OPL-0401 / Sanofi, Valo Health - LARVOL DELTA

Drug Development. (PubMed, Alzheimers Dement) - "Out of the 63 compounds, the top 17 showed promising potency and selectivity for 4 to 19 kinases. The strong performance and selective nature of these compounds make them potential candidates for treating Alzheimer's disease by reducing its symptoms with fewer side effects."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • AMPK • CHEK1 • MAP2K1 • MAP2K2 • MAPK8 • MAPKAPK2 • RHOA

Oral therapies for diabetic retinopathy: Addressing an unmet need or a distant prospect? (PubMed, J Int Med Res) - "We appraised the following key therapeutic oral classes: (a) peroxisome proliferator-activated receptor alpha agonists (fenofibrate), which consistently demonstrate prevention-of-worsening signals; (b) protein kinase C beta inhibitors (ruboxistaurin), showing mixed efficacy but reduced vision-threatening outcomes in specific subsets; (c) redox transcription modulators (APX3330/Ref-1), exhibiting binocular prevention-of-worsening signals; (d) vascular adhesion protein-1/ amine oxidase copper-3 inhibitors, with variable phase-2 results; and (e) rho kinase inhibitors (OPL-0401), which have shown neutral primary endpoints to date. Finally, we outlined current gaps-such as limited phase-3 data beyond fenofibrate, endpoint heterogeneity, and the need for robust prevention trials-and proposed a concise research agenda. As a narrative synthesis, this review emphasizes clinical interpretation rather than quantitative meta-analytic estimation."

Journal • Diabetic Retinopathy • Retinal Disorders • AOC3 • PPARA • PRKCB • PRKCH

EXPLORING ROCK1 INHIBITION IN SILICO: IMPLICATIONS FOR ISCHEMIC STROKE TREATMENT OPTIMIZATION (WSC 2024) - "Three-dimensional structures of eight ligands/inhibitors (fasudil, dimethyl-fasudil, ripasudil, hydroxy-fasudil, FSD-C10, SNJ-1656, SAR407899, and Y27632) were generated using Marvinsketch and converted to PDB format. Conclusions Inhibitors with high binding affinity could hinder substrate entry to the ROCK1 active site, decreasing its activity. Assessing the selectivity of ROCK inhibitors (in silico) towards ROCK1 may serve as a predictive tool for evaluating therapeutic efficacy and potential adverse effects before conducting in vitro studies."

Cardiovascular • CNS Disorders • Ischemic stroke • Vascular Neurology • ROCK1

Phase 2 Spectra Study to Evaluate the Safety and Efficacy of OPL-0401 in Patients With Diabetic Retinopathy (clinicaltrials.gov) - P2 | N=114 | Active, not recruiting | Sponsor: Valo Health, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetic Retinopathy • Retinal Disorders

Phase 2 Spectra Study to Evaluate the Safety and Efficacy of OPL-0401 in Patients With Diabetic Retinopathy (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Valo Health, Inc. | N=66 ➔ 90

Enrollment change • Diabetic Retinopathy • Retinal Disorders

Phase 2 Spectra Study to Evaluate the Safety and Efficacy of OPL-0401 in Patients With Diabetic Retinopathy (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Valo Health, Inc. | N=120 ➔ 66 | Trial completion date: Mar 2024 ➔ Aug 2024 | Trial primary completion date: Feb 2024 ➔ Jul 2024

Enrollment change • Trial completion date • Trial primary completion date • Diabetic Retinopathy • Retinal Disorders

Spectra: Phase 2 Study to Evaluate the Safety and Efficacy of OPL-0401 in Patients With Non-proliferative Diabetic Retinopathy (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Valo Health, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetic Retinopathy • Retinal Disorders

Epoxyeicosatrienoic Acid and Prostanoid Crosstalk at the Receptor and Intracellular Signaling Levels to Maintain Vascular Tone. (PubMed, Int J Mol Sci) - "We set out to determine the contribution of endothelial CYP450 to murine vascular function using isolated aortic ring preparations from tamoxifen-inducible endothelial cell-specific POR knockout mice (ecPOR). The deletion of POR affected the expression of genes in this pathway and the inhibition of Rho-GTPase with SAR407899 decreased sensitivity to U46619. These data suggest that EET and prostanoid crosstalk at the receptor level and that lack of EET production sensitizes vessels to vasoconstriction via the induction of the Rho kinase system."

Journal • RHOA

Tumor Necrosis Factor Alpha (TNF- &[alpha]) and Rho-kinase 2 (ROCK2) Inhibitors Improve Erectile Function in a Bilateral Cavernous Nerve Injury Rat Model (AUA 2022) - "The current study was designed to investigate selective inhibition of ROCK2 (SAR407899) and TNF- a (Infliximab) in a pre-clinical model of post-radical prostatectomy ED to prevent penile neuroinflammation, fibrosis, and preserve penile hemodynamics. Despite histologic findings that suggest synergistic benefit from combination therapy, erectile parameters did not. Our immune infiltrate data also showed disparate finding with combination treatment compared to single agents alone which may allude to conflicting mechanisms of action"

Preclinical • Erectile Dysfunction • Fibrosis • Immunology • Inflammation • Oncology • Pain • ITGAM • PTPRC • TNFA

Spectra: Phase 2 Study to Evaluate the Safety and Efficacy of OPL-0401 in Patients With Non-proliferative Diabetic Retinopathy (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Valo Health, Inc.

New P2 trial • Diabetic Retinopathy • Retinal Disorders

Sanofi delivers solid 2012 results despite patent expirations (Sanofi Press Release) - "One project in Phase I (SAR407899 in diabetic nephropathy) has been discontinued."

Discontinued • Renal Disease