The research
behind LionBio
We're developing a nasal formulation of semaglutide in a biodegradable polymer nanoparticle. Academic animal studies informed the approach. Our current work focuses on drug distribution, release, and preparation for clinical studies.
Stage: preclinical development
Where we started
Academic studies in animals examined drug distribution, weight change, and retching.
The olfactory lining in the upper nose connects to the brain through the olfactory nerves.4 We're investigating this route for peptide delivery.
Weight change in mice
Nasal tirzepatide nanoparticles reduced body weight in a four-week mouse study. The nasal dose was higher than the injected dose, so the study does not establish equivalence to injection.1
The formulation matters. In a separate eight-day study, free tirzepatide given through the nose at the same dose did not show the same effect as the nanoparticle formulation.1
Study context +
Four-week study: diet-induced obese mice, male; 8 vehicle, 8 nasal, 7 injected; one dose a day; body weight reported as change from each group's starting weight; the nasal dose was five times the injected dose. The vehicle group also lost some weight, which the authors attribute to daily handling and single housing.
Eight-day study: diet-induced obese mice, male; 7 vehicle, 7 nanoparticle, 8 free drug; one nasal dose a day; endpoint body weight. One comparison of one tirzepatide formulation in mice; it does not show that every unencapsulated nasal peptide fails.
Both studies used tirzepatide, not semaglutide.
Distribution and tolerability
Tracing distribution
Researchers detected a fluorescent label in the olfactory bulb after nasal dosing. This shows where the label was detected, not how much intact drug reached the brain.1
Representative mouse brain images one hour after a single dose of labelled tirzepatide, one animal per group. The nasal dose was five times the injected dose. Fluorescence tracks the label, not necessarily intact drug. Unpublished academic study.1
Study context +
Mice, male; tirzepatide carrying a fluorescent dye; imaging one hour after a single dose (3 vehicle, 4 nasal, 3 injected) and blood sampling over 24 hours (3, 6, 5). The nasal dose was five times the injected dose, so the two routes are not compared like for like. The assay detects the label, not necessarily intact drug; it is not a concentration, a brain-to-blood ratio or proof of a transport route.
Retching in minks
A small exploratory study found fewer retching episodes with nasal semaglutide nanoparticles than injection in one subgroup of minks, in a single-dose study.123
Study context +
Minks were used because, unlike mice and rats, they can vomit. Mixed-sex groups of 6 vehicle, 7 nasal and 6 injected animals; a single dose, with retching counted for two hours; the nasal dose was five times the injected dose. The difference was seen in the female animals; the males showed no difference between routes. Per-sex group sizes are not stated in the summary we have, so the female subgroup is smaller than the totals above.
Unpublished animal studies. Results may not translate to people. The mink study used unequal doses between routes.
Where we are, and where we're going
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Complete · 2024
Academic studies
Initial animal studies informed the formulation and delivery approach.
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Underway · Q3 2026
Rat studies
Measuring semaglutide in blood and brain after nasal dosing.
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Planned · Q1 2027
Non-human primate studies
Studying nasal delivery and drug exposure in non-human primates.
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In progress · Q4 2026
Formulation and manufacturing
Developing a consistent formulation and a process for larger batches.
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Target: Q4 2027
First clinical study
Preparing to test the formulation in people.
The clinical timeline depends on preclinical results, manufacturing readiness, and the required regulatory and ethics approvals.
LionBio's nasal formulation is investigational. Its safety and effectiveness in people have not been established, and it is not approved for human use.
Beyond semaglutide
We're exploring how the nanoparticle approach could be adapted to other GLP-1s and neuropeptides. Nasal delivery of several brain peptides has been studied in people.4 These are research directions; each molecule needs its own formulation and studies.
Potential research directions, not announced LionBio development programs.
Insulin Cognition and memory +
Nasal insulin has been studied in people; clinical findings are mixed.
A 2020 randomized trial enrolled 289 people with mild cognitive impairment or Alzheimer's dementia, with 240 in the primary device cohort. After 12 months the cognitive endpoint did not differ from placebo. Craft et al., JAMA Neurology, 2020 ↗
Oxytocin Apathy in frontotemporal dementia +
A phase 2 nasal study found a small improvement in apathy ratings.
The trial enrolled 94 participants with frontotemporal dementia across adaptive crossover stages, with six-week treatment periods. The selected intermittent schedule produced a small improvement in apathy ratings. This is a signal for a defined symptom, not broad cognitive benefit. Coleman et al., Lancet Neurology, 2025 ↗
Orexin-A Wakefulness +
Small nasal studies in narcolepsy provide an early reason to investigate this peptide.
A double-blind crossover nasal study in 14 people with narcolepsy with cataplexy reported changes in REM-related measures and fewer false responses on an attention task. This was a small acute study, not evidence of sustained benefit. Weinhold et al., Behavioural Brain Research, 2014 ↗
Growth hormone-releasing hormone Sleep +
A nasal GHRH study in healthy men increased slow-wave and REM sleep later in the night.
A double-blind crossover study gave 12 young and 11 older healthy men nasal GHRH or placebo before bedtime. GHRH increased slow-wave sleep and REM sleep, mostly in the second half of the night, with no difference by age. This was a single-night study, not evidence of treatment benefit. Perras et al., Psychoneuroendocrinology, 1999 ↗
Neuropeptide Y Stress-related disorders +
Early human nasal research has examined tolerability and anxiety responses in PTSD.
A small dose-ranging crossover study randomized 26 participants with PTSD, with 24 completing both visits. It found a dose-related signal on one anxiety scale but not another; it did not establish lasting treatment efficacy. Randomized nasal NPY study, 2018 ↗
- Wan Q, Li Z, Ding S, Shi M-Y, et al. GLP-1 drug targets the olfactory bulb to combat obesity. Manuscript in preparation (Peking University, Columbia University, University of Science and Technology of China). Unpublished academic study, not peer reviewed; animal data summarised here.
- Horn CC, et al. Why can't rodents vomit? A comparative behavioral, anatomical, and physiological study. PLoS One 2013;8:e60537. PubMed
- Zhang F, et al. Value of mink vomit model in study of anti-emetic drugs. World J Gastroenterol 2006;12:1300-1302. PubMed
- Lochhead JJ, Thorne RG. Intranasal delivery of biologics to the central nervous system. Adv Drug Deliv Rev 2012;64:614-628. PubMed
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