solcitinib (GSK2586184) / Galapagos - LARVOL DELTA

Different Effects of Selective Janus Kinase (JAK) Inhibitors in Murine Bone Marrow Failure (ASH 2024) - "Previously, we found that ruxolitinib (RUX), a broad JAK inhibitor (JAKi), demonstrated efficacy and extended overall survival (OS) in our well-established murine BMF model (Groarke EM, Blood 2023)...BMF mice were either untreated or treated with 1 of 4 investigational JAKi by oral gavage for comparative analysis : baricitinib (BAR, selective JAK1/2 and TYK2 inhibitor) at 25 mg/kg once daily; tofacitinib (TOF, strong JAK3 and weak JAK1/2 inhibitor) at 15 mg/kg twice daily (BID); fedratinib (FED, selective JAK2 inhibitor) at 80 mg/kg BID; and solcitinib (SOL, selective JAK1 inhibitor) at 60 mg/kg BID...Our results support the hypothesis that combined JAK1 and JAK2 blockade is essential to ameliorate the immune environment in BMF, whereas strong JAK3 combined with weak JAK1/2 inhibition (TOF), and very selective JAK1 (SOL) or JAK2 (FED) blockade, were inferior. None of the tested JAKi had apparent hematological toxicity."

Preclinical • Anemia • Aplastic Anemia • Hematological Disorders • CD8 • ITGAM • JAK3 • KIT • TYK2

Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion. (PubMed, Pharm Biol) - "In vitro, MDSCs were treated with PLY (0.67, 2 and 6 μM) or solcitinib (10 μM, positive control) for 48 or 96 h, and their proliferation, expansion, and differentiation into M-MDSCs were examined by flow cytometry...In mice, PLY (40 mg/kg) treatment alleviated EAE and inhibited inflammatory infiltration, demyelination, and MDSCs and Th17 cells infiltration into the spinal cord. PLY may be an excellent candidate for the treatment of MS and other autoimmune diseases."

Journal • Myeloid-derived suppressor cells • CNS Disorders • Immunology • Multiple Sclerosis • Oncology • Solid Tumor • CSF2 • IL6

The efficacy and safety of tofacitinib, peficitinib, solcitinib, baricitinib, abrocitinib, and deucravacitinib in plaque psoriasis - A network meta-analysis. (PubMed, J Eur Acad Dermatol Venereol) - "Our study confirmed that JAK inhibitors had promising treatment efficacy for moderate-to-severe plaque psoriasis. Tofacitinib showed superior efficacy and safety over peficitinib, solcitinib, baricitinib, abrocitinib, and deucravacitinib."

Clinical • Journal • Retrospective data • Review • Dermatology • Immunology • Psoriasis

A Scoping Review on Use of Drugs Targeting the JAK/STAT Pathway in Psoriasis. (PubMed, Front Med (Lausanne)) - "Nine different drugs administered through various routes were identified (systemic: peficitinib, baricitinib, solcitinib, itacitinib, abrocitinib, deucravacitinib, and brepocitinib; topical: ruxolitinib; and both: tofacitinib)...Only tofacitinib and deucravacitinib have undergone phase III clinical trials, being the only ones tested with active comparators etanercept and apremilast, respectively...Psoriasis treatment is currently symptomatic and could potentially present a significant risk of toxicity. Therefore, the design of principal efficacy outcome measures considering the impact of the outcome on quality of life and a drug assessment methodology aimed at improving safety would probably strengthen the evidence and decision-making process."

Clinical • Review • Dermatology • Immunology • Infectious Disease • Psoriasis • Respiratory Diseases

JAK Inhibitors: Prospects in Connective Tissue Diseases. (PubMed, Clin Rev Allergy Immunol) - "We also discuss the efficacy of the first- and second-generation JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib, filgotinib, upadacitinib, solcitinib, itacitinib, decernotinib, R333, and pf-06651600) for CTDs including RA, systemic lupus erythematosus, dermatomyositis, systemic sclerosis, Sjögren's syndrome, and vasculitis, based on laboratory and clinical research findings. However, it is recommended that JAK inhibitors should be avoided in pregnant and breastfeeding women. More clinical data, especially on highly selective inhibitors, are required to judge the efficacy and safety of JAK inhibition in CTDs."

Journal • Review • Dermatomyositis • Immunology • Lupus • Myositis • Pediatrics • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • Vasculitis

Charles River Laboratories to acquire Galapagos’ Argenta and BioFocus service operations for up to €134 million (Galapagos Press Release) - "Galapagos NV...announces the signing of a definitive agreement to sell the BioFocus and Argenta service division operations to Charles River Laboratories International, Inc...for a total consideration of up to €134 million. The transaction is subject to customary closing conditions and is expected to close early in the second quarter of 2014."; Proceeds will be used for Galapagos’ pipeline progress.

Anticipated M & A • Financing • Immunology • Inflammatory Bowel Disease • Psoriasis • Rheumatoid Arthritis

Galapagos cash position of €232 M provides solid basis for R&D pipeline investment (Galapagos Press Release) - P2, N=595; DARWIN1 (NCT01888874); Sponsor: Galapagos; Anticipated P2 data for RA in Mar 2015; P2, N=282; DARWIN2 (NCT01894516); Anticipated topline 12 week and 24 week data for RA in Q2 2015 and Q3 2015 respectively; P2, N=180; NCT02048618; Anticipated  topline P2 data of GLPG0634 for Crohn's disease in Q2 2015; "For ulcerative colitis and psoriasis, GSK has elected to terminate development principally as a result of the statin drug-drug interaction (DDI) study. Development options for GSK2586184 in other potential indications are presently being explored by GSK."

Anticipated new indication • Anticipated P2 data • Discontinued • Immunology • Inflammatory Bowel Disease • Psoriasis • Rheumatoid Arthritis

Galapagos reports 2013 financial results (Galapagos Press Release) - P2, N=595; DARWIN1 (NCT01888874); Sponsor: Galapagos; Anticipated topline 12 week P2b data with GLPG0634 in RA in H2 2014; P2, N=64; NCT01782664; Sponsor: GlaxoSmithKline; P2, N=45; NCT01829321; Sponsor: Galapagos; Anticipated P2 data from GSK2586184 for psoriasis and GLPG0974 data in ulcerative colitis in H1 2014; "The Company expects to make significant progress in both partnered and non-partnered R&D programs as the pipeline continues to mature across a broad range of therapeutic  areas, resulting in multiple additional clinical and pre-clinical stage programs by end 2014."

Anticipated P2 data • Pipeline update • Immunology • Inflammatory Bowel Disease • Psoriasis • Rheumatoid Arthritis

An adaptive phase II study to evaluate the efficacy, pharmacodynamics, safety and tolerability of GSK2586184 (clinicaltrials.gov) - P2, N=250; Sponsor: GlaxoSmithKline; Not yet recruiting; New P2 trial.

New molecule • New P2 trial • Lupus

Safety, tolerability, efficacy and pharmacodynamics of the selective JAK1 inhibitor GSK2586184 in patients with systemic lupus erythematosus. (PubMed) - Lupus - P2; "Safety of Estrogen in Lupus National Assessment-SLE Disease Activity Index scores were not analysed due to the small number of patients completing the study. The study futility and safety data described for GSK2586184 do not support further evaluation in patients with SLE.Study identifiers: GSK Study JAK115919; ClinicalTrials.gov identifier:NCT01777256."

Biomarker • Journal • Biosimilar • Immunology • Lupus

Galapagos provides status update for GSK2586184 in GSK's psoriasis, lupus, and ulcerative colitis clinical studies (Galapagos Press Release) - P2, N=64; Sponsor: GlaxoSmithKline; NCT01782664; "Topline efficacy and safety results from this study [psoriasis] are expected in the first half of 2014....The Phase 2 study in systemic lupus erythematosis has been stopped at the planned first interim analysis by GSK due to a lack of effect. GSK notified Galapagos that the pre-defined stopping criteria were clearly met, triggering GSK to discontinue the lupus study with GSK2586184. GSK has put the exploratory Phase 1/2 study in ulcerative colitis on hold."

Anticipated P2 data • Discontinued • Trial status • Immunology • Inflammatory Bowel Disease • Lupus • Psoriasis

GSK2586184 met primary endpoint in phase 2a psoriasis study (Galapagos Press Release) - P2a, N=64; Sponsor: GlaxoSmithKline; NCT01782664; "Preliminary results showed that a significantly higher proportion of patients treated with GSK2586184 at the 400mg bid dose met the primary endpoint compared to placebo....A final analysis of the data from study JAK116679 will be submitted for presentation at an upcoming scientific congress and/or a peer-reviewed publication."; P2, N=45, Sponsor: Galapagos; NCT01829321; Anticipated P2 data of GLPG0974 for ulcerative colitis in June 2014; "Galapagos...to receive from GSK up to €34M in additional milestones..."

Anticipated commercial • Anticipated P2 data • Anticipated P2a data • P2a data • Immunology • Inflammatory Bowel Disease • Psoriasis

Galapagos announces GSK2586184 JAK1 molecule moves into phase 2 for ulcerative colitis (Galapagos Press Release) - P2, N=64; Sponsor: GlaxoSmithKline; NCT01782664; P2, N=250; Sponsor: GlaxoSmithKline; NCT01777256; "Galapagos...announced today that GlaxoSmithKline plan to initiate an exploratory Phase 2 study with GSK2586184 (formerly GLPG0778) in patients with ulcerative colitis, a third indication for this investigational molecule, in addition to psoriasis and lupus....The Phase 2 studies with GSK2586184 in ulcerative colitis, psoriasis, and lupus are scheduled to be completed in November 2014, March 2014, and November 2015, respectively."

Anticipated trial completion date • New indication • Immunology • Inflammatory Bowel Disease • Lupus • Psoriasis

Galapagos: Investor Presentation (Galapagos) - "Phase 2 studies with GSK2586184"; "Phase 2 in psoriasis met primary endpoint"; "Significantly higher proportion met targeted PASI75% at 400 mg BID dose"; "Most common adverse event was headache"

P2 data • Immunology

Safety and Tolerability Study of GSK2586184 in Patients With Moderate to Severely Active Ulcerative Colitis. (clinicaltrials.gov) - P1; N=2; Terminated; Sponsor: GlaxoSmithKline; Trial primary completion date: Nov 2014 ->Aug 2014

Trial primary completion date • Biosimilar • Immunology • Inflammation • Inflammatory Bowel Disease