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Icosabutate Latest Data Shows Direct and Potent Anti-Fibrotic Effect in Both Differentiated Rodent NASH Models and Human Stellate Cells

Results to be presented at the AASLD congress 2018, 9-13 November

  • In a biopsy-confirmed fibrotic ob/ob NASH mouse model, icosabutate reduced hepatic fibrosis in association with a 45% decrease in myofibroblast content in pre- versus post-treatment liver biopsies
  • In a CDAA NASH mouse model, icosabutate reduced fibrosis levels to baseline despite delayed onset of treatment in association with a >50% reduction in collagen fiber number
  • Highly significant anti-proliferative effects of icosabutate demonstrated in human stellate cells in vitro
  • Extensive changes in the hepatic concentrations of multiple lipotoxic NASH-associated lipid species
  • Superior anti-fibrotic and anti-inflammatory efficacy versus other late-stage NASH drugs under development
  • Strong impetus for phase 2b NASH trial initiation in 2019 Q2

Naarden, The Netherlands, November 09, 2018 / B3C newswire / — NorthSea Therapeutics B.V. (‘NST’), a newly established Dutch biotech company developing novel and innovative strategies for the treatment of NASH and other metabolic, inflammatory and fibrotic diseases, today announces the publication of two posters to be presented at the AASLD The Liver Meeting™ 2018 in San Francisco on 9-13 November. The posters will outline the Company’s latest research data of its lead product’s anti-fibrotic effect in both differentiated rodent NASH models and human stellate cells.

NorthSea Therapeutics’ lead product, icosabutate, is a structurally designed fatty acid that regulates pivotal lipid signalling pathways involved in hepatic inflammation and fibrosis.

Commenting on the newest data, Dr. David A. Fraser, NorthSea’s CSO, stated,“Icosabutate exhibits consistent anti-fibrotic effects in multiple NASH models, but it was unclear whether these effects were indirect. The new data in proliferating human stellate cells suggest these effects are not dependent on paracrine signals from other cell types. These findings are of considerable relevance given the association between degree of fibrosis and clinical outcomes and the complexity of indirect targeting of fibrosis in a highly heterogenous patient population.”

All experiments were carried out in the laboratories of Professor Detlef Schuppan, Professor Scott Friedman and with Gubra (CRO), where pre- and post-treatment liver biopsies allowed longitudinal comparisons to be assessed in a well-established NASH ob/ob mouse model.

Both posters highlight the superior efficacy of icosabutate versus other late-stage NASH drugs on multiple fibrosis endpoints in rodent models. Data collected utilising an advanced optical imaging technique showing that the reduction in fibrosis after icosabutate treatment is associated with a >50% reduction in collagen fiber number, with no significant change after treatment with a GLP-1R agonist used as control.

Professor Scott Friedman, Scientific Advisory Board member and expert in stellate cell biology, liver fibrosis and NASH, added, “Proliferation of myofibroblasts is a key driver of fibrogenesis and thus represents an attractive target for novel anti-fibrotic therapies. Icosabutate’s ability to inhibit proliferative responses without reducing cell viability is a promising attribute of the compound and, while the mechanism is being explored, could translate into a potential benefit of reducing hepatic fibrosis in NASH.”

Commenting on the combined preclinical and clinical results, Professor John J. Kastelein, Scientific and Advisory Board member, added: “We frequently see that the improved efficacy of a drug is offset by a worsening in the safety profile. On the contrary, icosabutate demonstrates  superior efficacy versus other NASH drugs under development and, based on its clinical profile in hyperlipidemic subjects, should also prove superior on both safety and treatment of comorbidities.”

Previous phase 1b and two phase 2 clinical studies on icosabutate in hyperlipidemic subjects have demonstrated significant improvements in atherogenic lipids/lipoproteins and glycemic control along with excellent safety. Icosabutate is on course to be phase 2b ready by Q2 2019 .

For more information please visit the NorthSea team in the poster area of the conference.

Poster 1

Icosabutate, a novel structurally engineered fatty-acid, exhibits potent anti-inflammatory and anti-fibrotic effects in a dietary mouse model resembling progressive human NASH

Session Date and Time: Saturday, November 10, 2018, 2:00 PM
Presentation Type: Poster Presentation
Location: Moscone Center North/South Building, Hall C

Poster 2

A liver-targeted structurally engineered fatty acid, icosabutate, potently reduces hepatic pro-fibrotic gene expression and improves glycemic control in an obese diet-induced mouse model of NASH

Session Date and Time: Sunday, November 11, 2018, 8:00 AM
Presentation Type: Poster Presentation
Location: Moscone Center North/South Building, Hall C