Motrem (nangibotide) / Inotrem - LARVOL DELTA

Climate-Resilient Bread Wheat for Arid Environments: Adaptation and Yield Performance of Diverse Genotypes Across Contrasting Growing Conditions. (PubMed, Plants (Basel)) - "Multivariate analyses, including principal component analysis, hierarchical clustering, and AMMI identified Riyadh-1, ACS-1454, ACS-1422, ACS-1372 and Maeaa as promising candidates for cultivation and breeding. Furthermore, the local landraces (LR-12 and LR-599) represent valuable sources of adaptive genetic diversity and grain quality for climate-resilient wheat cultivars."

Journal

TREM1-mediated macrophage activation drives voriconazole-induced hepatic steatosis: Diagnostic and therapeutic implications. (PubMed, J Pharm Anal) - "Voriconazole (VCZ)-induced hepatotoxicity lacks effective early biomarkers and targeted interventions. This study elucidated a TREM1-centered signaling network linking VCZ-induced inflammation to steatosis. sTREM1 showed potential as a translational biomarker for early detection of liver injury, and TREM1 inhibition (LR12) offers a promising therapeutic strategy for antifungal-related hepatotoxicity."

IO biomarker • Journal • Hepatology • Inflammation • Liver Failure • Metabolic Disorders • IL1B • NLRP3 • TLR4

Collagen-Enriched Immunomodulatory Hydrogel for Tendon Regeneration. (PubMed, Gels) - "The objective of this study was to engineer and evaluate the immunocompatibility of a tendon-mimetic hydrogel composed of a chitosan-polyvinyl alcohol (PVA) blend incorporated with Collagen-I and to assess LR12 delivery for addressing TREM1-driven inflammation in RCTI management...Additionally, the CPHA hydrogel displayed an increased TGFβ/TLR4 ratio (0.24), whereas the CPHA-C (-0.52) system showed a decreased ratio upon exposure to tenocytes and macrophages. Overall, the findings highlight the potential of CPHA and CPHA-C hydrogels as candidates for tendon regenerative applications."

Journal • Inflammation • TGFB1 • TLR4

TREM-1 inhibition with LR12 attenuates in-stent neoatherosclerosis through modulating macrophage polarization in a rabbit model: An optical coherence tomography study. (PubMed, Atherosclerosis) - "Pharmacological inhibition of TREM-1 using LR12 effectively suppresses ISNA development without compromising stent healing, probably by inhibiting pro-inflammatory M1 polarization and promoting anti-inflammatory M2 macrophage phenotypes through modulation of the JAK1-STAT1/STAT3 signaling pathway. These results motivate further trials evaluating LR12 as a promising therapeutic strategy targeting inflammation to prevent ISNA in patients."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Inflammation • Thrombosis • IL12A • IL6 • JAK1 • TNFA

The TREM Receptor Family in Cardiovascular Diseases: Functions, Mechanisms and Therapeutic Perspectives. (PubMed, Int Immunopharmacol) - "The TREM family constitutes a pivotal immunoregulatory axis in CVD, with the TREM1/TREM2 balance critically determining inflammatory burden and tissue outcomes. Targeting this family, particularly through dual strategies of TREM1 inhibition and TREM2 activation, represents a promising frontier for immunomodulatory therapy in CVD. Overcoming challenges related to ligand identification, cellular specificity, and species divergence will be crucial for successful clinical translation."

Journal • Review • Atherosclerosis • Cardiomyopathy • Cardiovascular • Coronary Artery Disease • Hematological Disorders • Infectious Disease • Inflammation • Ischemic stroke • Myocardial Infarction • Septic Shock • Thrombosis

Inhibition of TREM1 attenuates myocardial ischemia-reperfusion injury-induced cardiomyocyte pyroptosis by suppressing the activation of the NF-κB signaling pathway. (PubMed, PLoS One) - "Our findings indicate that inhibition of TREM-1 alleviates cardiomyocyte pyroptosis during MIRI by suppressing activation of the NF-κB signaling pathway. Therefore, TREM-1 may represent a promising therapeutic target for the treatment of myocardial ischemia-reperfusion injury."

Journal • Atherosclerosis • Atrial Fibrillation • Cardiovascular • Fibrosis • Immunology • Infectious Disease • Inflammation • Myocardial Ischemia • Reperfusion Injury • NLRP3

Spatially Resolved Transcriptomics Reveal Macrophage Heterogeneity in Giant Cell Arteritis (ACR Convergence 2025) - "In vitro functional analyses included THP-1-derived macrophages cultured and a TREM-1 inhibition assay using nangibotide. Spatial transcriptomics showed TREM-1 signaling among top upregulated pathways in media-infiltrating CD68⁺ macrophages from GCA lesions, alongside Th1, IL-6, and interferon signaling pathways, and identified IFN-γ and TLR activation as major upstream regulators using Ingenuity Pathway Analysis... TREM-1 and TREM-2 define distinct macrophage subsets in GCA. TREM-1 is associated with inflammation and monocyte recruitment, while TREM-2 may mediate homeostatic functions. These findings position TREM-1 as a promising therapeutic target."

Heterogeneity • Giant Cell Arteritis • Immunology • Inflammation • Vasculitis • CD4 • CD68 • GPNMB • IFNG • IL13 • IL17A • IL4 • IL6 • MERTK • SPP1 • TREM2

The role of Toll-like receptors in liver regeneration after partial hepatectomy. (PubMed, Prz Gastroenterol) - "One group of each type was sacrificed at 12 h (LR12 and Sh12), 24 h (LR24 and Sh24), 36 h (LR36 and Sh36), and 168 h (LR168 and Sh168)...TLR expression was significantly higher in mice that underwent partial hepatectomy than the controls. Further research is required to investigate their potential as therapeutic targets in the management of acute or chronic liver failure after partial hepatectomy."

IO biomarker • Journal • Hepatology • Liver Failure • IRAK4 • MYD88 • TLR1 • TLR2

Mechanism of TREM1-regulated pro-inflammatory polarization in macrophages mediating voriconazole-induced liver injury (IDDF 2025) - "TREM1 inhibitor LR12 could attenuate hepatic inflammation and steatosis, suppressing PI3K/AKT-NFκB-NLRP3 signaling axis activation while restoring lipid metabolic homeostasis.Download figure Open in new tab Download powerpoint Abstract IDDF2025-ABS-0173 Figure 1 Graphical abstractConclusions This study identified TREM1-mediated macrophage inflammatory polarization through the TLR4-PI3K/Akt-NFκB-NLRP3 signaling axis, concurrently promoting hepatic steatosis. These findings identify TREM1 as a potential diagnostic biomarker and therapeutic target for DILI. Preclinical evidence confirms the efficacy of TREM1 inhibitors in animal models, providing a theoretical basis for the development of targeted drugs."

Hepatology • Inflammation • Liver Failure • IL1B • NLRP3 • TLR4

Ligand-Independent TREM-1 Blockade Ameliorates Pulmonary Inflammation and Fibrosis (ATS 2025) - "Multiplicity and promiscuity of TREM-1 ligands significantly increase the risk of failure of traditional, ligand-dependent approaches to TREM-1 inhibition (e.g., anti-TREM-1 blocking antibodies and decoy peptides) in clinical efficacy testing. Despite promising preclinical data and safety in humans, the first clinical inhibitor of TREM-1, a decoy peptide LR12 (nangibotide), failed in phase IIb sepsis trial... Ligand-independent TREM-1 blockade for the first time has been shown to ameliorate pulmonary inflammation and fibrosis in animal models, warranting further development of a novel, first-in-class TREM-1 therapy for human ARDS and PF."

Acute Lung Injury • Acute Respiratory Distress Syndrome • Fibrosis • Immunology • Infectious Disease • Inflammation • Pneumonia • Septic Shock

Inhibition of Triggering Receptor Expressed on Myeloid Cells 1 (TREM1) Attenuates Allergic Airway Inflammation in a Mouse Model of Allergic Asthma (ATS 2025) - "Our findings demonstrated that LR12 partially modulates Th2-mediated inflammation in HDM-induced asthma, suggesting it may attenuate allergen sensitization and response. These results support further study of TREM-1 inhibition as a promising non-steroidal asthma controller therapy."

Preclinical • Asthma • Immunology • Inflammation • Respiratory Diseases • CXCL8 • IL1B • IL4 • IL5 • IL6

A mechanism-based prognostic enrichment strategy for the development of the TREM-1 inhibitor nangibotide in septic shock. (PubMed, Intensive Care Med) - No abstract available

Journal • Septic Shock

Stearyl amine coated liposome of rotigotine alleviates cognitive deficit in Parkinson's disease induced mice model: modulation of oxidative stress, and motor coordination. (PubMed, Drug Dev Ind Pharm) - "The study was conducted to evaluate the brain targeted delivery of cationic liposomes of rotigotine via nasal route, addressing the limitations in brain penetration for Parkinson's disease intervention...The optimized liposome, LR12, was surface modified with stearylamine at three concentrations to confer a cationic charge...The cationic liposome RTG-LP3 demonstrated effective delivery of liposomes with superior therapeutic effects in treating PD via nasal route. These findings highlight the potential of cationic liposomes as a viable method for improving brain penetration and neuroprotection in PD therapy."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Recent advances of precision immunotherapy in sepsis. (PubMed, Burns Trauma) - "Suggested strategies to attenuate the immune responses are anakinra, nangibotide and tocilizumab...Suggested strategies to restore SII are nivolumab, recombinant human interferon-gamma, CYT107, granulocyte macrophage colony stimulating factor and IgM-enriched immunoglobulin prepapations. Biomarkers that guide their use are the expression of the human leukocyte antigen DR on blood monocytes, the absolute lymphocyte count and blood levels of immunoglobulin M. One recently suggested strategy to restore vascular tone is adrecizumab, the use of which is guided by blood levels of bio-adrenomedulin. The use of these precision treatment strategies is still hampered by the need for large-scale randomized controlled trials."

IO biomarker • Journal • Review • Infectious Disease • Septic Shock • CRP • IFNG

Inhibition of TREM-1 ameliorates angiotensin II-induced atrial fibrillation by attenuating macrophage infiltration and inflammation through the PI3K/AKT/FoxO3a signaling pathway. (PubMed, Cell Signal) - "This study discovered the critical role of TREM-1 in the pathogenesis of atrial fibrillation and its underlying molecular mechanisms. Inhibition of TREM-1 provides a new therapeutic strategy for the treatment of AF."

Journal • Atrial Fibrillation • Cardiovascular • Fibrosis • Immunology • Inflammation • NLRP3

Enhancing sepsis biomarker development: key considerations from public and private perspectives. (PubMed, Crit Care) - "Biomarker-guided interventions for sepsis to identify patients that would benefit more from therapy, such as sTREM-1-guided Nangibotide treatment or Adrenomedullin-guided Enibarcimab treatment, appear promising but require further evaluation. Artificial intelligence also has great potential in the sepsis biomarker discovery field through capability to analyse high volume complex data and identify complex multiparametric patient endotypes or trajectories. To conclude, biomarker development in sepsis requires (i) a comprehensive and multidisciplinary approach employing the most advanced analytical tools, (ii) the creation of a platform that collaboratively merges scientific and commercial needs and (iii) the support of an expedited regulatory approval process."

Biomarker • Journal • Review • Critical care • Infectious Disease • Pediatrics • Septic Shock • ADM

Single-Cell RNA Sequencing Reveals Transcriptional Landscape of Neutrophils and Highlights the Role of TREM-1 in EAE. (PubMed, Neurol Neuroimmunol Neuroinflamm) - "Our 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."

Journal • CNS Disorders • Immunology • Multiple Sclerosis

Targeting Oncostatin M Receptor to Attenuate Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine. (PubMed, Cardiol Cardiovasc Med) - "OSM and p27KIP1 expression in carotid arteries with angioplasty and treatment with either scrambled peptide or LR12, an inhibitor of triggering receptor expressed on myeloid cell (TREM)-1, were compared between the experimental groups and with contralateral carotid artery. The results of this study elucidated the presence of OSM and p27KIP1 in carotid arteries with plaque and their association with arterial plaque and vulnerability. The findings suggest that targeting OSM and p27KIP1 axis regulating VSMC proliferation may have therapeutic significance to stabilize plaque."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Infectious Disease • Inflammation • OSMR

Race and Virulence Dynamics of Puccinia triticina in China During 2007 to 2021. (PubMed, Plant Dis) - "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...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."

Journal

Studying a collection of common-wheat varieties for leaf rust resistance, crop yield and grain quality in the environmental conditions of Novosibirsk region. (PubMed, Vavilovskii Zhurnal Genet Selektsii) - "The presence of Lr41 in a winter type line (KS 93 U 62) allowed it to maintain resistance against a leaf rust pathogen clone kLr24, despite the presence of Lr24 in the genotype. Varieties Doka and Cheshskaya 17 may act as donors of resistance genes Lr26 + Lr34 and Lr9 + Lr12 + Lr13 + Lr34, as well as sources of dwarfing without losses in winter hardiness and yield under West Siberian conditions."

Journal • Infectious Disease

Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies. (PubMed, Crit Care) - "However, only one of them, nangibotide, has entered clinical trials, which have yielded promising data for future treatment of sepsis, septic shock, and other inflammatory disease such as COVID-19. This review discusses the TREM-1 pathway and important ligands, and highlights the development of novel inhibitors as well as their clinical potential for targeted treatment of various inflammatory conditions."

Journal • Review • Infectious Disease • Inflammation • Novel Coronavirus Disease • Septic Shock

Microglia TREM1-mediated neuroinflammation contributes to central sensitization via the NF-κB pathway in a chronic migraine model. (PubMed, J Headache Pain) - "Our findings suggest that TREM1 regulates microglia and NLRP3 activation via the NF-κB pathway, thereby contributing to central sensitization and implicating its involvement in chronic migraine pathogenesis."

Journal • CNS Disorders • Immunology • Inflammation • Migraine • Pain • FOS • NLRP3

Development of TREM-1 Inhibitors: A Novel Treatment for Neuroinflammation (CAP 2023) - "Design: In exploring hearing loss, 42 mice that were 6 to 8 weeks of age were exposed to 106 decibels (dB) of noise for 2 hours and transtympanically injected with a single dose of one of the TREM-1 inhibitors (peptide LR12), small molecules (GJ073 or GJ004), or a control substance (hydrogel)... This study offers insight into the possible role of TREM-1, GJ073, and GJ004 in neuroinflammatory pathways. The difference in recovery of hearing thresholds could indicate differences in drug efficacy or potency and guide development of therapeutic interventions."

CNS Disorders • Inflammation • Mood Disorders • Otorhinolaryngology

Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID-19 receiving respiratory support: the ESSENTIAL randomised, double-blind trial. (PubMed, EClinicalMedicine) - P2 | "The relationship between sTREM-1 and both risk of death and treatment response merits further evaluation of nangibotide using precision medicine approaches in life threatening viral pneumonitis. The study was sponsored by Inotrem SA."

Journal • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Nangibotide for precision immunomodulation in septic shock and COVID-19. (PubMed, Lancet Respir Med) - No abstract available

Immunomodulating • Journal • Immune Modulation • Immunology • Infectious Disease • Novel Coronavirus Disease • Septic Shock