RiboX Therapeutics Secures FDA IND Clearance for RXIM002, the First Circular RNA-Based In Vivo CAR-T Therapy
核心洞察
The FDA cleared RiboX Therapeutics (搜索)' IND application for RXIM002 (搜索), the world's first circular RNA-based in vivo CAR-T therapy delivered via targeted lipid nanoparticles.
RXIM002 (搜索) encodes a CD19 (搜索)-targeting CAR and is designed to generate functional CAR-T cells directly inside the patient, bypassing complex ex vivo manufacturing.
The therapy targets autoimmune cytopenias (搜索), with the Phase 1 POPULUS-1 trial initially enrolling patients with relapsed or refractory immune thrombocytopenia (搜索) (ITP).
RiboX Therapeutics (搜索) Ltd., a global clinical-stage biotechnology company with operations in Shanghai, Cambridge, Mass., and Israel, announced that the U.S. Food and Drug Administration has cleared its Investigational New Drug application for RXIM002 (搜索) — the world's first circular RNA-based in vivo CAR-T therapy delivered by a targeted lipid nanoparticle (tLNP). The clearance marks a watershed moment for the field, as circRNA-based in vivo CAR-T officially advances into clinical development.
RXIM002 (搜索) employs tLNP-encapsulated circular RNA encoding a CD19 (搜索)-targeting chimeric antigen receptor for the treatment of autoimmune cytopenias (搜索). By delivering circRNA directly to T cells in vivo, the therapy enables durable CAR expression and generates functional CAR-T cells within the patient's body. This "in situ generation" approach fundamentally bypasses the complex, costly, and time-consuming ex vivo manufacturing processes required by conventional CAR-T therapies, potentially expanding patient access significantly.
"In autoimmune diseases, deep B cell depletion driven by the in vivo generated CAR-T cells has the potential to induce immune reset and durable drug-free remission," the company stated in its announcement.
Clinical Evidence Supporting Accelerated Development
Prior to the IND submission, RXIM002 (搜索) was evaluated in investigator-initiated trials in China involving autoimmune disease patients. Follow-up remains ongoing, with some patients now exceeding six months of observation. RiboX submitted complete IIT data as part of the IND package to the FDA, encompassing safety and early efficacy results from all treated patients.
Based on the integrity and robustness of this full dataset, the FDA permitted an accelerated dose-titration scheme and granted a subcutaneous formulation as part of clinical development. This regulatory flexibility paves the way for potentially outpatient administration — a paradigm shift that could fundamentally transform how CAR-T therapies are delivered.
"The FDA IND clearance for RXIM002 (搜索) is a pivotal milestone for RiboX and for the field of circRNA medicines," said Weiyi Zhang, Ph.D., Chief Executive Officer of RiboX Therapeutics (搜索). "As the first-in-class circRNA in vivo CAR-T therapy to enter the clinic, RXIM002 exemplifies our ability to translate robust pre-clinical results and rigorous early clinical evidence into an accelerated development path."
The POPULUS-1 Phase 1 Trial
The Phase 1 POPULUS-1 study will evaluate the safety, pharmacokinetics, pharmacodynamics, and early efficacy of RXIM002 (搜索) in patients with relapsed or refractory autoimmune cytopenias (搜索). The trial will initially enroll participants with relapsed or refractory immune thrombocytopenia (搜索) (ITP), the most prevalent autoimmune cytopenia, characterized by low platelet counts and an increased risk of bruising and bleeding.
ITP is driven by pathogenic autoantibodies resulting from aberrant B-cell activation. RXIM002 (搜索) is being developed to induce transient in vivo CAR T-cell-mediated depletion of pathogenic B cells while potentially preserving immune competence.
Platform Validation and Strategic Implications
To the company's knowledge, RXIM002 (搜索) is the world's first tLNP-circRNA in vivo CAR therapy to achieve FDA IND clearance. This milestone validates RiboX's proprietary tLNP platform and reinforces the company's leadership position in precision RNA therapeutics. RiboX develops proprietary circRNA and targeted LNP platforms designed to enable durable expression, precision tissue targeting, and broad therapeutic applicability across multiple disease areas.
Zhang added: "This achievement brings us closer to delivering a transformative treatment option for patients living with debilitating autoimmune diseases. We are committed to advancing clinical research of RXIM002 (搜索) across multiple regions worldwide to address the significant unmet needs."