CAMBRIDGE, Mass. — Mirai Bio said new preclinical data presented at the American Society of Gene and Cell Therapy Annual Meeting show rapid advancement of its CD8-targeted lipid nanoparticle platform from design to functional proof-of-concept in non-human primates.
The Cambridge-based company, which works with partners developing next-generation nucleic acid medicines, said it advanced a CD8-targeted LNP from concept to non-human primate data in 10 months. The company said the results support the platform’s potential for in vivo RNA CAR-T programs.
T cells are a major target for delivery technologies because of their role in immune biology and relevance to autoimmune diseases, oncology and other immune-mediated conditions. Mirai said its data address key requirements for in vivo T-cell targeting, including T-cell specificity, reduced liver-directed delivery, scalable production, tolerability and functional activity in relevant models.
“Nucleic acid medicine programs can only move as fast as their delivery systems allow,” said Jagesh V. Shah, Ph.D., SVP, Head of Platform at Mirai Bio. “These data show that Mirai can help partners move from delivery concept to functional NHP proof-of-concept with the speed and translational relevance needed to make confident development decisions. For in vivo T-cell programs, that means generating the proof points that matter, including functional activity, tolerability, and a clear path toward the clinic.”
In the first poster, Mirai described the discovery and evaluation of novel ionizable lipids and long-circulating LNP compositions designed to support targeted mRNA delivery to T cells outside the liver. The company said it used a modular lipid discovery platform to generate structurally diverse ionizable lipid libraries and screen LNPs with dual mRNA cargoes to assess liver expression and tissue distribution.
Lead particles were reformulated into long-circulating compositions that reduced hepatic expression and supported extrahepatic delivery in mice. Mirai said the optimized base particles were then converted into CD8-targeted LNPs, which showed selective CD8+ T-cell expression with minimal CD4+ T-cell or B-cell transfection.
When loaded with CD20 CAR mRNA, the CD8-targeted LNPs produced dose-dependent CAR expression and B-cell depletion in CD34+ humanized mice, linking particle design to functional immune-cell activity.
In the second poster, Mirai said it extended the CD8-targeted LNP platform into non-human primate-scale production and functional in vivo evaluation. The company generated CD8-targeted LNPs carrying mRNA encoding a second-generation anti-CD20 CAR designed to be cross-reactive in humans and cynomolgus monkeys.
After systemic administration in non-human primates, a single dose generated CAR-expressing endogenous CD8+ T cells and rapidly depleted circulating CD20+ B cells through seven days after dosing. Mirai also reported reduced CD20+ cells in the spleen at 72 hours.
The company said the results showed a tolerability profile supportive of continued translational development. Cytokine and clinical chemistry findings were monitored and controlled across studies, and Mirai reported no major clinical observations in non-human primates through the end of the study.
