Is nangibotide FDA-approved, and what does the research show?

What is nangibotide?

Nangibotide is an investigational peptide drug studied mainly for septic shock, in patients in intensive care ¹, ⁵. It is not FDA-approved ³. It is not a wellness, weight-loss, immune-boosting or performance product. A peptide is a short chain of amino acids, the building blocks of proteins. The trial records also call nangibotide LR12 and MOTREM, and they name the company Inotrem as sponsor ², ⁷.

The trial papers call it a TREM-1 inhibitor ¹, ⁵. TREM-1 stands for "triggering receptor expressed on myeloid cells-1" ¹. A receptor is a protein that passes signals into a cell, and myeloid cells are a family of white blood cells. An inhibitor is a drug meant to dampen its target's activity. Nangibotide is a 12-amino-acid peptide fragment derived from TREM-like transcript-1 (TLT-1), a receptor protein of the TREM-1 family ⁸.

Septic shock is a severe complication of infection, treated in an intensive care unit, the hospital ward for the most seriously ill ¹. In the ASTONISH trial it meant infection with failing organs, raised blood lactate, and blood pressure that needed vasopressors despite fluids ⁴. Lactate is a substance that builds up in the blood when tissues get too little oxygen, and vasopressors are drugs that raise blood pressure. In an earlier, smaller septic shock trial, patients received nangibotide as a continuous infusion into a vein for up to five days ⁵. ASTONISH treated patients for at least three and at most five days ⁴.

Is nangibotide FDA-approved?

Nangibotide is not FDA-approved: Drugs@FDA lists no approved nangibotide product as of November 9, 2026 ³. It is an investigational drug: the ClinicalTrials.gov record of ASTONISH, the largest of the four trials cited here, reads "Active, not recruiting," last update posted April 11, 2023 ⁴. The record gives its completion date, May 9, 2023, as estimated ⁴. ASTONISH's results appeared in a paper published online on May 31, 2023 ¹.

The same Drugs@FDA read returned no product under the names LR12 or MOTREM ³. Drugs@FDA lists no approved nangibotide product, so no FDA label is cited here ³.

A search of ClinicalTrials.gov, the U.S. registry of clinical studies, for nangibotide as the intervention listed four studies on November 10, 2026 ², ⁴, ⁶, ⁷. One is a phase 1 study and three are phase 2 trials, each sponsored by Inotrem ², ⁴, ⁶, ⁷. Phase 1 studies test safety in small groups, and phase 2 trials test doses and early signs of effect. Phase 3 trials are the large ones that support an application for approval. Three of the four records read "Completed," with last updates posted on October 8, 2024, May 3, 2023 and February 10, 2025 ², ⁶, ⁷.

None of the sources cited here states a lawful route to nangibotide outside a clinical trial. Compounding means a licensed pharmacy making a drug product from a bulk ingredient.

FDA's list of bulk substances nominated for compounding under section 503A of the federal drug law, updated May 14, 2026, does not name nangibotide ⁹. Nor does the companion list under section 503B, updated March 21, 2025 ¹⁰. Section 503B covers outsourcing facilities, compounders that register with FDA. The European Medicines Agency records that nangibotide was designated an orphan medicine for sickle cell disease on November 21, 2025 ¹¹. EMA's page says "Orphan designation does not mean the medicine is available or authorised for use" ¹¹.

See the FDA status of every peptide, updated weekly.

How does nangibotide work?

The ASTONISH paper opens: "Activation of the triggering receptor expressed on myeloid cells-1 (TREM-1) pathway is associated with septic shock outcomes" ¹. Proposed: its authors write that modulating this pathway "in patients with activated TREM-1 might improve survival" ¹. That is the hypothesis the trials were built to test, not a result. Studied in animals: the phase 2a paper says nangibotide "tempered deleterious host-pathogens interactions, restored vascular function, and improved survival, in animal septic shock models" ⁵. The ASTONISH protocol paper reports preclinical modeling in "rodent, porcine and primate septic shock" ¹².

The septic shock trials measured soluble TREM-1, or sTREM-1, a form of the receptor found loose in plasma, the liquid part of blood, rather than fixed to a cell ¹, ⁵. The ASTONISH authors call it "a potential mechanism-based biomarker," a blood marker that might show whose TREM-1 pathway is active ¹. Both analyzed results by each patient's sTREM-1 level at the start ¹, ⁵. The ESSENTIAL paper says nangibotide "binds the TREM-1 agonist ligand and thereby modulates the amplification of the immune response" ⁸.

What does the research show?

Studied in people: ASTONISH, a randomized, double-blind, placebo-controlled phase 2b trial, 355 adults with septic shock, change in organ-failure score at day 5 ¹. Randomized means chance decided each patient's group, and double-blind means neither patients nor investigators knew the group. A placebo is a dummy infusion. The paper calls the trial phase 2b, the later, larger stage of phase 2, and the registry record calls it phase 2 ¹, ⁴.

The trial ran in 42 hospitals in seven countries ¹. It enrolled patients aged 18 to 85 with a documented or suspected lung or abdominal infection, or a urinary infection at 65 or older ¹. They had to start within 24 hours of their first vasopressor ¹. Of 402 patients screened, 355 entered the main analysis: 116 on placebo, 118 on low-dose nangibotide and 121 on high-dose nangibotide ¹.

The primary outcome, in the paper's words, was "the mean difference in total Sequential Organ Failure Assessment (SOFA) score from baseline to day 5 in the low-dose and high-dose groups compared with placebo, measured in the predefined high sTREM-1 (≥ 400 pg/mL) population and in the overall modified intention-to-treat population" ¹. The SOFA score rates how badly a patient's organs are failing. A modified intention-to-treat population counts patients in the group they were assigned to, leaving out a few the trial defines, often those never treated. A pg/mL is a picogram per milliliter, a measure of how much sTREM-1 a set volume of plasma holds.

In the overall population, the difference from placebo was 0.20 points in the low-dose group (95% confidence interval −1.09 to 1.50; p = 0.76) ¹. In the high-dose group it was 1.06 points (−0.23 to 2.35; p = 0.108) ¹. A confidence interval is the range likely to hold the true difference, and both ranges include zero, the value for no difference. A p value is the chance of a difference at least this large if the drug had no effect, and under 0.05 is the usual bar for statistical significance.

The predefined high sTREM-1 population held 253 of the 355 patients: 75 on placebo, 90 on low-dose and 88 on high-dose ¹. There the differences from placebo were 0.21 points (−1.45 to 1.87; p = 0.80) and 1.39 points (−0.28 to 3.06; p = 0.104) ¹. Those ranges include zero as well. The paper's own summary reads: "This trial did not achieve the primary outcome of improvement in SOFA score at the predefined sTREM-1 value" ¹.

The abstract then reports a result at a higher cutoff. High-dose nangibotide, it says, "led to a clinically relevant improvement in SOFA score (of two points or more) from baseline to day 5 over placebo in those with higher cutoff concentrations (≥532 pg/mL) of sTREM-1 at baseline" ¹.

The abstract calls the 400 cutoff "predefined" and does not use that word for the 532 cutoff ¹. It gives no patient count, confidence interval or p value for that group ¹. The authors conclude: "Future studies are needed to confirm the benefit of nangibotide at higher concentrations of TREM-1 activation" ¹. The trial's published protocol set the cutoff at 400 pg/mL and planned exploratory analyses to confirm the best cutoff ¹².

Death from any cause by day 28 was a secondary endpoint, an outcome a trial measures beside its primary one ¹. In the overall population, 29 patients on placebo had died (25%), against 38 on low-dose (32%) and 30 on high-dose (25%) ¹. In the predefined high sTREM-1 population, the figures were 23 on placebo (31%), 35 on low-dose (39%) and 25 on high-dose (28%) ¹. The abstract reports no statistical test of these death rates ¹.

Studied in people: a randomized, placebo-controlled phase 2a trial, 49 adults with septic shock, with adverse events and death as its primary safety outcomes ⁵. Phase 2a is the early stage of phase 2, here aimed at safety. Patients received placebo or one of three dose levels of nangibotide, starting within 24 hours of shock onset ⁵.

The paper counts 49 patients randomized ⁵. The registry counts 50, one of whom died before receiving the study drug ². It lists 12 patients on placebo and 13, 12 and 12 on the three nangibotide dose levels ².

On its primary outcomes, the paper reports: "No significant differences were observed in TEAEs between treatment groups" ⁵. TEAEs are treatment-emergent adverse events, health problems that begin or worsen after treatment starts, whatever their cause. The paper also reports that nangibotide "did not significantly affect pharmacodynamic markers," the blood measures used to track a drug's effect on the body ⁵.

Organ function and mortality were exploratory endpoints, analyzed "according to baseline sTREM-1 concentrations" ⁵. An exploratory endpoint is measured to guide later trials, not to prove an effect. The paper reports that the SOFA change to day 5 "in pooled nangibotide groups versus placebo was - 0.7 (± 0.85) in the randomized population and - 1.5 (± 1.12) in patients with high baseline plasma sTREM-1 concentrations (non-significant)" ⁵.

Studied in people: ESSENTIAL, a randomized, double-blind, placebo-controlled phase 2 trial, 220 adults in intensive care with COVID-19 who needed respiratory support ⁶. The registry lists two primary outcomes: adverse events to day 28 in the trial's first part, and clinical status at day 28 in its second ⁶. Clinical status was rated on a "7-point Ordinal Scale," one that ranks a patient's condition in seven ordered steps ⁶.

The record's description gives "14 sites in France and Belgium" and "an initially planned sample size of 370 patients" ⁶. The paper reports 14 hospitals in France and Belgium; the record's locations list names 17 sites ⁶, ⁸. The record reads "Completed," last update posted May 3, 2023, and carried no posted results when read on November 10, 2026 ⁶.

ESSENTIAL stopped early for low recruitment. Of 219 analyzed, 64.7 percent on nangibotide improved in clinical status by day 28, against 52.0 percent on placebo (odds ratio 1.79, 95% CI 1.02 to 3.14) ⁸.

Studied in people: a placebo-controlled phase 1 study, 27 healthy men, single doses given into a vein in rising steps, with adverse events as the primary outcome ⁷. None of the sources cited here studies nangibotide for weight loss, wellness, immune support or athletic performance. None of the four registry records listed on November 10, 2026 is a phase 3 trial ², ⁴, ⁶, ⁷.

What are the side effects?

The septic shock trials enrolled critically ill patients, and adverse events were common in every group, placebo included. In ASTONISH, treatment-emergent adverse events occurred in 111 patients on placebo (96%) ¹. They occurred in 113 on low-dose nangibotide (96%) and 115 on high-dose (95%) ¹. Serious events occurred in 28 patients on placebo (24%), 26 on low-dose (22%) and 31 on high-dose (26%) ¹. The paper calls both counts "similar between all three groups" ¹.

The phase 2a trial's registry record gives counts by group, and the groups were small ². At least one adverse event was recorded in 10 of 12 patients on placebo ². On the lowest, middle and highest nangibotide doses the counts were 12 of 13, 12 of 12 and 11 of 12 ². Serious adverse events were recorded in 7 of 12 on placebo, against 4 of 13, 2 of 12 and 4 of 12 ².

The record counts deaths in two tables. Its adverse-events table, which runs from baseline to day 28, counts 3 deaths among 12 on placebo, against 4 of 13, 2 of 12 and 4 of 12 ². Its participant-flow table gives death as the reason for not completing for 2 patients on placebo, against 1, 1 and 3 ².

The two most often recorded non-serious events in the phase 2a record were anemia, a shortage of red blood cells, and atrial fibrillation, an irregular heart rhythm ². Anemia was recorded in 3 of 12 on placebo, against 3 of 13, 2 of 12 and 3 of 12 ². Atrial fibrillation was recorded in 1 of 12 on placebo, against 5 of 13, 2 of 12 and 3 of 12 ². The paper adds: "No drug withdrawal linked to TEAE nor appearance of anti-drug antibodies were reported" ⁵. Anti-drug antibodies are immune proteins a patient may form against a drug.

In the phase 1 study of 27 healthy men, at least one adverse event was recorded in 1 of 6 on placebo ⁷. Of the eight nangibotide dose groups, each of one to three men, five recorded one man with an adverse event and three recorded none ⁷. The record states: "All TEAEs were mild in severity, and considered unrelated to the study drug. There was no SAE and no TEAE leading to treatment stop" ⁷. An SAE is a serious adverse event.

ASTONISH's registry record lists known pregnancy, prolonged QT syndrome and immunosuppressive therapy after a transplant in the past six months among its exclusions ⁴. Prolonged QT syndrome is a heart-rhythm condition, and immunosuppressive therapy is treatment that dampens the immune system.

In sport

Nangibotide is not named on the 2026 Prohibited List of WADA, the World Anti-Doping Agency ¹³. Nor does the list name LR12, MOTREM or TREM-1 ¹³. The phase 2a septic shock trial gave nangibotide by continuous infusion into a vein ⁵. The list's method rule M2.2 prohibits "Intravenous infusions and/or injections of more than a total of 100 mL per 12-hour period except for those legitimately received in the course of hospital treatments, surgical procedures or clinical diagnostic investigations" ¹³.

Section S0 of the list reads: "Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development or discontinued, designer drugs, substances approved only for veterinary use) is prohibited at all times" ¹³. Drugs@FDA lists no approved nangibotide product as of November 9, 2026 ³.

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JumpstartMD does not prescribe nangibotide. Our peptide library covers it so you have the facts on its FDA status and the evidence, current as of November 10, 2026.

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Compounded medications are not FDA-approved, and FDA does not review their safety, effectiveness, or quality before they are marketed. A licensed clinician decides after an evaluation whether a peptide is appropriate for you, and not every patient will qualify.