Management
InOctober 2022 ,Merck announced that its board of directors unanimously electedRobert M. Davis , currently Chief Executive Officer and President, to serve as chairman of the board, effectiveDecember 1, 2022 . He will succeedKenneth C. Frazier ,who will retire onNovember 30, 2022 .
Business Developments
Below is a summary of significant business development activity thus far in 2022. See Note 3 to the condensed consolidated financial statements for additional information.
InSeptember 2022 ,Merck exercised its option to jointly develop and commercialize personalized cancer vaccine mRNA-4157/V940 pursuant to the terms of an existing collaboration and license agreement with Moderna, Inc. (Moderna), which resulted in a$250 million charge in Research and development expenses in the third quarter and first nine months of 2022. The payment to Moderna was made in the fourth quarter of 2022. mRNA-4157/V940 is currently being evaluated in combination with Keytruda (pembrolizumab),Merck 's anti-PD-1 therapy, as adjuvant treatment for patients with high-risk melanoma in a Phase 2 clinical trial being conducted by Moderna. Under the 2016 agreement, as amended in 2018,Merck and Moderna will collaborate on development and commercialization and will share costs and any profits equally under this worldwide collaboration. InAugust 2022 ,Merck and Orna Therapeutics (Orna), a biotechnology company pioneering a new investigational class of engineered circular RNA (oRNA) therapies, entered into a collaboration agreement to discover, develop, and commercialize multiple programs, including vaccines and therapeutics in the areas of infectious disease and oncology. Under the terms of the agreement,Merck made an upfront payment to Orna of$150 million , which was recorded in Research and development expenses in the third quarter and first nine months of 2022. In addition, Orna is eligible to receive future contingent development-related payments, as well as regulatory and sales-based milestone payments contingent upon the progress of the multiple vaccine and therapeutic programs, as well as royalties on any approved products derived from the collaboration.Merck also invested$100 million in Orna's Series B preferred shares in the fourth quarter of 2022. InJuly 2022 ,Merck and Orion Corporation (Orion) announced a global co-development and co-commercialization agreement for Orion's investigational candidate ODM-208 (MK-5684) and other drugs targeting cytochrome P450 11A1 (CYP11A1), an enzyme important in steroid production. ODM-208 is an oral, non-steroidal inhibitor of CYP11A1 currently being evaluated in a Phase 2 clinical trial for the treatment of patients with metastatic castration-resistant prostate cancer.Merck made an upfront payment to Orion of$290 million , which was recorded in Research and development expenses in the third quarter and first nine months of 2022. Also inJuly 2022 ,Merck andSichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (Kelun-Biotech) closed a license and collaboration agreement in whichMerck gained exclusive worldwide rights for the development, manufacture and commercialization of an investigational antibody drug conjugate (ADC) (MK-1200) for the treatment of solid tumors. Under the terms of the agreement,Merck and Kelun-Biotech will collaborate on the early clinical development of the investigational ADC.Merck made an upfront payment of$35 million , which was recorded in Research and development expenses in the third quarter and first nine months of 2022. Kelun-Biotech is also eligible to receive future contingent developmental, regulatory and sales-based milestone payments, as well as tiered royalties on future net sales. InMay 2022 , in connection with an existing arrangement,Merck exercised its option to obtain an exclusive license outside ofChina for the development, manufacture and commercialization of Kelun-Biotech's trophoblast antigen 2 (TROP2)-targeting ADC programs, including its lead compound, SKB-264 (MK-2870). SKB-264 is currently being evaluated in Phase 2 trials for non-small-cell lung cancer (NSCLC) and advanced solid tumors. Under the terms of the agreement,Merck and Kelun-Biotech will collaborate on certain early clinical development plans, including evaluating the potential of SKB-264 as a monotherapy and in combination with Keytruda for advanced solid tumors. Upon option exercise,Merck made a payment of$30 million , which was recorded in Research and development expenses in the first nine months of 2022, and agreed to make additional payments upon completion of specified project activities, technology transfer, as well as payments to fund Kelun-Biotech's ongoing research and development activities. In addition, Kelun-Biotech is eligible to receive future contingent developmental and sales-based milestone payments and royalties on future net sales. Spin-Off of Organon & Co. OnJune 2, 2021 ,Merck completed the spin-off of products from its women's health, biosimilars and established brands businesses into a new, independent, publicly traded company named Organon & Co. (Organon) through a distribution of Organon's publicly traded stock to Company shareholders. The distribution is expected to qualify and has been treated as tax-free to the Company and its shareholders forU.S. federal income tax purposes. The established brands included in the transaction consisted of dermatology, non-opioid pain management, respiratory, select cardiovascular products, as well as the rest ofMerck 's diversified brands franchise.Merck 's existing research pipeline programs continue to be owned and developed - 33 -
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Notes to Condensed Consolidated Financial Statements (unaudited) (continued)
within
Other Developments War inUkraine InFebruary 2022 ,Russia invadedUkraine . The Company's primary concerns are the safety and well-being of its employees and ensuring patients and customers have continued access to medicines and vaccines needed for patient and public health. The Company is working cross-functionally across the globe to monitor and mitigate interruptions to business continuity resulting from the war, including its impact onMerck 's supply chain, operations and clinical trials. For humanitarian reasons, the Company is continuing to supply essential medicines and vaccines inRussia while working to maintain compliance with evolving international sanctions.Merck is donating profits resulting from its operations inRussia to humanitarian causes. The Company does not have research or manufacturing facilities inRussia , currently does not plan to make further investments inRussia , and has suspended screening and enrollment in ongoing clinical trials as well as planning for new studies inRussia , although the Company continues to treat patients already enrolled in existing clinical trials and collect data from these studies. The Company is also using its resources to help alleviate the humanitarian crisis inUkraine , including through donations of funds and products. The financial impacts of the war were immaterial to the Company's consolidated financial statements for the third quarter and first nine months of 2022. Combined sales toRussia andUkraine were approximately 1% of totalMerck consolidated sales for the full year of 2021. The combination ofRussia's invasion ofUkraine , as well as the resultant economic sanctions imposed by theU.S. , theEuropean Union (EU) and other governments are having pervasive effects in markets worldwide. The Company is unable to determine at this time the future impacts of this war either directly or indirectly on the Company's business.
COVID-19
Although COVID-19-related disruptions had some negative effects on sales for the third quarter and first nine months of 2022,Merck continues to believe that global health systems and patients have largely adapted to the impacts of the COVID-19 pandemic.Merck 's sales of Lagevrio (molnupiravir), an investigational oral antiviral COVID-19 medicine, were$436 million and$4.9 billion in the third quarter and first nine months of 2022, respectively. In the third quarter and first nine months of 2021, COVID-19-related disruptions resulted in an estimated negative impact to Pharmaceutical segment sales of approximately$350 million and$1.3 billion , respectively, because a substantial portion ofMerck 's Pharmaceutical segment revenue is comprised of physician-administered products, which were unfavorably affected by social distancing measures and fewer well visits. InApril 2021 ,Merck announced it was discontinuing the development of MK-7110 for the treatment of hospitalized patients with COVID-19, which was obtained as part ofMerck 's acquisition of OncoImmune (see Note 3 to the condensed consolidated financial statements). This decision resulted in charges of$207 million to Cost of sales in the first nine months of 2021. InMarch 2021 ,Merck announced it had entered into multiple agreements to support efforts to expand manufacturing capacity and supply of SARS-CoV-2/COVID-19 medicines and vaccines. TheBiomedical Advanced Research and Development Authority (BARDA), a division of theOffice of the Assistant Secretary for Preparedness and Response within theU.S. Department of Health and Human Services , providedMerck with$102 million of funding in the first quarter of 2022 to adapt and make available a number of existing manufacturing facilities for the production of SARS-CoV-2/COVID-19 vaccines and medicines. The funding was recognized as a reduction to Cost of sales over the production period throughSeptember 30, 2022 , offsetting the depreciation expense related to the amounts that were capitalized in connection with the modification of the manufacturing facilities.Merck and Johnson & Johnson have commenced an arbitration regarding a dispute concerning two agreements pursuant to whichMerck was supporting the manufacturing and supply of Johnson & Johnson's SARS-CoV-2/COVID 19 vaccine and vaccine drug product. The amounts included in the condensed consolidated financial statements for these agreements were immaterial for the third quarter and first nine months of 2022.Merck does not believe the outcome of the arbitration will have a material impact on the Company's financial results.
Pricing
Global efforts toward health care cost containment continue to exert pressure on product pricing and market access worldwide. Changes to theU.S. health care system enacted in prior years as part of health care reform, as well as increased purchasing power of entities that negotiate on behalf of Medicare, Medicaid, and private sector beneficiaries, have contributed to pricing pressure. In several international markets, government-mandated pricing actions have reduced prices of generic and patented drugs. In addition, the Company's sales performance in the first nine months of 2022 was negatively affected by other cost-reduction measures taken by governments and other third parties to lower health care costs. In theU.S. ,Congress recently passed the Inflation Reduction Act, which makes significant changes to how drugs are covered and paid for under the Medicare - 34 - -------------------------------------------------------------------------------- program, including the creation of financial penalties for drugs whose prices rise faster than the rate of inflation, redesign of the Medicare Part D program to require manufacturers to bear more of the liability for certain drug benefits, and government price-setting for certain Medicare Part D drugs, starting in 2026, and Medicare Part B drugs starting in 2028. The Company anticipates all of these actions and additional actions in the future will negatively affect sales and profits.
Supply Chain
As a result of global macroeconomic conditions, the Company is experiencing some disruption and volatility in its global supply chain network, and the Company may in the future experience disruptions in availability and delays in shipments of raw materials and packaging, as well as related cost inflation. Operating Results Sales % Change % Change Three Months Ended Excluding Nine Months Ended Excluding September 30, Foreign September 30, Foreign ($ in millions) 2022 2021 % Change Exchange 2022 2021 % Change Exchange United States$ 7,322 $ 6,276 17 % 17 %$ 20,927 $ 16,166 29 % 29 % International 7,637 6,878 11 % 19 % 24,526 19,017 29 % 35 % Total$ 14,959 $ 13,154 14 % 18 %$ 45,453 $ 35,183 29 % 32 %
Worldwide sales grew 14% to$15.0 billion in the third quarter of 2022 primarily due to higher sales in the oncology franchise, largely driven by strong growth of Keytruda (pembrolizumab) and increased alliance revenue from Reblozyl (luspatercept-aamt) and Lynparza (olaparib), as well as higher sales in the virology franchise driven by Lagevrio (molnupiravir). Also contributing to revenue growth in the third quarter of 2022 were higher sales in the vaccines franchise, primarily attributable to growth of Gardasil (Human Papillomavirus Quadrivalent [Types 6, 11, 16 and 18] Vaccine, Recombinant) and Gardasil 9 (Human Papillomavirus 9-valent Vaccine, Recombinant), as well as higher sales of hospital acute care products, including Bridion (sugammadex) Injection and Zerbaxa (ceftolozane and tazobactam). Higher revenue related to third-party manufacturing arrangements also contributed to revenue growth in the third quarter of 2022. Worldwide sales rose 29% to$45.5 billion in the first nine months of 2022. Revenue growth was attributable in part to higher sales in the virology franchise driven by Lagevrio. Also contributing to revenue growth in the first nine months of 2022 were higher sales in the oncology franchise largely driven by strong growth of Keytruda and increased alliance revenue from Lenvima (lenvatinib), Reblozyl and Lynparza, as well as higher sales in the vaccines franchise, primarily attributable to growth of Gardasil and Gardasil 9. Higher sales of hospital acute care products, including Bridion and Zerbaxa, as well as higher revenue related to third-party manufacturing arrangements also drove revenue growth in the first nine months of 2022. As discussed above, COVID-19-related disruptions had some negative effects on sales in the third quarter and first nine months of 2022, but to a lesser extent than in the same periods of 2021 which benefited year-over-year sales growth in both periods. Revenue growth in the third quarter and first nine months of 2022 was partially offset by lower combined sales of diabetes products Januvia (sitagliptin) and Janumet (sitagliptin and metformin HCl), lower sales of Pneumovax 23 (pneumococcal vaccine polyvalent) and lower sales of virology products Isentress/Isentress HD (raltegravir). Lower revenue from the receipt of upfront and milestone payments for out-licensing arrangements also partially offset sales growth in the third quarter and first nine months of 2022. See Note 16 to the condensed consolidated financial statements for details on sales of the Company's products. A discussion of performance for select products in the franchises follows. - 35 -
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Pharmaceutical Segment Oncology % Change % Change Three Months Ended Excluding Nine Months Ended Excluding September 30, Foreign September 30, Foreign ($ in millions) 2022 2021 % Change Exchange 2022 2021 % Change Exchange Keytruda$ 5,426 $ 4,534 20 % 26 %$ 15,487 $ 12,609 23 % 28 % Alliance Revenue - Lynparza (1) 284 246 16 % 23 % 825 721 14 % 20 % Alliance Revenue - Lenvima (1) 202 188 7 % 11 % 660 498 33 % 36 % Alliance Revenue - Reblozyl 39 - - - 124 - - -
(1) Alliance revenue represents
Keytruda is an anti-PD-1 (programmed death receptor-1) therapy that has been approved as monotherapy for the treatment of certain patients with cervical cancer, classical Hodgkin lymphoma, cutaneous squamous cell carcinoma, endometrial carcinoma, esophageal or gastroesophageal junction (GEJ) carcinoma, head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), NSCLC, melanoma, Merkel cell carcinoma, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) cancer (solid tumors) including MSI-H/dMMR colorectal cancer, primary mediastinal large B-cell lymphoma, tumor mutational burden-high (TMB-H) cancer (solid tumors), and urothelial carcinoma including non-muscle invasive bladder cancer. Additionally, Keytruda is approved as monotherapy for the adjuvant treatment of certain patients with renal cell carcinoma (RCC) or stage IIB, IIC or III melanoma. Keytruda is also approved for certain patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. In addition, Keytruda is approved for the treatment of certain patients in combination with chemotherapy for metastatic squamous and nonsquamous NSCLC, in combination with chemotherapy, with or without bevacizumab for cervical cancer, in combination with chemotherapy for esophageal cancer, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for human epidermal growth factor 2 (HER-2)-positive gastric or GEJ adenocarcinoma, in combination with chemotherapy for HNSCC, in combination with chemotherapy for metastatic TNBC, in combination with axitinib for advanced RCC, and in combination with Lenvima for both endometrial carcinoma and RCC. The Keytruda clinical development program includes studies across a broad range of cancer types. See "Research and Development Update" below. Global sales of Keytruda grew 20% and 23% in the third quarter and first nine months of 2022, respectively. Sales growth was primarily driven by higher demand as the Company continues to launch Keytruda with multiple new indications globally. Sales in theU.S. continue to build across the multiple approved metastatic indications, in particular for the treatment of certain types of RCC, HNSCC, and MSI-H cancers. Keytruda sales growth in theU.S. also benefited from increased uptake across recent launches in earlier-stage indications including in high-risk, early stage TNBC, as well as certain types of RCC and melanoma. Keytruda sales growth in international markets reflects continued uptake predominately for the NSCLC, HNSCC and RCC indications, particularly inEurope .
Keytruda received the following regulatory approvals thus far in 2022.
Date ApprovalEuropean Commission (EC) approval as monotherapy for the
adjuvant treatment of
following nephrectomy and resection of metastatic lesions,
based on the
KEYNOTE-564 trial.Japan Ministry of Health, Labour and Welfare (MHLW)
approval of the combination of
CLEAR (Study 307)/KEYNOTE-581 trial. JapanPharmaceuticals and Medical Devices Agency approval
for the treatment of
after chemotherapy (limited to use when difficult to treat
with standard of care)
based on the KEYNOTE-158 trial.U.S. Food and Drug Administration (FDA) approval as a
single agent for the
treatment of patients with advanced endometrial carcinoma
that is MSI-H or dMMR
are not candidates for curative surgery or radiation,
based on the KEYNOTE-158
trial (Cohorts D & K). EC approval in combination with chemotherapy, with or
without bevacizumab, for the
whose tumors express PD-L1, based on the KEYNOTE-826
trial.
EC approval as monotherapy for the treatment of certain
adult patients with
biliary cancer, as well as advanced or recurrent
MSI-H/dMMR endometrial cancer,
based on the KEYNOTE-164 and KEYNOTE-158 trials. - 36 - -------------------------------------------------------------------------------- EC approval in combination with chemotherapy as
neoadjuvant treatment, and then
locally advanced or early-stage TNBC at high risk of
recurrence, based on the
KEYNOTE-522 trial. EC approval as monotherapy for the adjuvant treatment of
adults and adolescents
aged 12 years and older with stage IIB or IIC melanoma
and
expanding the indications in advanced (unresectable or
metastatic) melanoma and
stage III melanoma with lymph node involvement (as
adjuvant treatment following
complete resection) to include adolescent patients aged
12 years and older.
Japan MHLW approval in combination with chemotherapy as
neoadjuvant treatment, and
hormone receptor-negative and HER2-negative breast
cancer at high risk of
recurrence, based on the KEYNOTE-522 trial. Japan MHLW approval as monotherapy for the adjuvant
treatment of certain patients
nephrectomy and resection of metastatic lesions, based
on the KEYNOTE-564 trial.
Japan MHLW approval in combination with chemotherapy,
with or without bevacizumab,
prior chemotherapywho are not amenable to curative
treatment, based on the
KEYNOTE-826 trial.
stage IIB or IIC melanoma after complete resection,
based on the KEYNOTE-716 trial.
Lynparza is an oral poly (ADP-ribose) polymerase (PARP) inhibitor being developed as part of a collaboration with AstraZeneca PLC (AstraZeneca) (see Note 4 to the condensed consolidated financial statements). Lynparza is approved for the treatment of certain types of ovarian, breast, pancreatic and prostate cancers. Alliance revenue related to Lynparza increased 16% and 14% in the third quarter and first nine months of 2022, respectively, largely driven by higher demand globally across the multiple approved indications, particularly in theU.S. largely attributable to uptake in the earlier-stage breast cancer indication following recent approval by the FDA. InMarch 2022 , Lynparza was approved by the FDA for the adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative high-risk early breast cancerwho have been treated with neoadjuvant or adjuvant chemotherapy, followed by approvals in the EU andJapan inAugust 2022 , based on theOlympiA trial. InSeptember 2022 , Lynparza was approved inChina as first-line maintenance treatment for adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancerwho are in complete or partial response to first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with homologous recombination deficiency-positive status. This approval was based on the PAOLA-1 trial. Lenvima is an oral receptor tyrosine kinase inhibitor being developed as part of a collaboration with Eisai Co., Ltd. (Eisai) (see Note 4 to the condensed consolidated financial statements). Lenvima is approved for the treatment of certain types of thyroid cancer, RCC, HCC, in combination with everolimus for certain patients with RCC, and in combination with Keytruda for both endometrial carcinoma and RCC. Alliance revenue related to Lenvima grew 7% and 33% in the third quarter and first nine months of 2022, respectively, reflecting uptake in the advanced RCC and advanced endometrial carcinoma indications, particularly in theU.S. Growth in the third quarter was partially offset by the timing of shipments inChina . Reblozyl is a first-in-class erythroid maturation recombinant fusion protein obtained as part ofMerck 'sNovember 2021 acquisition of Acceleron Pharma Inc. that is being developed and commercialized through a global collaboration with Bristol Myers Squibb (see Note 4 to the condensed consolidated financial statements). Reblozyl is approved for the treatment of certain types of anemia.Merck recorded alliance revenue of$39 million (consisting of royalties) in the third quarter of 2022 related to this collaboration.Merck recorded alliance revenue of$124 million in the first nine months of 2022, which includes royalties of$104 million , as well as the receipt of a regulatory approval milestone payment of$20 million . Vaccines % Change % Change Three Months Ended Excluding Nine Months Ended Excluding September 30, Foreign September 30, Foreign ($ in millions) 2022 2021 % Change Exchange 2022 2021 % Change Exchange Gardasil/Gardasil 9$ 2,294 $ 1,993 15 % 20 %$ 5,428 $ 4,144 31 % 35 % ProQuad 264 244 8 % 10 % 640 598 7 % 9 % M-M-R II 124 127 (2) % (1) % 330 295 12 % 14 % Varivax 280 290 (3) % (2) % 746 733 2 % 3 % RotaTeq 256 227 12 % 16 % 644 593 9 % 11 % Pneumovax 23 131 277 (53) % (50) % 457 600 (24) % (21) % - 37 -
-------------------------------------------------------------------------------- Combined worldwide sales of Gardasil and Gardasil 9, vaccines to help prevent certain cancers and other diseases caused by certain types of human papillomavirus (HPV), grew 15% and 31% in the third quarter and first nine months of 2022, respectively, driven primarily by strong demand outside of theU.S. , particularly inChina , which also benefited from increased supply. Sales of Gardasil 9 in theU.S. increased in the third quarter and first nine months of 2022 due to public sector buying patterns.China's National Medical Products Administration expanded the use of Gardasil 9 for use in girls and women ages 9 to 45. The vaccine was previously approved for use in girls and women ages 16 to 26. Global sales of ProQuad (Measles, Mumps, Rubella and Varicella Virus Vaccine Live), a pediatric combination vaccine to help protect against measles, mumps, rubella and varicella, increased 8% and 7% in the third quarter and first nine months of 2022, respectively, primarily reflecting higher demand inEurope and higher pricing in theU.S.
Worldwide sales of MMR II (Measles, Mumps and Rubella Virus Vaccine Live), a
vaccine to help protect against measles, mumps and rubella, grew 12% in the
first nine months of 2022 primarily due to higher pricing and demand in the
Global sales of Varivax (Varicella Virus Vaccine Live), a vaccine to help
prevent chickenpox (varicella), grew 2% in the first nine months of 2022
primarily attributable to higher pricing in the
Global sales of RotaTeq (Rotavirus Vaccine, Live Oral, Pentavalent), a vaccine to help protect against rotavirus gastroenteritis in infants and children, grew 12% and 9% in the third quarter and first nine months of 2022, respectively, primarily due to public sector buying patterns and higher pricing in theU.S. Higher volumes inChina also contributed to RotaTeq sales growth in the third quarter of 2022. Worldwide sales of Pneumovax 23, a vaccine to help prevent pneumococcal disease, declined 53% and 24% in the third quarter and first nine months of 2022, respectively, primarily reflecting lower demand in theU.S. as the market continues to shift toward newer adult pneumococcal conjugate vaccines following changes in the recommendations of theU.S. Centers for Disease Control and Prevention's (CDC 's)Advisory Committee on Immunization Practices (ACIP) in 2021. The Company expects the decline inU.S. sales of Pneumovax 23 will continue. Lower demand inEurope also contributed to the Pneumovax 23 sales declines in the third quarter and first nine months of 2022. InJune 2022 , the FDA approved an expanded indication for Vaxneuvance (Pneumococcal 15-valent Conjugate Vaccine) to include use in infants and children. Vaxneuvance is now indicated for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F in individuals 6 weeks of age and older. TheFDA's approval was based on data from seven randomized, double-blind clinical studies assessing safety, tolerability and immunogenicity of Vaxneuvance in infants and children. Vaxneuvance was previously approved by the FDA in 2021 for use in adults 18 years of age and older. Also inJune 2022 , theCDC 's ACIP unanimously voted to include Vaxneuvance as a recommended option for vaccination in infants and children, including routine use in children under 2 years of age. These recommendations subsequently were adopted by the director of theCDC and theU.S. Department of Health and Human Services , and published in theCDC 's Morbidity and Mortality Weekly Report (MMWR). The ACIP also unanimously voted to include Vaxneuvance in the Vaccines for Children program. InOctober 2022 , the EC approved an expanded indication for Vaxneuvance to include active immunization for the prevention of invasive disease, pneumonia and acute otitis media caused by Streptococcus pneumoniae (S. pneumoniae) in infants, children and adolescents from 6 weeks to less than 18 years of age. Vaxneuvance was previously approved for use in the EU for individuals 18 years of age and older. InSeptember 2022 , Vaxneuvance was approved inJapan for use in adult patients. Vaxneuvance remains under review inJapan for use in pediatric patients. Hospital Acute Care % Change % Change Three Months Ended Excluding Nine Months Ended Excluding September 30, Foreign September 30, Foreign ($ in millions) 2022 2021 % Change Exchange 2022 2021
% Change Exchange Bridion$ 423 $ 369 15 % 22 %$ 1,244 $ 1,096 13 % 19 % Zerbaxa 43 (2) * * 120 (11) * *
*Calculation not meaningful.
Worldwide sales of Bridion, for the reversal of two types of neuromuscular blocking agents used during surgery, grew 15% and 13% in the third quarter and first nine months of 2022, respectively, due to higher demand globally, particularly in theU.S. , largely attributable to Bridion's growing share among neuromuscular blockade reversal agents and an increase in surgical procedures. - 38 - -------------------------------------------------------------------------------- InDecember 2020 , the Company temporarily suspended sales of Zerbaxa, a combination antibacterial and beta-lactamase inhibitor for the treatment of certain bacterial infections, and subsequently issued a product recall, following the identification of product sterility issues. The phased resupply for Zerbaxa that was initiated in the fourth quarter of 2021 has been completed during 2022. Cardiovascular % Change % Change Three Months Ended Excluding Nine Months Ended Excluding September 30, Foreign September 30, Foreign ($ in millions) 2022 2021 % Change Exchange 2022 2021 % Change Exchange Alliance Revenue - Adempas/Verquvo (1)$ 88 $ 100 (12) % 12 %$ 258 $ 248 4 % 4 % Adempas 57 59 (5) % 12 % 181 188 (4) % 8 %
(1) Alliance revenue represents
Adempas (riociguat) and Verquvo (vericiguat) are part of a worldwide collaboration with Bayer AG (Bayer) to market and develop soluble guanylate cyclase (sGC) modulators (see Note 4 to the condensed consolidated financial statements). Adempas is approved for the treatment of certain types of pulmonary arterial hypertension. Verquvo was approved in theU.S. inJanuary 2021 to reduce the risk of cardiovascular death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient intravenous diuretics in adults with symptomatic chronic heart failure and reduced ejection fraction. Verquvo was also approved inJapan inJune 2021 and in the EU inJuly 2021 . Alliance revenue from the collaboration declined 12% and grew 4% in the third quarter and first nine months of 2022, respectively. Revenue also includes sales of Adempas and Verquvo inMerck 's marketing territories. Virology % Change % Change Three Months Ended Excluding Nine Months Ended Excluding September 30, Foreign September 30, Foreign ($ in millions) 2022 2021 % Change Exchange 2022 2021 % Change Exchange Lagevrio$ 436 $ - - -$ 4,859 $ - - - Isentress/Isentress HD 161 189 (15) % (11) % 466 590 (21) % (17) % Lagevrio is an investigational oral antiviral COVID-19 medicine being developed in a collaboration with Ridgeback (see Note 4 to the condensed consolidated financial statements). Lagevrio has received multiple authorizations or approvals worldwide. Sales of Lagevrio were$436 million in the third quarter of 2022 primarily consisting of sales inAustralia ,South Korea ,Japan and theUnited Kingdom (UK ).Merck 's initial supply commitment of Lagevrio to theU.S. was fulfilled in the first quarter of 2022; therefore, there were no sales of Lagevrio in theU.S. in the second or third quarters of 2022. Sales of Lagevrio were$4.9 billion in the first nine months of 2022 primarily consisting of sales in theU.S. , theUK ,Japan andAustralia .Merck has entered into advance purchase and supply agreements for Lagevrio in more than 40 markets. The Company expects full-year 2022 Lagevrio sales to be between$5.2 billion and$5.4 billion . Global combined sales of Isentress/Isentress HD, an HIV integrase inhibitor for use in combination with other antiretroviral agents for the treatment of HIV-1 infection, declined 15% and 21% in the third quarter and first nine months of 2022, respectively, primarily due to lower global demand, reflecting in part competitive pressure inEurope and theU.S. The Company expects competitive pressure for Isentress/Isentress HD to continue. Diabetes % Change % Change Three Months Ended Excluding Nine Months Ended Excluding September 30, Foreign September 30, Foreign ($ in millions) 2022 2021 % Change Exchange 2022 2021 % Change Exchange Januvia/Janumet$ 1,133 $ 1,339 (15) % (9) %$ 3,599 $ 3,895 (8) % (2) % Worldwide combined sales of Januvia and Janumet, medicines that help lower blood sugar levels in adults with type 2 diabetes, declined 15% and 8% in the third quarter and first nine months of 2022, respectively, primarily reflecting the loss of exclusivity in several markets inEurope and theAsia Pacific region, as well as lower demand in theU.S. The sales decline in the first nine months of 2022 was partially offset by higher demand inChina , increased demand inLatin America reflecting in part higher government tenders, as well as the impact of a prior year unfavorable adjustment to rebate reserves in theU.S. The Company anticipatesU.S. pricing pressure will unfavorably affect sales of Januvia and Janumet in future periods. Januvia and Janumet lost patent exclusivity with respect to the sitagliptin compound patent inChina inJuly 2022 , although not with respect to the patent claiming the specific sitagliptin salt form, which expires inJune 2024 . In addition, the Company lost market - 39 - -------------------------------------------------------------------------------- exclusivity with respect to Januvia in the EU inSeptember 2022 , and additional exclusivity afforded Janumet that expires inApril 2023 is being challenged. The Company anticipates sales of Januvia and Janumet in these markets will decline substantially in future periods following the loss of exclusivity. The Company will lose sitagliptin compound patent protection for Januvia and Janumet in theU.S. inJanuary 2023 . However, inSeptember 2022 , theU.S. Court of Appeals for the Federal Circuit ruled in favor ofMerck in a patent challenge related to the specific sitagliptin salt form that is the active ingredient in Januvia and Janumet, affirming theMay 2021 decision inMerck 's favor by theU.S. Patent Office in an inter partes review. Also inSeptember 2022 , theU.S. District Court for the Northern District of West Virginia ruled in favor of the Company in an infringement suit related to the same sitagliptin salt patent, as well as a Janumet formulation patent, finding bothMerck patents valid and infringed. The rulings from theU.S. Court of Appeals and the U.S District Court inWest Virginia provide Januvia and Janumet patent protection throughMay 2027 ; althoughMerck has settled with multiple generic companies, providing that these generic companies can bring their products to the market inMay 2026 or earlier under certain circumstances. The decision from theU.S. District Court inWest Virginia is under appeal to theU.S. Court of Appeals for the Federal Circuit . (See Note 9 to the condensed consolidated financial statements.) Combined sales of Januvia and Janumet inChina ,Europe and theU.S. represented 10%, 21% and 34%, respectively, of total combined Januvia and Janumet sales for the first nine months of 2022. In response to a request from a regulatory authority,Merck evaluated its sitagliptin-containing products for the presence of nitrosamines. Nitrosamines are organic compounds found at trace levels in water and food. Nitrosamines can also result from chemical reactions and can form in drugs either due to the drug's manufacturing process, chemical structure, or the conditions in which the drugs are stored or packaged. The Company detected a nitrosamine identified as Nitroso-STG-19 (NTTP) in some batches of its sitagliptin-containing medicines. The Company has engaged with major health authorities around the world and has implemented additional quality controls to ensure its portfolio of sitagliptin-containing products meet health authorities' interim acceptable NTTP limits for continuing distribution of product to the market. The Company does not anticipate any significant impact on supply of these medicines. Animal Health Segment % Change % Change Three Months Ended Excluding Nine Months Ended Excluding September 30, Foreign September 30, Foreign ($ in millions) 2022 2021 % Change Exchange 2022 2021
% Change Exchange Livestock$ 829 $ 864 (4) % 4 %$ 2,486 $ 2,503 (1) % 6 % Companion Animal 542 553 (2) % 4 % 1,834 1,804 2 % 6 % Sales of livestock products declined 4% and 1% in the third quarter and first nine months of 2022, respectively. Excluding the unfavorable effect of foreign exchange in both periods, livestock sales performance primarily reflects higher pricing, as well as increased demand for poultry and ruminant products. Sales of companion animal products declined 2% in the third quarter of 2022 and grew 2% in first nine months of 2022. Excluding the unfavorable effect of foreign exchange in both periods, sales performance primarily reflects higher pricing and demand in the companion animal portfolio, led by the Bravecto (fluralaner) line of products, partially offset by lower sales of vaccines due to supply constraints. Sales of the Bravecto line of products represented approximately 20% of animal health sales in the first nine months of 2022.
Costs, Expenses and Other
Three Months Ended Nine Months Ended September 30, September 30, ($ in millions) 2022 2021 % Change 2022 2021 % Change Cost of sales$ 3,934 $ 3,450 14 %$ 13,530 $ 9,752 39 % Selling, general and administrative 2,520 2,336 8 % 7,355 6,804 8 % Research and development 4,399 2,445 80 % 9,773 9,177 6 % Restructuring costs 94 107 (12) % 288 487 (41) % Other (income) expense, net 429 (450) * 1,576 (1,007) *$ 11,376 $ 7,888 44 %$ 32,522 $ 25,213 29 % *Calculation not meaningful. Cost of Sales Cost of sales increased 14% and 39% in the third quarter and first nine months of 2022, respectively. Cost of sales includes$234 million and$2.6 billion in the third quarter and first nine months of 2022, respectively, related to the collaboration with Ridgeback for Lagevrio (see Note 4 to the condensed consolidated financial statements). Cost of sales also - 40 - -------------------------------------------------------------------------------- includes the amortization of intangible assets recorded in connection with acquisitions, collaborations and licensing arrangements, which totaled$445 million and$346 million in the third quarter of 2022 and 2021, respectively, and$1.6 billion and$1.2 billion in the first nine months of 2022 and 2021, respectively. Amortization expense in the first nine months of 2022 and 2021 includes$250 million and$153 million , respectively, of cumulative catch-up amortization related toMerck 's collaborations with AstraZeneca and Bayer, respectively, (see Note 4 to the condensed consolidated financial statements). Additionally, costs in the first nine months of 2021 include charges of$225 million related to the discontinuation of COVID-19 development programs. Also included in cost of sales are expenses associated with restructuring activities which amounted to$54 million and$48 million in the third quarter of 2022 and 2021, respectively, and$167 million and$113 million in the first nine months of 2022 and 2021, respectively, including accelerated depreciation and asset write-offs related to the planned sale or closure of manufacturing facilities. Separation costs associated with manufacturing-related headcount reductions have been incurred and are reflected in Restructuring costs as discussed below. Gross margin was 73.7% in the third quarter of 2022 compared with 73.8% in the third quarter of 2021. Gross margin was 70.2% in the first nine months of 2022 compared with 72.3% in the first nine months of 2021. The gross margin declines primarily reflect the impacts of higher revenue from third-party manufacturing arrangements and sales of Lagevrio, both of which have lower gross margins, as well as higher amortization of intangible assets (noted above). The gross margin declines were partially offset by the favorable effects of product mix and foreign exchange. The gross margin decline in the first nine months of 2022 was also partially offset by charges in 2021 related to the discontinuation of COVID-19 development programs.
Selling, General and Administrative
Selling, general and administrative (SG&A) expenses increased 8% in both the third quarter and first nine months of 2022 primarily due to higher administrative costs, including compensation and benefits, as well as higher promotional spending and restructuring costs, partially offset by the favorable effect of foreign exchange. Research and Development Research and development (R&D) expenses increased to$4.4 billion and$9.8 billion in the third quarter and first nine months of 2022, respectively, from$2.4 billion and$9.2 billion in the third quarter and first nine months of 2021, respectively. The increase in both periods was primarily due to$887 million of intangible asset impairment charges related toArQule, Inc. (see Note 8 to the condensed consolidated financial statements), higher charges related to collaborations and licensing arrangements, increased clinical development spending, increased investments in technology in support of the digital enablement ofMerck 's research operations, as well as higher compensation and benefit costs, partially offset by the favorable effect of foreign exchange. In addition, the increase in R&D expenses in the first nine months of 2022 was partially offset by a$1.7 billion charge in the prior year period related to the acquisition ofPandion Therapeutics, Inc. (Pandion). R&D expenses are comprised of the costs directly incurred byMerck Research Laboratories (MRL), the Company's research and development division that focuses on human health-related activities, which were$2.0 billion and$1.8 billion for the third quarter of 2022 and 2021, respectively, and were$5.6 billion and$5.3 billion for the first nine months of 2022 and 2021, respectively. Also included in R&D expenses areAnimal Health research costs, licensing costs and costs incurred by other divisions in support of R&D activities, including depreciation, production and general and administrative, which in the aggregate were approximately$1.5 billion and$710 million for the third quarter of 2022 and 2021, respectively, and$3.2 billion and$2.1 billion for the first nine months of 2022 and 2021, respectively. The increase in these expenses in the third quarter and first nine months of 2022 compared with the same periods of 2021 largely reflects$690 million of upfront and option payments in the aggregate for collaborations and licensing agreements with Orion, Moderna and Orna. Additionally, R&D expenses in the first nine months of 2022 include$887 million of intangible assets impairment charges and in the first nine months of 2021 include a$1.7 billion charge for the acquisition of Pandion as noted above. See Note 3 for additional information related to business development activity in the current and prior year.
Restructuring Costs
In 2019,Merck approved a global restructuring program (Restructuring Program) as part of a worldwide initiative focused on further optimizing the Company's manufacturing and supply network, as well as reducing its global real estate footprint. This program is a continuation of the Company's plant rationalization and builds on prior restructuring programs. The actions currently contemplated under the Restructuring Program are expected to be substantially completed by the end of 2023, with the cumulative pretax costs to be incurred by the Company to implement the program estimated to be approximately$3.5 billion .Merck expects to record charges of approximately$600 million for the full year of 2022 related to the Restructuring Program. The Company anticipates the actions under the Restructuring Program will result in annual net cost savings of approximately$900 million by the end of 2023. - 41 - -------------------------------------------------------------------------------- Restructuring costs, primarily representing separation and other related costs associated with these restructuring activities, were$94 million and$107 million for the third quarter of 2022 and 2021, respectively, and$288 million and$487 million for the first nine months of 2022 and 2021, respectively. Separation costs incurred were associated with actual headcount reductions, as well as estimated expenses under existing severance programs for headcount reductions that were probable and could be reasonably estimated. Also included in restructuring costs are asset abandonment, facility shut-down and other related costs, as well as employee-related costs such as curtailment, settlement and termination charges associated with pension and other postretirement benefit plans and share-based compensation plan costs. For segment reporting, restructuring costs are unallocated expenses. Additional costs associated with the Company's restructuring activities are included in Cost of sales, Selling, general and administrative expenses and Research and development costs. The Company recorded aggregate pretax costs of$175 million and$168 million in the third quarter of 2022 and 2021, respectively, and$559 million and$630 million for the first nine months of 2022 and 2021, respectively, related to restructuring program activities (see Note 5 to the condensed consolidated financial statements).
Other (Income) Expense, Net
Other (income) expense, net, was$429 million of expense in the third quarter of 2022 compared with$450 million of income in the third quarter of 2021. Other (income) expense, net, was$1.6 billion of expense for the first nine months of 2022 compared with$1.0 billion of income for the first nine months of 2021. The change in both periods is primarily due to net unrealized losses from investments in equity securities recorded in the third quarter and first nine months of 2022 compared with net realized and unrealized gains from investments in equity securities recorded in the third quarter and first nine months of 2021. The unfavorability in both periods was partially offset by lower pension costs.
For details on the components of Other (income) expense, net, see Note 12 to the condensed consolidated financial statements.
Segment Profits Three Months Ended Nine Months Ended September 30, September 30, ($ in millions) 2022 2021 2022 2021 Pharmaceutical segment profits$ 9,590 $ 8,606 $ 28,263 $ 22,450 Animal Health segment profits 515 505 1,672 1,629 Other (6,522) (3,845) (17,004) (14,109) Income from Continuing Operations Before Taxes$ 3,583
Pharmaceutical segment profits are comprised of segment sales less standard costs, as well as SG&A expenses directly incurred by the segment.Animal Health segment profits are comprised of segment sales, less all cost of sales, as well as SG&A and R&D expenses directly incurred by the segment. For internal management reporting presented to the chief operating decision maker,Merck does not allocate the remaining cost of sales not included in segment profits as described above, R&D expenses incurred by MRL, or general and administrative expenses, nor the cost of financing these activities. Separate divisions maintain responsibility for monitoring and managing these costs, including depreciation related to fixed assets utilized by these divisions and, therefore, they are not included in segment profits. Also excluded from the determination of segment profits are costs related to restructuring activities and acquisition and divestiture-related costs, including the amortization of intangible assets and amortization of purchase accounting adjustments, intangible asset impairment charges, and expense or income related to changes in the estimated fair value measurement of liabilities for contingent consideration. Additionally, segment profits do not reflect other expenses from corporate and manufacturing cost centers and other miscellaneous income or expense. These unallocated items are reflected in "Other" in the above table. Also included in "Other" are miscellaneous corporate profits (losses), as well as operating profits (losses) related to third-party manufacturing arrangements. Pharmaceutical segment profits increased 11% and 26% in the third quarter and first nine months of 2022, respectively, reflecting higher sales, partially offset by higher administrative and promotional costs, as well as the unfavorable effect of foreign exchange.Animal Health segment profits grew 2% in the third quarter of 2022 reflecting favorable product mix, partially offset by the unfavorable effect of foreign exchange.Animal Health segment profits grew 3% in the first nine months of 2022 reflecting higher sales, partially offset by higher selling and administrative costs and the unfavorable effect of foreign exchange. - 42 -
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Taxes on Income
The effective income tax rates from continuing operations were 9.2% and 13.2% for the third quarter of 2022 and 2021, respectively, and 11.0% and 14.4% for the first nine months of 2022 and 2021, respectively. The effective income tax rates from continuing operations reflect the beneficial impact of foreign earnings. The effective income tax rates from continuing operations in the third quarter and first nine months of 2022 also include the favorable impact of net unrealized losses from investments in equity securities and intangible asset impairment charges, which were taxed at theU.S. tax rate. The effective income tax rate from continuing operations in the first nine months of 2021 reflects the unfavorable effect of a charge for the acquisition of Pandion for which no tax benefit was recognized, as well as a net tax benefit of$207 million related to the settlement of certain federal income tax matters as discussed below. In the first quarter of 2021, the Internal Revenue Service (IRS) concluded its examinations ofMerck 's 2015-2016U.S. federal income tax returns. As a result, the Company was required to make a payment of$190 million (of which$172 million related to continuing operations and$18 million related to discontinued operations). The Company's reserves for unrecognized tax benefits for the years under examination exceeded the adjustments relating to this examination period and therefore the Company recorded a$236 million net tax benefit in the first nine months of 2021 (of which$207 million related to continuing operations and$29 million related to discontinued operations). This net benefit reflects reductions in reserves for unrecognized tax benefits and other related liabilities for tax positions relating to the years that were under examination.
Non-GAAP Income and Non-GAAP EPS from Continuing Operations
Non-GAAP income and non-GAAP EPS are alternative views of the Company's performance thatMerck is providing because management believes this information enhances investors' understanding of the Company's results since management uses non-GAAP measures to assess performance. Non-GAAP income and non-GAAP EPS exclude certain items because of the nature of these items and the impact that they have on the analysis of underlying business performance and trends. The excluded items (which should not be considered non-recurring) consist of acquisition and divestiture-related costs, restructuring costs, income and losses from investments in equity securities, and certain other items. These excluded items are significant components in understanding and assessing financial performance. Non-GAAP income and non-GAAP EPS are important internal measures for the Company. Senior management receives a monthly analysis of operating results that includes a non-GAAP EPS metric. Management uses non-GAAP measures internally for planning and forecasting purposes and to measure the performance of the Company along with other metrics. In addition, senior management's annual compensation is derived in part using a non-GAAP pretax income metric. Since non-GAAP income and non-GAAP EPS are not measures determined in accordance with GAAP, they have no standardized meaning prescribed by GAAP and, therefore, may not be comparable to the calculation of similar measures of other companies. The information on non-GAAP income and non-GAAP EPS should be considered in addition to, but not as a substitute for or superior to, net income and EPS prepared in accordance with generally accepted accounting principles in theU.S. (GAAP). In 2022, the Company changed the treatment of certain items for purposes of its non-GAAP reporting. Historically,Merck 's non-GAAP results excluded expenses for upfront and milestone payments related to collaborations and licensing agreements, as well as charges related to pre-approval assets obtained in transactions accounted for as asset acquisitions, to the extent the charges were considered by the Company to be significant to the results of a particular period (as well as any related adjustments recorded in a subsequent period). Beginning in 2022,Merck 's non-GAAP results no longer exclude charges related to these items. Prior periods have been recast to conform to the current presentation. - 43 - --------------------------------------------------------------------------------
A reconciliation between GAAP financial measures and non-GAAP financial measures (from continuing operations) is as follows:
Three Months Ended Nine Months Ended September 30, September 30, ($ in millions except per share amounts) 2022 2021 2022 2021
Income from continuing operations before taxes as reported under GAAP
$ 3,583 $ 5,266 $ 12,931 $ 9,970 Increase (decrease) for excluded items: Acquisition and divestiture-related costs 1,344 445 2,512 1,445 Restructuring costs 175 168 559 630 Loss (income) from investments in equity securities, net 350 (684) 1,268 (1,503)
Other items: Charges for the discontinuation of COVID-19 development programs
- - - 225 Non-GAAP income from continuing operations before taxes 5,452 5,195 17,270 10,767
Taxes on income from continuing operations as reported under GAAP
330 695 1,423 1,436 Estimated tax benefit (provision) on excluded items (1) 414 (29) 965 84
Net tax benefit from the settlement of certain federal income tax matters
- - - 207 Non-GAAP taxes on income from continuing operations 744 666 2,388 1,727 Non-GAAP net income from continuing operations 4,708 4,529 14,882 9,040
Less: Net income attributable to noncontrolling interests as reported under GAAP
5 4 6 9
Non-GAAP net income from continuing operations attributable to
$ 4,703 $ 4,525 $ 14,876 $ 9,031
EPS assuming dilution from continuing operations as reported under GAAP
$ 1.28 $ 1.80 $ 4.53 $ 3.36 EPS difference 0.57 (0.02) 1.33 0.20
Non-GAAP EPS assuming dilution from continuing operations
$ 1.78 $ 5.86 $ 3.56
(1) The estimated tax impact on the excluded items is determined by applying the statutory rate of the originating territory of the non-GAAP adjustments.
Acquisition and Divestiture-Related Costs
Non-GAAP income and non-GAAP EPS exclude the impact of certain amounts recorded in connection with acquisitions and divestitures of businesses. These amounts include the amortization of intangible assets and amortization of purchase accounting adjustments to inventories, as well as intangible asset impairment charges, and expense or income related to changes in the estimated fair value measurement of liabilities for contingent consideration. Also excluded are integration, transaction, and certain other costs associated with acquisitions and divestitures of businesses. Non-GAAP income and non-GAAP EPS also exclude amortization of intangible assets related to collaborations and licensing arrangements.
Restructuring Costs
Non-GAAP income and non-GAAP EPS exclude costs related to restructuring actions (see Note 5 to the condensed consolidated financial statements). These amounts include employee separation costs and accelerated depreciation associated with facilities to be closed or divested. Accelerated depreciation costs represent the difference between the depreciation expense to be recognized over the revised useful life of the asset, based upon the anticipated date the site will be closed or divested or the equipment disposed of, and depreciation expense as determined utilizing the useful life prior to the restructuring actions. Restructuring costs also include asset abandonment, facility shut-down and other related costs, as well as employee-related costs such as curtailment, settlement and termination charges associated with pension and other postretirement benefit plans and share-based compensation costs.
Income and Losses from Investments in
Non-GAAP income and non-GAAP EPS exclude realized and unrealized gains and losses from investments in equity securities either owned directly or through ownership interests in investment funds.
Certain Other Items
Non-GAAP income and non-GAAP EPS exclude certain other items. These items are adjusted for after evaluating them on an individual basis, considering their quantitative and qualitative aspects. Typically, these consist of items that are unusual in nature, significant to the results of a particular period or not indicative of future operating results. Excluded from non-GAAP income and non-GAAP EPS in 2021 are charges related to the discontinuation of COVID-19 development programs (see Note 3 to the condensed consolidated financial statements) and a net tax benefit related to the settlement of certain federal income tax matters (see Note 13 to the condensed consolidated financial statements). - 44 - --------------------------------------------------------------------------------
Research and Development Update
The Company currently has several candidates under regulatory review in the
MK-4482, Lagevrio, is an investigational oral antiviral medicine for the treatment of mild to moderate COVID-19 in adultswho are at risk for progressing to severe disease.Merck is developing Lagevrio in collaboration with Ridgeback. The FDA granted Emergency Use Authorization for Lagevrio inDecember 2021 ; last reissued inOctober 2022 , to authorize Lagevrio for the treatment of mild to moderate COVID-19 in adults with positive results of direct SARS-CoV-2 viral testing, andwho are at high risk for progression to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options approved or authorized by the FDA are not accessible or clinically appropriate. The authorization is based on the Phase 3 MOVe-OUT trial. Lagevrio is not approved for any use in theU.S. and is authorized only for the duration of the declaration that circumstances exist justifying the authorization of its emergency use under the Food, Drug and Cosmetic Act, unless the authorization is terminated or revoked sooner. Lagevrio has also received Conditional Marketing Authorization in theUK and Special Approval for Emergency inJapan . InNovember 2021 , theEuropean Medicines Agency (EMA) issued a positive scientific opinion for Lagevrio, which is intended to support national decision-making on the possible use of Lagevrio prior to marketing authorization. InOctober 2021 , the EMA initiated a rolling review for Lagevrio for the treatment of COVID-19 in adults.Merck plans to work with the Committee for Medicinal Products for Human Use of the EMA to complete the rolling review process to facilitate initiating the formal review of the Marketing Authorization Application. Applications to other regulatory bodies are underway. Lagevrio is also being evaluated for post-exposure prophylaxis in the Phase 3 MOVe-AHEAD trial, which is evaluating the efficacy and safety of Lagevrio for the prevention of COVID-19 in adultswho reside with a person with COVID-19. InOctober 2022 ,Merck provided an update on new clinical and non-clinical studies of Lagevrio. A preliminary analysis of theUniversity of Oxford's PANORAMIC study, conducted in theUK in highly-vaccinated adults mostly over 65 years of age, showed no evidence of a difference between Lagevrio added to usual care compared to usual care alone for the reduction of hospitalizations and deaths through Day 28 (primary endpoint was not met); the incidence of hospitalizations and death through Day 28 was very low overall. The main secondary endpoint (time to first self-reported recovery) in the PANORAMIC study was 6 days shorter with the Lagevrio group compared to the usual care group; in addition, the use of Lagevrio also was associated with earlier recovery across a wide range of other symptom measures, as compared to the usual care group. Additionally, an analysis of real-world data from a separate study conducted by investigators inIsrael (known as the Clalit study) showed that in a cohort of non-hospitalized, high-risk patients, Lagevrio reduced hospitalizations and mortality due to COVID-19 in patients 65 years and above; no evidence of benefit was found in younger adults ages 40 to 64 years. Also,Merck reported results from a separate, non-clinical 6-month carcinogenicity study in transgenic mice, which demonstrated that Lagevrio was not carcinogenic at any dose tested. MK-7264, gefapixant, is an investigational, orally administered, selective P2X3 receptor antagonist, for the treatment of refractory chronic cough or unexplained chronic cough in adults under review by the FDA and EMA. The marketing applications for gefapixant are based on results from the COUGH-1 and COUGH-2 clinical trials. InJanuary 2022 , the FDA issued a Complete Response Letter (CRL) regardingMerck 's New Drug Application (NDA) for gefapixant. In the CRL, the FDA requested additional information related to the cough counting system that was used to assess efficacy. The CRL was not related to the safety of gefapixant. The Company is performing additional analyses and anticipates submitting this information to the FDA in the first half of 2023 in response to the CRL. The review period in the EU has been extended pending the receipt of additional information from the Company. The Company plans to submit the information to the EMA in the first half of 2023. MK-3475, Keytruda, is an anti-PD-1 therapy approved for the treatment of many cancers that is in clinical development for expanded indications. These approvals were the result of a broad clinical development program that currently consists of more than 1,650 clinical trials, including more than 1,200 trials that combine Keytruda with other cancer treatments. These studies encompass more than 30 cancer types including: biliary, estrogen receptor positive breast cancer, cervical, colorectal, cutaneous squamous cell, endometrial, esophageal, gastric, glioblastoma, head and neck, hepatocellular, Hodgkin lymphoma, non-Hodgkin lymphoma, non-small-cell lung, small-cell lung, melanoma, mesothelioma, ovarian, prostate, renal, triple-negative breast, and urothelial, many of which are currently in Phase 3 clinical development. Further trials are being planned for other cancers. Keytruda is under review by the FDA for the treatment of patients with previously treated advanced HCC. This submission is based on data from the Phase 3 KEYNOTE-394 trial along with supportive data from the KEYNOTE-240 and KEYNOTE-224 trials. Keytruda is approved for this indication in theU.S. under theFDA's accelerated approval process. This submission is to convert the accelerated approval to full (regular) approval. Keytruda is also under review by the FDA for the adjuvant treatment of patients with stage IB (?4 centimeters), II or IIIA NSCLC following complete surgical resection. The supplemental Biologics License Application is based on data from the pivotal Phase 3 KEYNOTE-091 trial, also known as EORTC-1416-LCG/ETOP-8-15 - PEARLS. The FDA set a Prescription - 45 - -------------------------------------------------------------------------------- Drug User Fee Act (PDUFA) date ofJanuary 29, 2023 , however, further data may be provided during the review process that may delay this date. Keytruda is also under review for this indication in the EU. InJuly 2022 ,Merck announced that the Phase 3 KEYNOTE-412 trial evaluating Keytruda with concurrent chemoradiation therapy (CRT) followed by Keytruda as maintenance therapy (the Keytruda regimen) did not meet its primary endpoint of event-free survival for the treatment of patients with unresected locally advanced HNSCC. At the final analysis of the study, there was an improvement in event-free survival for patientswho received the Keytruda regimen compared to placebo plus CRT; however, these results did not meet statistical significance per the pre-specified statistical plan. Results were presented at the 2022European Society for Medical Oncology (ESMO) congress. InAugust 2022 ,Merck announced that the Phase 3 KEYNOTE-921 trial evaluating Keytruda in combination with chemotherapy (docetaxel) compared to chemotherapy alone did not meet its dual primary endpoints of overall survival and radiographic progression-free survival for the treatment of patients with metastatic castration-resistant prostate cancer. In the study, there were modest trends toward an improvement in both overall survival and radiographic progression-free survival for patientswho received Keytruda plus chemotherapy compared with chemotherapy alone; however, these results did not meet statistical significance per the pre-specified statistical plan. Results will be presented at an upcoming medical meeting.
MK-7339, Lynparza, is an oral PARP inhibitor currently approved for certain types of ovarian, breast, pancreatic and prostate cancers being co-developed for multiple cancer types as part of a collaboration with AstraZeneca.
InAugust 2022 , the FDA granted priority review for a supplemental NDA for Lynparza in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with metastatic castration-resistant prostate cancer. The supplemental NDA was based on results from the Phase 3 PROpel trial, which were presented at the 2022American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium and later published in NEJM Evidence. The FDA set a PDUFA date in the fourth quarter of 2022. Lynparza is also under review in the EU andJapan for the treatment of certain patients with metastatic castration-resistant prostate cancer based on the PROpel clinical trial. InMarch 2022 ,Merck announced that it would stop the Phase 3 KEYLYNK-010 trial investigating Keytruda in combination with Lynparza for the treatment of patients with metastatic castration-resistant prostate cancerwho progressed after treatment with chemotherapy and either abiraterone acetate or enzalutamide.Merck has discontinued the study following the recommendation of an independent Data Monitoring Committee (DMC) after the DMC reviewed data from a planned interim analysis. At the interim analysis, the combination of Keytruda and Lynparza did not demonstrate a benefit in overall survival, one of the study's dual primary endpoints, compared to the control arm of either abiraterone acetate or enzalutamide. The trial's other dual primary endpoint, radiographic progression free survival, was evaluated at an earlier interim analysis and did not demonstrate improvement compared to the control arm. Results from the study were presented at the 2022 ESMO congress. InJuly 2022 ,Merck announced it will stop the Phase 3 LYNK-003 trial investigating Lynparza with or without bevacizumab for the treatment of patients with unresectable or metastatic colorectal cancerwho have not progressed following first-line induction. This action follows the recommendation of an independent DMC, after the DMC reviewed the data from a planned interim analysis. At the pre-specified interim analysis for progression-free survival, the efficacy of Lynparza as a monotherapy and in combination with bevacizumab relative to control met the criteria for futility by the DMC and accordingly, both experimental arms were discontinued. Data from this study will be shared in a future scientific forum. MK-7902, Lenvima, is an oral receptor tyrosine kinase inhibitor being developed as part of a collaboration with Eisai.Merck and Eisai are studying the Keytruda plus Lenvima combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program. InAugust 2022 ,Merck and Eisai announced that the Phase 3 LEAP-002 trial investigating Keytruda plus Lenvima versus Lenvima monotherapy did not meet its dual primary endpoints of overall survival and progression-free survival as a first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). There were trends toward improvement in overall survival and progression-free survival for patientswho received Keytruda plus Lenvima versus Lenvima monotherapy; however, these results did not meet statistical significance per the pre-specified statistical plan. Results were presented at the 2022 ESMO congress. InJuly 2020 ,Merck and Eisai announced that the FDA issued a CRL regardingMerck 's and Eisai's applications seeking accelerated approval of Keytruda plus Lenvima for the first-line treatment of patients with uHCC based on data from the Phase 1b KEYNOTE-524/Study 116 trial. Given the results of the LEAP-002 trial noted above,Merck no longer intends to pursue the application. InOctober 2022 ,Merck announced positive top-line results from the pivotal Phase 3 STELLAR trial evaluating the safety and efficacy of sotatercept, an investigational activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein being evaluated as an add-on to stable background therapy for the treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO ] Group 1). The trial met its primary efficacy outcome measure, demonstrating a statistically significant and - 46 - -------------------------------------------------------------------------------- clinically meaningful improvement in 6-minute walk distance (6MWD, which measures how far patients can walk in 6 minutes). Eight of nine secondary efficacy outcome measures achieved statistical significance, including the outcome measure of proportion of participants achieving multicomponent improvement (defined as improvement in 6MWD, improvement in N-terminal pro-B-type natriuretic peptide level, and either improvement inWHO Functional Class [FC] or maintenance ofWHO FC II), and the outcome measure of time to death or the first occurrence of a clinical worsening event. The Cognitive/Emotional Impacts domain score of PAH-SYMPACT®, which was assessed as the ninth and final secondary outcome measure, did not achieve statistical significance. Results from the study will be presented at an upcoming scientific congress. InSeptember 2022 ,Merck announced it will initiate a new Phase 3 clinical program with once-daily islatravir for the treatment of people with HIV-1 infection. These new Phase 3 studies will evaluate a once-daily oral combination of doravirine 100 mg and a lower dose of islatravir (DOR/ISL). One study will evaluate DOR/ISL in previously untreated adults with HIV-1 infection and two studies will evaluate DOR/ISL as a switch in antiretroviral therapy in adults with HIV-1 infectionwho are virologically suppressed. The investigational new drug application for the once-daily oral DOR/ISL treatment program remains under a partial clinical hold for any studies that would use doses higher than the dose to be studied in the new Phase 3 program. The Phase 2 clinical trial evaluating an investigational oral once-weekly combination treatment regimen of islatravir and Gilead Sciences' lenacapavir in adults with HIV-1 infectionwho are virologically suppressed will resume under an amended protocol with a lower dose of islatravir. The investigational new drug application under which the islatravir + lenacapavir once-weekly treatment regimen is being investigated remains under a partial clinical hold for any studies that would use weekly oral islatravir doses higher than the doses considered for the revised clinical program. Additionally,Merck announced it will discontinue the development of once-monthly oral islatravir for pre-exposure prophylaxis (PrEP). InJune 2022 ,Merck announced the presentation of positive results from a Phase 1/2 study evaluating the safety, tolerability and immunogenicity of V116, the Company's investigational 21-valent pneumococcal conjugate vaccine (PCV), in pneumococcal vaccine-naïve adults 18-49 years of age (Phase 1) and 50 years of age and older (Phase 2). In both populations, V116 met the primary immunogenicity objectives and was well-tolerated with an overall safety profile generally comparable to Pneumovax 23 across age groups. InApril 2022 ,Merck announced that V116 received Breakthrough Therapy Designation from the FDA for the prevention of invasive pneumococcal disease and pneumococcal pneumonia caused by Streptococcus pneumoniae serotypes 3, 6A/C, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B/C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B in adults 18 years of age and older. The Breakthrough Therapy Designation is an FDA program designed to expedite the development and review of products intended for serious or life-threatening conditions. To qualify for this designation, preliminary clinical evidence must indicate that the product may demonstrate substantial improvement over currently available options on at least one clinically significant endpoint. Enrollment in several Phase 3 trials evaluating V116 is ongoing. InOctober 2022 ,Merck and Royalty Pharma plc (Royalty Pharma) entered into a funding arrangement under which Royalty Pharma paidMerck $50 million to co-fundMerck 's development costs for a Phase 2b trial of MK-8189, an investigational oral Phosphodiesterase 10A (PDE10A) inhibitor, which is being evaluated for the treatment of schizophrenia. Under the agreement, Royalty Pharma has no rights to MK-8189 and has no decision-making authority over the program. IfMerck elects to advance MK-8189 into a Phase 3 study, Royalty Pharma has the option to provide additional funding of 50% of the development costs up to$375 million for the Phase 3 trial. If such additional funding is provided, Royalty Pharma becomes eligible to receive future regulatory milestone payments contingent upon certain marketing approvals, as well as royalties. The charts below reflect the Company's research pipeline as ofNovember 3, 2022 . Candidates shown in Phase 3 include the date such candidate entered into Phase 3 development. Candidates shown in Phase 2 include the most advanced compound with a specific mechanism or, if listed compounds have the same mechanism, they are each currently intended for commercialization in a given therapeutic area. Small molecules and biologics are given MK-number designations and vaccine candidates are given V-number designations. Except as otherwise noted, candidates in Phase 1, additional indications in the same therapeutic area (other than with respect to cancer) and additional claims, line extensions or formulations for in-line products are not shown. - 47 - --------------------------------------------------------------------------------
Phase 2 Cancer Cancer Cancer MK-0482(2) MK-6440 (ladiratuzumab vedotin)(1)(3) MK-7902 Lenvima(1)(2) Non-Small-Cell Lung Breast Biliary MK-1026 (nemtabrutinib) Esophageal Glioblastoma Hematological Malignancies Gastric Pancreatic MK-1308 (quavonlimab)(2) Head and Neck Prostate Non-Small-Cell Lung Melanoma Small-Cell Lung MK-1308A (quavonlimab+pembrolizumab) Non-Small-Cell Lung V940(1) Colorectal Prostate Melanoma Hepatocellular Small-Cell Lung Chikungunya Virus Vaccine Melanoma MK-6482 Welireg(3) V184 Small-Cell Lung Biliary Dengue Fever Virus Vaccine MK-2140 (zilovertamab vedotin) Colorectal V181 Breast Endometrial HIV-1 Infection Gastric Esophageal MK-8591B (islatravir+MK-8507)(4) Hematological Malignancies Hepatocellular MK-8591D (islatravir+lenacapavir)(1)(5) Non-Small-Cell Lung Pancreatic Hypercholesterolemia Ovarian Rare cancers MK-0616 Pancreatic Von Hippel-Lindau Disease-Associated Tumors (EU) Nonalcoholic Steatohepatitis (NASH) MK-2870(1)(3) MK-7119 Tukysa(1) MK-3655 Neoplasm Malignant Advanced Solid Tumors MK-6024 MK-3475 Keytruda Biliary Overgrowth Syndrome Advanced Solid Tumors Bladder MK-7075 (miransertib) MK-4280 (favezelimab)(2) Cervical Pulmonary Arterial Hypertension Non-Small-Cell Lung Endometrial MK-5475 MK-4280A (favezelimab+pembrolizumab) Gastric Pulmonary Hypertension Due To Left Heart Disease Esophageal Non-Small-Cell Lung MK-7962 (sotatercept) Renal Cell MK-7339 Lynparza(1)(3) Schizophrenia Small-Cell Lung Advanced Solid Tumors MK-8189(6) MK-4830(2) MK-7684 (vibostolimab)(2) Thrombosis Colorectal Melanoma MK-2060 Esophageal MK-7684A (vibostolimab+pembrolizumab) Treatment Resistant Depression Melanoma Biliary MK-1942 Non-Small-Cell Lung Breast Ovarian Cervical Renal Cell Colorectal Small-Cell Lung Endometrial MK-5684(1) Esophageal Prostate Head and Neck MK-5890 (boserolimab)(2) Hematological Malignancies Non-Small-Cell Lung Hepatocellular Small-Cell Lung Prostate - 48 -
-------------------------------------------------------------------------------- Phase 3 (Phase 3 entry date) Under Review Antiviral COVID-19 New Molecular
Entities/Vaccines Certain Supplemental Filings
MK-4482 Lagevrio (
Cancer
Cancer MK-4482 Lagevrio (EU)(1) MK-3475 Keytruda MK-1308A (quavonlimab+pembrolizumab) Cough • Second-Line Hepatocellular Cancer Renal Cell (April 2021) MK-7264 (gefapixant) (U.S.)(8) (KEYNOTE-394) (U.S.) MK-3475 Keytruda (EU) • Adjuvent Non-Small-Cell Lung Cancer Biliary (September 2019) (KEYNOTE-091) (U.S.) (EU) Cutaneous Squamous Cell (August 2019 ) (EU) Gastric (May 2015) (EU) MK-7339 Lynparza(1) Hepatocellular (May 2016 ) (EU)
• First-Line Metastatic Prostate Cancer
Mesothelioma (
(PROpel) (U.S. ) (EU) (JPN) Ovarian (December 2018 ) Prostate (May 2019 ) Small-Cell Lung (May 2017 ) MK-3475 (pembrolizumab subcutaneous) Non-Small-Cell Lung (August 2021 ) MK-4280A (favezelimab+pembrolizumab) Colorectal (November 2021 ) Hematological Malignancies (October 2022 ) MK-6482 Welireg(3) Renal Cell (February 2020 ) MK-7119 Tukysa(1) Breast (October 2019 ) Colorectal (August 2022 ) MK-7339 Lynparza(1)(3) Non-Small-Cell Lung (June 2019 ) Footnotes: Small-Cell Lung (December 2020 ) (1) Being developed in a
collaboration.
MK-7684A (vibostolimab+pembrolizumab) (2) Being developed in combination with Keytruda. Non-Small-Cell Lung (April 2021 ) (3) Being developed as monotherapy and/or in combination with Keytruda. Small-Cell Lung (March 2022 ) (4) On FDA clinical hold. MK-7902 Lenvima(1)(2) (5) On FDA partial clinical hold. Colorectal (April 2021 ) (6) Phase 2b development costs are being co-funded. Esophageal (July 2021 ) (7) Available in theU.S. under Emergency Use Authorization. Gastric (December 2020 ) (8) In response to the CRL received from the FDA for this application in Head and Neck (February 2020 )January 2022 ,Merck is performing additional analyses and anticipates Melanoma (March 2019 ) submitting this information to the FDA in the first half of 2023. Non-Small-Cell Lung (March 2019 ) HIV-1 Infection MK-8591A (doravirine+islatravir) (February 2020)(5) Pneumococcal Vaccine Adult V116 (July 2022 ) Pulmonary Arterial Hypertension MK-7962 (sotatercept) (January 2021 ) Respiratory Syncytial Virus MK-1654 (clesrovimab) (November 2021 )
Liquidity and Capital Resources
($ in millions) September 30, 2022 December 31, 2021 Cash and investments $ 12,232 $ 8,466 Working capital 10,563 6,394 Total debt to total liabilities and equity 28.4 %
31.3 %
Cash provided by operating activities of continuing operations was$14.7 billion in the first nine months of 2022 compared with$8.0 billion in the first nine months of 2021 reflecting stronger operating performance, including the impact of Lagevrio (see Note 4 to the condensed consolidated financial statements). Cash provided by operating activities of continuing operations in the first nine months of 2022 was reduced by$1.8 billion of milestone payments related to collaborations compared with$432 million of milestone and option payments related to collaborations in the first nine months of 2021. Cash provided by operating activities of continuing operations continues to be the Company's primary source of funds to finance operating needs, with excess cash serving as the primary source of funds to finance capital expenditures, dividends paid to shareholders and treasury stock purchases. As a result of the mandatory change in R&D capitalization rules that are effective for tax years beginning afterDecember 31, 2021 (related to the Tax Cuts and Jobs Act of 2017), the Company has paid higher taxes in theU.S. in the first nine months of 2022 compared with the same prior year period. Cash used in investing activities of continuing operations was$3.2 billion in the first nine months of 2022 compared with$4.4 billion in the first nine months of 2021. The lower use of cash in investing activities of continuing operations was primarily due to lower cash used for acquisitions and higher proceeds from the sale of securities and other investments, partially offset by higher purchases of securities and other investments. - 49 - -------------------------------------------------------------------------------- Cash used in financing activities of continuing operations was$7.6 billion in the first nine months of 2022 compared with$2.1 billion in the first nine months of 2021. The increase in cash used in financing activities of continuing operations was primarily due to the cash distribution in 2021 received from Organon in connection with the spin-off (see Note 2 to the condensed consolidated financial statements) coupled with higher payments on long-term debt and higher dividends paid to shareholders in the current period. The increase in cash used in financing activities was partially offset by net repayments of short-term borrowings and treasury stock purchases in the prior year period that did not occur in the current period.
Capital expenditures totaled
The Company has accounts receivable factoring agreements with financial institutions in certain countries to sell accounts receivable. The Company factored$2.3 billion and$2.8 billion of accounts receivable atSeptember 30, 2022 andDecember 31, 2021 , respectively, under these factoring arrangements, which reduced outstanding accounts receivable. The cash received from the financial institutions is reported within operating activities in the Condensed Consolidated Statement of Cash Flows. In certain of these factoring arrangements, for ease of administration, the Company will collect customer payments related to the factored receivables, which it then remits to the financial institutions. The net cash flows relating to these collections are reported as financing activities in the Condensed Consolidated Statement of Cash Flows. Dividends paid to stockholders were$5.3 billion and$5.0 billion for the first nine months of 2022 and 2021, respectively. InMay 2022 , the Board of Directors declared a quarterly dividend of$0.69 per share on the Company's stock for the third quarter that was paid inJuly 2022 . InJuly 2022 , the Board of Directors declared a quarterly dividend of$0.69 per share on the Company's stock for the fourth quarter that was paid inOctober 2022 . InFebruary 2022 , the Company's$1.25 billion , 2.35% notes matured in accordance with their terms and were repaid. InSeptember 2022 , the Company's$1.0 billion , 2.40% notes matured in accordance with their terms and were repaid. InJanuary 2021 , the Company's$1.15 billion , 3.875% notes matured in accordance with their terms and were repaid. In 2018,Merck 's Board of Directors authorized purchases of up to$10 billion ofMerck 's common stock for its treasury. The treasury stock purchase authorization has no time limit and will be made over time in open-market transactions, block transactions on or off an exchange, or in privately negotiated transactions. The Company did not purchase any shares of its common stock during the first nine months of 2022. As ofSeptember 30, 2022 , the Company's remaining share repurchase authorization was$5.0 billion . The Company has a$6.0 billion credit facility that matures inJune 2026 . The facility provides backup liquidity for the Company's commercial paper borrowing facility and is to be used for general corporate purposes. The Company has not drawn funding from this facility.
Critical Accounting Estimates
The Company's significant accounting policies, which include management's best estimates and judgments, are included in Note 2 to the consolidated financial statements for the year endedDecember 31, 2021 included inMerck 's Form 10K filed onFebruary 25, 2022 . See Note 1 to the condensed consolidated financial statements for information on the adoption of new accounting standards during 2022. A discussion of accounting estimates considered critical because of the potential for a significant impact on the financial statements due to the inherent uncertainty in such estimates are disclosed in the Critical Accounting Estimates section of Management's Discussion and Analysis of Financial Condition and Results of Operations included inMerck 's Form 10-K. There have been no significant changes in the Company's critical accounting estimates sinceDecember 31, 2021 .
Recently Issued Accounting Standards
For a discussion of recently issued accounting standards, see Note 1 to the condensed consolidated financial statements.
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