Nangibotide

Summary

Nangibotide (LR12) is an investigational immunomodulatory peptide that modulates TREM-1 signaling to attenuate excessive inflammation in sepsis and septic shock. It has been evaluated in preclinical models and Phase 1/2 clinical trials for safety, tolerability, and efficacy signals in patients with septic shock.

Mechanism of Action

Nangibotide is a 12-amino-acid peptide derived from the extracellular domain of TLT-1 (TREM-like transcript 1). It acts as a partial agonist/ligand of TREM-1 (Triggering Receptor Expressed on Myeloid cells-1), modulating excessive TREM-1-mediated inflammatory signaling without fully blocking it. This dampens hyperinflammation while preserving basal innate immune function, potentially reducing organ damage in sepsis.

Routes of Administration

Goals & Uses

• Reduction of mortality in septic shockCritical Care / Anti InflammatoryModerate
• Attenuation of TREM-1-mediated hyperinflammationImmunomodulationModerate
• Organ dysfunction prevention in sepsisOrgan ProtectionModerate
• Biomarker-guided patient stratification in sepsisPrecision MedicineModerate

Contraindications

• Known hypersensitivity to nangibotide or excipientsAllergyHigh
• Severe immunocompromised statesImmunologicalModerate

Adverse Effects

• Elevated liver enzymes (transient)HepaticRare
• HypotensionCardiovascularUncommonLow blood pressure
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• Infusion-related reactionsHypersensitivityUncommon

Drug Interactions

• Vasopressors (norepinephrine, vasopressin)Low
• CorticosteroidsModerate

Population Constraints

• Pediatric patientsAgeRelative
• Pregnant or lactating womenReproductiveRelative
• Patients with chronic autoimmune conditions on immunosuppressantsComorbidityRelative

Regulatory Status

• European UnionInvestigationalPhase 2 clinical trials conducted partly in European centers; not approved by EMA.
• United StatesInvestigationalInvestigational use only; no FDA approval or BLA submitted as of last available data.
• United KingdomInvestigationalNo MHRA approval; research/trial use only.

Not approved by any regulatory agency. Investigated under clinical trial frameworks in Europe and the US. Phase 2 trial (ASTONISH) conducted in septic shock patients. Orphan or fast-track designations not publicly confirmed as of last available data.

Evidence & Sources

No sources recorded yet.