CPL’280 / Celon Pharma - LARVOL DELTA

Discovery of potent free fatty acid receptor 1 full agonists with a novel scaffold bearing conjugated double bond linker. (PubMed, Bioorg Med Chem) - "Based on patent research, we combined the highly compatible linker with CPL207280, a GPR40 partial agonist that metabolized mainly through oxidation, to design a potent GPR40 full agonist with a novel scaffold. We explored the linker, tail and acid head and finally found compound H1-2 with excellent glucose-lowering ability."

Journal • Diabetes • Genetic Disorders • Hypoglycemia • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Recent Developments in Drug Design of Oral Synthetic Free Fatty Acid Receptor 1 Agonists. (PubMed, Drug Des Devel Ther) - "Over the past two decades, synthetic FFAR1 agonists such as TAK-875 and TSL1806 have undergone meticulous design and extensive clinical trials...Recent studies have concentrated on developing low-molecular-weight compounds that more closely resemble natural products, with CPL207280 showing promising potential and liver safety, currently in Phase II clinical trials. Moreover, ongoing research continues to explore the potential applications of FFAR1 agonists in diabetes management, as well as in conditions such as non-alcoholic fatty liver disease (NAFLD) and cerebrovascular diseases. Utilizing advanced technologies such as artificial intelligence and computer-aided design, the development of compact molecules that mimic natural structures represents a hopeful direction for future research and development."

Journal • Review • CNS Disorders • Diabetes • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Vascular Neurology

First-in-human study of CPL207280, a novel G-protein-coupled receptor 40/free fatty acid receptor 1 agonist, in healthy volunteers after single and multiple administration. (PubMed, Diabetes Obes Metab) - "CPL207280 was found to be safe and well tolerated by healthy volunteers (with a low risk of hepatotoxicity) for up to 14 days of administration. The PK profile of CPL207280 supports single-daily administration and justifies further development of this therapy for patients with T2D."

Journal • P1 data • Diabetes • Hepatology • Metabolic Disorders • Type 2 Diabetes Mellitus

Preclinical efficacy of the novel GPR40 agonist CPL207-280 in neuropathy (EASD 2023) - "Postdrug values were obtained at 30 min, 2 h, 7 h, 12 h, and 24 h and compared to pregabalin...This antiallodynic effect of CPL207280-51 was separated from its metformin content. Mechanistically, the antiallodynic effect of CPL207280-51 was lowered by pretreatment with Rimonabant (CB1 receptor antagonist) (p < 0.01) and Naltrexone (μ-opioid receptor antagonist) (p < 0.001)... CPL207280-51 displays potent anti-allodynic activity in models of neuropathy involving the action of CB1 and opioid receptors without producing addiction."

Preclinical • Diabetes • Metabolic Disorders

Efficacy, Safety and Pharmacokinetics Study of CPL207280 After 2-weeks Administration in Subjects With Type 2 Diabetes (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Nov 2022 ➔ Jun 2023 | Trial primary completion date: Sep 2022 ➔ Jun 2023

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy, Safety and Pharmacokinetics Study of CPL207280 After 2-weeks Administration in Subjects With Type 2 Diabetes (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Celon Pharma SA

New P2 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

[VIRTUAL] Safety and pharmacokinetic study of CPL207280, a novel GPR40 receptor agonist, after a multiple-dose in healthy volunteers (EASD 2021) - P1 | "First in class developed and evaluated in clinical trials GPR40 agonist - fasiglifam, was great hope for diabetic society - both patients and clinicians - as it might have offered a new modality for the treatment of diabetes. The administration of CPL207280 for 14 days was safe and well-tolerated. The pharmacokinetic profile of CPL207280 confirms findings from the single administration study in healthy volunteers, supports once-daily administration and justify further development of the therapy for patients suffering from T2D."

Clinical • PK/PD data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Evaluation of the hepatotoxicity of the novel GPR40 (FFAR1) agonist CPL207280 in the rat and monkey. (PubMed, PLoS One) - "The most advanced GPR40 agonist TAK-875 exhibited satisfactory glucose-lowering effects in phase II and III studies. The study presents promising data on the feasibility of creating a liver-safe GPR40 agonist. Additionally, it can be concluded that DILI is not a hallmark of GPR40 agonists; it is linked to the intrinsic properties of an individual agonist."

Journal • Preclinical • Diabetes • Hepatology • Liver Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

Discovery and development of CPL207280 as new GPR40/FFA1 agonist. (PubMed, Eur J Med Chem) - "The most advanced clinical candidate, TAK-875, was withdrawn from phase III clinical trials due to liver safety issues. The introduction of small, nature-inspired acyclic structural fragments resulted in compounds with retained high potency and a satisfactory pharmacokinetic profile. Optimized synthesis and upscaling provided a stable, solid form of CPL207280-51 (45) with the properties required for the toxicology studies and ongoing clinical trials."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Safety and Pharmacokinetics Study of CPL207280 Compound in Healthy Volunteers. (clinicaltrials.gov) - P1; N=68; Completed; Sponsor: Celon Pharma SA; Active, not recruiting ➔ Completed

Trial completion

CPL207280 - a novel GPR40/FFA1-specific agonist shows a favorable safety profile and exerts anti-diabetic effects in type 2 diabetic animals. (PubMed, Mol Pharmacol) - "However, the most clinically advanced GPR40 agonist - TAK-875 (fasiglifam) - was withdrawn from phase III due to its hepatotoxicity resulting from the inhibition of pivotal bile acid transporters. This study is the first to show the safety and effects of CPL207280, a novel GPR40/FFA1 agonist, on glucose homeostasis both in vitro and in vivo in different diabetic animal models. Therefore, we propose the CPL207280 compound as a novel, glucose-lowering agent, overcoming T2D patients' unmet medical needs."

Journal • Diabetes • Hepatology • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

[VIRTUAL] Safety and Pharmacokinetic Study of GPR40 Agonist (CPL207280) after a Single Dose in Healthy Subjects (ADA 2021) - "Pharmacokinetics of CPL207280 supports once daily dosing regimen. The results justify further clinical development."

Clinical • PK/PD data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Safety and Pharmacokinetics Study of CPL207280 Compound in Healthy Volunteers. (clinicaltrials.gov) - P1; N=68; Active, not recruiting; Sponsor: Celon Pharma SA; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Celon Pharma Announces CPL’280, Second Generation Oral GPR40 Agonist, Meets Primary Endpoint in Phase 1 Trial (GlobeNewswire) - P1; N=NA; "Celon Pharma S.A. today announced the successful completion of a Phase 1 trial of its second generation GPR40 agonist, CPL’280. This agent is in development for the treatment of Diabetes and Diabetic Neuropathy and met its primary endpoint, with no adverse safety signals detected....'We are very pleased with the results from this Phase 1 trial, demonstrating that CPL’280 is safe and well tolerated...'Celon Pharma plans to initiate Phase 2 proof-of-concept studies with CPL’280 in Type 2 Diabetes and Diabetic Neuropathy in the coming months and has submitted data on CPL’280 for publication.'"

New P2 trial • P1 data • P2 data • Trial completion • CNS Disorders • Diabetes • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain