Zetomipzomib

Enrolment into the Phase I trial investigating Kezar’s solid tumour drug KZR-261 has been halted. Credit: PeopleImages.com – Yuri A via Shutterstock. Clinical stage biopharma Kezar Life Sciences will drop its Phase I solid tumour drug to streamline focus on its lead autoimmune disease drug zetomipzomib. The San Francisco-based biotech shared this update in its 2Q financial results. The candidate, dubbed KZR-261, was being investigated in a Phase I trial (NCT05047536) in patients with solid tumours. Of the 61 enrolled patients, five experienced stable disease for four months or longer, with two of these patients experiencing stable disease for a year or longer. No objective responses have been reported. Enrolment in the trial has been halted, but the 61 patients will continue to have access to KZR-261. All eyes will now be on zetomipzomib, a selective immunoproteasome inhibitor. The candidate is being evaluated in a Phase IIb PALIZADE clinical trial (NCT05781750) for lupus nephritis and a Phase IIa PORTOLA clinical trial (NCT05569759) for autoimmune hepatitis. Everest Medicines secured the Greater China, South Korea, and South-East Asia rights for zetomipzomib in September 2023. The first patient in China has already been dosed with zetomipzomib as part of the PALIZADE trial, with topline data expected in mid-2026, as per Kezar. See Also: Madrigal plans to solidify Rezdiffra’s position in MASH despite start being slower than expected Pfizer touts positive topline data for RSV vaccine Abrysvo The PORTOLA trial has enrolled 24 patients so far, randomised to receive 60mg of zetomipzomib or a placebo for 24 weeks. Kezar said that topline data from this trial is anticipated in the first half of next year. Zetomipzomib has previously been studied in lupus nephritis, with the company reporting positive data from the Phase II MISSION trial investigating zetomipzomib in 69 patients with that autoimmune condition. Data highlighted that 64.7% of the trial subjects attained the trial’s primary efficacy endpoint of overall renal response (ORR). Kezar, a spinout from Amgen , slashed its workforce by 41% back in October 2023 to extend its cash runway. Though clinical development of zetomipzomib and KZR-261 survived the restructuring, the company halted all of its preclinical programmes. The company ended the 2Q with $164m in cash and equivalents. According to GlobalData’s Pharma Intelligence Center, if approved, zetomipzomib could be set to pull in sales of $498m in 2030. GlobalData is the parent company of Pharmaceutical Technology. In the announcement accompanying the business update, Kezar’s CEO Chris Kirk said: “We are thrilled to announce the completion of enrolment to our PORTOLA trial and look forward to sharing topline results earlier than expected in the first half of 2025. “This important milestone brings us one step closer to delivering zetomipzomib as a new treatment option for patients suffering from autoimmune hepatitis, a disease of significant unmet medical need.”

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )-- Kezar Life Sciences, Inc . (Nasdaq: KZR), a clinical-stage biotechnology company developing novel small molecule therapeutics to treat unmet needs in immune-mediated diseases and cancer, today reported financial results for the second quarter ended June 30, 2024, and provided a business update. “We are thrilled to announce completion of enrollment to our PORTOLA trial and look forward to sharing topline results earlier than expected in the first half of 2025. This important milestone brings us one step closer to delivering zetomipzomib as a new treatment option for patients suffering from autoimmune hepatitis, a disease of significant unmet medical need,” said Chris Kirk, PhD, Kezar’s Co-founder and Chief Executive Officer. “In addition, we are continuing to see strong enrollment activity in our global PALIZADE trial and look to continue this momentum by focusing our clinical resources on zetomipzomib development programs going forward. I want to thank our team for their hard work and commitment across all of our clinical trials and share our gratitude to the patients, their families and the study investigators, for their participation in these studies.” Zetomipzomib: Selective Immunoproteasome Inhibitor PALIZADE – Phase 2b clinical trial of zetomipzomib in patients with active lupus nephritis (LN) (ClinicalTrials.gov: NCT05781750 ) PALIZADE is a global, placebo-controlled, randomized, double-blind Phase 2b clinical trial evaluating the efficacy and safety of two dose-levels of zetomipzomib in patients with active LN. Target enrollment will be 279 patients, randomly assigned (1:1:1) to receive 30 mg of zetomipzomib, 60 mg of zetomipzomib or placebo subcutaneously once weekly for 52 weeks, in addition to standard background therapy. Background therapy can, but will not be mandated to, include standard induction therapy. Over the initial 16 weeks, there will be a mandatory corticosteroid taper to 5 mg per day or less. End-of-treatment assessments will occur at Week 53. The primary efficacy endpoint is the proportion of patients who achieve a complete renal response (CRR) at Week 37, including a urine protein-to-creatine ratio (UPCR) of 0.5 or less without receiving rescue or prohibited medications. Our partner, Everest Medicines, announced that the first patient in China was dosed with zetomipzomib as part of our global PALIZADE trial. Kezar entered into a collaboration and license agreement with Everest Medicines in September 2023 to develop and commercialize zetomipzomib in Greater China, South Korea and Southeast Asia. Kezar expects to report topline data from PALIZADE in mid-2026. PORTOLA – Phase 2a clinical trial of zetomipzomib in patients with autoimmune hepatitis (AIH) (ClinicalTrials.gov: NCT05569759 ) PORTOLA is a placebo-controlled, randomized, double-blind Phase 2a clinical trial evaluating the efficacy and safety of zetomipzomib in patients with AIH that are insufficiently responding to standard of care or have relapsed. The study has completed enrollment of 24 patients, randomized (2:1) to receive 60 mg of zetomipzomib or placebo in addition to background therapy for 24 weeks, with a protocol-suggested steroid taper. The primary efficacy endpoint will measure the proportion of patients who achieve a complete biochemical response by Week 24 measured as normalization of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Immunoglobulin G (IgG) values (if elevated at baseline), with steroid dose levels not higher than baseline. Kezar expects to report topline data from PORTOLA in the first half of 2025. KZR-261: Broad-Spectrum Sec61 Translocon Inhibitor KZR-261-101 – Phase 1 clinical trial of KZR-261 in patients with locally advanced or metastatic solid malignancies (ClinicalTrials.gov: NCT05047536 ) The Phase 1 clinical trial of KZR-261 is being conducted in two parts: dose escalation and dose expansion in tumor-specific solid tumors. The study is designed to evaluate safety and tolerability, pharmacokinetics and pharmacodynamics, identify a recommended Phase 2 dose and explore the preliminary anti-tumor activity of KZR-261 in patients with locally advanced or metastatic disease. Enrollment has been stopped in the KZR-261 Phase 1 study, and clinical resources are being reallocated toward development of zetomipzomib in AIH and LN. Patients already enrolled in the study will continue to have access to KZR-261. A total of 61 patients enrolled across the dose-escalation and dose expansion portions of the study, which included seven patients enrolled in the melanoma cohort of the dose-expansion portion at a dose level of 60 mg/m 2 . No objective responses have been observed to date in the study. Five patients (two with melanoma) within the dose escalation portion of the study experienced stable disease for four months or longer, of which two patients (melanoma; head and neck) experienced stable disease for twelve months or longer. KZR-261 has demonstrated consistent pharmacokinetics across all dose levels to date, and evidence of dose-dependent inhibition of Sec61 has been observed in patient blood samples. Kezar plans to report full data at a medical conference following completion of the study. Financial Results Cash, cash equivalents and marketable securities totaled $164.2 million as of June 30, 2024, compared to $201.4 million as of December 31, 2023. The decrease was primarily attributable to cash used in operations to advance clinical-stage programs. Research and development (R&D) expenses for the second quarter of 2024 decreased by $4.7 million to $16.3 million, compared to $21.0 million in the second quarter of 2023. This decrease was primarily due to the Company’s strategic restructuring in October 2023 to prioritize its clinical-stage programs, reducing personnel-related costs and spending in its early-stage research activities. The decrease was partially offset by the increased clinical trial costs related to the PALIZADE and PORTOLA trials. General and administrative (G&A) expenses for the second quarter of 2024 decreased by $0.2 million to $5.6 million compared to $5.8 million in the second quarter of 2023. The decrease was primarily due to a decrease in legal and professional service expenses. Restructuring and impairment charges for the second quarter of 2024 were $1.5 million. The charges were primarily related to an impairment loss of the right-of-use asset related to vacated space in the company’s leased office facilities. Net loss for the second quarter of 2024 was $21.5 million, or $0.30 per basic and diluted common share, compared to a net loss of $24.3 million, or $0.34 per basic and diluted common share, for the second quarter of 2023. Total shares of common stock outstanding were 72.9 million shares as of June 30, 2024. Additionally, there were options to purchase 15.3 million shares of common stock at a weighted-average exercise price of $2.18 per share and 0.2 million restricted stock units outstanding as of June 30, 2024. About Kezar Life Sciences Kezar Life Sciences is a clinical-stage biopharmaceutical company developing novel small molecule therapeutics to treat unmet needs in immune-mediated diseases and cancer. Zetomipzomib, a selective immunoproteasome inhibitor, is currently being evaluated in a Phase 2b clinical trial for lupus nephritis and a Phase 2a clinical trial for autoimmune hepatitis. This product candidate also has the potential to address multiple chronic immune-mediated diseases. Kezar’s oncology product candidate, KZR-261, targeting the Sec61 translocon and protein secretion pathway, is being evaluated in an open-label Phase 1 clinical trial to assess safety, tolerability and preliminary tumor activity in solid tumors. For more information, visit www.kezarlifesciences.com , and follow us on LinkedIn , Facebook , Twitter and Instagram . 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,” “can,” “should,” “expect,” “believe,” “potential,” “anticipate” 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 design, initiation, progress, timing, scope and results of clinical trials, the enrollment and expected timing of reporting topline data from our clinical trials, the development of zetomipzomib in additional indications, the likelihood that data will support future development and therapeutic potential, the association of data with treatment outcomes and the likelihood of obtaining regulatory approval of Kezar’s product candidates. Many factors may cause differences between current expectations and actual results, including clinical trial site activation or enrollment rates that are lower than expected, unexpected safety or efficacy data observed during clinical studies, difficulties enrolling and conducting our clinical trials, 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. KEZAR LIFE SCIENCES, INC. Selected Balance Sheets Data (In thousands) June 30, 2024 December 31, 2023 (unaudited) Cash, cash equivalents and marketable securities $ 164,182 $ 201,372 Total assets 179,921 221,235 Total current liabilities 17,495 17,744 Total noncurrent liabilities 11,741 15,921 Total stockholders' equity 150,685 187,570 Summary of Operations Data (In thousands except share and per share data) Three Months Ended Six Months Ended June 30 June 30 2024 2023 2024 2023 (unaudited) (unaudited) Operating expenses: Research and development $ 16,298 $ 20,999 $ 33,470 $ 39,317 General and administrative 5,603 5,785 12,142 11,991 Restructuring and impairment charges 1,482 - 1,482 - Total operating expenses 23,383 26,784 47,094 51,308 Loss from operations (23,383 ) (26,784 ) (47,094 ) (51,308 ) Interest income 2,237 2,861 4,690 5,556 Interest expense (401 ) (385 ) (801 ) (755 ) Net loss $ (21,547 ) $ (24,308 ) $ (43,205 ) $ (46,507 ) Net loss per common share, basic and diluted $ (0.30 ) $ (0.34 ) $ (0.59 ) $ (0.64 ) Weighted-average shares used to compute net loss per common share, basic and diluted 72,845,869 72,461,850 72,822,890 72,395,410