搜索
ss
ss
新闻动态
News Center
15
2022-04

Biotheus Shares Latest Research & Development Updates on Multiple Programs During AACR, 2022 and SITC, 2021

Time of issue: : 2022-04--15
Biotheus Inc., participated at the 113th Annual Meeting of the American Association of Cancer Research, 2022, sharing six posters including four bispecifics: PM1022 (PD-L1 x TIGIT), PM1009 (TIGIT x PVRIG), PM4008 (CEACAM5&6 x CD3) and PM1032 (CLDN18.2 x 4-1BB); and two other monoclonal antibodies: PM1038 (CD39) and PM1015 (CD73). Biotheus also previously presented at the Annual SITC meeting in 2021 on programs PM1003 (PD-L1/4-1BB) and their novel CAB-T cell therapy platform. Details of these programs are below.   AACR2022 PM1022 (PD-L1 x TIGIT): https://www.abstractsonline.com/pp8/#!/10517/presentation/17744 PM1009 (TIGIT x PVRIG): https://www.abstractsonline.com/pp8/#!/10517/presentation/17746 PM4008 (CEACAM5&6 x CD3): https://www.abstractsonline.com/pp8/#!/10517/presentation/17774 PM1032 (CLDN18.2 x 4-1BB): https://www.abstractsonline.com/pp8/#!/10517/presentation/17775 PM1015 (CD73): https://www.abstractsonline.com/pp8/#!/10517/presentation/18034 PM1038 (CD39): https://www.abstractsonline.com/pp8/#!/10517/presentation/17747 SITC2021 PM1003: http://dx.doi.org/10.1136/jitc-2021-SITC2021.895 CAB-T platform: http://dx.doi.org/10.1136/jitc-2021-SITC2021.206   BD enquiries and supplemental material requests Please contact du.yl@biotheus.com or tsun.a@biotheus.com for partnering opportunities and high-resolution PDFs of these posters.   About Biotheus Founded in 2018, Biotheus focuses on the research and development of next generation multispecific antibodies for oncology and inflammatory diseases. As a clinical-stage biotech company, Biotheus currently has two programs at phase II clinical development and a further six programs at phase I. For more information, please visit www.biotheus.com.   PM1022 (PD-L1 x TIGIT): AACR2022 Abstract #5525 BACKGROUND: TIGIT (T-cell immunoglobulin and ITIM domain), which is primarily expressed on activated and 'exhausted' T and NK cells, is one of the most promising 'next generation' immune checkpoint target. Engagement of TIGIT to its ligands (i.e., PVR and PVRL2) leads to inhibitory signaling in T cells and promotes the functional exhaustion of tumor-infiltrating T lymphocytes. Anti-TIGIT monoclonal antibodies have shown clinical benefit when combined with anti-PD-L1 agents in NSCLC. Here, we describe our novel anti-PD-L1 × TIGIT bispecific antibody (PD-L1 × TIGIT biAb) that blocks both the PD-L1/PD-1 and TIGIT/PVR/PVRL2 pathways and has the potential to exhibit equal clinical benefit compared to current combination therapies. RESULTS: The PD-L1 × TIGIT biAb binds with high affinity to the extracellular domain of human TIGIT and PD-L1 and can bind to TIGIT and PD-L1 simultaneously. In a competition assay, the PD-L1 × TIGIT biAb efficiently blocked the interaction between TIGIT and PVR/PVRRL2, and likewise PD-L1 to PD-1. The PD-L1 × TIGIT biAb induced higher luciferase signals than the anti-TIGIT or anti-PD-L1 mAbs alone in a luciferase reporter-based cell system and enhanced IFN-γ production in an MLR assay. In vivo, the PD-L1 × TIGIT biAb demonstrates similar anti-tumor efficacy to the combination of anti-TIGIT and anti-PD-L1 mAbs, which is stronger than the single-agents alone. We have also completed GLP-toxicity studies that have shown excellent safety. CONCLUSIONS: We have discovered a novel PD-L1 × TIGIT biAb, which induces strong immune responses in vitro and in vivo, supporting its clinical development for the treatment of human cancers. Clinical trials shall be initiating in early 2022. PM1009 (TIGIT x PVRIG): AACR2022 Abstract #5527 BACKGROUND: TIGIT (T-cell immunoglobulin and ITIM domain), which is primarily expressed on activated and 'exhausted' T and NK cells, is one of the promising 'next generation' immune checkpoint molecules. Engagement of TIGIT to its ligands (i.e., PVR and PVRL2) leads to inhibitory signaling in T cells, promoting functional exhaustion of tumor-infiltrating T lymphocytes. Anti-TIGIT monoclonal antibodies have shown clinical benefit when combined with anti-PD-L1 agents in NSCLC. However, the single-agent efficacy of anti-TIGIT therapies have been limited. PVRIG (PVR-related immunoglobulin domain containing), which is another coinhibitory receptor of the DNAM/TIGIT/CD96 nectin family, binds with high affinity to PVRL2 and suppresses T-cell function, and shows nonredundant inhibitory effects alongside the TIGIT/PVR/PVRL2 axis. Here, we report a fully-human anti-TIGIT × PVRIG bispecific antibody (anti-TIGIT × PVRIG biAb), which blocks both the PVRIG/PVRL2 and TIGIT/PVR/PVRL2 pathways, that maintains the efficacy of the combination of the two mono-agents. The anti-TIGIT × PVRIG biAb is also highly efficacious when combined with PD1/PD-L1 inhibitors in mouse tumor models. RESULTS: The anti-TIGIT × PVRIG biAb binds with high affinity to the extracellular domain of human TIGIT/PVRIG and can bind to TIGIT and PVRIG simultaneously. In a competition assay, the anti-TIGIT × PVRIG biAb efficiently blocked the interaction betwee
查看详情 查看详情
Previous page
1

Copyright © 2022 Biotheus Inc. All Rights Reserved  粤ICP备2021122492号