Formulated and/or co-formulated liposome compositions containing PD-1 antagonist prodrugs useful in the treatment of cancer and methods thereof

Inventors

Stover, David • Bharali, Dhruba • Hay, Bruce A • Safaie, Tahmineh

Assignees

Nammi Therapeutics Inc

Abstract

Formulated and/or co-formulated nanocarriers (e.g., LNPs and/or SLNPs) comprising PD-1 Prodrugs and methods of making the nanocarriers are disclosed herein. The PD-1 Prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit PD-1-L1/L2. The PD-1 Prodrugs can be formulated and/or co-formulated into a nanocarrier to provide a method of treating cancer, immunological disorders, and other disease by utilizing a targeted drug delivery vehicle.

Core Innovation

The invention provides PD-1 prodrug compositions that include a drug moiety comprising a PD-1 antagonist, a lipid moiety, and a linkage unit that conjugates the drug moiety with the lipid moiety. The PD-1 prodrugs are defined by specified chemical structures and include variants such as PD3 through PD7, with lipid moieties such as cholesterol, DPPG, DMPG, Lyso PC, (9-cis) PG, Soy Lyso PC, PG, C16 PEG2000 ceramide, and CHEMS.

A key aspect is the use of a linkage unit that is biologically cleavable or cleavable by esterases, so cleavage releases an active PD-1 inhibitor from the nanocarrier. The disclosure describes liposome forms and solid-lipid nanoparticle forms containing the PD-1 prodrug, including cholesterol-based and DPPG-based formulations conjugated with PD1 through PD7 via LU esters.

The disclosure further describes helper lipids and helper lipid components for incorporation into liposomes and solid-lipid nanoparticles, and co-formulation options with immune modulators and chemotherapeutics. These include toll receptor agonists, ICD-inducing chemotherapeutics, doxorubicin, IDO-1 inhibitors or prodrugs, TGFβ antagonists or prodrugs, and A2aR antagonists or prodrugs.

Claims Coverage

The independent claims cover three inventive features: a PD-1 prodrug composition, a nanocarrier that releases an active PD-1 inhibitor after LU cleavage, and a method of treating a subject diagnosed with cancer using such a nanocarrier. Across the claims, the core inventive subject matter is the conjugation architecture of a PD-1 antagonist drug moiety, a lipid moiety, and a linkage unit, together with LU-cleavage-mediated release in a nanocarrier context.

Overall, the claims cover PD-1 prodrug compositions defined by a PD-1 antagonist drug moiety conjugated to a lipid moiety via a linkage unit, nanocarriers that release an active PD-1 inhibitor after LU cleavage, and cancer-treatment use of such nanocarriers.

Stated Advantages

Documented Applications