KZR-540 / Enodia Therapeutics, Aurinia Pharmaceuticals - LARVOL DELTA

Fledgling French biotech pens $128M deal for Kezar's preclinical protein degrader program (FierceBiotech) - "Kezar’s program is a good fit for Paris-based Enodia, which has a platform also focused on Sec61. Specifically, Enodia has been exploring how modulating the Sec61 complex could prevent cells from producing disease-relevant proteins in order to develop a pipeline of its own small-molecule inhibitors."

Licensing / partnership • Oncology • Solid Tumor

Quantitative proteomic profiling of KZR-540, a novel small molecule oral Sec61 inhibitor that selectively inhibits PD-1 expression (SITC 2023) - P1 | "1 Here we utilized LC/MS-based quantitative proteomic profiling to study the unique selectivity of KZR-540 in contrast to the promiscuous Sec61 inhibitor KZR-261 and its analog KZR-834. KZR-261 is currently being evaluated in a phase-1 clinical trial in solid tumors (NCT05047536). Follow-up in vivo studies will examine the differential impact of KZR-540 and KZR-261/834 on the tumor-draining lymph nodes (TDLNs) and plasma proteomes of human-PD-1 knock-in mice bearing human-PD-L1 MC38 tumors."

IO biomarker • Oncology • Solid Tumor • PD-L1 • SEC61G

KZR-540 is a novel oral small molecule inhibitor of Sec61 cotranslational translocation that potently and selectively blocks PD-1 expression (SITC 2022) - P1 | "Targeting Sec61 with small molecule inhibitors such as KZR-261, currently in a clinical trial for solid tumors ( NCT05047536 ), has anti-tumor effects through inhibiting the expression of multiple therapeutic targets, including PD-1, in preclinical models. Future studies will examine whether there is an enhanced anti-tumor response in a tumor model. Ethics Approval Animal studies were approved by the Institutional Animal Use and Care Committee."

IO biomarker • Melanoma • Oncology • Solid Tumor • IFNG • SEC61G

Kezar Life Sciences Reports Third Quarter 2022 Financial Results and Provides Business Update (Businesswire) - "KZR-540 – Kezar will introduce promising preclinical data on KZR-540, an oral small molecule inhibitor that selectively blocks PD-1 expression via inhibition of the Sec61 translocon, on November 11, 2022 at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting in Boston, MA. KZR-540 illustrates that the Sec61 translocon can be selectively inhibited for specific anti-tumor effects and validates Sec61 inhibition as a platform for additional new chemical entities."

Preclinical • Oncology • Solid Tumor