Belatacept

PRINCETON, N.J.--( BUSINESS WIRE )-- Bristol Myers Squibb (NYSE: BMY) today reports results for the fourth quarter and full year of 2024. “ We made good progress in 2024, which was capped by a fourth quarter of strong topline growth driven by key products and important pipeline advancements. We also achieved the landmark U.S. approval of Cobenfy last year for the treatment of schizophrenia in adults, and we expect this medicine to have a meaningful impact on patients and the company as a new growth driver,” said Christopher Boerner, Ph.D. , board chair and chief executive officer, Bristol Myers Squibb. “ Our collective focus on execution has established a solid foundation to navigate the multi-year journey toward achieving top-tier sustainable growth and long-term shareholder returns.” Fourth Quarter $ in millions, except per share amounts 2024 2023 Change Change Excl. F/X** Total Revenues $12,342 $11,477 8% 9% Earnings Per Share - GAAP* 0.04 0.87 (95)% N/A Earnings Per Share - Non-GAAP* 1.67 1.70 (2)% N/A Acquired IPRD Charge and Licensing Income Net Impact on Earnings Per Share 0.01 (0.20 ) N/A N/A *GAAP and Non-GAAP earnings per share include the net impact of Acquired IPRD charges and licensing income. **See "Use of Non-GAAP Financial Information". Full Year $ in millions, except per share amounts 2024 2023 Change Change Excl. F/X** Total Revenues $48,300 $45,006 7% 9% (Loss)/Earnings Per Share - GAAP* (4.41 ) 3.86 N/A N/A Earnings Per Share - Non-GAAP* 1.15 7.51 (85)% N/A Acquired IPRD Charge and Licensing Income Net Impact on Earnings Per Share (6.39 ) (0.28 ) N/A N/A *GAAP and Non-GAAP earnings per share include the net impact of Acquired IPRD charges and licensing income. **See "Use of Non-GAAP Financial Information". FOURTH QUARTER RESULTS All comparisons are made versus the same period in 2023 unless otherwise stated. Bristol Myers Squibb posted fourth quarter revenues of $12.3 billion, an increase of 8%, or 9% when adjusted for foreign exchange impacts, primarily driven by the Growth Portfolio and higher demand for Eliquis , partially offset by the impact of generics on Sprycel, Revlimid, Abraxane and Pomalyst . U.S. revenues increased 9% to $8.6 billion, primarily driven by higher demand for the Growth Portfolio and Eliquis , partially offset by the impact of generics within the Legacy Portfolio. International revenues increased 5% to $3.7 billion, or 9% when adjusted for foreign exchange impacts, primarily driven by higher demand for the Growth Portfolio, partially offset by the impact of generics within the Legacy Portfolio. On a GAAP basis, gross margin decreased from 76.1% to 61.0%, primarily driven by intangible asset impairment charges and product mix. On a non-GAAP basis, gross margin decreased from 76.4% to 74.0%, primarily due to product mix. On a GAAP and non-GAAP basis, marketing, selling and administrative expenses remained relatively flat at $2.1 billion. On a GAAP basis, research and development expenses increased 29% to $3.2 billion, primarily due to the impact of recent acquisitions and IPRD impairment charges. On a non-GAAP basis, research and development expenses increased 13% to $2.8 billion, primarily due to the impact of recent acquisitions. On a GAAP and non-GAAP basis, Acquired IPRD decreased to $30 million from $600 million. On a GAAP and non-GAAP basis, licensing income was $48 million compared to $67 million. On a GAAP basis, amortization of acquired intangible assets decreased 26% to $1.7 billion, primarily due to lower amortization expense related to Revlimid , partially offset by the RayzeBio acquisition in 2024. On a GAAP basis, the effective tax rate was 56.6%, primarily due to the impact of intangible asset impairments and amortization of acquired intangible assets. In 2023, the income tax benefit was $88 million despite pre-tax earnings of $1.7 billion, primarily due to a valuation allowance reversal and foreign currency. On a non-GAAP basis, the effective tax rate changed from 14.9% to 19.9%, primarily due to jurisdictional earnings mix. On a GAAP basis, the company reported net income attributable to Bristol Myers Squibb of $72 million, or $0.04 per share, during the fourth quarter of 2024 compared to net earnings of $1.8 billion, or $0.87 per share, for the same period a year ago. The company reported non-GAAP net earnings attributable to Bristol Myers Squibb of $3.4 billion, or $1.67 per share, during the fourth quarter of 2024 compared to $3.5 billion, or $1.70 per share, for the same period a year ago. FOURTH QUARTER PRODUCT REVENUE HIGHLIGHTS ($ amounts in millions) Quarter Ended December 31, 2024 % Change from Quarter Ended December 31, 2023 % Change from Quarter Ended December 31, 2023 Ex-F/X** U.S. Int'l (c) WW (d) U.S. Int'l (c) WW (d) Int'l (c) WW (d) Growth Portfolio Opdivo $ 1,423 $ 1,056 $ 2,479 2% 7% 4% 15% 7% Orencia 750 250 1,000 (1)% 9% 2% 15% 3% Yervoy 428 247 675 26% 9% 19% 15% 22% Reblozyl 445 102 547 65% 104% 71% 110% 72% Opdualag 233 21 254 25% >200% 34% >200% 34% Breyanzi 209 54 263 146% >200% 160% >200% 162% Camzyos 201 22 223 142% >200% 153% >200% 153% Zeposia 115 43 158 15% 30% 19% 33% 20% Abecma 59 46 105 5% 5% 5% 5% 5% Sotyktu 64 19 83 14% 171% 32% 171% 32% Krazati 36 3 39 N/A N/A N/A N/A N/A Augtyro 13 2 15 >200% N/A >200% N/A >200% Cobenfy 10 — 10 N/A N/A N/A N/A N/A Other Growth Products (a) 186 326 512 13% 104% 58% 106% 59% Total Growth Portfolio 4,172 2,191 6,363 19% 24% 21% 31% 23% Legacy Portfolio Eliquis 2,221 974 3,195 19% (3)% 11% (2)% 11% Revlimid 1,169 170 1,339 (6)% (17)% (8)% (15)% (7)% Pomalyst/Imnovid 685 138 823 9% (48)% (8)% (47)% (7)% Sprycel 135 63 198 (67)% (45)% (62)% (41)% (61)% Abraxane 91 83 174 (48)% 17% (30)% 28% (26)% Other Legacy Products (b) 123 127 250 46% (14)% 8% (15)% 7% Total Legacy Portfolio 4,424 1,555 5,979 —% (14)% (4)% (12)% (3)% Total Revenues $ 8,596 $ 3,746 $ 12,342 9% 5% 8% 9% 9% ** See "Use of Non-GAAP Financial Information". (a) Includes Nulojix, Onureg, Inrebic, Empliciti and royalty revenue. (b) Includes other mature brands. (c) Beginning in 2024, Puerto Rico revenues are included in International revenues. Prior period amounts have been reclassified to conform to the current presentation. (d) Worldwide (WW) includes U.S. and International (Int'l). FOURTH QUARTER PRODUCT REVENUE HIGHLIGHTS Growth Portfolio Growth Portfolio worldwide revenues increased to $6.4 billion compared to $5.3 billion in the prior year period, representing growth of 21% on a reported basis, or 23% when adjusted for foreign exchange impacts. Growth Portfolio revenues were primarily due to higher demand for Reblozyl, Breyanzi , Camzyos , Yervoy and Opdualag. Legacy Portfolio Revenues for the Legacy Portfolio in the fourth quarter were $6.0 billion compared to $6.2 billion in the prior year period, representing a decline of 4% on a reported basis and 3% when adjusted for foreign exchange impacts. Legacy Portfolio revenues were lower primarily due to the impact of generics on Sprycel, Revlimid, Abraxane and Pomalyst , partially offset by higher demand for Eliquis . PRODUCT AND PIPELINE UPDATE Neuroscience Category Asset Milestone Clinical & Research Cobenfy TM (xanomeline and trospium chloride) Long-term data from the Phase 3 EMERGENT-4 and EMERGENT-5 trials evaluating Cobenfy in adults with schizophrenia showed that Cobenfy was generally well tolerated over 52 weeks, with continued improvements in symptoms and a side effect profile consistent with prior trials of the treatment in this indication. Oncology Category Asset Milestone Regulatory Opdivo ® (nivolumab) + Yervoy ® (ipilimumab) The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended approval of Opdivo + Yervoy for the first-line treatment of adult patients with unresectable or advanced hepatocellular carcinoma. The recommendation is based on results of the Phase 3 CheckMate -9DW trial. The CHMP opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union. Augtyro TM (repotrectinib)* The EC approved Augtyro , a next-generation tyrosine kinase inhibitor (TKI), as a treatment for adult patients with ROS1-positive advanced non-small cell lung cancer and for the treatment of adult and pediatric patients 12 years of age and older with advanced solid tumors expressing a NTRK gene fusion, and who have received a prior NTRK inhibitor, or have not received a prior NTRK inhibitor and treatment options not targeting NTRK provide limited clinical benefit, or have been exhausted. The approval is based on results from the TRIDENT-1 and CARE trials. *Approval received on January 13, 2025, and announced today by the company. Opdivo Qvantig TM (nivolumab and hydaluronidase-nyhy) The U.S. Food and Drug Administration (FDA) approved Opdivo Qvantig injection for subcutaneous use in most previously approved adult, solid tumor Opdivo indications as monotherapy, monotherapy maintenance after completion of Opdivo plus Yervoy combination therapy, or in combination with chemotherapy or cabozantinib. The approval is based on results from the Phase 3 randomized, open-label CheckMate -67T trial. Opdivo + Yervoy The EC approved Opdivo plus Yervoy for the first-line treatment of adult patients with microsatellite instability-high or mismatch repair deficient unresectable or metastatic colorectal cancer (mCRC). The approval is based on results from the CheckMate -8HW trial. Clinical & Research Opdivo + Yervoy Results from an analysis of the Phase 3 CheckMate -8HW trial evaluating Opdivo plus Yervoy versus Opdivo monotherapy across all lines of therapy for microsatellite instability-high/mismatch repair-deficient mCRC demonstrated a statistically significant and clinically meaningful improvement at a median follow up of 47 months in the dual primary endpoint of progression-free survival as assessed by Blinded Independent Central Review. Hematology Category Asset Milestone Clinical & Research Breyanzi ® (lisocabtagene maraleucel) Five-year overall survival data from the Phase 1 TRANSCEND NHL 001 study supported deep and durable responses of Breyanzi in patients with relapsed or refractory large B-cell lymphoma (LBCL) with median overall survival (OS) of 27.5 months and an estimated OS rate at five years of 38 percent. Breyanzi continued to demonstrate an established safety profile with no new safety signals. In addition, new circulating tumor DNA (ctDNA) from the Phase 3 TRANSFORM study supported the superiority of Breyanzi to achieve deeper responses over the former standard of care in second-line LBCL. Regulatory Breyanzi The CHMP of the EMA recommended approval of Breyanzi for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy. The recommendation is based on data from the Phase 2 TRANSCEND FL study. The CHMP opinion will now be reviewed by the EC. Cardiovascular Category Asset Milestone Clinical & Research Camzyos ® (mavacamten) In Europe, following an opinion from the CHMP of the EMA, Camzyos received a label update to reduce the frequency of required echocardiography monitoring once a patient treated for obstructive hypertrophic cardiomyopathy is on a stable dose. In addition, the company is today announcing the receipt of an April Prescription Drug User Fee Act (PDUFA) goal date from the FDA in the same setting. Immunology Category Asset Milestone Clinical & Research Sotyktu ® (deucravacitinib) Results from the Phase 3 POETYK PsA-1 and POETYK PsA-2 trials evaluating the efficacy and safety of Sotyktu in adults with active psoriatic arthritis (PsA) met their primary endpoint, with a significantly greater proportion of Sotyktu -treated patients achieving at least a 20 percent improvement in signs and symptoms of disease after 16 weeks of treatment compared with placebo. In addition, both trials met secondary endpoints across PsA disease activity at Week 16. In both studies, Sotyktu was well-tolerated and demonstrated safety consistent with the established safety profile of Sotyktu observed in a Phase 2 PsA clinical trial and Phase 3 moderate-to-severe plaque psoriasis clinical trials. FULL-YEAR FINANCIAL RESULTS All comparisons are made versus the same period in 2023 unless otherwise stated. Bristol Myers Squibb posted revenues of $48.3 billion, an increase of 7%, or 9% when adjusted for foreign exchange impacts, primarily driven by the Growth Portfolio and higher demand for Eliquis , partially offset by the impact of generics on Sprycel, Revlimid and Abraxane . U.S. revenues increased 9% to $34.1 billion, primarily due to higher demand for the Growth Portfolio and Eliquis , partially offset by the impact of generics on Sprycel, Revlimid and Abraxane . International revenues increased 3% to $14.2 billion, or 8.0% when adjusted for foreign exchange impacts, primarily due to demand for Growth Portfolio products, partially offset by the impact of generics within the Legacy Portfolio. On a GAAP basis, gross margin decreased from 76.2% to 71.1%, primarily driven by intangible asset impairment charges and product mix. On a non-GAAP basis, gross margin decreased from 76.6% to 75.3%, primarily due to product mix. On a GAAP and non-GAAP basis, marketing, selling and administrative expenses increased 8% to $8.4 billion and 4% to $8.0 billion, respectively. The increase is primarily due to the timing of spend and the impact of recent acquisitions. On a GAAP basis, research and development expenses increased 20% to $11.2 billion, primarily due to the impact of recent acquisitions and IPRD impairment charges. On a non-GAAP basis, research and development expenses increased 7% to $9.8 billion, primarily due to the impact of recent acquisitions. On a GAAP and non-GAAP basis, Acquired IPRD increased from $913 million to $13.4 billion driven by a one-time Acquired IPRD charge from the Karuna asset acquisition and SystImmune collaboration. On a GAAP and non-GAAP basis, licensing income was $122 million during the year compared to $142 million in 2023. On a GAAP basis, amortization of acquired intangible assets decreased 2% to $8.9 billion, primarily due to lower amortization expense related to Revlimid , partially offset by the RayzeBio acquisition in 2024. On a GAAP basis, income tax expense was $554 million despite a pre-tax loss of $8.4 billion, primarily due to a $12.1 billion non-tax deductible charge for the Karuna acquisition. The 2023 GAAP effective tax rate was impacted by a non-U.S. tax ruling on statutory impairment deductibility, changes in tax reserves, valuation allowances, and IRS guidance on non-U.S. R&D expense deductibility. On a non-GAAP basis, the effective tax rate increased from 14.7% to 56.8%, primarily due to the non-tax deductible charge. The company reported on a GAAP basis net loss attributable to Bristol Myers Squibb of $8.9 billion, or $(4.41) per share, compared to earnings attributable to Bristol Myers Squibb of $8.0 billion, or $3.86 per share for the same period a year ago. On a non-GAAP basis the company reported net earnings attributable to Bristol Myers Squibb of $2.3 billion, or $1.15 per share, compared to earnings attributable to Bristol Myers Squibb of $15.6 billion, or $7.51 per share for the same period a year ago. In addition to the non-GAAP drivers noted above, non-GAAP EPS was impacted by higher interest expense. FULL-YEAR PRODUCT REVENUE HIGHLIGHTS ($ amounts in millions) Year Ended December 31, 2024 % Change from Year Ended December 31, 2023 % Change from Year Ended December 31, 2023 Ex-F/X** U.S. Int'l (c) WW (d) U.S. Int'l (c) WW (d) Int'l (c) WW (d) Growth Portfolio Opdivo $ 5,350 $ 3,954 $ 9,304 2% 5% 3% 14% 7% Orencia 2,770 912 3,682 2% 2% 2% 10% 4% Yervoy 1,599 931 2,530 16% 8% 13% 15% 16% Reblozyl 1,444 329 1,773 80% 61% 76% 65% 77% Opdualag 870 58 928 41% >200% 48% >200% 48% Breyanzi 591 156 747 95% 156% 105% 162% 106% Camzyos 543 59 602 141% >200% 161% >200% 161% Zeposia 403 163 566 26% 42% 30% 42% 30% Abecma 242 164 406 (32)% 44% (14)% 47% (13)% Sotyktu 190 56 246 21% >200% 45% >200% 46% Krazati 118 8 126 N/A N/A N/A N/A N/A Augtyro 36 2 38 >200% N/A >200% N/A >200% Cobenfy 10 — 10 N/A N/A N/A N/A N/A Other Growth Products (a) 674 931 1,605 9% 58% 33% 61% 34% Total Growth Portfolio 14,840 7,723 22,563 17% 16% 17% 24% 19% Legacy Portfolio Eliquis 9,631 3,702 13,333 14% (1)% 9% —% 9% Revlimid 4,999 774 5,773 (4)% (14)% (5)% (11)% (5)% Pomalyst/Imnovid 2,695 850 3,545 15% (23)% 3% (22)% 3% Sprycel 983 303 1,286 (31)% (40)% (33)% (36)% (32)% Abraxane 541 334 875 (23)% 11% (13)% 25% (8)% Other Legacy Products (b) 416 509 925 25% (19)% (4)% (18)% (3)% Total Legacy Portfolio 19,265 6,472 25,737 4% (10)% —% (8)% 1% Total Revenues $ 34,105 $ 14,195 $ 48,300 9% 3% 7% 8% 9% ** See "Use of Non-GAAP Financial Information". (a) Includes Nulojix, Onureg, Inrebic, Empliciti and royalty revenue. (b) Includes other mature brands. (c) Beginning in 2024, Puerto Rico revenues are included in International revenues. Prior period amounts have been reclassified to conform to the current presentation. (d) Worldwide (WW) includes U.S. and International (Int'l). FULL-YEAR PRODUCT REVENUE HIGHLIGHTS Growth Portfolio Growth Portfolio worldwide revenues increased to $22.6 billion compared to $19.4 billion in the prior year period, representing growth of 17% on a reported basis, or 19% when adjusted for foreign exchange impacts. Growth Portfolio revenues were primarily driven by higher demand for Reblozyl, Breyanzi , Camzyos and Opdualag. Legacy Portfolio Revenues for the Legacy Portfolio remained relatively flat at $25.7 billion compared to $25.6 billion in the prior year period, and increased 1% when adjusted for foreign exchange impacts. Legacy Portfolio revenues were primarily driven by higher demand for Eliquis , offset by the impact of generics on Sprycel, Revlimid, Abraxane and Pomalyst . Update on Strategic Productivity Initiative Bristol Myers Squibb is expanding its existing strategic productivity initiative to include approximately $2 billion in additional annualized cost savings by the end of 2027. Under this expanded initiative, savings will be driven by changes in organizational design and efforts to enhance operational efficiency. These savings will be removed from our cost structure to contribute to a leaner, more efficient company while investing behind growth brands and promising areas of science. Financial Guidance Bristol Myers Squibb is providing key 2025 non-GAAP line-item guidance assumptions as outlined below. We estimate total revenues to be approximately $45.5 billion, reflecting, as previously expected, the near-term impact of generics across Revlimid , Pomalyst , Sprycel and Abraxane , which we expect to result in a revenue decline of approximately 18-20% of the Legacy Portfolio. This is expected to be partially offset by the continued strength of our Growth Portfolio. This guidance also reflects an approximate $500 million expected negative impact to revenue due to foreign exchange. 2025 Non-GAAP 1 Line-Item Guidance Total Revenues (Reported & Ex-F/X) ~$45.5 billion Gross Margin % ~72% Operating Expenses 2 ~$16 billion Other Income/(Expense) ~$30 million Tax Rate ~18% Diluted EPS $6.55-$6.85 1 See "Use of Non-GAAP Financial Information." 2 Operating Expenses = MS&A and R&D, excluding Acquired IPRD and Amortization of acquired intangible assets. The 2025 financial guidance excludes the impact of any potential future strategic acquisitions, divestitures, specified items that have not yet been identified and quantified, and the impact of future Acquired IPRD charges. To the extent we have quantified the impact of significant R&D charges or other income resulting from upfront or contingent milestone payments in connection with asset acquisitions or licensing of third-party intellectual property rights, we may update this information from time to time on our website www.bms.com , in the "Investors" section. Non-GAAP guidance assumes current exchange rates. The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release. A reconciliation of forward-looking non-GAAP measures, including non-GAAP EPS, to the most directly comparable GAAP measures is not provided because comparable GAAP measures for such measures are not reasonably accessible or reliable due to the inherent difficulty in forecasting and quantifying measures that would be necessary for such reconciliation. Namely, we are not, without unreasonable effort, able to reliably predict the impact of accelerated depreciation and impairment charges, legal and other settlements, gains and losses from equity investments and other adjustments. In addition, the company believes such a reconciliation would imply a degree of precision and certainty that could be confusing to investors. These items are uncertain, depend on various factors and may have a material impact on our future GAAP results. See "Cautionary Statement Regarding Forward-Looking Statements" and "Use of Non-GAAP Financial Information." Conference Call Information Bristol Myers Squibb will host a conference call today, Thursday, February 6, 2025, at 8:00 a.m. ET, during which company executives will review quarterly and annual financial results and address inquiries from investors and analysts. Investors and the general public are invited to listen to a live webcast of the call at http://investor.bms.com . Investors and the public can register for the live conference call here . Those unable to register can access the live conference call by dialing in the U.S. toll-free 1-833-816-1116 or international +1 412-317-0705. Materials related to the call will be available at http://investor.bms.com prior to the start of the conference call. A replay of the webcast will be available at http://investor.bms.com approximately three hours after the conference call concludes. A replay of the conference call will be available beginning at 11:30 a.m. ET on February 6, 2025, through 11:30 a.m. ET on February 20, 2025, by dialing in the U.S. toll free 1-877-344-7529 or international +1 412-317-0088, confirmation code: 5943651. 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 , X , YouTube , Facebook , and Instagram . corporatefinancial-news Use of Non-GAAP Financial Information In discussing financial results and guidance, the company refers to financial measures that are not in accordance with U.S. Generally Accepted Accounting Principles (GAAP). The non-GAAP financial measures are provided as supplemental information to the financial measures presented in this press release that are calculated and presented in accordance with GAAP and are presented because management has evaluated the company’s financial results both including and excluding the adjusted items or the effects of foreign currency translation, as applicable, and believes that the non-GAAP financial measures presented portray the results of the company's baseline performance, supplement or enhance management's, analysts' and investors' overall understanding of the company’s underlying financial performance and trends and facilitate comparisons among current, past and future periods. In addition, non-GAAP gross margin, which is gross profit excluding certain specified items, as a percentage of revenues, non-GAAP operating margin, which is gross profit less marketing, selling and administrative expenses and research and development expenses excluding certain specified items as a percentage of revenues, non-GAAP operating expenses, which is marketing, selling and administrative and research and development expenses excluding certain specified items, non-GAAP marketing, selling and administrative expenses, which is marketing, selling and administrative expenses excluding certain specified items, and non-GAAP research and development expenses, which is research and development expenses excluding certain specified items, are relevant and useful for investors because they allow investors to view performance in a manner similar to the method used by our management and make it easier for investors, analysts and peers to compare our operating performance to other companies in our industry and to compare our year-over-year results. This earnings release and the accompanying tables also provide certain revenues and expenses, as well as non-GAAP measures, excluding the impact of foreign exchange ("Ex-Fx"). We calculate foreign exchange impacts 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. Ex-Fx financial measures are not accounted for according to GAAP because they remove the effects of currency movements from GAAP results. Non-GAAP financial measures such as non-GAAP earnings and related EPS information are adjusted to exclude certain costs, expenses, gains and losses and other specified items that are evaluated on an individual basis after considering their quantitative and qualitative aspects and typically have one or more of the following characteristics, such as being highly variable, difficult to project, unusual in nature, significant to the results of a particular period or not indicative of past or future operating results. These items are excluded from non-GAAP earnings and related EPS information because the company believes they neither relate to the ordinary course of the company’s business nor reflect the company’s underlying business performance. Similar charges or gains were recognized in prior periods and will likely reoccur in future periods, including amortization of acquired intangible assets, including product rights that generate a significant portion of our ongoing revenue and will recur until the intangible assets are fully amortized, unwinding of inventory purchase price adjustments, acquisition and integration expenses, restructuring costs, accelerated depreciation and impairment of property, plant and equipment and intangible assets, costs of acquiring a priority review voucher, divestiture gains or losses, stock compensation resulting from acquisition-related equity awards, pension, legal and other contractual settlement charges, equity investment and contingent value rights fair value adjustments (including fair value adjustments attributed to limited partnership equity method investments), income resulting from the change in control of the Nimbus Therapeutics TYK2 Program and amortization of fair value adjustments of debt acquired from Celgene in our 2019 exchange offer, among other items. Deferred and current income taxes attributed to these items are also adjusted for considering their individual impact to the overall tax expense, deductibility and jurisdictional tax rates. Certain other significant tax items are also excluded such as the impact resulting from a non-U.S. tax ruling regarding the deductibility of a statutory impairment of subsidiary investments and release of income tax reserves relating to the Celgene acquisition. Because the non-GAAP financial measures are not calculated in accordance with GAAP, they should not be considered superior to and are not intended to be considered in isolation or as a substitute for the related financial measures presented in the press release that are prepared in accordance with GAAP and may not be the same as or comparable to similarly titled measures presented by other companies due to possible differences in method and in the items being adjusted. We encourage investors to review our financial statements and publicly-filed reports in their entirety and not to rely on any single financial measure. Reconciliations of the non-GAAP financial measures to the most comparable GAAP measures are provided in the accompanying financial tables and will also be available on the company’s website at www.bms.com . Within the accompanying financial tables presented, certain columns and rows may not add due to the use of rounded numbers. Percentages and EPS amounts presented are calculated from the underlying amounts. A reconciliation of forward-looking non-GAAP measures, including non-GAAP EPS, to the most directly comparable GAAP measures is not provided because comparable GAAP measures for such measures are not reasonably accessible or reliable due to the inherent difficulty in forecasting and quantifying measures that would be necessary for such reconciliation. Namely, we are not, without unreasonable effort, able to reliably predict the impact of accelerated depreciation and impairment charges, legal and other settlements, gains and losses from equity investments and other adjustments. In addition, the company believes such a reconciliation would imply a degree of precision and certainty that could be confusing to investors. These items are uncertain, depend on various factors and may have a material impact on our future GAAP results. Website Information We routinely post important information for investors on our website, BMS.com, in the “Investors” section. We may use this website as a means of disclosing material, non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investors section of our website, in addition to following our press releases, Securities and Exchange Commission (SEC) filings, public conference calls, presentations and webcasts. We may also use social media channels to communicate with our investors and the public about our company, our products and other matters, and those communications could be deemed to be material information. The information contained on, or that may be accessed through, our website or social media channels are not incorporated by reference into, and are not a part of, this document. Cautionary Statement Regarding Forward-Looking Statements This earnings release and the related attachments (as well as the oral statements made with respect to information contained in this release and the attachments) contain certain “forward-looking” statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, regarding, among other things, the company’s 2025 financial guidance, its Strategic Productivity Initiative, its business development and capital allocation strategy, anticipated developments in the company’s pipeline, expectations with respect to the company’s future market position and the projected benefits of the company’s alliances and other business development activities. These statements may be identified by the fact that they use words such as “should,” “could,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe,” “will” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance, although not all forward-looking statements contain such terms. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. No forward-looking statement can be guaranteed, and there is no assurance that the company will achieve its financial guidance and long-term targets, that the company’s future clinical studies will support the data described in this release, that the company’s product candidates will receive necessary clinical and manufacturing regulatory approvals, that the company’s pipeline products will prove to be commercially successful, that clinical and manufacturing regulatory approvals will be sought or obtained within currently expected timeframes, or that contractual milestones will be achieved. Forward-looking statements are based on current expectations and projections about the company’s 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 the company’s control and could cause the company’s future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. Such risks, uncertainties and other matters include, but are not limited to: increasing pricing pressures from market access, pharmaceutical pricing controls and discounting; market actions taken by private and government payers to manage drug utilization and contain costs; the company’s ability to retain patent and market exclusivity for certain products; regulatory changes that result in lower prices, lower reimbursement rates and smaller populations for whom payers will reimburse; changes under the 340B Drug Pricing Program; the company’s ability to obtain and maintain regulatory approval for its product candidates; the possibility of difficulties and delays in product introduction and commercialization; increasing industry competition; potential difficulties, delays and disruptions in manufacturing, distribution or sale of products; the company’s ability to identify potential strategic acquisitions, licensing opportunities or other beneficial transactions; failure to complete, or delays in completing, collaborations, acquisitions, divestitures, alliances and other portfolio actions and the failure to achieve anticipated benefits from such transactions and actions; exposure to litigation and/or regulatory actions or investigations; the impact of any healthcare reform and legislation or regulatory action in the United States and international markets; increasing market penetration of lower-priced generic products; the failure of the company’s suppliers, vendors, outsourcing partners, alliance partners and other third parties to meet their contractual, regulatory and other obligations; the impact of counterfeit or unregistered versions of the company’s products and from stolen products; product label changes or other measures that could result in declining sales; safety or efficacy concerns regarding the company’s products or any product in the same class as the company’s products; the risk of cyber-attacks and unauthorized disclosure of trade secrets or other confidential data; the company’s ability to execute its financial, strategic and operational plans; the company’s ability to attract and retain key personnel; the impact of the company’s significant indebtedness; political and financial instability of international economies and sovereign risk; interest rate and currency exchange rate fluctuations, credit and foreign exchange risk management; risks relating to the use of social media platforms; issuance of new or revised accounting standards; and risks relating to public health outbreaks, epidemics and pandemics. Forward-looking statements in this earnings release should be evaluated together with the many risks and uncertainties that affect the company’s business and market, particularly those identified in the cautionary statement and risk factors discussion in the company’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by the company’s subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the SEC. 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, the company 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. BRISTOL-MYERS SQUIBB COMPANY CONSOLIDATED STATEMENTS OF EARNINGS (Unaudited, dollars and shares in millions except per share data) Three Months Ended December 31, Twelve Months Ended December 31, 2024 2023 2024 2023 Net product sales $ 11,811 $ 11,168 $ 46,778 $ 43,778 Alliance and other revenues 531 309 1,522 1,228 Total Revenues 12,342 11,477 48,300 45,006 Cost of products sold (a) 4,812 2,745 13,968 10,693 Marketing, selling and administrative 2,136 2,073 8,414 7,772 Research and development 3,191 2,478 11,159 9,299 Acquired IPRD 30 600 13,373 913 Amortization of acquired intangible assets 1,693 2,278 8,872 9,047 Other (income)/expense, net 305 (371 ) 893 (1,158 ) Total Expenses 12,167 9,803 56,679 36,566 (Loss)/Earnings Before Income Taxes 175 1,674 (8,379 ) 8,440 Provision for Income Taxes 99 (88 ) 554 400 Net (Loss)/Earnings 76 1,762 (8,933 ) 8,040 Noncontrolling Interest 4 — 15 15 Net (Loss)/Earnings Attributable to BMS $ 72 $ 1,762 $ (8,948 ) $ 8,025 Weighted-Average Common Shares Outstanding: Basic 2,029 2,027 2,027 2,069 Diluted 2,037 2,033 2,027 2,078 (Loss)/Earnings per Common Share: Basic $ 0.04 $ 0.87 $ (4.41 ) $ 3.88 Diluted 0.04 0.87 (4.41 ) 3.86 Other (income)/expense, net Interest expense (b) $ 496 $ 316 $ 1,947 $ 1,166 Royalty income - divestitures (284 ) (239 ) (1,104 ) (862 ) Royalty and licensing income (204 ) (420 ) (736 ) (1,488 ) Provision for restructuring 77 44 635 365 Investment income (114 ) (145 ) (478 ) (449 ) Integration expenses 70 62 284 242 Litigation and other settlements 13 3 84 (390 ) Acquisition expense — 32 50 32 Intangible asset impairments — — 47 29 Equity investment (gains)/losses 205 (53 ) (16 ) 160 Divestiture losses 10 — 15 — Other 36 29 165 37 Other (income)/expense, net $ 305 $ (371 ) $ 893 $ (1,158 ) (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 DECEMBER 31, 2024 AND 2023 (Unaudited, dollars in millions) Change vs. 2023 2024 2023 GAAP Excl. F/X** U.S. Int'l (c) WW (d) U.S. Int'l (c) WW (d) U.S. Int'l (c) WW (d) U.S. Int'l (c) WW (d) Growth Portfolio Opdivo $ 1,423 $ 1,056 $ 2,479 $ 1,401 $ 986 $ 2,387 2% 7% 4% 2% 15% 7% Orencia 750 250 1,000 755 230 985 (1)% 9% 2% (1)% 15% 3% Yervoy 428 247 675 340 226 566 26% 9% 19% 26% 15% 22% Reblozyl 445 102 547 270 50 320 65% 104% 71% 65% 110% 72% Opdualag 233 21 254 186 4 190 25% >200% 34% 25% >200% 34% Breyanzi 209 54 263 85 16 101 146% >200% 160% 146% >200% 162% Camzyos 201 22 223 83 5 88 142% >200% 153% 142% >200% 153% Zeposia 115 43 158 100 33 133 15% 30% 19% 15% 33% 20% Abecma 59 46 105 56 44 100 5% 5% 5% 5% 5% 5% Sotyktu 64 19 83 56 7 63 14% 171% 32% 14% 171% 32% Krazati 36 3 39 — — — N/A N/A N/A N/A N/A N/A Augtyro 13 2 15 1 — 1 >200% N/A >200% >200% N/A >200% Cobenfy 10 — 10 — — — N/A N/A N/A N/A N/A N/A Other Growth Products (a) 186 326 512 165 160 325 13% 104% 58% 13% 106% 59% Total Growth Portfolio 4,172 2,191 6,363 3,498 1,761 5,259 19% 24% 21% 19% 31% 23% Legacy Portfolio Eliquis 2,221 974 3,195 1,872 1,002 2,874 19% (3)% 11% 19% (2)% 11% Revlimid 1,169 170 1,339 1,244 206 1,450 (6)% (17)% (8)% (6)% (15)% (7)% Pomalyst/Imnovid 685 138 823 627 263 890 9% (48)% (8)% 9% (47)% (7)% Sprycel 135 63 198 411 115 526 (67)% (45)% (62)% (67)% (41)% (61)% Abraxane 91 83 174 176 71 247 (48)% 17% (30)% (48)% 28% (26)% Other Legacy Products (b) 123 127 250 84 147 231 46% (14)% 8% 46% (15)% 7% Total Legacy Portfolio 4,424 1,555 5,979 4,414 1,804 6,218 —% (14)% (4)% —% (12)% (3)% Total Revenues $ 8,596 $ 3,746 $ 12,342 $ 7,912 $ 3,565 $ 11,477 9% 5% 8% 9% 9% 9% ** See "Use of Non-GAAP Financial Information". (a) Includes Onureg , Inrebic, Nulojix , Empliciti and royalty revenues. (b) Includes other mature brands. (c) Beginning in 2024, Puerto Rico revenues are included in International revenues. Prior period amounts have been reclassified to conform to the current presentation. (d) Worldwide (WW) includes U.S. and International (Int'l). BRISTOL-MYERS SQUIBB COMPANY PRODUCT REVENUES FOR THE TWELVE MONTHS ENDED DECEMBER 31, 2024 AND 2023 (Unaudited, dollars in millions) Change vs. 2023 2024 2023 GAAP Excl. F/X** U.S. Int'l (c) WW (d) U.S. Int'l (c) WW (d) U.S. Int'l (c) WW (d) U.S. Int'l (c) WW (d) Growth Portfolio Opdivo $ 5,350 $ 3,954 $ 9,304 $ 5,246 $ 3,763 $ 9,009 2% 5% 3% 2% 14% 7% Orencia 2,770 912 3,682 2,709 892 3,601 2% 2% 2% 2% 10% 4% Yervoy 1,599 931 2,530 1,379 859 2,238 16% 8% 13% 16% 15% 16% Reblozyl 1,444 329 1,773 804 204 1,008 80% 61% 76% 80% 65% 77% Opdualag 870 58 928 615 12 627 41% >200% 48% 41% >200% 48% Breyanzi 591 156 747 303 61 364 95% 156% 105% 95% 162% 106% Camzyos 543 59 602 225 6 231 141% >200% 161% 141% >200% 161% Zeposia 403 163 566 319 115 434 26% 42% 30% 26% 42% 30% Abecma 242 164 406 358 114 472 (32)% 44% (14)% (32)% 47% (13)% Sotyktu 190 56 246 157 13 170 21% >200% 45% 21% >200% 46% Krazati 118 8 126 — — — N/A N/A N/A N/A N/A N/A Augtyro 36 2 38 1 — 1 >200% N/A >200% >200% N/A >200% Cobenfy 10 — 10 — — — N/A N/A N/A N/A N/A N/A Other Growth Products (a) 674 931 1,605 620 591 1,211 9% 58% 33% 9% 61% 34% Total Growth Portfolio 14,840 7,723 22,563 12,736 6,630 19,366 17% 16% 17% 17% 24% 19% Legacy Portfolio Eliquis 9,631 3,702 13,333 8,482 3,724 12,206 14% (1)% 9% 14% —% 9% Revlimid 4,999 774 5,773 5,195 902 6,097 (4)% (14)% (5)% (4)% (11)% (5)% Pomalyst/Imnovid 2,695 850 3,545 2,339 1,102 3,441 15% (23)% 3% 15% (22)% 3% Sprycel 983 303 1,286 1,422 508 1,930 (31)% (40)% (33)% (31)% (36)% (32)% Abraxane 541 334 875 702 302 1,004 (23)% 11% (13)% (23)% 25% (8)% Other Legacy Products (b) 416 509 925 334 628 962 25% (19)% (4)% 25% (18)% (3)% Total Legacy Portfolio 19,265 6,472 25,737 18,474 7,166 25,640 4% (10)% —% 4% (8)% 1% Total Revenues $ 34,105 $ 14,195 $ 48,300 $ 31,210 $ 13,796 $ 45,006 9% 3% 7% 9% 8% 9% ** See "Use of Non-GAAP Financial Information". (a) Includes Onureg , Inrebic, Nulojix , Empliciti and royalty revenues. (b) Includes other mature brands. (c) Beginning in 2024, Puerto Rico revenues are included in International revenues. Prior period amounts have been reclassified to conform to the current presentation. (d) Worldwide (WW) includes U.S. and International (Int'l). BRISTOL-MYERS SQUIBB COMPANY INTERNATIONAL REVENUES (a) FOREIGN EXCHANGE IMPACT (%) (Unaudited) Three Months Ended December 31, 2024 Twelve Months Ended December 31, 2024 Revenue Change % F/X % Favorable/ (Unfavorable) ** Revenue Change % Ex- F/X ** Revenue Change % F/X % Favorable/ (Unfavorable) ** Revenue Change % Ex- F/X ** Growth Portfolio Opdivo 7% (8)% 15% 5% (9)% 14% Orencia 9% (6)% 15% 2% (8)% 10% Yervoy 9% (6)% 15% 8% (7)% 15% Reblozyl 104% (6)% 110% 61% (4)% 65% Opdualag >200% NM >200% >200% NM >200% Breyanzi >200% NM >200% 156% (6)% 162% Camzyos >200% NM >200% >200% NM >200% Zeposia 30% (3)% 33% 42% —% 42% Abecma 5% —% 5% 44% (3)% 47% Sotyktu 171% —% 171% >200% NM >200% Krazati N/A N/A N/A N/A N/A N/A Augtyro N/A N/A N/A N/A N/A N/A Cobenfy N/A N/A N/A N/A N/A N/A Other Growth Products (b) 104% (2)% 106% 58% (3)% 61% Total Growth Portfolio 24% (7)% 31% 16% (8)% 24% Legacy Portfolio Eliquis (3)% (1)% (2)% (1)% (1)% —% Revlimid (17)% (2)% (15)% (14)% (3)% (11)% Pomalyst/Imnovid (48)% (1)% (47)% (23)% (1)% (22)% Sprycel (45)% (4)% (41)% (40)% (4)% (36)% Abraxane 17% (11)% 28% 11% (14)% 25% Other Legacy Products (c) (14)% 1% (15)% (19)% (1)% (18)% Total Legacy Portfolio (14)% (2)% (12)% (10)% (2)% (8)% Total Revenues 5% (4)% 9% 3% (5)% 8% NM Not meaningful ** See "Use of Non-GAAP Financial Information". (a) Beginning in 2024, Puerto Rico revenues are included in International revenues. Prior period amounts have been reclassified to conform to the current presentation. (b) Includes Onureg , Nulojix , Empliciti and royalty revenues. (c) Includes other mature brands. BRISTOL-MYERS SQUIBB COMPANY WORLDWIDE REVENUES (a) FOREIGN EXCHANGE IMPACT (%) (Unaudited) Three Months Ended December 31, 2024 Twelve Months Ended December 31, 2024 Revenue Change % F/X % Favorable/ (Unfavorable) ** Revenue Change % Ex- F/X ** Revenue Change % F/X % Favorable/ (Unfavorable) ** Revenue Change % Ex- F/X ** Growth Portfolio Opdivo 4% (3)% 7% 3% (4)% 7% Orencia 2% (1)% 3% 2% (2)% 4% Yervoy 19% (3)% 22% 13% (3)% 16% Reblozyl 71% (1)% 72% 76% (1)% 77% Opdualag 34% —% 34% 48% —% 48% Breyanzi 160% (2)% 162% 105% (1)% 106% Camzyos 153% —% 153% 161% —% 161% Zeposia 19% (1)% 20% 30% —% 30% Abecma 5% —% 5% (14)% (1)% (13)% Sotyktu 32% —% 32% 45% (1)% 46% Krazati N/A N/A N/A N/A N/A N/A Augtyro >200% NM >200% >200% NM >200% Cobenfy N/A N/A N/A N/A N/A N/A Other Growth Products (b) 58% (1)% 59% 33% (1)% 34% Total Growth Portfolio 21% (2)% 23% 17% (2)% 19% Legacy Portfolio Eliquis 11% —% 11% 9% —% 9% Revlimid (8)% (1)% (7)% (5)% —% (5)% Pomalyst/Imnovid (8)% (1)% (7)% 3% —% 3% Sprycel (62)% (1)% (61)% (33)% (1)% (32)% Abraxane (30)% (4)% (26)% (13)% (5)% (8)% Other Legacy Products (c) 8% 1% 7% (4)% (1)% (3)% Total Legacy Portfolio (4)% (1)% (3)% —% (1)% 1% Total Revenues 8% (1)% 9% 7% (2)% 9% NM Not meaningful ** See "Use of Non-GAAP Financial Information". (a) Worldwide (WW) includes U.S. and International (Int'l). (b) Includes Onureg , Nulojix , Empliciti and royalty revenues. (c) Includes other mature brands. BRISTOL-MYERS SQUIBB COMPANY RECONCILIATION OF GAAP AND NON-GAAP GROWTH DOLLARS AND PERCENTAGES EXCLUDING FOREIGN EXCHANGE IMPACT * (Unaudited, dollars in millions) THREE MONTHS 2024 2023 Change $ Change % Favorable / (Unfavorable) F/X $ ** 2024 Excl. F/X ** Favorable / (Unfavorable) F/X % ** % Change Excl. F/X ** Revenues $ 12,342 $ 11,477 $ 865 8 % $ (142) $ 12,484 (1)% 9% Gross profit 7,530 8,732 (1,202 ) (14 )% N/A N/A N/A N/A Gross profit excluding specified items (a) 9,130 8,770 360 4 % N/A N/A N/A N/A Gross margin (b) 61.0 % 76.1 % Gross margin excluding specified items 74.0 % 76.4 % Marketing, selling and administrative 2,136 2,073 63 3 % 21 2,157 1% 4% Marketing, selling and administrative excluding specified items (a) 2,105 2,064 41 2 % 21 2,126 1% 3% Research and development 3,191 2,478 713 29 % 8 3,199 —% 29% Research and development excluding specified items (a) 2,788 2,476 312 13 % 8 2,796 —% 13% Operating margin (c) 17.8 % 36.4 % Operating margin excluding specified items 34.3 % 36.9 % TWELVE MONTHS 2024 2023 Change $ Change % Favorable / (Unfavorable) F/X $ ** 2024 Excl. F/X ** Favorable / (Unfavorable) F/X % ** % Change Excl. F/X ** Revenues $ 48,300 $ 45,006 $ 3,294 7 % $ (654) $ 48,954 (2)% 9% Gross profit 34,332 34,313 19 — % N/A N/A N/A N/A Gross profit excluding specified items (a) 36,351 34,488 1,863 5 % N/A N/A N/A N/A Gross margin (b) 71.1 % 76.2 % Gross margin excluding specified items 75.3 % 76.6 % Marketing, selling and administrative 8,414 7,772 642 8 % 89 8,503 1% 9% Marketing, selling and administrative excluding specified items (a) 7,992 7,678 314 4 % 89 8,081 1% 5% Research and development 11,159 9,299 1,860 20 % 40 11,199 —% 20% Research and development excluding specified items (a) 9,782 9,112 670 7 % 40 9,822 1% 8% Operating margin (c) 30.6 % 38.3 % Operating margin excluding specified items 38.5 % 39.3 % * 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 below for further details. (b) Represents gross profit as a percentage of Revenues. (c) Operating margin represents gross profit less marketing, selling and administrative expenses and research and development expenses, as a percentage of Revenues. BRISTOL-MYERS SQUIBB COMPANY SPECIFIED ITEMS (Unaudited, dollars in millions) Three Months Ended December 31, Twelve Months Ended December 31, 2024 2023 2024 2023 Inventory purchase price accounting adjustments $ 13 $ — $ 47 $ 84 Intangible asset impairment 1,559 27 1,839 27 Site exit and other costs 28 11 133 64 Cost of products sold 1,600 38 2,019 175 Acquisition related charges (a) — — 372 — Site exit and other costs 31 9 50 94 Marketing, selling and administrative 31 9 422 94 IPRD impairments 390 — 980 80 Priority review voucher — — — 95 Acquisition related charges (a) — — 348 — Site exit and other costs 13 2 49 12 Research and development 403 2 1,377 187 Amortization of acquired intangible assets 1,693 2,278 8,872 9,047 Interest expense (b) (12 ) (13 ) (49 ) (52 ) Equity investment (gain)/losses 204 (54 ) (18 ) 152 Acquisition expenses — 32 50 32 Integration expenses 70 62 284 242 Divestiture losses 10 — 15 — Litigation and other settlements — — 61 (397 ) Provision for restructuring 77 44 635 365 Intangible asset impairment — — 47 29 Other 9 — 120 (6 ) Other (income)/expense, net 358 71 1,145 365 Increase to Earnings before income taxes 4,085 2,398 13,835 9,868 Income taxes on items above (749 ) (695 ) (2,045 ) (1,639 ) Income tax reserve releases — — (502 ) — Income taxes attributed to a non-U.S. tax ruling — — — (656 ) Income taxes (749 ) (695 ) (2,547 ) (2,295 ) Increase to net earnings $ 3,336 $ 1,703 $ 11,288 $ 7,573 (a) Includes cash settlement of unvested stock awards, and other related costs incurred in connection with the recent acquisitions of Karuna, RayzeBio and Mirati. (b) Includes amortization of purchase price adjustments to Celgene debt. BRISTOL-MYERS SQUIBB COMPANY RECONCILIATION OF CERTAIN GAAP LINE ITEMS TO CERTAIN NON-GAAP LINE ITEMS (Unaudited, dollars and shares in millions except per share data) Three Months Ended December 31, 2024 Twelve Months Ended December 31, 2024 GAAP Specified Items (a) Non-GAAP GAAP Specified Items (a) Non-GAAP Gross profit $ 7,530 $ 1,600 $ 9,130 $ 34,332 $ 2,019 $ 36,351 Marketing, selling and administrative 2,136 (31 ) 2,105 8,414 (422 ) 7,992 Research and development 3,191 (403 ) 2,788 11,159 (1,377 ) 9,782 Amortization of acquired intangible assets 1,693 (1,693 ) — 8,872 (8,872 ) — Other (income)/expense, net 305 (358 ) (53 ) 893 (1,145 ) (252 ) Earnings/(Loss) before income taxes 175 4,085 4,260 (8,379 ) 13,835 5,456 Provision for income taxes 99 749 848 554 2,547 3,101 Net earnings/(loss) attributable to BMS used for diluted EPS calculation $ 72 $ 3,336 $ 3,408 $ (8,948 ) $ 11,288 $ 2,340 Weighted-average common shares outstanding—diluted 2,037 2,037 2,037 2,027 2,032 2,032 Diluted earnings/(loss) per share $ 0.04 $ 1.63 $ 1.67 $ (4.41 ) $ 5.56 $ 1.15 Effective tax rate 56.6 % (36.7 )% 19.9 % (6.6 )% 63.4 % 56.8 % Three Months Ended December 31, 2023 Twelve Months Ended December 31, 2023 GAAP Specified Items (a) Non-GAAP GAAP Specified Items (a) Non-GAAP Gross profit $ 8,732 $ 38 $ 8,770 $ 34,313 $ 175 $ 34,488 Marketing, selling and administrative 2,073 (9 ) 2,064 7,772 (94 ) 7,678 Research and development 2,478 (2 ) 2,476 9,299 (187 ) 9,112 Amortization of acquired intangible assets 2,278 (2,278 ) — 9,047 (9,047 ) — Other (income)/expense, net (371 ) (71 ) (442 ) (1,158 ) (365 ) (1,523 ) Earnings before income taxes 1,674 2,398 4,072 8,440 9,868 18,308 Provision for income taxes (88 ) 695 607 400 2,295 2,695 Net earnings attributable to BMS used for diluted EPS calculation $ 1,762 $ 1,703 $ 3,465 $ 8,025 $ 7,573 $ 15,598 Weighted-average common shares outstanding—diluted 2,033 2,033 2,033 2,078 2,078 2,078 Diluted earnings per share $ 0.87 $ 0.83 $ 1.70 $ 3.86 $ 3.65 $ 7.51 Effective tax rate (5.3 )% 20.2 % 14.9 % 4.7 % 10.0 % 14.7 % (a) Refer to the Specified Items schedule above for further details. Effective tax rate on the Specified Items represents the difference between the GAAP and Non-GAAP effective tax rate. BRISTOL-MYERS SQUIBB COMPANY NET DEBT CALCULATION AS OF DECEMBER 31, 2024 AND DECEMBER 31, 2023 (Unaudited, dollars in millions) December 31, 2024 December 31, 2023 Cash and cash equivalents $ 10,346 $ 11,464 Marketable debt securities - current 513 816 Marketable debt securities - non-current 320 364 Cash, cash equivalents and marketable debt securities $ 11,179 $ 12,644 Short-term debt obligations (2,046 ) (3,119 ) Long-term debt (47,603 ) (36,653 ) Net debt position $ (38,470 ) $ (27,128 )

OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769 随着对自免发病机制的了解，靶向炎性细胞因子、免疫细胞和细胞内激酶的生物药和小分子抑制剂已成为治疗自免疾病的标准手段，也成了创新药竞相争夺的一块肥肉！ 图注：部分已上市产品的获批适应症布局（人工整理，累惨本猫，或有偏颇，持续修订） 今天我们聊一聊自免领域能够成药的靶点，都有哪些？ 01 细胞因子 1.1 TNF TNF是一种主要由髓系细胞和活化T细胞分泌促炎细胞因子，和多种自免疾病的发病有关。 阻断TNF通路可以对多种自免疾病起到治疗作用，包括，类风关（RA）RA、幼年特发性关节炎（JIA）、强直性脊柱炎（AS）、银屑病和银屑病关节炎（PsA）等。 而这个靶点也造就了曾经的全球“药王”阿达木单抗！除此外还有多款该靶点药物获得FDA批准，相关药物以及批准适应症情况如下表： 1.2 IL-17 IL-17A，通常称为IL-17，是Th17细胞亚群的标志性细胞因子，关于靶点的基本介绍在我们之前的文章也有写过（在文后有统一的合集，欢迎感兴趣的读者查看）。 来自动物和临床研究的证据表明，IL-23/IL-17轴是多种自身免疫性疾病（如AS、PsA和RA）的治疗靶标。目前靶向IL-17药物包括，IL-17A（苏金单抗和依奇珠单抗）和IL-17RA（Brodalumab）等。 1.3 IL-23 IL-23作为IL-12家族的一员，是一种由DC和活化的巨噬细胞分泌的促炎细胞因子。IL-23和IL-12共用p40 亚基，但IL-23更广泛地参与自身免疫性疾病的发病机制。 通过靶向IL-12/IL-23p40或IL-23p19，可以阻断IL-23信号。IL-23的阻断可有效治疗银屑病和PsA。 从目前上市的药物看，靶向IL-12/IL-23p40抗体药物为乌司奴单抗，可阻断IL-12和IL-23；靶向IL-23p19的药物包括：Guselkumab、Tildrakizumab、Risankizumab和Mirikizumab，这些药物仅抑制IL-23。 1.4 IL-1 IL-1家族包括IL-1α和IL-1β，是和先天免疫反应密切相关的促炎细胞因子。IL-1和受体的结合，需要IL-1R1与IL-1R3形成异源三聚体，随后募集髓MYD88，并触发随后的激酶级联反应，从而促进炎症反应。 目前研究认为在自免中IL-1β比IL-1α更重要。靶向IL-1的药物已有3种被批准：Canakinumab和Gevokizumab，这两种抗体药均靶向IL-1β；Anakinra，重组IL-1受体拮抗剂；Rilonacept，IL-1R1-Fc融合蛋白。 抗IL-1疗法更广泛地用于自身炎症性疾病，如全身性 JIA、AOSD和 CAPS。其他具有高炎症负荷的疾病，如痛风和复发性心包炎，也可通过 IL-1 靶向治疗进行控制。 另外，由于IL-1在炎症性疾病中的广泛作用，IL-1阻断有望在治疗顽固性自身免疫性疾病（包括SLE和系统性硬化症）及控制过度的促炎反应（如细胞因子释放综合征和巨噬细胞活化综合征）方面提供临床益处。 1.5 IL-6 IL-6是一种多效细胞因子，由各种类型细胞在感染、炎症和恶性肿瘤的情况下产生。 IL-6在生理和病理条件下具有多种生物学功能。生理状态下，IL-6负责巨噬细胞分化为M2状态，通过成骨细胞RANK配体表达的增加进行破骨细胞生成，及通过肝脏中的JAK-STAT通路进行急性期反应。 病理（炎症）条件下，IL-6 通过调节FOXP3、RORC和IL-23R表达，参与Th17分化，同时IL-6对滤泡辅助性T细胞的发育和B细胞的成熟也很重要。 阻断IL6通路可以通过靶向IL-6、IL-6R、gp130、JAK和STAT3来实现。这其中由于副作用，gp130和STAT3无法成药。目前抗IL-6抗体、抗IL-6R抗体和JAK抑制剂已被批准用于自免疾病的治疗。 经典的IL-6抗体药物托珠单抗，目前被批准用于治疗RA、JIA、AOSD、巨细胞动脉炎和细胞因子释放综合征。 1.6 I型IFN I型IFN，包括IFN-α、IFN-β、IFN-ε、IFN-κ和IFN-ω。研究表明，IFN-α在自身免疫性疾病，尤其是SLE的发病机制中起着至关重要的作用，IFN-α以外的IFN 的作用尚不清楚。 在SLE中，IFN-α通过刺激髓系DC、Th1细胞和B细胞及抑制Treg细胞来促进促炎反应，使用重组IFN-α治疗后产生的SLE样综合征的发展也表明 1 型IFN 在自身免疫性疾病中的病理作用。 IFN-α在SLE中的病理生理学意义,使得导致了I型IFN靶向免疫治疗的发展。Rontalizumab和Sifalimumab是靶向IFN-α的抗体，但在SLE中未能控制疾病活动。 02 靶向B细胞 随着对B细胞功能的研究，B细胞被认为是自身免疫性疾病的积极参与者。B细胞耗竭疗法在RA和多发性硬化症（MS）中的成功也证明了B细胞在自免中的病理意义。 除了在抗体产生中发挥作用外，B细胞还通过抗原呈递、三级淋巴组织的形成和细胞因子（如IL-6、TNF、IFN-γ和GM-CSF）的产生参与到自身免疫中。 2.1 CD20 CD20仅在pro-B细胞到记忆B细胞谱系中表达，不在浆细胞中表达。过去几十年，抗CD20疗法一直是B细胞耗竭的主要工具。 利妥昔单抗是一种靶向CD20的嵌合抗体，可有效消除 CD20+ B细胞，耗尽分泌自身抗体的浆母细胞的细胞来源，并阻止不依赖抗体的B细胞功能，从而减轻自身免疫性炎症，已经在RA和MS中获得临床试验的成功。 除利妥昔单抗外，多种具有不同结合表位、不同给药途径和效果的抗CD20药物在开发中。其中Ocrelizumab和Ofatumumab是人源化抗CD20 抗体，已被批准用于复发性MS。 2.2 CD19 CD19在CD20+ B 细胞以及 CD20- 浆母细胞和一些浆细胞上表达，可以起到针对抗 CD20 治疗耐药的B 细胞耗竭作用。 人源化抗CD19抗体Inebilizumab已经被批准用于治疗视神经脊髓炎谱系疾病，并且正在进行临床试验以治疗其他炎症性神经系统疾病。 2.3 B细胞活化靶点 抑制B细胞的另一种方法是阻断与B 细胞成熟和存活密切相关的因子这包括：BAFF受体（BAFF-R），在除浆细胞外的大多数B 细胞亚群上表达；B细胞成熟抗原（BCMA），在浆母细胞和浆细胞上表达。 贝利尤单抗是一种人源化抗BAFF抗体药物，是FDA批准的用于SLE的第一个靶向免疫疗法。然而，贝利尤单抗并不对所有SLE患者具有疗效。Ianalumab是一种抗BAFF-R的单克隆抗体，在原发性干燥综合征（pSS）患者的II期试验中显示出有希望的结果。 Telitacicept是一种TACI-Ig融合蛋白，基于其对BAFF/APRIL系统的抑制作用，也正在临床开发中。 03 靶向T细胞 作为适应性免疫的关键参与者，T细胞在自身免疫的发生和发展中起着关键作用。因此靶向T细胞也是自免靶向药物开发的重要考量因素。 3.1 CD28 CD28信号通过激活MAPK、AKT和NF-κB通路激活T细胞。 CTLA-4是CD28的负反馈调节因子通过占据 CD80 和CD86 来抑制 CD28 信号传导。基于CTLA-4的负向调节，设计了CTLA4 胞外结构域和IgG Fc 区（阿巴西普，CTLA4-Ig）组成的融合蛋白，目前阿巴西普已经被批准用于治疗RA 和 JIA，已证实对控制炎症性关节炎有效。 其它类似药物还包括Belatacept 和MEDI5256，正处于临床研究阶段。 3.2 CD40 CD40通路是T细胞的主要激活信号，与CD40L连接后，上调CD80和 CD86 表达。活化T 细胞的CD40L与靶细胞CD40结合时，多个激酶级联反应会激活转录因子，如NF-κB和AP1，以诱导细胞存活、增殖和分化。 CD40信号转导对于参与T 细胞依赖的抗体产生、生发中心形成和记忆 B 细胞分化的B 细胞-T 细胞相互作用尤为重要。 由于其在 B 细胞功能中的关键作用，靶向CD40 信号转导的治疗潜力已在临床前和临床研究中得到研究。Iscalimab（一种人源化抗 CD40 mAb）最近的II 期试验显示pSS 患者的临床改善，随后的 III 期试验正在进行中。 3.3 其它 靶向其他共刺激信号转导的免疫疗法，如ICOS和OX40 通路，也正在开发中，以抑制自身免疫性疾病中的 T 细胞效应功能。 作为在活化的CD4+ T 细胞上表达的共刺激分子，ICOS和OX40参与T细胞的存活、分化和活化。 04 激酶靶向治疗 JAK家族由JAK1、JAK2、JAK3和TYK2组成，与细胞因子受体（包括IL-2R、IL-4R、IL-5R、IL-6R、IL-13R 和1型IFN）、生长激素和促红细胞生成素有关。 由于JAK在细胞因子通路的关键作用，JAK抑制剂已经被批准用于RA、PsA和溃疡性结肠炎。 除JAK抑制剂外，布鲁顿酪氨酸激酶（BTK）抑制剂也有望通过调节 B 细胞功能来改善自身免疫性炎症。目前正在研究 BTK 抑制剂在各种自身免疫性疾病中的应用，包括 RA、MS、pSS 和SLE。 05 结论 过去几十年，靶向免疫药物的进步彻底改变了自免疾病患者的治疗和临床结果。 目前的靶向免疫疗法通过阻断炎性细胞因子、细胞表面分子和细胞内激酶来抑制主要的促炎信号通路。尽管靶向治疗在自身免疫性疾病中取得了巨大成功，但在药物疗效和长期安全性方面仍未满足医疗需求。 除了阻断炎症通路外，未来的疗法还旨在诱导长期的免疫耐受，同时保持保护性免疫功能。希望生物技术的进步和疾病知识将为开发具有更高治疗效果和最小不良反应的新药提供机会。 END 免责声明：本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769