Efficacy and Safety Study Exploring Nangibotide Treatment in COVID-19 pAtients With ventiLatory Support (ESSENTIAL) A Randomized, Double-blind, Placebo-controlled Study With Adaptive Features

This is a randomized, double-blind, placebo-controlled, in which one dose of nangibotide will be tested versus placebo.
All patients with a diagnosis of COVID-19, and a requirement for respiratory support will be considered for study participation. The applicable local requirements for informed consent will be followed. Where permissible, an emergency consent procedure will be followed for patients unable to provide consent by themselves. All potential study patients will receive standard of care treatment throughout the study. Patients will receive a continuous intravenous (i.v.) infusion of nangibotide at 1.0 mg/kg/h or a matching placebo. Treatment with study drug must be initiated as early as possible but no later than 48 hours after the initiation of ventilatory support (Patients will be treated for 5 days or until discharge from critical care, whichever is sooner). Follow-up visits will be performed on days 8 and 14. The end of study visit is at day 28. A further follow up visit will be undertaken on day 60.

Start Date23 Sep 2020

Sponsor / Collaborator

Inotrem SA

EUCTR2020-001504-42-BE

/ Not yet recruitingPhase 2/3

Efficacy and Safety Study Exploring Nangibotide Treatment in COVID-19 pAtients with ventiLatory support (The ESSENTIAL Study). A randomized, double-blind, placebo-controlled study with adaptive features.

Start Date12 Jun 2020

Sponsor / Collaborator-

NCT04055909

/ Active, not recruitingPhase 2

Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study

This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo.

Start Date13 Nov 2019

Sponsor / Collaborator

Inotrem SA

100 Clinical Results associated with Nangibotide

100 Translational Medicine associated with Nangibotide

100 Patents (Medical) associated with Nangibotide

Literatures (Medical) associated with Nangibotide

01 Sep 2024·Neurology Neuroimmunology & Neuroinflammation

Single-Cell RNA Sequencing Reveals Transcriptional Landscape of Neutrophils and Highlights the Role of TREM-1 in EAE

Article

Author: Cui, Xiaoyang ; Yi, Le ; Ba, Yongbing ; Quan, Moyuan ; Bi, Yanwei ; Zhang, Huining ; Li, Bin ; Han, Xianxian

BACKGROUND AND OBJECTIVESNeutrophils, underestimated in multiple sclerosis (MS), are gaining increased attention for their significant functions in patients with MS and the experimental autoimmune encephalomyelitis (EAE) animal model. However, the precise role of neutrophils in cervical lymph nodes (CLNs), the primary CNS-draining lymph nodes where the autoimmune response is initiated during the progression of EAE, remains poorly understood.METHODSApplying single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive immune cell atlas of CLNs during development of EAE. Through this atlas, we concentrated on and uncovered the transcriptional landscape, phenotypic and functional heterogeneity of neutrophils, and their crosstalk with immune cells within CLNs in the neuroinflammatory processes in EAE.RESULTSNotably, we observed a substantial increase in the neutrophil population in EAE mice, with a particular emphasis on the significant rise within the CLNs. Neutrophils in CLNs were categorized into 3 subtypes, and we explored the specific roles and developmental trajectories of each distinct neutrophil subtype. Neutrophils were found to engage in extensive interactions with other immune cells, playing crucial roles in T-cell activation. Moreover, our findings highlighted the strong migratory ability of neutrophils to CLNs, partly regulated by triggering the receptor expressed on myeloid cells 1 (TREM-1). Inhibiting TREM1 with LR12 prevents neutrophil migration both in vivo and in vitro. In addition, in patients with MS, we confirmed an increase in peripheral neutrophils with an upregulation of TREM-1.DISCUSSIONOur research provides a comprehensive and precise single-cell atlas of CLNs in EAE, highlighting the role of neutrophils in regulating the periphery immune response. In addition, TREM-1 emerged as an essential regulator of neutrophil migration to CLNs, holding promise as a potential therapeutic target in MS.

01 Feb 2024·Plant Disease

Race and Virulence Dynamics of Puccinia triticina in China During 2007 to 2021

Article

Author: Huang, Liang ; Zhang, Hao ; Li, Hongfu ; Chen, Wanquan ; Liu, Bo ; Gao, Li ; Liu, Taiguo

The challenge of wheat leaf rust on wheat production is a recurring issue. Race identification of Puccinia triticina (Pt) serves as the foundation for preventing and controlling this disease. In a 15-year study, we identified 2,900 isolates of Pt from 20 provinces, cities, or autonomous regions in China during 2007 to 2021 and found 332 virulence phenotypes with 11 predominant phenotypes: PHT (8.3%), THT (5.4%), PHK (4.5%), PHJ (3.7%), THJ (3.6%), SHJ (3.5%), THS (3.3%), FGD (2.9%), THK (2.6%), PHS (2.4%), and PHD (2.0%). The virulence frequency for 40 Lr genes was identified across different years and areas; one major reason for the race dynamics was the attenuation to Lr1 and Lr26, which was more evident in southwest China. Lr9, Lr24, Lr28, Lr38, and Lr42 maintained effectiveness in China, while Lr2c, Lr10, Lr12, Lr14a, Lr14b, Lr22a, Lr33, and Lr36 nearly lost their effectiveness against wheat leaf rust disease. No significant difference was found among predominant phenotypes in different areas (P > 0.1). However, 12 Lr sites were found to have differences in virulence frequencies with values greater than 20% across various locations; furthermore, the lowest and highest virulence values were observed in north China (Area 1) and northwest China (Area 5), respectively. According to phenotype dynamics, PHT, THT, FGD, THK, and PHS are more likely to persist over time. In addition, much attention should be given toward discovering rising combinations of virulent phenotypes.

01 Oct 2023·The Lancet. Respiratory medicine

Nangibotide for precision immunomodulation in septic shock and COVID-19.

Article

Author: Neupane, Maniraj ; Kadri, Sameer S

News (Medical) associated with Nangibotide

27 Feb 2024

·www.businesswire.com

Sepsis Drug Pipeline Research Report 2024: Insights from 30 Companies and 35 Pipeline Drugs - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "Sepsis - Pipeline Insight, 2024" clinical trials has been added to ResearchAndMarkets.com's offering. This report provides comprehensive insights about 30+ companies and 35+ pipeline drugs in Sepsis pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. The report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Sepsis pipeline landscape is provided which includes the disease overview and Sepsis treatment guidelines. The assessment part of the report embraces, in depth Sepsis commercial assessment and clinical assessment of the pipeline products under development In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Sepsis collaborations, licensing, mergers and acquisition, funding, designations and other product related details. Report Highlights The companies and academics are working to assess challenges and seek opportunities that could influence Sepsis R&D. The therapies under development are focused on novel approaches to treat/improve Sepsis. Sepsis Emerging Drugs Chapters This segment of the Sepsis report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Sepsis Emerging Drugs Thymosin alpha 1: SciClone Pharmaceuticals Thymosin alpha 1, referred to as thymalfasin, is a synthetic 28-amino acid peptide with multiple biological activities primarily directed towards immune response enhancement. SciClone developed and launched Thymosin alpha 1, under the trade name Zadaxin, for the treatment of hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infections. The drug is also being developed for the treatment of COVID 2019 infections. Scientific and clinical studies have shown that Thymosin alpha 1 helps to stimulate and direct the body's immune response to eradicate infectious diseases, such as HBV, HCV, bacterial, and fungal infections; to fight certain cancers such as melanoma and liver cancer; and to enhance response to vaccines. Clinical trials have shown that Thymosin alpha 1 improves survival in patients in intensive care units being treated for sepsis from severe bacterial infections. The therapy is being evaluated in Phase III stage to treat Sepsis. Currently, the drug is in Phase III stage of its development for the treatment of sepsis. Enibarcimab: AdrenoMed AG Enibarcimab (HAM8101; former name: Adrecizumab) a clinical-stage, first-in-class drug targeting loss of vascular integrity. The strong rationale for Enibarcimab is supported by the elegance of its mode of action, a monoclonal antibody that on binding to its target Adrenomedullin preserves its functionality as regulator of vascular integrity. Enibarcimab targets Adrenomedullin (ADM), a vasoprotective peptide hormone. ADM that remains in the bloodstream, however, has a different effect, one that helps mitigate sepsis: promoting stability of the endothelial barrier by restoring the cell junctions between endothelial cells that ordinarily regulate molecule transport and leakage. In health, levels of ADM in the bloodstream and extravascular space are in equilibrium so that endothelial barrier integrity is maintained and blood pressure remains normal. Currently, the drug is in Phase II stage of its development for the treatment of sepsis. M 6229: Matisse Pharmaceuticals Matisse's platform technology is based on the discovery that in many patients suffering from sepsis, proteins called histones are released by the innate immune system and dying cells into the blood stream, where they are toxic to other cells. Due to a self-enforcing cascade, people may die from organ failure within one or two days. Preclinical results have shown that by neutralizing the toxic histones with Matisse's product M6229, the negative cascade is terminated by neutralization of cationic histones by anionic M6229. Matisse claims to have identified an elegant solution for treating one of the major complications in sepsis by using a non-anticoagulant fraction of heparin called M6229 to neutralize toxic circulatory histones .Currently, the drug is in Phase I stage of its development for the treatment of sepsis. SNIPR 001: SNIPR Biome SNIPR001 is a novel, orally-administered antibiotic that is designed to precisely target difficult-to-treat bacterial infections. It is developed using SNIPR Biome's CRISPR-Guided VectorsT (CGVT Technology), which is designed to deliver CRISPR reagents into target bacterial cells. SNIPR001 is designed to target certain E. coli bacteria in the gut and thus prevent their translocation to the bloodstream, without affecting beneficial bacteria in the microbiome. It contains four CRISPR-armed phages that selectively target and eliminate E. coli strains that are resistant to fluoroquinolone, with demonstrated efficacy in animal disease models. Currently, the drug is in preclinical stage of its development for the treatment of sepsis. Sepsis: Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Sepsis therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Sepsis drugs. Sepsis: Therapeutic Assessment Phases Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Products have been categorized under various ROAs such as Oral Intravenous Subcutaneous Parenteral Topical Molecule Type Products have been categorized under various Molecule types such as Recombinant fusion proteins Small molecule Monoclonal antibody Peptide Polymer Gene therapy Product Type Sepsis Report Insights Sepsis Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs Sepsis Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players SciClone Pharmaceuticals AdrenoMed AG Matisse Pharmaceuticals SNIPR Biome Tianjin Chase Sun Pharmaceutical Beijing Scitech-Mq Pharmaceuticals Recce Pharmaceuticals Inotrem Octapharma Shaperon Shionogi Pharmazz Seres Therapeutics Key Products Thymosin alpha 1 Enibarcimab M 6229 SNIPR 001 Kukoamine B ST-1830 RECCE 327 Nangibotide OctaplasLG HY209 Cefiderocol Centhaquine SER 155 For more information about this clinical trials report visit https://www.researchandmarkets.com/r/ixi7k5 About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

Phase 2Phase 3Phase 1

08 Jan 2024

·www.biospace.com

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. 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:

Phase 3ImmunotherapyPhase 2

06 Nov 2023

·www.biospace.com

Inotrem Receives Milestone Funding From the Crohn’s & Colitis Foundation IBD Ventures Program to Advance Its Inflammatory Bowel Disease Pipeline

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:

Immunotherapy

100 Deals associated with Nangibotide

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KEGG	Wiki	ATC	Drug Bank
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Indication	Highest Phase	Country/Location	Organization	Date
Shock, Septic	Phase 3	NL	Inotrem SA	03 Jul 2017
Myocardial Infarction	Phase 3	FR	Inotrem SA	-
Shock, Septic	Phase 2	ES	Inotrem SA	03 Jul 2017
Shock, Septic	Phase 2	FR	Inotrem SA	03 Jul 2017
Shock, Septic	Phase 2	BE	Inotrem SA	03 Jul 2017
COVID-19	Preclinical	BE	Inotrem SA	06 Jul 2020

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04055909 (ASTONISH, Pubmed \| Lancet Respir Med)	Phase 2	Shock, Septic	355	Nangibotide 0.3 mg/kg per h	(kyaevlmpcz) = pwevumarkk ilclozdjsp (ucnjpzvqgf )	Negative	01 Oct 2023
				Nangibotide 1.0 mg/kg per h	(kyaevlmpcz) = qzxhfdzqet ilclozdjsp (ucnjpzvqgf )
NCT04429334 (ESSENTIAL, Pubmed)	Phase 2	COVID-19	220	Nangibotide	pihmpiyqoo(gusjzyebzi): odds ratio = 1.79 (95% CI, 1.02 - 3.14), P-Value = 0.043	Positive	01 Jun 2023
				Placebo
NCT04429334 (ESSENTIAL, Biospace) Manual	Phase 2	COVID-19	220	nangibotide	xzrggafvph(lzkhxlrybj): P-Value = 0.040 View more	Positive	25 Oct 2022
				Placebo
NCT04055909 (ASTONISH, PipelineReview) Manual	Phase 2	Shock, Septic	-	Nangibotide	(hdxelouioj) = 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 jgflwgpwyi (onlclqdwxj )	Positive	13 Oct 2022
				Standard of Care
NCT03463044 (Pubmed \| Br J Clin Pharmacol)	Phase 1	Acute Disease	27	Nangibotide	aginvgkccp(wnyduybynh) = There were only few adverse events and they were mild in severity and considered unrelated to treatment nzpwxvqcns (uqmcmwlvbx )	-	01 Oct 2018

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