Resunab (lenabasum) / Corbus Pharma, Kaken Pharma - LARVOL DELTA

Comparative Efficacy of Immunosuppressive Therapies in the Treatment of Diffuse Cutaneous Systemic Sclerosis. (PubMed, ACR Open Rheumatol) - "Taken together, our findings robustly support routine use of MMF in dcSSc and show benefit especially in early-stage disease. Those patients with high-risk antibodies for lung fibrosis might be especially suitable for MMF treatment."

Journal • Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Development and Evaluation of the Dermatomyositis Outcomes for Muscle and Skin as an Outcome Measure in Dermatomyositis Clinical Trials. (PubMed, JID Innov) - "In this study, data were analyzed from the phase 3 trial of lenabasum in DM...The Dermatomyositis Outcomes for Muscle and Skin score displayed a statistically significantly greater treatment effect of 25.9-40.0 points for responders than for nonresponders, depending on the response assessed and the time point. Dermatomyositis Outcomes for Muscle and Skin is a more sensitive composite measure that reflects improvement from baseline in both skin and muscle disease activity, suggesting usefulness for use in future DM clinical trials."

Journal • Dermatomyositis • Immunology • Myositis • Rheumatology

Baseline Fibroblast Immunophenotype Predicts Clinical Improvement Among Individuals with Early Diffuse Cutaneous Systemic Sclerosis (ACR Convergence 2024) - " Baseline skin biopsies and clinical data were analyzed from 105 patients with dcSSc enrolled in the Lenabasum (N=79), Belimumab (N=18), or Nilotinib (N=8) clinical trials...A multiple logistic regression model for improvement among 68 mycophenolate mofetil (MMF) users as a function of baseline predictors was developed... Early vs. later SSc at trial enrollment was associated with lower CD34, higher aSMA, and increased B cells, despite similar baseline mRSS. In early SSc, high CD34 and aSMA are associated with increased likelihood of improvement on MMF."

Clinical • Immunology • Scleroderma • Systemic Sclerosis • CD123 • CD20 • CD34 • IL3RA

Long-Term Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: Follow-Up Data from a 3-Year Open-Label Extension Study. (PubMed, JID Innov) - P2 | "Data from OLE and subsequent follow-up periods demonstrate lenabasum's efficacy in maintaining disease stability, reducing flares, and improving DM symptoms, suggesting that it is a promising option for patients with treatment-resistant skin-predominant DM."

Clinical • Journal • Dermatology • Dermatomyositis • Immunology • Infectious Disease • Myositis • Pruritus • Rheumatology • CD4

Evaluating the Abuse Potential of Lenabasum, a Selective CB2 Cannabinoid Receptor Agonist. (PubMed, J Pharmacol Exp Ther) - "CB1 and CB2 agonists exhibit broad anti-inflammatory properties, suggesting their potential to treat inflammatory diseases...Three doses of lenabasum (20, 60, and 120mg) were compared to placebo, and nabilone (3 and 6mg)...Significance Statement This work provides evidence that in people with a history of recreational cannabis use, lenabasum was safe and well-tolerated, although it did demonstrate abuse potential. This work supports further development of lenabasum for potential therapeutic indications."

Journal • CNS Disorders • Inflammation

The Features of Shared Genes among Transcriptomes Probed in Atopic Dermatitis, Psoriasis, and Inflammatory Acne: S100A9 Selection as the Target Gene. (PubMed, Protein Pept Lett) - "Overall, our approach may become an effective strategy for discovering new disease candidate genes for inflammatory skin diseases with a reevaluation of clinical data."

Journal • Acne Vulgaris • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Psoriasis • AURKA • CCNB1 • CDC20 • CEP55 • CHEK1 • GZMB • LCK • MCM10 • RRM2 • S100A9 • SERPINB3 • TRIP13

Corbus Pharmaceuticals to Present at the Oppenheimer 25th Annual Healthcare Conference on December 10, 2014 (Yahoo Finance UK) - "Corbus Pharmaceuticals Holdings, Inc...announced today it will be presenting at the Oppenheimer & Co. 25th Annual HealthCare Conference being held December 10-11, 2014, at the Crowne Plaza Hotel in New York, New York. The Company's Chief Executive Officer, Yuval Cohen, Ph.D., is scheduled to present a corporate overview on Wednesday, December 10, 2014, at 8:35 a.m. Eastern Standard Time. The presentation will include an update on the clinical development of Resunab, the Company's lead rare disease product candidate. Resunab is a novel synthetic oral specialized pro-resolving mediator (SPM) drug with unique anti-inflammatory and anti-fibrotic activity. The Company is developing Resunab for therapeutic indications in cystic fibrosis (CF) and diffuse cutaneous systemic sclerosis (scleroderma)."

Clinical • Cystic Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

Efficacy and Safety of Cannabis Use in Rheumatology: a Scoping Review of Condition- Specific Outcomes (CRA-AHPA 2024) - "CbMs used include inhaled cannabis products, cannabis oils, CBD products, delta 9-THC, and synthetic cannabinoids like lenabasum, nabilone, and nabiximols. The available evidence suggests CbMs are generally safe and could improve pain, sleep, mood, and quality of life for rheumatology patients. However, the current literature focuses on fibromyalgia and data for other rheumatologic conditions is sparse. Future studies should include a broader range of rheumatologic conditions and gather more long-term safety data using more robust methodologies, such as randomized controlled trials."

Clinical • Review • Ankylosing Spondylitis • Fibromyalgia • Fibrosis • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology • Scleroderma • Seronegative Spondyloarthropathies • Systemic Sclerosis • Xerostomia

Syntheses of Cannabinoid Metabolites: Ajulemic Acid and HU-210. (PubMed, Molecules) - "Herein, we optimized the key allylic oxidation step to introduce the C-11 hydroxy group with a high yield. A series of compounds was prepared with this condition applied including HU-210, 11-nor-Δ-tetrahydrocannabinol (THC)-carboxylic acid and Δ-THC-carboxylic acid."

Journal

Performance of the Revised CRISS in a Phase 3 Trial of Early Systemic Sclerosis (ACR Convergence 2023) - "Our objective was to assess the performance of Revised CRISS in a phase 3 clinical trial of lenabasum in early dcSSc at week 52 2... We propose a new preliminary definition of the Revised CRISS that is undergoing the FDA Qualification. The mRSS and CGA drove the Revised CRISS in this RCT, and the future trials should enrich for more severe skin involvement (progressive skin phenotype and less regressive disease) to limit improvement in mRSS (as part of the natural history). In addition, stratification by autoantibodies and background immunosuppressives may balance the Revised CRISS response."

P3 data • Fibrosis • Immunology • Rheumatology • Scleroderma • Systemic Sclerosis

A Revised Outcome Measure for Dermatomyositis Clinical Trials: The Dermatomyositis Outcomes for Muscle and Skin (DMOMS) (ACR Convergence 2023) - " Data was collected from the lenabasum phase 3 trial in DM... Compared to TIS, DMOMS is a simpler composite score, with four versus six component measures, and does not contain the redundant measure of EMGA. DMOMS also contains a skin-specific measure scored equally to a muscle-specific measure and assigns greater weight to PtGAto reflect clinical benefit as assessed by patients. It provides about twice the treatment effect for R vs NR in both muscle and skin response, without any increase in score in NR."

Clinical • Dermatomyositis • Immunology • Myositis

Validation of Cutaneous Dermatomyositis Disease Area and Severity Index Activity Score and Other Efficacy Outcomes as Measures of Skin Disease in Dermatomyositis in the Lenabasum Phase 3 Trial. (PubMed, J Invest Dermatol) - "EMGA and TIS generally showed increasing levels of improvement as the degree of patient and physician-reported improvement in skin disease increased, but these are composite measures and are not specific to improvement in DM skin disease. To measure clinically meaningful improvement in skin disease in a DM trial, CDASI-A is the more sensitive outcome measure across timepoints."

Journal • P3 data • Dermatology • Dermatomyositis • Immunology • Myositis

Efficacy and Safety of Lenabasum, a Cannabinoid Type 2 Receptor Agonist, in a Phase 3 Randomized Trial in Diffuse Cutaneous Systemic Sclerosis. (PubMed, Arthritis Rheumatol) - "A benefit of lenabasum in dcSSc was not demonstrated. The majority of patients were treated with background IST, and treatment with MMF in particular was associated with better outcomes. This supports the use of IST in the treatment of dcSSc, and highlights the challenge of demonstrating a treatment effect when investigational treatment is added to standard of care IST. These findings have relevance to trial design in SSc, as well as clinical care."

Journal • P3 data • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

The total improvement score (TIS) in a phase 3 clinical trial for dermatomyositis (DM): Room for improvement? (ISID 2023) - "To compare efficacy of scores, data from a Phase 3 trial of lenabasum in DM were evaluated (Baseline vs Week 52)...It provides about twice the treatment effect for R vs NR in both muscle and skin without any increase in score in NR and assigns greater weight to PtGA. DMOMS may be better suited to detect treatment effect in DM clinical trials that include patients with all DM phenotypes, even with a smaller sample size."

Clinical • P3 data • Dermatomyositis • Immunology • Myositis

Session III Treatment of Dermatomyositis: Safety of lenabasum in the Phase 3 DeterMine Trial in dermatomyositis (DM) (ISID 2023) - "Lenabasum, a CB2agonist that activates resolution of inflammation, improved skin disease, patient-reportedoutcomes, and biomarkers in a Phase 2 study of DM patients with active skin disease.The objective was to evaluate the efficacy and safety of lenabasum in a Phase 3 doubleblind study in DM. When restricting analysis ofparticipants without muscle weakness (MMT-8 = 150), improvement in CDASI activityscore was greater in the lenabasum 20 mg BID group vs placebo at Week 28, p = 0.0461,and Week 52, p = 0.0059. Related TEAEs leading to withdrawal of study product wereinfrequent."

Clinical • P3 data • Dermatology • Dermatomyositis • Immunology • Myositis

Session II Basic and Clinical Studies of Rheumatic Diseases:The total improvement score (TIS) in a phase 3 clinical trial for dermatomyositis(DM): Room for improvement? (ISID 2023) - "It also includes the Cutaneous DermatomyositisDisease Area and Severity Index-Activity (CDASI-A) score, weighted the same as MMT.To compare efficacy of scores, data from a Phase 3 trial of lenabasum in DM wereevaluated (Baseline vs Week 52)...Itprovides about twice the treatment effect for R vs NR in both muscle and skin withoutany increase in score in NR and assigns greater weight to PtGA. DMOMS may be bettersuited to detect treatment effect in DM clinical trials that include patients with all DMphenotypes, even with a smaller sample size."

Clinical • P3 data • Dermatomyositis • Myositis • Rheumatology

CDASI-activity vs IGA scores for dermatomyositis in the lenabasum phase 3 trial (ISID 2023) - "For IGA, this value is less than a 1-point change and is smaller than the currently used 2-point change threshold for meaningful change. This study is a novel assessment of the CDASI-A and IGA outcomes from the investigator’s perspective in the largest DM study, and suggests preferential use of CDASI-A scores in future DM trials."

P3 data • Dermatomyositis • Immunology • Myositis

Lenabasum and its interaction with dermatomyositis leukocyte signaling pathways (ISID 2023) - "These cells were also stained for IFN-b, IFN-g, and NFKb as markers for inflammatory activity. The results of this study will aid in uncovering the mechanisms behind the response to a CB2R agonist and allow clinicians to better understand the heterogeneity of cellular signaling and response that can account for variability of clinical response."

Dermatomyositis • Immunology • Myositis • CD19 • CD4 • CD8 • IFNG • PPARG • STING • TLR4

Lenabasum: Expiry of patents related to compositions and methods for treating disease between 2031 and 2034 (Corbus Pharmaceuticals) - Annual Report 2022: Expiry of patents in US related to the use of pharmaceutical compositions for the treatment of dermatomyositis, fibrotic diseases, systemic sclerosis, cystic fibrosis, and inflammatory diseases on February 12, 2034; Patent exclusivity in US until February 12, 2034

Commercial • Patent • CNS Disorders • Cystic Fibrosis • Dermatomyositis • Systemic Sclerosis

Changes in Skin Fibroblast Polarization Gene Expression Herald Clinical Improvement in Early, Diffuse Cutaneous Systemic Sclerosis (ACR Convergence 2022) - "Background/Purpose: We previously identified a group of genes associated with high alpha-smooth muscle actin (aSMA) and low CD34 fibroblast staining in lesional systemic sclerosis (SSc) skin that decreased with clinical improvement in patients treated with belimumab or nilotinib... Skin biopsies were analyzed from 81 patients with dcSSc enrolled in the Phase III RESOLVE-1 clinical trial of lenabasum in SSc... The gene expression signature of aSMA/CD34 polarization decreases significantly from baseline to 52 weeks among clinical improvers but is unchanged in those who do not improve. These results validate previous findings that aSMA/CD34 polarization gene expression signatures decrease in patients with clinical improvement and suggest fibroblasts can recover, potentially by repopulating or differentiating, in the improving skin of patients with SSc.Figure 1. Change in aSMA/CD34 polarization genes expressed in skin from baseline to 52 weeks among individuals with diffuse..."

Clinical • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis • CD34

Lenabasum Reduces IFNγ and pIRF3 in Dermatomyositis Skin: Biomarker Results from a Double-Blind Phase 3 International Randomized Controlled Trial (ACR Convergence 2022) - "These results suggest clinical benefit of lenabasum on skin disease in DM may be mediated in part through reduction of IFNγ, pIRF3 (Type 1 Interferon related pathway), and IL-31 expression. These results support and extend previous findings.No significant change in cell counts from week 0 to 16 when comparing treatment with 20mg BID of Lenabasum to placebo.Lenabasum significantly decreased phosphorylated interferon regulatory transcription factor 3 (pIRF3) and interferon gamma (IFNy) (p < 0.05) at 16 weeks compared to placebo. There was a trend towards a decrease in interleukin (IL) -31 (p=0.08).Subset analysis of subjects who received 20mg twice a day of Lenabasum showed that changes in the cutaneous dermatomyositis disease area and severity index activity (CDASI-A) score were positively correlated with change in the median pixel intensity in IL31."

Biomarker • Clinical • P3 data • Dermatology • Dermatomyositis • Immunology • Inflammation • Myositis • Rheumatology • CD4 • IFNB1 • IFNG • IL4 • TCF3

Lenabasum, a Cannabinoid Type 2 Receptor Agonist, Activates Diverse Cell-specific Pathways in Whole Blood Leukocytes in Dermatomyositis (ACR Convergence 2022) - "Altogether, these results show that lenabasum has a cell-specific pathway preference in the blood and the efficacy of the treatment could vary across patients due to potential baseline cell-to-cell differences in CB2R and PPARγ levels.Figure 1. Flow Cytometry of IFNβ levels in DM whole blood leukocytes show a diverse cell-specific pathway activation upon treatment with lenabasum.Figure 2. Flow Cytometry of COX2 and 15LOX1 levels in DM whole blood leukocytes across various cell lines in DM responders and non-responders to lenabasum."

Dermatomyositis • Immunology • Inflammation • Myositis • IFNB1 • PPARG

A Phase 2, Double-blind, Randomized, Placebo-Controlled Multicenter Study to Evaluate Efficacy, Safety, and Tolerability of JBT-101/Lenabasum in Systemic Lupus Erythematosus, an Autoimmunity Centers of Excellence Study (ALE09) (ACR Convergence 2022) - P2 | " Adults (18-70 years) meeting SLE ACR criteria with active MSK symptoms (SLEDAI arthritis or BILAG 2004 mild/moderate arthritis), on stable SLE medications and prednisone ≤10 mg daily, with average maximum daily pain scores ≥ 4 on a 10-point numerical rating scale (NRS), were randomized to 12 weeks treatment with placebo (PBO), or 10mg (low), 20mg (med), or 40mg (high) daily of JBT-101. JBT-101 was safe and well-tolerated. While the pre-specified mixed effects model did not identify significant differences between changes in NRS pain scores in active arms vs. PBO, the frequency of pain category improvement at Day 84 was notably higher in the active arms vs PBO."

Clinical • P2 data • Fibromyalgia • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Rheumatology • Systemic Lupus Erythematosus

Cutaneous Manifestations, Clinical Trials, Safety Efficacy and Safety of Lenabasum in the Phase 3 DeterMine Trial in Dermatomyositis (ACR Convergence 2022) - "Lenabasum, a CB2 agonist that activates resolution of inflammation, improved skin disease, patient-reported outcomes, and biomarkers in a Phase 2 study of DM patients with active skin disease. DM patients ≥ 18 years old with active skin with or without muscle involvement were enrolled in 55 sites in North America, Europe, and Asia-Pacific. Although, primary or secondary endpoints were not met in the study, subgroup analysis of patients with muscle weakness and without muscle weakness, showed improvement in muscle strength and rash, respectively in lenabasum 20 mg BID group vs placebo. Lenabasum was administered safely and was well-tolerated in this study.Figure 1. Change over time of entire study population: A. TIS; B. CDASI-A."

Clinical • P3 data • Dermatology • Dermatomyositis • Immunology • Inflammation • Musculoskeletal Pain • Myositis • Pain

Lenabasum, a Cannabinoid Type 2 Receptor Agonist, Exerts Anti-Inflammatory Effects in Dermatomyositis in Th1 Cells (ACR Convergence 2022) - "These data suggest there is an increase in CB2R expression on Th1 cells compared to Th2 cells. Lenabasum may exert specific anti-inflammatory effects in DM, particularly on Th1 cells and myeloid cell lineages such as moDCs. Lenabasum also suppressed Th1-derived IL31 and moDC-derived IL31, a cytokine implicated in the pruritus of DM.Figure 1."

Dermatology • Dermatomyositis • Immunology • Myositis • Pruritus • CD14 • CD163 • CD68 • IFNB1 • IFNG • IL4 • ITGAX • TNFA