Mat2A

Targeting two independent Phase 2 clinical efficacy updates for darovasertib in neoadjuvant uveal melanoma (UM) in mid-2024, including from the Phase 2 IST and Phase 2 company-sponsored study Targeting FDA regulatory guidance on darovasertib in neoadjuvant UM indication in 2024 Ongoing enrollment of IDE397 and AMG 193 Phase 1 combo in MTAP solid tumors and targeting development of joint Amgen / IDEAYA publication strategy in 2024 Established clinical study collaboration with Gilead Sciences to evaluate IDE397 and Trodelvy® combo in MTAP bladder cancer with FPI targeted for mid-year 2024 Targeting IDE161 clinical program update(s) and enabling of clinical combination(s) in 2024 Targeting Werner IND-filing in 2024 ($7.0 million milestone upon IND clearance) in collaboration with GSK Targeting multiple wholly-owned next generation development candidate nominations in 2024, including in MTAP, representing 7 or more potential first-in-class programs $632.6 million cash balance as of December 31, 2023, supplemented by net proceeds of $342.3 million from January 2024 ATM offerings, expected to fund operations into 2028 SOUTH SAN FRANCISCO, Calif., Feb. 20, 2024 /PRNewswire/ -- IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, provided a business update and announced financial results for the quarter and full-year ended December 31, 2023. "We believe the ongoing clinical advancement of darovasertib in neoadjuvant Uveal Melanoma, IDE397 and AMG 193 clinical combination in MTAP solid tumors, and IDE161 and GSK101 both in HRD solid tumors, represent important clinical initiatives for IDEAYA in 2024 as potential first-in-class opportunities that address high unmet medical needs. Next, we are targeting this year the Werner IND-filing and multiple development candidate nominations, including in MTAP, representing 7 or more potential first-in-class programs and further advancing our vision to build a leading precision medicine oncology company," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences. "We have seen compelling results from our Phase 2 darovasertib and crizotinib program in patients with MUM and are targeting two clinical efficacy updates from our Phase 2 company sponsored neoadjuvant UM study and Phase 2 IST in mid-year 2024. Our IDE397 program trials remain on track, and we established a new clinical trial collaboration with Gilead Sciences to evaluate IDE397 in combination with Trodelvy® in patients with bladder cancer, with trial initiation activities now underway. Additionally, IND-enabling studies of the Werner helicase inhibitor for microsatellite instability (MSI)-high cancers are progressing well, further expanding our pipeline of first-in-class precision medicine candidates." added Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences. Recent Key Developments Reported top-line results of darovasertib and crizotinib combination demonstrating evidence of superior clinical efficacy in any-line and first-line MUM patients compared to standard of care as a Proffered Paper oral presentation at the 2023 European Society for Medical Oncology's Congress (ESMO). Expanded Phase 2 trial evaluating the darovasertib and crizotinib combination in GNAQ/11 metastatic cutaneous melanoma based on preliminary clinical efficacy observed. Selected Werner helicase inhibitor development candidate and progressing IND-enabling GLP studies in collaboration with GSK; received $3.0 million milestone and eligible to receive $17.0 million aggregate milestones payments through early Phase 1 clinical studies, including $7.0 million upon investigational new drug (IND) clearance. IDEAYA is also eligible to receive future aggregate development milestones of up to $465.0 million and commercial milestones of up to $475.0 million and 50% of U.S. net profits. Established clinical study collaboration with Gilead Sciences to evaluate IDE397 and Trodelvy® combination in MTAP-deletion bladder cancer. Significantly expanded balance sheet Raised gross proceeds of approximately $352.0 million in January 2024 through at-the-market offerings. Raised gross proceeds of approximately $143.7 million in October 2023 through a follow-on public offering. Hosted an R&D Investor Day in December 2023 showcasing the synthetic lethality pipeline, including IDE397 in Phase 2, IDE161 in Phase 1, GSK101/IDE705 in Phase 1, and the Werner Helicase program, as well as its next generation initiatives for MTAP-deletion. Clinical Programs Update and Upcoming Milestones Darovasertib Program in Tumors with GNAQ or GNA11 Mutations Darovasertib is a potent and selective protein kinase C (PKC) inhibitor for which the Company owns the worldwide commercial rights, subject to certain economic obligations pursuant to its exclusive, worldwide license with Novartis. IDEAYA is developing darovasertib to broadly address primary and metastatic UM. Darovasertib is currently being evaluated in four ongoing clinical trials, three of which are in collaboration with Pfizer. The darovasertib + crizotinib combination in MUM has U.S. Food & Drug Administration (FDA) Fast Track designation. IDE196-002: Phase 2/3 Potential Registration-Enabling Clinical Trial of Darovasertib + Crizotinib combination in First-Line HLA-A2*02:01(-) MUM This study (NCT05987332) has an accelerated approval trial design and international site activation, and double-digit patient enrollment has been achieved to date. The company has several clinical sites open and is targeting to open an aggregate of over 50 clinical sites across U.S., Canada, Europe and Australia to support this registrational study. Clinical program update(s) are anticipated in 2024. IDE196-001: Phase 1/2 Clinical Trial Evaluating Darovasertib + Crizotinib Combination in MUM A clinical update of preliminary data from 20 evaluable first-line and 63 evaluable any-line patients from the study (NCT03947385) at the expansion dose of 300 mg twice-a-day darovasertib and 200 mg twice-a-day crizotinib was presented at ESMO 2023. Darovasertib and crizotinib combination treatment demonstrated evidence of superior clinical efficacy in any-line and first-line compared to standard of care. The detailed results can be found here. Phase 2 Clinical Trial Evaluating Darovasertib Combination in Cutaneous Melanoma Based on the Cancer Genome Atlas, about 5% of patients with cutaneous melanoma harbor the GNAQ/11 mutation. Therefore, the annual incidence is estimated to be 5,000 patients in the U.S. and 8,000 patients in the EU-28, and the estimated total prevalence of GNAQ/11 cutaneous melanoma is approximately 70,000 patients in the U.S. and 110,000 patients in the EU-28. There are currently no FDA approved therapies in this genetically-defined GNAQ/11 cutaneous melanoma patient population. Hence, GNAQ/11 metastatic cutaneous melanoma presents a potentially significant expansion opportunity for darovasertib, reflecting approximately double or more of the annual addressable metastatic patient population of metastatic uveal melanoma alone, especially given that GNAQ/11 is available on multiple next-generation sequencing and liquid biopsy platforms, enabling patient identification. Along with other available data and IDEAYA's strategic priority to broaden its darovasertib program to the multiple solid tumor setting, in October 2023, the Company expanded its Phase 2 expansion of the darovasertib and crizotinib combination in metastatic cutaneous melanoma. The expansion was based on preliminary clinical activity observed in three cohorts of patients treated with darovasertib, either as monotherapy or in combination with either binimetinib or crizotinib. The detailed results were reported in October 2023 and can be found here. Phase 1 and 2 Trials Darovasertib as Neoadjuvant / Adjuvant Therapy in Primary UM Darovasertib is being evaluated as monotherapy in two clinical trials as neoadjuvant / adjuvant therapy: IDE196-009: a company-sponsored Phase 2 trial (NCT05907954) evaluating darovasertib as neoadjuvant treatment of UM prior to primary interventional treatment of enucleation or radiation therapy, and as adjuvant therapy following the primary treatment. Phase 1 Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma, or NADOM: an investigator-sponsored trial (IST) Phase 1 study (NCT05187884). The study is being led by Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent's Hospital in Sydney with additional participating sites in Melbourne, Australia. The clinical objectives of neoadjuvant therapy are to save the eye by avoiding enucleation and/or to reduce the tumor thickness in the eye, enabling treatment with less radiation to preserve vision. As an adjuvant therapy, a clinical goal is to potentially extend relapse free survival. Preliminary clinical data of darovasertib as neoadjuvant treatment showed evidence of anti-tumor activity and supported further clinical evaluation of darovasertib to determine its potential as a neoadjuvant therapy or an adjuvant therapy. As of February 1, 2024, double digit patients have been dosed with several sites open and actively recruiting additional patients into the company-sponsored Phase 2 clinical trial. Two independent clinical efficacy updates for darovasertib in neoadjuvant UM are anticipated in mid-2024, including from the Phase 2 IST study and IDEAYA's Phase 2 company-sponsored study. A regulatory guidance update is planned in 2024. In preliminary results from the Phase 1 NADOM trial darovasertib demonstrated eye preservation in 3 of 6 (50%) evaluable patients treated with darovasertib as neoadjuvant therapy for primary UM. The detailed results can be found here. IDE397 Program in Solid Tumors and Bladder Cancer with MTAP Deletion IDE397 is a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2 alpha (MAT2A) in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion. MTAP deletion is found in 15% of solid tumors and is estimated to have annual incidence of greater than 50,000 patients in the US, EU5 and Japan across priority solid tumor types of non-small cell lung cancer (NSCLC), bladder, gastric, and esophageal cancers. The Company is focused on evaluating IDE397 in select monotherapy indications and in high conviction clinical combinations with AMG 193, Amgen's investigational MTA-cooperative PRMT5 inhibitor, and in combination with Gilead's Trop-2 directed antibody-drug conjugate (ADC) Trodelvy (Sacituzumab-govitecan-hziy). IDEAYA owns all rights, title, and interest in and to the IDE397 and MAT2A program, including all worldwide commercial rights thereto. IDE397-001: Phase 2 IDE397 Monotherapy Expansion in MTAP-Deletion NSCLC and Bladder Cancer The Company-sponsored IDE397 monotherapy Phase 2 expansion trial (NCT04794699) is continuing to enroll patients with MTAP-deletion squamous NSCLC and bladder cancers. Preliminary clinical data demonstrated responses in multiple MTAP-deletion high-priority tumor types based on experience across several patients in the early phase of the monotherapy dose expansion: RECIST 1.1 compete response in a bladder cancer patient and a 33% tumor reduction in squamous NSCLC patient as measured by CT-PET. Multiple ctDNA molecular responses were observed in NSCLC and bladder cancer patients. Low rates of discontinuations and serious adverse events (SAEs) were observed. As of October 13, 2023: 8 patients have been dosed in the IDE397 monotherapy expansion in the priority tumor types, and 2 patients have not yet had a first tumor scan assessment. Phase 1/2 trial of IDE397 + AMG 193 in MTAP-Deletion NSCLC Enrollment is ongoing in the dose escalation portion of the Amgen-sponsored Phase 1/2 trial (NCT05975073) evaluating IDE397 and AMG 193 (PRMT5MTA)) combination in patients with MTAP-deletion solid tumors. Additionally, in 2024, the Company will develop a joint publication strategy with Amgen. Phase 1 trial of IDE397 + Trodelvy in MTAP-Deletion Bladder Cancer The Company-sponsored Phase 1 (NCT04794699) in patients with MTAP-deletion bladder cancer will evaluate IDE397 in combination with Trodelvy, a Trop-2 directed ADC which is currently approved in the U.S. for the treatment of HR+/HER2- metastatic breast cancer, metastatic triple-negative breast cancer and metastatic urothelial cancer. Trial initiation activities are under way and the first-patient-in is anticipated in mid-2024. IDE161 Program in Tumors with Homologous Recombination Deficiency IDE161 is a potential first-in-class inhibitor of poly(ADP-ribose) glycohydrolase (PARG), a novel, mechanistically distinct target in the same clinically validated biological pathway as poly(ADP-ribose) polymerase (PARP). IDEAYA owns or controls all commercial rights to IDE161 and its PARG program, subject to certain economic obligations pursuant to its exclusive, worldwide license with Cancer Research UK and University of Manchester. IDE161 received two FDA Fast Track designations in platinum-resistant advanced or metastatic ovarian cancer patients having tumors with BRCA1/2 mutations, and pretreated advanced or metastatic HR+, Her2-, BRACA1/2 mutant breast cancer. IDE161-001: Phase 1/2 of IDE161 Monotherapy Dose Escalation and Expansion in HRD Solid Tumors The Phase 1 trial (NCT05787587) is evaluating the safety, tolerability, pharmacokinetic and pharmacodynamic properties and preliminary efficacy of IDE161 in patients having tumors with homologous recombination deficiency (HRD). Early clinical data from the dose escalation cohorts showed: Multiple partial responses (PRs) by RECIST 1.1 and tumor shrinkage observed in multiple HRD solid tumor patients, including: An endometrial cancer subject with a first imaging assessment of a PR, which was subsequently confirmed by RECIST 1.1 at the second scan and an 87% reduction of the CA-125 marker. A colorectal cancer subject with a second imaging assessment of a PR, which was subsequently confirmed by RECIST 1.1 Over 50% reduction in prostate-specific antigen (PSA) in prostate cancer patient with non-measurable disease No drug related discontinuations or SAEs at the IDE161 expansion dose observed. Phase 1 dose optimization is ongoing to confirm move forward Phase 2 expansion dose. The Phase 1 expansion trial continues to enroll in HRD solid tumor types, including ER+ HER-breast, colorectal, endometrial, and prostate cancers. Clinical program update(s) are expected in 2024. IDEAYA is also validating IDE161 combination opportunities preclinically and is targeting identification of potential combination(s) in 2024. GSK-Partnered Programs GSK101 (IDE705) Program in Tumors with Homologous Recombination Mutations or HRD GSK101 (IDE705) is a potential first-in-class small molecule inhibitor of Pol Theta Helicase being developed as a combination treatment with niraparib for advanced solid tumors with HRD. IND clearance was obtained from the U.S. FDA to enable the GSK-sponsored Phase 1/2 clinical trial to evaluate GSK101 in combination with niraparib, the GSK small molecule inhibitor of PARP, for patients having solid tumors with BRCA or other HR mutations, or with HRD. IDEAYA earned a $7.0 million milestone payment for IND clearance and will receive an additional $10.0 million upon initiation of Phase 1 clinical dose expansion, as well as potential further aggregate later-stage development and regulatory milestones of up to $465.0 million. GSK is the sponsor of the Phase 1/2 clinical trial and will lead clinical development for the Pol Theta program pursuant to its global, exclusive license from IDEAYA. GSK is responsible for all research and development costs for the program. Werner Helicase Inhibitor in Tumors with High Microsatellite Instability IDEAYA, in collaboration with GSK, selected a Werner Helicase inhibitor for further development and IDEAYA earned a $3.0 million milestone from GSK in connection with IND-enabling studies. IDEAYA has the potential to earn up to an additional $17.0 million aggregate milestones through early Phase 1, including $7.0 million upon IND effectiveness. IDEAYA is entitled to receive up to $465.0 million in additional later-stage development and regulatory milestones. The companies are targeting IND submission in 2024. Subject to IND submission and clearance, GSK will lead clinical development for the Werner Helicase program pursuant to its global, exclusive license to develop and commercialize the Werner Helicase Inhibitor DC. GSK is responsible for 80% of global research and development costs and IDEAYA is responsible for 20% of such costs. Next-Generation Precision Medicine Pipeline Programs IDEAYA has initiated early preclinical research programs focused on pharmacological inhibition of several new targets for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures. These research programs have the potential for discovery and development of first-in-class or best-in-class therapeutics with multiple wholly owned development candidate nominations targeted in 2024, including to treat MTAP-deletion solid tumors. Select Fourth Quarter and Full-Year 2023 Financial Results As of December 31, 2023, IDEAYA had cash, cash equivalents and marketable securities of $632.6 million, compared to $373.1 million as of December 31, 2022. The increase was primarily driven by total net proceeds of $323.3 million from underwritten public follow-on offerings completed in April and October 2023 partially offset by cash used in operations. Subsequent to the reporting period for the quarter ended December 31, 2023, the Company generated gross proceeds of approximately $352.0 million from the sale of shares of its common stock through at-the-market (ATM) offerings in January 2024. IDEAYA believes that its cash, cash equivalents and marketable securities of $632.6 million as of December 31, 2023, supplemented by estimated net proceeds of $342.3 million, after deducting underwriting discounts and commissions and other offering expenses, from the January 2024 ATM sales of common stock, will be sufficient to fund its planned operations into 2028. These funds will support the Company's efforts through potential achievement of multiple preclinical and clinical milestones across multiple programs. Collaboration revenue for the three months ended December 31, 2023, totaled $3.9 million compared to $4.0 million for the three months ended December 31, 2022. Collaboration revenue was recognized for the performance obligations satisfied through December 31, 2023, under the GSK Collaboration Agreement, and the Werner Helicase program's GLP toxicology study initiation milestone achievement. As of December 31, 2023, IDEAYA has fully recognized the contract liability related to the upfront payment research and development performance obligations under the GSK Collaboration Agreement. Research and development (R&D) expenses for the three months ended December 31, 2023, totaled $38.8 million compared to $24.7 million for the three months ended December 31, 2022. The increase was primarily due to higher personal-related expenses, consulting expenses and clinical trial expenses to support the portfolio growth. General and administrative (G&A) expenses for the three months ended December 31, 2023, totaled $7.1 million compared to $5.8 million for the three months ended December 31, 2022. The increase was primarily due to higher personnel-related expenses, higher legal and audit fees. The net loss for the three months ended December 31, 2023, was $34.0 million compared to the net loss of $24.2 million for the three months ended December 31, 2022. Total stock compensation expense for the three months ended December 31, 2023, was $4.8 million compared to $3.0 million for the same period in 2022. The net loss for the year ended December 31, 2023, was $113.0 million compared to $58.7 million for the same period in 2022. Total stock compensation expense for the year ended December 31, 2023, was $18.5 million compared to $11.6 million for the same period in 2022. About IDEAYA Biosciences IDEAYA is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA's approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies. IDEAYA is applying its research and drug discovery capabilities to synthetic lethality – which represents an emerging class of precision medicine targets. IDEAYA's updated corporate presentation is available on its website, at its Investor Relations page: . Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to (i) the timing, content and venue of clinical program updates, (ii) the timing of FDA regulatory guidance, (iii) the timing for the development of a joint Amgen/IDEAYA publication strategy, (iv) the timing of a first-patient-in in the IDE397 and Trodelvy combination study, (v) additional clinical combinations, (vi) the timing of IND submission for the Werner Helicase inhibitor DC, (vii) the timing of designation of next generation development candidates, (viii) the extent to which IDEAYA's existing cash, cash equivalents, and marketable securities will fund its planned operations, (ix) the potential therapeutic benefits of IDEAYA therapeutics, (x) the translation of preliminary clinical trial results into future clinical trial results, (xi) the estimate of patient populations, and (xii) the receipt of development and regulatory milestones. Such forward-looking statements involve substantial risks and uncertainties that could cause IDEAYA's preclinical and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including IDEAYA's programs' early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, IDEAYA's ability to successfully establish, protect and defend its intellectual property, the effects on IDEAYA's business of the worldwide COVID-19 pandemic, the ongoing military conflict between Russia and Ukraine, banking sector volatility, and other matters that could affect the sufficiency of existing cash to fund operations. IDEAYA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of IDEAYA in general, see IDEAYA's Annual Report on Form 10-K dated February 20, 2024 and any current and periodic reports filed with the U.S. Securities and Exchange Commission. Investor and Media Contact IDEAYA Biosciences Andres Ruiz Briseno SVP, Head of Finance and Investor Relations [email protected] SOURCE IDEAYA Biosciences, Inc.

THOUSAND OAKS, Calif., Feb. 6, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced financial results for the fourth quarter and full year 2023 versus comparable periods in 2022. "2023 was another year of performance and progress for our company," said Robert A. Bradway, chairman and chief executive officer. "Our marketed products are reaching many more patients around the world, and we anticipate more than a dozen significant pipeline milestones in 2024." Key results include: For the fourth quarter, total revenues increased 20% to $8.2 billion in comparison to the fourth quarter of 2022. Product sales grew 20%, driven by 23% volume growth, partially offset by 3% lower net selling price. Nine brands(1) achieved record sales in the quarter, and Repatha® (evolocumab), EVENITY® (romosozumab-aqqg), Prolia® (denosumab) and BLINCYTO® (blinatumomab) delivered double-digit volume growth globally. U.S. volume grew 26% and ex-U.S. volume grew 15%, including 46% volume growth in the Asia Pacific region. Our performance included $954 million of sales for the period of Oct. 6 - Dec. 31 from our recent Horizon Therapeutics (Horizon) acquisition, driven by several first-in-class, early-in-lifecycle medicines such as TEPEZZA® (teprotumumab-trbw), KRYSTEXXA® (pegloticase) and UPLIZNA® (inebilizumab-cdon). Excluding the impact of these sales from Horizon, our product sales grew 5%, driven by volume growth of 9%. For the full year, total revenues increased 7% to $28.2 billion, resulting from a 9% increase in product sales. Product sales growth was driven by 15% volume growth, partially offset by 3% lower net selling price, 1% unfavorable changes from estimated sales deductions and 1% negative impact from foreign exchange. GAAP earnings per share (EPS) decreased 53% from $3.00 to $1.42 in the fourth quarter, driven by acquisition-related expenses and incremental operating expenses from Horizon, partially offset by increased revenues. For the full year, GAAP EPS increased 3% from $12.11 to $12.49 driven by net gains on our BeiGene, Ltd equity investment in 2023 and higher revenues, partially offset by higher operating expenses, including acquisition-related expenses and incremental expenses from Horizon. For the fourth quarter, GAAP operating income decreased from $2.2 billion to $1.3 billion, and GAAP operating margin decreased 17.8 percentage points to 16.2%. For the full year, GAAP operating income decreased from $9.6 billion to $7.9 billion, and GAAP operating margin decreased 9.3 percentage points to 29.3%. Non-GAAP EPS increased 15% from $4.09 to $4.71 in the fourth quarter and increased 5% from $17.69 to $18.65 for the full year, driven by increased revenues, partially offset by higher operating expenses, including incremental expenses from Horizon. Fourth quarter non-GAAP EPS was also unfavorably impacted by higher interest expense. For the fourth quarter, non-GAAP operating income increased from $3.0 billion to $3.7 billion, and non-GAAP operating margin increased 0.8 percentage points to 46.7%. For the full year, non-GAAP operating income increased from $12.8 billion to $13.4 billion, and non-GAAP operating margin decreased 1.7 percentage points to 49.8%. The Company generated $7.4 billion of free cash flow for the full year versus $8.8 billion in 2022. The decrease in 2023 was primarily driven by transaction expenses related to the Horizon acquisition and higher repatriation tax payments. (1) Includes product sales for the full fourth quarter of 2023 from UPLIZNA and KRYSTEXXA in connection with Horizon acquisition. References in this release to "non-GAAP" measures, measures presented "on a non-GAAP basis," "free cash flow" (computed by subtracting capital expenditures from operating cash flow), "EBITDA, or earnings before interest, taxes, depreciation and amortization" (computed by adding interest expense, provision for income taxes, and depreciation and amortization expense to GAAP net income) and "debt leverage ratio" (calculated as the ratio of GAAP total debt to EBITDA) refer to non-GAAP financial measures. Adjustments to the most directly comparable GAAP financial measures and other items are presented on the attached reconciliations. Refer to Non-GAAP Financial Measures below for further discussion. Product Sales Performance Total product sales increased 20% for the fourth quarter of 2023 versus the fourth quarter of 2022. Volume grew 23%, partially offset by 3% lower net selling price. Full year product sales increased 9% versus 2022, driven by 15% volume growth, partially offset by 3% lower net selling price, 1% unfavorable changes from estimated sales deductions and 1% negative impact from foreign exchange. General Medicine Repatha® sales increased 25% year-over-year for the fourth quarter, driven by 35% volume growth, partially offset by lower net selling price. Full year sales increased 26%, driven by 37% volume growth, partially offset by lower net selling price. Repatha remains the global proprotein convertase subtilisin/kexin type 9 (PCSK9) segment leader, with over 2.5 million patients treated since launch. Prolia® sales increased 12% year-over-year, to a record $1.1 billion for the fourth quarter, and 12% for the full year, primarily driven by volume growth and higher net selling price. Volume grew 10% for the quarter and 9% for the full year. In 2023, over 7.5 million patients were treated with Prolia. EVENITY® sales increased 41% year-over-year to a record $318 million for the fourth quarter and 47% for the full year, driven by strong volume growth. U.S. volume grew 44% year-over-year and volume outside the U.S. grew 55% for the full year. Aimovig® (erenumab-aooe) sales decreased 32% year-over-year for the fourth quarter and 22% for the full year, driven by lower net selling price. Oncology BLINCYTO® sales increased 47% year-over-year to a record $241 million for the fourth quarter and 48% for the full year, driven by 55% and 49% volume growth, respectively. Volume growth was supported by broad prescribing across academic and community settings for patients with B-cell precursor acute lymphoblastic leukemia. Vectibix® (panitumumab) sales increased 5% year-over-year for the fourth quarter and 10% for the full year, driven by 5% and 10% volume growth, respectively. KYPROLIS® (carfilzomib) sales increased 8% year-over-year for the fourth quarter and 13% for the full year, driven by 8% and 12% volume growth, respectively. LUMAKRAS®/LUMYKRAS™ (sotorasib) sales increased 8% year-over-year for the fourth quarter, driven by 5% volume growth and higher net selling price. Full year sales decreased 2%, driven by unfavorable changes to estimated sales deductions, including changes related to ongoing reimbursement negotiations in France. Full year sales were also impacted by lower net selling price and lower inventory levels, partially offset by 16% volume growth. XGEVA® (denosumab) sales increased 9% year-over-year for the fourth quarter and 5% for the full year, primarily driven by higher net selling price. Nplate® (romiplostim) sales decreased 18% year-over-year for the fourth quarter, driven by volume decline related to timing of orders placed by the U.S. government, partially offset by volume growth across our U.S. and ex-U.S. regions. U.S. government orders were $207 million in Q4'22 compared to $62 million in Q4'23. Full year sales increased 13%, primarily driven by volume growth, including U.S. government orders. U.S. government orders were $207 million for FY'22 compared to $286 million for FY'23. Excluding these U.S. government orders, Nplate sales grew 23% year-over-year for the fourth quarter and 8% for the full year. MVASI® (bevacizumab-awwb) sales decreased 8% year-over-year for the fourth quarter, primarily driven by lower net selling price, partially offset by 12% volume growth. Full year sales decreased 11%, primarily driven by lower net selling price, partially offset by 13% volume growth. Going forward, we expect continued net selling price erosion driven by increased competition. KANJINTI® (trastuzumab-anns) sales decreased 33% year-over-year for the fourth quarter and 50% for the full year, driven by lower net selling price and volume decline. Inflammation TEZSPIRE® (tezepelumab-ekko) generated $177 million of sales in the fourth quarter. Quarter-over-quarter sales increased 10%, driven by 18% volume growth that benefited from the pre-filled, single-use pen, which was approved for self-administration by the U.S. Food and Drug Administration (FDA) in the first quarter. Healthcare providers recognize TEZSPIRE's unique, differentiated profile and its broad potential to treat the 2.5 million patients worldwide with severe asthma who are uncontrolled, without any phenotypic or biomarker limitation. Otezla® (apremilast) sales increased 2% year-over-year for the fourth quarter, driven by favorable changes to estimated sales deductions and 3% volume growth, partially offset by lower inventory levels and lower net selling price. Full year sales decreased 4%, driven by lower net selling price and lower inventory levels, partially offset by 2% volume growth. We expect future growth for Otezla to be driven by its established efficacy and safety profile, strong payer coverage with limited prior authorization requirements and ease of administration. Otezla remains the only approved oral systemic therapy with a broad indication and is well-positioned to help the 1.5 million U.S. patients with mild-to-moderate psoriasis who cannot be optimally addressed by a topical and can benefit from a systemic treatment like Otezla. Enbrel® (etanercept) sales decreased 8% year-over-year for the fourth quarter, driven by a 4% impact from unfavorable changes to estimated sales deductions and lower net selling price. Full year sales decreased 10%, driven by lower net selling price, lower inventory levels and a 3% impact from unfavorable changes to estimated sales deductions. Year-over-year volume remained flat, with U.S. volume growing 1% in the fourth quarter, supported by an increase in new patients starting treatment as a result of improved payer coverage. Going forward, we expect net selling price to continue to decline year-over-year, driven by higher rebates to maintain broad first-line payer coverage and changes in patient mix. We expect Otezla and Enbrel to follow the historical pattern of lower sales in the first quarter relative to subsequent quarters due to the impact of benefit plan changes, insurance reverification and increased co-pay expenses as U.S. patients work through deductibles. AMJEVITA®/AMGEVITA™ (adalimumab) sales increased 34% year-over-year for the fourth quarter and 36% for the full year, primarily driven by 35% and 46% volume growth, respectively. Ex-U.S. sales increased 9% for the full year, driven by 20% volume growth, partially offset by lower net selling price. U.S. sales increased 43% quarter-over-quarter, driven by higher inventory levels and higher net selling price, partially offset by volume decline. Rare Disease Excluding TAVNEOS®, the products listed below were acquired from our Horizon transaction on Oct. 6, 2023. Sales figures reflect only sales in the period from Oct. 6 2023 through the end of the year, and not the full quarter. TEPEZZA® (teprotumumab-trbw) generated $448 million of sales for the period. TEPEZZA is the first and only FDA-approved treatment for thyroid eye disease (TED). KRYSTEXXA® (pegloticase) generated $272 million of sales for the period. KRYSTEXXA is the first and only FDA-approved treatment for chronic refractory gout. UPLIZNA® (inebilizumab-cdon) generated $65 million of sales for the period. UPLIZNA is used to treat adults with neuromyelitis optica spectrum disorders (NMOSD). TAVNEOS® (avacopan) generated $44 million of sales in the fourth quarter. Quarter-over-quarter sales increased 19%, primarily driven by volume growth. U.S. volume grew 23% quarter-over-quarter. In the U.S., approximately 2,700 patients have now been treated with TAVNEOS. Ultra rare products, which consist of RAVICTI® (glycerol phenylbutyrate), PROCYSBI® (cysteamine bitartrate), ACTIMMUNE® (interferon gamma-1b), BUPHENYL® (sodium phenylbutyrate) and QUINSAIR® (levofloxacin) generated $164 million of sales for the period. Established Products Total sales of our established products, which consist of EPOGEN® (epoetin alfa), Aranesp® (darbepoetin alfa), Parsabiv® (etelcalcetide) and Neulasta® (pegfilgrastim), decreased 10% year-over-year for the fourth quarter, primarily driven by lower net selling price and volume declines, partially offset by favorable changes to estimated sales deductions. Full year sales decreased 19%, driven by lower net selling price and volume declines. In the aggregate, we expect the year-over-year net selling price and volume declines for this portfolio of products to continue. Product Sales Detail by Product and Geographic Region Operating Expense, Operating Margin and Tax Rate Analysis On a GAAP basis: Total Operating Expenses increased 50% year-over-year for the fourth quarter. For the full year, Total Operating Expenses increased 21%. Cost of Sales as a percentage of product sales increased 13.0 percentage points in the fourth quarter primarily driven by higher amortization expense from acquisition-related assets as well as higher profit share and royalties, partially offset by Puerto Rico excise tax, changes in product mix, and lower manufacturing cost. For the full year, cost of sales as a percentage of product sales increased 5.6 percentage points primarily driven by higher amortization expense from acquisition-related assets, higher profit share and royalties, and changes in product mix, partially offset by Puerto Rico excise tax. Research & Development (R&D) expenses increased 16% in the fourth quarter and increased 8% for the full year driven by higher spend in later-stage clinical programs and marketed products support, including spend from programs acquired from the Horizon acquisition. Selling, General & Administrative (SG&A) expenses increased 45% in the fourth quarter and increased 14% for the full year primarily driven by higher acquisition-related costs, in addition to commercial and general administrative expenses related to the Horizon acquisition. For the full year, this was partially offset by a decline in other marketed product spend. Other operating expenses for the full year consisted of net impairment charges for AMG 340 and Teneobio IPR&D assets in addition to expenses related to our restructuring plan initiated in the first quarter of 2023. Operating Margin as a percentage of product sales decreased 17.8 percentage points to 16.2% in the fourth quarter and decreased 9.3 percentage points for the full year to 29.3%. Tax Rate increased 2.4 percentage points in the fourth quarter and increased 3.7 percentage points for the full year, primarily driven by the 2022 Puerto Rico tax law change that replaced the excise tax with an income tax beginning in 2023. For the fourth quarter this was partially offset by the change in earnings mix. On a non-GAAP basis: Total Operating Expenses increased 18% for the fourth quarter and increased 9% for the full year. Cost of Sales as a percentage of product sales remained flat in the fourth quarter primarily driven by higher profit share and royalties, offset by Puerto Rico excise tax, changes in product mix, and lower manufacturing cost. For the full year, cost of sales as a percentage of product sales increased 1.1 percentage points primarily driven by higher profit share and royalties and changes in product mix, partially offset by Puerto Rico excise tax. R&D expenses increased 16% in the fourth quarter and increased 8% for the full year driven by higher spend in later-stage clinical programs and marketed products support, including spend from programs acquired from the Horizon acquisition. SG&A expenses increased 20% in the fourth quarter and increased 5% for the full year primarily driven by higher commercial and general administrative expenses related to the Horizon acquisition. For the full year, this was partially offset by a decline in other marketed product spend. Operating Margin as a percentage of product sales increased 0.8 pts. percentage points to 46.7% in the fourth quarter and decreased 1.7 percentage points for the full year to 49.8%. Tax Rate increased 2.5 percentage points in the fourth quarter and increased 2.7 percentage points for the full year primarily due to the 2022 Puerto Rico tax law change that replaced the excise tax with an income tax beginning in 2023. Cash Flow and Balance Sheet The Company generated $0.3 billion of free cash flow in the fourth quarter of 2023 versus $2.3 billion in the fourth quarter of 2022, primarily driven by timing of federal and repatriation tax payments. The Company generated $7.4 billion of free cash flow for the full year 2023 versus $8.8 billion in 2022. The Company's fourth quarter 2023 dividend of $2.13 per share was declared on October 24, 2023, and was paid on December 8, 2023, to all stockholders of record as of November 17, 2023, representing a 10% increase from 2022. During the fourth quarter, there were no repurchases of shares of common stock. Cash and investments totaled $10.9 billion and debt outstanding totaled $64.6 billion as of December 31, 2023. Debt leverage was approximately 4.4 times EBITDA as of December 31, 2023. 2024 Guidance For the full year 2024, the Company expects: Total revenues in the range of $32.4 billion to $33.8 billion. On a GAAP basis, EPS in the range of $8.42 to $9.87, and a tax rate in the range of 11.5% to 13.0%. On a non-GAAP basis, EPS in the range of $18.90 to $20.30, and a tax rate in the range of 16.0% to 17.0%. Capital expenditures to be approximately $1.1 billion. Share repurchases not to exceed $500 million. Fourth Quarter Product and Pipeline Update The Company provided the following updates on selected product and pipeline programs: General Medicine Maridebart cafraglutide (AMG 133) A Phase 2 study of maridebart cafraglutide, a multispecific molecule that inhibits the gastric inhibitory polypeptide receptor (GIPR) and activates the glucagon like peptide 1 (GLP-1) receptor, in overweight or obese adults with or without type 2 diabetes mellitus has completed enrollment, with topline data anticipated in late 2024. The Company recently added a Part 2 to this study which explores durable weight loss beyond 52 weeks. Planning for a comprehensive Phase 3 program across multiple indications remains on track. In February 2024, results of preclinical studies and the Phase 1 study of maridebart cafraglutide were published in Nature Metabolism. AMG 786 A Phase 1 study of AMG 786, a small molecule obesity program, is ongoing with initial data readout anticipated in H1 2024. This molecule has a different target than maridebart cafraglutide and is not an incretin-based therapy. Olpasiran (AMG 890) A Phase 3 cardiovascular outcomes study of olpasiran, a potentially best-in-class small interfering ribonucleic acid (siRNA) molecule that reduces lipoprotein(a) (Lp(a)) synthesis in the liver, in patients with atherosclerotic cardiovascular disease and elevated Lp(a) continues to enroll patients. To date, over 7,000 patients have been enrolled, with enrollment completion anticipated in H1 2024. Repatha EVOLVE-MI, a Phase 4 study of Repatha administered within 10 days of an acute myocardial infarction to reduce the risk of cardiovascular events, continues to enroll patients. A Phase 3 cardiovascular outcomes study (VESALIUS-CV) in patients at high cardiovascular risk without prior myocardial infarction or stroke is ongoing. Oncology Tarlatamab (AMG 757) The U.S. Food and Drug Administration (FDA) has granted Priority Review for the Company's Biologics License Application (BLA) for tarlatamab, a first-in-class investigational delta-like ligand 3 (DLL3) targeting BiTE® (bispecific T-cell engager) molecule. The BLA is based on the results from the Phase 2 DeLLphi-301 clinical trial, which demonstrated antitumor activity with a durable response and encouraging survival outcomes in previously treated small cell lung cancer (SCLC). The safety profile was consistent with the Phase 1 trial. Based on the Priority Review designation, the Prescription Drug User Fee Act (PDUFA) date for tarlatamab is June 12, 2024. DeLLphi-304, a Phase 3 study comparing tarlatamab with standard of care chemotherapy in second-line SCLC, continues to enroll patients. DeLLphi-306, a Phase 3 study comparing tarlatamab with placebo in limited-stage SCLC, was initiated. DeLLphi-305, a Phase 3 study comparing tarlatamab and durvalumab with durvalumab alone in first-line, extensive-stage SCLC, will be initiated in H1 2024. DeLLphi-300, a Phase 1 study of tarlatamab in relapsed/refractory SCLC, continues to enroll patients. DeLLphi-302, a Phase 1b study of tarlatamab in combination with AMG 404, an anti-programmed cell death protein 1 (PD1) monoclonal antibody, in second-line or later SCLC, is ongoing.   DeLLphi-303, a Phase 1b study of tarlatamab in combination with standard of care in first-line SCLC, continues to enroll patients. DeLLpro-300, a Phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer, is ongoing. BLINCYTO The FDA granted Priority Review for the Company's supplemental BLA for BLINCYTO in early-stage, CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) based in part on the Phase 3 E1910 study conducted by the National Cancer Institute, the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network Cancer Research Group. Based on the Priority Review designation, the PDUFA date for BLINCYTO is June 21, 2024. Additional global regulatory authority submissions are underway. Golden Gate, a Phase 3 study of BLINCYTO alternating with low-intensity chemotherapy in older adults with newly diagnosed Philadelphia chromosome-negative (Ph-) B-ALL, continues to enroll patients. The Company is planning to amend the Golden Gate Phase 3 study to include an evaluation of blinatumomab subcutaneous administration with initiation anticipated in H2 2024. A Phase 1/2 study of subcutaneous blinatumomab in adults with relapsed or refractory Ph- B-ALL continues to enroll patients. Xaluritamig (AMG 509) A Phase 1b monotherapy and combination dose-escalation and -expansion study of xaluritamig, a first-in-class bispecific T-cell engager targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1) in metastatic castrate resistant prostate cancer continues to enroll patients in the dose-expansion portion of the study, where enrollment is almost complete. A reduced monitoring cohort was also initiated. Two additional Phase 1 studies of xaluritamig to evaluate preliminary efficacy and safety in patients with early prostate cancer are planned. AMG 193 The Phase 1/1b/2 study of AMG 193, a first-in-class small molecule methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, continues to enroll patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors. To date, responses have been seen in nine patients across seven tumor types. Master protocols in thoracic and gastrointestinal malignancies exploring combinations with standard of care will be initiated in H1 2024. A Phase 1/2 study of AMG 193 in combination with IDE397, an investigational methionine adenosyltransferase 2A (MAT2A) inhibitor, is enrolling patients. Nplate A Phase 3 study of Nplate in chemotherapy-induced thrombocytopenia in gastrointestinal, pancreatic, or colorectal malignancies is fully enrolled. Data readout is anticipated in H2 2024. LUMAKRAS/LUMYKRAS A U.S. regulatory submission is planned for the Phase 3 CodeBreaK 300 trial in H1 2024. This study evaluated two doses of LUMAKRAS (960 mg or 240 mg) in combination with Vectibix in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer (CRC). A Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI in first-line KRAS G12C-mutated CRC was initiated. A Phase 3 study of LUMAKRAS plus chemotherapy vs. pembrolizumab plus chemotherapy in first-line KRAS G12C-mutated and programmed cell death protein ligand-1 (PD-L1) negative advanced non-small cell lung cancer (NSCLC) is enrolling patients. Regulatory review by the European Medicines Agency (EMA) of the CodeBreaK 200 Phase 3 trial of adults with previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC along with data from the Phase 2 dose-comparison substudy is ongoing. The FDA completed its review of the Company's supplemental New Drug Application seeking full approval of LUMAKRAS based on the CodeBreaK 200 trial results. The FDA issued a new postmarketing requirement for an additional confirmatory study to support full approval to be completed no later than February 2028, while also concluding that LUMAKRAS at 960 mg once-daily will remain the dose for patients with KRAS G12C-mutated NSCLC under accelerated approval. Bemarituzumab FORTITUDE-101, a Phase 3 study of bemarituzumab, a first-in-class fibroblast growth factor receptor 2b (FGFR2b) targeting monoclonal antibody, plus chemotherapy in first-line gastric cancer, continues to enroll patients. FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab in first-line gastric cancer, continues to enroll patients in the Phase 3 portion of the study. FORTITUDE-103, a Phase 1b/2 study of bemarituzumab plus oral chemotherapy regimens with or without nivolumab in first-line gastric cancer, continues to enroll patients. FORTITUDE-301, a Phase 1b/2 basket study of bemarituzumab monotherapy in solid tumors with FGFR2b overexpression, is ongoing. Inflammation TEZSPIRE In severe asthma, the WAYFINDER Phase 3b study is fully enrolled. The PASSAGE Phase 4 real-world effectiveness study and the SUNRISE Phase 3 study continue to enroll patients. A Phase 3 study of TEZSPIRE in chronic rhinosinusitis with nasal polyps is fully enrolled. Primary analysis is anticipated in H2 2024. A Phase 3 study of TEZSPIRE in eosinophilic esophagitis continues to enroll patients. A Phase 2 study of TEZSPIRE in chronic obstructive pulmonary disease is fully enrolled. Data readout is anticipated in H1 2024. Rocatinlimab (AMG 451/KHK4083) The ROCKET Phase 3 program, now composed of eight studies evaluating rocatinlimab, a first in class monoclonal antibody targeting OX40, in moderate to severe atopic dermatitis, continues to enroll adult and adolescent patients. To date, over 2,400 patients have been enrolled in the ROCKET program. The Phase 3 HORIZON study (part of the ROCKET program) evaluating rocatinlimab monotherapy vs. placebo in adults with moderate to severe atopic dermatitis is fully enrolled. Data readout is anticipated in H2 2024. A Phase 2 study of rocatinlimab in asthma will be initiated in H1 2024 and a Phase 3 study of rocatinlimab in prurigo nodularis will be initiated in H2 2024. Otezla In November 2023, data were presented from the MOSAIC and FOREMOST studies: In the MOSAIC Phase 4 study, primary and key secondary outcomes highlighted that Otezla led to better inflammatory disease control in psoriatic arthritis patients with moderate clinical disease activity than in patients with high disease activity. In the FOREMOST Phase 4 study, Otezla when added to standard of care, significantly improved disease activity in patients with early oligoarticular (few joints involved) psoriatic arthritis at 16 weeks compared to placebo. Efavaleukin alfa (AMG 592) A Phase 2b study of efavaleukin alfa, an interleukin 2 (IL 2) mutein Fc fusion protein, in ulcerative colitis continues to enroll patients. Ordesekimab (AMG 714/PRV-015) A Phase 2b study of AMG 714, a monoclonal antibody that binds interleukin-15, in nonresponsive celiac disease has completed enrollment. Rare Disease TAVNEOS In November 2023, data were presented from the Phase 3 ADVOCATE trial demonstrating that outcomes in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis favored TAVNEOS versus a prednisone taper across subgroups of patients 65 years and older, patients with kidney involvement and albuminuria, and patients with diffuse alveolar hemorrhage at baseline. TEPEZZA In December 2023, TEPEZZA received orphan drug designation in Japan for patients with moderate to severe active thyroid eye disease (TED). A New Drug Application was submitted for TEPEZZA in Japan based on the results from the OPTIC-J study evaluating TEPEZZA in patients with active TED. A Phase 3 study of TEPEZZA in Japan for chronic or low clinical activity score (CAS) TED continues to enroll patients. The Company plans to initiate a Phase 3 study evaluating the subcutaneous route of administration of TEPEZZA in patients with TED in H1 2024. UPLIZNA A Phase 3 study of UPLIZNA in myasthenia gravis is fully enrolled. Data readout is anticipated in H2 2024. A Phase 3 study of UPLIZNA for the prevention of flare in immunoglobulin G4- (IgG4) related disease is fully enrolled. Data readout is anticipated in H2 2024. Dazodalibep A Phase 3 study of dazodalibep, a cluster of differentiation 40 (CD40) ligand inhibitor fusion protein in Sjögren's syndrome is enrolling patients. Daxdilimab A Phase 2 study of daxdilimab, a fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7), in moderate-to-severe active primary discoid lupus erythematosus refractory to standard of care is enrolling patients. A Phase 2 study of daxdilimab in dermatomyositis and antisynthetase inflammatory myositis is enrolling patients. Fipaxalparant (formerly AMG 670 / HZN 825) A Phase 2 study of fipaxalparant, a lysophosphatidic acid receptor 1 (LPAR1) antagonist, in idiopathic pulmonary fibrosis is enrolling patients. Data readout is anticipated in H2 2024. A Phase 2 study of fipaxalparant in diffuse cutaneous systemic sclerosis is enrolling patients. Biosimilars The clinical comparative study portion of a randomized, double-blind pivotal study evaluating pharmacokinetic (PK) similarity of ABP 206 compared with OPDIVO® (nivolumab) in resected stage III or stage IV melanoma patients in the adjuvant setting is enrolling patients. TEZSPIRE is being developed in collaboration with AstraZeneca. Rocatinlimab, formerly AMG 451/KHK4083, is being developed in collaboration with Kyowa Kirin. Ordesekimab, formerly AMG 714 and also known as PRV-015, is being developed in collaboration with Provention Bio, a Sanofi Company. For the purposes of the collaboration, Provention Bio conducts a clinical trial and leads certain development and regulatory activities for the program. Xaluritamig, formerly AMG 509, is being developed pursuant to a research collaboration with Xencor, Inc. IDE397 is an investigational MAT2A inhibitor from IDEAYA Biosciences. OPDIVO is a registered trademark of Bristol-Myers Squibb Company. Non-GAAP Financial Measures In this news release, management has presented its operating results for the fourth quarters and full years of 2023 and 2022, in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on a non-GAAP basis. In addition, management has presented its full year 2024 EPS and tax guidance in accordance with GAAP and on a non-GAAP basis. These non-GAAP financial measures are computed by excluding certain items related to acquisitions, divestitures, restructuring and certain other items from the related GAAP financial measures. Beginning January 1, 2022, following industry guidance from the U.S. Securities and Exchange Commission, the Company no longer excludes adjustments for upfront license fees, development milestones and in-process research and development (IPR&D) expenses of pre-approval programs related to licensing, collaboration and asset acquisition transactions from its non-GAAP financial measures. Management has presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the fourth quarters and full years of 2023 and 2022. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP. Management has also presented Earnings Before Interest, Taxes, Depreciation and Amortization (EBITDA) and debt leverage ratio for 2023, both of which are non-GAAP financial measures. EBITDA is computed by adding interest expense, provision for income taxes, and depreciation and amortization expense to GAAP net income. Debt leverage ratio is calculated as the ratio of GAAP total debt to EBITDA. The Company believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. The Company uses certain non-GAAP financial measures to enhance an investor's overall understanding of the financial performance and prospects for the future of the Company's normal and recurring business activities by facilitating comparisons of results of normal and recurring business operations among current, past and future periods. The Company believes that FCF provides a further measure of the Company's liquidity. The Company believes its debt leverage ratio provides a supplemental operating metric for the full year period as it compares the amount of cash generated by our operations for the year. The Company uses the non-GAAP financial measures set forth in the news release in connection with its own budgeting and financial planning internally to evaluate the performance of the business, including to allocate resources and to evaluate results relative to incentive compensation targets. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. About Amgen Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2023, Amgen was named one of "America's Greatest Workplaces" by Newsweek, one of "America's Climate Leaders" by USA Today and one of the "World's Best Companies" by TIME. For more information, visit Amgen.com and follow us on X (formerly known as Twitter), LinkedIn, Instagram, TikTok, YouTube and Threads. Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon (including the prospective performance and outlook of Horizon's business, performance and opportunities and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. We or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. ### CONTACT: Amgen, Thousand Oaks Jessica Akopyan, 805-440-5721 (media) Justin Claeys, 805-313-9775 (investors) * The known adjustments are presented net of their related tax impact, which amount to approximately $2.60 per share. (a) The adjustments include noncash amortization of intangible assets and fair value step-up of inventory acquired in business combinations. Our GAAP diluted EPS guidance does not include the effect of GAAP adjustments triggered by events that may occur subsequent to this press release such as acquisitions, asset impairments, litigation, changes in fair value of our contingent consideration obligations and changes in fair value of our equity investments. SOURCE Amgen

CAMBRIDGE, Mass., Dec. 6, 2023 /PRNewswire/ -- Myeloid Therapeutics, Inc. ("Myeloid"), a clinical stage oncology company, has appointed Matthew Maurer, M.D. as Chief Medical Officer. Dr. Maurer is an experienced physician-scientist with over fifteen years of clinical oncology experience as a drug developer and a principal investigator advancing multiple cancer programs through the early and late stages of development at biotechnology and large pharmaceutical companies. In his new role, Dr. Maurer will be responsible for leading and expanding Myeloid's clinical portfolio and will serve as a key member of its executive management team. "We are very pleased that Matt has joined Myeloid as our Chief Medical Officer. Matt is a well-respected oncology expert with significant expertise in leading clinical teams that have advanced important anti-cancer therapies through all stages of development," said Daniel Getts, Ph.D., Myeloid CEO. "This is an exciting time at Myeloid, with our first in vivo candidate MT-302 recently entering Phase 1 for patients with TROP2-expressing tumors. With Matt coming on board, we believe his proven track record in running successful oncology studies will strengthen our capabilities and enable us to expand our in vivo mRNA programming clinical franchise." Dr. Maurer has joined Myeloid from IDEAYA Biosciences, where he was VP, Head of Medical Affairs and Clinical Oncology and participated in leading the strategy and execution of the company's oncology portfolio and achieved clinical proof-of-concept for darovasertib, initial first-in-human testing of a MAT2A inhibitor and an IND for a PARG inhibitor in solid tumors. Prior to IDEAYA, Dr. Maurer was a senior director at Bristol Myers Squibb (BMS) where he participated in leading the early development and proof-of-concept of relatlimab in advanced melanoma as well as multiple approvals of immunotherapy combinations in renal cell carcinoma. Prior to BMS, Dr. Maurer was a physician investigator and Assistant Professor of Medicine at Columbia University College of Physicians and Surgeons, where he served as a breast cancer specialist. Dr. Maurer received a BSE in Mechanical Engineering from Princeton University and earned his medical degree from the Mount Sinai School of Medicine. Dr. Maurer is an author on over 30 peer-reviewed publications in preclinical and clinical oncology and was the principal investigator on over 15 clinical oncology trials. Dr. Maurer added, "I have been impressed with Myeloid's strategic approach and leadership position with in vivo mRNA programming. I am enthusiastic about MT-302 and the full clinical potential of the Myeloid pipeline. I look forward to leading the team and continuing to harness myeloid biology and bring unmatched product designs with transformative full-immune engagement to patients with cancer, in an effort to improve and save lives." About in vivo mRNA Programming Myeloid's novel in vivo engineering platform is designed to program myeloid cells in vivo, so these cells recognize tumor cells, resulting in direct tumor cell killing and the elicitation of broad anti-tumor adaptive immunity. Myeloid has demonstrated that its novel CAR constructs can selectively program myeloid cells and do so directly in vivo, leading to potent tumor killing in multiple "cold tumor" preclinical models where alternative therapies, including CAR Ts and checkpoints show no activity. Myeloid's current in vivo programming portfolio consists of novel CAR constructs that have been tailored for selective expression in various immune cells, including myeloid cells, NK cells and T-cells. Active programs within Myeloid's in vivo preclinical pipeline include known tumor antigens as well as confidential novel epitopes. About Myeloid's ATAK™ CAR receptors Myeloid's novel class of CARs, known as ATAK™ Receptors, combine tumor recognition with multiple proprietary innate-immune signaling domains. Myeloid scientists have screened multiple unexplored combinations of innate-immune signals and uncovered optimal multi-signal pathways. The combination of cancer recognition binders with these novel intracellular signaling domains allows myeloid cells to be reprogrammed with previously unexplored combinations of immune signals, leading to tumor killing and broad systemic anti-tumor responses. About Myeloid Therapeutics Myeloid Therapeutics is a clinical stage oncology company developing novel therapies for cancer. Integrating the fields of mRNA-based therapeutics, immunology, and cancer biology, the Company's proprietary platform provides clinical solutions for patients with solid tumors. For more information, visit . Investor and Media Contact Amy Conrad Juniper Point [email protected] SOURCE Myeloid