Inotrem Successfully Reaches Agreement with the FDA for a Phase 3 Registration Trial for Nangibotide in Septic Shock

• 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
  

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. www.inotrem.com

Contacts

Media contact for Inotrem
Anne REIN
Strategies & Image (S&I)
anne.rein@strategiesimage.com
+33 6 03 35 92 05

Inotrem Announces Publication of Two Key Articles on Nangibotide Phase II Programs in Peer-reviewed Medical Journals

• Data of ASTONISH Phase 2 trial in septic shock patients is published in The Lancet Respiratory Medicine and data of ESSENTIAL Phase 2 study in critically ill COVID-19 patients is published in eClinicalMedicine.

• Both studies show that a therapeutic intervention with nangibotide can control the TREM-1 pathway in major life-threatening immune dysregulations caused by severe infections, whether it is septic shock or severe forms of COVID-19, leading to improved patient outcome.

Inotrem, an advanced clinical stage biotech company specializing in immunotherapies for acute and chronic inflammatory conditions, announced today the publication of the results of two phase 2 clinical studies in the The Lancet Respiratory Medicine and in eClinicalMedicine. The first article presents the ASTONISH Phase 2b trial in septic shock patients and the second one the ESSENTIAL Phase 2 trial for the treatment of critically ill COVID-19 patients. Both studies reveal that the TREM-1 pathway plays a central role in major life-threatening immune dysregulations caused by severe infections, whether it is septic shock or severe forms of COVID-19. The findings presented further validate Inotrem’s innovative approach to treat inflammatory diseases by targeting TREM-1.

The two studies suggest that nangibotide, which targets TREM-1, is pathogen agnostic and has the potential to treat those very severe inflammatory conditions caused by both viral and bacterial infections. Both studies highlight the potential of nangibotide in the treatment of septic shock patients and of patients with severe forms of COVID-19 with a biomarker guided approach using soluble TREM-1 as predictive marker of response to targeted therapy.

The first manuscript in The Lancet Respiratory Medicine is entitled “Prospective evaluation of the efficacy, safety, and the optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock: a double-blind, randomized, controlled, phase 2b trial” and presents results from 355 septic shock patients. The primary outcome was the change in SOFA at day 5 compared to placebo in the pre-defined high soluble TREM-1 (≥ 400 pg/ml) group and in the overall population. Planned evaluation of the optimal sTREM-1 cut-off revealed increased clinically relevant benefits of high dose nangibotide at higher cutoffs (sTREM-1 ≥ 532 pg/ml). The manuscript can be accessed via the following link: The Lancet Respiratory Medicine.

The second manuscript in eClinicalMedicine, entitled “Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID19 receiving respiratory support: results of the ESSENTIAL randomized, double-blind trial” presents the Phase 2 results obtained in 220 COVID-19 patients receiving ventilatory support. In this study, nangibotide has a significant and positive impact on the clinical progression of the disease, as well as on the severity of the respiratory failure, secondary infection rates and notably mortality. The trial showed that sTREM-1 is an effective prognostic marker of outcome in severe COVID-19. The manuscript can be accessed via the following link: eClinicalMedicine.

“Nangibotide is the first TREM-1 inhibitor and has the potential to become the first causal treatment of life-threatening immune dysregulations. This is an area with a major unmet medical need” said Professor Bruno François, Limoges University Hospital, and lead author on the two manuscripts.

“We are excited to see this data published in The Lancet Respiratory Medicine and in eClinicalMedicine, two of the most established peer-reviewed medical journals in our field. These two publications come as a strong recognition of Inotrem’s innovative scientific leadership regarding the role of the TREM-1 pathway and of our solid therapeutic approaches” said Sven Zimmermann, CEO of Inotrem. “We look forward to bringing this potential new treatment option to patients suffering from severe and often fatal inflammatory conditions.”

About nangibotide

Nangibotide is a TREM-1 inhibitor peptide with the potential to restore appropriate inflammatory response, vascular function, and improve post septic shock survival. Nangibotide is the formulation of the active ingredient LR12, which is a 12 amino-acid peptide prepared by chemical synthesis. LR12 is a specific TREM-1 inhibitor, acting as a decoy receptor and interfering in the binding of TREM-1 and its ligand. In preclinical septic shock models, nangibotide was able to restore appropriate inflammatory response, vascular function, and improved animals’ survival post septic shock. Nangibotide in septic shock has been granted the fast-track status in September 2019 by the FDA and the PRIME status in 2017 by the EMA.

About ASTONISH Study

The Efficacy, Safety and Tolerability of nangibotide in Patients with Septic Shock (ASTONISH) phase 2b trial is a Randomized, Double-blind, Placebo Controlled Dose Selection Study that was performed in Europe and in the US. The study compared the effect of nangibotide at two different doses (0.3 and 1mg/kg/h continuous i.v. infusion for 3 to 5 days) versus standard of care. Results for Phase IIb ASTONISH clinical trial in septic shock patients were disclosed for the first time at the International Sepsis Forum held in Barcelona on October 13. 2022.

About ESSENTIAL Study

The ESSENTIAL phase 2 trial is a double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1·0 mg/kg/h) compared to placebo. The study was stopped after 220 patients had been recruited; of them, 219 were included in the mITT analysis. Patients aged 18-75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48 hours of onset invasive or non-invasive respiratory support because of COVID-19-related ARDS. ESSENTIAL data were disclosed for the first time at the ESICM meeting held in Paris in October 25. 2022.

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 a number of therapeutic indications such as septic shock, severe forms of COVID-19 and myocardial infarction. 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 America

Inotrem Receives Funding from the Crohn’s & Colitis Foundation to help develop new therapeutic approaches in Inflammatory Bowel Disease (IBD)

The funding will support the development of INO-02 a new long-acting therapeutic approach to modulate the TREM-1 pathway.

Inotrem, an advanced clinical stage biotech company specialized in immunotherapies for acute and chronic inflammatory syndromes, announced today it received funding from the Crohn’s & Colitis Foundation’s IBD Ventures under a program to accelerate research and development that aim to improve the quality of life for patients with IBD. The funding will support the development of a new therapeutic approach in IBD focusing on the TREM-1 pathway.

The funding follows a R&D collaboration between Inotrem, and the Crohn’s & Colitis Foundation announced in April 2022. The R&D collaboration seeks to pave the way of a personalized medicine approach in IBD patients based on TREM-1. Under the terms of the agreement, Inotrem has access to data and bio-samples from Foundation’s IBD Plexus®, which is the largest IBD database in the US with data from over 25,000 patients. Last over 18 months, the project will be a cornerstone in the design of Inotrem’s first-in-human clinical study with INO-02.

There are today 10 million people worldwide suffering from IBD, and the need for new therapeutic options remains very strong. Approximately 30% of patients are unresponsive to existing therapies and even among the initial responders, in up to 10% the drugs lose efficacy over time. For a decade, Inotrem has been elucidating the biology of TREM-1 as a regulator of the immune response in both acute as well as chronic inflammatory diseases. TREM-1 is a potential important contributor to IBD pathophysiology and targeting this pathway may offer a new treatment option for IBD patients with immune dysregulation.

“We are grateful for the support of such a well-respected organization as The Crohn’s & Colitis Foundation. This funding will help us to expand our patented technology platform centered around the TREM-1 pathway and dedicated to developing new therapies for chronic inflammatory syndromes next to our existing modalities for acute diseases,” indicates Sven Zimmermann, CEO of Inotrem.

“Beyond the financial support, this is a strong recognition of Inotrem’s scientific leadership regarding the role of the TREM-1 pathway in inflammatory processes as well as our robust therapeutic approaches targeting that biological target,” says Marc Derive, Chief Scientific Officer and Cofounder of Inotrem.

About Inotrem

Inotrem S.A. is an advanced clinical stage biotech company specialized in immunotherapies 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 a number of therapeutic indications such as septic shock and myocardial infarction. In parallel, Inotrem has also launched another 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. Sebastien Gibot and Dr Marc Derive. Inotrem is supported by leading European and North American investors. www.inotrem.com

About the Crohn’s & Colitis Foundation

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. For more information, visit crohnscolitisfoundation.org, call 888-694-8872, or email info@crohnscolitisfoundation.org.

Inotrem Announces That Its ESSENTIAL Phase II Study for the Treatment of Critically ill COVID-19 Patients Meets Its Primary and Key Secondary Endpoints

• Results demonstrate statistically significant efficacy of drug candidate nangibotide in the treatment of patients with severe forms of COVID-19

• Nangibotide treatment improves patients’ clinical status and shows a relative 43% reduction in mortality

• The company will consult with regulatory authorities to advance a new treatment option to severe COVID-19 patients

• ESSENTIAL was made possible thanks to the strong support from French public authorities and their commitment to fight COVID-19

Inotrem, an advanced clinical stage biotech company specializing in immunotherapies for acute and chronic inflammatory syndromes, announced today at the European Society of Intensive Care Medicine’s Annual Congress, held in Paris, positive results for ESSENTIAL, its Phase II clinical trial in COVID-19 patients hospitalized in critical care units and experiencing acute respiratory distress. The study was funded as part of the Capacity Building call for proposals, financed by the Programme d’Investments d’Avenir (PIA), operated on behalf of the French government by Bpifrance, the French national investment bank.

The ESSENTIAL study was terminated at 220 randomized ICU patients requiring ventilatory support (stage 5 or 6 on a 7-point clinical status ordinal scale) and compared infusion of nangibotide at 1mg/kg/hr for up to 5 days of treatment with standard of care. Despite a lower than anticipated sample size, the study met its primary endpoint of an improvement in clinical status according to 7-point clinical status ordinal scale from baseline to Day 28 (p value = 0.040).

Nangibotide treatment also showed a statistically and clinically meaningful 12% absolute and 43% relative reduction 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 more pronounced, amounting to 20% and 47%, respectively (p value = 0.023).

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

Jean-Jacques Garaud, Senior VP Head of scientific and medical affairs at Inotrem said: "This new trial brings compelling evidence that the TREM-1 pathway plays a central role in major life-threatening immune dysregulations caused by severe infections, whether it is severe forms of COVID-19 or septic shock. This study strongly suggests that nangibotide, which targets TREM-1, is pathogen agnostic and has the potential to treat those very severe inflammatory conditions caused by both viral and bacterial infections."

Sven Zimmermann, CEO of Inotrem, added: "We are grateful for the continued financial support and confidence awarded to us by the French public authorities to fight COVID-19. This attests of the relevance of our innovative approach to treat inflammatory diseases. The data we obtained is extremely encouraging, and we plan on quickly consulting regulatory authorities in the US and EU."

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

Substantial support from public funding to fight COVID-19

At the start of the pandemic in 2020, Inotrem team set out to build on the similarities between the immune dysregulation in severe forms of COVID-19 with those observed in septic shock patients. 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 drug lead candidate, nangibotide, for COVID-19 patients in the ICU.

In July 2020, the CoviTREM-1 consortium which includes the Nancy and Limoges university hospitals and Inotrem, obtained a first public funding of 7.5 million euros under a call for projects operated by the Secretary General for Investment and Bpifrance. In December 2020, the trial was declared a "Research National Priority" by the French government. In July 2021, Inotrem was authorized to pursue the clinical development of nangibotide up to registration for COVID-19 patients and can draw on additional public funding of up to 45 million euros from Bpifrance, as part of the Programme d’Investments d’Avenir ("PIA").

About the drug candidate nangibotide

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

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 a number of therapeutic indications such as septic shock, severe forms of COVID-19 and myocardial infarction. 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. www.inotrem.com

Inotrem announces the outcome of its Phase II ASTONISH trial in septic shock patients demonstrating efficacy of nangibotide

• ASTONISH confirms the therapeutic potential of nangibotide in septic shock patients with excessive activation of the TREM-1 pathway

• ASTONISH confirms that the soluble TREM-1 biomarker predicts response to nangibotide treatment.

Inotrem, an advanced clinical stage biotech company specializing in immunotherapies for acute and chronic inflammatory syndromes, disclosed for the first time today at the International Sepsis Forum held in Barcelona the results for its Phase IIb ASTONISH clinical trial in septic shock patients.

ASTONISH was designed to show the efficacy of nangibotide in septic shock with a precision medicine approach aiming to identify patients who benefit the most from this innovative treatment. This global study enrolled 361 patients across 41 clinical sites in 6 European countries and the United States and succeeded in demonstrating a therapeutic benefit of nangibotide in patients with high levels of the TREM-1 pathway activation marker, soluble TREM-1 (sTREM-1).

ASTONISH studied as a primary endpoint the improvement of a well-established morbidity score evaluating patient clinical evolution and organ function, the SOFA score. The change of this score at 5 days after initiation of treatment in the nangibotide-treated arms was compared to the placebo arm in all patients and in patients with a high level of sTREM-1. Importantly, and as part of the prespecified analysis for defining the optimal sTREM-1 cut-off, the benefit of nangibotide high dose treatment versus placebo was clinically and statistically significant at higher concentrations of sTREM-1, representing about 50% of the study population.

Consistent with prior preclinical, observational and Phase IIa trial data in this setting, ASTONISH confirmed that excessive TREM-1 activity is associated with severe immune dysregulation, organ dysfunction and ultimately death.

ASTONISH demonstrates that TREM-1 modulation with nangibotide improves respiratory, cardiovascular and renal function. The study also provided evidence that nangibotide meaningfully impacts other relevant clinical parameters, displaying a trend towards improvement in All-Cause Mortality at day 28 and the proportion of patients Alive and free of organ support at day 28.

Jean-Jacques Garaud, Senior VP Head of scientific and medical affairs at Inotrem, said: “The ASTONISH trial was designed as a Phase III enabling trial and it did generate important insights about nangibotide’s therapeutic activity and our precision medicine approach in septic shock. We are enthusiastic about this study and Inotrem’s capacity to bring a first in class product in an area with a major unmet medical need”.

“These results represent a major advancement for patients suffering from septic shock. They provide compelling evidence that Inotrem’s innovative solution targeting the TREM-1 pathway has the potential to become the first causal treatment for this severe and often fatal indication,” said Sven Zimmermann, CEO of Inotrem. “Based on these data, we intend to advance nangibotide towards registration studies in septic shock. We look forward to discussing next steps with regulatory authorities.”

Professor Bruno François, Limoges University Hospital and coordinating investigator added: “We observed that the TREM-1 pathway was activated in severe infections leading to septic shock. Nangibotide is the first TREM-1 inhibitor and ASTONISH confirms its potential as a new therapeutic option for the septic shock patient population. We are looking forward to bringing definitive evidence, in a Phase III clinical study that nangibotide can reduce mortality in these critically ill patients”.

Septic shock is the ultimate complication of sepsis and currently constitutes a high unmet medical need. The incidence of septic shock continuously raises, and mortality remains elevated: it is the 10th leading cause of death in developed countries and the 1st cause of death in intensive care units. There is currently no specific therapy approved for this indication besides antibiotics and symptomatic treatment. Inotrem’s solution has the potential to become the first mechanism-based treatment for septic shock.

About nangibotide

Nangibotide is a TREM-1 inhibitor peptide with the potential to restore appropriate inflammatory response, vascular function, and improve post septic shock survival. Nangibotide is the formulation of the active ingredient LR12, which is a 12 amino-acid peptide prepared by chemical synthesis. LR12 is a specific TREM-1 inhibitor, acting as a decoy receptor and interfering in the binding of TREM-1 and its ligand. In preclinical septic shock models, nangibotide was able to restore appropriate inflammatory response, vascular function, and improved animals’ survival post septic shock. Nangibotide in septic shock has been granted the fast-track status in September 2019 by the FDA and the PRIME status in 2017 by the EMA. Nangibotide has also been tested in a Phase II trial in severe forms of COVID-19 (ESSENTIAL). ESSENTIAL data will be communicated on October 25. 2022 at the next ESICM meeting in Paris.

About ASTONISH Study

The Efficacy, Safety and Tolerability of nangibotide in Patients with Septic Shock (ASTONISH) phase IIb trial is a Randomized, Double-blind, Placebo Controlled Dose Selection Study that was performed in Europe and in the US. The study compared the effect of nangibotide at two different doses (0.3 and 1mg/kg/h continuous i.v. infusion for 3 to 5 days) versus standard of care.

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 a number of therapeutic indications such as septic shock, severe forms of COVID-19 and myocardial infarction. 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. www.inotrem.com

Inotrem announce the appointment of Luke Beshar as Chairman of Board of Directors

Inotrem, an advanced clinical stage biotech company developing TREM- 1 targeting immunotherapies for acute and chronic inflammatory syndromes, announced today the appointment of Luke Beshar as Chairman of its Board of Directors, effective May 25, 2022. Mr. Beshar succeeds Thierry Hercend who served as Chairman since 2014 and remains a member of the Board of Directors.

“We are pleased to welcome Luke Beshar to the Inotrem Board. Luke's deep experience in strategic development of biotech companies, in both executive and Board level positions of several public and private life science companies will be invaluable to Inotrem as we grow our business and pursue our mission to bring new treatments to patients suffering from inflammatory conditions” said Sven Zimmermann, Chief Executive Officer of Inotrem. “On behalf of the entire Inotrem team, I would like to thank Thierry Hercend for the exceptional work he has accomplished over the years as our Chairman and look very much forward to continue working with him as an Independent Non-executive Board member.”

“I feel privileged to take on this role at such an exciting time for Inotrem,” said Luke Beshar. “I am impressed by the quality of the pioneering work the team has accomplished on the biology of TREM-1 and its clinical translation in severe conditions such as septic shock and severe COVID-19. I’m also really excited about the anti-TREM1 pre-clinical monoclonal antibody programs in chronic inflammation and immuno-oncology. I look forward to working with Sven and the team on Inotrem’s accelerating growth and next stage of development.”

Luke Beshar is a seasoned biotechnology executive and financial expert with more than 35 years of general and financial management experience at various public and private companies. Mr. Beshar currently serves as Chairman of the Board of Protara Therapeutics, Inc., a publicly held company focused on immuno-oncology. Mr. Beshar also serves as director and chair of the audit committee of Omega Therapeutics and previously served as a director at Trillium Therapeutics Inc., a publicly held immuno-oncology company, from 2014 until it was acquired by Pfizer in November 2021 and was chair of its audit and compensation committees. Mr. Beshar previously served as a director and chair of audit committee of REGENXBIO Inc. from 2015 (pre-IPO) to 2021. Prior to this, Mr. Beshar served as Executive Vice President and Chief Financial Officer of NPS Pharmaceuticals, Inc. from November 2007 until it was sold to Takeda (Shire plc) in February 2015 and Executive Vice President and Chief Financial Officer of Cambrex Corporation, from 2002 to 2007. Mr. Beshar holds a B.S. degree in Accounting and Finance from Michigan State University and is a Certified Public Accountant.

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, LR12 (nangibotide), with potential applications in a number of therapeutic indications such as septic shock and myocardial infarction. In parallel, Inotrem has also launched another 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. www.inotrem.com

Inotrem and the Crohn’s & Colitis Foundation Sign a R&D Collaboration Agreement to Support the Development of a New Therapeutic Approach in Inflammatory Bowel Disease (IBD)

Inotrem will leverage cohort resources from the Foundation to identify a new therapeutic target focusing on the TREM-1 pathway.

Inotrem, an advanced clinical stage biotech company specialized in immunotherapies for acute and chronic inflammatory syndromes, announced today a R&D collaboration agreement with the Crohn’s & Colitis Foundation to support the development of a new therapeutic approach in IBD. The Crohn’s & Colitis Foundation is one of world’s largest and most influential non-profit organization dedicated to finding cures for Crohn’s disease and ulcerative colitis.

The objective of the R&D collaboration is to confirm the relationship between the activation of the TREM-1 pathway and the severity and progression of IBD in patients, with the ultimate intention of developing a new treatment. Inotrem will conduct this project in partnership with the Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York. Under the terms of the agreement, Inotrem will access data and bio-samples from Foundation’s IBD Plexus®, which is the largest IBD database in the US with data from over 25,000 patients. The project is expected to last 18 months and will be a cornerstone in the design of Inotrem’s new drug candidate first-in-human clinical study.

There are today 10 million people worldwide suffering from IBD (Crohn’s disease and ulcerative colitis), a lifelong illness for which the medical need continues to be important despite improvement over the last 30 years. Approximately 30% of patients are primarily unresponsive to existing therapies and even among responders, up to 10% will lose their response to the drug every year.

For a decade, Inotrem has been pioneering the biology of TREM-1 as a regulator of the immune response in acute and chronic inflammatory diseases. TREM-1 has been reported as a likely contributor to IBD pathophysiology, and targeting this biological pathway could offer a new treatment option for IBD patients with immune dysregulation.

Sven Zimmermann, CEO of Inotrem, says: "We are looking forward to collaborating with such a recognized and well-respected organization as The Crohn’s & Colitis Foundation. The robustness and diversity of their IBD patient database is unparalleled and will allow for in-depth analysis of TREM-1 potential as a therapeutic target in IBD patients. This agreement marks the beginning a long and fruitful partnership".

"We are dedicated to finding cures for Crohn’s disease and ulcerative colitis and improving the quality of life for those affected by these diseases," said Dr. Caren Heller, Chief Scientific Officer for the Crohn’s & Colitis Foundation. "We are pleased to work with Inotrem, a company that has developed a strong scientific leadership around the TREM-1 pathway, and look forward to understanding the potential ways that the TREM-1 pathway may play a role in the treatment of inflammatory bowel disease."

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, LR12 (nangibotide), with potential applications in a number of therapeutic indications such as septic shock and myocardial infarction. In parallel, Inotrem has also launched another 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. www.inotrem.com

Contacts

Media contact for Inotrem

Anne REIN
Strategies & Image (S&I)
anne.rein@strategiesimage.com
+33 6 03 35 92 05

Inotrem Receives Approval to Expand Nangibotide Clinical Trial in Critically Ill COVID-19 Patients and Receives Additional Public Funding of €45 Million

• Inotrem’s phase 2/3 clinical trial “ESSENTIAL” will enroll up to 730 patients in Europe to demonstrate the safety and efficacy of nangibotide to treat critically ill COVID-19 patients with respiratory failure.

• Recent preclinical studies have strengthened the body of evidence for targeting the TREM-1 pathway which is activated in a subset of patients suffering from severe COVID-19.

Inotrem S.A., a biotechnology company specializing in the development of immunotherapies targeting the TREM-1 pathway, announces that it has obtained authorization to pursue the clinical development of nangibotide up to registration in COVID-19 patients from both the French and Belgian competent authorities.

As part of this program, Inotrem receives additional 45 million euros in public funding under the "Capacity Building" Call for Expression of Interest, operated on behalf of the French government by Bpifrance, the French national investment bank, as part of the Programme d’investissements d’avenir (PIA) and the France Recovery Plan, bringing French state support for the project to a total of 52,5 million euros. This public funding will support Inotrem’s clinical program including the phase 2/3 study “ESSENTIAL” which aims to demonstrate the efficacy and safety of nangibotide in treating patients in respiratory distress with severe forms of COVID-19.

The primary endpoint is evaluation of the impact of nangibotide on the progression of disease in patients receiving ventilatory support due to COVID-19 as well as on the severity of the respiratory failure, duration of mechanical ventilation, length of stay in intensive care and mortality. In “ESSENTIAL”, a Phase 2/3 clinical program, up to 730 patients will be enrolled initially in France and Belgium and, possibly in other European countries. Pre-defined interim analyses will be conducted by an independent Data Monitoring Board to test futility and to allow for the study design to be adapted as necessary. “ESSNTIAL” is the continuation of a 60 patients phase 2a evaluating the safety and efficacy of nangibotide in patients suffering from severe COVID-19. In July 2020, the CoviTREM-1 consortium, which includes the Nancy and Limoges university hospitals and Inotrem, obtained public funding of 7,5 million euros under the “PSPC-COVID” call for projects, operated on behalf of the French government by Bpifrance

New pre-clinical studies with nangibotide have demonstrated that the administration of nangibotide in murine models infected with SARS-CoV-2 was associated with a decrease in inflammatory mediators and an improvement of clinical signs, in particular respiratory function, and survival. Inotrem also confirmed in 3 different and independent cohorts that sTREM-1, a marker of the activation of the TREM-1 biological pathway, is associated with both severity and mortality in critically ill COVID-19 patients.

Leveraging the results of these preclinical studies and the implications for the role of the TREM-1 pathway in COVID-19, Inotrem has filed additional patents to cover nangibotide use in severe forms of COVID-19 as well as the use of sTREM-1 as a biomarker and companion diagnostic. This significantly strengthens Inotrem’s already broad patent estate.

Jean-Jacques Garaud, Executive Vice-President, Head of Scientific and Medical Affairs and Inotrem’s co-founder said :“We are eager to pursue the development of nangibotide in these severe forms of COVID-19. Nangibotide is a TREM-1 inhibitor which has already demonstrated a trend towards efficacy in septic shock patients and has the potential to modulate the dysregulated immune response in critically ill COVID-19 patients. With this large clinical study, we can demonstrate efficacy for nangibotide in a further indication with the goals of reducing the duration of hospitalization and mortality.”

Sven Zimmerman, CEO of Inotrem, also declared: “The size of the financial support awarded to us as part of the French government’s initiative against COVID-19 is a testimony to the relevance of targeting the TREM-1 pathway with nangibotide in these severely ill patients. We are delighted by the confidence placed in our technology and our team. Everyone at Inotrem is fully committed to deliver on this ambitious program alongside nangibotide’s ongoing Phase 2b trial in septic shock patients.”

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, LR12 (nangibotide), with potential applications in a number of therapeutic indications such as septic shock and myocardial infarction. In parallel, Inotrem has also launched another 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.

www.inotrem.com

About TREM-1 pathway

TREM-1 pathway is an amplification loop of the immune response that triggers an exuberant and hyperactivated immune state which is known to play a crucial role in the pathophysiology of septic shock and acute myocardial infarction.

About Nangibotide

Nangibotide is the formulation of the active ingredient LR12, which is a 12 amino-acid peptide prepared by chemical synthesis. LR12 is a specific TREM-1 inhibitor, acting as a decoy receptor and interfering in the binding of TREM-1 and its ligand. In preclinical septic shock models, nangibotide was able to restore appropriate inflammatory response, vascular function, and improved animals’ survival post septic shock.

About ESSENTIAL study:

The Efficacy and Safety Study Exploring Nangibotide Treatment in COVID-19 pAtients with ventiLatory support, is a randomized, double-blind, placebo-controlled confirmatory study with adaptive features that will be performed in Europe. This is a pivotal study and it is expected that based on its results, nangibotide could be registered in this indication. The first part of the study (i.e.: 60 patients) has been already finalized and assessed by an independent data monitoring committee with excellent safety results. The study will recruit up to 730 patients in up to 40 sites. Several interim and futility analyses are foreseen as part of the adaptive design of the study.

About Bpifrance

Bpifrance is the French national investment bank: it finances businesses – at every stage of their development – through loans, guarantees, equity investments and export insurances. Bpifrance also provides extra-financial services (training, consultancy...) to help entrepreneurs meet their challenges (innovation, export…).

For more information, please visit: www.bpifrance.fr and presse.bpifrance.fr

Follow us on Twitter: @Bpifrance

Inotrem announces positive outcome of interim futility analysis for its Phase IIB ASTONISH trial in septic shock patients to demonstrate nangibotide efficacy

• Independent Data Monitoring Committee recommends continuation of the trial with no changes.

• This milestone triggers the payment of the second tranche of €17M of the Series B financing.

Inotrem, an advanced clinical stage biotech company specialized in immunotherapies for acute and chronic inflammatory syndromes, announced today that the ASTONISH Independent Data Monitoring Committee (IDMC) completed the planned safety and efficacy assessment for futility of the company’s ongoing Phase IIB ASTONISH trial in septic shock patients.

The ASTONISH Phase IIB study aims at demonstrating safety and clinical efficacy of nangibotide in septic shock patients. It is a global, multicentric study conducted in 48 centers. Four hundred and fifty patients are planned to be enrolled in this study. The study compares the effect of nangibotide at two different doses versus standard of care. The futility analysis has been conducted on the first 225 patients enrolled. The primary endpoint for futility analysis was the delta SOFA score between the treatment groups and the standard of care/placebo group at day 5. A delta of 1 to 1.5 was observed in a previous Phase IIa trial in a subpopulation of septic shock patients with high concentration of soluble TREM-1, a mechanism-based biomarker. In addition, the ASTONISH study intends to validate a personalized medicine approach using soluble TREM-1 as potential companion diagnostic test to identify patients more likely to benefit from nangibotide treatment.

The IDMC’s decision marks a significant milestone for Inotrem’s development as it triggers the payment of the second tranche of 17 M€ of the Series B financing raised in 2020 from top-tier international investors.

“We are pleased with the IDMC's recommendation to continue the ASTONISH trial as it advances our understanding of the safety, tolerability and efficacy of nangibotide, our lead drug candidate, for septic shock patients. It is an important step toward establishing a potential new treatment for septic shock, a severe and often fatal condition for which there are currently no specific targeted therapies”, said Jean-Jacques Garaud, Executive Vice-President, Head of Scientific and Medical Affairs and Inotrem’s co-founder.

“We look forward to sharing updates from the ASTONISH trial in the coming months. The payment of this €17M tranche strengthens our strategic ability to move towards the completion of our the septic shock program as well as the active development of our drug pipeline in chronic inflammatory conditions”, said Sven Zimmermann, CEO of Inotrem.

Septic shock is the ultimate complication of sepsis and currently constitutes a high unmet medical need. It represents a significant economic burden for the European healthcare system. Recent works have also emphasized the health economic impact of long term patients’ outcomes; indeed 30% of septic shock survivors are re-hospitalized in the three months following a first shock and between 20% and 30% have long term morbidities at twelve months. The incidence of septic shock is bound to increase as the population ages, leading to a rise in ICU admissions. Elderly patients are predisposed to septic shock due to existing co-morbidities, repeated and prolonged hospitalizations, reduced immunity, functional limitations and as well as the effects of aging itself. Europe is therefore poised to see a continuous rise in septic shock in the coming decades. We estimate that by 2025 the incidence of septic shock in Europe will be as high as 500,000 cases leading to 150,000 deaths per year. There is currently no specific therapy approved for this indication besides antibiotics and symptomatic treatment. Inotrem’s solution is based on a novel approach of immunomodulation which targets the TREM-1 pathway: a crucial mediator of the septic shock and has the potential to become the first mechanism-based treatment for septic shock.

About Inotrem

Inotrem S.A. is an advanced clinical stage biotech company specialized in immunotherapy for 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 a number of therapeutic indications such as septic shock and COVID-19. In parallel, Inotrem has launched a program to develop new therapeutic modalities 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. For more information please visit: www.inotrem.com

Media contact for Inotrem

Anne REIN
S&I
anne.rein@strategiesimage.com
+33 6 03 35 92 05

Inotrem bolsters leadership team with the appointment of Sven Zimmermann as new CEO

Inotrem, an advanced clinical stage biotech company specialized in immunotherapies for acute and chronic inflammatory syndromes, announced today the appointment of Sven Zimmermann as Chief Executive Officer, effective April 19th, 2021. Sven brings an extensive leadership experience in biotech companies’ financial and corporate strategy.

Jean-Jacques Garaud, who co-founded Inotrem and successfully led the company over the last 6 years, will continue to play a key role in the development of the company as Executive VP, Head of Scientific and Medical Affairs.

Prior to joining Inotrem, Sven served as Chief Financial Officer at MetrioPharm, a Swiss biopharmaceutical company. He benefits from a wide-ranging international experience in corporate finance, M&A and private and public fund raisings. He has been involved in several recent exits such as Novimmune’s asset sale to Swedish Orphan Biovitrum, Auris Medical’s IPO on Nasdaq as well as the acquisition of PregLem by Gedeon Richter. Prior to this, Sven worked for UBS Investment Bank and holds a PhD in molecular biology from the University of Zurich.

“We are excited that Sven is coming onboard. He brings a broad set of experiences in the development of advanced clinical biotech companies. With his successful financial and corporate strategy track record, and his deep understanding of the immunomodulation field, he has the ideal profile to lead Inotrem’s next phase of strategic growth,” says Thierry Hercend, Chairman of the Board of Directors at Inotrem.

“I am delighted to have been given the opportunity to lead Inotrem through its next growth phase. Its concept of immunomodulation targeting the TREM-1 pathway to control unbalanced inflammatory responses is very innovative and allows for potential treatments for many indications. I am also looking forward to work with Jean-Jacques Garaud as a visionary co-founder and Inotrem’s talented team to bring targeted therapeutic solutions to patients with inflammatory diseases, both acute as well as chronic,” says Sven Zimmermann.

“Over the past few years, the team has accomplished a remarkable work. Thanks to its dedication, the company achieved numerous milestones and successfully diversified its portfolio focused on the role of the TREM-1 pathway in innate and also adaptive immunity. Today, Inotrem is in an extremely favorable position as it engages its next stage of growth focusing on product development and making regulatory advances. I look forward to contributing to Inotrem’s continued success” says Jean-Jacques Garaud.

Based in Paris with a Research Center in Nancy, Inotrem today employs 20 people with the support of leading European and North American investors. Its lead product candidate, nangibotide, currently undergoes two Phase II clinical trials. One is the Phase IIb ASTONISH trial 450 in Patients with Septic Shock being performed in 50 clinical sites in Europe and the US. The second Phase II trial with nangibotide targets the severe forms of COVID-19 in initially 60 patients in 7 sites globally. The latter was declared “National Priority Research” by the French government. In addition, Inotrem is also developing an antibody program for chronic inflammatory diseases and immuno-oncology applications. Moreover, the company has secured a strategic licensing agreement with Roche Diagnostic for a companion diagnostics test to stratify septic shock patients. Inotrem was recently chosen for the second year in a row, to join the French Tech 120, a government program dedicated to support the development of fast-growing startups.

About Inotrem

Inotrem S.A. is an advanced clinical stage biotech company specialized in immunotherapy for 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 a number of therapeutic indications such as septic shock and COVID-19. In parallel, Inotrem has launched a program to develop new therapeutic modalities 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.

For more information please visit: www.inotrem.com

Media contact for Inotrem

Anne REIN
Strategies & Image (S&I)
anne.rein@strategiesimage.com
+33 6 03 35 92 05

Inotrem announces Data Monitoring Committee (DMC) recommends continuation of Phase IIa study of nangibotide for the treatment of severe forms of COVID-19

Inotrem S.A., a biotechnology company specialized in the development of immunotherapies targeting the TREM-1 pathway, announces today that an independent Data Monitoring Committee (DMC) recommends continuation of the Phase IIa study of nangibotide for the treatment of severe forms of COVID-19 hospitalized in intensive care units (ICU). The DMC was composed of unblinded external medical experts and based its decision on a pre-planned interim analysis of safety. This positive decision will allow Inotrem and its partners, the CHRU of Nancy and the CHU of Limoges, to carry on without modification its Phase IIa trial.

The first interim analysis was based on the first 20 patients enrolled. Inotrem expects to complete patients’ enrollment in France, Belgium, and the United States no later than the end the first quarter of 2021. The goal of this study is to determine the safety, tolerability and potential signals of efficacy of nangibotide in critically ill patients with COVID-19. Nangibotide is expected to have a positive impact on the severity of the respiratory failure, reduce duration of mechanical ventilation, length of stay in ICU and reduce mortality.

This study follows an observational study in 27 patients, conducted by Prof. Sébastien Gibot at the CHRU of Nancy, which reported an increased expression of the TREM-1 pathway in severe COVID-19 patients. TREM-1 is an immunomodulatory receptor expressed on innate immune cells which amplifies and maintains inflammation.

In parallel, Inotrem is also currently conducting a Phase IIb trial (ASTONISH) to treat septic shock patients with nangibotide in six European countries and in the United States. Previous clinical studies with nangibotide in septic shock demonstrated that it was safe, well tolerated and showed signals. towards clinically relevant efficacy. Pre-clinical models have shown that nangibotide modulates the amplification of the immune response caused by the activation of TREM-1 and is able to restore appropriate inflammatory response and vascular function, resulting in improved survival in septic shock models.

To conduct the Phase IIa COVID-19 trial, Inotrem and its partners received a non-dilutive funding by the Investments d’Avenir Program which is managed on behalf of the French government by Bpifrance, France’s public investment bank.

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, LR12 (nangibotide), with potential applications in a number of therapeutic indications such as septic shock and myocardial infarction. In parallel, Inotrem has also launched another 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. www.inotrem.com

About TREM-1 pathway

TREM-1 pathway is an amplification loop of the immune response that triggers an exuberant and hyperactivated immune state which is known to play a crucial role in the pathophysiology of septic shock and acute myocardial infarction.

About Nangibotide

Nangibotide is the formulation of the active ingredient LR12, which is a 12 amino-acid peptide prepared by chemical synthesis. LR12 is a specific TREM-1 inhibitor, acting as a decoy receptor and interfering in the binding of TREM-1 and its ligand. In preclinical septic shock models, nangibotide was able to restore appropriate inflammatory response, vascular function, and improved animals’ survival post septic shock.

Media contact for Inotrem

Anne REIN
Strategies & Image (S&I)
anne.rein@strategiesimage.com
+33 6 03 35 92 05

Inotrem expands its Leadership Team with the appointment Delphine Joyeux as Director of Regulatory Affairs and Quality Assurance and of Simon Lambden as Head of Medical Science

Inotrem S.A., a biotechnology company specialized in the development of immunotherapies targeting the TREM-1 pathway, announced today the appointment of Delphine Joyeux as Director of Regulatory Affairs and Quality Assurance and Simon Lambden as Head of Medical Science.

Delphine Joyeux brings 20 years of leadership experience in worldwide Regulatory Affairs and Product Development with a global vision across all disciplines of product development. She will report to Chief Development Officer, Margarita Salcedo-Magguilli. Through this newly created position, Delphine will be responsible for developing and implementing the firm’s regulatory strategies. She will also be in charge of implementing and supervising quality management for the firm. Before joining Inotrem, Delphine was Head of Regulatory Affairs at AB Science. She started her career at Boehringer-Ingelheim, and over the years served both in large global pharmaceutical companies such as Laboratoires Servier, Pfizer and Onxeo. Delphine graduated in 1997 from the School of Pharmacy Paris Sud.

Simon Lambden brings extensive experience in the field of clinical and academic Intensive Care and Internal Medicine. He has completed specialist training in anaesthesia and intensive care alongside which his doctoral and postdoctoral research explored the mechanisms underlying critical illness, work for which he has secured a number of prizes. Simon will report to Dr. Jean-Jacques Garaud, CEO of Inotrem. Through this newly created position, Simon will be responsible for the medical supervision of all ongoing and future clinical research activities at Inotrem. He will also be the safety officer for the products portfolio. Simon is a Clinical Research Associate in Intensive Care Medicine at the University of Cambridge, and an Honorary Consultant in Intensive Care Medicine at Cambridge University Hospitals NHS Foundation Trust.

“We are thrilled to welcome such talented individuals in our leadership team and look forward to their guidance and contributions as we advance our immunotherapy products pipeline. We started collaborating with Simon during Inotrem’s Covid-19 Phase II clinical trial that was launched a few weeks ago and are excited to have him onboard as we are accelerating our development. Delphine has successfully spearheaded regulatory and quality efforts in a number of global biopharmaceutical companies, where she managed European and US clinical trial applications, INDs and marketing authorizations, and will bring great value to the team”, declares Jean-Jacques Garaud, CEO of Inotrem.

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, LR12 (nangibotide), with potential applications in a number of therapeutic indications such as septic shock. In parallel, Inotrem has also launched another 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 belongs to the French Tech 120 program which has been set up by the French President and the Prime Minister to support the development of start-ups with top growth potential. www.inotrem.com

Media contact for Inotrem

Anne REIN

Strategies & Image (S&I)

anne.rein@strategiesimage.com

+33 6 03 35 92 05

Inotrem receives clearance from French, Belgian and US authorities to launch a Phase II clinical trial aimed at assessing nangibotide in mechanically ventilated patients with COVID-19

Inotrem’s clinical study on Covid-19 was selected by the French government to be part of its €78 M action plan aimed at reinforcing the countries’ research capabilities for therapeutic solutions.

Pre-clinical studies have demonstrated that nangibotide has a positive effect on controlling inflammatory syndromes and restores an appropriate immune response by targeting the TREM-1 pathway which is activated in patients suffering from COVID-19.

Inotrem S.A., a biotechnology company specialized in the development of immunotherapies targeting the TREM-1 pathway, announced today that it has obtained authorization to launch its phase IIa clinical trial in COVID-19 patients in France, Belgium and the USA.

For this study, Inotrem received a non-dilutive funding as part of the call for proposals PSPC Covid, financed by the Investments d’Avenir Program which managed on behalf of the French government by Bpifrance, France’s public investment bank. Inotrem with its partners the CHRU of Nancy and the CHU of Limoges, was one of the 6 French biotech companies who benefited from this programme to support the research and development of therapeutic solutions targeting COVID-19.

The goal of this first exploratory study is to determine the safety and tolerability and potential signals of efficacy of nangibotide in critically ill patients with COVID-19 with inflammatory syndromes. The objective of this project is to have a positive impact on the severity of the respiratory failure, reduce duration of mechanical ventilation, length of stay in ICU and reduce mortality. Sixty patients will be enrolled in Europe and in the United States. This study follows an observational study in 27 patients, conducted by Prof. Sébastien Gibot at the CHRU of Nancy, which showed an increased expression of the TREM-1 pathway in severe COVID-19 patients. TREM-1 is an immunomodulatory receptor expressed on innate immune cells which amplifies and maintains inflammation.

Previous clinical studies with nangibotide demonstrated its safety and tolerability in patients suffering from septic shock, which is also characterized by an acute inflammatory syndrome. Pre-clinical models have shown that nangibotide inhibits the amplification of the immune response caused by the activation of TREM-1 and was able to restore appropriate inflammatory response, vascular function, and improved survival in septic shock models. Inotrem is currently conducting a Phase IIb trial (ASTONISH) to treat septic shock patients with nangibotide in 6 European countries and the United States. It is also developing, with Roche Diagnostics, a companion diagnostic test to identify patients more likely to benefit from its nangibotide treatment. Coronavirus disease 2019 is a new pandemic disease that arises as a consequence of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The optimum treatment strategy in the management of critically ill patients with COVID-19 continues to evolve and, in addition to supportive therapies such as mechanical ventilation, vasopressors and renal replacement therapy, may include immunomodulatory approaches, such as nangibotide, in patients with severe disease.

Professor Sébastien Gibot, Nancy University Hospital and coordinating investigator said “We observed that the TREM-1 pathway was activated in severe forms of COVID-19. Nangibotide is a TREM-1 inhibitor and has the potential to restore an appropriate immune response. We are hoping to demonstrate that nangibotide will reduce the duration of hospitalization and mortality of critically ill patients suffering from COVID-19”.

Jean-Jacques Garaud, CEO of Inotrem, declared: “We are very pleased with both the granting of this financial support and the clearance to start our clinical trial. The French administration has been very effective in working in a coordinated and rapid fashion.”

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, LR12 (nangibotide), with potential applications in a number of therapeutic indications such as septic shock and myocardial infarction. In parallel, Inotrem has also launched another 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. www.inotrem.com

About TREM-1 pathway

TREM-1 pathway is an amplification loop of the immune response that triggers an exuberant and hyperactivated immune state which is known to play a crucial role in the pathophysiology of septic shock and acute myocardial infarction. Today, there is an increasing number of publications indicating that the TREM-1 pathway is also implicated in chronic inflammatory diseases.

About Nangibotide

Nangibotide is the formulation of the active ingredient LR12, which is a 12 amino-acid peptide prepared by chemical synthesis. LR12 is a specific TREM-1 inhibitor, acting as a decoy receptor and interfering in the binding of TREM-1 and its ligand. In preclinical septic shock models, nangibotide was able to restore appropriate inflammatory response, vascular function, and improved animals’ survival post septic shock.

About ASTONISH Study

The Efficacy, Safety and Tolerability of nangibotide in Patients with Septic Shock (ASTONISH) phase IIb trial is a Randomized, Double-blind, Placebo Controlled Dose Selection Study that will be performed Europe and the US. Four hundred and fifty patients are planned to be included in this study in 48 clinical sites. The study will compare the effect of nangibotide at two different doses versus standard of care.

About Bpifrance

Bpifrance is the French national investment bank: it finances businesses – at every stage of their development – through loans, guarantees, equity investments and export insurances. Bpifrance also provides extrafinancial services (training, consultancy.). to help entrepreneurs meet their challenges (innovation, export…). For more information, please visit: www.bpifrance.fr and presse.bpifrance.fr - Follow us on Twitter: @Bpifrance - @BpifrancePresse

About French Strategic Investment Program

Endowed with 57 billion euros, the “French Strategic Investment Program” (PIA), lead by the General Secretary for Investment under the authority of the Prime minister, has been implemented to finance innovative and promising investments all over the territory, in order to allow France to increase its potential for long-term growth and jobs creation. The third component of the PIA, endowed with 10 billion euros, is part of the 57 billion euros Grand Plan d’Investissement (GPI) committed by the Government in 2017 and for a five years period in order to support structural reforms and respond to four major challenges in France : carbon neutrality, better access to employment, competitiveness through innovation and building the digital state.

Media contact for Inotrem

Anne REIN

S&I

anne.rein@strategiesimage.com

+33 6 03 35 92 05

Inotrem expands Series B financing to €58 Million with a mix of Equity and Debt, adding new investors Fountain Healthcare Partners, Kreos and BPI France

• New investor Fountain Healthcare Partners provides a further €5 M capital increase adding on the initial €39 M announced last September

• Inotrem also secured a €13 M credit line from Kreos Capital and a €1 M loan from BPI France.

• Proceeds will be used to advance the Company’s applications in septic shock and chronic inflammatory diseases.

Inotrem S.A., a biotechnology company specialized in the development of immunotherapies targeting the TREM-1 pathway with potential applications for acute and chronic inflammatory syndromes, announced a €5M capital increase financed by Fountain Healthcare Partners, a leading Irish venture capital firm with offices in Dublin and New York. This fundraising brings Inotrem’s Series B financing to a final closing amount of €44M. In addition, the Company secured a €13M credit line from Kreos Capital, Europe's largest provider of specialty finance to growth companies, and a €1M loan from BPI France, France’s public investment bank.

The financing will support Inotrem’s R&D effort, in particular of its lead drug candidate, nangibotide, which is currently undergoing a global multicentric Phase IIb trial in septic shock patients (ASTONISH trial) in 5 European countries and the United States, and of a companion diagnostic tool aimed at selecting those septic shock patients that are more likely to respond favorably to treatment. Financing will also allow the Company to expand its TREM-1 franchise to address chronic inflammatory diseases.

“With Fountain Healthcare Partners joining our pool of world-class investors, Inotrem is in an ideal position to advance its market-breaking technology platform centered on the TREM-1 pathway and bring new immunotherapies to patients and the medical community” said Jean-Jacques Garaud, CEO of Inotrem.

Based on a novel approach of immunomodulation which targets the TREM-1 pathway, Inotrem has developed a proprietary technology platform and leverages its extensive knowledge of the TREM-1 pathway biology to develop programs in several indications with inflammatory syndromes for which there is a major and today unsatisfied therapeutic need. Its lead compound, nangibotide, targets septic shock which is the ultimate complication of sepsis. The incidence of septic shock continuously raises and mortality remains elevated (35%) in developed countries. There is currently no specific mechanism-based therapy approved for this indication. Inotrem’s solution has the potential to become the first mechanism-based treatment for septic shock.

“Inotrem has demonstrated its ability to reach several critical milestones and we are delighted to back this team. The TREM-1 pathway is extremely compelling and has great potential to bring solutions to patients that today lack effective therapies”, indicated Ena Prosser of Fountain Healthcare Partners.

In conjunction with the financing, Ena Prosser of Fountain Healthcare Partners will become a member of Inotrem’s Board of Directors, and Aris Contantinides of Kreos Capital will become an observer on Inotrem’s Board of Directors.

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, LR12 (nangibotide), with potential applications in a number of therapeutic indications such as septic shock and myocardial infarction. In parallel, Inotrem has also launched another 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 a FrenchTech120 company: it was chosen to join the program launched by the French President of the Republic and the Prime Minister to support the development of fast growing startups. For more information please visit: www.inotrem.com

About Fountain Healthcare Partners

Fountain Healthcare Partners is a life science venture capital fund with offices in Dublin, and New York. Founded in 2008, Fountain is Ireland’s largest dedicated life science venture capital fund with more than €294 million under management. Fountain invests in entrepreneurs and companies with disruptive technologies or products that have a clear pharmacoeconomic benefit and a defined pathway to commercialisation, value enhancement and exit. Fountain typically leads or co-leads its investments and has sourced private and public deals from start-ups, corporate spin-outs and turnaround situations. The Fountain Healthcare Partners team brings to investees over 70 years of collective experience in the pharmaceutical industry, corporate venture capital and VC across multiple investment and market cycles. For more information please visit: www.fh-partners.com

About Kreos Capital

Kreos Capital is the leading provider of growth-debt financing to high-growth companies in Europe and Israel with revenues up to EUR 300 million. Since 1998, as the pioneer growth debt provider across Europe and Israel, Kreos has completed 540 transactions and committed more than EUR 2.3 billion in 16 different countries. Kreos is dedicated to supporting management teams and their equity investors with flexible loan structures for all stages of a growth company's development and to address the needs for growth capital, working capital, acquisition financings, lower mid-market buy-outs, roll-up strategies, banks re-financings as well as pre- and post-IPO financings. Kreos's most recent fund, EUR 700 million Kreos VI, was launched in January 2019. The Kreos global team has extensive debt financing, management and equity investing experience, covering the markets in Europe and Israel from its locations in London, Tel-Aviv and Stockholm.

Media contact for Inotrem

Anne REIN S&I | STRATEGIES&IMAGE

anne.rein@strategiesimage.com

+33 6 03 35 92 05