Matisse Pharmaceuticals meets primary objectives in study with M6229 in critically ill sepsis patients.

Geleen, January 30, 2024.

Matisse Pharmaceuticals B.V., a clinical stage company developing a medicinal product for the treatment of sepsis, today 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 neutralizing the toxic histones with Matisse’s product M6229, the negative cascade is inhibited by neutralization 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 favorable 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.

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 organization.

“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.

About M6229
Matisse claims to have identified an elegant solution for treating sepsis by using its lead compound M6229 to neutralize toxic circulatory histones. 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 neutralizing the toxic histones with Matisse’s product M6229, the negative cascade is inhibited by neutralization of cationic histones by highly anionic M6229. Currently, there is no effective treatment against sepsis. According to the WHO, sepsis is the leading cause of death. From the 49 million patients globally suffering from sepsis every year, more than 20% die. According to a study by Buchman et al., published in the Journal of Critical Care Medicine, sepsis is the most common cause of in-hospital deaths, costing over $62 billion annually in the USA alone.

About Matisse Pharmaceuticals
Matisse Pharmaceuticals BV was founded in 2014 in Geleen, the Netherlands. Matisse targets life-threatening inflammation by neutralizing cytotoxic components of the inflammatory system. Its main development program is the development of a medicine to fight sepsis and septic shock.
This study has been financed by the Dutch Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships.

For more information, please contact:
Marcel Jacobs, CEO
(T) +31 6 575 27 541
(E) m.jacobs@matissepharmaceuticals.com
(W) www.matissepharmaceuticals.com