FX-5A / KineMed - LARVOL DELTA

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Cardiovascular

Acylated Toll-like Receptor (TLR) agonists enhance platelet procoagulant phenotype via CD36 (ISTH 2025) - "The time to half of maximum fibrin generation was also significantly delayed for platelets in the presence of Fx-5A when stimulated with TLR2 but not PAR4 agonist. Similarly, Fx-5A pretreatment decreased TLR2- but not PAR4-driven platelet-neutrophil interactions."

Cardiovascular • Hematological Disorders • Inflammation • Thrombosis • ANXA5 • CD36 • SCARB1 • TLR2

Generation of human induced pluripotent stem cell (hiPSC) lines (UKMi009-A and UKMi011-A) harboring a homozygous and heterozygous HCN4 variant from a family with inherited sinus node dysfunction (SND). (PubMed, Stem Cell Res) - "Generated hiPSCs enable further cardiomyocyte cell differentiation to provide unique patient-derived SND in-vitro disease models in a gene-dose dependent manner. Both cell lines exhibited normal karyotype, cell morphology, hiPSC marker expression, and differentiation into all three germ layers, confirmed by immunofluorescence staining."

Journal

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Jun 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Cardiovascular

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Cardiovascular

Red Blood Cell Membrane Cholesterol May Be a Key Regulator of Sickle Cell Disease Microvascular Complications. (PubMed, Membranes (Basel)) - "We showed that incubation of RBC from SCD patients with human HDL or the HDL-mimetic peptide Fx5A improves the impaired RBC deformability and decreases intracellular reactive oxygen species levels. We propose that the main physiological role of HDL is to regulate the cholesterol/phospholipid ratio (C/PL), which is fundamental to the transport of oxygen and its delivery to peripheral tissues."

Journal • Review • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Sickle Cell Disease • Type 2 Diabetes Mellitus

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers (clinicaltrials.gov) - P1; N=64; Recruiting; Sponsor: National Heart, Lung, and Blood Institute (NHLBI); Trial completion date: Jun 2022 ➔ Jun 2023; Trial primary completion date: Jun 2022 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • Cardiovascular

"#سروات @Hlashuel @hlmmy3 @_AskJeddah_ @Barjasbh @Salary_Date @MohammedAladrei @FaresALhemyary @SAlghobari @a_shmeri @hasanikm2011" (@halabdli1)

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers (clinicaltrials.gov) - P1; N=64; Recruiting; Sponsor: National Heart, Lung, and Blood Institute (NHLBI); Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cardiovascular

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers (clinicaltrials.gov) - P1; N=64; Not yet recruiting; Sponsor: National Heart, Lung, and Blood Institute (NHLBI); Trial completion date: Dec 2020 ➔ Jun 2022; Trial primary completion date: Dec 2020 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Cardiovascular

Pre-clinical evaluation of KM-011 for the treatment of atherosclerosis (KineMed) - Pre-clinical evaluation of KM-011 for the treatment of atherosclerosis

Preclinical • Dyslipidemia

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers (clinicaltrials.gov) - P1; N=64; Not yet recruiting; Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Clinical • New P1 trial

Anti-drug Antibodies Against a Novel Humanized Anti-CD20 Antibody Impair Its Therapeutic Effect on Primary Biliary Cholangitis in Human CD20- and FcγR-Expressing Mice. (PubMed, Front Immunol) - "Beginning at 4-6 weeks of age, equivalent to stage I/II human PBC, female mice were given weekly injections of an anti-hCD20 antibody (TKM-011) or vehicle control, and monitored for liver histology as well as a broad panel of immunological readouts...In mice that developed ADAs, clinical improvements were less pronounced. Sustained treatment with B cell-targeted therapies may broadly inhibit effector pathways in PBC, but may need to be administered early in the natural history of PBC."

Journal • Preclinical

Intravenous toxicity and toxicokinetics of an HDL mimetic, Fx-5A peptide complex, in cynomolgus monkeys. (PubMed, Regul Toxicol Pharmacol) - "Finally, Fx-5A exhibited sporadic non-appreciable detection of anti-Fx-5A antibodies and a dose-dependent linear toxicokinetics with T value ranges from 2.7 to 6.2 h. In conclusion, the No Observed Adverse Effect Level was considered to be 75 mg/kg/day with associated exposures average C and AUC of 453 μg/mL and 2232 h μg/mL, respectively, on Day 27."

Journal