KZR News & Events

Kezar Life Sciences announced that the FDA Division of Hepatology and Nutrition has granted Kezar a Type C meeting for the first quarter to discuss the development of zetomipzomib, a novel, selective inhibitor of the immunoproteasome, in patients with autoimmune hepatitis. The Type C meeting will involve review of a potential global, randomized Phase 2b clinical study of zetomipzomib in patients with relapsed and refractory AIH. As part of the briefing package submitted to the FDA, Kezar submitted pharmacokinetic and hepatic safety data analyses from previously conducted clinical trials to support a proposal for parallel AIH and hepatic impairment studies. Kezar also submitted additional safety data and an updated risk-mitigation plan aimed to modify the previous requirement issued from the FDA to require 48-hour in-unit patient monitoring in future AIH studies.

Kazia Therapeutics announced new data from two presentations at the 2025 San Antonio Breast Cancer Symposium, or SABCS, providing compelling mechanistic and early clinical evidence supporting the activity of paxalisib, the Company's brain-penetrant dual PI3K/mTOR inhibitor, across both HER2-positive metastatic breast cancer and triple-negative breast cancer, or TNBC. The results, originating from advanced liquid biopsy profiling, immune phenotyping, and early clinical readouts, highlight paxalisib's potential to disrupt highly aggressive circulating tumor cell, or CTC, clusters, reverse epigenetically-driven resistance pathways, and reinvigorate exhausted T- and B-cell populations, thereby enhancing responsiveness to immunotherapy. In HER2-positive metastatic breast cancer, a population in which nearly all patients eventually relapse despite HER2-directed therapies, investigators observed that even patients who were radiographically responding continued to harbor substantial burdens of therapy-resistant CTC clusters-a key driver of metastatic spread. Poster Presentation: PS2-10-02 : Liquid Biopsy Tracking of PI3K-mTOR Residual Disease Signatures in Metastatic HER2+ Breast Cancer. Key findings include: Paxalisib reduced single CTCs by 42% and CTC clusters by 78% ex vivo, including large clusters, which are strongly associated with metastatic progression, CTC clusters expressed a highly aggressive mesenchymal phenotype marked by Vimentin/Snail/NRF2, which paxalisib significantly disrupted. Early longitudinal biomarker data from the first patient treated in the PaxPlus-ABC Phase 1b study indicate that paxalisib has had measurable biological activity after only a single cycle. Poster Presentation: PS5-08-04: A phase 1b, multi-centre, open-label, randomized study to evaluate the safety, tolerability, and clinical activity of combining paxalisib with olaparib or pembrolizumab/chemotherapy in patients with advanced breast cancer. Highlights from first patient include: Marked reduction in CTC clusters following the first cycle of paxalisib; Epigenetic reprogramming of CTCs toward less aggressive phenotypes, confirmed through digital pathology and Nanostring profiling. CT imaging has demonstrated overall primary tumor volume reduction from baseline 14mm x 11mm to 12mm x 3 mm. Notably, a temporary interruption of paxalisib resulted in a rapid resurgence of CTC clusters. Resumption of paxalisib after a short 3-week pause restored suppression of CTC clusters, indicating that pembrolizumab alone could not control these metastatic drivers and highlighting paxalisib's unique mechanistic role.

In October, Kezar announced that it has been unable to align with the Food and Drug Administration (FDA) on a potential registrational clinical trial of zetomipzomib, a novel, selective inhibitor of the immunoproteasome, in patients with relapsed and refractory autoimmune hepatitis (AIH). Kezar initiated a process to explore a full range of strategic alternatives focused on maximizing shareholder value. Kezar has retained TD Cowen to support it with the strategic review process. In connection with the evaluation of strategic alternatives, Kezar is in the process of implementing cost-containment and cash conservation measures.