Until now, the best way to get cancer drugs directly to the tumor has been by using an antibody-drug conjugate (ADC). ADC's are made up of a tumor-targeting agent and payload, connected by a linker, which is cleaved through internalization by the cell.
Patient benefit from targeted payload delivery by ADCs has been limited by off-target toxicities. The fundamental problem is that the payload follows the usual elimination route of the targeting modality , because they are attached. This leads to significant normal tissue exposure and toxicity.
CAPAC is made up of two separate components: a clickable binder and a clickable payload.
These are reunited at the tumor via an in-vivo click chemistry reaction, leading to active payload at the tumor and greater benefit for patients.
First, we infuse the clickable binder that binds receptors at the tumor. Anything that doesn’t bind to the tumor is rapidly eliminated without toxicity.
Then, we infuse the clickable payload. The components reunite at the tumor via an in-vivo click chemistry reaction. Any inert payload that doesn’t click with the binder is rapidly cleared, limiting normal tissue exposure.
CAPAC is designed to widen the therapeutic window of ADCs and targeted radiopharmaceutical approaches, by maximizing activity and lowering toxicity. Additional benefits include opening up new targets and payload cycling.
Click chemistry enables activation that is not dependent on the biology of the cell.
We can activate payloads at receptors that do not internalize, expanding the number of targets that can be drugged.
It is possible to localize an antigen-targeting activator at the tumor and use it to activate any one of our protodrugs.
This means you can cycle through different payloads over the patient’s journey, and administer combinations of different payloads with complementary mechanisms of action during a treatment cycle.
We have clinically validated the specificity and safety of CAPAC in patients with advanced soft tissue sarcoma and demonstrated proof of concept with one of our assets, SQ3370. This activates a doxorubicin protodrug at the tumor with an intratumorally injected biopolymer.
In our phase 1 study, SQ3370 was well-tolerated with no dose-limiting toxicities, even in patients receiving >15x the conventional dose-equivalent of doxorubicin per cycle.
Importantly, we showed that our technology works inside human patients: the protodrug was inert until activated, and there was rapid release of active doxorubicin at all doses levels with increasing exposure, consistent with selective activation.
