Motrem (nangibotide) / Inotrem - LARVOL DELTA

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

Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial. (PubMed, Lancet Respir Med) - P2 | "This trial did not achieve the primary outcome of improvement in SOFA score at the predefined sTREM-1 value. Future studies are needed to confirm the benefit of nangibotide at higher concentrations of TREM-1 activation."

Biomarker • Journal • P2b data • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Septic Shock

TREM-1 triggers necroptosis of macrophages through mTOR-dependent mitochondrial fission during acute lung injury. (PubMed, J Transl Med) - "In this study, we reported that TREM-1 acted as a necroptotic stimulus of AlvMs, fueling inflammation and aggravating ALI. We also provided compelling evidence suggesting that mTOR-dependent mitochondrial fission is the underpinning of TREM-1-triggered necroptosis and inflammation. Therefore, regulation of necroptosis by targeting TREM-1 may provide a new therapeutic target for ALI in the future."

Journal • Acute Lung Injury • Inflammation • Pneumonia • Respiratory Diseases

Efficacy and Safety Study of Nangibotide in Patients With COVID-19 Receiving Ventilatory Support and Features of Systemic Inflammation. (clinicaltrials.gov) - P2 | N=220 | Completed | Sponsor: Inotrem | Recruiting ➔ Completed | N=370 ➔ 220 | Trial completion date: Jun 2023 ➔ Jun 2022 | Trial primary completion date: Jun 2023 ➔ May 2022

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease

Efficacy and Safety Study of Nangibotide in Patients With COVID-19 Receiving Ventilatory Support and Features of Systemic Inflammation. (clinicaltrials.gov) - P2 | N=370 | Recruiting | Sponsor: Inotrem | Phase classification: P2/3 ➔ P2 | N=730 ➔ 370

Enrollment change • Phase classification • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease

TREM-1 exacerbates bleomycin-induced pulmonary fibrosis by aggravating alveolar epithelial cell senescence in mice. (PubMed, Int Immunopharmacol) - "Herein, we report that the prophylactical blockade of TREM-1 using a decoy peptide dodecapeptide (LR12) exerted protective effects against BLM-induced PF in mice, with a higher survival rate, attenuated tissue injury, and less extracellular matrix deposition. Furthermore, prophylactic or therapeutic blockade of TREM-1 protected MLE12 cells from senescence induced by BLM or HO. In conclusion, our findings elucidate a pro-fibrotic effect of TREM-1 by inducing AECs senescence in PF, providing a potential strategy for fibrotic disease treatment."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CDKN1A

TREM-1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway. (PubMed, FEBS J) - "In mice subjected to caecal ligation and puncture, the TREM-1 inhibitor LR12 decreased the expression of NLRP3 and attenuated cardiomyocyte pyroptosis, leading to improved cardiac function and prolonged survival of septic mice. Our work demonstrates that, under septic conditions, TREM-1 plays a critical role in cardiomyocyte pyroptosis. Targeting TREM-1 and its associated molecules may therefore lead to novel therapeutic treatments for septic cardiomyopathy."

Journal • Cardiomyopathy • Cardiovascular • Infectious Disease • Septic Shock • IL1B • NLRC5 • NLRP3