ROC-101 / Sanofi, AllRock Bio - LARVOL DELTA

Results from a phase 1, randomized, double-blind, single and multiple ascending oral dose study characterizing the PK, safety, and target engagement of the Rho kinase 1 and 2 inhibitor ROC-101 in healthy volunteers (PHA 2026) - "The ROCK1&2 inhibitor fasudil has been approved for >30 years in Japan and China for the treatment of cerebral vasospasm and has been evaluated in several studies for the treatment of PH and PAH. Compared with fasudil, exposure of free ROC-101 was observed to be up to 25-fold higher. Together, these data support initiation of a phase 2, proof-of-concept study in patients who have PAH or PH due to interstitial lung disease."

Clinical • First-in-human • P1 data • Cardiovascular • Constipation • Gastroenterology • Gastrointestinal Disorder • Hypotension • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • IL17A

Phase 2a (ROCSTAR) Clinical Trial Design Evaluating ROC-101, a Novel, Pan-ROCK Inhibitor with Disease Modifying Potential in PAH and ILD-PH Patients (ISHLT 2026) - P2 | "The Phase 2a trial will evaluate ROC-101 in combination with standard-of-care (SOC) therapy in PAH and ILD-PH patients.Methods The Phase 2a ROCSTAR clinical trial (NCT07175038) is a 24-week study enrolling approximately 40 adults across three patient cohorts all on SOC: PAH not receiving sotatercept (n=15), PAH receiving stable sotatercept (n=15) and ILD-PH (n=10). Participants will receive once-daily oral ROC-101 during the open label treatment period, with an optional long-term extension.Endpoints The primary endpoints include the change in pulmonary vascular resistance (PVR) assessed via right heart catheterization (RHC) from baseline versus at Week 24 and the number of participants who experienced an adverse event (AE). Secondary endpoints include:-Change in 6-minute Walk Distance (6MWD) from baseline versus at Week 24-Change in NT-proBNP from baseline versus at Week 24-Percentage of participants who improve World Health Organization Functional Classification..."

Clinical • Late-breaking abstract • P2a data • Cardiovascular • Fibrosis • Hypotension • Interstitial Lung Disease • Pulmonary Arterial Hypertension

AllRock Bio Doses First Patients in Phase 2a Trial of ROC-101 for Pulmonary Hypertension (PRNewswire) - "As part of the ROCSTAR trial, NCT07175038, up to 30 PAH and 10 ILD-PH patients, World Health Organization (WHO) functional class II and III, will receive ROC-101 in combination with standard of care therapy."

Trial status • Interstitial Lung Disease • Pulmonary Arterial Hypertension

Pharmacological Profile and Therapeutic Evaluation of ROC-101, a Potent and Selective ROCK Inhibitor, in Arterial Hypertension and Pulmonary Fibrosis. (PubMed, Pharmacol Res) - "Herein, we present a novel selective inhibitor of ROCK1 and ROCK2 (pan-ROCK), ROC-101 (previously known as KD045), and demonstrate its activity as an antifibrotic agent. ROC-101 was efficacious in three different rodent models of pulmonary parenchymal, vascular, and airway diseases: 1) ROC-101 treatment reduced airway hypersensitivity to methacholine in an ovalbumin-induced asthma model and had blood pressure-lowering effects consistent with the role of ROCK in smooth muscle contractility and confirming in vivo target engagement; 2) ROC-101 showed efficacy in attenuating pulmonary arterial hypertension in the semaxanib/hypoxia-induced disease model; and 3) in the bleomycin-induced lung fibrosis model, ROC-101 demonstrated disease-modifying activity in the fibrotic lung, lowering collagen deposition, improving histology, reducing immune cell infiltration, and decreasing ROCK target phosphorylation. These in vivo and functional assessments support the development of..."

Journal • Asthma • Cardiovascular • Fibrosis • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CTGF

Engineered cord blood megakaryocytes evade killing by allogeneic T-cells for refractory thrombocytopenia. (PubMed, Front Immunol) - "This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, resulting in liberation of increased numbers of functional platelets both in-vitro and in-vivo; (2) To evade HLA class I T-cell-driven killing of these expanded MKs, we employed CRISPR-Cas9-mediated β-2 microglobulin (β2M) gene knockout (KO)...Finally, β2M KO allowed MKs to evade killing by allogeneic T-cells. Overall, our approaches offer a novel, readily translatable roadmap for producing adult donor-independent platelet products for a variety of clinical indications."

Journal • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura • CD34