Kezar Life Sciences Highlights Therapeutic Potential of Protein Secretion Inhibitors at the 61st American Society of Hematology Annual Meeting

Kezar Life Sciences, Inc. (Nasdaq: KZR ), a clinical-stage biotechnology company discovering and developing novel small molecule therapeutics to treat unmet needs in autoimmune disease and cancer, highlighted work from its research and development platform focusing on Sec61 translocon inhibition during the 61st American Society of Hematology (ASH) Annual Meeting and Exposition taking place in Orlando, FL from December 7-10, 2019.

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 Christopher Kirk, President and Chief of Scientific Officer of Kezar. “The preclinical data generated with our first clinical candidate, KZR-261, increases our confidence that inhibiting the Sec61 translocon may prove effective in treating a variety of solid and hematologic tumor types. To that end, we have initiated activities towards an Investigational New Drug filing for an initial study in multiple solid tumor types, which we anticipate in Q1 2021.”

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 Eric Rowinsky, MD, Chief Scientific Officer, Oncology, Clearpath Development, “The range of validated targets blocked by Kezar’s unique approach underscores the exciting potential for this new modality, which has the potential to act like a combination therapy via a single drug.”

Presentation details are below:

Oral Presentations

Abstract Number: 408 Title: Blocking Protein Secretion with Novel Small Molecule Inhibitors of Sec61 Represents a Potential Treatment Strategy Against Hematologic Malignancies Date: Sunday, December 8, 2019 Time: 10:45am 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 Date: Monday, December 9, 2019 Time: 4:30 PM Oral Session: 605. Molecular Pharmacology, Drug Resistance—Lymphoid and Other Poster Presentation

Abstract Number: 2076 Title: Proteomic Profiling and Mechanistic Investigating of a Novel Anti-Cancer Small Molecule Inhibitor of Sec61 Date: Saturday, December 7, 2019 Time: 5:30 PM - 7:30 PM Poster Session: 802. Chemical Biology and Experimental Therapeutics: Poster I

About KZR-261

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.

About Kezar Life Sciences

Based in South San Francisco, Kezar Life Sciences is a clinical-stage biotechnology company committed to revolutionizing treatments for patients with autoimmune diseases and cancer. Kezar is translating its innovative research on the immunoproteasome and protein secretion pathways to advance novel therapeutic approaches. KZR-616, a first-in-class selective immunoproteasome inhibitor, is being evaluated in severe autoimmune diseases, including systemic lupus erythematosus (SLE), lupus nephritis (LN), dermatomyositis (DM), polymyositis (PM), autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Additionally, Kezar has nominated KZR-261 as its first clinical candidate for the treatment of cancer from its protein secretion program and is undergoing IND-enabling studies for the program. For more information, visit www.kezarlifesciences.com .

Cautionary Note on Forward-looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “should,” “expect,” “believe” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Kezar’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause Kezar’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the timing, scope and outcome of preclinical studies and clinical trials, the clinical application of Kezar’s product candidates, the likelihood that data will support future development, the association of data with treatment outcomes, and the timing of regulatory filings for Kezar’s product candidates. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, the uncertainties and timing of the regulatory approval process, and unexpected litigation or other disputes. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Kezar’s filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” contained therein. Except as required by law, Kezar assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

CONTACT: Celia Economides SVP, Strategy & External Affairs [email protected]