s monlunabant and Sanofi’s rimonabant, respectively, as well as Phase 1 data from nimacimab were used to develop a model to determine whether peripheral CB1 inhibition alone is sufficient for weight loss, or if central inhibition is also required for optimal efficacy. The results showed that central inhibition of CB1 alone was not sufficient for weight loss with P2 data for monlunabant, and demonstrated that increasing drug levels in the brain did not improve efficacy."

Clinical data • PK/PD data • Obesity

Skye Bioscience Reports First Quarter 2025 Results and Highlights Nimacimab Differentiation in Obesity (GlobeNewswire) - "Nimacimab in combination with tirzepatide improves weight loss effect over tirzepatide alone, and shows comparable weight loss to monlunabant and tirzepatide alone in preclinical diet-induced obesity model. Expanded preclinical study data to be presented at ADA in June 2025....Research and development (R&D) expenses for the three months ended March 31, 2025, were $7.2 million, as compared to $1.9 million for the same period in 2024. The increase was primarily due to contract manufacturing and clinical trial costs associated with our Phase 2a clinical study for nimacimab, salaries and stock based compensation, consulting and depreciation expense."

Commercial • Preclinical • Obesity

Skye Bioscience Demonstrates Over 30% Weight Loss with Nimacimab and Tirzepatide Combination in Preclinical Model (GlobeNewswire) - "Skye Bioscience, Inc...announced new preclinical data for its novel CB1 antibody, nimacimab. In a murine diet-induced obesity (DIO) model, after 25 days of treatment, results demonstrated: Greater than 30% weight loss when nimacimab was combined with the dual GLP-1/GIP agonist, tirzepatide; Nimacimab alone demonstrated 23.5% weight loss, comparable to monlunabant and tirzepatide alone."

Preclinical • Obesity

Skye Bioscience Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Enrollment completed in Phase 2a CBeyond trial of CB1 inhibitor, nimacimab, in obesity and overweight. Faster-than-expected enrollment enables full top-line Phase 2a data in late Q3/early Q4 2025, ahead of schedule; interim analysis removed. Phase 2a dosing extended to 52 weeks to enhance long-term safety, tolerability, and efficacy data....Two independent data safety monitoring board reviews have been successfully completed. 16 US Clinical Sites: Welcomed a leading academic center of excellence in obesity as a clinical trial site during Q1 2025....Upcoming Milestones: Q2 2025: Nimacimab preclinical data being presented at scientific/medical conferences."

DSMB • P2a data • Preclinical • Trial status • Obesity

CBeyond: Study to Evaluate the Effect on Obesity of Once Weekly Nimacimab Injection and Once Weekly Nimacimab Injection Co-administered With Semaglutide Injection Versus Placebo (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Skye Bioscience, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

CBeyond: Study to Evaluate the Effect on Obesity of Once Weekly Nimacimab Injection and Once Weekly Nimacimab Injection Co-administered With Semaglutide Injection Versus Placebo (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Skye Bioscience, Inc.

New P2 trial • Genetic Disorders • Obesity

Bird Rock Bio files IND application for phase 2 study of nimacimab for treatment of renal diseases (PRNewswire) - "Bird Rock Bio, Inc....announced today that the Company has filed an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) for the initiation of a phase 2 clinical study of nimacimab, also known as RYI-018, in patients with one of the following renal diseases: diabetic kidney disease, focal segmental glomerulosclerosis (FSGS), or immunoglobulin A (IgA) nephropathy."

IND • Focal Segmental Glomerulosclerosis

Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Exploratory Efficacy of Nimacimab in Patients With Diabetic Gastroparesis (clinicaltrials.gov) - P2; N=6; Active, not recruiting; Sponsor: Bird Rock Bio, Inc.; Recruiting ➔ Active, not recruiting; N=14 ➔ 6; Trial completion date: Dec 2019 ➔ Apr 2020

Clinical • Enrollment change • Enrollment closed • Trial completion date

Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Exploratory Efficacy of Nimacimab in Patients With Diabetic Gastroparesis (clinicaltrials.gov) - P2; N=14; Recruiting; Sponsor: Bird Rock Bio, Inc.; Not yet recruiting ➔ Recruiting; Initiation date: May 2019 ➔ Aug 2019

Clinical • Enrollment open • Trial initiation date

Safety Tolerability, and PK of RYI-018 After Repeat Dosing in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD) (clinicaltrials.gov) - P1; N=84; Completed; Sponsor: Bird Rock Bio, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion