TREM1

Novel biomarker-guided Phase 3 registration trial in septic shock with an enrichment strategy-based patient selection. Historic paradigm shift in Primary endpoint: from all causes of mortality at Day 29 to proportion of patients alive and free of organ support at Day 29. PARIS--(BUSINESS WIRE)-- Inotrem, an advanced clinical stage biotech company specializing in immunotherapies for acute and chronic inflammatory syndromes, today announced the outcome of its regulatory interactions with the US Food and Drug Administration (FDA) to finalize the design of a single Phase 3 registration trial (ACCURATE) for nangibotide in septic shock. The ACCURATE trial design is built upon Phase 2 (ASTONISH) data that confirmed nangibotide’s strong efficacy and safety profile. The FDA accepts Inotrem’s innovative biomarker-driven precision medicine approach. The ACCURATE study will be centered on patients with high risk of mortality and morbidity as defined by a high concentration of the blood based sTREM-1 biomarker representing about 50 percent of the septic shock patients. This unique biomarker-guided approach allows for a single Phase 3 registration trial with a manageable number of subjects. The overall size of ACCURATE will be about 1,300 patients, with a primary analysis group of 900 patients. The primary endpoint of ACCURATE will be the proportion of patients alive and free of organ support at Day 29. ACCURATE will run globally and enroll patients in about 100 sites in the Americas, Europe and Japan. Inotrem is collaborating with Roche Diagnostics since 2017 to develop a sTREM-1 assay on the Elecsys/COBAS platform to identify patients that are both more at risk and more likely to benefit from nangibotide treatment. All sTREM-1 measurements in ACCURATE will be carried out on the Roche platform paving the way for the test to be available as a companion diagnostic at the time of nangibotide approval. “Inotrem is now in a leading position to conduct a single Phase 3 registration trial in a prospectively defined population of septic shock patients that are at high risk of morbidity and mortality. Our innovative, biomarker-guided strategy along with a new patient-related primary endpoint gives us the best possible chance of success in this challenging indication,” said Margarita Salcedo-Magguilli, Chief Development Officer of Inotrem. “The successful End of Phase 2 meeting with the FDA is a testament to the dedication and expertise of our team. We are energized by the support and guidance from the FDA which will enable us to accelerate the development of nangibotide and, ultimately, bring a potentially transformative treatment to septic shock patients in need of new alternatives," added Sven Zimmermann, Chief Executive Officer of Inotrem. Septic shock is the ultimate complication of sepsis and constitutes a high unmet medical need. The incidence of septic shock continuously raises and mortality remains elevated: it is the main cause of death in intensive care units. There is currently no specific therapy approved for this indication. Inotrem’s solution has the potential to become the first mechanism-based treatment for septic shock. With nangibotide, Inotrem has developed a novel approach of immunomodulation targeting the TREM-1 pathway to restore appropriate inflammatory response, vascular function and improve post septic shock survival. Based on its scientific leadership on TREM-1, next to acute inflammatory syndromes, the company has expanded its TREM-1 franchise into chronic inflammatory diseases. About Inotrem Inotrem S.A. is a biotechnology company specialized in immunotherapy for acute and chronic inflammatory syndromes. The company has developed a new concept of immunomodulation that targets the TREM-1 pathway to control unbalanced inflammatory responses. Through its proprietary technology platform, Inotrem has developed the first-in-class TREM-1 inhibitor, nangibotide, with potential applications in life-threatening immune dysregulations caused by severe infections such as septic shock and severe forms of COVID-19. In parallel, Inotrem has 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, a former head of research and early development at the Roche Group, Prof. Sébastien Gibot and Dr Marc Derive. Inotrem is supported by leading European and North American investors. Inotrem is part of the French Tech 120, a government program dedicated to support the development of fast-growing startups. View source version on businesswire.com: Contacts Media contact for Inotrem Anne REIN Strategies & Image (S&I) anne.rein@strategiesimage.com +33 6 03 35 92 05 Source: Inotrem View this news release online at:

Funding was provided on the basis of strong interim data successfully supporting the company’s innovative approach targeting the TREM-1 pathway to treat chronic inflammatory conditions. PARIS--(BUSINESS WIRE)-- Inotrem, an advanced clinical stage biotech company specialized in immunotherapies for acute and chronic inflammatory syndromes, announced today it received the second milestone-based funding from the American Crohn’s & Colitis Foundation’s IBD Ventures program. After initial support in December 2022, continuation of funding follows a thorough review of Inotrem’s interim data, successfully supporting the proof of concept of the company’s antibody program (INO-02). This program targets the TREM-1 pathway for Inflammatory Bowel Disease (IBD) and develops a biomarker-based personalized approach to identify the patients most likely to benefit from the treatment. The Crohn’s & Colitis Foundation, the leading nonprofit organization with the mission of curing Crohn’s disease and ulcerative colitis, decided to continue funding based on Inotrem’s successful achievement of the planned interim milestones. Launched in January 2023, the R&D project was designed to last over 12 months and will be a cornerstone in the preparation of Inotrem’s first-in-human clinical trial for INO-02. Inotrem’s antibody program targeting chronic inflammatory indications, such as IBD, is the company’s second asset next to nangibotide, dedicated to the treatment of acute inflammatory diseases (septic shock, Covid-19, myocardial infarction). Based on its cutting-edge proprietary technology platform and strong scientific leadership around the TREM-1 pathway, Inotrem has built a diversified drug portfolio targeting several inflammatory indications for which there are today no or limited specific treatment. “The continuous support of The Crohn’s & Colitis Foundation is a strong recognition of the potential of our therapeutic approach targeting the TREM-1 pathway and eloquently speaks to Inotrem’s ability to deploy its vision and strategy,” says Sven Zimmermann, CEO of Inotrem. “After our stringent evaluation, Inotrem has met predetermined research milestone expectations. We are looking forward to continuing this fruitful collaboration to advance our common quest for cures and the improvement of the quality of life of patients affected by inflammatory bowel diseases,” says Andrés Hurtado-Lorenzo PhD, SVP of Translational Research & IBD Ventures at The Crohn’s & Colitis Foundation. About Inotrem Inotrem S.A. is a biotechnology company specialized in immunotherapy for acute and chronic inflammatory syndromes. The company has developed a new concept of immunomodulation that targets the TREM-1 pathway to control unbalanced inflammatory responses. Through its proprietary technology platform, Inotrem has developed the first-in-class TREM-1 inhibitor, nangibotide, with potential applications in life-threatening immune dysregulations caused by severe infections such as septic shock and severe forms of COVID-19. In parallel, Inotrem has 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, a former head of research and early development at the Roche Group, Prof. Sébastien Gibot and Dr Marc Derive. Inotrem is supported by leading European and North American investors Inotrem is part of the French Tech 120, a government program dedicated to support the development of fast-growing startups. About the American Crohn’s & Colitis Foundation’s IBD Ventures The Crohn's & Colitis Foundation is the leading non-profit organization focused on both research and patient support for inflammatory bowel disease (IBD), with the mission of curing Crohn's disease and ulcerative colitis, and of improving the quality of life of the millions of Americans living with IBD. The Foundation’s work is dramatically accelerating the research process through investment in research initiatives, while also providing extensive educational and support resources for patients and their families, medical professionals, and the public. IBD-Ventures is a dedicated funding mechanism to support product-oriented research and development programs. For more information, visit crohnscolitisfoundation.org, call 888-694-8872, or email info@crohnscolitisfoundation.org. View source version on businesswire.com: Contacts Media contact for Inotrem Anne REIN Strategies & Image (S&I) anne.rein@strategiesimage.com +33 6 03 35 92 05 Source: Inotrem View this news release online at:

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Celsius Therapeutics, a biotechnology company pioneering new precision medicines for patients with inflammatory disease by harnessing the power of single-cell RNA sequencing and human biology at scale, today announced the initiation of dosing in the company’s first-in-human Phase 1 clinical trial of CEL383 in healthy volunteers. CEL383 is a potential first-in-class anti-TREM1 antibody that Celsius is advancing for the treatment of inflammatory bowel disease (IBD). “The initiation of this study marks an important milestone for Celsius as we advance the first clinical candidate identified through our SCOPE platform into the clinic,” said Tariq Kassum, M.D., President and CEO of Celsius. “A substantial and growing body of evidence shows that TREM-1 plays a central role in ulcerative colitis and Crohn’s disease, chronic inflammatory conditions that can significantly impact patient lives. We believe a precision therapy like CEL383 has the potential to offer a clinically meaningful treatment option that could improve the quality of life for people suffering with IBD.” The first-in-human, randomized, double-blind, placebo-controlled, single ascending dose study was designed to evaluate the safety, tolerability, and pharmacokinetics of CEL383 in healthy volunteers. Additionally, the study includes an exploratory assessment of target engagement as measured by receptor occupancy. To learn more about the CEL383 clinical trial, visit clinicaltrials.gov (Identifier: NCT05901883). About CEL383 CEL383, Celsius’ first clinical candidate, is an antibody directed towards Triggering Receptor Expressed on Myeloid Cells 1 (TREM1). In preclinical assays, CEL383 has been shown to inhibit TREM1 signaling, reducing the levels of multiple inflammatory mediators of high clinical relevance in inflammatory conditions, such as TNFα and IL23. Celsius has also identified biomarkers of TREM1 pathway dependence that may enable a precision approach to patient selection for CEL383 in ulcerative colitis and Crohn’s disease. About Celsius Therapeutics Celsius Therapeutics is a clinical-stage biotechnology company developing novel precision medicines in inflammatory disease by harnessing the power of single cell RNA sequencing and human biology at scale. The company’s first therapeutic candidate is an anti-TREM1 antibody for the treatment of IBD. Celsius is based in Cambridge, Mass. For more information, please visit , or follow us on LinkedIn or Twitter.