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

Extension Study Fully Enrolled (GlobeNewswire) - "Data from the 26-week extension is expected in Q1 2026 and will provide information on the potential full treatment duration of 52 weeks followed by a 12-week follow-up period; In the combination arms, patients will continue with blinded treatment with nimacimab or placebo and will continue receiving semaglutide (Wegovy). Patients in the monotherapy arm will receive a higher dose of nimacimab (300 mg), which we expect will assist in refining our PK model."

P2 data • Trial status • Obesity

CBeyond™, A Phase 2 Trial for Weight Loss With a Peripherally Acting CB1 Receptor Antibody (OBESITY WEEK 2025) - "Nimacimab is a peripherally acting inhibitory anti-CB1 antibody that has been shown to cause meaningful weight loss compared to placebo in humanized DIO mice. It is not expected to cross the blood-brain barrier, which helps mitigate concerns about neuropsychiatric adverse events found with small molecule-based CB1 inhibitors. Phase 1 studies support excellent safety and tolerability."

P2 data • Diabetes • Genetic Disorders • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Psychiatry

Skye Bioscience Late-Breaking Oral Abstract at ObesityWeek 2025 to Highlight Improvement in Rebound Weight Gain (GlobeNewswire) - "The presentation will highlight recent topline data from CBeyond, a Phase 2 proof-of-concept study of nimacimab....New data from an analysis of participants 12 weeks post-treatment demonstrated that nimacimab 200 mg (subcutaneous, weekly) plus semaglutide blunted rebound weight gain compared to semaglutide alone (18.1% versus 49.8% weight regain over 12 weeks). Moreover, at 12 weeks post-treatment, the nimacimab plus semaglutide group maintained significant weight loss compared to the placebo group (p=0.006), while the semaglutide alone group lost significance over the placebo group (p=0.12)..."

Late-breaking abstract • P2a data • Obesity

Skye Bioscience Reports Topline CBeyond Phase 2a Data from Nimacimab Monotherapy and Combination Clinical Trial (GlobeNewswire) - "In CBeyond, the nimacimab monotherapy arm did not achieve the primary endpoint of weight loss compared to placebo (-1.52% vs. -0.26 for placebo, mITT1). Preliminary pharmacokinetic analysis showed an association between exposure and response, suggesting that the 200 mg, subcutaneous weekly dose was suboptimal as a monotherapy...In the combination cohort, nimacimab 200 mg (subcutaneous, weekly) plus semaglutide demonstrated a clinically meaningful magnitude of weight loss compared to semaglutide alone (-13.2% vs -10.25%, p=0.0372, mITT), with no plateau being observed through Week 26....The next set of detailed results from the 26-week treatment period of the CBeyond trial will be presented at ObesityWeek in November."

P2a data • Obesity

Skye Presents Phase 1b Data for its Peripheral CB1-inhibiting Antibody, Nimacimab, at European Association for the Study of Diabetes (EASD) Annual Meeting (GlobeNewswire) - "The study demonstrated that nimacimab was safe, well-tolerated, and exhibited predictable pharmacokinetics and low immunogenicity across multiple ascending dose cohorts. Importantly, there were no serious adverse events, no discontinuations due to adverse events, and no evidence of neuropsychiatric safety signals. Gastrointestinal side effects were infrequent and mild, underscoring the potential differentiated tolerability profile of this peripheral CB1-inhibiting antibody."

P1 data • Metabolic Dysfunction-Associated Steatotic Liver Disease

A multiple dose study to evaluate the safety and tolerability of nimacimab, a peripherally restricted, inhibitory CB1 antibody in subjects with metabolic associated fatty liver disease (EASD 2025) - P1 | "Nimacimab administered once weekly for 4 weeks at doses of 0.6, 1.2, and 2.5 mg/kg was well tolerated and demonstrated an overall favorable safety profile. Nimacimab does not cross the blood brain barrier, thus minimizing potential CNS-related side effects seen with small molecule CB1 inhibitors. Encouraging trends observed in markers of metabolism and tissue fibrosis warrant further clinical investigation of nimacimab for treatment of metabolic diseases."

Clinical • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Skye’s CB1 Inhibitor, Nimacimab, Demonstrates Superior Weight Loss and Differentiated Mechanisms from Monlunabant, and Continues to Show Enhanced Combination with Tirzepatide with Durable Post-Treatment Weight Maintenance in DIO Model (GlobeNewswire) - "Nimacimab + tirzepatide demonstrates over 40% weight loss in multiple preclinical DIO studies. Nimacimab demonstrates durable post-treatment weight loss compared to tirzepatide. Nimacimab reduced rebound weight gain following treatment with tirzepatide or nimacimab + tirzepatide....Top-line data from Phase 2 CBeyond study expected to be reported in late Q3/early Q4 2025."

P2 data • Preclinical • Obesity

Skye Completes 26-week Treatment Phase in Phase 2a CBeyond Study (GlobeNewswire) - "Skye expects to report topline data from the trial in late Q3/early Q4 of 2025...Skye has also completed enrollment of the 26-week extension of the Phase 2a trial that it announced in July 2025. This extension is designed to obtain data from 52 weeks of treatment using nimacimab as monotherapy or in combination with semaglutide (Wegovy), offering longer-term insight into weight loss driven by a peripheral CB1 inhibitor antibody...Skye expects to report data from the extension study in Q1 2026."

P2a data • Trial status • Obesity

Skye Bioscience to Host Virtual KOL Event and Provide Perspectives on Upcoming CBeyond Phase 2a Topline Clinical Data Readout (GlobeNewswire) - "Virtual KOL event will begin at 8:00 AM ET on Thursday, September 4, 2025."

P2a data • Obesity

Clinical Highlights: CBeyond Phase 2a Obesity Trial (GlobeNewswire) - "Phase 2a Study Update: Patients enrolled in the original Phase 2a study continue to receive active treatment and are progressing through scheduled follow-ups, supported by ongoing collaboration between the clinical team and study sites; Extension Study Enrolling: In July, the 26-week extension study began enrolling patients in both the combination and monotherapy arms and will potentially provide up to 52-week safety and efficacy data. We expect approximately 50% of patients from the original study will be eligible for enrollment....The independent Data Safety Monitoring Committee has completed four unblinded reviews with no concerns raised. The study continues per protocol."

DSMB • Trial status • Obesity

Research and Development Highlights (GlobeNewswire) - "New DIO Data Provides Further Evidence for 1) Potential Combination with Incretins; 2) Superior Post-treatment Durability of Weight Loss and 3) Weight Loss Maintenance Post-incretin Treatment; Combination efficacy: The preclinical DIO mouse study findings demonstrated that at day 25 the combination of nimacimab and a suboptimal tirzepatide dose (3nmol/kg daily) yielded 44% vehicle-adjusted weight loss (29.6% weight loss with an average of 30g mice)...In a comparison of nimacimab and tirzepatide following cessation of treatment in the preclinical DIO mouse model, nimacimab demonstrated superior durability of weight loss. Specifically, the low-dose tirzepatide group regained most of their original weight back 8 days after coming off therapy, regaining 29.7% of weight by day 24 post-treatment....when nimacimab was added following treatment with low-dose tirzepatide, nimacimab reduced rebound weight gain from 29.7% to 12.8%."

Preclinical • Obesity

Skye Bioscience Highlights Nimacimab’s Promise in Obesity Treatment, Anticipates Phase 2a Data (Yahoo Finance) - "On June 23, Skye Bioscience unveiled its 'Anatomy of Progress' nimacimab development update video series....The four-part 'Anatomy of Progress' video series highlights unmet needs in obesity treatment, the benefits of nimacimab as a peripheral CB1-receptor-targeting antibody for healthy weight loss, and its development progress. Nimacimab’s unique mechanism targets receptors in the periphery while being greater than 99% excluded from the brain. This peripheral restriction aims to deliver weight loss and metabolic benefits similar to first-gen CB1 inhibitors, but without the neuropsychiatric side effects that plagued earlier small-molecule counterparts....Interim data from the Phase 2a clinical trial are expected in late Q3 or early Q4 2025, after the initial patient cohort completes a 26-week treatment period."

P2a data • Preclinical • Obesity

Innovation Hub - Mechanistic Insights into Weight Loss and Metabolic Regulation of Obese Mice Treated with Nimacimab, a Peripherally Restricted CB1 Inhibitor (ADA 2025) - "This presentation will highlight recent preclinical data that underscores key mechanisms supporting the therapeutic potential of Skye's antibody-based peripherally restricted CB1 inhibitor, nimacimab, including in vitro systems and in vivo diet-induced obesity models, both alone and in combination with incretin-based drugs like tirzepatide. (*) Continuing Education Credit Is Not Awarded for this Session."

Preclinical • Metabolic Disorders • 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) - "Nimacimab restored metabolic homeostasis via peripheral CB1 inhibition in obese mice. Weight loss with improved body composition was observed. Hormone and inflammatory markers were restored to those of non-obese mice."

Preclinical • Metabolic Disorders • Obesity • CNR1

Skye Bioscience to Present Expanded Preclinical CB1 Antibody Data at the American Diabetes Association’s 85th Scientific Sessions (GlobeNewswire) - "Skye Bioscience, Inc...today announced that it was selected to present new nimacimab data in its expanded preclinical model at the upcoming American Diabetes Association’s (ADA) 85th Scientific Sessions. Skye will present in multiple forums at the ADA conference, which is being held June 20th – 23rd, 2025, at the McCormick Place Convention Center in Chicago, Illinois."

Preclinical • Obesity

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

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