RiboX Therapeutics announced that the US 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 delivered through a targeted Lipid Nanoparticle (tLNP).

The company describes RXIM002 as the first tLNP-circRNA in vivo CAR-T therapy to receive FDA IND clearance, marking a significant milestone in the development of circRNA-based cell therapies and enabling the programme to advance into clinical development.

RXIM002 uses a tLNP to deliver circRNA encoding a CD19-directed Chimeric Antigen Receptor (CAR) directly to T cells inside the patient's body. The approach is designed to generate functional CAR-T cells in vivo, enabling sustained, non-integrating CAR expression without the complex ex vivo cell collection, genetic modification and manufacturing processes associated with conventional CAR-T therapies.

RiboX is initially developing RXIM002 for autoimmune cytopenias, a group of disorders driven by pathogenic immune responses. The company believes that targeted depletion of disease-causing B cells by in vivo-generated CAR-T cells could potentially reset the immune system and support prolonged, drug-free remission.

Before submitting the IND application, RXIM002 was evaluated in investigator-initiated trials in China involving patients with autoimmune diseases. Follow-up remains ongoing, with some patients monitored for more than six months. RiboX included the available safety and early efficacy data from all treated patients in its FDA submission.

According to the company, the strength of the clinical dataset enabled the FDA to permit an accelerated dose-titration approach and include a subcutaneous formulation in the clinical development programme. The latter could potentially facilitate outpatient administration and further differentiate the approach from conventional CAR-T treatment models.

Weiyi Zhang, Ph.D., Chief Executive Officer of RiboX Therapeutics, said that the FDA clearance represents an important milestone for both the company and the broader field of circRNA medicines. He added that RXIM002 demonstrates RiboX's ability to translate preclinical research and early clinical evidence into an accelerated development programme for autoimmune diseases with significant unmet medical needs.

The next stage of development will be evaluated through POPULUS-1, a Phase 1 clinical trial designed to assess the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of RXIM002 in patients with relapsed or refractory autoimmune cytopenias.

The trial will initially focus on Immune Thrombocytopenia (ITP), the most common autoimmune cytopenia. ITP is characterised by abnormally low platelet levels and an increased risk of bruising and bleeding, with pathogenic autoantibodies associated with abnormal B-cell activity playing a key role in disease progression.

Through transient in vivo generation of CAR-T cells, RXIM002 is intended to selectively deplete pathogenic B cells while potentially preserving broader immune function. The programme is designed as an off-the-shelf therapeutic approach that could overcome some of the logistical and manufacturing challenges associated with autologous CAR-T therapies.

RiboX's technology combines proprietary circRNA engineering with targeted LNP delivery, with the aim of enabling durable protein expression and precision delivery to specific tissues. The company is developing its platforms for applications across multiple therapeutic areas.

With FDA IND clearance now secured, RXIM002 becomes a clinical-stage programme and provides RiboX with an opportunity to further evaluate whether in vivo CAR-T generation using circRNA can deliver the efficacy and accessibility benefits needed to expand CAR-T technology beyond oncology and into autoimmune diseases.