New ADC homes in on Trop-2 glycoprotein to target cancer cells
Immunomedics has developed an antibody drug conjugate (ADC) called sacituzumab govitecan, which directly delivers chemotherapy SN-38 to triple negative breast cancer (TNBC) tumours, which highly express the glycoprotein Trop-2 and represents an unmet need within a highly treated cancer type.
GlobalData’s pharmaceutical technology writer Allie Nawrat says: “The New Jersey-based firm has developed a novel ADC platform centred around its specialised hydrolysable linker, which delivers potent chemotherapy metabolites directly to cancer tumour sites and their microenvironments.
“Immunomedics’ lead candidate, sacituzumab govitecan, is currently being developed for heavily treated TNBC patients. The company has received US Food and Drug Administration breakthrough designation and recently re-submitted its biologics license application for the drug in this indication.”
Immunomedics chief commercial officer Brendan Delaney explains: “We decided to focus on TNBC because of the level of unmet medical need that exists here. Our ADC technology really strongly aligns with the biology of TNBC. It targets Trop-2, which happens to be highly expressed on the surface of TNBC cells. It’s a highly attractive target and it’s able to internalise an antibody drug conjugate pretty quickly.
“Because Trop-2 is overexpressed, sacituzumab govitecan is able to deliver SN-38, which is the active metabolite of chemotherapy irinotecan, directly to the tumour.
“Our linker allows the cytotoxic payload to stay bound to the monoclonal antibody – in this case Trop-2 – as it finds its way to Trop-2 expressing tumours. Once the ADC is docked at the binding site on the tumour cell, SN-38 is taken into the cell, where the payload is released and has its cell kill effect, but because of the hydrolysable linker, some of that payload comes off on the outside of the cell, [creating] a pretty substantial bystander effect in the tumour micro-environment.”
“In the future, we have hopes to explore every tumour type where Trop-2 has any expression. This includes non-small cell lung cancer where we are enrolling a clinical trial currently – the Tropics-03 trial. It’s a basket trial looking at different expression levels of Trop-2 in various patients.”
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