Oncolytics Biotech Inc ONCY

RE:RE:RE:AstraZeneca's ADC disappoints - on severe adverse events

[Noteable]

The search for better target tumor antigens (Ags,) particularly for solid tumors, is ongoing, as well as an effort to develop better linkers and payloads for ADCs. Given the speed of progress in each of these areas, it is likely that new and active ADCs will continue to be developed and evaluated. However, “old” challenges may still threaten ADCs development, like patient selection and biomarker assessment. 

The ideal target antigen should prompt ADC internalization upon interaction with the ligand. Besides, research efforts are focusing on finding cell surface Ags that show high expression on cancer cells, while displaying low or no expression on healthy tissues.

Theoretically, such antigens would favor anti-cancer activity, while avoiding on-target off-tumor toxicities. Certainly, the complexity of ADC design and development goes far beyond seeking the ideal target. In fact, complex manufacturing issues related to linker stability, payload charge and membrane-permeability, as well as the overall interaction of the three core components are major issues to tackle. 

Future ADCs not only will be equipped with higher drug-to-antibody ratio (DARs) but might also benefit from the conjugation with compounds that go beyond chemotherapeutical payloads. In this case conjugate ADCs could be equipped with a chemotherapeutical, plus an immune-stimulant molecule payload, such as ONCY's oncolytic virus (pelareorep), which is able to induce targeted antitumoral immune responses, activate the innate and adpative immune system, remodel the TME, and synergize with immune checkpoint inhibitiors to effectively treat multiple cancers.

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