Atacicept

-- Povetacicept demonstrates greater reductions in disease activity in a mouse model of lupus compared to WT TACI-Ig or B cell depletion -- -- Povetacicept exhibits greater distribution to disease-related end organs compared with WT TACI-Ig -- -- A phase 2 study in SLE (DENALI) is in preparation for initiation in 2H 2024 -- 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, announced today that the Company presented new translational data for povetacicept (ALPN-303) at the SLEuro 14th European Lupus Meeting in Bruges, Belgium, March 19-22, 2024. Presentation Highlights Include: BAFF- and APRIL-related genes are increased in myeloid and B cells in systemic lupus erythematosus (SLE) patients compared to healthy adults. Povetacicept significantly reduces multiple disease parameters in the NZB/W mouse model of lupus, more effectively than WT TACI-Ig or B cell depletion. Povetacicept exhibits greater distribution to multiple tissues – 19-fold higher in the kidney and 3-4-fold higher in the lung, skin, and brain – in normal mice, compared to WT TACI-Ig, potentially related to advantageous differences in molecular weight, target affinity and/or isoelectric point. "We have long known that povetacicept possesses unique molecular attributes that were conferred by our discovery platform’s directed evolution process,” remarked Stanford Peng, MD, PhD, President and Head of Research and Development at Alpine. “At least one of these attributes is its ability to distribute to disease-relevant tissues to a greater extent than wild-type TACIs, which may explain its superiority in multiple preclinical or translational disease models. These findings are particularly intriguing considering that these organs are of particular relevance to our lead indications, systemic lupus erythematosus and IgA nephropathy. These findings further support our intent to initiate both a pivotal trial in IgA nephropathy, RAINIER, as well as a phase 2 study in SLE, DENALI, later this year.” Table 1: Greater Tissue Distribution vs. WT TACI-Ig Tissue % Positive (Mean ± SE) Fold Difference (Povetacicept/Telitacicept) Povetacicept Telitacicept Kidney 1.9 ± 0.2 0.1 ± 0.0 19.0 Lung 0.49 ± 0.13 0.13 ± 0.05 3.8 Skin 2.7 ± 0.4 0.8 ± 0.2 3.4 Brain 0.10 ± 0.03 0.03 ± 0.01 3.3 Table 2: Molecular Attributes Attribute Povetacicept Telitacicept MW (kDa)1 62.6 75.3-75.42 pI1 6.5-7.0 7.1-8.4 KD, BAFF 59 pM 491 pM KD, APRIL 1 pM CNBD 1 Theoretical, calculated by Expasy (web.expasy.org/compute_pi/), Prot pI (Protpi.ch/Calculator/Protein Tool), or at Alpine based on Anal. Biochem 179:319 (1989). 2 MW reported as 80.24 kDa in J Clin Pharmacol 56:948 (2016) SLEuro 14th European Lupus Meeting Poster Presentation Details Date: Thursday, March 21, 2024 Poster Title: The Enhanced Dual BAFF/APRIL Inhibitor Povetacicept (TACI vTD-Fc; ALPN-303) More Potently Reduces Disease Activity in Murine Lupus Compared to CD20 Depletion and WT TACI-Ig, Associated with Greater End-Organ Distribution Poster Number: Tour 2, P104 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 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.

Presented positive 72-week data from the Phase 2b ORIGIN clinical trial, setting a new standard in IgAN with no loss of kidney function over the duration of treatment Actively adding sites and enrolling pivotal Phase 3 ORIGIN 3 study of atacicept for the treatment of IgAN; topline data expected in 1H 2025 Completed $287.5 million financing, further strengthening the Company’s balance sheet and extending the Company’s expected cash runway through potential approval and commercial launch BRISBANE, Calif., March 20, 2024 (GLOBE NEWSWIRE) -- Vera Therapeutics, Inc. (Nasdaq: VERA), a late clinical-stage biotechnology company focused on developing and commercializing transformative treatments for patients with serious immunologic diseases, today reported its business highlights and financial results for the fourth quarter and year ended December 31, 2023. “Over the past year, we have strengthened the integrated data package for atacicept as a potentially disease-modifying treatment for patients with IgA Nephropathy (IgAN) and rapidly advanced the pivotal Phase 3 ORIGIN 3 clinical trial, which is expected to support our BLA submission to the FDA next year,” said Marshall Fordyce, M.D., Founder and CEO of Vera Therapeutics. “We believe atacicept 72-week data from the Phase 2b ORIGIN trial are consistent with a pro true disease modification. Our clinical successes to date, including the announcement of multiple positive data readouts from the Phase 2b ORIGIN trial of atacicept in patients with IgAN, as well as executing on the ORIGIN 3 study, have gained broad attention across the clinical landscape, and we have attracted several respected industry veterans to expand our team in support of our advancing pipeline.” “The 72-week data we recently announced from the ORIGIN 2b study supports our belief that atacicept has the potential to provide IgAN patients with long-term disease modification, evidenced by deep reductions in pathogenic Gd-IgA1, hematuria, proteinuria and most importantly, with stable eGFR. In aggregate, this quartet of findings provides support for our previous hypothesis that atacicept has the potential to be a transformative advancement for IgAN patients and may become the cornerstone treatment for this disease. The ORIGIN 2b results also provide us with even greater confidence in the ongoing ORIGIN Phase 3 trial, which continues to be on track with regard to enrollment,” stated Robert Brenner, M.D., Chief Medical Officer of Vera Therapeutics. Key Fiscal Year 2023 and Recent Business Highlights Presented positive 72-week data from ORIGIN Phase 2b trial of atacicept in IgAN that show consistent and sustained reductions in Gd-IgA1, hematuria, and UPCR, with stable eGFR over the duration of treatment Actively adding sites and enrolling pivotal Phase 3 clinical trial (ORIGIN 3) of atacicept for the treatment of IgAN since initiating enrollment in June 2023 Appointed industry veterans Robert M. Brenner, M.D., as Chief Medical Officer and William D. Turner as Chief Development Officer Completed $287.5M upsized public offering of its Class A common stock in February 2024 that further strengthened the balance sheet Upcoming Milestones Completion of Phase 3 full enrollment for primary endpoint estimated in the second half of 2024 Present 96-week data from ORIGIN Ph 2b clinical trial of atacicept in IgAN in the fourth quarter Topline data from the pivotal ORIGIN 3 trial expected to be presented in the first half of 2025 Financial Results for the Quarter and Year Ended December 31, 2023 For the year ended December 31, 2023, the company reported a net loss of $96.0 million, or a net loss per diluted share of $2.25, compared to a net loss of $89.1 million, or a net loss per diluted share of $3.35, for the same period last year. During the year ended December 31, 2023, net cash used in operating activities was $92.2 million, compared to $67.6 million for the same period last year. Vera reported $160.7 million in cash, cash equivalents, and marketable securities as of December 31, 2023. Subsequent to December 31, 2023, the Company strengthened its balance sheet upon completing an upsized public offering of its Class A common stock with gross proceeds of approximately $287.5 million, before deducting underwriting discounts and commissions and offering expenses. About Vera Vera Therapeutics is a late clinical-stage biotechnology company focused on developing treatments for serious immunological diseases. Vera’s mission is to advance treatments that target the source of immunologic diseases in order to change the standard of care for patients. Vera’s lead product candidate is atacicept, a fusion protein self-administered as a subcutaneous injection once weekly that blocks both B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL), which stimulate B cells and plasma cells to produce autoantibodies contributing to certain autoimmune diseases, including IgAN, also known as Berger’s disease, and lupus nephritis. In addition, Vera is evaluating additional diseases where the reduction of autoantibodies by atacicept may prove medically useful. Vera is also developing MAU868, a monoclonal antibody designed to neutralize infection with BK virus (BKV), a polyomavirus that can have devastating consequences in certain settings such as kidney transplant. Vera retains all global developmental and commercial rights to atacicept and MAU868. For more information, please visit . About Atacicept Atacicept is an investigational recombinant fusion protein that contains the soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) receptor that binds to the cytokines B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL). These cytokines are members of the tumor necrosis factor family that promote B-cell survival and autoantibody production associated with certain autoimmune diseases, including IgAN and lupus nephritis. The Phase 2b ORIGIN clinical trial of atacicept in IgAN met its primary endpoint and showed a statistically significant and sustained reduction in mean proteinuria versus baseline, as well as stabilized eGFR, at weeks 24, 36, and 72. Vera believes atacicept is positioned for best-in-class potential, targeting B cells and plasma cells to reduce autoantibodies and having been administered to more than 1,500 patients in clinical studies across different indications. About MAU868 MAU868, a potential first-in-class monoclonal antibody, has the potential to neutralize infection by blocking BKV virions from binding to host cells. BKV is a polyoma virus that can be reactivated in settings of immunosuppression, such as in kidney transplant. It is a leading cause of kidney transplant loss and transplant-associated morbidity; there are currently no approved treatments for BKV. Vera holds an exclusive worldwide license from Amplyx Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., for the development and commercialization of MAU868 in all indications. Forward-looking Statements Statements contained in this press release regarding matters, events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, atacicept’s potential to be a transformational treatment for patients with IgAN and become a cornerstone treatment for IgAN, Vera’s plans to complete enrollment of its pivotal Phase 3 study in the second half of 2024, expectations regarding reporting 96-week data from the ORIGIN Phase 2b trial in 2024, Vera’s plans to receive and share topline data from the pivotal Phase 3 trial in the first half of 2025, Vera’s expectations to submit a BLA for atacicept for IgAN to the FDA in 2025, and Vera’s product candidates, strategy, and regulatory matters. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “potential,” “expect,” “plan,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Vera’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks related to the regulatory approval process, results of earlier clinical trials may not be obtained in later clinical trials, preliminary results may not be predictive of topline results, risks and uncertainties associated with Vera’s business in general, the impact of macroeconomic and geopolitical events, and the other risks described in Vera’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Vera undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. For more information, please contact: Investor Contact: Joyce Allaire LifeSci Advisors 212-915-2569 jallaire@lifesciadvisors.com Media Contact: Mari Purpura LifeSci Advisors mpurpura@lifesciadvisors.com VERA THERAPEUTICS, INC. Condensed Statements of Operations and Comprehensive Loss (in thousands, except share and per share amounts) For the Year Ended December 31, 2023 2022 Operating expenses: Research and development $ 78,225 $ 68,993 General and administrative 23,787 21,910 Total operating expenses 102,012 90,903 Loss from operations (102,012 ) (90,903 ) Other income, net 6,023 1,848 Provision for income taxes (1 ) (1 ) Net loss $ (95,990 ) $ (89,056 ) Change in unrealized gain/loss on marketable securities 251 (224 ) Comprehensive loss $ (95,739 ) $ (89,280 ) Net loss per share attributable to common stockholders, basic and diluted $ (2.25 ) $ (3.35 ) Weighted-average shares used in computing net loss per share attributable to common stockholders, basic and diluted 42,707,072 26,570,676 VERA THERAPEUTICS, INC. Condensed Balance Sheets (in thousands) December 31, 2023 December 31, 2022 Assets Current assets: Cash, cash equivalents and short-term marketable securities $ 160,716 $ 114,653 Prepaid expenses and other current assets 11,307 11,045 Total current assets 172,023 125,698 Operating lease right-of-use assets 2,949 5,173 Non-marketable equity securities 11 58 Other noncurrent assets 563 506 Total assets $ 175,546 $ 131,435 Liabilities and stockholders' equity Current liabilities: Accounts payable $ 11,118 $ 11,991 Operating lease liabilities 2,436 2,645 Accrued expenses and other current liabilities 8,749 10,964 Total current liabilities 22,303 25,600 Long-term debt 49,877 24,810 Operating lease liabilities, noncurrent 1,395 3,831 Accrued and other noncurrent liabilities 286 286 Total liabilities 73,861 54,527 Stockholders' equity Common stock 44 28 Additional paid-in-capital 410,492 290,216 Accumulated other comprehensive gain/loss 251 (224 ) Accumulated deficit (309,102 ) (213,112 ) Total stockholders' equity 101,685 76,908 Total liabilities and stockholders' equity $ 175,546 $ 131,435