Lion TCR presents two abstracts of Phase 1 clinical trial data for lead product LioCyx-M at the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting

SINGAPORE – November 10, 2020 – Lion TCR announced today that it has presented two abstracts at the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting on November 9-14. Each of these abstracts highlights the good safety profile and efficacy of LioCyx-M and the promising use of HBV-specific TCR-T therapy in HBV-related HCC. ‍ TCR-T immunotherapy involves the bioengineering reprogramming of the human body’s natural immune defenders, T cells, to enhance their cytolytic specificity function against tumour cells. Our clinical data presented in these abstracts supports the use of Lion TCR’s lead T-cell product, LioCyx-M is a promising TCR-T immunotherapy for primary hepatocellular carcinoma (HCC) and recurrence post liver transplantation. ‍ Each of these abstracts highlights the good safety profile and efficacy of our lead product LioCyx-M, autologous T cells modified to express Hepatitis B virus (HBV)-specific TCR, as monotherapy in either unresectable HBV-associated hepatocellular carcinoma (HCC) or recurrent HCC post liver transplantation in two independent Phase I studies. These data demonstrate the promising use of HBV-specific TCR-T therapy in HBV-related HCC. ‍ Details of the posters are as follows: Title: Use of LioCyx-M, Autologous Hepatitis B Virus (HBV)-Specific T cell receptor (TCR) T-cells, in Advanced HBV-related Hepatocellular Carcinoma (HCC) ‍ Abstract #: 272 ‍ Co-corresponding authors: Antonio Bertoletti and Fu-Sheng Wang ‍ Presenting Author: Fanping Meng ‍ ClinicalTrials.gov number: NCT03899415 ‍ ‍ Title: Phase I Study of LioCyx-M, Autologous Hepatitis B Virus (HBV)-Specific T cell receptor (TCR) T-cells, in Recurrent HBV-Related Hepatocellular Carcinoma (HCC) Post-Liver Transplantation ‍ Abstract #: 273 ‍ Co-corresponding authors: Antonio Bertoletti and Qi Zhang ‍ Presenting Author: Jintao Cheng ‍ ClinicalTrials.gov number: NCT02719782 ‍ The full abstracts are attached in this release and are also published online on 8 a.m. EST on Monday, Nov. 9, 2020 in Journal for ImmunoTherapy of Cancer (JITC). ‍ Click here for: Online publication in JITC for Abstract 272 Click here for: Online publication in JITC for Abstract 273 ‍ About Lion TCR Lion TCR is a Singapore based clinical-stage biotechnology company, focused on the development of T cell receptor (TCR)-T cell therapy against life-threatening viral infections and viral-related cancers pertinent in Asia. ‍ About LioCyx-M LioCyx-M, including several well-established product derivatives, are autologous T cells modified to express HBV-specific TCR. These modified T cells have been shown to be able to lyse HBV-infected HCC cells upon target recognition in in vivo pre-clinical studies and in patients (Koh et al, Mol. Ther. Nucleic Acids, 2013; Kah et al, J. Clin. Invest., 2017; Tan et al, Gastroenterology 2019). ‍ ‍ ‍ Abstract ID: 272 Use of LioCyx-M, Autologous Hepatitis B Virus (HBV)-Specific T cell receptor (TCR) T-cells, in Advanced HBV-related Hepatocellular Carcinoma (HCC) Fu-Sheng Wang1*, Fanping Meng1, Jiehua Jin 1, Yuanyuan Li 1, Regina Wanju Wong2, Anthony Tanoto Tan3, Tingting Wang2, Antonio Bertoletti2,3,4* 1Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. 2Lion TCR Pte Ltd, Singapore 3Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 4Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore *co-corresponding author ‍ Background We have demonstrated the ability of Hepatitis-B-virus (HBV)-specific T cell receptor (TCR) bioengineered T cells to recognize and lyse Hepatocellular carcinoma (HCC) cells expressing HBV antigens derived from HBV-DNA integration in patients with liver transplant1. LioCyx-M is an immunotherapeutic product composing of autologous T cells transiently modified with in-vitro transcribed mRNA encoding HBV-specific TCR. The transient TCR expression makes LioCyx -M amenable to a dose escalating posology. ‍ Methods The primary endpoint of this Phase 1 trial is to assess the safety and tolerability of LioCyx-M in patients with advanced HBV-HCC without curative treatment options. Eligible patients were diagnosed with Barcelona clinic liver cancer stage B or C HCC (Child-Pugh < 7 points), receiving >1 year antiviral treatment prior to enrollment. These patients had matching HLA class I genotypes which present HBV encoded antigen. Peripheral blood was collected from each patient prior to each dose for LioCyx-M manufacturing. Patients received four escalating doses of 1×10E04 cells/kg, 1×10E05 cells/kg, 1×10E06 cells/kg, 5×10E06 cells/kg bodyweight (BW) in the first treatment cycle, each intravenously administered weekly. Patients underwent one-month safety assessment post the fourth infusion, according to Common Terminology NCI CTCAE Version 4.0.3. If there were no dose associated toxicities, patients were eligible to continue administration of LioCyx-M at dose of 5 x10E06 cells/kg BW weekly. Tumor response per RECIST 1.1 criteria and survival time were assessed. ‍ Results At data cutoff (30 April 2020), eight patients were enrolled, with a median age of 53 (range: 49 – 67). These patients received a median number of six (range: 4 – 12) infusions of LioCyx-M. One patient developed Grade 3 elevations in alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and bilirubin after receiving LioCyx-M at dose level of 1×10E05 cells/kg BW. Another patient had Grade 1 transient fever after receiving LioCyx-M at dose level 5×10E06 cells/kg BW in the 4th, 5th and 6th infusions. No treatment-related adverse events (trAEs) such as cytokine release syndrome or neurotoxicity were observed. No fatal trAEs were observed. The median time to progression was 1.9 months (range: 0.2 – 9.5 months). The median overall survival was 34 months (range: 3 – 38.2 months). ‍ Conclusion The encouraging clinical outcome and tolerable safety highlight the good benefit-risk profile of LioCyx-M. Therefore, further exploration of efficacy of LioCyx-M treatment for advanced HBV-HCC is warranted in a Phase 2 proof-of-concept clinical study. Funding: Lion TCR. Clinical trial information: NCT03899415 1. Tan AT et al. Use of Expression Profiles of HBV DNA Integrated into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy, Gastroenterology. 2019; 156(6):1862-1876.e9 doi:https://doi.org/10.1053/j.gastro.2019.01.251. ‍ Abstract ID: 273 Phase I Study of LioCyx-M, Autologous Hepatitis B Virus (HBV)-Specific T cell receptor (TCR) T-cells, in Recurrent HBV-Related Hepatocellular Carcinoma (HCC) Post-Liver Transplantation Wenjie Chen1, Jintao Cheng1, Xiaofang Zheng1, Fan Yang1, Xiaofang Zheng1, Royce Fam2, Sarene Koh2,3, Lu-En Wai2,3, Tingting Wang2, Antonio Bertoletti2,3,4*, Qi Zhang1* 1Biotherapy Center, Third Affiliated Hospital, Sun Yat-Sen University 2Lion TCR Pte Ltd, Singapore 3Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore 4Emerging Infectious Diseases, Duke-NUS Medical School, Singapore *co-corresponding author ‍ Background LioCyx-M is an immunotherapeutic product based on autologous T cells transiently modified with in vitro transcribed mRNA encoding HBV-specific T-cell receptors (TCR). We have previously shown, in a compassionate setting, the ability of LioCyx-M cells to recognize and lyse hepatocellular carcinoma (HCC) expressing HBV antigens derived from HBV-DNA integration in patients with HCC recurrence post-liver transplant1. Here, we report our Phase I study aimed to determine the feasibility, safety and preliminary efficacy of LioCyx-M in recurrent HBV-related HCC post-liver transplantation. ‍ Methods Eligible patients with HBsAg-positive recurrent HCC as well as HLA-matched to selected TCRs were enrolled in this study. All patients underwent leukapheresis prior to treatment and peripheral blood mononuclear cells (PBMC) were collected for LioCyx-M manufacturing. During the first treatment cycle, patients received four escalating doses of 1×10E04 cells/kg, 1×10E05 cells/kg, 1×10E06 cells/kg, 5×10E06 cells/kg bodyweight (BW) intravenously every seven days. Adverse events were evaluated by Common Terminology Criteria for Adverse Events Version 4.0. In the second treatment cycle, one infusion of LioCyx-M at dose of 1-5 x10E06 cells/kg BW was intravenously administrated every seven days for four weeks. The anti-tumour efficacy of LioCyx-M was evaluated per RECIST 1.1 criteria and survival was followed-up during the study. ‍ Results Six patients were enrolled, with a median age of 35.5 (range: 28 – 47). These patients received a median number of 6.5 doses of LioCyx-M therapy (range: 4 – 12). Only fever was observed as treatment-related AEs. Grade 1 fever was observed at dose levels of 1 x 10E04 cells/kg BW (n=1) and 1-5 x 10E06 cells/kg BW (n=3) respectively. No cytokine release syndrome- and neurotoxicity-like AEs were observed. Out of four patients evaluable for tumor response, the median of time to progression was at 1.3 months (range: 1.2 – 1.6 months). The median overall survival was 14 months (range: 4 – 22 months). At data cutoff (30 April 2020), one patient was still alive and five had passed on. ‍ Conclusion Our data showed that multiple infusions of LioCyx-M are well tolerated at all dose levels administrated in recurrent HCC post liver transplantation, with no adverse effect to the transplanted liver. This calls for further assessment in a Phase 2 study. Funding: Lion TCR. Clinical trial information: NCT02719782 1. Tan AT et al. Use of Expression Profiles of HBV DNA Integrated into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy, Gastroenterology. 2019; 156(6):1862-1876.e9 doi:https://doi.org/10.1053/j.gastro.2019.01.251. ‍

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