RiboX Advances First-in-Class CAR-T Therapy Designed to Generate CAR-T Cells in the Body

RiboX Therapeutics Ltd. announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for RXIM002, an investigational circular RNA (circRNA)-based in vivo CAR-T therapy for autoimmune cytopenias. Delivered through a targeted lipid nanoparticle (tLNP), RXIM002 is designed to generate functional CAR-T cells directly inside the patient’s body, potentially bypassing the complex, costly, and time-consuming ex vivo manufacturing process used for conventional CAR-T therapies.

The IND clearance supports the initiation of the Phase 1 POPULUS-1 clinical trial. RiboX describes RXIM002 as the world’s first tLNP-circRNA in vivo CAR therapy to achieve FDA IND clearance.

Disease Background

Autoimmune cytopenias involve immune-mediated destruction of blood cells or blood-cell components. RXIM002 is initially being developed for patients with relapsed or refractory autoimmune cytopenias, with the POPULUS-1 study initially enrolling patients with relapsed or refractory immune thrombocytopenia (ITP).

ITP is the most prevalent autoimmune cytopenia and is characterized by a low platelet count and an increased risk of bruising and bleeding. According to RiboX, ITP involves pathogenic autoantibodies driven by aberrant B-cell activation.

Drug Overview & Mechanism

Target & Platform: RXIM002 uses a tLNP-encapsulated circRNA encoding a CD19-targeting chimeric antigen receptor (CAR).

In Vivo Generation: The circRNA is delivered to T cells in vivo, with the aim of generating functional CAR-T cells directly within the patient’s body. The approach is designed to provide durable, non-integrating CAR expression.

Therapeutic Goal: The resulting CAR-T cells are designed to target CD19-positive B cells. RiboX is investigating whether deep depletion of pathogenic B cells could promote immune reset and potentially lead to durable, drug-free remission in B-cell-driven autoimmune diseases.

Unlike conventional CAR-T therapies, which require T cells to be collected, genetically modified, and expanded outside the body before being administered back to the patient, RXIM002 is designed to generate CAR-T cells directly in vivo. This approach could potentially bypass the complex manufacturing process associated with conventional ex vivo CAR-T therapy.

Clinical Development & Trial Data

Investigator-Initiated Trials (IITs): Clinical development is supported by prior investigator-initiated trials conducted in China in patients with autoimmune diseases. Follow-up remains ongoing, with some patients having exceeded six months of follow-up.

FDA Package & Regulatory Outcomes: RiboX submitted the complete IIT dataset to the FDA as part of its IND package. According to the company, the dataset included safety and early efficacy results from all treated patients.

According to RiboX, based on the integrity and robustness of the submitted dataset, the FDA permitted an accelerated dose-titration scheme and included a subcutaneous formulation as part of the clinical development program. The subcutaneous formulation could potentially support outpatient administration, although its clinical utility remains to be established through clinical evaluation.

POPULUS-1 Phase 1 Trial: POPULUS-1 is a Phase 1 clinical trial evaluating the safety, pharmacokinetics (PK), pharmacodynamics (PD), and early efficacy of RXIM002 in patients with relapsed or refractory autoimmune cytopenias. The study will initially enroll patients with relapsed or refractory ITP.

Summary of Key Takeaways

• First-in-Class Milestone: RiboX describes RXIM002 as the world’s first tLNP-circRNA in vivo CAR therapy to achieve FDA IND clearance.
• In Vivo CAR-T Generation: RXIM002 is designed to generate functional CAR-T cells directly within the patient’s body, potentially bypassing conventional ex vivo manufacturing.
• Subcutaneous Formulation: The FDA included a subcutaneous formulation in the clinical development program, which could potentially support outpatient administration.
• Clinical Evaluation: POPULUS-1 will evaluate the safety, pharmacokinetics, pharmacodynamics, and early efficacy of RXIM002, initially in patients with relapsed or refractory ITP.
• Safety Remains Under Evaluation: The IIT dataset submitted to the FDA included safety results from all treated patients, but detailed adverse-event data were not provided in the announcement. RXIM002 remains investigational, and its safety profile will be further evaluated in POPULUS-1.

Expert Perspective

“The FDA IND clearance for RXIM002 is a pivotal milestone for RiboX and for the field of circRNA medicines. 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.”

— Weiyi Zhang, Ph.D., Chief Executive Officer of RiboX Therapeutics

Zhang said RiboX plans to advance clinical research on RXIM002 across multiple regions to address unmet needs in autoimmune diseases.

Patient Impact & Future Path

RXIM002 represents an investigational approach to treating B-cell-driven autoimmune diseases through in vivo generation of CAR-T cells. By targeting CD19-positive B cells, the therapy is designed to deplete pathogenic B cells and potentially promote immune reset and sustained disease remission.

If clinical studies demonstrate safety and efficacy, the approach could potentially offer an off-the-shelf model for CAR-T therapy while reducing some of the manufacturing complexity associated with conventional ex vivo CAR-T treatment.

However, FDA IND clearance permits clinical testing and does not establish the safety or efficacy of RXIM002. The Phase 1 POPULUS-1 study will provide prospective clinical data on the therapy’s safety, pharmacokinetics, pharmacodynamics, and early efficacy.

Continued follow-up of patients from the earlier IITs, together with results from POPULUS-1, will help determine the clinical potential of RXIM002 and the broader applicability of RiboX’s circRNA and targeted LNP platform in autoimmune diseases.

Reference

RiboX Therapeutics Announces FDA IND Clearance for RXIM002, the first Circular RNA-Based in vivo CAR Therapy for Autoimmune Cytopenias