NewLimit reports more than a 314-fold increase in production of its liver cell rejuvenation treatment since the start of the year and guidance from regulators; its first human trial is planned for 2027
NewLimit reports more than a 314-fold increase in production of its liver cell rejuvenation treatment since the start of the year and guidance from regulators; its first human trial is planned for 2027
On 21 October, NewLimit published its summer report. According to the report, a single batch of the treatment produced over the summer exceeded its entire output for 2025.
NewLimit’s treatment consists of mRNA encoding several transcription factors, proteins that switch genes on and off. The RNA is packaged in lipid nanoparticles, small fat-based capsules, and cells produce the proteins for a short time. According to the company’s description, the approach was inspired by the Yamanaka factors: four proteins that can return old cells to a youthful state and, when briefly activated in old animals, can rejuvenate several tissues. However, these factors suppress the activity of genes that define an adult cell’s identity and pose a risk of tumors. NewLimit is looking for combinations of factors that restore youthful gene activity in old cells while preserving their identity as liver cells.
The first target is the liver. Its cells, called hepatocytes, naturally take up fats from the blood, allowing nanoparticles to reach them without a targeting molecule. Because hepatocytes are poorly suited to conventional cell culture, the combinations are tested in mice with human livers. Gene activity is used to identify which combinations make old cells resemble young ones. The best combinations are then tested in old mice. According to the company, treated mice show better liver regeneration after surgery than control mice and lower blood levels of liver injury markers after an alcohol-containing diet.
Before the treatment can be tested in humans, the company needs to demonstrate that it can be manufactured and establish its safety in preclinical studies. The report identifies manufacturing as the first bottleneck: as company head Jacob Kimmel writes, the processes used to make initial batches rarely transfer successfully to larger volumes. NewLimit estimates that early experiments require less than 1 mg of the treatment, pivotal safety studies require more than 100 mg, and a clinical trial requires more than 1000 mg. Since the start of the year, production scale has increased more than 314-fold, and several measures of quality have improved more than 13-fold.
The treatment produced using the scaled-up process was then tested for delivery, since its activity depends on how much RNA reaches liver cells. In the animal model the company considers most suitable, RNA was detected in liver cells at each of the three doses, with higher doses delivering more RNA. The company views this as definitive confirmation that its efforts to scale up production and improve quality were successful.
The report lists the first studies in large animals and clear regulatory guidance on the program among the summer’s milestones. The company plans to begin human trials in 2027. As Fierce Biotech reported in June, the first participants will be patients with fatty liver disease.
According to the report, new combinations are 2–3 times more effective than the previous best combinations at restoring the regenerative capacity of old liver cells, both in human cells within mice and in mouse cells. The company sees this as evidence that the effect is shared across species. Two additional combinations restored both regeneration and resistance to injury from a damaging diet in these cells.
The vascular program aims to restore youthful function to the endothelium, the cells lining the inside of blood vessels, starting with the kidneys. In mice, an RNA marker delivered by nanoparticles was detected in the glomeruli, the kidney’s small filtering structures. According to the report, the AI model that selects combinations for testing is also trained on liver and T-cell data, reducing the amount of vascular data it needs by more than fivefold.