Next Generation Bispecific Antibody Drug Conjugates Improves Targeting of Solid Tumors with Dr. Mayank Gandhi NEOK Bio

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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