Until now, the best way to get a cancer drug directly to the tumor has been by using an antibody-drug conjugate (ADC). An ADC is made up of a tumor-targeting agent and a payload, connected by a linker, which is cleaved through internalization by the cell.
CAPAC is made up of two separate components: an antigen-targeting activator and a protodrug, an inert version of an active cancer drug.
These are reunited at the tumor using click chemistry.
First, we infuse the antigen-targeting activator that binds receptors at the tumor. Anything that doesn’t bind to the tumor is rapidly cleared.
Then, we infuse the protodrug. The protodrug is inert until it finds the activator at the tumor, releasing active drug. Any inert payload is rapidly cleared.
The unique features of CAPAC create unprecedented flexibility that can lead to greater activity and lower toxicities than have previously been possible.
The amount of payload delivered is not tied to the amount of antigen-targeting agent dosed, as is the case for ADCs.
This allows you to optimize the ratio of antigen-targeting to payload throughout development (including in the clinic) to achieve the highest activity and the lowest toxicity.
Our protodrugs are inert and stable in plasma until they click with antigen-targeting activators. Activators that do not bind receptors and protodrugs that are not activated are rapidly cleared.
This limits prolonged exposure to the payload and minimizes off-target toxicities.
Click chemistry enables activation that is not dependent on the biology of the cell,
e.g. enzymatic cleavage of a linker.
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.
We are rapidly advancing a number of antigen-targeted
combinations towards the clinic.