Inotrem Announces Its ESSENTIAL Phase II Study for the Treatment of Critically Ill Patients with COVID-19 Achieves Key Primary and Secondary Endpoints

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PARIS–(BUSINESS WIRE)–Inotrem, a late-stage clinical-stage biotechnology company specializing in immunotherapies for acute and chronic inflammatory syndromes, announced today at the annual congress of the European Society for Intensive Care Medicine, held in Paris , positive results for ESSENTIAL, its phase II clinical trial in COVID -19 patients hospitalized in intensive care and in acute respiratory distress. The study was funded as part of the Capacity Building call for projects, financed by the Program d’Investissements d’Avenir (PIA), operated on behalf of the French government by Bpifrance, the French national investment bank. .

The ESSENTIAL study was completed in 220 randomized intensive care patients requiring ventilatory support (stage 5 or 6 on a 7-point ordinal clinical status scale) and compared nangibotide infusion at 1 mg/kg/ h for up to 5 days of treatment with standard of care. Despite a smaller than expected sample size, the study met its primary endpoint of improvement in clinical status on the 7-point Ordinal Clinical Status Scale from baseline to day 28 (p-value=0.040).

Nangibotide treatment also showed a statistically and clinically significant reduction of 12% absolute and 43% relative in day 28 mortality (key secondary endpoint) in the overall trial population (p-value=0.030). Among the subpopulation of patients with levels of the TREM-1 pathway activation marker soluble TREM-1 (sTREM-1) above the median, the absolute and relative reduction in mortality was even greater. pronounced, amounting to 20% and 47%, respectively. (p-value=0.023).

The study showed that nangibotide has a significant and positive impact on disease progression in patients receiving ventilatory support due to COVID-19, as well as the severity of respiratory failure and length of stay in intensive care. The trial showed that sTREM-1 is an effective prognostic marker of severe COVID-19 outcome and, consistent with the results of the company’s previous ASTONISH study, confirmed that sTREM-1 is a predictive marker of a positive response to nangibotide treatment.

Jean-Jacques Garaud, Senior VP Head of Scientific and Medical Affairs at Inotrem said: “This new trial provides compelling evidence that the TREM-1 pathway plays a central role in the major life-threatening immune dysregulations caused by serious infections, whether severe forms of COVID-19 or shock. septic. This study strongly suggests that nangibotide, which targets TREM-1, is pathogen independent and has the potential to treat these life-threatening inflammatory conditions caused by viral and bacterial infections.

Sven Zimmermann, CEO of Inotrem, added: “We are grateful for the continued financial support and trust placed in us by the French public authorities to fight against COVID-19. This attests to the relevance of our innovative approach to treating inflammatory diseases. The data we have obtained is extremely encouraging and we plan to consult with regulatory authorities in the US and EU soon. »

Thierry Hercend, Independent Board Member of Inotrem, said: “The effect of nangibotide on severe forms of COVID 19 added to the recent announcement of ASTONISH Phase II data in septic shock confirms that the targeting of the TREM-1 pathway is beneficial in other conditions, infectious or not, resulting in severe immune dysregulation in the intensive care setting.

Substantial public funding support to fight COVID-19

At the start of the pandemic in 2020, the Inotrem team focused on building on the similarities between immune dysregulations in severe forms of COVID-19 and those observed in patients with septic shock. Building on its deep scientific and medical understanding of the TREM-1 pathway, and with the strong support of the French government, Inotrem launched ESSENTIAL, its clinical trial to assess the efficacy of its lead drug candidate, nangibotide, for COVID-19 patients in the ICU.

In July 2020, the CoviTREM-1 consortium, which brings together the University Hospitals of Nancy and Limoges and Inotrem, obtained initial public funding of 7.5 million euros as part of a call for projects operated by the General Secretariat at the ‘Investment and Bpifrance. In December 2020, the trial was declared a “National Research Priority” by the French government. In July 2021, Inotrem was authorized to continue the clinical development of nangibotide until registration for COVID-19 patients and can benefit from additional public funding of up to 45 million euros from Bpifrance, in the framework of the Future Investments Program (“PIA”).

About the nangibotide drug candidate

Nangibotide is a TREM-1 inhibitory peptide with the potential to restore proper inflammatory response, vascular function and improve survival after septic shock. Nangibotide is the formulation of the active ingredient LR12, which is a 12 amino acid peptide prepared by chemical synthesis. LR12 is a specific inhibitor of TREM-1, acting as a decoy receptor and interfering in the binding of TREM-1 and its ligand. In preclinical models of septic shock, nangibotide was able to restore proper inflammatory response, vascular function, and improve animal survival after septic shock. Nangibotide in septic shock was granted accelerated status in September 2019 by the FDA and PRIME status in 2017 by the EMA and recently reported positive results from a phase IIb trial (ASTONISH) in patients with septic shock .

About Inotrem

Inotrem SA is a biotechnology company specializing in the immunotherapy of acute and chronic inflammatory syndromes. The company has developed a novel immunomodulation concept that targets the TREM-1 pathway to control imbalanced inflammatory responses. Thanks to its proprietary technology platform, Inotrem has developed the first TREM-1 inhibitor, nangibotide, with potential applications in a number of therapeutic indications such as septic shock, severe forms of COVID-19 and infarction myocardium. In parallel, Inotrem also launched an antibody-based program to develop a new therapeutic modality targeting chronic inflammatory diseases. The company was founded in 2013 by Dr Jean-Jacques Garaud, former head of research and early development of the Roche group, Pr Sébastien Gibot and Dr Marc Derive. Inotrem is backed by leading European and North American investors Inotrem is part of the French Tech 120, a government program dedicated to supporting the development of high-growth startups. www.inotrem.com

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