On April 4, 2023 iBio, Inc. (NYSEA:IBIO) ("iBio" or the "Company"), an AI-driven innovator of precision antibody immunotherapies, reported that a presentation given today by its VP & Head of Machine Learning & Platform Technologies, Matt Greving, Ph.D., during Carterra’s "Unlocking High-Throughput Biology and Drug Discovery" symposium in San Diego, CA, revealed the discovery of a panel of CD3 T-cell binding antibodies, representing an important first step for the Company into bispecific immuno-oncology therapies (Press release, iBioPharma, APR 4, 2023, View Source [SID1234629798]).
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T-cell-redirecting bispecific antibodies are a new class of therapeutic antibodies designed to simultaneously bind to T cells via CD3 and to tumor cells via tumor-specific antigens ("TSA") or tumor-associated antigens ("TAA"), inducing T-cell-mediated killing of tumor cells.1
Early studies of CD3-based T-cell engagers showed promising clinical efficacy, but were hampered by severe dose-limiting toxicities, due in large part to anti-CD3 binders with high potency.2 Another hurdle in the development of CD3-based T-cell engagers has been the often-observed lack of cross-reactivity with non-human primates. This has made it difficult to assess the potential of CD3 antibody therapies in humans, potentially delaying their clinical development.3
With the aim of overcoming these challenges, iBio employed its patented epitope steering technology to guide antibodies towards specific CD3 epitopes. The Company’s AI-based antibody optimizer, combined with its mammalian display technology broadened the range of CD3 affinities, identified antibodies with cross-reactivity to non-human primates and increased the humanness of the antibody sequences.
Dr. Greving explained, "Our leading epitope-steering and mammalian-display integration enabled efficient discovery of a diverse panel of CD3 antibodies. With our technology stack, we were able to overcome key challenges associated with CD3 antibody discovery, including identifying T-cell binding antibodies with non-human primate cross-reactivity."
In response to the Company’s latest AI platform success, iBio’s Interim Chief Executive Officer and Chief Scientific Officer, Martin Brenner, DVM, Ph.D., affirmed that, "By combining two of our platform technologies, we were successful in generating anti-CD3 antibodies with highly desirable characteristics. By adding CD3-based T-cell engaging antibodies as a tumor cell killing modality, we now have a valuable option to tune efficacy and safety of our future and existing pipeline programs."
References
1. L. Haber, K. Olson, M. P. Kelly, A. Crawford, D. J. DiLillo, R. Tavaré, E. Ullman, S. Mao, L. Canova, O. Sineshchekova, J. Finney, A. Pawashe, S. Patel, R. McKay, S. Rizvi, E. Damko, D. Chiu, K. Vazzana, P. Ram, K. Mohrs, A. D’Orvilliers, J. Xiao, S. Makonnen, C. Hickey, C. Arnold, J. Giurleo, Y. P. Chen, C. Thwaites, D. Dudgeon, K. Bray, A. Rafique, T. Huang, F. Delfino, A. Hermann, J. R. Kirshner, M. W. Retter, R. Babb, D. MacDonald, G. Chen, W. C. Olson, G. Thurston, S. Davis, J. C. Lin, E. Smith, Generation of T-cell-redirecting bispecific antibodies with differentiated profiles of cytokine release and biodistribution by CD3 affinity tuning. Sci Rep. 11, 14397 (2021).
2. O. Vafa, N. D. Trinklein, Perspective: Designing T-Cell Engagers With Better Therapeutic Windows. Frontiers in Oncology. 10 (2020) (available at https://www.frontiersin.org/articles/10.3389/fonc.2020.00446).
3. F. R. Brennan, J. Cavagnaro, K. McKeever, P. C. Ryan, M. M. Schutten, J. Vahle, G. F. Weinbauer, E. Marrer-Berger, L. E. Black, Safety testing of monoclonal antibodies in non-human primates: Case studies highlighting their impact on human risk assessment. mAbs. 10, 1–17 (2018).