Nangibotide
A short synthetic peptide that dampens the TREM-1 inflammation amplifier, tested by infusion in septic shock and severe COVID-19
Nangibotide (LR12) is a 12-amino-acid peptide copied from a stretch of TLT-1, a protein related to the immune receptor TREM-1. It acts as a decoy that blocks TREM-1, which boosts the inflammatory response in sepsis. Given as a continuous intravenous infusion, it was well tolerated in healthy volunteers and in patients with septic shock. Its phase 2b trial missed its main goal, though patients with the most TREM-1 activity seemed to gain; a smaller COVID-19 trial was more positive before it stopped early. It is not approved anywhere.
Used in human trials: 0.3 or 1.0 mg/kg/h, Continuous infusion, Intravenous (Trial: phase 2b ASTONISH, septic shock, 355 patients) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
TREM-1 is a receptor on neutrophils and monocytes that amplifies the inflammation set off when the immune system detects bacteria. In sepsis it is strongly switched on, and a fragment shed from it, soluble TREM-1 (sTREM-1), rises in the blood and tracks outcome. Nangibotide is a 12-residue peptide taken from TLT-1, a related protein; it is thought to work as a decoy that stops TREM-1 from engaging its ligand. A 2024 review notes that of the many TREM-1 blockers tested in animals, it is the only one to have reached clinical trials.
Before people, it was tested in animals. In monkeys given bacterial endotoxin, it kept blood pressure normal where untreated animals lost 25 to 40% of theirs, and it softened the drop in white cells and the cytokine surge, which the authors saw as the step towards human trials.
Nangibotide is cleared very fast. In the first human study, in 27 healthy adults, its effective half-life was about 3 minutes, consistent with breakdown by enzymes in the blood, and it stayed mostly within blood and the fluid around cells. That is why every trial has given it as a continuous infusion, with the dose expressed per kilogram per hour. No anti-drug antibodies were found up to 28 days later.
In septic shock, a phase 2a trial in 49 patients found no safety signal at three infusion rates and a non-significant hint of benefit in patients with high sTREM-1. The phase 2b ASTONISH trial then randomised 355 patients across 42 hospitals to two doses or placebo. It missed its primary goal, a better organ-failure score by day 5, in the predefined high-sTREM-1 group and overall. Patients with the highest sTREM-1 levels did improve by two points or more on the higher dose, which the sponsor is now testing as a way to pick patients.
The ESSENTIAL trial gave the higher dose to 219 adults with COVID-19 who needed breathing support. More patients improved by day 28 with nangibotide, and fewer had died, though the trial was stopped early for slow recruitment and these were not definitive results. Outside sepsis, rodent studies have tested it in atherosclerosis, stented arteries, osteoarthritis and liver failure. It is an investigational drug, not available for use outside trials.
Mechanism of Action
Nangibotide damps TREM-1, an amplifier of the innate immune response, rather than switching inflammation off.
Blood pressure in endotoxin shock
In monkeys given endotoxin it prevented the fall in blood pressure and softened the cytokine surge (PMID 24270127).
Gone in minutes
With an effective half-life of about 3 minutes, it acts only while it is being infused (PMID 29885068).
Published Research
These studies were read from their PubMed abstracts on October 29, 2026: the first-in-human study, the septic shock and COVID-19 trials, the animal studies that led to them, and laboratory and rodent work in other conditions. Studies that name the peptide only in their abstract are listed under References.
First in humans: safe, with a 3-minute half-life
Twenty-seven healthy adults received single intravenous doses in an ascending, placebo-controlled study, from short 15-minute infusions to infusions of almost 8 hours after a loading dose. Adverse events were few, mild and judged unrelated. Exposure rose in proportion to dose, the effective half-life was about 3 minutes, and no anti-drug antibodies appeared within 28 days.
Phase 2a in septic shock
Forty-nine patients were randomised to placebo or one of three infusion rates, started within 24 hours of shock and continued for up to 5 days. Adverse events did not differ from placebo and no antibodies were found. Organ-failure scores improved slightly more on the drug, more so in patients with high baseline sTREM-1, but none of these differences was significant.
The ASTONISH protocol
The published protocol planned 450 septic shock patients in up to 50 centres in seven countries, randomised to placebo or one of two doses, with the change in organ-failure score analysed first in patients with raised sTREM-1 and then in everyone, and a point-of-care sTREM-1 test developed alongside.
ASTONISH: primary goal missed
Of 355 patients analysed, organ-failure scores by day 5 were not significantly better on either dose than placebo, in the high-sTREM-1 group or overall. Day-28 deaths were 25% on placebo, 32% on the low dose and 25% on the high dose overall. Serious adverse events were similar across groups. At a higher sTREM-1 cutoff, the high dose improved the score by two points or more.
ESSENTIAL: COVID-19 with breathing support
Stopped early after 220 patients, this phase 2 trial found more patients improved by day 28 on nangibotide (65% versus 52%), and day-28 deaths fell from 28% to 16%, an adjusted absolute reduction of about 12 percentage points; the gap was larger in patients with high sTREM-1. Adverse event rates were similar to placebo.
Monkeys given endotoxin
Twelve cynomolgus monkeys received endotoxin and then the peptide or placebo as a bolus and 8-hour infusion. Placebo animals lost 25 to 40% of their blood pressure while treated animals stayed normotensive, with a smaller fall in white cells, less cytokine release and no obvious side effects. The authors saw this as the bridge to human trials.
Measuring it in blood
Researchers validated a liquid chromatography method with fluorescence detection to measure the peptide in rat whole blood, and in a small rat study tracked both the peptide and its disulfide-linked dimer, its main breakdown product.
Gum-disease bacteria and human monocytes
Lipopolysaccharide from Porphyromonas gingivalis raised TREM-1 and inflammatory cytokines in human monocytes; adding the peptide partly prevented that activation.
Liver repair in mice
In mice with chemically induced acute liver failure, the peptide reduced liver inflammation and helped liver cells regenerate, an effect that depended on the chemokine CCL20 released by macrophages.
Osteoarthritis in mice
In a ligament-cut model of knee osteoarthritis, treatment reduced cartilage breakdown and loss of the bone under the cartilage and protected bone-forming cells from death, apparently by damping TGF-beta signalling.
Plaque inside stents in rabbits
In 40 rabbits on a high-fat diet fitted with drug-eluting stents, treatment cut new plaque inside the stent by about 40% at one month and 49% at three months on imaging, without slowing healing of the vessel lining, and shifted macrophages towards an anti-inflammatory type.
Dosing Data
Nangibotide is not approved, so there is no label dose. These are the infusion rates published trials gave, per kilogram of body weight per hour, as their abstracts and registry records state them.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no regulator's label that says in what form Nangibotide is supplied. It is prepared and given by clinical staff, not bought and mixed at home: the next part says where.
Mixing a vial: a worked example
Nothing to mix at home, and no syringe units to work out: Nangibotide is prepared and given by clinical staff, in intensive care.
In the carded trials it was infused into a vein for up to 5 days, starting within 24 hours of septic shock.
Source: PMID 32468087 (a study carded under Research below).
Storage before and after mixing
Unknown: no label on file says how Nangibotide is stored. It is kept and prepared by the hospital or clinic that gives it (see the part above); the home rules for a mixed vial in the mixing guide do not apply to it.
How it is taken
As it was given in human studies: Intravenous (Continuous infusion; Trial: phase 2b ASTONISH, septic shock, 355 patients).
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of about 3 minutes (effective half-life, healthy volunteers). After about five half-lives almost none is left.
How long the doses were given: Trial: phase 2b ASTONISH, septic shock, 355 patients: Duration not stated in the abstract; Trial: phase 2a, septic shock, 49 patients: Up to 5 days; Trial: ESSENTIAL, COVID-19 with respiratory support, 219 patients: Up to 120 hours (registry record NCT04429334).
When effects appear: unknown; no source on this page gives a time to effect for Nangibotide. Results reported in the studies are under Published Research.
Source: half-life: PMID 29885068; Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: In healthy volunteers, few adverse events, all mild and judged unrelated (PMID 29885068); In septic shock, adverse and serious adverse events at rates similar to placebo (PMID 32468087, PMID 37269870); Day-28 deaths of 32% on the lower dose against 25% on placebo in ASTONISH overall, a difference not shown to be significant (PMID 37269870); No anti-drug antibodies detected in the phase 1 and phase 2a studies. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Nangibotide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the trials above”).
Interactions
Unknown: a PubMed search for human interaction studies of Nangibotide (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Nangibotide products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Nangibotide's expected mass, 1,343.5 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: In Clinical Trials (Not approved: Drugs@FDA and the EMA medicines list hold no record (searched October 28, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the trials above.
Contraindications & Cautions
There is no label. Trial entry criteria are the only guide.
Legal Status
Nangibotide is an investigational drug developed for septic shock.
Frequently Asked Questions
?What is nangibotide?
A 12-amino-acid synthetic peptide, also called LR12, that blocks the TREM-1 pathway, an amplifier of inflammation that is strongly switched on in septic shock.
?Does nangibotide work in septic shock?
Not proven. The phase 2b ASTONISH trial missed its main goal; patients with the highest soluble TREM-1 levels did better on the higher dose, and that idea needs a confirmatory trial.
?Why is it given as an infusion?
Its effective half-life in people is about 3 minutes, so it is cleared almost as soon as an injection ends. Trials infused it continuously, dosed per kilogram per hour.
?What happened in the COVID-19 trial?
ESSENTIAL gave nangibotide to adults needing breathing support. More improved and fewer died by day 28 than on placebo, but the trial stopped early after 220 patients, so the result is not definitive.
?What is soluble TREM-1?
A fragment of the TREM-1 receptor shed into blood when the pathway is active. The trials used it to identify the patients most likely to benefit.
?Can I buy nangibotide?
No approved product exists. The drug is available only inside clinical trials, and nothing sold online as LR12 has been tested as a trial product.
References
- [clinical-trial] Cuvier V, et al. "A first-in-man safety and pharmacokinetics study of nangibotide, a new modulator of innate immune response through TREM-1 receptor inhibition." Br J Clin Pharmacol, 2018;84(10):2270-2279. PMID: 29885068.
- [clinical-trial] François B, et al. "Nangibotide in patients with septic shock: a Phase 2a randomized controlled clinical trial." Intensive Care Med, 2020;46(7):1425-1437. PMID: 32468087.
- [clinical-trial] Francois B, et al. "Rationale and protocol for the efficacy, safety and tolerability of nangibotide in patients with septic shock (ASTONISH) phase IIb randomised controlled trial." BMJ Open, 2021;11(7):e042921. PMID: 34233965.
- [clinical-trial] François B, et al. "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." Lancet Respir Med, 2023;11(10):894-904. PMID: 37269870.
- [clinical-trial] François B, et al. "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." EClinicalMedicine, 2023;60:102013. PMID: 37350989.
- [pubmed] Derive M, et al. "Attenuation of responses to endotoxin by the triggering receptor expressed on myeloid cells-1 inhibitor LR12 in nonhuman primate." Anesthesiology, 2014;120(4):935-42. PMID: 24270127.
- [pubmed] Parent M, et al. "LR12-peptide quantitation in whole blood by RP-HPLC and intrinsic fluorescence detection: Validation and pharmacokinetic study." Biomed Chromatogr, 2017;31(5). PMID: 27790740.
- [pubmed] Dubar M, et al. "Effects of Porphyromonas gingivalis LPS and LR12 peptide on TREM-1 expression by monocytes." J Clin Periodontol, 2018;45(7):799-805. PMID: 29779263.
- [pubmed] Wang Y, et al. "LR12 Promotes Liver Repair by Improving the Resolution of Inflammation and Liver Regeneration in Mice with Thioacetamide- (TAA-) Induced Acute Liver Failure." Mediators Inflamm, 2021;2021:2327721. PMID: 34135689.
- [pubmed] Zhong Y, et al. "Nangibotide attenuates osteoarthritis by inhibiting osteoblast apoptosis and TGF-β activity in subchondral bone." Inflammopharmacology, 2022;30(3):1107-1117. PMID: 35391646.
- [pubmed] Jiang M, et al. "TREM-1 inhibition with LR12 attenuates in-stent neoatherosclerosis through modulating macrophage polarization in a rabbit model: An optical coherence tomography study." Atherosclerosis, 2026;415:120701. PMID: 41832836.
- [pubmed] Neupane M, et al. "Nangibotide for precision immunomodulation in septic shock and COVID-19." Lancet Respir Med, 2023;11(10):855-857. PMID: 37269869.
- [other] PubChem compound record for nangibotide: synonyms list the sequence Leu-Gln-Glu-Glu-Asp-Ala-Gly-Glu-Tyr-Gly-Cys-Met-NH2 and the codes LR12 and Motrem. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/Nangibotide
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT03158948 (phase 2, completed), NCT04055909 (phase 2b, ASTONISH, active, not recruiting), NCT04429334 (phase 2, COVID-19, completed) and NCT03463044 (phase 1, completed).
- [other] ChEMBL CHEMBL4297793, nangibotide (synonyms include LR12, Motrem): maximum clinical phase 2 in the ChEMBL molecule record, read October 2, 2026 (the Registry's ChEMBL harvest). https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL4297793/
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026 (a PubMed search for nangibotide, LR12 and Motrem returned 173 records, most of them unrelated uses of 'LR12'). Trial arms were checked against ClinicalTrials.gov (NCT03158948, NCT04055909, NCT04429334) the same day. Status from Drugs@FDA and the EMA medicines list. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.