ELU001 exhibits potent efficacy against established s.c.
In contrast, an anti-FRα ADC based ADC mirvetuximab soravtansine exhibits lower potency (>100 nM IC 50) against SK-OV-3 and HCC827 cells and 40 nM IC 50 against OVCAR-3 cells. ELU001 exhibits potency in the low single digit nanomolar to sub-nanomolar range against cancer cells that express 3+ (KB, IGROV-1) and 2+ (SK-OV-3, HCC827 and OVCAR-3) levels of FRα after a 6-hr exposure in a 7-day viability study. ELU001 is rapidly internalized into FRα expressing cells and is trafficked to the lysosome where the payload is released from the CDC. ELU001 is a CDC functionalized with ~20 molecules of the topoisomerase-1 inhibitor exatecan linked via a proteolytic cleavable linker as a payload and ~15 folic acids to provide targeting to FRα overexpressing cancers. The silica core is covalently coated with a layer of polyethylene glycol which is then functionalized with targeting moieties and payloads. CDCs are composed of a silica core, in which Cy5, a far red dye is covalently encapsulated. CDCs are capable of targeting tumors in the brain and pancreas that are difficult to access, while exhibiting limited exposure to normal tissues due their efficient renal elimination.
CDCs are novel ultra-small (6-7 nm) nanoparticle drug conjugates that have been demonstrated to be capable of faster tumor targeting and deeper tumor penetration than antibody drug conjugates in animal models.
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