By Fineline Cube 
In a landmark announcement, Lion TCR disclosed that the U.S. Food and Drug Administration (FDA) has granted approval to initiate a Phase Ib/II clinical trial of its novel mRNA‑encoded TCR‑T cell therapy, LioCyx‑M004, for the treatment of chronic hepatitis B (CHB).
How LioCyx‑M004 Works
- Autologous Platform: The therapy employs a patient’s own T cells, genetically reprogrammed with mRNA to express a T‑cell receptor (TCR) that specifically recognizes the hepatitis B surface antigen (HBsAg).
- Targeted Cytotoxicity: Engineered T cells home to liver cells infected with HBV, selectively killing them while sparing healthy hepatocytes.
- Transient, Safe Expression: The mRNA‑based approach delivers short‑lived TCR expression, reducing long‑term off‑target risks; multiple infusions further optimize safety and therapeutic benefit.
First‑In‑Class Achievement
- Global First: LioCyx‑M004 is the first TCR‑T therapy approved by the FDA for chronic hepatitis B worldwide.
- Fast‑Track Designation: It also becomes the first HBV‑specific TCR‑T therapy to receive FDA Fast‑Track status, expediting development and review timelines.
Implications for CHB Treatment
Chronic hepatitis B remains a leading cause of liver cirrhosis and hepatocellular carcinoma, yet current antiviral regimens rarely achieve functional cure. LioCyx‑M004 offers a precision immunotherapy that could eradicate infected hepatocytes, potentially transforming the therapeutic landscape for HBV‑related liver disease.
Next Steps
Lion TCR will commence the Phase Ib/II study in the first quarter of 2026, enrolling patients with treatment‑naïve or treatment‑experienced CHB. The company anticipates pivotal data collection by 2028, with the possibility of accelerated regulatory pathways should the trial demonstrate robust safety and efficacy.-Fineline Info & Tech