Lupus Nephritis

-- Clinical data on povetacicept in IgA nephropathy will be updated at the upcoming WCN meeting, including follow up at 80 mg and initial data at 240 mg SC once every four-weeks -- -- Povetacicept advancing towards a pivotal phase 3 trial in IgA nephropathy and a phase 2 trial in systemic lupus erythematosus -- SEATTLE--(BUSINESS WIRE)-- Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for autoimmune and inflammatory diseases, today reported full year 2023 financial results and company highlights for the fourth quarter ended December 31, 2023. “2023 was a transformational year for Alpine, with initial IgA nephropathy (IgAN) data presented at the American Society of Nephrology Kidney Week 2023 suggesting a best-in-class pro povetacicept, our next-generation dual BAFF/APRIL inhibitor. With our encouraging data set in IgAN, convenient once monthly dosing regimen, and strong balance sheet, we are rapidly advancing development of povetacicept as a potentially meaningful new therapeutic option for patients living with IgAN, systemic lupus erythematosus (SLE), and multiple other autoantibody-related diseases,” said Mitchell H. Gold, MD, Executive Chairman and Chief Executive Officer of Alpine. Dr. Gold continued, “Looking ahead, Alpine is well positioned for a year of meaningful catalysts, with multiple updates for povetacicept in IgAN and other indications, and the planned initiation of RAINIER, a pivotal phase 3 study of povetacicept in IgAN, and DENALI, a phase 2 study of povetacicept in SLE. In addition to updates on our clinical studies, we look forward to sharing translational data that further supports the best-in-class potential of povetacicept in multiple inflammatory diseases.” Fourth Quarter 2023 Corporate Updates Povetacicept (ALPN-303) First clinical data in IgAN demonstrate that povetacicept 80 mg administered once every four-weeks (Q4W) reduced proteinuria (as assessed by urine protein to creatinine ratio, UPCR) by greater than 50% and was associated with stable renal function (as assessed by estimated glomerular filtration rate, eGFR) at six months. In addition, povetacicept was well tolerated during subcutaneous administration, with no instances of IgG < 3 g/L, and no severe infections (2023 American Society of Nephrology Kidney Week). In a model of murine experimental autoimmune myasthenia gravis, povetacicept improved disease activity, with clinical scores superior to treatment with either the FcRn inhibitor efgartigimod or an anti-CD20 depleting antibody (2023 American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting). New translational data from povetacicept in systemic lupus erythematosus demonstrate that povetacicept, as compared to single BAFF or APRIL pathway inhibitors, more potently downregulates genes associated with activation in B cells and significantly reduces multiple disease parameters in a mouse model of lupus, more effectively than WT TACI-Fc or conventional B cell depletion (2023 American College of Rheumatology Convergence). Throughout 2023, the Company presented multiple oral and poster presentations on povetacicept at scientific conferences (Full List of Company Publications and Presentations). Corporate Updates The Company plans to present additional data on povetacicept in IgA nephropathy, including follow up data from the 80 mg Q4W and initial data from the IgAN 240 mg Q4W dose cohorts, during a Late Breaking Abstract session at the World Congress of Nephrology 2024 on Monday April 15th at 4:45 PM ET. The Company plans to present new preclinical data on povetacicept, demonstrating its greater distribution to disease-related end organs compared with WT TACI-Ig, at the 14th European Lupus Meeting. These findings correlate with povetacicept’s improved efficacy in multiple preclinical disease models. The Company intends to initiate RAINIER, a pivotal phase 3 study of povetacicept in IgA nephropathy and DENALI, a phase 2 study of povetacicept in systemic lupus erythematosus in the second half of 2024, pending regulatory agreement. The Company plans to share initial data from RUBY-4 in autoimmune cytopenias in the first half of 2024 at a relevant scientific congress. The Company amended its option and license agreement on acazicolcept with AbbVie, stopping enrollment in the phase 2 study in systemic lupus erythematosus (Synergy), and facilitating early assessment of data. The Company ended the year with $368.2 million in cash and investments as of December 31, 2023, which the Company anticipates should be sufficient to fund its planned operations into 2026. 2023 Financial Results Cash Position and Runway: As of December 31, 2023, Alpine’s cash and investments totaled $368.2 million compared to $273.4 million as of December 31, 2022. The Company anticipates its current cash and investments are sufficient to fund planned operations into 2026. Collaboration Revenue: For the year ended December 31, 2023, collaboration revenue was $58.9 million compared to $30.1 million for the same period in 2022. The increase in collaboration revenue relates primarily to a $24.9 million increase in AbbVie revenue, of which $20.4 million relates to a cumulative catch-up adjustment resulting from the completion of enrollment in Synergy per the amendment with AbbVie, and a $4.5 million increase in Amgen revenue, driven primarily by the expiration of Amgen’s option to select a third Research Program. These increases were partially offset by a $0.6 million decrease in Adaptimmune revenue as we completed our final deliverables under the agreement in June 2023. Research and Development Expense: For the year ended December 31, 2023, research and development expense, inclusive of non-cash expenses, were $80.9 million compared to $70.2 million for the same period in 2022. The increase of $10.7 million was driven by an $8.2 million increase in povetacicept costs, primarily related to higher clinical trial costs, process development, and manufacturing, a $1.3 million increase in acazicolcept costs, due primarily to process development and manufacturing costs, and a $7.7 million increase in personnel costs. General and Administrative Expenses: For the year ended December 31, 2023, general and administrative expenses, inclusive of non-cash expenses, were $22.2 million compared to $18.0 million for the same period in 2022. The increase of $4.3 million was primarily attributable to increases in personnel costs and professional services. Net Loss: Net loss for the year ended December 31, 2023, was $32.2 million compared to $57.8 million for the same period in 2022. Alpine Immune Sciences, Inc. Selected Consolidated Balance Sheet Data (In thousands) December 31, 2023 December 31, 2022 (unaudited) Cash and cash equivalents $ 43,921 $ 13,376 Short-term investments 283,491 224,265 Total current assets 330,034 240,993 Long-term investments 40,556 35,481 Total assets 379,852 286,686 Total current liabilities 41,980 57,996 Total stockholders’ equity 327,941 179,420 Total liabilities and stockholders’ equity 379,852 286,686 Consolidated Statement of Operations and Comprehensive Income (Loss) Data (In thousands, except share and per share amounts) Years Ended December 31, 2023 2022 (unaudited) Collaboration revenue $ 58,876 $ 30,064 Operating expenses: Research and development 80,904 70,243 General and administrative 22,222 17,968 Total operating expenses 103,126 88,211 Loss from operations (44,250 ) (58,147 ) Other income (expense): Interest income 11,852 3,288 Interest expense (98 ) (476 ) Other, net 415 (97 ) Loss before taxes (32,081 ) (55,432 ) Income tax (expense) benefit (103 ) (2,330 ) Net loss $ (32,184 ) $ (57,762 ) Comprehensive income (loss): Unrealized gain (loss) on investments 1,493 (901 ) Unrealized gain (loss) on foreign currency translation 25 53 Comprehensive loss $ (30,666 ) $ (58,610 ) Weighted-average shares used to compute basic and diluted net loss per share 50,000,339 33,435,280 Basic and diluted net loss per share $ (0.64 ) $ (1.73 ) About Povetacicept (ALPN-303) Povetacicept (ALPN-303) is a dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation and/or survival of B cells, particularly antibody-secreting cells, as well as T cells and innate immune cells. Based upon an engineered TACI (transmembrane activator and CAML interactor) domain, povetacicept has exhibited greater potency in preclinical studies versus other inhibitors of BAFF and/or APRIL alone and B cell depletion. Povetacicept is in development for multiple autoimmune diseases, including IgA nephropathy and other autoimmune kidney diseases, systemic lupus erythematosus, and autoimmune cytopenias. About RUBY-3 RUBY-3 (NCT05732402) is a multiple ascending dose, multi-cohort, open label, phase 1b/2a study of povetacicept in autoimmune glomerulonephritis, including IgA nephropathy, primary membranous nephropathy, lupus nephritis, and renal ANCA-associated vasculitis, where povetacicept is being administered subcutaneously for up to 104 weeks. Key endpoints include proteinuria, eGFR, renal response, and disease-related autoantibodies. About RUBY-4 RUBY-4 (NCT05757570) is a multi-cohort, open label, phase 1b study of povetacicept in immune thrombocytopenia, autoimmune hemolytic anemia, and cold agglutinin disease, where povetacicept is being administered subcutaneously for up to 48 weeks. Key endpoints include respective blood cell counts, including durable responses, as well as disease-related autoantibodies. About Alpine Immune Sciences Alpine Immune Sciences is committed to leading a new wave of immune therapeutics. With world-class research and development capabilities, a highly productive scientific platform, and a proven management team, Alpine is seeking to create first- or best-in-class multifunctional immunotherapies via unique protein engineering technologies to improve patients’ lives. Alpine has entered into strategic collaborations with leading global biopharmaceutical companies and has a diverse pipeline of clinical and preclinical candidates in development. For more information, visit . Follow @AlpineImmuneSci on X and LinkedIn. Forward-Looking Statements This release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding our platform technology and potential therapies; the timing of and results from clinical trials and preclinical development activities; clinical and regulatory objectives and the timing thereof; expectations regarding the sufficiency of cash, including cash equivalents and restricted cash, and investments to fund our planned operations into 2026; our ability to achieve additional milestones in our collaborations and proprietary programs; the progress and potential of our development programs; future development plans and clinical and regulatory milestones and objectives, including the timing and achievement thereof; the efficacy of our clinical trial designs; anticipated enrollment in our clinical trials and the timing thereof; expectations regarding the anticipated reporting of data from our ongoing and planned clinical trials and potential publication of future clinical data; our ability to potentially advance povetacicept directly into a pivotal trial in the second half of 2024 as well as a phase 2 study in systemic lupus erythematosus, pending engagement with and approval of the Food and Drug Administration; and the potential efficacy, safety profile, addressable market, regulatory success and commercial or therapeutic potential of our product candidates. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions and include words such as “may,” “will,” “should,” “would,” “expect,” “plan,” “intend,” and other similar expressions, among others. These forward-looking statements are based on current assumptions that involve risks, uncertainties, and other factors that may cause actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical trials may not demonstrate safety and efficacy of any of our product candidates; our ongoing discovery and preclinical efforts may not yield additional product candidates; our discovery stage and preclinical programs may not advance into the clinic or result in approved products; any of our product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; the impact of competition; adverse conditions in the general domestic and global economic markets; we may be unable to advance povetacicept directly into a pivotal trial or a phase 2 study in systemic lupus erythematosus in the second half of 2024; the impact of pandemics, or other related health crises on our business, research and clinical development plans and timelines and results of operations, including the impact on our clinical trial sites, collaborators, and contractors who act for or on our behalf; as well as the other risks identified in our filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof and we undertake no obligation to update forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements. The RUBY and Alpine logos are registered trademarks of Alpine Immune Sciences, Inc. in various jurisdictions.

PALIZADE Phase 2b clinical trial of zetomipzomib in patients with active lupus nephritis actively enrolling; reiterating guidance of topline data in mid-2026 PORTOLA Phase 2a clinical trial of zetomipzomib in patients with autoimmune hepatitis actively enrolling; reiterating guidance of topline data in mid-2025 KZR-261 dose escalation study currently enrolling ninth cohort; data update by year-end Cash, cash equivalents and marketable securities totaled $201.4 million as of December 31, 2023 SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company developing breakthrough treatments for immune-mediated and oncologic disorders, today reported financial results for the fourth quarter and year ended December 31, 2023 and provided a business update. "The efforts over the past year by the team at Kezar have put us in a strong position as we advance our promising, first-in-class immunology and oncology programs," said Chris Kirk, Kezar’s Co-founder and Chief Executive Officer. “We remain focused with the zetomipzomib program on bringing this important new agent to patients with autoimmune hepatitis and lupus nephritis, both severe and poorly treated autoimmune disorders. Our PORTOLA and PALIZADE trials remain on track for readouts in 2025 and 2026, which we expect to demonstrate the potential of zetomipzomib as a promising new agent for the treatment of a wide range of autoimmune disorders. Additionally, we are eager to share data from the KZR-261 program in solid tumors in the fourth quarter of 2024, which will include dose escalation and initial dose expansion safety, PK/PD, and exploratory efficacy analyses. With our strong team and solid balance sheet, we are well positioned to deliver meaningful results across our programs, for the patients and our shareholders.” Zetomipzomib: Selective Immunoproteasome Inhibitor Clinical Development: PALIZADE – Phase 2b clinical trial of zetomipzomib in patients with active 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. PORTOLA – Phase 2a clinical trial of zetomipzomib in patients with autoimmune hepatitis (AIH) who have not benefited from standard-of-care treatment (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. Target enrollment will be 24 patients, randomized (2:1) to receive 60 mg of zetomipzomib or placebo in addition to background corticosteroid therapy for 24 weeks, with a protocol-mandated steroid taper by Week 14. The primary efficacy endpoint will measure the proportion of patients who achieve a complete response measured as normalization of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels with a successful corticosteroid taper by Week 24. Collaboration with Everest Medicines: In September 2023, Kezar entered into a collaboration and license agreement with Everest Medicines to develop and commercialize zetomipzomib in Greater China, South Korea and Southeast Asia. Everest Medicines is joining Kezar on the PALIZADE clinical trial and will contribute their local regulatory and clinical trial expertise to enroll patients in these geographies. In February 2024, the Centre for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) approved the investigational new drug (IND) application for the initiation of PALIZADE in China. In addition to PALIZADE, Kezar and Everest Medicines have the opportunity to collaborate on future clinical trials and indications for the continued development of zetomipzomib. 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 to explore the preliminary anti-tumor activity of KZR-261 in patients with locally advanced or metastatic disease. The KZR-261 trial is currently enrolling Cohort 9 (80 mg/m2). Previously, Cohort 1 (1.8 mg/m2) through Cohort 8 (60 mg/m2) enrolled a total of 35 patients and completed rapid dose escalation without significant safety concerns. To date, KZR-261 has shown dose-proportional exposure and no signs of accumulation or altered pharmacokinetics with repeated dosing. Financial Results Cash, cash equivalents and marketable securities totaled $201.4 million as of December 31, 2023, compared to $276.6 million as of December 31, 2022. The decrease was primarily attributable to cash used in operations to advance clinical-stage programs and preclinical research and development. Revenue for the year of 2023 was $7.0 million resulting from the upfront payment under the collaboration and license agreement with Everest Medicines. Research and development (R&D) expenses for the fourth quarter of 2023 increased by $7.7 million to $22.6 million, compared to $14.9 million in the fourth quarter of 2022. Full year R&D expenses increased by $34.7 million to $85.7 million in 2023, compared to $51.0 million in 2022. This increase was primarily due to clinical trial costs related to the PALIZADE and PORTOLA trials, a milestone payment made to Onyx Therapeutics, and an increase in non-cash stock-based compensation and facility-related expenses. General and administrative (G&A) expenses for the fourth quarter of 2023 increased by $0.6 million to $5.8 million compared to $5.2 million in the fourth quarter of 2022. Full year G&A expenses increased by $6.4 million to $26.5 million in 2023, compared to $20.1 million in 2022. The increase was primarily due to an increase in legal and professional service expense in connection with the collaboration and license agreement with Everest Medicines and an increase in non-cash stock-based compensation, personnel and facility-related expenses. Restructuring and impairment charges for the fourth quarter of 2023 were $6.2 million. The charges comprised primarily of one-time employee termination benefits and long-lived assets impairment costs related to the right-of-use asset and certain property and equipment no longer utilized. Net loss for the fourth quarter of 2023 was $32.3 million, or $0.44 per basic and diluted common share, compared to a net loss of $18.2 million, or $0.25 per basic and diluted common share, for the fourth quarter of 2022. Net loss for 2023 was $101.9 million, or $1.40 per basic and diluted common share, compared to a net loss of $68.2 million, or $1.01 per basic and diluted common share, in 2022. Total shares of common stock outstanding were 72.8 million shares as of December 31, 2023. Additionally, there were options to purchase 13.1 million shares of common stock at a weighted-average exercise price of $2.60 per share and 0.2 million restricted stock units outstanding as of December 31, 2023. About Kezar Life Sciences Kezar Life Sciences is a clinical-stage biopharmaceutical company developing novel treatments for immune-mediated and oncologic disorders. 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 dose-escalation Phase 1 clinical trial to assess safety, tolerability and preliminary tumor activity in solid tumors. For more information, visit , 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 company’s position to deliver meaningful results across its programs, for patients and shareholders, the design, initiation, progress, timing, scope and results of clinical trials, the expected timing of reporting topline data from our clinical trials, collaboration on clinical trials and development of zetomipzomib in additional indications, the enrollment of clinical trials, anticipated therapeutic benefit and regulatory development of Kezar’s product candidates, 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, disputes or failure to perform under the collaboration and license agreement, 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) December 31, 2023 December 31, 2022 Cash, cash equivalents and marketable securities $ 201,372 $ 276,561 Total assets 221,235 299,568 Total current liabilities 17,744 10,997 Total noncurrent liabilities 15,921 18,699 Total stockholders' equity 187,570 269,872 Summary of Operations Data (In thousands except share and per share data) Three Months Ended Year Ended December 31 December 31 2023 2022 2023 2022 Collaboration revenue $ — $ — $ 7,000 $ — Operating expenses: Research and development 22,643 14,859 85,697 51,009 General and administrative 5,759 5,175 26,540 20,153 Restructuring and impairment charges 6,187 — 6,187 — Total operating expenses 34,589 20,034 118,424 71,162 Loss from operations (34,589 ) (20,034 ) (111,424 ) (71,162 ) Interest income 2,728 2,202 11,104 4,108 Interest expense (399 ) (349 ) (1,550 ) (1,185 ) Net loss $ (32,260 ) $ (18,181 ) $ (101,870 ) $ (68,239 ) Net loss per common share, basic and diluted $ (0.44 ) $ (0.25 ) $ (1.40 ) $ (1.01 ) Weighted-average shares used to compute net loss per common share, basic and diluted 72,736,956 72,231,697 72,553,645 67,368,935

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )--Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company developing breakthrough treatments for immune-mediated and oncologic disorders, today announced that the Compensation Committee of the company’s Board of Directors granted one employee a nonqualified stock option to purchase 36,000 shares of its common stock with an exercise price of $1.03 per share, which is equal to the closing price of Kezar’s common stock on March 5, 2024, the grant date of the award. The stock option was granted as an inducement award material to the individual entering into employment with Kezar, in accordance with Nasdaq Listing Rule 5635(c)(4). The stock option will vest over a four-year period, with 25% of the option vesting on the first anniversary of the employee’s start date, and 1/48th of the total shares vesting monthly thereafter, subject to continued employment on each vesting date. The option is subject to the terms and conditions of Kezar’s 2022 Inducement Plan and the stock option agreement covering the grant. About Kezar Life Sciences Kezar Life Sciences is a clinical-stage biopharmaceutical company developing novel treatments for immune-mediated and oncologic disorders. 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 dose-escalation 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 .