Factor XIIa

We recently introduced an oral Factor XIIa inhibitor program which we believe represents the next generation of therapies that may further improve the treatment of HAE for patients.

Factor XIIa is an enzyme that plays a key role in HAE as the most upstream mechanism in the biochemical pathway that initiates HAE attacks. For this reason, we believe that inhibition of Factor XIIa will block the underlying causes of HAE attacks, including the uncontrolled generation of both plasma kallikrein and bradykinin, which cause swelling and pain. Clinical studies of Factor XIIa antibodies have demonstrated efficacy in preventing HAE attacks, and there are no known safety implications of long-term inhibition of this enzyme.

While injectable Factor XIIa antibody therapies are currently in clinical studies for HAE prophylaxis and other indications, developing oral Factor XIIa inhibitors has been a significant scientific challenge, and our newly announced program represents a major breakthrough in this area. Our internal research team has discovered multiple series of low nanomolar potency Factor XIIa inhibitors with high degrees of selectivity and oral bioavailability. We are pursuing comprehensive IP protection for this advanced medicinal chemistry program that is currently in lead optimization. We anticipate starting IND-enabling studies in 2021.