In this study, we used ONX 0914, an LMP7/LMP2-selective inhibitor of the IP, to study the effect of IP inhibition on B cells and antibody production...Furthermore, IP inhibition neither impaired vaccine-induced antibody responses, nor affected different B cell populations in two different vaccination models. These findings suggest that IP inhibition does not compromise vaccination efficacy and anti-viral humoral immunity, supporting the potential of IP-targeted therapies for autoimmune diseases.

P2, N=24, Completed, Kezar Life Sciences, Inc. | Trial completion date: Aug 2025 --> Apr 2025 | Active, not recruiting --> Completed

The safety profile of FAP-IL2v in combination with pembrolizumab was manageable and consistent with the known safety profile. However, further exploration of FAP-IL2v and pembrolizumab was precluded in melanoma patients with prior CPI due to the lack of clinical activity.

P2, N=84, Terminated, Kezar Life Sciences, Inc. | N=279 --> 84 | Trial completion date: Jul 2026 --> Nov 2024 | Suspended --> Terminated | Trial primary completion date: May 2026 --> Nov 2024; Sponsor Decision.

The safety profile of FAP-IL2v in combination with cetuximab was acceptable and pharmacodynamic markers support the proposed mode-of-action of this combination, but the overall low antitumor activity does not warrant further clinical exploration in HNSCC. [Part C of Study BP29842 (NCT02627274).].

FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC.

P2, N=279, Suspended, Kezar Life Sciences, Inc. | Recruiting --> Suspended

P2, N=24, Active, not recruiting, Kezar Life Sciences, Inc. | Trial completion date: Mar 2025 --> Aug 2025 | Trial primary completion date: Sep 2024 --> Feb 2025

P2, N=24, Active, not recruiting, Kezar Life Sciences, Inc. | Recruiting --> Active, not recruiting

These results suggest that ONX-0914 prevents the internal destructive cleavage of WT1235 by IP, thereby promoting the specific presentation of the WT1 epitope by MESO-4. In conclusion, selective IP inhibitors might offer a means to modulate cancer cell immunogenicity by directing the presentation of particular tumor epitopes.

P2; FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.

Administration of YU102 in the DSS-treated colitis model mice caused suppression of the NLRP3 protein levels and accompanied inflammatory cytokine release in the intestinal epithelium. Taken together, we demonstrated that inhibiting IP under inflammatory conditions induces E3 ligase TRIM31-mediated NLRP3 degradation, leading to attenuation of the NLRP3 inflammatory response that triggers disruption of intestinal barrier.