IRF5

Engineered ARMMs efficiently deliver CRISPR/Cas9 complexes, base editing complexes and RNA therapeutics Additional presentations demonstrate biodistribution to a range of tissue types and scalable manufacturing processes CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vesigen Therapeutics, Inc., a biotechnology company developing a novel non-viral delivery platform for gene editors, RNA, and protein-based therapeutics, showcased eight data presentations at the American Society of Gene & Cell Therapy (ASGCT) 26th Annual Meeting held May 16-20, 2023 in Los Angeles. New data demonstrate the potential for the Company’s ARMM (ARrestin-domain 1 Mediated Microvesicles) technology to functionally deliver therapeutics to a broad range of disease-relevant cells and tissues. “We were pleased to share a robust data package highlighting the transformative capacity of our non-viral ARMMs technology to overcome fundamental delivery challenges that limit the potential of promising new treatment modalities,” said Paulash Mohsen, Chief Executive Officer at Vesigen. “Based on the substantial evidence generated to date, we believe our approach enables highly efficient, tunable, and re-dosable delivery of multiple emerging therapeutic modalities. As we advance toward the clinic, we continue to evaluate partnerships where we may combine our ARMM delivery technology with novel therapeutic modalities in order to develop more effective, next-generation medicines.” In Vivo and in Vitro Functional Delivery of Gene Editing Complexes and Therapeutic RNA Molecules Data presentations demonstrated engineering of ARMMs to package and functionally deliver CRISPR/Cas9 complexes, base editing complexes, messenger RNA (mRNA), and short hairpin RNA (shRNA) to a diverse range of cell types in vitro and in vivo. In vivo, a single intranasal administration of ARMMs loaded with gene or base editors targeting the immune modulatory genes NLRP3 or IRF5 resulted in 60+% on-target editing in macrophages and blunted the release of associated cytokines in murine lung tissue. In vitro evaluation of Vesigen-engineered ARMMs loaded with CRISPR/Cas9 or base editors, in collaboration with David Liu, Ph.D., Professor at the Broad Institute and Harvard University, resulted in efficient editing of multiple genomic loci across a range of human and murine cell types, including primary and post-mitotic cells. ARMMs loaded with mRNA or shRNA were shown to result in robust translation of delivered transcript or knockdown of target gene, respectively. In Vivo Biodistribution of Engineered ARMMs Two data presentations highlighted in vivo biodistribution of engineered ARMMs in non-human primates and rodents. In mouse models, functional delivery of engineered ARMMs was observed in the retina, lung, spleen, liver, and other tissues. In non-human primates, data showed delivery of engineered ARMMs intrathecally to cells in the peripheral nervous system. Advances in Process Development Three data presentations, including collaborations with Lonza Cell and Gene Technologies and NanoFCM, highlighted development of scalable approaches to produce and characterize ARMMs. The presentations provided evidence supporting production, purification, and characterization processes that enable GMP manufacturing of engineered ARMMs at scale. The use of standard unit operations and readily available starting materials support cost-efficient future manufacturability for clinical trials and commercialization. Presentation materials are available upon request. Vesigen Poster Presentations at ASGCT 2023: Wednesday, May 17 Targeted Delivery of Genome Editors Complexed with Guide RNA Using ARMMs for Non-Viral In Vivo Delivery (Abstract 498) ARRDC1-Mediated Microvesicles (ARMMs) as a Novel Non-Viral Modality for Efficient Functional Delivery of Adenine and Cytidine Base Editor Proteins Complexed with Guide RNA (Abstract 530; collaboration with the laboratory of David Liu, Ph.D., Broad Institute, Harvard University) ARMMs as a Versatile Non-Viral Delivery Platform for Therapeutic RNA Molecules (Abstract 560) Scalable Suspension Cell-Based Production and Purification of Engineered ARMMs as a Platform for Non-Viral Therapeutics (Abstract 561) Novel Approach for Fluorescent Labeling of Intraluminal Protein Payloads in ARMMs as a Model Extracellular Vesicle (Abstract 562; collaboration with NanoFCM) Thursday, May 18 Biodistribution of Engineered ARRDC1-Mediated Microvesicles for Delivery of Intracellular Payloads In Vivo (Abstract 909) Friday, May 19 Delivery of PMP22-targeting shRNA by ARMMs as A Disease-Modifying Therapeutic Approach for Charcot Marie Tooth 1A (Abstract 1307) Production, Purification and Characterization of Engineered ARRDC1-Mediated Microvesicles Using a Scalable Manufacturing Platform (Abstract 1321; collaboration with Lonza) About Vesigen Therapeutics Vesigen Therapeutics is a biotechnology company developing a novel, non-viral delivery technology for gene editing, RNA, and protein-based therapeutics. Vesigen’s patented technology, called ARMMs (ARRDC1 Mediated Microvesicles), can be used to precisely deliver a wide range of payloads to a unique set of tissue and cell types. Vesigen has demonstrated highly efficient in vitro and in vivo functional delivery of a range of payloads across multiple cell types and is committed to developing transformative medicines that address current unmet medical needs. ARMMs were discovered and engineered into a drug delivery system at the Harvard T.H. Chan School of Public Health. For additional information visit .

Winning projects will explore new potential treatment approaches to prevent lupus from developing or prevent or slow disease progression. NEW YORK, April 20, 2023 /PRNewswire/ -- The Lupus Research Alliance (LRA) today announced the newest Lupus Mechanisms and Targets Award grant recipients. The winning four projects collectively test potential treatment approaches to prevent lupus from developing or reducing lupus disease activity. Lupus has a broad range of causes and symptoms, and these multiple approaches are important for designing customized therapies that can provide better outcomes for a wide range of patients. The LRA LMTA grants offer up to $600,000 over three years for research focusing on investigating molecular pathways or targets leading to the development of new or improved therapies for patients with cutaneous and systemic lupus erythematosus (SLE). "These four new LMTA awards support innovative lupus researchers whose work is poised to deliver much needed new information for the lupus field. We are proud to be able to offer this financial support, with the ultimate goal of improving outcomes for lupus patients," said Teodora Staeva, Ph.D., vice president and chief scientific officer of LRA. Lupus Mechanisms and Targets Award Winners Jennifer Anolik, M.D., Ph.D.; University of Rochester Medical Center Dr. Anolik will investigate if sodium-glucose cotransporter-2 (SGLT2) inhibitors – a class of drugs approved to treat type 2 diabetes and associated kidney disease – can improve outcomes in lupus nephritis, which is inflammation in the kidneys caused by lupus that affects 40 to 70 percent of lupus patients. Current treatment approaches target inflammation with little impact on fibrosis and injury. Dr. Anolik will study mice with lupus nephritis to see if SGLT2 inhibitors reduce kidney hypoxia, inflammatory CD8 T cells, and kidney injury. She will also begin to investigate the effects of treatment with SGLT2i on clinical outcomes and pathogenic CD8 T cells in the blood and urine of patients with lupus nephritis. Betsy Barnes, Ph.D.; The Feinstein Institutes for Medical Research Systemic lupus erythematosus (SLE) has heritable components that can be passed on to children through gene variants. Variants in the interferon regulatory factor 5 (IRF5) gene, which controls the production of type I interferons, can be inherited, and they increase the risk of developing SLE. Dr. Barnes has recently identified a new regulator of IRF5 function– STK25 – that turns on IRF5 in SLE immune cells. Using this award, Dr. Barnes will compare STK25 activity in healthy people with and without IRF5 gene variants and in SLE patients. She will also aim to determine how STK25 activates IRF5 in response to SLE triggers and investigate if loss of the STK25 gene protects against lupus in lupus-prone mice, which will aid future clinical trials focused on targeting STK25 and/or IRF5 as new therapeutics. Michelle Kahlenberg, M.D., Ph.D.; University of Michigan Dr. Kahlenberg recently found that abnormal activity of Hippo proteins turns on the overproduction of immune system molecules (interferons) in lupus patients' blood and skin. Dr. Kahlenberg will use this award to study whether turning off these Hippo proteins will decrease the amount of type I interferons, one of the hallmarks of cutaneous lupus and SLE. Her investigation will determine if Hippo proteins could serve as new therapeutic targets. Dr. Kahlenberg's work builds on decades of pioneering studies on type I interferons funded by the LRA. Jillian Richmond, Ph.D.; University of Massachusetts Chan Medical School T cells are immune cells that can cause lupus flares in the skin. Dr. Richmond found that skin T cells in both people and mice have a protein on their cell surface called CXCR6. The T cell CXCR6 interacts with a protein called CXCL16 on skin cells, similar to how a lock and key fit together. Dr. Richmond will use this award to determine if the CXCL16-CXCR6 interaction is important in keeping the harmful T cells in the skin of patients with cutaneous lupus. She will also investigate if targeting these two molecules will provide a lasting treatment response in pet dogs with skin lupus through a veterinary clinical trial. This project could provide new information about the molecules on the surface of lupus-causing immune cells that could be targeted to prevent or slow lupus disease progression. About Lupus Lupus is a chronic, complex autoimmune disease that affects millions of people worldwide. More than 90 percent of people with lupus are women; lupus most often strikes during the childbearing years of 15-45. Black/African Americans, Hispanic/Latino, Asians, and Native Americans are two to three times at greater risk than Caucasians. In lupus, the immune system, which is designed to protect against infection, creates antibodies that can attack any part of the body including the kidneys, brain, heart, lungs, blood, skin, and joints. About the Lupus Research Alliance The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately a cure for lupus. Because the Lupus Research Alliance's Board of Directors funds all administrative and fundraising costs, 100% of all donations goes to support lupus research programs. SOURCE Lupus Research Alliance

Reports Full-Year Diluted EPS of $6.63 on a GAAP Basis, an Increase of 2.8 Percent; Adjusted Diluted EPS of $13.77 , an Increase of 16.4 Percent; These Results Include an Unfavorable Impact of $0.39 Per Share related to 2022 Acquired IPR&D and Milestones Expense 1 Delivers Full-Year Net Revenues of $58.054 Billion , an Increase of 3.3 Percent on a Reported Basis and 5.1 Percent on an Operational Basis Full-Year Global Net Revenues from the Immunology Portfolio Were $28.924 Billion , an Increase of 14.4 Percent on a Reported Basis, or 16.0 Percent on an Operational Basis; Global Humira Net Revenues Were $21.237 billion ; Global Skyrizi Net Revenues Were $5.165 Billion ; Global Rinvoq Net Revenues Were $2.522 Billion Full-Year Global Net Revenues from the Hematologic Oncology Portfolio Were $6.577 Billion , a Decrease of 9.0 Percent on a Reported Basis, or 7.6 Percent on an Operational Basis; Global Imbruvica Net Revenues Were $4.568 Billion ; Global Venclexta Net Revenues Were $2.009 Billion Full-Year Global Net Revenues from the Neuroscience Portfolio Were $6.528 Billion , an Increase of 10.1 Percent on a Reported Basis, or 11.6 Percent on an Operational Basis; Global Botox Therapeutic Net Revenues Were $2.719 Billion ; Global Vraylar Net Revenues Were $2.038 Billion Full-Year Global Net Revenues from the Aesthetics Portfolio Were $5.333 Billion , an Increase of 1.9 Percent on a Reported Basis, or 5.1 Percent on an Operational Basis; Global Botox Cosmetic Net Revenues Were $2.615 Billion ; Global Juvederm Net Revenues Were $1.428 Billion Reports Fourth-Quarter Diluted EPS of $1.38 on a GAAP Basis, a decrease of 38.9 Percent; Adjusted Diluted EPS of $3.60 , an increase of 16.9 Percent; These Results Include an Unfavorable Impact of $0.13 Per Share Related to Fourth-Quarter 2022 Acquired IPR&D and Milestones Expense Delivers Fourth-Quarter Net Revenues of $15.121 Billion , an Increase of 1.6 Percent on a Reported Basis and 3.8 Percent on an Operational Basis Provides 2023 Adjusted Diluted EPS Guidance Range of $10.70 to $11.10 , which Excludes Any Unfavorable Impact Related to Acquired IPR&D and Milestones Expense NORTH CHICAGO, Ill. , Feb. 9, 2023 /PRNewswire/ -- AbbVie (NYSE:ABBV) announced financial results for the fourth quarter and full year ended December 31, 2022 . "2022 was another highly productive year capping a decade of outstanding performance. Since our inception, we have built a diverse portfolio of growth products with significant leadership positions, developed a robust pipeline of innovative assets and created a culture of strong execution," said Richard A. Gonzalez , chairman and chief executive officer, AbbVie. "Looking forward, we have a solid foundation which will allow us to absorb the U.S. Humira loss of exclusivity, return to strong top-line growth in 2025 and drive top-tier financial performance over the long term." Note: "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year's foreign exchange rates. 1 Beginning in the first quarter 2022, AbbVie includes the impact of upfront and milestone payments related to collaborations, licensing agreements and other asset acquisitions in its reported non-GAAP financial measures. Fourth -Quarter Results Worldwide net revenues were $15.121 billion , an increase of 1.6 percent on a reported basis, or 3.8 percent on an operational basis. Global net revenues from the immunology portfolio were $7.925 billion , an increase of 17.5 percent on a reported basis, or 19.5 percent on an operational basis. Global Humira net revenues of $5.579 billion increased 4.6 percent on a reported, or 6.0 percent on an operational basis. U.S. Humira net revenues were $5.006 billion , an increase of 9.9 percent. Internationally, Humira net revenues were $573 million , a decrease of 26.5 percent on a reported basis, or 16.9 percent on an operational basis. Global Skyrizi net revenues were $1.576 billion , an increase of 76.1 percent on a reported basis, or 78.9 percent on an operational basis. Global Rinvoq net revenues were $770 million , an increase of 49.0 percent on a reported basis, or 55.4 percent on an operational basis. Global net revenues from the hematologic oncology portfolio were $1.631 billion , a decrease of 12.9 percent on a reported basis, or 11.2 percent on an operational basis. Global Imbruvica net revenues were $1.115 billion , a decrease of 19.5 percent, with U.S. net revenues of $841 million and international profit sharing of $274 million . Global Venclexta net revenues were $516 million , an increase of 5.7 percent on a reported basis, or 12.2 percent on an operational basis. Global net revenues from the neuroscience portfolio were $1.710 billion , an increase of 3.4 percent on a reported basis, or 5.1 percent on an operational basis. Global Botox Therapeutic net revenues were $728 million , an increase of 8.5 percent on a reported basis, or 10.7 percent on an operational basis. Global Vraylar net revenues were $565 million , an increase of 15.5 percent. Global Ubrelvy net revenues were $197 million , an increase of 7.7 percent. Global net revenues from the aesthetics portfolio were $1.287 billion , a decrease of 8.5 percent on a reported basis, or 4.2 percent on an operational basis. Global Botox Cosmetic net revenues were $642 million , an increase of 2.6 percent on a reported basis, or 7.1 percent on an operational basis. Global Juvederm net revenues were $322 million , a decrease of 25.4 percent on a reported basis, or 19.0 percent on an operational basis. On a GAAP basis, the gross margin ratio in the fourth quarter was 72.4 percent. The adjusted gross margin ratio was 86.0 percent. On a GAAP basis, selling, general and administrative (SG&A) expense was 22.6 percent of net revenues. The adjusted SG&A expense was 20.8 percent of net revenues. On a GAAP basis, research and development (R&D) expense was 11.8 percent of net revenues. The adjusted R&D expense was 11.5 percent of net revenues, reflecting funding actions supporting all stages of our pipeline. Acquired IPR&D and milestones expense was 1.6 percent of net revenues. On a GAAP basis, the operating margin in the fourth quarter was 36.4 percent. The adjusted operating margin was 52.1 percent. Net interest expense was $476 million . On a GAAP basis, the tax rate in the quarter was 16.6 percent. The adjusted tax rate was 13.4 percent. Diluted EPS in the fourth quarter was $1.38 on a GAAP basis. Adjusted diluted EPS, excluding specified items, was $3.60 . These results include an unfavorable impact of $0.13 per share related to acquired IPR&D and milestones expense. Note: "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year's foreign exchange rates. Recent Events AbbVie announced the European Commission (EC) approved Skyrizi (risankizumab, 600 mg intravenous induction and 360 mg subcutaneous maintenance therapy) as the first specific interleukin-23 (IL-23) inhibitor for the treatment of adults with moderately to severely active Crohn's disease (CD) who have had inadequate response, lost response or were intolerant to conventional or biologic therapy. The approval is supported by results from three Phase 3 studies in which Skyrizi demonstrated significant improvement in clinical remission and endoscopic response, compared to placebo, as both induction and maintenance therapy. This approval marks the third indication for Skyrizi in the European Union (EU). Skyrizi is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally. At the American College of Rheumatology's (ACR) annual meeting, AbbVie shared 36 abstracts that underscore AbbVie's commitment to advancing research to help more people living with rheumatic diseases. Analyses presented showcased data from the clinical trial programs evaluating Rinvoq (upadacitinib) for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (AS) as well as data evaluating Skyrizi for the treatment of psoriasis (PsO) and PsA. AbbVie announced that the U.S. Food and Drug Administration (FDA) accepted, for priority review, the Biologics License Application (BLA) for epcoritamab, an investigational subcutaneous bispecific antibody for the treatment of adult patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Additionally, AbbVie announced the European Medicines Agency (EMA) validated AbbVie's Marketing Authorization Application (MAA) for epcoritamab for the treatment of adult patients with r/r diffuse LBCL. Both applications are supported by data from the EPCORE NHL-1 Phase 2 trial evaluating the safety and preliminary efficacy of subcutaneous epcoritamab in adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (NHL). Epcoritamab is being co-developed by Genmab and AbbVie. At the American Society of Hematology (ASH) Annual Meeting, AbbVie presented results from nearly 65 abstracts, including 15 oral presentations, across eight types of cancer. Highlights included four oral presentations evaluating investigational epcoritamab for the treatment of r/r follicular lymphoma (FL), previously untreated FL, r/r diffuse LBCL as well as Richter's syndrome; data from cohort three of the Phase 2 REFINE study evaluating navitoclax in combination with ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (MF); data from the Phase 2 CAPTIVATE and Phase 3 GLOW studies evaluating fixed-duration treatment in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) who received the Imbruvica (ibrutinib) + Venclexta (venetoclax) combination regimen. AbbVie also presented multiple abstracts evaluating Venclexta in approved CLL and acute myeloid leukemia (AML) indications and the investigational multiple myeloma (MM) indication. Imbruvica is jointly developed and commercialized with Janssen Biotech, Inc. Venetoclax is being developed by AbbVie and Roche and is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. AbbVie announced that the FDA approved Vraylar (cariprazine) as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults. The approval marks the fourth indication for Vraylar, which is now the first and only dopamine and serotonin partial agonist FDA-approved for the most common forms of depression – as an adjunctive treatment for MDD and the treatment of depressive episodes associated with bipolar I disorder. The approval is supported by clinical data demonstrating the efficacy and well-established tolerability of Vraylar as an adjunctive treatment for MDD with an antidepressant therapy. Vraylar is being co-developed by AbbVie and Gedeon Richter Plc. At the European Headache Federation Congress (EHC) 2022, AbbVie shared 15 abstracts which underscore its commitment to people living with migraine. Presentations highlighted late-breaking data from the Chronic Migraine Epidemiology and Outcomes - International (CaMEO-I) study, evaluating the frequency and burden of neck pain with headache among people with and without migraine, as well as results from the Phase 3 PROGRESS trial evaluating Qulipta (atogepant) for the preventive treatment of chronic migraine (CM) in patients living in Europe . AbbVie announced new results from its exploratory NOVA phase 2 dose-ranging study evaluating the efficacy and safety of AGN-151607, a novel investigational neurotoxin for the prevention of postoperative atrial fibrillation (POAF) in cardiac surgery patients, at the American Heart Association Scientific Sessions meeting. The study's primary endpoint was not met for the modified intent-to-treat (mITT) population; however, the data showed relative risk reduction in specific study populations such as coronary artery bypass graft (CABG) patients and patients aged 65 years and older, as well as overall lower rates of rehospitalization within 30 days compared to placebo. Adverse Events (AEs) were numerically similar across all treatment groups. AbbVie and HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of small molecule allosteric therapies for the treatment of cancer and autoimmune diseases, announced an exclusive worldwide collaboration and option to license agreement for HotSpot's discovery-stage interferon regulatory factor 5 (IRF5) inhibitor program for the potential treatment of autoimmune diseases. AbbVie and Immunome, a clinical-stage biopharmaceutical company that utilizes its human memory B cell platform to discover and develop first-in-class antibody therapeutics, announced a worldwide collaboration and option agreement directed to the discovery of up to 10 novel antibody-target pairs arising from three specified tumor types using Immunome's Discovery Engine. AbbVie and Anima Biotech, announced a collaboration to discover and develop mRNA biology modulators for three targets across Immunology and Oncology. Anima will use its mRNA Lightning platform to discover novel mRNA biology modulators against the collaboration targets providing AbbVie exclusive rights to license and further develop and commercialize the programs. Full-Year 2023 Outlook AbbVie is issuing its adjusted diluted EPS guidance for the full-year 2023 of $10.70 to $11.10 . The company's 2023 adjusted diluted EPS guidance excludes any impact from acquired IPR&D and milestones that may be incurred during 2023, as both cannot be reliably forecasted. About AbbVie AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, and gastroenterology, in addition to products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com . Follow @abbvie on Twitter, Facebook or LinkedIn . Conference Call AbbVie will host an investor conference call today at 8:00 a.m. Central time to discuss our fourth-quarter performance. The call will be webcast through AbbVie's Investor Relations website at investors.abbvie.com . An archived edition of the call will be available after 11:00 a.m. Central time . Non-GAAP Financial Results Financial results for 2022 and 2021 are presented on both a reported and a non-GAAP basis. Reported results were prepared in accordance with GAAP and include all revenue and expenses recognized during the period. Non-GAAP results adjust for certain non-cash items and for factors that are unusual or unpredictable, and exclude those costs, expenses, and other specified items presented in the reconciliation tables later in this release. Beginning in the first quarter of 2022, the company includes the impact of upfront and milestone payments related to collaborations, licensing agreements, and other asset acquisitions in its reported non-GAAP financial measures. Prior periods have been revised to conform to the current period presentation. AbbVie's management believes non-GAAP financial measures provide useful information to investors regarding AbbVie's results of operations and assist management, analysts, and investors in evaluating the performance of the business. Non-GAAP financial measures should be considered in addition to, and not as a substitute for, measures of financial performance prepared in accordance with GAAP. Forward-Looking Statements Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2021 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its Quarterly Reports on Form 10-Q and in other documents that AbbVie subsequently files with the Securities and Exchange Commission that update, supplement or supersede such information. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. AbbVie Inc. Key Product Revenues Quarter Ended December 31, 2022 (Unaudited) % Change vs. 4Q21 Net Revenues (in millions) Reported Operational a U.S. Int'l. Total U.S. Int'l. Total Int'l. Total NET REVENUES $  12,192 $  2,929 $  15,121 4.4 % (8.7) % 1.6 % 1.8 % 3.8 % Immunology 6,975 950 7,925 22.5 (9.5) 17.5 3.2 19.5 Humira 5,006 573 5,579 9.9 (26.5) 4.6 (16.9) 6.0 Skyrizi 1,403 173 1,576 84.3 29.1 76.1 47.9 78.9 Rinvoq 566 204 770 48.6 50.1 49.0 74.5 55.4 Hematologic Oncology 1,110 521 1,631 (18.7) 2.6 (12.9) 8.8 (11.2) Imbruvica b 841 274 1,115 (24.6) 1.6 (19.5) 1.6 (19.5) Venclexta 269 247 516 7.7 3.7 5.7 17.0 12.2 Aesthetics 835 452 1,287 (4.7) (14.8) (8.5) (3.4) (4.2) Botox Cosmetic 422 220 642 6.4 (4.0) 2.6 8.3 7.1 Juvederm Collection 128 194 322 (28.3) (23.3) (25.4) (12.4) (19.0) Other Aesthetics 285 38 323 (5.3) (21.4) (7.6) (11.7) (6.2) Neuroscience 1,506 204 1,710 4.7 (5.7) 3.4 7.2 5.1 Botox Therapeutic 614 114 728 9.6 2.8 8.5 16.2 10.7 Vraylar 564 1 565 15.4 n/m 15.5 n/m 15.5 Duodopa 23 84 107 (18.3) (15.8) (16.3) (3.2) (6.5) Ubrelvy 197 — 197 7.5 n/m 7.7 n/m 7.7 Qulipta 52 — 52 >100.0 n/m >100.0 n/m >100.0 Other Neuroscience 56 5 61 (66.2) (8.8) (64.5) (1.1) (64.3) Eye Care 338 252 590 (49.7) (12.4) (38.5) (1.3) (35.2) Lumigan/Ganfort 56 67 123 (22.1) (13.0) (17.4) (3.3) (12.4) Alphagan/Combigan 41 33 74 (59.4) (16.2) (47.4) (4.5) (44.1) Restasis 103 7 110 (70.5) (49.0) (69.6) (45.0) (69.4) Other Eye Care 138 145 283 (7.7) (7.8) (7.7) 4.5 (1.4) Other Key Products 791 195 986 (1.5) (18.4) (5.4) (6.2) (2.6) Mavyret 193 187 380 (1.8) (18.8) (11.0) (6.5) (4.4) Creon 337 — 337 3.0 n/m 3.0 n/m 3.0 Linzess/Constella 261 8 269 (6.5) (7.5) (6.6) 2.2 (6.3) a "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year's foreign exchange rates. b Reflects profit sharing for Imbruvica international revenues. n/m = not meaningful AbbVie Inc. Key Product Revenues Twelve Months Ended December 31, 2022 (Unaudited) % Change vs. 12M21 Net Revenues (in millions) Reported Operational a U.S. Int'l. Total U.S. Int'l. Total Int'l. Total NET REVENUES $  45,713 $  12,341 $  58,054 5.1 % (2.7) % 3.3 % 5.5 % 5.1 % Immunology 24,897 4,027 28,924 18.1 (4.0) 14.4 5.7 16.0 Humira 18,619 2,618 21,237 7.4 (22.2) 2.6 (14.9) 3.8 Skyrizi 4,484 681 5,165 80.4 50.4 75.7 67.1 78.3 Rinvoq 1,794 728 2,522 41.2 91.4 52.8 >100.0 58.1 Hematologic Oncology 4,435 2,142 6,577 (15.6) 8.6 (9.0) 13.9 (7.6) Imbruvica b 3,426 1,142 4,568 (20.7) 5.1 (15.5) 5.1 (15.5) Venclexta 1,009 1,000 2,009 8.0 12.9 10.4 24.6 16.1 Aesthetics 3,324 2,009 5,333 (0.8) 6.7 1.9 15.6 5.1 Botox Cosmetic 1,654 961 2,615 16.2 18.9 17.2 28.8 20.8 Juvederm Collection 548 880 1,428 (16.7) 0.3 (7.0) 8.9 (2.1) Other Aesthetics 1,122 168 1,290 (11.5) (14.9) (12.0) (8.3) (11.1) Neuroscience 5,681 847 6,528 12.3 (2.3) 10.1 7.7 11.6 Botox Therapeutic 2,255 464 2,719 12.1 5.6 10.9 15.3 12.6 Vraylar 2,037 1 2,038 17.9 n/m 17.9 n/m 17.9 Duodopa 95 363 458 (6.7) (11.3) (10.4) (0.8) (2.0) Ubrelvy 680 — 680 23.2 n/m 23.3 n/m 23.3 Qulipta 158 — 158 >100.0 n/m >100.0 n/m >100.0 Other Neuroscience 456 19 475 (30.5) 4.8 (29.6) 9.0 (29.5) Eye Care 1,603 1,098 2,701 (33.3) (5.7) (24.3) 3.7 (21.2) Lumigan/Ganfort 242 272 514 (11.0) (11.3) (11.2) (3.0) (6.8) Alphagan/Combigan 202 144 346 (45.8) (7.9) (34.6) 2.5 (31.5) Restasis 621 45 666 (49.6) (20.2) (48.3) (13.8) (48.0) Other Eye Care 538 637 1,175 2.3 (1.2) 0.4 8.7 5.9 Other Key Products 3,036 818 3,854 2.9 (17.2) (2.2) (7.9) 0.1 Mavyret 755 786 1,541 0.2 (17.8) (9.9) (8.5) (4.7) Creon 1,278 — 1,278 7.3 n/m 7.3 n/m 7.3 Linzess/Constella 1,003 32 1,035 (0.4) 0.3 (0.3) 7.6 (0.1) a "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year's foreign exchange rates. b Reflects profit sharing for Imbruvica international revenues. n/m = not meaningful AbbVie Inc. Consolidated Statements of Earnings (Unaudited) (in millions, except per share data) Fourth Quarter Ended December 31 Twelve Months Ended December 31 2022 2021 2022 2021 Net revenues $       15,121 $       14,886 $       58,054 $       56,197 Cost of products sold 4,170 4,320 17,414 17,446 Selling, general and administrative 3,417 3,260 15,260 12,349 Research and development a 1,790 1,827 6,510 6,922 Acquired IPR&D and milestones a 243 405 697 1,124 Other operating (income) expense, net (1) — 56 432 Total operating costs and expenses 9,619 9,812 39,937 38,273 Operating earnings 5,502 5,074 18,117 17,924 Interest expense, net 476 571 2,044 2,384 Net foreign exchange loss 40 16 148 51 Other expense, net 2,021 216 2,448 2,500 Earnings before income tax expense 2,965 4,271 13,477 12,989 Income tax expense 493 226 1,632 1,440 Net earnings 2,472 4,045 11,845 11,549 Net earnings (loss) attributable to noncontrolling interest (1) 1 9 7 Net earnings attributable to AbbVie Inc. $          2,473 $          4,044 $        11,836 $        11,542 Diluted earnings per share attributable to AbbVie Inc. $            1.38 $            2.26 $            6.63 $            6.45 Adjusted diluted earnings per share b $            3.60 $            3.08 $          13.77 $          11.83 Weighted-average diluted shares outstanding 1,778 1,778 1,778 1,777 a During the three months ended March 31, 2022, AbbVie changed its classification of development milestone expense associated with licensing and collaboration arrangements in the consolidated statement of earnings. Milestone payments incurred prior to regulatory approval, which were previously included in research and development expense, are now presented as acquired IPR&D and milestones expense. The reclassification decreased research and development expense and increased acquired IPR&D and milestones expense by $162 million for the twelve months ended December 31, 2021 and had no impact on the three months ended December 31, 2021. The company believes this presentation assists users of the financial statements to better understand the total upfront and subsequent development milestone payments incurred to acquire in-process research and development projects. Prior periods have been revised to conform to the current period presentation. The reclassification had no impact on total operating costs and expenses, operating earnings, net earnings, net earnings attributable to AbbVie, Inc., earnings per share, or total equity. b Refer to the Reconciliation of GAAP Reported to Non-GAAP Adjusted Information for further details. Weighted-average diluted shares outstanding includes the effect of dilutive securities. AbbVie Inc. Reconciliation of GAAP Reported to Non-GAAP Adjusted Information (Unaudited) 1.     Specified items impacted results as follows: Quarter Ended December 31, 2022 (in millions, except per share data) Earnings Diluted Pre-tax After-tax a EPS As reported (GAAP) $              2,965 $              2,473 $                1.38 Adjusted for specified items: Intangible asset amortization 1,961 1,636 0.92 Acquisition and integration costs 215 199 0.11 Change in fair value of contingent consideration 2,114 2,113 1.19 Income tax items — (143) (0.08) Other 157 144 0.08 As adjusted (non-GAAP) $              7,412 $              6,422 $                3.60 a Represents net earnings attributable to AbbVie Inc. Acquisition and integration costs primarily include costs related to the Allergan acquisition. Income tax items include a benefit of $323 million related to tax law changes partially offset by certain other tax related items. Other primarily includes restructuring charges associated with streamlining global operations. Beginning in the first quarter of 2022, the company includes acquired IPR&D and milestones expense in its reported non-GAAP financial measures. Reported GAAP earnings and adjusted non-GAAP earnings for the three months ended December 31, 2022 included acquired IPR&D and milestones expense of $243 million on a pre-tax and after-tax basis, representing an unfavorable impact of $0.13 to both diluted EPS and adjusted diluted EPS. 2.     The impact of the specified items by line item was as follows: Quarter Ended December 31, 2022 (in millions) Cost of products sold SG&A R&D Other operating income, net Other expense, net As reported (GAAP) $      4,170 $      3,417 $            1,790 $                   (1) $           2,021 Adjusted for specified items: Intangible asset amortization (1,961) — — — — Acquisition and integration costs 1 (205) (11) — — Change in fair value of contingent consideration — — — — (2,114) Other (99) (62) (38) 1 41 As adjusted (non-GAAP) $      2,111 $      3,150 $             1,741 $                  — $              (52) 3.     The adjusted tax rate for the fourth quarter of 2022 was 13.4 percent, as detailed below: Quarter Ended December 31, 2022 (dollars in millions) Pre-tax earnings Income taxes Tax rate As reported (GAAP) $             2,965 $                493 16.6 % Specified items 4,447 498 11.2 % As adjusted (non-GAAP) $             7,412 $                991 13.4 % AbbVie Inc. Reconciliation of GAAP Reported to Non-GAAP Adjusted Information (Unaudited) 1.     Specified items impacted results as follows: Quarter Ended December 31, 2021 (in millions, except per share data) Earnings Diluted Pre-tax After-tax a EPS As reported (GAAP) $              4,271 $              4,044 $                2.26 Adjusted for specified items: Intangible asset amortization 1,806 1,490 0.84 Acquisition and integration costs (191) (212) (0.12) Change in fair value of contingent consideration 232 232 0.13 Litigation matters 200 167 0.09 Impacts related to tax law changes — (265) (0.15) Other 41 58 0.03 As adjusted (non-GAAP) $              6,359 $              5,514 $                3.08 a Represents net earnings attributable to AbbVie Inc. Acquisition and integration costs reflect a recovery of certain Allergan acquisition-related regulatory fees partially offset by Allergan-related integration costs and Soliton acquisition costs. Other primarily includes COVID-19 related expenses and certain tax related items. Beginning in the first quarter of 2022, the company includes acquired IPR&D and milestones expense in its reportednon-GAAP financial measures. Reported GAAP earnings and adjusted non-GAAP earnings for the three months ended December 31, 2021 included acquired IPR&D and milestones expense of $405 million on a pre-tax and after-tax basis, representing an unfavorable impact of $0.23 to both diluted EPS and adjusted diluted EPS. 2.     The impact of the specified items by line item was as follows: Quarter Ended December 31, 2021 (in millions) Cost of products sold SG&A R&D Other expense, net As reported (GAAP) $    4,320 $             3,260 $             1,827 $              216 Adjusted for specified items: Intangible asset amortization (1,806) — — — Acquisition and integration costs (43) 250 (16) — Change in fair value of contingent consideration — — — (232) Litigation matters — (200) — — Other (23) (3) (13) (2) As adjusted (non-GAAP) $    2,448 $             3,307 $             1,798 $               (18) 3.     The adjusted tax rate for the fourth quarter of 2021 was 13.3 percent, as detailed below: Quarter Ended December 31, 2021 (dollars in millions) Pre-tax earnings Income taxes Tax rate As reported (GAAP) $             4,271 $                226 5.3 % Specified items 2,088 618 29.6 % As adjusted (non-GAAP) $             6,359 $                844 13.3 % AbbVie Inc. Reconciliation of GAAP Reported to Non-GAAP Adjusted Information (Unaudited) 1.     Specified items impacted results as follows: Twelve Months Ended December 31, 2022 (in millions, except per share data) Earnings Diluted Pre-tax After-tax a EPS As reported (GAAP) $           13,477 $          11,836 $                6.63 Adjusted for specified items: Intangible asset amortization 7,689 6,430 3.61 Intangible asset impairment 770 604 0.34 Acquisition and integration costs 810 766 0.43 Change in fair value of contingent consideration 2,761 2,770 1.55 Pylera divestiture (172) (126) (0.07) Litigation matters 2,506 2,028 1.13 Income tax items — (26) (0.02) Other 429 315 0.17 As adjusted (non-GAAP) $           28,270 $          24,597 $              13.77 a Represents net earnings attributable to AbbVie Inc. Acquisition and integration costs primarily include costs related to the Allergan acquisition. Litigation matters primarily include a charge related to a potential settlement of litigation involving Allergan's past sales of opioid products. Income tax items include a benefit of $323 million related to tax law changes partially offset by certain other tax related items. Other primarily includes restructuring charges associated with streamlining global operations. Beginning in the first quarter of 2022, the company includes acquired IPR&D and milestones expense in its reported non-GAAP financial measures. Reported GAAP earnings and adjusted non-GAAP earnings for the twelve months ended December 31, 2022 included acquired IPR&D and milestones expense of $697 million on a pre-tax and $682 million on an after-tax basis, representing an unfavorable impact of $0.39 to both diluted EPS and adjusted diluted EPS. 2.     The impact of the specified items by line item was as follows: Twelve Months Ended December 31, 2022 (in millions) Cost of products sold SG&A R&D Other operating expense, net Other expense, net As reported (GAAP) $      17,414 $    15,260 $             6,510 $                  56 $           2,448 Adjusted for specified items: Intangible asset amortization (7,689) — — — — Intangible asset impairment (770) — — — — Acquisition and integration costs (83) (468) (30) (229) — Change in fair value of contingent consideration — — — — (2,761) Pylera divestiture — — — 172 — Litigation matters — (2,506) — — — Other (259) (160) (45) 1 34 As adjusted (non-GAAP) $        8,613 $    12,126 $             6,435 $                  — $             (279) 3.     The adjusted tax rate for the full-year 2022 was 13.0 percent, as detailed below: Twelve Months Ended December 31, 2022 (dollars in millions) Pre-tax earnings Income taxes Tax rate As reported (GAAP) $           13,477 $             1,632 12.1 % Specified items 14,793 2,032 13.7 % As adjusted (non-GAAP) $           28,270 $             3,664 13.0 % AbbVie Inc. Reconciliation of GAAP Reported to Non-GAAP Adjusted Information (Unaudited) 1.     Specified items impacted results as follows: Twelve Months Ended December 31, 2021 (in millions, except per share data) Earnings Diluted Pre-tax After-tax a EPS As reported (GAAP) $           12,989 $           11,542 $                6.45 Adjusted for specified items: Intangible asset amortization 7,718 6,419 3.60 Acquisition and integration costs 344 215 0.12 Change in fair value of contingent consideration 2,679 2,677 1.50 Litigation matters 307 253 0.14 Impacts related to tax law changes — (265) (0.15) Other 360 313 0.17 As adjusted (non-GAAP) $           24,397 $           21,154 $              11.83 a Represents net earnings attributable to AbbVie Inc. Acquisition and integration costs reflect Allergan integration costs, Soliton acquisition costs as well as amortization of the acquisition date fair value step-up for inventory related to the Allergan acquisition partially offset by a recovery of certain Allergan acquisition-related regulatory fees. Other primarily includes the purchase of FDA priority review vouchers from third parties, COVID-19 related expenses, restructuring charges associated with streamlining global operations and certain tax related items. Beginning in the first quarter of 2022, the company includes acquired IPR&D and milestones expense in its reported non-GAAP financial measures. Reported GAAP earnings and adjusted non-GAAP earnings for the twelve months ended December 31, 2021 included acquired IPR&D and milestones expense of $1.1 billion on a pre-tax and after-tax basis, as well as other operating expense related to the Calico collaboration of $500 million on a pre-tax and after-tax basis, representing an unfavorable impact of $0.90 to both diluted EPS and adjusted diluted EPS. 2.     The impact of the specified items by line item was as follows: Twelve Months Ended December 31, 2021 (in millions) Cost of products sold SG&A R&D Other operating expense, net Other expense, net As reported (GAAP) $    17,446 $    12,349 $             6,922 $               432 $            2,500 Adjusted for specified items: Intangible asset amortization (7,718) — — — — Acquisition and integration costs (215) (25) (104) — — Change in fair value of contingent consideration — — — — (2,679) Litigation matters — (307) — — — Other (88) (53) (300) 68 13 As adjusted (non-GAAP) $      9,425 $    11,964 $             6,518 $               500 $              (166) 3.     The adjusted tax rate for the full-year 2021 was 13.3 percent, as detailed below: Twelve Months Ended December 31, 2021 (dollars in millions) Pre-tax earnings Income taxes Tax rate As reported (GAAP) $           12,989 $            1,440 11.1 % Specified items 11,408 1,796 15.8 % As adjusted (non-GAAP) $           24,397 $            3,236 13.3 % SOURCE AbbVie