NovaRock Biotherapeutics Announces Two E-Posters to be Presented at the American Association for Cancer Research (AACR) Annual Meeting 2021
Ewing, NJ, March 30, 2021 – NovaRock Biotherapeutics Ltd, a clinical-stage biotechnology company focusing on the development of innovative antibody therapies for cancer and autoimmune diseases, will present two posters at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2021. One poster highlights the novel mechanism of action of an IND-enabling stage TNFR2 antibody, NBL-020. The second poster discusses a panel of Nectin-4 antibodies with differentiating functions for antitumor therapies. The AACR Annual Meeting will take place in a virtual format on April 10-15 and May 17-21, 2021.
Details on the E-posters and corresponding abstracts are shown below
E-Poster #: 1869
Title: Novel TNFR2 antibodies to overcome T cell exhaustion and suppressive tumor microenvironment
Authors: Chi Shing Sum, Makenzie Danton, Qihui Hu, Alla Pristsker, Ray Lin, Raymond Yu, Kevin Chen, Fangqiang Tang, Thomas Pohl, Samantha Wallner, Ahmed Hassan, Huarui Lu, Haichun Huang, Yi Pei, Zhong Liu, Han Li, Ming Lei
Session Category: Therapeutic Antibodies
Date: Saturday, April 10, 2021
TNFR2 is highly expressed on the surface of activated T effector cells, T regulatory cells and myeloid cells, and it plays essential roles in modulating the tumor microenvironment. In most cancer types, higher TNFR2 expression correlates with increased immune cell infiltration. Furthermore, the TNFR2 gene is differentially expressed in various cancer types, including breast, lung, renal, liver and skin cancers. In cancers such as head and neck cancer and cutaneous melanoma, high TNFR2 expression correlates with better overall survival. The therapeutic potential of antibodies targeting TNFR2 has been demonstrated by agonist antibodies for the T effector cells, and antibodies that antagonize or deplete the T regulatory cells and suppressive myeloid cells. We discovered novel TNFR2 antibodies that demonstrate unique mechanisms to overcome T cell exhaustion and the suppressive tumor microenvironment for more effective immunotherapy. In vitro studies have shown that our antibodies block TNFα ligand binding and potently inhibit TNFR2 signaling in the monocytic cells. Moreover, these antibodies enhance CD8 T cell function to overcome the suppressive effect from the T regulatory cells and can invigorate exhausted CD8 T cells in an FcγR-dependent manner. In a humanized mouse model, our antibodies demonstrate strong anti-tumor efficacy as single agents or in combination with a PD-L1 inhibitor. Therefore, these antibodies offer potential advantages when the tumor microenvironment is enriched in the exhausted T cells, the suppressive myeloid cells, or the regulatory T cells, as found in anti-PD-1/PD-L1 resistant and PD-1 refractory patients. In conclusion, the data obtained indicate that our TNFR2 antibodies are a novel and promising class of drug candidates for cancer immunotherapeutics. Our lead antibody is currently at the IND-enabling stage with the target of entering clinical studies in early 2022.
E-Poster #: 920
Title: Harnessing multiple mechanisms of action to target Nectin-4 as anti-tumor therapeutics
Authors: Yi Pei, Thomas Pohl, Ahmed Hassan, Anna Przybyla, Raymond Yu, Huarui Lu, Fangqiang Tang, Kevin Chen, Wei Jin, Krizia Dominguez, Samantha Wallner, Jeffrey Wong, Tina Van Voorhies, Meera Mysore, Ray Lin, Haichun Huang, Ming Lei, Zhong Liu, Han Li
Session Category: Antibody Technologies
Date: Saturday, April 10, 2021
Nectin-4 belongs to an immunoglobulin superfamily (IgSF) of cell adhesion molecules that mediate cell-cell adhesion through homophilic or heterophilic interactions. In addition to the role in cell-cell adhesion, the Nectin family plays important role in regulating a diverse range of physiologic cellular activities, in viral entry, and in immune modulation. Nectin-4 has been reported to be upregulated in various epithelial cell cancers, such as breast cancer, lung cancer, and bladder cancer. The therapeutic value of Nectin-4 as an anti-tumor target has been demonstrated by a recently approved antibody-drug conjugate (ADC), Enfortumab vedotin. To fully exploit the potential of Nectin-4 as an anti-tumor target, we discovered a panel of monoclonal antibodies. These antibodies not only bind specifically to human Nectin-4 with high affinity, but also show differentiating characteristics including cell internalization, blockage of interaction with Nectin-1, blockage of interaction with TIGIT, and ADC-independent cytotoxicity. Our results suggest that in addition to ADC, other mechanisms targeting Nectin-4 can be utilized for therapeutics, such as immunomodulation and antibody- or immune cell-mediated tumor cell killing.