olamkicept (FE999301) / Ferring, I-Mab, Conaris - LARVOL DELTA

Assessment of IL-6 Pathway Inhibition in Gastrointestinal Behçet's Disease from Immunological and Clinical Perspectives. (PubMed, Biomedicines) - "Given the current paucity of data, we reflected on the potential of IL-6 inhibitors such as tocilizumab and olamkicept based on immunopathogenic considerations and available clinical data in patients with inflammatory bowel disease (IBD), in whom clinical response or remission was induced. Still, the benefits of IL-6 inhibitors for patients with GIBD need to be evaluated in appropriate proof-of-concept studies. The clinical outcomes of IL-6 inhibitors in IBD are promising and may suggest their potential relevance in GIBD."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Rare Diseases • Vasculitis • IL6 • TNFA

Investigating the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Olamkicept in Healthy Japanese Persons (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Ferring Pharmaceuticals | Recruiting ➔ Completed

Trial completion • Gastroenterology • CRP

A Study Investigating the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Olamkicept in Healthy Persons (clinicaltrials.gov) - P1 | N=49 | Completed | Sponsor: Ferring Pharmaceuticals | Recruiting ➔ Completed

Trial completion • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • CRP

Obesity Arrhythmias: Role of IL-6 Trans-Signaling. (PubMed, Int J Mol Sci) - "The first selective inhibitor of IL-6 trans-signaling, olamkicept, has shown encouraging results in phase II clinical studies for inflammatory bowel disease. Nevertheless, the connection between IL-6 trans-signaling and obesity-linked ventricular arrhythmias remains unexplored. Therefore, understanding how IL-6 trans-signaling elicits a cellular pro-arrhythmic phenotype and its use as an anti-arrhythmic target in a model of obesity remain unmet clinical needs."

Journal • Review • Atrial Fibrillation • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Heart Failure • Immunology • Inflammation • Inflammatory Bowel Disease • Obesity • IL6

Investigating the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Olamkicept in Healthy Japanese Persons (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Ferring Pharmaceuticals

New P1 trial • Gastroenterology • CRP

Longitudinal single-cell data informs deterministic modelling of inflammatory bowel disease. (PubMed, NPJ Syst Biol Appl) - "Finally, we tested the translational relevance of the mathematical model by deconvolution of longitudinal bulk mRNA-sequencing data from a cohort of human IBD patients treated with olamkicept. We found that neutrophil depletion may contribute to IBD patients entering remission. The predictive power of IBD deterministic modelling highlights its potential to advance our understanding of immune dynamics in health and disease."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Safety, tolerability, and pharmacokinetics of single- and multiple-ascending doses of olamkicept: Results from randomized, placebo-controlled, first-in-human phase I trials. (PubMed, Clin Transl Sci) - "Complete target engagement (inhibition of phosphorylation of signal transducer and activator of transcription-3) was achieved in blood around or above olamkicept serum concentrations of 1-5 μg/mL. Overall, these results suggest that olamkicept is safe and well-tolerated in healthy subjects and patients with CD after single intravenous/SC and multiple intravenous administrations."

Clinical • Journal • P1 data • P1 data • PK/PD data • Cough • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Musculoskeletal Pain • Pain • Respiratory Diseases • IL6

A Study Investigating the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Olamkicept in Healthy Persons (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Ferring Pharmaceuticals

New P1 trial • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • CRP

Nonspecific Inhibition of IL6 Family Cytokine Signalling by Soluble gp130. (PubMed, Int J Mol Sci) - "These data show that sgp130Fc does not exclusively block IL6 trans-signalling and reveal instead that broad inhibition of gp130 signalling likely underlies its therapeutic effects. This proposes global or modular inhibition of gp130 as a therapeutic approach for treating human disease."

Journal • Oncology • ADAM10 • IL6 • IL6R • OSMR

Differential Roles of Interleukin-6 in Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Cardiometabolic Diseases. (PubMed, Cardiol Discov) - "However, the efficacy of inhibition of IL-6 signaling in metabolic diseases, such as obesity and diabetes, may depend in part on cell type-dependent actions of IL-6 in controlling lipid metabolism, glucose uptake, and insulin sensitivity owing to complexities that remain to be elucidated. The present review sought to summarize and discuss the current understanding of how and whether targeting IL-6 signaling ameliorates outcomes following SARS-CoV-2 infection and associated clinical complications, focusing predominantly on metabolic and cardiovascular diseases."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Obesity • Respiratory Diseases • IL6

An epithelial gene signature of trans-IL-6 signaling defines a subgroup of type 2-low asthma. (PubMed, Respir Res) - "sIL-6Rα amplifies IL-6 signaling in bronchial epithelial cells. Higher local airway IL-6 + sIL-6Rα signaling is observed in asthma patients with low sputum eosinophils."

Gene Signature • Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL6

DISCRIMINATION OF THE DIFFERENTIAL EFFECTS OF SELECTIVE SUPPRESSION OF IL-6 TRANS-SIGNALING BY OLAMKICEPT IN MODERATE-TO-SEVERE ULCERATIVE COLITIS (UEGW 2023) - P2 | "In the developed in silico model of colonic inflammation, inhibition of IL-6 signaling was associated with attenuation of Th17 mediated inflammation in the gut. Pan-inhibition of IL-6 signaling was associated with impaired tissue healing, however this was not observed for olamkicept, where homeostatic, classical IL-6 signaling was preserved.This study provides quantitative support to therapeutic strategies targeting IL-6 trans-signaling in UC to reduce the cytokine's undesirable effects while preserving its beneficial functions."

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • CD4 • CRP • IL6

SIL-6Rα amplified IL-6 signaling in bronchial epithelial cells defines a subgroup of asthma patients low in sputum eosinophils (ERS 2023) - " Human airway epithelial cells were stimulated with different combinations of IL-6, sIL-6Rα, sgp130 (Olamkicept), and anti-IL6 (Tocilizumab) to assess their effect on signaling pathway activation, epithelial barrier integrity, and gene expression. sIL-6Rα amplifies IL-6 signaling in bronchial epithelial cells. We find evidence for higher local airway IL-6/sIL-6Rα signaling in asthma patients with low sputum eosinophils. These findings provide a rationale for the evaluation of olamkicept as a potential drug to be repositioned for patients with non-eosinophilic IL-6 high asthma.; Endoscopy and interventional pulmonology; Imaging; Pulmonary function testing; Pulmonary rehabilitation; Transplantation; General respiratory patient care; Physiology; Cell and molecular biology"

Clinical • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • Transplantation • IL6

Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11. (PubMed, Immunol Invest) - "Besides, IL-11 and ADAM10 were also elevated in the skin and pulmonary of bleomycin-induced SSc mouse. Fibroblasts co-stimulated with IL-11 and ionomycin showed increased expression of COL3 and phosphorylation of STAT3, which could be inhibited by TJ301 or WP1066...IL-11 induces fibrosis in SSc by regulating the trans-signaling pathway. Blockage of sgp130Fc or inhibition of the JAK2/STAT3 pathway could ameliorate the profibrotic effect of IL-11."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immune Modulation • Immunology • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis • ADAM10 • ADAM17 • CD163

Dissecting Interleukin-6 Classic and Trans-signaling in Inflammation and Cancer. (PubMed, Methods Mol Biol) - "This protein under the WHO name Olamkicept has successfully undergone phase II clinical trials in patients with autoimmune diseases. Here, in this chapter, we describe several molecular tools to differentiate between IL-6 classic and trans-signaling and to analyze the consequences of cellular IL-6 signaling in vivo."

Journal • Immunology • Oncology • IL6 • IL6R

Worldwide attention for the therapy for chronic intestinal inflammation developed in Kiel [Google translation] (University Hospital Schleswig-Holstein) - "'The successful phase II study in JAMA now gives many patients with inflammatory diseases new hope. The path from the discovery of a new biochemical principle to clinical application follows our mission statement of sustainability in medical research. This success is a milestone in precision medicine. Stefan Schreiber....Prof. Dr. Stefan Schreiber...and his team made significant progress in developing the active ingredient."

Media quote

Olamkicept induces clinical response in nearly 60% of patients with active UC (Healio) - "Olamkicept represents a novel mechanism of action for the treatment of ulcerative colitis. This is a first-in-class, selective inhibitor of the s-interleukin-6R/IL-6 complex that is being studied for UC....we move closer to a precision-medicine approach to the treatment of IBD patients and the administration of medications based on a patient's molecular profile."

Media quote

Targeting IL-6 trans-signalling: past, present and future prospects. (PubMed, Nat Rev Immunol) - "The first selective inhibitor of IL-6 trans-signalling, sgp130, has shown therapeutic potential in various preclinical models of disease and olamkicept, a sgp130Fc variant, had promising results in phase II clinical studies for inflammatory bowel disease. Technological developments have already led to next-generation sgp130 variants with increased affinity and selectivity towards IL-6 trans-signalling, along with indirect strategies to block IL-6 trans-signalling. Here, we summarize our current understanding of the biological outcomes of IL-6-mediated signalling and the potential for targeting this pathway in the clinic."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Immune Modulation • Immunology • Inflammatory Bowel Disease • Oncology • IL6

Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis: A Randomized Clinical Trial. (PubMed, JAMA) - P2 | "Further research is needed for replication and to assess longer-term efficacy and safety. ClinicalTrials.gov Identifier: NCT03235752."

Clinical • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • IL6

Defining the role of Interleukin-6 for the development of perioperative neurocognitive disorders: Evidence from clinical and preclinical studies. (PubMed, Front Aging Neurosci) - "Olamkicept, a highly selective IL-6 trans-signaling blocker has shown to be efficacious and safe in clinical trials involving patients with inflammatory bowel disease, another condition for which IL-6 trans-signaling is the mediating mechanism. Subject to a demonstration that olamkicept is effective in preventing cognitive impairment in vulnerable (aged and Alzheimer's Disease) preclinical PND models, clinical trials involving aged and/or cognitively impaired surgical patients should be undertaken to study olamkicept's utility for PNDs."

Journal • Preclinical • Review • Alzheimer's Disease • Anesthesia • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Musculoskeletal Diseases • Orthopedics • IL6

Interleukin-11 Promotes Fibrosis Through Classic and Trans-signaling Pathway in Systemic Sclerosis (ACR Convergence 2022) - "Fibroblasts stimulated with IL-11 with iono could induce COL3 expression and STAT3 phosphorylation, and the pro-fibrotic effect could be inhibited by TJ301 or WP1066. Besides classic signaling pathway, IL-11 contributes to pro-fibrosis in SSc through regulating trans-signaling pathway. Intervention of IL-11 trans-signaling pathway or JAK2/STAT3 pathway could ameliorate the pro-fibrotic response of IL-11.Figure. Pro-fibrotic effect of IL-11"

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Respiratory Diseases • Scleroderma • Systemic Sclerosis • ADAM10 • TGFB1

Satralizumab might not be enough. Olamkicept (sgp130Fc) in Neuromyelitis Optica Spectrum Disorder. (PubMed, Mult Scler Relat Disord) - No abstract available

Journal • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases

Olamkicept(sgp130Fc): The missing trial in Neuromyelitis optica spectrum disorder. (PubMed, Clin Immunol) - "Targeting IL-6 or IL-6 Receptor(like Satralizumab does) results in inhibition of both pro and anti-inflammatory pathways of IL-6. Sgp130FC(Olamkicept) is a monoclonal antibody that prevents only the proinflammatory pathway of IL-6 to be activated, and could represent a better way to target IL-6 pathway in Neuromyelitis optica spectrum disorder."

Journal • CNS Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases • IL6R

"$IMAB Ferring Announces New Collaboration for Development of Olamkicept https://t.co/JzqiFltAeK" (@stock_titan)

Ferring Announces New Collaboration for Development of Olamkicept (Businesswire) - "Ferring Pharmaceuticals today announced it has entered into a strategic collaboration with I-Mab to further develop olamkicept in inflammatory bowel disease (IBD) and related inflammatory conditions....Ferring had previously entered into a license agreement with I-Mab in 2016 that granted I-Mab exclusive rights to develop and commercialize olamkicept in Greater China and South Korea. This new collaboration enables Ferring to invest in the development of olamkicept globally and provides an option for I-Mab to collaborate with Ferring in the future development of olamkicept at a pre-defined development milestone. The financial details of this deal are undisclosed."

Licensing / partnership • Inflammatory Bowel Disease • Ulcerative Colitis