Peptides / Immune and antimicrobial

Synthetic fragment · 12 amino acids

Nangibotide

Nangibotide is an experimental twelve-amino-acid peptide that blocks the TREM-1 inflammation pathway, in phase 2 trials and not approved. Studies in people with septic shock or COVID-19 tested it on intensive care outcomes and survival, and tracked side effects. PepBank shows 36 results on nangibotide from 4 studies in people, and 104 from animal and lab studies. The strongest evidence is a randomized trial in people. Data as of 2026-10-30.

Also known as LR-12, LR12, MOTREM

Evidence level: Some studies in people36 of 140 results come from studies in people.

Results in people

26% of 140 results

Results in animals

63% of 140 results

Results in lab cells

11% of 140 results

From computer models

0% of 140 results

Overview

Nangibotide at a glance

What it is	Synthetic fragment, 12 amino acids
Approval	Regulatory status not recorded
In sport	Status unknown
Studies	24 studies with results. 21 of them gave nangibotide, with 140 results. 36 in people88 in animals16 in lab cells
Best study in people	Randomized controlled trial with 219 people (2023)
Clinical trials	1 registered: 1 active or planned, 0 with posted results

The science

What is nangibotide?

A twelve-residue TREM-1 pathway modulator studied in inflammatory disorders.

Amino acids in one chain

The history of nangibotide

2013
The oldest paper on nangibotide in PepBank is from 2013.
2019November
A registered trial of nangibotide started (NCT04055909).

Nangibotide structure and chemistry

The key facts about the molecule. Long codes are in the closed section below.

Structure

Nangibotide is a synthetic fragment of 12 amino acids, with no ring, 1 changed amino acid.

CAS number

2014384-91-7

Target

Triggering receptor expressed on myeloid cells 1 (gene TREM1): inhibitorEvidence: The phase 1 paper describes TREM-1 pathway inhibition. NCI describes sequestration of its ligand.

Development

Inotrem. Highest phase: phase 2.

Identifiers

ChEMBL CHEMBL4297793, UNII 59HD7BLX9H

See charge, composition and 3D structure on the Scientific page

The evidence

What nangibotide studies show

Results grouped by what the studies measured. Each card shows where its results come from.

Some studies in people36 of 140 results come from studies in people.

Survival and serious illness

15 results · 12 in people · 3 animal

In septic shock patients with high sTREM-1, low-dose nangibotide did not significantly improve organ function scores versus placebo. The Lancet. Respiratory medicine, 2023

Top results

In septic shock patients with high sTREM-1, low-dose nangibotide did not significantly improve organ function scores versus placebo. (The Lancet. Respiratory medicine, 2023)
In COVID-19 patients receiving respiratory support, day 28 mortality was 16.0% with nangibotide versus 28.0% with placebo. (EClinicalMedicine, 2023)
In mice given lethal LPS doses, LR12 significantly improved survival. (Scientific reports, 2016)

Overall treatment results

5 results · 5 in people

In septic shock patients, SOFA score change did not differ significantly between pooled nangibotide groups and placebo. Intensive care medicine, 2020

Top results

In septic shock patients, SOFA score change did not differ significantly between pooled nangibotide groups and placebo. (Intensive care medicine, 2020)
In patients receiving respiratory support for COVID-19, clinical improvement occurred in 64.7% with nangibotide versus 52.0% with placebo. (EClinicalMedicine, 2023)
In patients with high baseline sTREM-1, SOFA score change did not differ significantly between pooled nangibotide groups and placebo. (Intensive care medicine, 2020)

Immune system and inflammation

30 results · 2 in people · 24 animal · 4 lab

In septic shock patients, no anti-drug antibodies were reported with nangibotide. Intensive care medicine, 2020

Top results

In septic shock patients, no anti-drug antibodies were reported with nangibotide. (Intensive care medicine, 2020)
In mice, LR12 reduced lung inflammation. (Scientific reports, 2016)
In mice lacking ApoE, LR12 reduced plaque inflammation. (Journal of the American College of Cardiology, 2016)

Heart and blood vessels

25 results · 24 animal · 1 lab

In minipigs with heart infarction, LR12 improved reduced cardiac index versus vehicle. ESC heart failure, 2015

Top results

In minipigs with heart infarction, LR12 improved reduced cardiac index versus vehicle. (ESC heart failure, 2015)
In mice, LR12 prevented impaired blood vessel reactivity associated with TREM-1 engagement. (Cardiovascular research, 2018)
In minipigs with heart infarction, LR12 improved reduced mean arterial pressure versus vehicle. (ESC heart failure, 2015)

Lungs and breathing

7 results · 7 animal

In mice, LR12 reduced lung tissue damage. Scientific reports, 2016

Top results

In mice, LR12 reduced lung tissue damage. (Scientific reports, 2016)
In minipigs with heart infarction, LR12 improved the blood oxygen ratio versus vehicle. (ESC heart failure, 2015)
In mice with bleomycin-induced lung fibrosis, preventive LR12 reduced tissue injury. (International immunopharmacology, 2022)

Bones and joints

8 results · 5 animal · 3 lab

In mice, nangibotide reduced cartilage damage induced by ACLT. Inflammopharmacology, 2022

Top results

In mice, nangibotide reduced cartilage damage induced by ACLT. (Inflammopharmacology, 2022)
In mice, nangibotide reduced MMP-13 expression induced by ACLT. (Inflammopharmacology, 2022)
In mice, nangibotide reduced bone loss beneath cartilage after ACLT. (Inflammopharmacology, 2022)

All 4 studies in people

In people

In COVID-19 patients receiving respiratory support, day 28 mortality was 16.0% with nangibotide versus 28.0% with placebo.

2023EClinicalMedicine219 people

In people

In septic shock patients, adverse events did not differ significantly between nangibotide and placebo groups.

2020Intensive care medicine49 people

In people

In septic shock patients with high sTREM-1, low-dose nangibotide did not significantly improve organ function scores versus placebo.

2023The Lancet. Respiratory medicine

In people

In healthy subjects, nangibotide exposure was proportional to dose.

2018British journal of clinical pharmacology

All 24 nangibotide studies by area Open the Scientific page

Key nangibotide studies

Studies in people come first, then studies in animals and in the lab.

People
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
François et al. 2023 · EClinicalMedicine · 219 people · cited by 13
5 results
People
Nangibotide in patients with septic shock: a Phase 2a randomized controlled clinical trial
François et al. 2020 · Intensive care medicine · 49 people · cited by 59
9 results
People
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
François et al. 2023 · The Lancet. Respiratory medicine · cited by 71
14 results
People
A first-in-man safety and pharmacokinetics study of nangibotide, a new modulator of innate immune response through TREM-1 receptor inhibition
Cuvier et al. 2018 · British journal of clinical pharmacology · cited by 38
8 results
Animals
Pharmacological inhibition of the triggering receptor expressed on myeloid cells-1 limits reperfusion injury in a porcine model of myocardial infarction
Lemarié et al. 2015 · ESC heart failure · 15 subjects · cited by 24
11 results

All 24 Nangibotide studies

Nangibotide clinical trials

ClinicalTrials.gov lists 1 trial of nangibotide. 1 is active or planned, and 0 have posted results. PepBank does not show trial results.

Solid bars are dates that happened. Hatched bars are planned dates. Data from ClinicalTrials.gov.

Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock

Phase 2active, not recruiting355 planned

Status and safety

Is nangibotide approved?

FDA

United States

Status unknown

Status unknown.

EMA

European Union

Status unknown

Status unknown.

WADA

Sport

Not recorded

Status unknown.

Regulatory status not recorded. Status unknown.

Laws and labels change, so check the regulator for the current status.

Nangibotide side effects and safety

PepBank has 18 safety results from studies of nangibotide. 17 of them come from studies in people.

Safety results from studies (18)

In septic shock patients, adverse events did not differ significantly between nangibotide and placebo groups. (Intensive care medicine, 2020)
In COVID-19 patients receiving respiratory support, day 28 mortality was 16.0% with nangibotide versus 28.0% with placebo. (EClinicalMedicine, 2023)
In septic shock patients with high sTREM-1, day 28 mortality was 39% with low-dose nangibotide versus 31% with placebo. (The Lancet. Respiratory medicine, 2023)
In healthy subjects, nangibotide was safe and well tolerated up to the highest tested dose. (British journal of clinical pharmacology, 2018)
In COVID-19 patients receiving respiratory support, adverse event rates were similar with nangibotide and placebo. (EClinicalMedicine, 2023)
In COVID-19 patients with high sTREM-1, day 28 mortality was 22.2% with nangibotide versus 41.8% with placebo. (EClinicalMedicine, 2023)
In septic shock patients with high sTREM-1, day 28 mortality was 28% with high-dose nangibotide versus 31% with placebo. (The Lancet. Respiratory medicine, 2023)
In septic shock patients overall, day 28 mortality was 32% with low-dose nangibotide versus 25% with placebo. (The Lancet. Respiratory medicine, 2023)
In septic shock patients overall, day 28 mortality was 25% with both high-dose nangibotide and placebo. (The Lancet. Respiratory medicine, 2023)
In septic shock patients, adverse events were similar with low-dose nangibotide and placebo, affecting 96% in each arm. (The Lancet. Respiratory medicine, 2023)
In septic shock patients, adverse events were similar with high-dose nangibotide and placebo, affecting 95% versus 96%. (The Lancet. Respiratory medicine, 2023)
In septic shock patients, serious adverse events were similar with low-dose nangibotide and placebo, affecting 22% versus 24%. (The Lancet. Respiratory medicine, 2023)
In septic shock patients, serious adverse events were similar with high-dose nangibotide and placebo, affecting 26% versus 24%. (The Lancet. Respiratory medicine, 2023)
In septic shock patients, no withdrawal linked to adverse events was reported with nangibotide. (Intensive care medicine, 2020)
In septic shock patients, no anti-drug antibodies were reported with nangibotide. (Intensive care medicine, 2020)
In healthy subjects, few adverse events occurred with nangibotide, and they were mild and considered unrelated to treatment. (British journal of clinical pharmacology, 2018)
In healthy subjects, no anti-drug antibodies were detectable up to 28 days after nangibotide administration. (British journal of clinical pharmacology, 2018)
In rabbits, LR12 did not impair vessel lining growth over stents compared with saline. (Atherosclerosis, 2026)

See every safety result on the Scientific page

Doses studied (5 shown)

The doses that these studies used. They are not recommendations.

Dose as reported	Class	Species	Route	Duration	Design	Source
1.0 mg/kg/h	Human	human	Not reported	Not reported	Randomized trial in people · n = 219	François 2023
0.3, 1.0, or 3.0 mg/kg/h	Human	human	continuous infusion	up to 5 days	Randomized trial in people · n = 49	François 2020
0·3 mg/kg per h	Human	human	intravenous	Not reported	Randomized trial in people	François 2023
1·0 mg/kg per h	Human	human	intravenous	Not reported	Randomized trial in people	François 2023
1 or 10 mg, or 0.03 to 6 mg/kg/h preceded by a loading dose of up to 5 mg/kg	Human	human	intravenous infusion	15 min, or 7 h 45 min preceded by a 15-minute loading dose	Randomized trial in people	Cuvier 2018

Questions and more

Ask a question about nangibotide

The answer links to every study it uses.

What does the evidence say about nangibotide?Is nangibotide tested in people?Compare with Vasoactive intestinal peptide (VIP, aviptadil)Compare with Thymosin alpha-1

Sources

Database: PepBank data for nangibotide (data version 308560)
Regulator: FDA status record
Regulator: EMA status record
Regulator: WADA status record
Trial registry: ClinicalTrials.gov

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

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Nangibotide

Nangibotide at a glance