Matisse Pharmaceuticals Meets Objectives in Study with M6229 in Critically Ill Sepsis Patients

Matisse Pharmaceuticals B.V., a clinical stage company developing a medicinal product for the treatment of sepsis, have announced topline results from the HistoSeps trial evaluating the safety, tolerability and pharmacokinetics of intravenously (IV) administered M6229 in critically ill sepsis patients.

According to the WHO, sepsis is the leading cause of death. Currently, there is no effective treatment against sepsis. Matisse's platform technology is based on the discovery that in most patients suffering from sepsis, proteins called histones are released by the innate immune system and apoptotic and/or necrotic cells into the blood stream, where they are toxic to other cells. Due to this self-enforcing cascade, people may die from organ failure within one or two days. Preclinical results have shown that by neutralising the toxic histones with Matisse's product M6229, the negative cascade is inhibited by neutralisation of cationic histones by highly anionic M6229.

In this first in human clinical study, performed at the intensive care unit (ICU) of the Amsterdam University Medical Center, in total 10 critically ill patients in ICU setting received a six-hour IV infusion of M6229. This study met its primary objectives, showing favourable safety and tolerability as well as close to dose-proportional pharmacokinetics of IV administered M6229 in critically ill patients with sepsis.

Preliminary semi-quantitative plasma histone H3 (H3) analysis executed by the University of Maastricht, showed a pharmacodynamic effect of M6229 by assessing plasma levels of extracellular histones in the study patients, before and at different time-points after M6229 administration.

A decrease in SOFA (Sequential Organ Failure Assessment) score was found for 70% of the patients following the three days after the infusion day. Further quantitative analyses on plasma histones H3 and H2b are ongoing.

"We are very pleased with the results confirming strong progress in the development of our lead compound M6229, as the first effective treatment for sepsis. The current data give strong guidance to us in the design of a successful phase 2b study, which we expect to run in the US and Europe," according to Kees Groen, Chief Development Officer at Matisse Pharmaceuticals.

Based on available data, it is concluded that the treatment infusion with M6229 should be started as soon as possible after patients are diagnosed with sepsis to be most effective. Matisse Pharmaceuticals is preparing for a Phase IIb clinical study in which critically ill sepsis patients will receive an IV infusion which should last until discharge from ICU, or organ support free for 24h, or severe adverse events, or the maximum allowed duration of infusion is reached.

The recently closed funding round will allow Matisse to effectively continue its preparation for the large scale phase IIb study in sepsis patients. In the course of 2024, Matisse aims to conclude an additional funding round which should cover the full execution of the phase IIb clinical trial, the production scale up to a commercial level and to progress on a number of R&D projects, thereby also further strengthening the organisation.