LioCyx-M / Lion TCR - LARVOL DELTA

Lion TCR Achieves Triple FDA Milestones with IND Clearance for Chronic Hepatitis B Following Earlier Fast Track and Orphan Drug Designations (The Manila Times) - "This approval represents the third major regulatory milestone for the same product candidate, which previously received both Fast Track and Orphan Drug Designations for the treatment of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC)."

Fast track • Orphan drug • Hepatitis B • Hepatocellular Cancer

Lion TCR Achieves Triple FDA Milestones with IND Clearance for Chronic Hepatitis B (The Manila Times) - "Lion TCR...announced that it has received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) to initiate phase1b/2 clinical trials for its proprietary TCR-T cell therapy, LioCyx-M004, in patients with chronic hepatitis B (CHB)."

IND • New P1/2 trial • Hepatitis B

HBV-Specific TCR-T Cell Therapy Combining mRNA Electroporation and Lentiviral Transduction: Treatment Regime for Recurrent HBV-Related HCC Post-Liver Transplantation. (PubMed, Clin Cancer Res) - P1 | "This study preliminarily suggests that the combination of mRNA-HBV-TCR-T cells and lenti-HBV-TCR-T cells could be a safe and potentially effective approach for treating patients following liver transplantation in the context of lifelong immunosuppression drug administration. Further studies are needed to refine treatment strategies and assess long-term safety and efficacy in this special patient population."

Journal • Hepatocellular Cancer • Oncology • Transplantation

HBV-TCR T cell therapy: Preclinical and clinical insights into specificity, safety and efficacy for treating HBV-related HCC. (ASCO 2025) - P1 | "Preclinical and clinical data demonstrate the specificity, safety and efficacy of multiple LioCyx-M infusions. LioCyx-M treatment reprograms patient's immunity from exhausted status to immune active status, implying its potential in cancer immunotherapy. Reference Tan et al."

Preclinical • Hepatitis B • Hepatocellular Cancer • CCR7 • CXCL10 • CXCL9 • HAVCR2 • HLA-A • IFNG

Autologous HBV-TCR T Cell Therapy (LioCyx-M) for the Treatment of Hepatocellular Carcinoma (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Lion TCR Pte. Ltd.

New P1 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Association of T cell epitope spreading with the clinical efficacy of HBV-TCR T cell therapy for HBV-related HCC (EASL 2025) - "We provided preliminary evidences that clinical efficacy of TCR-T cell therapy in patients with HBV-related HCC is not directly proportional to the quantity and persistence of infused TCR-T cells but to their ability to induce inflammation and trigger a T cell response against novel T cell epitopes through a possible process of T cell epitope spreading."

Clinical • Hematological Disorders • Hematological Malignancies • Hepatitis B • Hepatocellular Cancer • CD8 • CXCL10

A rapid method to assess the in vivo multi-functionality of adoptively transferred engineered TCR T cells (APASL 2025) - "These findings support the utility of the whole blood cytokine release assay in monitoring the in vivo function and quantity of engineered T cell products following adoptive transfer."

Preclinical • Hepatocellular Cancer • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor

Association of T cell epitope spreading with the clinical efficacy of HBV-TCR T cell therapy for HBV-related HCC (APASL 2025) - "We provided preliminary evidences that clinical efficacy of TCR-T cell therapy in patients with HBV-related HCC is not directly proportional to the quantity and persistence of infused TCR-T cells but to their ability to induce inflammation and trigger a T cell response against novel T cell epitopes through a possible process of T cell epitope spreading."

Clinical • Hematological Disorders • Hematological Malignancies • Hepatitis B • Hepatocellular Cancer • CD8 • CXCL10

HBV-Specific TCR-T Cell Therapy Combined with Nucleos(t)ide Analogues in Chronic Hepatitis B Patients (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Changhai Hospital

New P1 trial • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Study of HBV-TCR T Cells (LioCyx-M) as Monotherapy or as Combination With Lenvatinib for HBV-related HCC (clinicaltrials.gov) - P2 | N=55 | Not yet recruiting | Sponsor: Lion TCR Pte. Ltd. | Phase classification: P1b/2 ➔ P2 | Trial completion date: May 2027 ➔ Dec 2028 | Trial primary completion date: Feb 2026 ➔ Dec 2026

Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Lion TCR's Liocyx-M004 Receives FDA Clearance to Launch Global Multicenter Phase 2 Clinical Trial in HBV-Related Hepatocellular Carcinoma (PRNewswire) - "On 12 Feb 2025 (Singapore Time), Lion TCR announced that its mRNA-encoded T-cell receptor (TCR)-T cell therapy product Liocyx-M004 has received clearance from the U.S. Food and Drug Administration (FDA) to initiate an international multicenter Phase 2 clinical trial. This significant progress further solidifies Lion TCR's leading position in the mRNA-based TCR-T field and brings new hope to patients with hepatocellular carcinoma (HCC)....The FDA-approved international multicenter Phase 2 clinical trial will evaluate the efficacy of Liocyx-M004 as a monotherapy and in combination with lenvatinib."

IND • New P2 trial • Hepatocellular Cancer

A rapid method to assess the in vivo multi-functionality of adoptively transferred engineered TCR T cells. (PubMed, Immunother Adv) - "The amount of cytokines secreted also showed an infusion-dose-dependent association. These findings support the utility of the whole blood cytokine release assay in monitoring the in vivo function and quantity of engineered T cell products following adoptive transfer."

Journal • Preclinical • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor

Mrna Based HBV-Specific Tcr T-Cell infusions Can induce Broad HBV T-Cell Response in HBV-Related HCC (APASL 2024) - P1 | "Our findings shed light on the safety and immunological responses to LioCyx-M, indicating its potential to trigger a broader immune response targeting various facets of HBV-related HCC."

Hepatitis B • Hepatocellular Cancer • Hepatology • Inflammation • CXCL10 • CXCL9 • GZMB • IFNG • IL2 • IL4

Redirected HBV-Specific T Cells in Patients With HBV-related HCC (SAFE-T-HBV) (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Lion TCR Pte. Ltd. | Trial completion date: Jul 2024 ➔ Jul 2028 | Trial primary completion date: Jul 2023 ➔ Jul 2026

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor • HLA-A

Lytic efficiency of immunosuppressive drug-resistant armoured T cells against circulating HBV-related HCC in whole blood. (PubMed, Immunother Adv) - "The assay was then used to quantify the efficacy of IDRA HBV-TCRs to lyse free-floating HBV-HCC cells in the presence of Tacrolimus and Mycophenolate Mofetil (MMF)...In conclusion, IDRA HBV-TCR T cells can lyse free-floating HBV-HCC cells in whole blood in the presence of Tacrolimus and MMF. The quantity of IDRA-HBV TCR T cells required can be achieved by the adoptive transfer of 5 × 10 IDRA-HBV TCR-T cells/kg, supporting the utilisation of IDRA HBV-TCR T cells to eliminate CTCs as prophylaxis against recurrence after LT."

Journal • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor • Transplant Rejection • Transplantation • GPC3 • PTPRC • VIM

Messenger RNA electroporated hepatitis B virus (HBV) antigen-specific T cell receptor (TCR) redirected T cell therapy is well-tolerated in patients with recurrent HBV-related hepatocellular carcinoma post-liver transplantation: results from a phase I trial. (PubMed, Hepatol Int) - P1 | "This study has demonstrated that multiple infusions of mRNA electroporated HBV-specific TCR T cells were well-tolerated in patients with HBV-positive recurrent HCC post-liver transplant."

Journal • P1 data • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor • Transplantation • HLA-A • HLA-B • HLA-C

ANALYSIS OF BIOCHEMICAL AND IMMUNOLOGICAL ALTERATIONS IN DISEASE CONTROL GROUP VS DISEASE PROGRESSION GROUP AFTER HEPATITIS B VIRUS (HBV)-SPECIFIC TCELL RECEPTOR (TCR) T CELL THERAPY FOR PRIMARY HBV-RELATED HEPATOCELLULAR CARCINOMA (AASLD 2022) - P1 | "These data collectively depict the differential liver function, viral and immune alterations in patient with and without clinical response, highlighting the importance of secondary immune response activation via the cancer-immunity cycle for durable anti-tumor effects of LioCyx-M. 1) Meng et al. Immunotherapy of HBV-related advanced hepatocellular carcinoma with short-term HBV-specific TCR expressed T cells: results of dose escalation, phase I trial."

IO biomarker • Late-breaking abstract • Gastrointestinal Cancer • Hematological Malignancies • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor • CD4 • CD8 • CXCL10 • CXCL9 • ENTPD1

Redirected HBV-Specific T Cells in Patients With HBV-related HCC (SAFE-T-HBV) (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Lion TCR Pte. Ltd. | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2022 ➔ Jul 2024 | Trial primary completion date: Jul 2022 ➔ Jul 2023

Enrollment open • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Oncology • Solid Tumor • HLA-A

A Study of TCR-Redirected T Cell Infusion to Prevent Hepatocellular Carcinoma Recurrence Post Liver Transplantation (clinicaltrials.gov) - P1 | N=13 | Completed | Sponsor: Lion TCR Pte. Ltd. | Unknown status ➔ Completed | N=10 ➔ 13 | Trial completion date: Nov 2020 ➔ Sep 2021 | Trial primary completion date: Nov 2017 ➔ Sep 2021

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Oncology • Solid Tumor • Transplantation

Immunological alterations after immunotherapy with short lived HBV-TCR T cells associates with long-term treatment response in HBV-HCC. (PubMed, Hepatol Commun) - "In contrast, signs of transient localized liver inflammation, activation of the T-cell compartment, and/or elevations of serum chemokine (C-X-C motif) ligand (CXCL) 9 and CXCL10 levels were detected in patients with long-term clinical benefit. We show that despite the reduced in vivo half-life (3-4 days), adoptive transfer of mRNA HBV-TCR T cells into patients with HBV-HCC show long-term clinical benefit that was associated with transient immunological alterations."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor • CXCL10

Lion TCR Receives FDA Fast Track Designation for its HBV-specific TCR T Cell Therapy for Hepatocellular Carcinoma (PRNewswire) - "Lion TCR Pte Ltd today announced that it has received Fast Track Designation from United States Food and Drug Administration (U.S. FDA) for LioCyx-M004, autologous T-cells transfected with mRNA encoding Hepatitis B surface antigen (HBsAg) specific TCR, for the treatment of HBV-related hepatocellular carcinoma (HBV-related HCC)....This designation was granted based on that the efficacy of LioCyx-M004, as demonstrated by an improvement in the overall survival in patients with HBsAg-positive HCC relapsed or refractory to prior systemic treatment."

Fast track designation • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Immunotherapy of HBV-related advanced hepatocellular carcinoma with short-term HBV-specific TCR expressed T cells: results of dose escalation, phase I trial. (PubMed, Hepatol Int) - P1 | "The adoptive transfer of HBV-TCR-T cells into advanced HBV-HCC patients were generally safe and well-tolerated. Observations of clinical efficacy support the continued development and eventual application of this treatment strategy in patients with advanced HBV-related HCC."

Journal • P1 data • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Oncology • Solid Tumor • Transplantation

Lion TCR Announces FDA IND Clearance for its LioCyx-M004 for Hepatocellular Carcinoma (PRNewswire) - P1, N=NA; "Lion TCR Pte Ltd...announced that it has received clearance from U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) Application for LioCyx-M004, autologous T-cells transfected with mRNA encoding Hepatitis B surface antigen (HBsAg) specific TCR...Lion TCR intends to initiate a Phase 1b/2 multi-center study for its lead investigational product, LioCyx-M004, for patients with advanced Hepatitis B Virus (HBV)-related hepatocellular carcinoma....The use of LioCyx-M004 has been tested in Phase 1 study in primary HBV-related HCC. LioCyx-M004 infusions were well-tolerated with no occurrence of cytokine release syndrome (CRS) nor neurotoxicity. Disease control rate was 60% and partial response (PR) as per RECIST 1.1 was observed with a duration of response of 27.7 months."

IND • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

"#LionTCR Announces #FDA #IND Clearance for its #LioCyxM004 for #HepatocellularCarcinoma https://t.co/vkYRYjxM6D" (@1stOncology)

Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor