SANA

Phase 1A/B trial in Australia (41 volunteers)

The randomized, double-blind, placebo-controlled first-in-human trial of SANA ran at CMAX Clinical Research in Adelaide and is registered with the Australian New Zealand Clinical Trials Registry as ACTRN12622001519741 (PMID: 40527924). Part A gave single oral doses of 200, 400 or 800 mg to healthy lean volunteers (17 in total, randomized 2:1 to SANA or placebo), and part B gave doses of 200 to 400 mg a day, split into two doses 12 hours apart for 14 days plus a final dose on day 15, to volunteers with overweight or obesity (24 in total, randomized 3:1) (PMID: 40527924). The primary end point was safety, pharmacokinetics were secondary, and body weight, glucose, insulin and fructosamine were exploratory end points (PMID: 40527924).

In the highest-dose SANA cohort (200 mg every 12 hours), participants lost about 3 percent of body weight over 15 days while living in the clinic on a provided high-carbohydrate diet, and fasting insulin, HOMA-IR and fructosamine improved; participants on placebo showed no such changes (PMID: 40527924). The authors state that the SANA trial was designed and powered for safety, that its efficacy results are preliminary, and that a longer phase 2 trial is needed (PMID: 40527924). Body weight could not be measured for two placebo and four SANA participants in the lowest cohort because of an error in the original protocol (PMID: 40527924).

Mouse studies

Mixed into food for mice on a high-fat diet, SANA prevented weight gain without changing food intake, stool energy or activity, reduced fat in every depot measured, and prevented fatty liver, the rise in liver enzymes and glucose intolerance; SANA did not change the weight of mice fed normal chow (PMID: 40527924). In mice made obese before treatment, SANA caused weight loss without lowering food intake and improved glucose control more than salicylate or metformin over 3 weeks (PMID: 40527924). Protection against diet-induced obesity also held in mice housed at 28 degrees Celsius, a thermoneutral temperature for mice (PMID: 40527924). SANA had its maximal effect on obesity at doses where salicylate was ineffective, and the 2023 preprint, which was not peer reviewed, reported effects at doses up to 40 times lower than salicylate (PMID: 40527924, PMID: 37502859).

Transplant models

SANA prolonged heart graft survival in rats and skin graft survival in mice, and in the mouse skin graft model the effect depended on TMEM176B, heme oxygenase-1 and regulatory T cells (PMID: 40691833). A commentary by Alain Le Moine in the same journal discussed the SANA graft study (PMID: 41082251).

Publication history

The SANA work first appeared in 2023 as a preprint on Research Square that was not peer reviewed (PMID: 37502859), which PubMed links to the 2025 Nature Metabolism paper as its updated version (PMID: 40527924).

No adverse events judged definitively drug-related occurred in the 15-day multiple-dose part of the SANA trial, and the most frequent possibly drug-related events were headache and soft stools (PMID: 40527924). No severe adverse events were recorded, liver function was normal in all participants after 15 days, and no moderate or severe gastrointestinal adverse effects were reported (PMID: 40527924). One participant in the lowest multiple-dose cohort was withdrawn because of mild proteinuria, which was judged unrelated to SANA and probably due to kidney disease missed at screening (PMID: 40527924). Participants reported no change in appetite or satiety on a questionnaire, and one participant in the highest-dose group had higher fasting glucose despite lower weight and insulin (PMID: 40527924).

Animal data

Eight weeks of SANA at 400 mg/kg a day in normal mice showed no signs of kidney or liver toxicity (PMID: 40527924). In mice lacking the mitochondrial creatine kinase CKMT1, SANA at room temperature was followed by a roughly 50 percent increase in mortality within a week, while no normal mice died, and housing at thermoneutrality prevented the deaths; the authors suggest SANA commits mice to creatine-dependent heat production at the expense of other heat-producing pathways (PMID: 40527924). In normal mice, SANA did not impair shivering, skeletal muscle creatine kinase or mitochondrial function, exercise capacity, or heart mitochondrial respiration and function, although it raised muscle creatine levels (PMID: 40527924).

What is not known

No human data on SANA beyond 15 days, in pregnancy, in children or with other medicines were found (PMID: 40527924).