pdl1

The Candidate

Our PD-L1xCD28 costimulatory bispecific 

Our bispecific molecule is designed to bind to immunosuppressive PD-L1 on tumor cells as well as to the CD28 costimulatory receptor on T cells.

Improving upon prior approaches
While CD28 agonism has shown some clinical promise, the efficacy seen with this approach has been limited due to dose-limiting toxicities that result from systemic activation of CD28. Our PD-L1/CD28 costimulatory bispecific is designed to conditionally agonize CD28 only in the presence of PD-L1, which is often overexpressed by tumors to avoid T cell mediated killing. In addition, engagement of PD-L1 by our costimulatory bispecific is designed to block PD-1 binding and provide checkpoint inhibition. We believe this unique combination of potential mechanisms of action could enhance anti-tumor responses and limit the systemic toxicity of CD28 agonism.

Preclinical Data

PD-L1xCD28-01

Low TCE single-agent activity is improved in combination with PDL1 x CD28

PD-L1xCD28-02

Inactive PD-L1 x CD28 single-agent activity is improved in combination with TCE

PD-L1xCD28-03
IV Bolus NHP PK

Dosing of our PD-L1 x CD28 costimulatory bispecific in NHPs had minimal effects on inflammatory cytokine levels, and several of these were below limits of quantification

PD-L1xCD28-04
Bispecific Cytokine Release in NHPs