U.S. Food and Drug Administration Approves Two Opdivo® -Based Regimens as First-Line Treatments for Unresectable Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Opdivo in combination with chemotherapy and Opdivo plus Yervoy ^® (ipilimumab) approved based on a Phase 3 trial showing improved overall survival versus chemotherapy alone ^1,2

Opdivo -based treatments are now approved for five indications in upper gastroesophageal cancers ¹

Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has approved both Opdivo ^® (nivolumab) (injection for intravenous use) in combination with fluoropyrimidine- and platinum-containing chemotherapy and Opdivo ^® plus Yervoy ^® (ipilimumab) as a first-line treatment for adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) regardless of PD-L1 status. The approvals are based on the Phase 3 CheckMate -648 trial, which evaluated Opdivo in combination with chemotherapy (n=321) and Opdivo plus Yervoy (n=325) each compared to chemotherapy alone (n=324), and was the largest Phase 3 trial of an immunotherapy in first-line ESCC. ¹

In the trial, Opdivo in combination with chemotherapy demonstrated superior overall survival (OS) compared to chemotherapy alone, both in all randomized patients, a secondary endpoint, which was hierarchically tested (Hazard Ratio [HR] 0.74, 95% Confidence Interval [CI]: 0.61 to 0.90, P =0.0021) and in patients whose tumors express PD-L1 (≥1%), a primary endpoint (HR 0.54, 95% CI: 0.41 to 0.71, P 1,2 In all randomized patients the median OS (mOS) was 13.2 months (95% CI: 11.1 to 15.7) with Opdivo in combination with chemotherapy versus 10.7 months (95% CI: 9.4 to 11.9) with chemotherapy alone. ¹ In patients whose tumors express PD-L1 (≥1%) the mOS was 15.4 months (95% CI: 11.9 to 19.5) for Opdivo in combination with chemotherapy versus 9.1 months (95% CI: 7.7 to 10) with chemotherapy alone. ¹ The median progression-free survival (PFS) in all randomized patients, which was a hierarchically tested secondary endpoint, was 5.8 months (95% CI: 5.6 to 7.0) for Opdivo in combination with chemotherapy and 5.6 months (95% CI: 4.3 to 5.9) for chemotherapy alone (HR= 0.81; 95% CI: 0.67 to 0.99, P =not significant). Per pre-specified analysis, PFS did not meet statistical significance. ¹ The median PFS in patients whose tumors express PD-L1 (≥1%), which was a co-primary endpoint, was 6.9 months (95% CI: 5.7 to 8.3) for Opdivo in combination with chemotherapy and 4.4 months (95% CI: 2.9 to 5.8) for chemotherapy alone (HR 0.65; 95% CI: 0.49 to 0.86, P =0.0023). ¹

Opdivo plus Yervoy also improved OS compared to chemotherapy in all-randomized patients, a secondary endpoint, which was hierarchically tested (HR 0.78, 95% CI: 0.65 to 0.95, P =0.0110) and patients whose tumors express PD-L1 (≥1%), a primary endpoint (HR 0.64, 95% CI: 0.49 to 0.84, P =0.0010). ^1,2 The mOS was 12.8 months (95% CI: 11.3 to 15.5) with Opdivo plus Yervoy versus 10.7 months (95% CI: 9.4 to 11.9) with chemotherapy alone in all randomized patients and 13.7 months (95% CI: 11.2 to 17.0) with Opdivo plus Yervoy versus 9.1 months (95% CI: 7.7 to 10) with chemotherapy alone in patients whose tumors express PD-L1 (≥1%). ¹ The median PFS in patients whose tumors express PD-L1 (≥1%), which was a co-primary endpoint, was 4.0 months (95% CI: 2.4 to 4.9) for Opdivo plus Yervoy and 4.4 months (95% CI: 2.9 to 5.8) for chemotherapy alone (HR 1.02; 95% CI: 0.78 to 1.34, P =not significant). Per pre-specified analysis, PFS did not meet statistical significance. ^1,2 Median PFS in the PD-L1 (≥1%) population was not statistically significant and therefore it was not hierarchically tested in the all comers population.

Opdivo alone and Opdivo plus Yervoy are associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials . ¹ Please see the Important Safety Information section below.

"Today brings welcome news for many advanced or metastatic esophageal squamous cell carcinoma patients and oncologists," said Jaffer A. Ajani, M.D., CheckMate -648 co-first author and lead U.S. investigator, and professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. "Unresectable advanced or metastatic esophageal squamous cell carcinoma is a challenging disease, and there's a need for additional treatment options that may extend survival in the first-line setting. ^3,4 In the CheckMate -648 trial, two nivolumab-based combinations showed a survival benefit compared to chemotherapy alone, offering new treatment options regardless of PD-L1 status." ¹

This application was reviewed under the FDA's Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible. ⁵

"At Bristol Myers Squibb, we recognize the need that exists for many patients facing upper gastroesophageal cancers, including advanced or metastatic esophageal squamous cell carcinoma, and we are focused on our goal to bring forward new treatment options with proven survival benefits regardless of PD-L1 status and histology," said Adam Lenkowsky, senior vice president and general manager, U.S., Cardiovascular, Immunology, Oncology, Bristol Myers Squibb. ⁶ "Today's approvals bring two first-line immunotherapy-based treatment options at once, Opdivo in combination with chemotherapy and Opdivo plus Yervoy as the first dual immunotherapy option, to newly diagnosed patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, further building on the role of Opdivo -based regimens in upper gastroesophageal cancers." ¹

About CheckMate -648

CheckMate -648 is a randomized Phase 3 study evaluating Opdivo plus Yervoy or Opdivo in combination with chemotherapy (fluorouracil and cisplatin) against chemotherapy (fluorouracil plus cisplatin) alone in adult patients with previously untreated unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma. ^1,2 The primary endpoints of the trial are overall survival (OS) and progression-free survival (PFS) determined by blinded independent central review (BICR) in patients whose tumors express PD-L1 (≥1%) for both Opdivo -based combinations versus chemotherapy. ² Secondary endpoints of the trial, including OS and PFS as determined by BICR in the all randomized population, were tested hierarchically only if corresponding primary endpoints were significant. ^1,2

In the Opdivo plus Yervoy arm, patients received treatment with Opdivo 3 mg/kg every 2 weeks and Yervoy 1 mg/kg every 6 weeks up to 2 years or until disease progression or unacceptable toxicity. ^1,2 In the Opdivo in combination with chemotherapy arm, patients received treatment with Opdivo 240 mg on Day 1 and Day 15, fluorouracil 800 mg/m²/day on Day 1 through Day 5 for five days, and cisplatin 80 mg/m² on Day 1 of a four-week cycle. ^1,2 Patients were treated with Opdivo until disease progression, unacceptable toxicity, or up to 2 years. ^1,2 In patients who received Opdivo in combination with chemotherapy and in whom either fluorouracil and/or cisplatin were discontinued, other components of the treatment regimen were allowed to be continued. ² Patients who discontinued combination therapy because of an adverse reaction attributed to ipilimumab were permitted to continue Opdivo as a single agent. ²

Select Safety Profile from CheckMate -648 Study

Opdivo and/or chemotherapy were discontinued in 39% of patients and were delayed in 71% of patients for an adverse reaction. ¹ Serious adverse reactions occurred in 62% of patients receiving Opdivo in combination with chemotherapy. ¹ The most frequent (≥2%) serious adverse reactions in patients receiving Opdivo in combination with chemotherapy were pneumonia (11%), dysphagia (7%), esophageal stenosis (2.9%), acute kidney injury (2.9%), and pyrexia (2.3%). ¹ Fatal adverse reactions occurred in 5 (1.6%) patients treated with Opdivo in combination with chemotherapy; these included pneumonitis, pneumatosis intestinalis, pneumonia, and acute kidney injury. ¹ The most common (≥20%) adverse reactions in patients treated with Opdivo in combination with chemotherapy were nausea (65%), decreased appetite (51%), fatigue (47%), constipation (44%), stomatitis (44%), diarrhea (29%), and vomiting (23%). ¹

Opdivo and/or Yervoy were discontinued in 23% of patients and were delayed in 46% of patients for an adverse reaction. ¹ Serious adverse reactions occurred in 69% of patients receiving Opdivo plus Yervoy . ¹ The most frequent (≥2%) serious adverse reactions in patients receiving Opdivo plus Yervoy were pneumonia (10%), pyrexia (4.3%), pneumonitis (4%), aspiration pneumonia (3.7%), dysphagia (3.7%), hepatic function abnormal (2.8%), decreased appetite (2.8%), adrenal insufficiency (2.5%), and dehydration (2.5%). ¹ Fatal adverse reactions occurred in 5 (1.6%) patients treated with Opdivo plus Yervoy ; these included pneumonitis, interstitial lung disease, pulmonary embolism, and acute respiratory distress syndrome. ¹ The most common (≥20%) adverse reactions in patients treated with Opdivo plus Yervoy were rash (31%), fatigue (28%), pyrexia (23%), nausea (22%), diarrhea (22%), and constipation (20%). ¹

About Esophageal Cancer

In the United States, it is estimated that approximately 20,640 new cases of esophageal cancer will be diagnosed and approximately 16,410 deaths will result from the disease in 2022 alone. ⁷ Esophageal cancer, which can impact the patient's ability to swallow and eat, is a type of gastroesophageal cancer that starts in the inner layer of the esophagus (the mucosa) and grows. ^8,9 The mucosa is normally lined with squamous cells. ⁹ Cancer starting in these cells is called squamous cell carcinoma, which is most often found in the upper and middle part of the esophagus, and accounts for less than 30% of esophageal cancers in the United States. ⁹ For about 39% of patients, esophageal cancer is diagnosed in the advanced stage, which is typically harder to treat. ¹⁰

INDICATIONS

OPDIVO ^® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

OPDIVO ^® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).

OPDIVO ^® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

OPDIVO ^® (nivolumab), in combination with ipilimumab, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

OPDIVO ^® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (

Immune-Mediated Colitis

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%).

Immune-Mediated Hepatitis and Hepatotoxicity

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%).

Immune-Mediated Endocrinopathies

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%).

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%).

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%).

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis.

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%).

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of cardiac/vascular : myocarditis, pericarditis, vasculitis; nervous system : meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal : pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue : myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine : hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO or YERVOY. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between OPDIVO or YERVOY and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO and YERVOY prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

In randomized clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Lactation

There are no data on the presence of OPDIVO or YERVOY in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.

Serious Adverse Reactions

In Attraction-3, serious adverse reactions occurred in 38% of patients receiving OPDIVO (n=209). Serious adverse reactions reported in ≥2% of patients who received OPDIVO were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia. The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%). In Checkmate 577, serious adverse reactions occurred in 33% of patients receiving OPDIVO (n=532). A serious adverse reaction reported in ≥2% of patients who received OPDIVO was pneumonitis. A fatal reaction of myocardial infarction occurred in one patient who received OPDIVO. In Checkmate 648, serious adverse reactions occurred in 62% of patients receiving OPDIVO in combination with chemotherapy (n=310). The most frequent serious adverse reactions reported in ≥2% of patients who received OPDIVO with chemotherapy were pneumonia (11%), dysphagia (7%), esophageal stenosis (2.9%), acute kidney injury (2.9%), and pyrexia (2.3%). Fatal adverse reactions occurred in 5 (1.6%) patients who received OPDIVO in combination with chemotherapy; these included pneumonitis, pneumatosis intestinalis, pneumonia, and acute kidney injury. In Checkmate 648, serious adverse reactions occurred in 69% of patients receiving OPDIVO in combination with YERVOY (n=322). The most frequent serious adverse reactions reported in ≥2% who received OPDIVO in combination with YERVOY were pneumonia (10%), pyrexia (4.3%), pneumonitis (4.0%), aspiration pneumonia (3.7%), dysphagia (3.7%), hepatic function abnormal (2.8%), decreased appetite (2.8%), adrenal insufficiency (2.5%), and dehydration (2.5%). Fatal adverse reactions occurred in 5 (1.6%) patients who received OPDIVO in combination with YERVOY; these included pneumonitis, interstitial lung disease, pulmonary embolism, and acute respiratory distress syndrome. In Checkmate 649, serious adverse reactions occurred in 52% of patients treated with OPDIVO in combination with chemotherapy (n=782). The most frequent serious adverse reactions reported in ≥2% of patients treated with OPDIVO in combination with chemotherapy were vomiting (3.7%), pneumonia (3.6%), anemia (3.6%), pyrexia (2.8%), diarrhea (2.7%), febrile neutropenia (2.6%), and pneumonitis (2.4%). Fatal adverse reactions occurred in 16 (2.0%) patients who were treated with OPDIVO in combination with chemotherapy; these included pneumonitis (4 patients), febrile neutropenia (2 patients), stroke (2 patients), gastrointestinal toxicity, intestinal mucositis, septic shock, pneumonia, infection, gastrointestinal bleeding, mesenteric vessel thrombosis, and disseminated intravascular coagulation.

Common Adverse Reactions

In Attraction-3, the most common adverse reactions (≥20%) in OPDIVO-treated patients (n=209) were rash (22%) and decreased appetite (21%). In Checkmate 577, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=532) were fatigue (34%), diarrhea (29%), nausea (23%), rash (21%), musculoskeletal pain (21%), and cough (20%). In Checkmate 648, the most common adverse reactions (≥20%) in patients treated with OPDIVO in combination with chemotherapy (n=310) were nausea (65%), decreased appetite (51%), constipation (44%), stomatitis (44%), fatigue (32%), diarrhea (29%), and vomiting (23%). In Checkmate 648, the most common adverse reactions reported in ≥20% of patients treated with OPDIVO in combination with YERVOY were rash (31%), fatigue (28%), pyrexia (23%), nausea (22%), diarrhea (22%), and constipation (20%). In Checkmate 649, the most common adverse reactions (≥20%) in patients treated with OPDIVO in combination with chemotherapy (n=782) were peripheral neuropathy (53%), nausea (48%), fatigue (44%), diarrhea (39%), vomiting (31%), decreased appetite (29%), abdominal pain (27%), constipation (25%), and musculoskeletal pain (20%).

Please see US Full Prescribing Information for OPDIVO and YERVOY .

Clinical Trials and Patient Populations

Attraction-3—esophageal squamous cell carcinoma; Checkmate 577—adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 648—previously untreated, unresectable advanced, metastatic esophageal squamous cell carcinoma in combination with fluoropyrimidine- and platinum-containing chemotherapy; Checkmate 648—previously untreated, unresectable advanced, or metastatic esophageal squamous cell carcinoma, in combination with YERVOY; Checkmate 649—previously untreated advanced or metastatic gastric or gastroesophageal junction or esophageal adenocarcinoma

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients' lives through science. The goal of the company's cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient's life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

About Bristol Myers Squibb's Patient Access Support

Bristol Myers Squibb remains committed to providing assistance so that cancer patients who need our medicines can access them and expedite time to therapy.

BMS Access Support ^® , the Bristol Myers Squibb patient access and reimbursement program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance, as well as co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support can be obtained by calling BMS Access Support at 1-800-861-0048 or by visiting www.bmsaccesssupport.com .

About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies' strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , Twitter , YouTube , Facebook and Instagram .

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

Cautionary Statement Regarding Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, whether Opdivo in combination with Yervoy or chemotherapy for the additional indications described in this release will be commercially successful, that any marketing approvals, if granted, may have significant limitations on their use, and that continued approval of such combination treatments for the additional indication described in this release may be contingent upon verification and description of clinical benefit in confirmatory trials. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb's business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2021, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

References

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American Cancer Society. Key Statistics for Esophageal Cancer. https://www.cancer.org/cancer/esophagus-cancer/about/key-statistics.html . Updated January 12, 2022. Accessed May 24, 2022.
PDQ ^® Adult Treatment Editorial Board. PDQ Esophageal Cancer Treatment (Adult). https://www.cancer.gov/types/esophageal/patient/esophageal-treatment-pdq . Last updated: November 18, 2021. Accessed May 24, 2022. Bethesda, MD: National Cancer Institute.
American Cancer Society. What Is Cancer of the Esophagus? https://www.cancer.org/cancer/esophagus-cancer/about/what-is-cancer-of-the-esophagus.html . Updated March 20, 2020. Accessed May 24, 2022.
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Bristol Myers Squibb
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Corporate Employers Accused of Increasing Risk Of Pension Shortfalls in Violation of Employee Retirement Income Security Act of 1974

Lawsuits have been filed alleging that a number of large corporate employers have offloaded billions of dollars in pension obligations to Athene Annuity and Life Company andor Athene Annuity & Life Assurance Company of New York, subsidiaries of Athene Holding Ltd. (collectively, "Athene") in violation of ERISA. In addition to AT&T Inc. (NYSE: T), Lockheed Martin Corporation (NYSE: LMT), and Alcoa Corporation (NYSE: AA), against which lawsuits have already been filed, according to SEC filings andor Athene's public statements, Bristol-Myers Squibb Company (NYSE: BMY), Armstrong World Industries, Inc. (NYSE: AWI), ATI, Inc. (NYSE: ATI), Weyerhaeuser Company (NYSE: WY), and General Electric (NYSE: GE) have offloaded pension obligations to Athene.

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Bristol Myers Squibb Announces Leadership Transition Plan

Giovanni Caforio, MD, Bristol Myers Squibb Chairman and CEO, to Retire as CEO, Effective November 1, 2023; Will Continue as Executive Chairman of the Board

Christopher Boerner, PhD, EVP, Chief Commercialization Officer, Appointed EVP, Chief Operating Officer, Effective Immediately; to Succeed Giovanni Caforio, MD, as CEO, Effective November 1, 2023

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Bristol Myers Squibb Strengthens Cell Therapy Capabilities by Adding New U.S. Manufacturing Facility for Viral Vector Production

Libertyville, Illinois facility bolsters long-term viral vector supply with multi-product, in-house viral vector production capabilities

Bristol Myers Squibb (NYSE: BMY) today announced expansion of its global cell therapy manufacturing network to enable in-house viral vector production through a U.S.-based manufacturing facility and its operations in Libertyville, Illinois, following the company's execution of an agreement with Novartis. The facility and its operations have capabilities to produce viral vector for both of Bristol Myers Squibb's CAR T cell therapies. This development advances the company's long-term ambitions in cell therapy.

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AMGEN ANNOUNCES 2025 FIRST QUARTER DIVIDEND

Amgen (NASDAQ:AMGN) today announced that its Board of Directors declared a $2.38 per share dividend for the first quarter of 2025. The dividend will be paid on March 7, 2025 to all stockholders of record as of the close of business on February 14, 2025 .

About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.

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AMGEN ANNOUNCES $1 BILLION MANUFACTURING EXPANSION IN NORTH CAROLINA

Investment Establishes Second Facility in Holly Springs ; Builds on Previous $550M Commitment

Amgen (NASDAQ: AMGN) today announced a $1 billion expansion to establish a second drug substance manufacturing facility in North Carolina . This brings the company's total planned investment in Holly Springs to more than $1.5 billion building on its previously announced $550 million commitment.

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	First Quarter

$ amounts in millions, except per share amounts	2023		2022		Change		Change Excl. F/X**
Total Revenues	$	11,337	$	11,648	(3	)%	(1)%
Earnings per share - GAAP*		1.07		0.59	81	%	N/A
Earnings per share - Non-GAAP*		2.05		1.96	5	%	N/A

* GAAP and non-GAAP earnings per share include the net impact of Acquired IPRD charges and licensing income of ($0.01) in 2023 compared to ($0.10) per share in 2022. ** See "Use of Non-GAAP Financial Information".

($ amounts in millions)	Quarter Ended March 31, 2023			% Change from Quarter Ended March 31, 2022			% Change from Quarter Ended March 31, 2022 (Excl. F/X) **
	U.S. ^(c)	Int'l	WW(d)	U.S. ^(c)	Int'l	WW(d)	Int'l	WW(d)
In-Line Products
Eliquis	$2,554	$869	$3,423	19%	(18)%	7%	(13)%	8%
Opdivo	1,290	912	2,202	17%	11%	15%	18%	17%
Pomalyst/Imnovid	545	287	832	(2)%	7%	1%	12%	2%
Orencia	562	202	764	(5)%	1%	(4)%	10%	(1)%
Sprycel	295	134	429	(3)%	(25)%	(11)%	(19)%	(9)%
Yervoy	314	194	508	1%	(5)%	(1)%	3%	2%
Mature and other products ^(a)	182	285	467	1%	(20)%	(13)%	(16)%	(10)%
Total In-Line Products	5,742	2,883	8,625	11%	(7)%	4%	(1)%	6%
New Product Portfolio
Reblozyl	158	48	206	18%	*	32%	*	33%
Abecma	118	29	147	*	*	*	*	*
Opdualag	116	1	117	*	N/A	*	N/A	*
Zeposia	52	26	78	*	73%	*	80%	*
Breyanzi	58	13	71	41%	*	61%	*	66%
Onureg	25	9	34	32%	*	48%	*	52%
Inrebic	17	8	25	13%	*	39%	*	39%
Camzyos	29	—	29	N/A	N/A	N/A	N/A	N/A
Sotyktu	15	1	16	N/A	N/A	N/A	N/A	N/A
Total New Product Portfolio	588	135	723	*	*	*	*	*
Total In-Line and New Product
Portfolio	6,330	3,018	9,348	15%	(4)%	8%	2%	10%
Recent LOE Products ^(b)
Revlimid	1,541	209	1,750	(24)%	(72)%	(37)%	(71)%	(37)%
Abraxane	162	77	239	(6)%	88%	12%	*	14%
Total Recent LOE Products	1,703	286	1,989	(23)%	(64)%	(34)%	(62)%	(33)%

Total Revenues	$8,033	$3,304	$11,337	4%	(16)%	(3)%	(11)%	(1)%

*		In excess of +100%
**		See "Use of Non-GAAP Financial Information".
(a)		Includes over-the-counter (OTC) products, royalty revenue and mature products.
(b)		Recent LOE Products includes products with significant expected decline in revenue from a prior reporting period as a result of a loss of exclusivity.
(c)		Includes Puerto Rico.
(d)		Worldwide (WW) includes International (Int'l) and U.S.

Category	Asset	Milestone
Regulatory	Camzyos ^® (mavacamten)	The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of Camzyos for the treatment of symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) in adult patients. The European Commission (EC), which has the authority to approve medicines for the European Union (EU), will now review the CHMP opinion. The positive opinion is based upon efficacy and safety results from two Phase 3 trials, EXPLORER- HCM and VALOR-HCM.
Clinical & Research	milvexian	The company, in collaboration with Janssen Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson, launched the Phase 3 Librexia program studying milvexian, an investigational oral factor XIa inhibitor (antithrombotic).The Librexia program will provide important data across three indication-seeking studies: Librexia STROKE for antiplatelet therapy for stroke prevention in acute ischemic stroke or high-risk transient ischemic stroke, Librexia ACS in addition to antiplatelet therapy for event reduction in acute coronary syndromes and Librexia AF which compares milvexian to apixaban in the prevention of stroke in patients with atrial fibrillation.

Category	Asset	Milestone
Regulatory	Opdivo ^® (nivolumab)	The U.S. Food and Drug Administration (FDA) accepted the supplemental Biologics License Application (sBLA) for Opdivo as a monotherapy in the adjuvant setting for the treatment of patients with completely resected stage IIB or IIC melanoma. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) date of October 13, 2023. In addition, the EMA validated the Type II Variation Marketing Authorization Application for Opdivo as a monotherapy in the adjuvant setting for the treatment of patients with completely resected stage IIB or IIC melanoma. The EMA's validation confirms the submission is complete and begins the start of the EMA's centralized review process. The submissions were based on results from the Phase 3 CheckMate-76K clinical trial.
Clinical & Research	Opdivo	Three-year follow-up results from Phase 3 CheckMate -816 trial demonstrated sustained clinical benefits with three cycles of Opdivo in combination with platinum-based chemotherapy for the neoadjuvant treatment of patients with resectable NSCLC. While overall survival (OS) remained immature at this analysis, there was a continued encouraging trend in OS favoring neoadjuvant Opdivo with chemotherapy over chemotherapy alone.
		Three-year follow-up results from Phase 3 CheckMate -274 trial demonstrated significant sustained clinical benefits with Opdivo for the adjuvant treatment of patients with surgically resected, high-risk muscle-invasive urothelial carcinoma.
		Three-year follow-up results from Phase 3 CheckMate -9ER trial demonstrated sustained survival and response rate benefits with the combination of Opdivo and Exelixis Inc.'s CABOMETYX (cabozantinib) versus sunitinib in the first-line treatment of advanced renal cell carcinoma.

	U.S. GAAP		Non-GAAP ²
	February (Prior)	April (Revised)	February (Prior)	April (Affirmed)
Total Revenues *(as reported)*	~2% increase	No change	~2% increase	No change
Total Revenues *(excl. F/X)*	~2% increase	No change	~2% increase	No change
*Revlimid*	~$6.5 billion	No change	~$6.5 billion	No change
Gross Margin %	~77%	No change	~77%	No change
Operating Expenses ¹	Mid single-digit decline	No change	Low single-digit decline	No change
Tax Rate	~22%	~21%	~17%	No change
Diluted EPS	$4.03-$4.33	$4.10-$4.40	$7.95-$8.25	No change
¹ Operating Expenses = MS&A and R&D, excluding Acquired IPRD and Amortization of acquired intangible assets. ² See "Use of Non-GAAP Financial Information."

Bristol-Myers Squibb COMPANY CONSOLIDATED STATEMENTS OF EARNINGS FOR THE THREE MONTHS ENDED MARCH 31, 2023 AND 2022 (Unaudited, dollars and shares in millions except per share data)

	March 31,
		2023			2022
Net product sales	$	11,048		$	11,308
Alliance and other revenues		289			340
Total Revenues		11,337			11,648
Cost of products sold ^(a)		2,566			2,471
Marketing, selling and administrative		1,762			1,831
Research and development		2,321			2,260
Acquired IPRD		75			333
Amortization of acquired intangible assets		2,256			2,417
Other (income)/expense, net		(413	)		649
Total Expenses		8,567			9,961
Earnings Before Income Taxes		2,770			1,687
Provision for Income Taxes		503			404
Net Earnings		2,267			1,283
Noncontrolling Interest		5			5
Net Earnings Attributable to BMS	$	2,262		$	1,278
Weighted-Average Common Shares Outstanding:
Basic		2,099			2,146
Diluted		2,113			2,164

Earnings per Common Share:
Basic	$	1.08		$	0.60
Diluted		1.07			0.59
Other (income)/expense, net
Interest expense ^(b)	$	288		$	326
Royalty and licensing income		(363	)		(306	)
Royalty income - divestitures		(188	)		(171	)
Equity investment losses		155			644
Integration expenses		67			105
Loss on debt redemption		—			275
Divestiture gains		—			(211	)
Litigation and other settlements		(325	)		(37	)
Investment income		(102	)		(10	)
Provision for restructuring		67			23
Other		(12	)		11
Other (income)/expense, net	$	(413	)	$	649

(a)		Excludes amortization of acquired intangible assets.
(b)		Includes amortization of purchase price adjustments to Celgene debt.

Bristol-Myers Squibb COMPANY PRODUCT REVENUES FOR THE THREE MONTHS ENDED MARCH 31, 2023 AND 2022 (Unaudited, dollars in millions)

													Change vs. 2022
	2023						2022						GAAP			Excl. F/X**
	U.S. ^(c)		Int'l		WW (d)		U.S. ^(c)		Int'l		WW (d)		U.S. ^(c)	Int'l	WW (d)	U.S. ^(c)	Int'l	WW (d)
In-Line Products
Eliquis	$	2,554	$	869	$	3,423	$	2,147	$	1,064	$	3,211	19%	(18)%	7%	19%	(13)%	8%
Opdivo		1,290		912		2,202		1,099		824		1,923	17%	11%	15%	17%	18%	17%
Pomalyst/Imnovid		545		287		832		557		269		826	(2)%	7%	1%	(2)%	12%	2%
Orencia		562		202		764		592		200		792	(5)%	1%	(4)%	(5)%	10%	(1)%
Sprycel		295		134		429		305		178		483	(3)%	(25)%	(11)%	(3)%	(19)%	(9)%
Yervoy		314		194		508		311		204		515	1%	(5)%	(1)%	1%	3%	2%
Mature and other
brands ^(a)		182		285		467		180		357		537	1%	(20)%	(13)%	1%	(16)%	(10)%
Total In-Line Products		5,742		2,883		8,625		5,191		3,096		8,287	11%	(7)%	4%	11%	(1)%	6%
New Product Portfolio
Reblozyl		158		48		206		134		22		156	18%	*	32%	18%	*	33%
Abecma		118		29		147		56		11		67	*	*	*	*	*	*
Opdualag		116		1		117		6		—		6	*	N/A	*	*	N/A	*
Zeposia		52		26		78		21		15		36	*	73%	*	*	80%	*
Breyanzi		58		13		71		41		3		44	41%	*	61%	41%	*	66%
Onureg		25		9		34		19		4		23	32%	*	48%	32%	*	52%
Inrebic		17		8		25		15		3		18	13%	*	39%	13%	*	39%
Camzyos		29		—		29		—		—		—	N/A	N/A	N/A	N/A	N/A	N/A
Sotyktu		15		1		16		—		—		—	N/A	N/A	N/A	N/A	N/A	N/A
Total New Product Portfolio		588		135		723		292		58		350	*	*	*	*	*	*
Total In-Line and New Product Portfolio		6,330		3,018		9,348		5,483		3,154		8,637	15%	(4)%	8%	15%	2%	10%
Recent LOE Products ^(b)
Revlimid		1,541		209		1,750		2,038		759		2,797	(24)%	(72)%	(37)%	(24)%	(71)%	(37)%
Abraxane		162		77		239		173		41		214	(6)%	88%	12%	(6)%	*	14%
Total Recent LOE Products		1,703		286		1,989		2,211		800		3,011	(23)%	(64)%	(34)%	(23)%	(62)%	(33)%

Total Revenues	$	8,033	$	3,304	$	11,337	$	7,694	$	3,954	$	11,648	4%	(16)%	(3)%	4%	(11)%	(1)%

Bristol-Myers Squibb COMPANY INTERNATIONAL AND WORLDWIDE REVENUES FOREIGN EXCHANGE IMPACT (%) FOR THE THREE MONTHS ENDED MARCH 31, 2023 (Unaudited)

	International			WW (c)
	Change %	Favorable/ (Unfavorable) F/X %	Change % Excl. F/X	Change %	Favorable/ (Unfavorable) F/X %	Change % Excl. F/X**
In-Line Products
Eliquis	(18)%	(5)%	(13)%	7%	(1)%	8%
Opdivo	11%	(7)%	18%	15%	(2)%	17%
Pomalyst/Imnovid	7%	(5)%	12%	1%	(1)%	2%
Orencia	1%	(9)%	10%	(4)%	(3)%	(1)%
Sprycel	(25)%	(6)%	(19)%	(11)%	(2)%	(9)%
Yervoy	(5)	(8)%	3%	(1)%	(3)%	2%
Mature and other products ^(a)	(20)%	(4)%	(16)%	(13)%	(3)%	(10)%
Total In-Line Products	(7)%	(6)%	(1)%	4%	(2)%	6%
New Product Portfolio
Reblozyl	*	*	*	32%	(1)%	33%
Abecma	*	*	*	*	*	*
Opdualag	N/A	N/A	N/A	*	*	*
Zeposia	73%	(7)%	80%	*	*	*
Breyanzi	*	*	*	61%	(5)%	66%
Onureg	*	*	*	48%	(4)%	52%
Inrebic	*	*	*	39%	—	39%
Camzyos	N/A	N/A	N/A	N/A	N/A	N/A
Sotyktu	N/A	N/A	N/A	N/A	N/A	N/A
Total New Product Portfolio	*	*	*	*	*	*
Total In-Line Products and New
Product Portfolio	(4)%	(6)%	2%	8%	(2)%	10%
Recent LOE Products ^(b)
Revlimid	(72)%	(1)%	(71)%	(37)%	—	(37)%
Abraxane	88%	(14)%	*	12%	(2)%	14%
Total Recent LOE Products	(64)%	(2)%	(62)%	(34)%	(1)%	(33)%
Total	(16)%	(5)%	(11)%	(3)%	(2)%	(1)%

*		In excess of +/- 100%.
**		See "Use of Non-GAAP Financial Information".
(a)		Includes over-the-counter (OTC) products, royalty revenue and other mature products.
(b)		Recent LOE products include products with significant expected decline in revenue from a prior reporting period as a result of a loss of exclusivity.
(c)		Worldwide (WW) includes International (Int'l) and U.S.

Bristol-Myers Squibb COMPANY SPECIFIED ITEMS FOR THE THREE MONTHS ENDED MARCH 31, 2023 AND 2022 (Unaudited, dollars in millions)

	March 31,
	2023				2022
Inventory purchase price accounting adjustments	$	53		$	52
Site exit and other costs		1			—
Cost of products sold		54			52
Site exit and other costs		—			2
Marketing, selling and administrative		—			2
IPRD impairments		20			40
Inventory purchase price accounting adjustments		—			87
Priority review voucher		95			—
Research and development		115			127
Amortization of acquired intangible assets		2,256			2,417
Interest expense ^(a)		(14	)		(27	)
Equity investment losses/(income)		150			643
Integration expenses		67			105
Loss on debt redemption		—			275
Divestiture losses/(gains)		—			(211	)
Litigation and other settlements		(335	)		(40	)
Provision for restructuring		67			23
Other		(5	)		—
Other (income)/expense, net		(70	)		768

Increase to pretax income		2,355			3,366
Income taxes on items above		(293	)		(398	)
Increase to net earnings	$	2,062		$	2,968

Bristol-Myers Squibb COMPANY RECONCILIATION OF CERTAIN GAAP LINE ITEMS TO CERTAIN NON-GAAP LINE ITEMS FOR THE THREE MONTHS ENDED MARCH 31, 2023 AND 2022 (Unaudited, dollars and shares in millions except per share data)

	Three Months Ended March 31, 2023
	GAAP			Specified Items ^(a)			Non-GAAP
Gross profit	$	8,771		$	54		$	8,825
Marketing, selling and administrative		1,762			—			1,762
Research and development		2,321			(115	)		2,206
Amortization of acquired intangible assets		2,256			(2,256	)		—
Other (income)/expense, net		(413	)		70			(343	)
Earnings before income taxes		2,770			2,355			5,125
Provision for income taxes		503			293			796
Net earnings attributable to BMS used for diluted EPS calculation	$	2,262		$	2,062		$	4,324
Weighted-average common shares outstanding - diluted		2,113			2,113			2,113
Diluted earnings per share	$	1.07		$	0.98		$	2.05
Effective tax rate		18.2	%		(2.7	)%		15.5	%

	Three Months Ended March 31, 2022
	GAAP			Specified Items ^(a)			Non-GAAP
Gross profit	$	9,177		$	52		$	9,229
Marketing, selling and administrative		1,831			(2	)		1,829
Research and development		2,260			(127	)		2,133
Amortization of acquired intangible assets		2,417			(2,417	)		—
Other (income)/expense, net		649			(768	)		(119	)
Earnings before income taxes		1,687			3,366			5,053
Provision for income taxes		404			398			802
Net earnings attributable to BMS used for diluted EPS calculation	$	1,278		$	2,968		$	4,246
Weighted-average common shares outstanding - diluted		2,164			2,164			2,164
Diluted earnings per share	$	0.59		$	1.37		$	1.96
Effective tax rate		23.9	%		(8.0	)%		15.9	%

*		Foreign exchange impacts were derived by converting our current-period local currency financial results using the prior period average currency rates and comparing these adjusted amounts to our current-period results.
**		See "Use of Non-GAAP Financial Information".
(a)		Refer to the Specified Items schedule above for further details.
(b)		Represents gross profit as a percentage of Revenues.

Bristol-Myers Squibb COMPANY NET DEBT CALCULATION AS OF MARCH 31, 2023 AND DECEMBER 31, 2022 (Unaudited, dollars in millions)

	March 31, 2023			December 31, 2022
Cash and cash equivalents	$	8,995		$	9,123
Marketable debt securities - current		274			130
Cash, cash equivalents and marketable debt securities		9,269			9,253
Short-term debt obligations		(2,752	)		(4,264	)
Long-term debt		(35,078	)		(35,056	)
Net debt position	$	(28,561	)	$	(30,067	)

Bristol-Myers Squibb COMPANY 2023 FULL YEAR PROJECTED DILUTED EPS FROM OPERATIONS EXCLUDING PROJECTED SPECIFIED ITEMS

		Full Year 2023
		Pre-tax		Tax		After-tax
Projected Diluted Earnings Attributable to Shareholders per Common Share - GAAP ^(a)		$4.10 to $4.40
Projected Specified Items:
Purchase price accounting adjustments ^(a)		4.27		0.54		3.73
Acquisition, restructuring and integration expenses ^(b)		0.17		0.03		0.14
Equity investment losses		0.07		0.01		0.06
Priority review voucher		0.04		0.01		0.03
Intangible asset impairment		0.01		—		0.01
Litigation and other settlements		(0.16	)	(0.04	)	(0.12	)
Total		4.40		0.55		3.85
Projected Diluted Earnings Attributable to Shareholders per Common Share - Non- GAAP ^(a)	$7.95 to $8.25

(a)		Includes amortization of acquired intangible assets, unwind of inventory fair value adjustments and amortization of fair value adjustments of debt assumed from Celgene.
(b)		Includes acquisition, restructuring and integration expenses recognized in Other (income)/expense, net.

The following table summarizes the company's 2023 financial guidance:
Line item	GAAP	Non-GAAP
Total reported revenues	~ 2% increase	~ 2% increase
Total revenues Ex-Fx ^(c)	~ 2% increase	~ 2% increase
Revlimid	~$6.5 billion	~$6.5 billion
Gross margin %	~ 77%	~ 77%
Operating expenses ^(d)	Mid single-digit decline	Low single-digit decline
Effective tax rate	~ 21%	~ 17%

(c)		Ex-FX excludes the impact of foreign exchange calculated by converting our current-period local currency financial results using the prior period average currency rates and comparing these adjusted amounts to our prior-period results.
(d)		Operating expenses consist of Marketing, selling and administrative expenses and Research and development expenses, excluding Acquired IPRD expenses.

U.S. Food and Drug Administration Approves Two Opdivo® -Based Regimens as First-Line Treatments for Unresectable Advanced or Metastatic Esophageal Squamous Cell Carcinoma

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