Kezar Life Sciences Highlights Therapeutic Potential of Protein Secretion Inhibitors at the 61st American Society of Hematology Annual Meeting
Two oral presentations and one poster presentation focus on novel inhibitors of the Sec61 translocon, which demonstrate high degrees of potency against a large number of therapeutically relevant oncology and immuno-oncology targets that are Sec61 client proteins, translating into broad anti-tumor activity.
“Our R&D efforts targeting the protein secretion pathway have progressed significantly, and we are thrilled to highlight this extremely compelling new therapeutic approach in our oral presentations and poster,” said
Presentation highlights from Kezar’s R&D efforts on the Sec61 translocon include:
- KZR-261 can induce simultaneous inhibition of multiple, clinically relevant proteins including oncogenic drivers, angiogenic factors, and immune checkpoints
- Kezar’s Sec61 inhibitors are efficacious in vitro and in vivo against multiple hematologic tumor types without inducing cell death in normal cells or significant toxicity in animals
- Genomic and proteomic analysis reveal a proteotoxic stress response as a potential biomarker for sensitivity across multiple tumor types
- Profound synergy with proteasome inhibitors in multiple myeloma models
“The Sec61 translocon is a highly novel target, and I’m encouraged by KZR-261’s anti-tumor activity in preclinical models of both solid and hematologic malignancies,” said
Presentation details are below:
- Abstract Number: 408
Title: Blocking Protein Secretion with Novel Small Molecule Inhibitors of Sec61 Represents a Potential Treatment Strategy Against Hematologic Malignancies
Sunday, December 8, 2019
Oral Session: 802. Chemical Biology and Experimental Therapeutics: Novel Compounds and Mechanisms of Action
- Abstract Number: 805
Title: Protein Translocation Inhibitors Overcome Cytokine-Induced Glucocorticoid Resistance in T-Cell Acute Lymphoblastic Leukemia
Monday, December 9, 2019
Oral Session: 605. Molecular Pharmacology, Drug Resistance—Lymphoid and Other
- Abstract Number: 2076
Title: Proteomic Profiling and Mechanistic Investigating of a Novel Anti-Cancer Small Molecule Inhibitor of Sec61
Saturday, December 7, 2019
5:30 PM - 7:30 PM
Poster Session: 802. Chemical Biology and Experimental Therapeutics: Poster I
KZR-261, a novel, first-in-class protein secretion inhibitor, is the first clinical candidate to be nominated from our research and discovery efforts targeting protein secretion pathways as potential therapies for oncology, immuno-oncology and autoimmune indications. KZR-261 is a broad-spectrum anti-tumor agent that acts through direct interaction and inhibition of Sec61 activity. The compound was discovered at Kezar through a medicinal chemistry campaign in which several scaffolds were progressed through the company’s proprietary work flow of Sec61 modulation. As a result, Kezar has established a unique and broad library of protein secretion inhibitors and a strong patent position around KZR-261 and its analogs. KZR-261 has demonstrated several encouraging features that exhibit its potential to be a new anti-cancer agent for the treatment of solid and hematologic malignancies. IND-enabling studies are currently underway, and an IND filing in solid tumors is expected in Q1 2021.
About Protein Secretion
In mammalian cells, the secretion of proteins such as cytokines and the expression of cell surface transmembrane proteins such as cytokine receptors involve a process called cotranslational translocation. For most proteins, this process occurs via the Sec61 translocon, a highly conserved multi-subunit protein complex found in the membrane of the endoplasmic reticulum of all cells. Kezar scientists have been researching the protein secretion pathway and ways to drug this key aspect of cellular function for more than 5 years. Kezar has developed several novel experimental platforms to study small molecule inhibitors of Sec61, which result in several physiologic outcomes, including altered cellular function, inhibition of cytokine release and/or cell death.
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SVP, Strategy & External Affairs
Source: Kezar Life Sciences, Inc.