NRL-1049 / Neurelis, BioAxone - LARVOL DELTA

Rho-associated kinase inhibitors in cerebral cavernous malformations: a preclinical systematic review. (PubMed, Neurosurg Rev) - "The primary outcome was lesion burden, and the secondary outcomes included non-heme iron deposition and ROCK activity. Systematic searches identified 389 records, of which 4 studies were included, demonstrating that fasudil, a ROCK inhibitor, consistently reduced non-heme iron deposition and lesion burden in preclinical CCM models in mice...One study demonstrated that BA-1049 caused a dose-dependent reduction in non-heme iron deposition and lesion burden. Studies have shown that ROCK pathway modulation reduces non-heme iron deposition and lesion burden. Further clinical investigations involving patients with CCM are essential to verify whether these experimental benefits can be reproduced in clinical settings."

Journal • Preclinical • Review • MSH2 • PDCD10 • RHOA

Safety, Tolerability, and Pharmacokinetics of NRL-1049, a Rho-Associated Kinase Inhibitor, in Healthy Volunteers: A Phase 1, First-in-Human, Single-Ascending Dose, Randomized, Placebo-Controlled Trial. (PubMed, CNS Drugs) - "The maximum tolerated dose of 150 mg NRL-1049 was associated with a favorable safety profile in healthy adult volunteers. Exposure of NRL-1049 and its active metabolite, NRL-2017, increased in a dose proportional or greater-than-dose proportional manner. These results support continued investigation and development of NRL-1049."

Clinical • Journal • P1 data • PK/PD data • CNS Disorders • Epilepsy • Hematological Disorders • Pain

The novel ROCK2 selective inhibitor NRL-1049 preserves the blood-brain barrier after acute injury. (PubMed, J Cereb Blood Flow Metab) - "Hemorrhagic transformation was also reduced. We show that NRL-1049, a selective ROCK2 inhibitor, is a promising drug candidate to preserve the BBB after brain injury."

Journal • Cardiovascular • CNS Disorders • Epilepsy • Hematological Disorders • Ischemic stroke • Vascular Neurology

Role of Rho-Associated Kinase in the Pathophysiology of Cerebral Cavernous Malformations. (PubMed, Neurol Genet) - "ROCK represents a potential therapeutic target, and direct (fasudil, NRL-1049) and indirect (statins) ROCK inhibitors have demonstrated various levels of efficacy in reducing lesion burden in preclinical models of CCM. Current (atorvastatin) and planned (NRL-1049) clinical studies will determine the efficacy of ROCK inhibitors for CCM in humans, for which no US Food and Drug Administration-approved or EU-approved pharmacologic treatment exists."

Journal • Review • Cerebral Hemorrhage • Hematological Disorders • Inflammation • RHOA • SMURF1

Inhibition of Rho-associated Protein Kinase for Treatment of Cerebral Cavernous Malformations (AES 2022) - "Seizure is a common presenting symptom of CCM, and there is an unmet need for nonsurgical treatment options in patients with CCM. NRL-1049 is a selective ROCK2 inhibitor that has exhibited efficacy to reduce lesion burden in animal models of CCM, potentially through stabilization of the vascular endothelium. A clinical development program is being initiated to investigate further the potential of NRL-1049 as a treatment for CCM."

Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Epilepsy • MSH2 • TP53

Nrl-1049, a selective rho-associated protein kinase 2 inhibitor, preserves the blood brain barrier in models of cold injury and ischemic stroke (Neuroscience 2022) - "In summary, we show that NRL-1049, a ROCK2 inhibitor, attenuates BBB dysfunction in animal models of acute cerebral injury and stroke. Future studies are needed to explore the effectiveness and safety of NRL-1049 in humans for treatment of both acute (ischemic stroke, traumatic injury) and chronic (vascular lesions) conditions that involve disruption of normal BBB structure and function."

Cerebral Hemorrhage • CNS Disorders • Epilepsy • Vascular Neurology