CAMBRIDGE, Mass. — Liberate Bio Inc. said new preclinical data support its lead in vivo CAR-M program, LIB820, as the biotechnology company prepares for its first human study by the end of 2026.
The Cambridge-based company, which is developing genetic medicines designed to deliver RNA therapies directly to immune cells, said the data expand evidence for selective in vivo programming of monocytes and macrophages, peripheral B-cell depletion and a differentiated cytokine profile. The results are being presented at the American Society of Gene and Cell Therapies conference in Boston by Walter R. Strapps, Ph.D., Liberate Bio’s chief scientific officer.
LIB820 uses a four-component lipid nanoparticle, or LNP, that incorporates a novel cationic lipid generated through Liberate’s RAPTOR LNP screening platform. The therapy includes mRNA encoding an anti-CD19 chimeric antigen receptor, or CAR, designed to reprogram monocytes and macrophages inside the body.
Liberate said previously reported non-human primate data showed that selective delivery of CAR-encoding mRNA to monocytes and macrophages resulted in up to 99% peripheral B-cell depletion at well-tolerated doses. The company said new findings from cellular systems, mouse models and non-human primates further support the role of CAR-expressing myeloid cells as direct effector cells.
The company also said the data reinforce a tolerability profile that includes modest and transient cytokine changes, with no evidence so far of T-cell-driven proliferation or other toxicity measures.
“We’ve made great strides over the last six months on demonstrating the robustness of our novel LNP,” said Walter R. Strapps, Ph.D., Chief Scientific Officer of Liberate Bio. “We’re able to demonstrate that CAR-expressing myeloid cells can act as effector cells to deplete B-cells in circulation, and we see no evidence of the cytokine spikes that likely drive CRS. We’re excited by the fact that this is a novel approach to target B-cells with a CAR – one that doesn’t require expressing CAR in T-cells.”
Liberate said its RAPTOR platform enables direct screening of lipid nanoparticles in non-human primates to identify delivery vehicles that target cells outside the liver. The company’s lead LNP is a four-component nanoparticle without conjugated targeting moieties. It is designed to selectively deliver CAR-encoding mRNA to monocytes and macrophages in circulation and bone marrow.
The approach could allow for a repeatable, systemically administered method of in vivo immune programming, the company said.
Ongoing dose-optimization studies are intended to extend the duration of CAR-M activity and improve tissue distribution across disease-relevant areas, including circulation, lymphoid tissue and bone marrow. Liberate said updated data are expected in the second half of 2026.
“The field has seen the promise of in vivo CAR-T and the potential to broaden access to this important class of therapeutics, but T-cell programming is not the only path to immune reset,” said Shawn P. Davis, Ph.D., Chief Executive Officer of Liberate Bio. “LIB820 is designed to harness monocytes and macrophages as programmable effector cells — delivering cell-therapy-like activity through a repeatable, off-the-shelf medicine while avoiding the T-cell activation biology associated with cytokine release syndrome and neurotoxicity. If successful, CAR-M could expand immune programming beyond the most severe patients and into broader autoimmune, oncology, and immune-mediated diseases where CAR-T has not been a practical option.”
Liberate plans to support an investigator-initiated trial of LIB820 in diffuse cutaneous systemic sclerosis in the third quarter of 2026. The company expects proof-of-concept data on B-cell depletion and durability by the end of 2026.
The company said the trial would move its platform from preclinical validation into human proof of concept. Liberate’s initial clinical focus includes autoimmune diseases such as systemic lupus erythematosus and multiple sclerosis.
The company also is developing an oncology program, LIB810, an anti-BCMA CAR-M therapy that will be explored for relapsed or refractory multiple myeloma.
