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

Unveiling the Origin of Regioselectivity in Iron(III)-Promoted Friedel-Crafts Synthesis of Cannabinoids: Theoretical Studies and Synthetic Applications. (PubMed, J Org Chem) - "Here, we report experimental and computational mechanistic studies that provide insight into the origin of this regioselectivity and support the involvement of a catalytically relevant iron(III)-olivetol complex, which reacts regioselectively with the carbocation generated from the terpenic unit. We also define the scope and limitations of the method and demonstrate its synthetic utility through the efficient formal synthesis of bioactive cannabinoid derivatives, including HU-210 and ajulemic acid."

Journal

Cannabinoids in Peripheral Neuropathic Pain: Resolving Mechanistic Mismatch Through CB2-Oriented Phenotype Stratification. (PubMed, Eur J Pharmacol) - "CB2 is framed as a hypothesis-driven precision target with strong preclinical support but limited clinical validation, the most informative signals emerging from prespecified subgroup analyses (olorinab CAPTIVATE; lenabasum RESOLVE-1 and DETERMINE) rather than primary endpoints. We therefore propose a tiered precision framework integrating sensory phenotyping, inflammatory biomarker profiling, endocannabinoid tone, and pharmacogenomic profiling, coupled with an operational trial template. Its predictive validity remains hypothesis-generating and requires prospective clinical testing."

Journal • Review • Immunology • Inflammation • Neuralgia • Pain • Peripheral Neuropathic Pain

Pruritus associated with systemic sclerosis: a systematic review of treatment-based clinical trials. (PubMed, Rheumatol Int) - "Oral lenabasum improved pruritus in a phase II trial; low-dose opioid receptor modulators and rituximab also showed qualitative improvement...Existing evidence regarding effective therapeutic options remains limited. Future research should prioritize pruritus as a predefined outcome and utilize validated assessment instruments to inform treatment strategies and enhance patient quality of life."

Journal • Review • Dermatology • Fibrosis • Immunology • Pruritus • Scleroderma • Systemic Sclerosis

In Silico Molecular Docking and Pharmacokinetic Evaluation of Cannabinoid Derivatives as Multi-Target Inhibitors for EGFR, VEGFR-1, and VEGFR-2 Proteins. (PubMed, Curr Issues Mol Biol) - "Among these, 2'-Hydroxy-Delta (9)-THC and Ajulemic Acid combined favorable multi-target binding with superior predicted pharmacokinetic properties compared with other cannabinoids and reference inhibitors (lapatinib, motesanib, and sorafenib). Toxicity predictions classified all compounds as moderately toxic, with Ajulemic Acid showing a comparatively more favorable safety profile. These findings do not demonstrate biological inhibition and should be interpreted strictly as hypothesis-generating computational evidence, providing a rational framework for future in vivo and in vitro validations."

Journal • PK/PD data • Oncology • EGFR • FLT1 • KDR

Lenabasum, a cannabinoid type 2 receptor agonist, exerts anti-inflammatory effects in Dermatomyositis. (PubMed, J Invest Dermatol) - "Our results show that Lenabasum acts through the CB2, promoting downregulation of proinflammatory cytokines. This may explain Lenabasum's greater effect on skin than in muscle in human studies."

Journal • Dermatology • Dermatomyositis • Immunology • Myositis • Pruritus • CD4

Machine Learning Model Incorporating Baseline and Early Follow-up Clinical Data Predicts 52-Week Cutaneous Outcomes in Systemic Sclerosis (ACR Convergence 2025) - "The purpose of this study is to develop a model for predicting 52-week cutaneous improvement in dcSSc using clinical data collected at baseline, 14, and 26 weeks. Clinical data were analyzed from 361 individuals enrolled in RESOLVE-1 (Lenabasum Phase III trial)...Immunosuppression (any) and mycophenolate mofetil use were more common among improvers vs. non-improvers (Table 1)... Improvement in mRSS at 52 weeks can be reliably predicted using baseline and early follow-up data, identifying those unlikely to improve on current therapy. This model may inform personalized clinical decision making as well as adaptive trial designs with early exit strategies for those highly unlikely to improve."

Clinical data • Machine learning • Immunology • Scleroderma • Systemic Sclerosis

Skin biopsies enhance prediction of clinical trajectory in diffuse cutaneous systemic sclerosis. (PubMed, Arthritis Rheumatol) - "Fibroblast immunophenotype varied by baseline disease duration and improved model performance for identifying those with improvement on MMF. Skin biopsies may be useful for refining prognosis and guiding patient management decisions."

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

Cannabinoid receptor 2 agonist, lenabasum, for the treatment of pulmonary exacerbations in cystic fibrosis. (PubMed, J Cyst Fibros) - "Lenabasum did not improve key clinical outcomes in this Phase 2b study in pwCF."

Clinical • Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Diverse Lenabasum pathway activation in dermatomyositis patients' blood. (PubMed, Sci Rep) - P3 | "Baseline cell-to-cell CB2R/PPARγ testing could be useful to select ideal lenabasum candidates.Trial Registration: Registered at ClinicalTrials.gov (Identifier: NCT03813160) on 2019-01-23. Sponsored by Corbus Pharmaceuticals Inc."

Journal • Dermatomyositis • Immunology • Myositis • CD4 • CD8 • IFNB1 • PPARG

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