Dr. Mayank Gandhi, CEO of NEOK Bio, discusses the company's work on bispecific antibody drug conjugates and the limitations of conventional ADCs, which target a single antigen. Using a bispecific antibody to target two unique antigens on a tumor can address the shortcomings of earlier approaches by improving delivery of the toxic payload, overcoming tumor heterogeneity, and reducing off-target toxicity. NEOK has drugs in development for prostate cancer, and lung, head, neck, and gastrointestinal tumors. The trend for ADCs is toward multi-specific and multi-payload drugs, though Mayank warns it is not a simple task to go from one to many in designing these drug conjugates.

Mayank explains, "There have been a lot of advancements in the last couple of decades, and especially the last few years, in various modalities in the treatment of hematological cancers, as well as to a certain degree in solid tumors. However, for many, many solid tumors, there's still a high unmet need given the still significant outcome, poor outcomes that patients experience, particularly with patients having metastatic disease across a variety of solid tumors. Now, if you look at specific modality like ADC or antibody drug conjugates, which is where NEOK Bio is, there's been a renaissance, if you will, with this modality in the last five to six years, particularly after the approval of a drug called Enhertu, which targets HER2 mutation. Now, many ADCs have been approved with different payloads. And so definitely that's made a dent in a variety of tumors, particularly in hematological cancers and select solid tumors as well."

"Conventional ADCs thus far target one antigen or one target on a tumor. So it's an antibody-based approach. The antibody is typically pursuing one specific antigen that's usually an antigen that's expressed on tumors selectively versus normal tissue or normal cells. And then you have a linker and a payload, usually a toxic payload that's conjugated via a linker to the antibody. So that's an antibody drug conjugate construct."

"Thus far, all the ADCs approved have been targeting only one antigen with a couple of different payloads. And so our bispecific approach is targeting two different antigens. If we use a bispecific antibody that targets two unique antigens on the tumor, we have more than one place that a potential antibody can bind and deliver the toxic payload. And then we have made some very significant improvements or changes in the antibody itself."

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