ROCK1

MONTREAL, June 17, 2024 /PRNewswire/ - Raya Therapeutic Inc., ("Raya") a mission-driven company focused on the treatment of ALS and other neurodegenerative diseases, is pleased to announce supportive clinical data for its lead compound, fasudil (RT1968, in the treatment of Amyotrophic Lateral Sclerosis (ALS)), as disclosed in a conference abstract for the ENCALS meeting by the investigators of the ROCK-ALS Phase 2 clinical trial. As shared in the conference abstract, the ROCK-ALS Phase 2 study was a randomized, double-blind, placebo-controlled trial that enrolled 120 patients across sites in Germany, France, and Switzerland. Subjects were randomly assigned (1:1:1) to receive 30 mg of fasudil, 60 mg of fasudil, or placebo intravenously (iv) over 20 treatment days. Assessments were performed at 45, 90 and 180 days after treatment initiation. Primary endpoints were tolerability and safety, and secondary endpoints included, among others, motor unit number index (MUNIX), which estimates how many motor neurons innervate a muscle, and slow vital capacity (SVC), which is a measure of respiratory function. In the intention-to-treat population (118 participants), safety and tolerability were not significantly different between groups. In the secondary outcomes, MUNIX showed a significantly reduced decline with Fasudil 60 mg at 26 and 90 days, and for Fasudil 30 mg at 90 days after treatment initiation. In addition, there was a directional difference in a slower loss of SVC favoring the 60 mg of fasudil treatment at day 26, which was statistically significant in a post-hoc subgroup analysis of females at all time points, as stated in the conference abstract. The authors, who include the principal investigators of this investigator-initiated trial, conclude the following regarding the results of this trial in the abstract: "Fasudil treatment was well tolerated and safe in ALS patients. MUNIX evaluation suggests a slower loss of motor units in fasudil-treated patients compared to placebo suggesting a benefit of fasudil to be explored in further clinical trials." These preliminary results were shared in the conference abstract and have not yet been peer-reviewed. "We are excited by the encouraging data from the ROCK-ALS trial of fasudil and remain steadfast in our mission to develop breakthrough therapies for ALS and other neurodegenerative disorders," said Anjan Aralihalli, President and founder of Raya. Based on these encouraging findings, Raya will now test fasudil in more extensive studies with a larger patient cohort to further assess the compound's efficacy in ALS. In addition, Raya has reformulated fasudil into a novel formulation to enhance ease of use, especially for the approximately 80% of ALS patients that suffer from dysphagia. Anjan Aralihalli continues: "With a comprehensive combination strategy on the horizon, along with plans to initiate clinical trials next year for both mono and combination therapies, we are optimistic about the future prospects of fasudil and our entire pipeline. We are especially grateful to our licensor, University Medical Center Göttingen (UMG), for their pivotal support and collaboration as the principal sponsor of this Phase 2 study. Their commitment and support have been instrumental in advancing fasudil for ALS patients." For more information about Raya and its innovative pipeline, visit or LinkedIn Members of the Raya management team will be attending the ENCALS Annual Meeting in Stockholm, Sweden from June 17-20. About Raya Raya is a mission-driven company focused on the treatment of ALS, leveraging the latest techniques for the selection and development of disease-modifying therapies. The company has a robust pipeline of five distinct clinical stage compounds that each target different pathways involved in motor neuron degeneration seen in ALS patients. The compounds were in-licensed following a rigorous selection process based on biological plausibility, clinical target engagement and functional clinical effects reflective of efficacy. This diversified approach may enable the development of combination therapies which may have a significant impact on disease progression. To develop further combination therapies, Raya entered into a strategic research collaboration with argenx last summer ( ). This partnership explores synergistic effects of their combined drug candidates in the hope of developing more effective treatment options for ALS patients. Raya is further supported by global experts and will leverage a unique patient-friendly platform trial design offering new hope in the fight against ALS. About Fasudil Fasudil is a small molecule inhibitor of the rho-associated kinase (ROCK) and is approved for the treatment of subarachnoid hemorrhage in a few Asian countries. In preclinical studies, fasudil attenuates neurodegeneration, modulates neuroinflammation, and fosters axonal regeneration. About UMG (University Medical Center Göttingen) The UMG located in Göttingen, Lower Saxony, Germany is one of the leading university medical facilities in Germany. It is comprised of a Medical Faculty engaged in research and teaching, a University Hospital providing patient care and Research allowing for the swift transfer of innovative therapy options into patient care and education.

This information is brought to you by the Lupus Research Alliance and Lupus Therapeutics and is not sponsored by, nor a part of, the American College of Rheumatology. 30+ presentations of studies funded by the LRA spanning a broad spectrum of research areas Positive results from Phase 2/3 clinical studies supported by LRA affiliate Lupus Therapeutics point to potential new treatments Lupus Therapeutics' PALS Program helps overcome challenges of diverse lupus patient trial participation SAN DIEGO, Nov. 6, 2023 /PRNewswire/ -- The Lupus Research Alliance (LRA), the largest non-governmental non-profit funder of lupus research worldwide, is pleased to announce results from more than 30 studies supported by the LRA and its clinical research affiliate Lupus Therapeutics will be presented at ACR Convergence 2023, the annual meeting of the American College of Rheumatology. Studies will represent the full continuum of research that the LRA and Lupus Therapeutics support, from innovative foundational research to lupus clinical trials evaluating potential new treatments. "The LRA and Lupus Therapeutics are extremely proud of the tremendous work we have supported that will contribute to the dynamic scientific dialogue at this important rheumatology meeting,' commented LRA President and CEO Albert T. Roy. "We also look forward to many presentations of exciting clinical research, including results from CAR-T cell therapy studies that built on pioneering work funded by the LRA and have the potential to shift the lupus treatment paradigm." FOUNDATIONAL RESEARCH FUNDED BY THE LRA LRA-funded investigators will be presenting their recent breakthroughs across a broad spectrum of lupus research, including the impact of lupus on various organs such as the skin, kidney, and brain, the contribution of the gut microbiome to lupus, dysregulation of a variety of immune cell types underlying lupus, and more. ORAL PRESENTATIONS Sunday, Nov. 12 APOL1 High Risk Genotype in SLE: A Genes in Context Story Abstract # NA, 12:00 PM – Room 11A-B ROCK1 Orchestrates B-cell Differentiation Under Stress Abstract #0729, 2:30 PM – Room 30D-E Lupus Nephritis Flares Linked to Platelet Activation During Gut Pathobiont Blooms Abstract #0851, 5:00 PM, Exhibit Hall A-B Monday, Nov. 13 CXCL13+ T cell differentiation in systemic lupus erythematosus is controlled by opposing effects of aryl hydrocarbon receptor and type I interferon Abstract #1580, 11:15 AM – Exhibit Hall A-B Metabolic Mechanisms that Control Inflammation and Immune-related Disorders Plenary Session II, 12:00 PM – Room 30D-E Keratinocyte VISTA Suppresses Skin IFN-I Production by Regulating DNA Damage Repair and Cytosolic DNA Sensing Abstract #1586, 2:15 PM – Room 32A-B Single-Cell RNA Sequencing Reveals Cellular Drivers of UV-mediated Skin Injury in Cutaneous Lupus Abstract #1599, 2:30 PM – Room 6F/6C Identifying Potential Neuroimaging Biomarkers of Neuropsychiatric Lupus in Children Using Deep Learning Abstract #1625, 3:00 PM – Room 7A-B Tuesday, Nov. 14 Longitudinal Gut Microbiome Analyses and Blooms of Pathogenic Strains during Lupus Disease Flares Abstract #NA, 8:20 AM – Room 6F/6C Development of Engineered Smith-Specific Regulatory T Cells to Treat Lupus Nephritis Abstract #2444, 2:15 PM – Room 26A-B Targeting of Endothelial Dysfunction in Lupus Nephritis: Effect on Human Renal Endothelial Cell Gene Expression and Outcomes in Murine Lupus Nephritis Abstract #2445, 2:30 PM – Room 26A-B UV Light Exposure Induces a Type I Interferon Dependent Activation and Migration of Inflammatory Dendritic Cells to Local Lymph Nodes Abstract #2448, 3:15 PM – Room 26A-B Wednesday, Nov. 15 In Situ Adaptive Immunity in Human Lupus Nephritis Abstract # N/A, 8:30 AM – Room 29A-D POSTER PRESENTATIONS – Poster Hall Sunday, Nov. 12 Elevated Serum Levels of S100A8/A9 Discriminate Systemic Lupus Erythematosus Patients with Cognitive Impairment from Patients Without Impairment Abstract #0558, 9:00 AM Comparison of Plasma Protein Profiles and Endothelial Function in Patients with Pediatric-Onset Systemic Lupus Erythematosus and Healthy Controls Abstract #0568, 9:00 AM Monday, Nov. 13 Specificity of Brain-Intrinsic and Hematopoietic-Derived Mechanisms in Mediating Neuropsychiatric Symptoms of Systemic Lupus Erythematosus Abstract #0890, 9:00 AM Adverse Childhood Experiences in a Paediatric Systemic Lupus Erythematosus Cohort Abstract #1241, 9:00 AM Agreement Between Parent- and Self-Report of Executive Function in Adolescents with Childhood-Onset Systemic Lupus Erythematosus Abstract #1242, 9:00 AM Proinflammatory Neutrophils and NETs Mediate Skin and Kidney Inflammation During Lupus Flare in Asymptomatic Lupus-prone Mice Triggered by UVB Abstract #0920, 9:00 AM IL-4 Acts Through Aryl Hydrocarbon Receptor to Antagonize TLR7-induced Double Negative 2 B Cells in Lupus Abstract #0925, 9:00 AM Examining the Relationship Between Socioenvironmental Factors and Cognitive Functioning in Youth with Childhood-Onset Systemic Lupus Erythematosus Abstract #1226, 9:00 AM Longitudinal Assessment of Self-reported Executive Function in Youth with Childhood-Onset Lupus Abstract #1229, 9:00 AM Complement Deposition on Extracellular Mitochondria Induces Platelet Activation in Vitro Abstract #0900, 9:00 AM The Cellular and Spatial Type I Interferon Response Following Skin Exposure to Ultraviolet Light Abstract #0894, 9:00 AM Tuesday, Nov. 14 Brain Activity Patterns and Behavioural Performance in SLE Patients During a Spatial Working Memory and Sustained Attention Task Abstract #2258, 9:00 AM The Effects of Systematic Lupus Erythematosus Related Cognitive Impairments on Activities of Daily Living and Life Role Participation: A Qualitative Framework Study Abstract #2259, 9:00 AM Association of Mycophenolate and Azathioprine Use with Cognitive Function in Systemic Lupus Using a Bayesian Longitudinal Item-response Theory Model Abstract #2290, 9:00 AM CLINICAL TRIALS SUPPORTED BY LUPUS THERAPEUTICS As the clinical research affiliate of the LRA, Lupus Therapeutics collaborates with biotechnology and pharmaceutical companies, as well as lupus experts from their Lupus Clinical Investigators Network (LuCIN) to help design and conduct high-quality, patient-centric, and diverse lupus studies, including several with results being presented at ACR Convergence 2023. ORAL PRESENTATIONS Tuesday, Nov. 14 Efficacy and Safety of ABBV-599 High Dose (Elsubrutinib 60 mg and Upadacitinib 30 mg) and Upadacitinib Monotherapy for the Treatment of Systemic Lupus Erythematosus: A Phase 2, Double-blind, Placebo-controlled Trial Abstract #2488, 2:00 PM – Ballroom 20D Phase 2 Safety and Efficacy of Subcutaneous (s.c.) Dose Ianalumab (VAY736; Anti-BAFFR mAb) Administered Monthly over 28 Weeks in Patients Abstract #2487, 2:00 PM – Ballroom 20D POSTER PRESENTATIONS – Poster Hall Monday, Nov. 13 Treatment with Upadacitinib in Patients with Systemic Lupus Erythematosus Results in the Inhibition of B-Cell–related Biomarkers: Analysis of the M19-130 (SLEek) Phase 2 Study Abstract #1489, 9:00 AM Disease Course and Complement as Predictors of Response to Standard of Care Plus Placebo in Patients with SLE: A Post Hoc Analysis of Dapirolizumab Pegol and Epratuzumab Clinical Trial Data Abstract #1503, 9:00 AM Steroid-sparing Effects of Afimetoran (BMS-986256), an Equipotent Toll-like Receptor (TLR)7 and TLR8 Antagonist, in a Lupus Mouse Model Abstract #0897, 9:00 AM Transcriptomic Analysis of the Impact of Iberdomide on Patients with SLE Abstract #1694, 4:00 PM Tuesday, Nov. 14 Dapirolizumab Pegol Impacts Important Immunologic Pathways in SLE: Pharmacodynamic Analysis of B Cell and Type I Interferon Pathways from a Phase 2b Trial Abstract #2333, 9:00 AM Modulation of B Cell and Interferon Pathways by Ianalumab in Patients with Systemic Lupus Erythematosus: Findings from a Phase 2 Clinical Trial Abstract #2342, 9:00 AM WORK CONDUCTED THROUGH THE LUPUS THERAPEUTICS PALS PROGRAM Patient Advocates for Lupus Studies (PALS) is a peer support program that aims to improve participation in lupus clinical trials through increased education and availability of information about clinical trials. Individuals living with lupus who have clinical research act as peer educators, or PALs, to deliver educational sessions to others living with lupus. The PALS program was piloted from 2019-2021 and demonstrated significant increases in knowledge about, attitudes toward, and intentions to participate in lupus clinical trials among program participants. POSTER PRESENTATION – Poster Hall Sunday, Nov. 12 Barriers and Facilitators to Recruiting Underrepresented Participants for Clinical Trials: Insights from the Lupus Clinical Investigators Network (LuCIN) Abstract #0183, 9:00 AM WORK CONDUCTED BY THE ACCELERATING MEDICINES PARTNERSHIP The LRA is a partner in Accelerating Medicines Partnership® Autoimmune Mediated Disease (AMP® AIM), which brings together 20 organizations from the public, private, and nonprofit sectors to accelerate the identification and validation of new therapeutic targets by reconstructing shared immune response pathways through spatial and multi-omics technologies. The project is managed by the FNIH and builds on the success of AMP RA/SLE in which LRA was also a partner. The presentation of results from an AMP® AIM lupus study is noted below. ORAL PRESENTATION Monday, Nov. 13 Single Cell Transcriptomics in Kidney Tissue from African American Patients Enrolled in the Accelerating Medicines Partnership (AMP) Implicates Tubular Cells in the Pathogenesis of APOL1 Associated Lupus Nephritis Abstract #1695, 4:30 PM – Room 6F/6C About Lupus Lupus is a chronic, complex autoimmune disease that affects millions of people worldwide. More than 90 percent of people with lupus are women, often striking during the childbearing years of 15-45. Blacks/African Americans, Hispanics, Asians, and Native Americans are at two to three times greater risk than Caucasians for developing lupus. In lupus, the immune system, meant to defend against infections, produces antibodies that mistakenly recognize the body's own cells as foreign, prompting other immune cells to attack and potentially damage organs such as the kidneys, brain, heart, lungs, blood, skin, and joints. About Lupus Research Alliance The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately, cure for lupus. Because the Lupus Research Alliance's Board of Directors funds all administrative and fundraising costs, 100% of all donations goes to support lupus research programs. About Lupus Therapeutics Lupus Therapeutics, the clinical research affiliate of the Lupus Research Alliance, aims to accelerate the development of curative treatments for all patients living with lupus. Lupus Therapeutics collaborates with academic institutions, biotechnology, and pharmaceutical partners through the unprecedented Lupus Clinical Investigators Network (LuCIN) to drive rapid and meaningful progress in the treatment of lupus patients. The organization elevates the patient voice, engages community stakeholders, and strives for representation of the diverse lupus community in the clinical research process with the most innovative and renowned experts throughout North America. Visit lupustherapeutics.org for more information. SOURCE Lupus Research Alliance

ROCK, also known as Rho-associated coiled-coil kinases, is a class of serine/threonine protein kinases that play an important role in various common cellular functions such as cell proliferation, cell apoptosis, and gene expression. ROCK is a downstream effector of RhoA. There are two subtypes, ROCK1 and ROCK2. ROCK1 is mainly expressed in non-neural tissues such as lungs, kidneys, and skeletal muscles, while ROCK2 is mainly expressed in the central nervous system, including hippocampal pyramidal neurons, the cerebral cortex, and cerebellar Purkinje cells. The Rho/ROCK signaling pathway is an important signaling transduction system involved in cell growth, differentiation, migration, and development. For example, in fibrotic diseases, the response of the myocyte to injury involves the reorganization of the actin cytoskeleton of various cells, and the assembly of actin filaments and the contraction of actin myosin are guided and regulated by the ROCK family proteins (including ROCK1 and ROCK2). Similarly, in chronic graft-versus-host disease (cGVHD), a complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), the transplanted immune cells attack the host's healthy cells, causing inflammatory reactions and fibrosis in multiple organs and tissues. The inhibition of ROCK2 kinase is expected to help restore immune balance. ROCK2 Competitive LandscapeAccording to the data provided by Patsnap Synapse-Global Drug Intelligence Database: the following figure shows that as of 25 Sep 2023, there are a total of 25 ROCK2 drugs worldwide, from 36 organizations, covering 45 indications, and conducting 60 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, organizations, clinical trials, clinical results, and drug patents related to this target. The analysis of the current competitive landscape of target ROCK2 reveals that Sanofi is the leading company with the highest stage of development. The indication analysis shows that drugs under this target have been approved for chronic graft-versus-host disease and glaucoma, open-angle. Small molecule drugs are progressing rapidly, indicating intense competition. The countries/locations developing fastest include the United States, China, Japan, South Korea, and various countries in the European Union. The future development of target ROCK2 holds potential for advancements in the treatment of various indications, including idiopathic pulmonary fibrosis, ocular hypertension, and rheumatoid arthritis. Approved ROCK2 Inhibitors for market launch: BelumosudilBelumosudilis a small molecule drug that targets ROCK1 and ROCK2. It falls under the therapeutic areas of Infectious Diseases, Skin and Musculoskeletal Diseases, Respiratory Diseases, and Immune System Diseases. The drug is indicated for the treatment of Chronic graft-versus-host disease, Bronchiolitis Obliterans, Scleroderma, Diffuse, and Idiopathic Pulmonary Fibrosis. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Belumosudil was developed by Kadmon Pharmaceuticals LLC, an originator organization in the pharmaceutical industry. It has reached the highest phase of development, with approvals in both the global market and China. The drug received its first approval in the United States in July 2021. In terms of regulations, Belumosudil has undergone Priority Review, indicating its potential to address unmet medical needs. It has also been designated as an Orphan Drug, which signifies its intended use for rare diseases. Additionally, the drug has been granted Breakthrough Therapy status, highlighting its promising clinical results and potential to provide significant benefits over existing treatments. The approval of Belumosudil marks a significant milestone in the field of biomedicine. Chronic graft-versus-host disease, Bronchiolitis Obliterans, Scleroderma, Diffuse, and Idiopathic Pulmonary Fibrosis are complex and challenging conditions that affect various organ systems. The targeted inhibition of ROCK1 and ROCK2 by Belumosudil offers a novel approach to managing these diseases. Overall, Belumosudil's approval represents a significant advancement in the treatment options available for patients with Chronic graft-versus-host disease, Bronchiolitis Obliterans, Scleroderma, Diffuse, and Idiopathic Pulmonary Fibrosis. Its unique mechanism of action and broad therapeutic areas make it a promising addition to the pharmaceutical industry's arsenal in combating these challenging diseases. Entering into Phase III Clinical Trials ROCK2 Inhibitors: SovesudilSovesudil is a small molecule drug that targets ROCK1 and ROCK2, and it is primarily used in the treatment of eye diseases. The active indications for Sovesudil include glaucoma, open-angle, ocular hypertension, and glaucoma. The drug is currently in Phase 3 of development, indicating that it has progressed through earlier stages of clinical trials and is now being tested on a larger scale. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Sovesudil is developed by Amakem NV, an originator organization in the pharmaceutical industry. As a small molecule drug, it is designed to interact with specific targets, in this case, ROCK1 and ROCK2. These targets are believed to play a role in the pathogenesis of eye diseases, particularly glaucoma. By targeting these specific proteins, Sovesudil aims to modulate their activity and potentially provide therapeutic benefits for patients with glaucoma and ocular hypertension. Glaucoma is a chronic eye condition characterized by increased intraocular pressure, which can lead to optic nerve damage and vision loss if left untreated. Open-angle glaucoma is the most common form of the disease, accounting for the majority of glaucoma cases. Ocular hypertension refers to elevated intraocular pressure without any signs of optic nerve damage or vision loss. By targeting ROCK1 and ROCK2, Sovesudil aims to reduce intraocular pressure and potentially slow down or prevent the progression of glaucoma. The fact that Sovesudil is in Phase 3 of its development is significant. Phase 3 trials are typically large-scale studies involving a larger number of patients to further evaluate the drug's safety and efficacy. This phase is crucial in determining whether the drug can be approved for commercialization and made available to patients. If Sovesudil successfully completes Phase 3 trials and demonstrates positive results, it may have the potential to become a valuable treatment option for individuals with glaucoma and ocular hypertension. In summary, Sovesudil is a small molecule drug developed by Amakem NV that targets ROCK1 and ROCK2. It is being developed for the treatment of eye diseases, specifically glaucoma, open-angle, ocular hypertension, and glaucoma. Currently in Phase 3 of its development, Sovesudil is undergoing large-scale clinical trials to assess its safety and efficacy. If successful, it may offer a promising therapeutic option for patients suffering from glaucoma and ocular hypertension.