Bendamustine Hydrochloride

Teva delivers 3 consecutive years of growth - 2025 revenues of $17.3 billion, an increase of 4% year-over-year (YoY) in U.S. dollars, or 3% in local currency (LC) terms, compared to 2024. Excluding Japan BV, revenues increased 5% YoY in LC.Key Innovative brands continued to drive growth and provide value for patients, with 2025 revenues surpassing $3 billion, +35% YoY in LC: AUSTEDO® global revenues of $2.26 billion, growing 34% YoY in LC. AJOVY® global revenues of $673 million, up 30% YoY in LC.UZEDY® revenues of $191 million, up 63% YoY in LC; underscoring Teva's commitment to drive new advances in neuroscience: Fastest growing long-acting injectable (LAI)1FDA expanded indication approval for Bipolar 1 Disorder. Q4 2025 marks the first quarter in which these key brands collectively delivered ~$1 billion of revenues. Generics portfolio stable: Increased by 2% in the U.S., decreased by 2% in Europe and decreased by 2% in International Markets, all in LC terms compared to 2024. Excluding Japan BV, revenues increased by 1% in International Markets in LC, compared to 2024. Biosimilars pipeline and portfolio fueling growth: – with the second-largest portfolio and most biosimilars launched across the industry since 2020.2 Innovative late-stage pipeline continued to drive transformation: 4 innovative product submissions targeted over the next 5 years.Up to $500 million in funding secured via Teva’s agreement with Royalty Pharma to fund the development of anti-IL-15 (TEV-’408) for vitiligo indication.duvakitug (anti-TL1A) Phase 3 initiated for ulcerative colitis and Crohn's disease.Preparing for olanzapine LAI U.S. launch, subject to regulatory approval; New Drug Application (NDA) submitted to FDA in December 2025.FDA fast track designations for emrusolmin for Multiple System Atrophy and anti-IL-15 for Celiac disease. Transforming and modernizing our business through Teva Transformation programs – combined with innovative product growth, expected to achieve 30% non-GAAP operating income margin by 2027. On track to deliver ~$700 million of net savings by 2027; In 2025, achieved $70 million savings and expect to realize two-thirds of the targeted savings by 2026. Q4 and FY 2025 Highlights: Q4 2025 FY 2025 Revenues $4.7 billion $17.3 billion GAAP diluted earnings per share $0.41 $1.21 Non-GAAP diluted EPS $0.96 $2.93 Cash flow generated from operating activities $1,158 million $1,649 million Free cash flow $1,298 million $2,396 million 2026 Business Outlook: Revenues of $16.4 - $16.8 billionNon-GAAP operating income of $4.55 - $4.8 billionAdjusted EBITDA of $5.0 - $5.3 billionNon-GAAP diluted EPS of $2.57 - $2.77Free cash flow of $2.0 - $2.4 billion TEL AVIV, Israel, Jan. 28, 2026 (GLOBE NEWSWIRE) -- Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today reported results for the year and the quarter ended December 31, 2025. Mr. Richard Francis, Teva's President and CEO, said: “In 2025, our Pivot to Growth strategy drove Teva's third year of consecutive growth, solidifying our transformation into a leading biopharmaceutical company. Our key innovative brands led our growth, reaching $1 billion in revenues in the fourth quarter of 2025 for the first time, and becoming a true engine of sustainable growth. Throughout the year, our teams executed with discipline across the business, driving momentum in innovative medicines, scaling our global generics and biosimilars portfolio, and further optimizing our operations and capital allocation. We also continue to make progress on our deleveraging, in line with our 2027 targets.” Mr. Francis continued: “Looking ahead, 2026 will be a milestone-rich year with multiple late-stage pipeline readouts across immunology and neurology; the anticipated FDA approval of olanzapine LAI, and important data expected for duvakitug, our anti-TL1A, and for our anti-IL-15 programs. Together, these pipeline assets represent a potential of over $10 billion, reinforcing our confidence in Teva’s ability to deliver durable, innovation-driven growth, creating real value for patients and shareholders alike." Pivot to Growth Strategy In 2025, we continued to execute on the four key pillars of our “Pivot to Growth” strategy, which we announced in May 2023. Delivering on our growth engines - We continued to showcase strong performance of our key innovative brands, mainly AUSTEDO, AJOVY, and UZEDY collectively, +35% YoY in revenues for 2025. During 2025, the FDA approved an expansion of AJOVY's indication, to include its use as an anti-CGRP preventive treatment for pediatric episodic migraine, as well as an expansion of UZEDY as treatment for adults living with Bipolar 1 Disorder. Stepping up innovation - We continued to accelerate the development of certain key pipeline assets. Teva submitted a New Drug Application for olanzapine LAI to the FDA in December 2025, and during the year we received FDA fast track designations for both emrusolmin in MSA and our IL-15 (TEV-‘408) for Celiac Disease. Phase 3 programs for duvakitug (anti-TL1A) in ulcerative colitis and Crohn's disease were initiated, and Teva is working with its partner Sanofi on targeting additional indications. By the end of 2025, we achieved the targeted initial enrollment for adult and pediatric populations for DARI’s (Dual-action Asthma Rescue Inhaler) Phase 3 trial. In January 2026, we announced a funding agreement to accelerate the development of anti-IL-15 (TEV-‘408) for vitiligo with Royalty Pharma.Sustaining our generics powerhouse - We continued to optimize our generics business and build a strong pipeline of biosimilars; For biosimilars, we launched SELARSDITM (ustekinumab-aekn) the biosimilar to Stelara® and EPYSQLI®(eculizumab-aagh) the biosimilar to Soliris®, and also received EMA approvals for PONLIMSI® (denosumab) the biosimilar to Prolia® and DEGEVMA® (denosumab) the biosimilar to Xgeva®.Focusing our business - We are actively transforming and modernizing our business through Teva Transformation programs. On May 7, 2025, we announced that these programs are expected to generate ~$700 million of net savings through 2027. In 2025, we achieved $70 million in savings and expect to realize two-thirds of the targeted savings by 2026. We continued to optimize our portfolio and global manufacturing footprint. In addition, we continue our deleveraging efforts, reducing our gross debt levels to $16.8 billion and net debt to $13.3 billion through cash flow, repayment and refinancing, and optimizing our working capital management. In response to our improved capital structure and stronger underlying performance, our credit ratings were upgraded by one level at three credit ratings agencies in 2025. 2025 Annual Consolidated Results Revenues in 2025 were $17,258 million, an increase of 4% in U.S. dollars, or 3%, in local currency terms, compared to 2024. This increase was mainly due to higher revenues from our key innovative products AUSTEDO, AJOVY and UZEDY and from development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), partially offset by lower revenues from our International Markets segment due to the divestment of our business venture in Japan, from certain other innovative products across all our segments, lower proceeds from the sale of certain product rights, and from generic products in our Europe segment. Exchange rate movements during 2025, net of hedging effects, positively impacted revenues by $152 million and negatively impacted both operating income and non-GAAP operating income by $48 million, each as compared to 2024. Gross profit was $8,938 million in 2025, an increase of 11% compared to 2024. Gross profit margin was 51.8% in 2025, compared to 48.7% in 2024. Non-GAAP gross profit was $9,647 million in 2025, an increase of 9% compared to 2024. Non-GAAP gross profit margin was 55.9% in 2025, compared to 53.3% in 2024. This increase in both gross profit margin and non-GAAP gross margin was mainly due to a favorable mix of products, primarily driven by higher revenues from AUSTEDO, and development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), partially offset by lower proceeds from the sale of certain product rights. Research and Development (R&D) expenses, net in 2025 were $1,013 million, an increase of 2% compared to $998 million in 2024. Our higher R&D expenses, net in 2025 compared to 2024, were mainly due to an increase in immunology and in immuno-oncology, as well as in neuroscience (mainly neurodegeneration), partially offset by the non-recurrence of milestone payments related to certain biosimilar projects and lower expenses related to generics projects. Selling and Marketing (S&M) expenses in 2025 were $2,686 million, an increase of 6% compared to 2024. This increase was mainly to support revenue growth in our innovative portfolio, primarily AUSTEDO, and due to a negative impact from exchange rate fluctuations. General and Administrative (G&A) expenses in 2025 were $1,287 million, an increase of 11% compared to 2024. This increase was mainly due to costs related to optimization activities of our global organization and operations in connection with our Transformation programs, as well as a negative impact from exchange rate fluctuations. Operating Income was $2,157 million in 2025, compared to an operating loss of $303 million in 2024. Operating Income as a percentage of revenues was 12.5% in 2025, compared to an operating loss as a percentage of revenues of 1.8% in 2024. This change was mainly due to the goodwill impairment charges incurred in 2024, and in 2025, due to lower other asset impairment, restructuring and other items, as well as higher gross profit and lower legal settlements and loss contingencies in 2025. Non-GAAP operating income was $4,905 million in 2025, or 28.4% of revenues compared to $4,329 million, or 26.2% of revenues in 2024. The increase in non-GAAP operating margin was mainly affected by higher non-GAAP gross profit margin, as discussed above. In 2025, financial expenses, net were $934 million, compared to $981 million in 2024. Financial expenses in 2025 were mainly comprised of net-interest expenses of $824 million. Financial expenses in 2024 were mainly comprised of net-interest expenses of $915 million. In 2025, we recognized a tax benefit of $180 million on a pre-tax income of $1,223 million. In 2024, we recognized a tax expense of $676 million on a pre-tax loss of $1,284 million. Our effective tax rate for 2025 was the result of a variety of factors, including the geographic mix and type of products sold during the year, different effective tax rates applicable to non‐Israeli subsidiaries that have tax rates different than Teva’s average tax rate, adjustments to valuation allowances on deferred tax assets, adjustments to uncertain tax positions and net deferred tax benefits from intellectual property related integration plans. Non-GAAP tax rate for 2025 was 15.8%, compared to 15.3% in 2024. Our non-GAAP tax rate for 2025 was the result of a variety of factors, including the geographic mix and type of products sold during the year, different effective tax rates applicable to non‐Israeli subsidiaries that have tax rates different than Teva’s average tax rate, adjustments to valuation allowances on deferred tax assets, adjustments to uncertain tax positions and net deferred tax benefits from intellectual property related integration plans. Net income attributable to Teva and diluted earnings per share in 2025 were $1,410 million and $1.21, respectively, compared to net loss attributable to Teva and loss per share of $1,639 million and $1.45, in 2024. This change was mainly due to the changes in operating income and income taxes, as discussed above, partially offset by net loss attributable to non-controlling interests in 2024. Non-GAAP net income attributable to Teva and non-GAAP diluted earnings per share in 2025 were $3,411 million and $2.93, respectively, compared to $2,860 million and $2.49 in 2024. Adjusted EBITDA was $5,305 million in 2025, compared to $4,781 million in 2024. As of December 31, 2025 and 2024, the fully diluted share count for purposes of calculating our market capitalization was approximately 1,184 million and 1,174 million, respectively. Non-GAAP information: non-GAAP adjustments for non-GAAP net income attributable to Teva and non-GAAP diluted EPS in 2025 were $2,001 million and consisted of the following adjustments: Amortization of purchased intangible assets totaling $581 million, of which $541 million is included in cost of goods sold and the remaining $40 million in S&M expenses;Legal settlements and loss contingencies of $473 million;Impairment of long-lived assets of $1,029 million;Restructuring expenses of $225 million;Equity compensation expenses of $157 million;Contingent consideration expenses of $54 million;Loss on sale of business of $22 million;Accelerated depreciation of $21 million;Financial expenses of $69 million;Items attributable to non-controlling interests of $2 million;Other non-GAAP items of $186 million; andCorresponding tax effects and unusual tax items of $819 million. We believe that excluding such items facilitates investors’ understanding of our business including underlying trends, thereby improving the comparability of our business performance results between reporting periods. For a reconciliation of the U.S. GAAP results to the adjusted non-GAAP figures and for additional information, see the tables below and the information included under “Non-GAAP Financial Measures.” Investors should consider non-GAAP financial measures in addition to, and not as replacement for, or superior to, measures of financial performance prepared in accordance with GAAP. Cash flow generated from operating activities in 2025 was $1,649 million, compared to $1,247 million in 2024. The increase in 2025 resulted mainly from development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), partially offset by higher legal settlement payments. Net changes in working capital items were neutral. During 2025, we generated free cash flow of $2,396 million, which we define as comprising $1,649 million in cash flow generated from operating activities, $1,214 million in beneficial interest collected in exchange for securitized accounts receivable (under our EU securitization program) and $34 million proceeds from divestitures of businesses and other assets, partially offset by $501 million in cash used for capital investments. During 2024, we generated free cash flow of $2,068 million, which we define as comprising $1,247 million in cash flow generated from operating activities, $1,291 million in beneficial interest collected in exchange for securitized accounts receivables (under our EU securitization program) and $43 million in proceeds from divestitures of businesses and other assets, partially offset by $498 million in cash used for capital investments and $15 million in cash used for acquisition of businesses, net of cash acquired. The increase in 2025 resulted mainly from higher cash flow generated from operating activities. As of December 31, 2025, our debt was $16,807 million, compared to $17,783 million as of December 31, 2024. This decrease was mainly due to repayment at maturity of $1,812 million of our senior notes, partially offset by an increase of $803 million due to exchange rate fluctuations. The portion of total debt classified as short-term as of December 31, 2025 was 11%, compared to 10% as of December 31, 2024. Our average debt maturity was approximately 5.6 years as of December 31, 2025, compared to 5.5 years as of December 31, 2024. Fourth Quarter 2025 Consolidated Results Revenues in the fourth quarter of 2025 were $4,711 million, an increase of 11% in U.S. dollars or 9% in local currency terms, compared to the fourth quarter of 2024. This increase was mainly due to development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A) and from higher revenues from our key innovative products, primarily AUSTEDO, partially offset by lower proceeds from the sale of certain product rights and lower revenues from our International Markets segment due to the divestment of our business venture in Japan. Exchange rate movements during the fourth quarter of 2025, net of hedging effects, positively impacted revenues by $99 million and negatively impacted both operating income and non-GAAP operating income by $18 million, each as compared to the fourth quarter of 2024. Gross profit in the fourth quarter of 2025 was $2,656 million, an increase of 25% compared to $2,120 million in the fourth quarter of 2024. Gross profit margin was 56.4% in the fourth quarter of 2025, compared to 50.1% in the fourth quarter of 2024. Non-GAAP gross profit was $2,840 million in the fourth quarter of 2025, an increase of 22%, compared to $2,319 million in the fourth quarter of 2024. Non-GAAP gross profit margin was 60.3% in the fourth quarter of 2025, compared to 54.8% in the fourth quarter of 2024. The increase in both gross profit margin and non-GAAP gross profit margin was mainly due to the development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), and a favorable mix of products, primarily driven by higher revenues from AUSTEDO, partially offset by lower proceeds from the sale of certain product rights. Research and Development (R&D) expenses, net in the fourth quarter of 2025 were $267 million, an increase of 8% compared to $248 million in the fourth quarter of 2024. Our higher R&D expenses, net in the fourth quarter of 2025, were mainly due to an increase in our late-stage innovative pipeline in immunology, partially offset by a decline in our late-stage innovative pipeline in neuroscience, the non-recurrence of milestone payments related to certain biosimilar projects, as well as lower expenses related to generics projects. Selling and Marketing (S&M) expenses in the fourth quarter of 2025 were $753 million, an increase of 16% compared to the fourth quarter of 2024. This increase was mainly to support revenue growth in our innovative portfolio, primarily AUSTEDO, and due to a negative impact from exchange rate fluctuations. General and Administrative (G&A) expenses in the fourth quarter of 2025 were $367 million, an increase of 22% compared to the fourth quarter of 2024. This increase was mainly due to costs related to optimization activities of Teva’s global organization and operations in connection with Teva’s Transformation programs, as well as a negative impact from exchange rate fluctuations. Operating income in the fourth quarter of 2025 was $300 million, compared to an operating loss of $29 million in the fourth quarter of 2024. Operating income as a percentage of revenues was 6.4% in the fourth quarter of 2025, compared to an operating loss as a percentage of revenues of 0.7% in the fourth quarter of 2024. This increase was mainly due to higher gross profit, as well as goodwill impairment charges in the fourth quarter of 2024, partially offset by higher charges related to other assets impairment, restructuring and other items. Non-GAAP operating income in the fourth quarter of 2025 was $1,532 million representing a non-GAAP operating margin of 32.5%, compared to non-GAAP operating income of $1,168 million representing a non-GAAP operating margin of 27.6% in the fourth quarter of 2024. The increase in non-GAAP operating margin in the fourth quarter of 2025 was due to an increase in non-GAAP gross profit margin, as discussed above. Financial expenses, net in the fourth quarter of 2025 were $220 million, mainly comprised of net-interest expenses of $200 million. In the fourth quarter of 2024, financial expenses, net were $218 million, mainly comprised of net-interest expenses of $224 million. In the fourth quarter of 2025, we recognized a tax benefit of $389 million, on a pre-tax income of $80 million. In the fourth quarter of 2024, we recognized a tax expense of $29 million, on a pre-tax loss of $247 million. Our effective tax rate for the fourth quarter of 2025 was the result of a variety of factors, including the geographic mix and type of products sold during the year, different effective tax rates applicable to non‐Israeli subsidiaries that have tax rates different than Teva’s average tax rate, adjustments to valuation allowances on deferred tax assets, net deferred tax benefits from intellectual property related integration plans and adjustments to uncertain tax positions. Non-GAAP tax rate in the fourth quarter of 2025 was 15.5%, compared to 14.8% in the fourth quarter of 2024. Our non-GAAP tax rate in the fourth quarter of 2025 was the result of a variety of factors, including the geographic mix and type of products sold during the year, different effective tax rates applicable to non‐Israeli subsidiaries that have tax rates different than Teva’s average tax rate, adjustments to valuation allowances on deferred tax assets, net deferred tax benefits from intellectual property related integration plans and adjustments to uncertain tax positions. Net income attributable to Teva and diluted earnings per share in the fourth quarter of 2025 were $480 million and $0.41, respectively, compared to net loss attributable to Teva and diluted loss per share of $217 million and $0.19, respectively, in the fourth quarter of 2024. This change was mainly due to higher gross profit and tax benefits as discussed above. Non-GAAP net income attributable to Teva and non-GAAP diluted earnings per share in the fourth quarter of 2025 were $1,130 million and $0.96, respectively, compared to $816 million and $0.71, respectively, in the fourth quarter of 2024. Adjusted EBITDA was $1,637 million in the fourth quarter of 2025, an increase of 28%, compared to $1,282 million in the fourth quarter of 2024. Non-GAAP information: non-GAAP adjustments for non-GAAP net income attributable to Teva and non-GAAP diluted EPS in the fourth quarter of 2025 were $649 million and consisted of the following adjustments: Amortization of purchased intangible assets of $145 million, of which $135 million is included in cost of sales and the remaining $10 million in S&M expenses;Impairment of long-lived assets in amount of $773 million;Legal settlements and loss contingencies of $164 million;Contingent consideration expenses of $8 million;Equity compensation expenses of $51 million;Restructuring expenses of $29 million;Loss on sale of business of $4 million;Accelerated depreciation of $9 million;Financial expenses of $11 million;Other non-GAAP items of $49 million; andCorresponding tax effects and unusual tax items of $594 million. We believe that excluding such items facilitates investors’ understanding of our business including underlying performance trends, thereby improving the comparability of our business performance results between reporting periods. For a reconciliation of the U.S. GAAP results to the adjusted non-GAAP figures and for additional information, see the tables below and the information included under “Non-GAAP Financial Measures.” Investors should consider non-GAAP financial measures in addition to, and not as replacement for, or superior to, measures of financial performance prepared in accordance with GAAP. Cash flow generated from operating activities during the fourth quarter of 2025 was $1,158 million, compared to $575 million in the fourth quarter of 2024. The higher cash flow generated from operating activities in the fourth quarter of 2025 resulted mainly from development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), as well as improvements in our net working capital, specifically accounts payable. During the fourth quarter of 2025, we generated free cash flow of $1,298 million, which we define as comprising $1,158 million in cash flow generated from operating activities, $282 million in beneficial interest collected in exchange for securitized accounts receivables (under our EU securitization program), partially offset by $142 million in cash used for capital investment. During the fourth quarter of 2024, we generated free cash flow of $790 million, which we define as comprising $575 million in cash flow generated from operating activities, $340 million in beneficial interest collected in exchange for securitized accounts receivables (under our EU securitization program) and $4 million proceeds from divestitures of businesses and other assets, partially offset by $129 million in cash used for capital investment. This increase resulted mainly from higher cash flow generated from operating activities. Segment Results for the Fourth Quarter of 2025 United States Segment The following table presents revenues, expenses and profit for our United States segment for the three months ended December 31, 2025 and 2024: Three months ended December 31, 2025 2024 (U.S. $ in millions / % of Segment Revenues) Revenues $ 2,643 100% $ 1,975 100% Cost of sales 820 31.0% 877 44.4% Gross profit 1,823 69.0% 1,097 55.6% R&D expenses 166 6.3% 158 8.0% S&M expenses 341 12.9% 260 13.2% G&A expenses 135 5.1% 109 5.5% Other § § 1 § Segment profit* $ 1,181 44.7% $ 569 28.8% *Segment profit does not include amortization and certain other items.§ Represents an amount less than $0.5 million or 0.5%, as applicable. Revenues from our United States segment in the fourth quarter of 2025 were $2,643 million, an increase of $668 million, or 34%, compared to the fourth quarter of 2024. This increase was mainly due to the development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), and higher revenues from our key innovative products, primarily AUSTEDO. Revenues by Major Products and Activities The following table presents revenues for our United States segment by major products and activities for the three months ended December 31, 2025 and 2024: Three months endedDecember 31, PercentageChange 2025 2024 2025-2024 (U.S. $ in millions) Generic products (including biosimilars) $ 673 $ 674 § AJOVY 105 63 68% AUSTEDO 725 518 40% BENDEKA®and TREANDA® 35 41 (14%) COPAXONE® 77 63 22% UZEDY 55 43 28% Anda 366 402 (9%) Other* 608 171 255% Total $ 2,643 $ 1,975 34% § Represents an amount less than 0.5%.*Other revenues in the fourth quarter of 2025 were mainly comprised of development milestone payments of $500 million received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A). Other revenues in the fourth quarter of 2024 include the sale of certain product rights. Generic products (including biosimilars) revenues in our United States segment in the fourth quarter of 2025 were $673 million, flat compared to the fourth quarter of 2024. Among the most significant generic products we sold in the United States in the fourth quarter of 2025 were Truxima® (the biosimilar to Rituxan®), epinephrine injectable solution (the generic equivalent of EpiPen® and EpiPen Jr®) and Fidaxomicin tablets (the generic equivalent of Dificid®). In the fourth quarter of 2025, our total prescriptions were approximately 254 million (based on trailing twelve months), representing 6.5% of total U.S. generic prescriptions, compared to approximately 283 million (based on trailing twelve months), representing 7.4% of total U.S. generic prescriptions in the fourth quarter of 2024, all according to IQVIA data. AJOVY revenues in our United States segment in the fourth quarter of 2025 were $105 million, an increase of 68% compared to the fourth quarter of 2024, mainly due to growth in volume. In the fourth quarter of 2025, AJOVY’s exit market share in the United States in terms of total number of prescriptions was 33.3% out of subcutaneous injectable anti-CGRP class, compared to 29.6% in the fourth quarter of 2024. AUSTEDO revenues (which include AUSTEDO XR®) in our United States segment in the fourth quarter of 2025 were $725 million, an increase of 40%, compared to $518 million in the fourth quarter of 2024. This increase was mainly due to growth in volume and a reduction in sales allowances. AUSTEDO XR (deutetrabenazine) extended-release tablets was approved by the FDA on February 17, 2023 in three doses of 6, 12 and 24 mg, and became commercially available in the U.S. in May 2023. The FDA approved AUSTEDO XR as a one pill, once-daily treatment option in doses of 30, 36, 42, and 48 mg in May 2024 and in 18 mg dose in July 2024. AUSTEDO XR is a once-daily formulation indicated in adults for tardive dyskinesia and chorea associated with Huntington’s disease, which is additional to the currently marketed twice-daily AUSTEDO. AUSTEDO XR is protected by 11 Orange Book patents expiring between 2031 and 2041. During 2025, Teva and the Centers for Medicare and Medicaid Services (“CMS”) negotiated a maximum fair price for AUSTEDO and AUSTEDO XR, based on CMS’s list of prescription medicines selected for price-setting discussions, in which they were originally included. The agreement was announced by the CMS in November 2025. The revised prices set by the U.S. Government will become effective on January 1, 2027 and will apply to eligible Medicare patients. UZEDY (risperidone) extended-release injectable suspension revenues in our United States segment in the fourth quarter of 2025 were $55 million, an increase of 28% compared to the fourth quarter of 2024, mainly due to growth in volume. BENDEKA and TREANDA combined revenues in our United States segment in the fourth quarter of 2025 were $35 million, a decrease of 14% compared to the fourth quarter of 2024, mainly due to competition from alternative therapies, as well as from generic bendamustine products. COPAXONE revenues in our United States segment in the fourth quarter of 2025 were $77 million, an increase of 22% compared to the fourth quarter of 2024, mainly due to reduction in sales allowances, partially offset by lower volumes. Anda revenues from third-party products in our United States segment in the fourth quarter of 2025 were $366 million, a decrease of 9%, compared to $402 million in the fourth quarter of 2024. This decrease was mainly due to lower volumes. Anda, our distribution business in the United States, distributes generic and innovative medicines and OTC pharmaceutical products from Teva and various third-party manufacturers to independent retail pharmacies, pharmacy retail chains, hospitals and physician offices in the United States. For information on a change to our reporting segments commencing January 1, 2026, see below under “Post-quarter Developments.” United States Gross Profit Gross profit from our United States segment in the fourth quarter of 2025 was $1,823 million, an increase of 66%, compared to $1,097 million in the fourth quarter of 2024. Gross profit margin for our United States segment in the fourth quarter of 2025 increased to 69.0%, compared to 55.6% in the fourth quarter of 2024. This increase was mainly due to the development milestone payments received in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A), and a favorable mix of products primarily driven by higher revenues from AUSTEDO. United States Profit Profit from our United States segment consists of revenues less cost of sales, R&D expenses, S&M expenses, G&A expenses and other expenses (income) related to this segment. Segment profit does not include amortization and certain other items. Profit from our United States segment in the fourth quarter of 2025 was $1,181 million, an increase of 108% compared to $569 million in the fourth quarter of 2024. This increase was mainly due to higher gross profit, as discussed above. Europe Segment Our Europe segment includes the European Union, the United Kingdom and certain other European countries. The following table presents revenues, expenses and profit for our Europe segment for the three months ended December 31, 2025 and 2024: Three months ended December 31, 2025 2024 (U.S. $ in millions / % of Segment Revenues) Revenues $ 1,314 100% $ 1,353 100% Cost of sales 606 46.1% 561 41.4% Gross profit 708 53.9% 792 58.6% R&D expenses 65 5.0% 56 4.2% S&M expenses 250 19.0% 221 16.3% G&A expenses 84 6.4% 75 5.6% Other 1 § 2 § Segment profit* $ 308 23.4% $ 438 32.4% *Segment profit does not include amortization and certain other items.§ Represents an amount less than $0.5 million or 0.5%, as applicable. Revenues from our Europe segment in the fourth quarter of 2025 were $1,314 million, a decrease of 3%, or $39 million, compared to the fourth quarter of 2024. In local currency terms, revenues decreased by 10% compared to the fourth quarter of 2024, mainly due to lower proceeds from the sale of certain product rights, lower revenues from generic and OTC products and COPAXONE, partially offset by higher revenues from AJOVY. In the fourth quarter of 2025, revenues were positively impacted by exchange rate fluctuations of $90 million, net of hedging effects, compared to the fourth quarter of 2024. Revenues in the fourth quarter of 2025 included a negligible hedging impact. Revenues in the fourth quarter of 2024 included $20 million from a positive hedging impact, which is included in “Other” in the table below. Revenues by Major Products and Activities The following table presents revenues for our Europe segment by major products and activities for the three months ended December 31, 2025 and 2024: Three months endedDecember 31, PercentageChange 2025 2024 2025-2024 (U.S. $ in millions) Generic products (including OTC and biosimilars) $ 1,033 $ 979 5% AJOVY 76 58 30% COPAXONE 45 50 (9%) Respiratory products 65 61 6% Other* 96 205 (53%) Total $ 1,314 $ 1,353 (3%) *Other revenues in the fourth quarter of 2025 and 2024 include the sale of certain product rights. Generic products revenues (including OTC and biosimilar products) in our Europe segment in the fourth quarter of 2025, were $1,033 million, an increase of 5% compared to the fourth quarter of 2024. In local currency terms, revenues decreased by 4%, mainly due to lower volumes and price reductions as a result of market dynamics, and lower sales of seasonal OTC products, partially offset by higher revenues from recently launched products. AJOVY revenues in our Europe segment in the fourth quarter of 2025 increased by 30% to $76 million, compared to $58 million in the fourth quarter of 2024. In local currency terms revenues increased by 19% due to growth in volume. COPAXONE revenues in our Europe segment in the fourth quarter of 2025 were $45 million, a decrease of 9% compared to the fourth quarter of 2024. In local currency terms revenues decreased by 17%, due to price reductions and lower volumes resulting from the availability of alternative therapies. Respiratory products revenues in our Europe segment in the fourth quarter of 2025 were $65 million, an increase of 6% compared to the fourth quarter of 2024. In local currency terms, revenues decreased by 2%, mainly due to net price reductions and lower volumes. Europe Gross Profit Gross profit from our Europe segment in the fourth quarter of 2025 was $708 million, a decrease of 11% compared to $792 million in the fourth quarter of 2024. Gross profit margin for our Europe segment in the fourth quarter of 2025 decreased to 53.9%, compared to 58.6% in the fourth quarter of 2024. This decrease was mainly due to lower proceeds from the sale of certain product rights, a negative impact from hedging activities and an unfavorable change in the mix of products. Europe Profit Profit from our Europe segment consists of revenues less cost of sales, R&D expenses, S&M expenses, G&A expenses and other expenses (income) related to this segment. Segment profit does not include amortization and certain other items. Profit from our Europe segment in the fourth quarter of 2025 was $308 million, a decrease of 30%, compared to $438 million in the fourth quarter of 2024. This decrease was mainly due to lower gross profit and higher operating expenses. International Markets Segment Our International Markets segment includes all countries in which we operate other than the United States and the countries included in our Europe segment. The International Markets segment covers a substantial portion of the global pharmaceutical industry, including more than 35 countries. The countries in our International Markets segment include highly regulated, mainly generic markets, such as Canada and Israel, and branded generics-oriented markets, such as Russia and certain Latin America markets. On March 31, 2025, we divested our Teva-Takeda business venture in Japan, which included generic products and legacy products. Since the establishment of the business venture and until the completion of its sale, Teva held 51% of the outstanding common stock of the business venture. On March 31, 2025, we deconsolidated the business venture from our financial statements. The following table presents revenues, expenses and profit for our International Markets segment for the three months ended December 31, 2025 and 2024: Three months ended December 31, 2025 2024 (U.S. $ in millions / % of Segment Revenues) Revenues $ 528 100% $ 661 100% Cost of sales 281 53.1% 315 47.7% Gross profit 247 46.9% 346 52.3% R&D expenses 27 5.2% 27 4.1% S&M expenses 121 23.0% 137 20.7% G&A expenses 40 7.6% 42 6.3% Other (11) § (1) § Segment profit* $ 70 13.3% $ 141 21.4% *Segment profit does not include amortization and certain other items.§ Represents an amount less than $0.5 million or 0.5%, as applicable. Revenues from our International Markets segment in the fourth quarter of 2025 were $528 million, a decrease of 20% in both U.S. dollars and local currency terms, compared to the fourth quarter of 2024. This decrease was mainly due to the divestment of our business venture in Japan, lower proceeds from the sale of certain product rights, as well as a negative hedging impact, partially offset by higher revenues from generic products in other markets and AJOVY. In the fourth quarter of 2025, revenues were positively impacted by exchange rate fluctuations of $2 million, net of hedging effects, compared to the fourth quarter of 2024. Revenues in the fourth quarter of 2025 included $14 million from a negative hedging impact, compared to a positive hedging impact of $13 million in the fourth quarter of 2024, which are included in “Other” in the table below. The following table presents revenues for our International Markets segment by major products and activities for the three months ended December 31, 2025 and 2024: Three months endedDecember 31, PercentageChange 2025 2024 2025-2024 (U.S. $ in millions) Generic products (including OTC and biosimilars) $ 422 $ 497 (15%) AJOVY 30 22 40% AUSTEDO 9 7 29% COPAXONE 6 9 (31%) Other* 60 126 (52%) Total $ 528 $ 661 (20%) *Other revenues in the fourth quarter of 2025 and 2024 include the sale of certain product rights. Generic products revenues (including OTC and biosimilar products) in our International Markets segment were $422 million in the fourth quarter of 2025, a decrease of 15% in U.S. dollars or 20% in local currency terms, compared to the fourth quarter of 2024, mainly due to the divestment of our business venture in Japan, partially offset by higher revenues in other markets. AJOVY revenues in our International Markets segment in the fourth quarter of 2025 were $30 million, compared to $22 million in the fourth quarter of 2024. In local currency terms, revenues increased by 35%, mainly due to growth in volume. AUSTEDO revenues in our International Markets segment in the fourth quarter of 2025 were $9 million compared to $7 million in the fourth quarter of 2024. In local currency terms, revenues increased by 21%. In February 2024, we announced a strategic partnership for the marketing and distribution of AUSTEDO in China. In April 2025, AUSTEDO received marketing authorization in South Korea. We continue to evaluate additional submissions in various other markets. COPAXONE revenues in our International Markets segment in the fourth quarter of 2025 were $6 million compared to $9 million in the fourth quarter of 2024. International Markets Gross Profit Gross profit from our International Markets segment in the fourth quarter of 2025 was $247 million, a decrease of 28% compared to $346 million in the fourth quarter of 2024. Gross profit margin for our International Markets segment in the fourth quarter of 2025 decreased to 46.9%, compared to 52.3% in the fourth quarter of 2024. This decrease was mainly due to lower proceeds from the sale of certain product rights and a negative hedging impact, partially offset by price increases due to inflationary pressures in certain markets and a favorable mix of products. International Markets Profit Profit from our International Markets segment consists of revenues less cost of sales, R&D expenses, S&M expenses, G&A expenses and other expenses (income) related to this segment. Segment profit does not include amortization and certain other items. Profit from our International Markets segment in the fourth quarter of 2025 was $70 million, a decrease of 50%, compared to $141 million in the fourth quarter of 2024. This decrease was mainly due to lower proceeds from the sale of certain product rights, a negative hedging impact, as well as the divestment of our business venture in Japan. Other Activities We have other sources of revenues, primarily the sale of APIs to third parties, certain contract manufacturing services and an out-licensing platform offering a portfolio of products to other pharmaceutical companies through our affiliate Medis. Our other activities are not included in our United States, Europe or International Markets segments described above. For information on a change to our reporting segments commencing January 1, 2026, see below under “Post Quarter Developments.” Revenues from other activities in the fourth quarter of 2025 were $226 million, a decrease of 6% in U.S. dollars, or 9% in local currency terms, compared to the fourth quarter of 2024, mainly due to a decrease in revenues from contract manufacturing services. API sales to third parties in the fourth quarter of 2025 were $136 million, a decrease of 4% in both U.S. dollars and local currency terms, compared to the fourth quarter of 2024. Post Quarter Developments To align with Teva's Pivot to Growth strategy, commencing January 1, 2026, Anda will no longer be reported under Teva's United States segment. This shift will allow the United States segment to continue to manage its entire product portfolio in the region, while strengthening focus on its biopharmaceutical business, growth engines and innovation. As a result, from that date, Anda will be reported as part of the Company’s Other Activities. In January 2026, we announced a funding agreement to accelerate the development of anti-IL-15 (TEV-‘408) for vitiligo with Royalty Pharma; in addition, Teva and Abingworth signed an amendment to the development funding agreement to increase the total development funding by an additional $50 million for DARI (ICS-SABA). 2026 Financial Outlook $ billions, except diluted EPS or as noted 2026 Outlook Revenues 16.4 - 16.8 AUSTEDO ($m) 2,400 - 2,550 AJOVY ($m) 750 - 790 UZEDY ($m) 250 - 280 Operating Income* 4.55-4.8 Adjusted EBITDA* 5.0-5.3 Finance Expenses* ($m) ~800 Tax Rate* 16% - 19% Diluted EPS* ($) 2.57 - 2.77 Free Cash Flow* 2.0 - 2.4 CAPEX 0.5 Foreign Exchange Volatile swings in FX can negativelyimpact revenue and income 1,177M shares *Certain items above are non-GAAP financial measures. For more information, see “Non-GAAP Financial Measures” below. Free Cash Flow includes cash flow generated from operating activities net of capital expenditures and deferred purchase price cash component collected for securitized trade receivables. Annual Report on Form 10-K Teva's Annual Report on Form 10-K for the year ended December 31, 2025, which will be filed with the SEC, will be available on Teva’s website: http://ir.tevapharm.com, as well as on the SEC’s website: http://www.sec.gov. Conference Call Teva will host a conference call and live webcast along with a slide presentation on Wednesday, January 28, 2026 at 8:00 a.m. ET to discuss its fourth quarter of 2025 and annual 2025 financial results and overall business environment. A question & answer session will follow. In order to participate, please register in advance here to obtain a local or toll-free phone number and your personal pin.A live webcast of the call will be available on Teva's website at: https://ir.tevapharm.com/Events-and-Presentations. About Teva Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is transforming into a leading innovative biopharmaceutical company, enabled by a world-class generics business. For over 120 years, Teva’s commitment to bettering health has never wavered. From innovating in the fields of neuroscience and immunology to providing complex generic medicines, biosimilars and pharmacy brands worldwide, Teva is dedicated to addressing patients’ needs, now and in the future. At Teva, We Are All In For Better Health. To learn more about how, visit www.tevapharm.com. Some amounts in this press release may not add up due to rounding. All percentages have been calculated using unrounded amounts. Non-GAAP Financial Measures This press release contains certain financial information that differs from what is reported under accounting principles generally accepted in the United States ("GAAP"). These non-GAAP financial measures, including, but not limited to, non-GAAP operating income, non-GAAP operating margin, non-GAAP gross profit, non-GAAP gross profit margin, Adjusted EBITDA, free cash flow, non-GAAP tax rate, non-GAAP net income (loss) attributable to Teva and non-GAAP diluted EPS, are presented in order to facilitate investors' understanding of our business. We utilize certain non-GAAP financial measures to evaluate performance in conjunction with other performance metrics. The following are examples of how we utilize the non-GAAP measures: our management and board of directors use the non-GAAP measures to evaluate our operational performance and, to compare our results against work plans and budgets, and ultimately to evaluate the performance of management; our annual budgets are prepared on a non-GAAP basis; and senior management’s annual compensation is derived, in part, using these non-GAAP measures. See the attached tables for a reconciliation of the GAAP results to the adjusted non-GAAP measures. Investors should consider non-GAAP financial measures in addition to, and not as replacements for, or superior to, measures of financial performance prepared in accordance with GAAP. We are not providing the most comparable forward-looking GAAP measures for non-GAAP metrics included in our financial outlook or a quantitative reconciliation of forward-looking non-GAAP financial measures to the most directly comparable GAAP measures because we are unable to predict with reasonable certainty the ultimate outcome of certain significant items including, but not limited to, the amortization of purchased intangible assets, legal settlements and loss contingencies, impairment of long-lived assets and goodwill impairment, without unreasonable effort. These items are uncertain, depend on various factors, and could be material to our results computed in accordance with GAAP. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. These forward-looking statements include statements concerning our plans, strategies, objectives, future performance and financial and operating targets, and any other information that is not historical information. You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe,” "outlook" and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance. Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully compete in the marketplace, including: that we are substantially dependent on our generic products; concentration of our customer base and commercial alliances among our customers; competition faced by our generic medicines from other pharmaceutical companies and changes in regulatory policy that may result in costs and delays; delays in launches of new generic products; our ability to develop and commercialize additional pharmaceutical products in a timely manner; intense competition for our innovative medicines; our ability to achieve expected results from investments in our product pipeline; our ability to successfully execute our Pivot to Growth strategy, including to expand our innovative and biosimilar medicines pipeline and profitably commercialize our innovative medicines and biosimilar portfolio, whether organically or through business development, to sustain and focus our portfolio of generic medicines, and to execute on our organizational transformation and to achieve expected cost savings; and the effectiveness of our patents and other measures to protect our intellectual property rights;our significant indebtedness, which may limit our ability to incur additional indebtedness, engage in additional transactions or make new investments; and our potential need to raise additional funds in the future, which may not be available on acceptable terms or at all;our business and operations in general, including: the impact of global economic conditions and other macroeconomic developments and the governmental and societal responses thereto, and our exposure to changes in international trade policies, including the imposition of tariffs in the jurisdictions in which we operate, and any effects of such developments on sales of our products and the pricing and availability of our raw materials; effectiveness of our optimization efforts; significant disruptions of information technology systems, including cybersecurity attacks, as well as risks and uncertainties related to the adoption of artificial intelligence technologies, and breaches of our data security; interruptions in our supply chain or problems with internal or third party manufacturing; challenges associated with conducting business globally, including political or economic instability, prolonged government shutdowns, widespread outbreaks of major diseases and major hostilities or acts of terrorism, such as the ongoing conflicts between Russia and Ukraine and in the Middle East; our ability to attract, hire, integrate and retain highly skilled personnel; our ability to successfully bid for suitable acquisition targets or licensing opportunities, or to consummate and integrate acquisitions; and our prospects and opportunities for growth if we sell assets or business units and close or divest plants and facilities, as well as our ability to successfully and cost-effectively consummate such sales and divestitures, including our planned divestiture of our API business;compliance, regulatory and litigation matters, including: failure to comply with complex legal and regulatory requirements, the effects of regulatory uncertainty and changes and the results of increased regulatory oversight, including expenditures required to ensure compliance with research, production and quality control regulations and remedial actions taken to address product issues, such as delayed product launches, product recalls, and facility shutdowns; the effects of governmental, regulatory and civil proceedings and litigation which we are, or in the future become, party to; the effects of reforms in healthcare regulation and related reductions in pharmaceutical pricing, reimbursement and coverage, including as a result of the One Big Beautiful Bill signed into law in the U.S. in July 2025 (“OBBBA”), which will likely reduce the number of insured in Medicaid and Health Insurance Exchange markets, which may alter utilization patterns and shift negotiating leverage among payors, U.S. Executive Orders issued in April and May 2025 intended to reduce the prices paid by Americans for prescription medicines, including Most-Favored-Nation pricing; legal and regulatory actions in connection with public concern over the abuse of opioid medications; our ability to timely make payments required under our nationwide opioids settlement agreement and provide our generic version of Narcan® (naloxone hydrochloride nasal spray) in the amounts and at the times required under the terms of such agreement; scrutiny from competition and pricing authorities around the world, including our ability to comply with and operate under our deferred prosecution agreement (“DPA”) with the U.S. Department of Justice (“DOJ”); potential liability for intellectual property right infringement; significant product liability claims; claims brought by regulatory agencies; failure to comply with complex Medicare, Medicaid and other governmental programs’ reporting and payment obligations; compliance with sanctions and trade control laws; environmental risks and changes in governmental, investor and societal responses to climate change and sustainability related issues; other financial and economic risks, including: our exposure to currency fluctuations and restrictions as well as credit risks; impairments of our long-lived assets; potential significant increases in tax liabilities; the effect on our overall effective tax rate of the termination or expiration of governmental programs or tax benefits, or of a change in our business; and the impact of any failure to maintain effective internal control over our financial reporting; and other factors discussed in this press release, in our Annual Report on Form 10-K for the year ended December 31, 2024, including in the section captioned "Risk Factors” and in other periodic reports we subsequently file with the SEC available on the SEC’s website: http://www.sec.gov. Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward‐looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements. Consolidated Statements of Income(U.S. dollars in millions, except share and per share data)Unaudited Three months ended Year ended December 31, December 31, 2025 2024 2025 2024Net revenues 4,711 4,229 17,258 16,544Cost of sales 2,056 2,109 8,320 8,481Gross profit 2,656 2,120 8,938 8,064Research and development expenses 267 248 1,013 998Selling and marketing expenses 753 650 2,686 2,541General and administrative expenses 367 302 1,287 1,161Intangible assets impairments 32 81 259 251Goodwill impairment - 280 - 1,280Other asset impairments, restructuring and other items.................................................... 778 457 1,050 1,388Legal settlements and loss contingencies........................................................................... 155 123 467 761Other (income) loss ............................................................................................................ 3 8 18 (14)Operating income (loss) 300 (29) 2,157 (303)Financial expenses, net 220 218 934 981Income (loss) before income taxes 80 (247) 1,223 (1,284)Income taxes (benefit)..................................................................................... (389) 29 (180) 676Share in (profits) losses of associated companies, net (11) (1) (15) (1)Net income (loss) 481 (275) 1,418 (1,959)Net income (loss) attributable to non-controlling interests § (58) 7 (320)Net income (loss) attributable to Teva 480 (217) 1,410 (1,639) Earnings (loss) per share attributable to Teva:Basic ($)0.42 (0.19) 1.23 (1.45) Diluted ($)0.41 (0.19) 1.21 (1.45)Weighted average number of shares (in millions):Basic1,149 1,133 1,145 1,131 Diluted1,173 1,133 1,163 1,131 Non-GAAP net income attributable to Teva for diluted earnings per share:* 1,130 816 3,411 2,860 Non-GAAP earnings per share attributable to Teva:*Diluted ($)0.96 0.71 2.93 2.49 Non-GAAP average number of shares (in millions):Diluted1,173 1,157 1,163 1,150 Amounts may not add up due to rounding. § Represents an amount less than $0.5 million. * See reconciliation attached. Condensed Consolidated Balance Sheets (U.S. dollars in millions)Audited December 31, December 31, 2025 2024 ASSETS Current assets: Cash and cash equivalents 3,556 3,300Accounts receivables, net of allowance for credit losses of $81 million and $78 million as of December 31, 2025 and December 31, 2024 3,709 3,059Inventories 3,179 3,007Prepaid expenses 1,122 1,006Other current assets 539 409Assets held for sale 1,842 1,771Total current assets 13,946 12,552Deferred income taxes 2,191 1,799Other non-current assets 405 462Property, plant and equipment, net 4,080 4,581Operating lease right-of-use assets 345 367Identifiable intangible assets, net 3,781 4,418Goodwill 16,000 15,147Total assets 40,748 39,326 LIABILITIES & EQUITY Current liabilities: Short-term debt 1,820 1,781Sales reserves and allowances 4,143 3,678Trade payables 2,531 2,203Employee-related obligations 739 624Accrued expenses 2,687 2,792Other current liabilities 1,182 1,020Liabilities held for sale 354 698Total current liabilities 13,456 12,796 Long-term liabilities: Deferred income taxes 296 483Other taxes and long-term liabilities 3,808 4,028Senior notes and loans 14,986 16,002Operating lease liabilities 288 296Total long-term liabilities 19,379 20,809Redeemable non-controlling interests - 340 Equity: Teva shareholders’ equity: 7,910 5,373Non-controlling interests....................................................... 4 7Total equity 7,914 5,380Total liabilities and equity 40,748 39,326 TEVA PHARMACEUTICAL INDUSTRIES LIMITEDCONSOLIDATED STATEMENTS OF CASH FLOWS(U.S. dollars in millions)Unaudited Year ended Three months ended December 31, December 31, 2025 2024 2025 2024 Operating activities: (Audited) (Audited) Unaudited UnauditedNet income (loss)........................................................................................... 1,418 —(1,959) $480 $(275)Adjustments to reconcile net income (loss) to net cash provided by operations: Impairment of goodwil - 1,280 - 280Impairment of long-lived assets and assets held for sale........... 1,028 1,275 773 517Depreciation and amortization....................................................................... 1,002 1,059 260 269Net change in operating assets and liabilities............................................... (1,366) (435) 181 (246)Deferred income taxes — net and uncertain tax positions......................... (671) (634) (595) 32Stock-based compensation............................................................................. 157 123 51 34Net loss (gain) from sale of business and long-lived assets - (22) - -Other items,net* ..................................................................................................... 81 560 8 (37)Net cash provided by (used in) operating activities.......................................................................................1,649 1,247 1,158 575 Investing activities: Beneficial interest collected in exchange for securitized trade receivables 1,214 1,291 282 340Purchases of property, plant and equipment and intangible assets............. (501) (498) (142) (129)Proceeds from sale of business and long lived assets................................. 34 43 - 4Purchases of investments and other assets................................................... (57) (71) (17) (15)Proceeds from sale of investments............................................................... 42 40 41 -Acquisitions of businesses, net of cash acquired ........................................ - (15) - -Other investing activities................................................................................ 5 2 1 2Net cash provided by (used in) investing activities............................... 737 792 165 202 Financing activities: Repayment of senior notes and loans and other long term liabilities........ (4,112) (1,641) - (685)Proceeds from senior notes, net of issuance costs..................................... 2,298 - - -Purchase of shares from redeemable and non-redeemable non-controlling interests (38) (64) - -Dividends paid to redeemable and non-redeemable non-controlling interests (340) (78) - -Other financing activities............................................................................... 41 (8) 40 10Net cash provided by (used in) financing activities.............................. (2,151) (1,791) 40 675Translation adjustment on cash, cash equivalents and restricted cash 21 (174) (10) (121)Net change in cash, cash equivalents and restricted cash$256 $74 $1,353 $(19)Balance of cash, cash equivalents and restricted cash at beginning of year 3,300 3,227 2,203 3,319Balance of cash, cash equivalents and restricted cash at end of year 3,556 3,300 3,556 3,300 Reconciliation of cash, cash equivalents and restricted cash reported in the consolidated balance sheets: Cash and cash equivalents 3,556 3,300 3,556 3,300Restricted cash included in other current assets - - - -Total cash, cash equivalents and restricted cash shown in the statements of cash flows 3,556 3,300 3,556 3,300 *"Other items, net" in the year ended December 31, 2024 includes mainly amounts related to an agreement with the Israeli Tax Authorities. Reconciliation of net income (loss) attributable to Tevato Non-GAAP net income (loss) attributable to Teva Unaudited Three months ended Year ended December 31, December 31,($ in millions except per share amounts) 20252024 2025 2024Net income (Loss) attributable to Teva($)480(217) ($)1,410 (1,639)Increase (decrease) for excluded items: Amortization of purchased intangible assets 145144 581 588 Legal settlements and loss contingencies(1) 164123 473 761 Goodwill impairment(2) -280 - 1,280 Impairment of long-lived assets(3) 773517 1,029 1,275 Restructuring costs(4) 2922 225 74 Equity compensation 5134 157 123 Contingent consideration(5) 8(2) 54 303 Loss (Gain) on sale of business 46 22 (15) Accelerated depreciation 95 21 13 Financial expenses 1113 69 49 Items attributable to non-controlling interests(3) -(63) 2 (339) Other non-GAAP items(6) 4967 186 229 Corresponding tax effects and unusual tax items(7) (594)(114) (819) 157Non-GAAP net income attributable to Teva($)1,130816 ($)3,411 2,860Non-GAAP tax rate(8) 15.5%14.8% 15.8% 15.3%GAAP diluted earnings (loss) per share attributable to Teva($)0.41(0.19) ($)1.21 (1.45)EPS difference(9) 0.550.90 1.72 3.94Non-GAAP diluted EPS attributable to Teva(9)($)0.960.71 ($)2.93 2.49Non-GAAP average number of shares (in millions)(9) 1,1731,157 1,163 1,150 (1)For the forth quarter of 2025, adjustments of legal settlements and loss contingencies mainly consisted of $81 million related to the provision for the opioid cases (mainly the effect of the passage of time on the net present value of the discounted payments), an update of $56 million related to the provision recorded for the carvedilol patent litigation. Adjustments for legal settlements and loss contingencies in 2025 were mainly related to an update to the estimated settlement provision of $220 million for the opioid cases (mainly the effect of the passage of time on the net present value of the discounted payments), an update of $56 million related to the provision recorded for the carvedilol patent litigation, an update of $55 million related to the estimated provision recorded for the claims brought by attorneys general representing states and territories throughout the United States in the generic drug antitrust litigation, as well as a provision of $35 million recorded for the antitrust litigation related to QVAR. Adjustments for legal settlements and loss contingencies in 2024 were mainly related to legal expenses of $357 million recorded in connection with a decision by the European Commission in its antitrust investigation into COPAXONE, and an update to the estimated settlement provision of $278 million for the opioid cases (mainly the effect of the passage of time on the net present value of the discounted payments and the settlement agreement with the city of Baltimore).(2)During the fourth quarter of 2024 a goodwill impairment charge of $280 million was recorded related to our API reporting unit. During the year ended December 31, 2024 goodwill impairment charges of $1,280 million were recorded related to our API reporting unit.(3)Adjustments for impairment of long-lived assets in the fourth quarter of 2025 primarily consisted of $726 million impairment charge in connection with manufacturing facility in Europe. Adjustments for impairment of long-lived assets and items attributable to non-controlling interests, in the fourth quarter of 2024 primarily consisted of $129 million and $63 million, respectively, related to the classification of the business venture in Japan as held for sale. In addition, in the fourth quarter of 2024 we recognized an impairment of $275 million related to the classification of our API business (including its R&D, manufacturing and commercial activities) as held for sale. Adjustments for impairment of long-lived assets in 2025 were mainly related to a $726 million impairment charge in connection with manufacturing facility in Europe. Adjustments for impairment of long-lived assets and items attributable to non-controlling interests in 2024 primarily consisted of $715 million and $342 million, respectively, related to the classification of our business venture in Japan as held for sale. In addition, in 2024 we recognized an impairment of $275 million related to the classification of our API business (including its R&D, manufacturing and commercial activities) as held for sale.(4)In 2025, Teva recorded $225 million of restructuring expenses primarily related to optimization activities in connection with Teva's Transformation programs related to Teva’s global organization and operations, mainly through headcount reduction.(5)Adjustments in 2024 primarily related to a change in the estimated future royalty payments to Allergan in connection with lenalidomide capsules (the generic version of Revlimid®) of $270 million.(6)Other non-GAAP items include other exceptional items that we believe are sufficiently large that their exclusion is important to facilitate an understanding of trends in our financial results, primarily related to the rationalization of our plants, certain inventory write-offs, material litigation fees and other unusual events.(7)Adjustments for corresponding tax effects and unusual tax items in the fourth quarter and year ended december 2025 include an income tax item in an amount of $246 million related to a valuation allowance release in the U.S. Adjustments for corresponding tax effects and unusual tax items in 2024 include a tax item in an amount of $495 million related to the settlement agreement with the ITA to settle certain litigation with respect to taxes payable for the Company’s taxable years 2008 through 2020.(8)Non-GAAP tax rate is tax expenses (benefit) excluding the impact of non-GAAP tax adjustments presented above as a percentage of income (loss) before income taxes excluding the impact of non-GAAP adjustments presented above.(9)EPS difference and diluted non-GAAP EPS are calculated by dividing our non-GAAP net income attributable to Teva by our non-GAAP diluted weighted average number of shares. Reconciliation of gross profit (loss) to Non-GAAP gross profit (loss) Unaudited Three months ended Year ended December 31, December 31,($ in millions) 20252024 20252024GAAP gross profit($)2,6562,120 ($)8,9388,064GAAP gross profit margin 56.4%50.1% 51.8%48.7%Increase (decrease) for excluded items:(1) Amortization of purchased intangible assets 135135 541543 Costs related to regulatory actions taken in facilities 53 68 Equity compensation 75 2423 Accelerated Depreciation 95 2013 Other non-GAAP items 2851 117164Non-GAAP gross profit($)2,8402,319 ($)9,6478,814Non-GAAP gross profit margin(2) 60.3%54.8% 55.9%53.3% (1)For further explanations, refer to the footnotes under the "Reconciliation of net income (loss) attributable to Teva to Non-GAAP net income (loss) attributable to Teva" table.(2)Non-GAAP gross profit margin is non-GAAP gross profit as a percentage of revenue. Reconciliation of net income (loss) to adjusted EBITDA Unaudited Three months ended Year ended, December 31, December 31,($ in millions) 20252024 20252024Net income (loss)$481(275) $1,418(1,959)Increase (decrease) for excluded items:(1) Financial expenses 220218 934981 Income taxes (389)29 (180)676 Share in profits (losses) of associated companies –net (11)(1) (15)(1) Depreciation 114119 421465 Amortization 145144 581588EBITDA 560235 3,159750 Legal settlements and loss contingencies 164123 473761 Goodwill impairment -280 -1,280 Impairment of long lived assets 773517 1,0291,275 Restructuring costs 2922 22574 Equity compensation 5134 157123 Contingent consideration 8(2) 54303 Loss (Gain) on sale of Business -6 -(15) Other non-GAAP items 5367 208229Adjusted EBITDA$1,6371,282 $5,3054,781 (1) For further explanations, refer to the footnotes under the "Reconciliation of net income (loss) attributable to Teva to Non-GAAP net income (loss) attributable to Teva" table. Reconciliation of operating income (loss) to Non-GAAP operating income (loss)Unaudited Three months ended Year ended, December 31, December 31,($ in millions) 20252024 20252024Operating income (loss)($)300(29) ($)2,157(303)Operating margin 6.4%(0.7%) 12.5%(1.8%)Increase (decrease) for excluded items:(1) Amortization of purchased intangible assets 145144 581588 Legal settlements and loss contingencies 164123 473761 Goodwill impairment -280 -1,280 Impairment of long-lived assets 773517 1,0291,275 Restructuring costs 2922 22574 Equity compensation 5134 157123 Contingent consideration 8(2) 54303 Loss (gain) on sale of business 46 22(15) Accelerated depreciation 95 2113 Other non-GAAP items 4967 186229Non-GAAP operating income (loss)($)1,5321,168 ($)4,9054,329Non-GAAP operating margin(2)($)32.5%27.6% ($)28.4%26.2% (1)For further explanations, refer to the footnotes under the "Reconciliation of net income (loss) attributable to Teva to Non-GAAP net income (loss) attributable to Teva" table.(2)Non-GAAP operating margin is Non-GAAP operating income as a percentage of revenues. Segment InformationUnaudited United States Europe International Markets Three months ended December 31, Three months ended December 31, Three months ended December 31, 2025 2024 2025 2024 2025 2024 (U.S. $ in millions) (U.S. $ in millions) (U.S. $ in millions) Revenues$2,643 $1,975 $1,314 $1,353 $528 $661Cost of sales 820 877 606 561 281 315Gross profit 1,823 1,097 708 792 247 346R&D expenses 166 158 65 56 27 27S&M expenses 341 260 250 221 121 137G&A expenses 135 109 84 75 40 42Other § 1 1 2 (11) (1)Segment profit*$1,181 $569 $308 $438 $70 $141 * Segment profit does not include amortization and certain other items. § Represents an amount less than $0.5 million. Segment InformationUnaudited United States Europe International Markets Year ended December 31, Year ended December 31, Year ended December 31, 2025 2024 2025 2024 2025 2024 (U.S. $ in millions) (U.S. $ in millions) (U.S. $ in millions) Revenues$9,186 $8,034 $5,040 $5,103 $2,162 $2,463Cost of sales 3,568 3,646 2,293 2,197 1,116 1,229Gross profit 5,618 4,388 2,747 2,905 1,046 1,235R&D expenses 633 633 247 229 103 112S&M expenses 1,172 1,049 902 826 475 534G&A expenses 458 410 295 272 147 150Other income § § 1 3 (14) (2)Segment profit$3,356 $2,296 $1,303 $1,575 $336 $440 * Segment profit does not include amortization and certain other items. § Represents an amount less than $0.5 million. Reconciliation of our segment profitto consolidated income (loss) before income taxesUnaudited Three months ended December 31, 2025 2024 (U.S.$ in millions) United States profit $1,181 $569Europe profit 308 438International Markets profit 70 141Total reportable segment profit 1,559 1,148Profit (loss) of other activities (27) 19Amounts not allocated to segments: Amortization 145 144Other asset impairments, restructuring and other items 778 458Goodwill impairment - 280Intangible asset impairments 32 81Legal settlements and loss contingencies 164 123Other unallocated amounts 112 110Consolidated operating income (loss) 300 (29)Financial expenses - net 220 218Consolidated income (loss) before income taxes $80 $(247) Reconciliation of our segment profitto consolidated income (loss) before income taxesUnaudited Year ended December 31, 2025 2024 (U.S.$ in millions) United States profit $3,356 $2,296Europe profit 1,303 1,575International Markets profit 336 440Total reportable segment profit 4,995 4,311Profit (loss) of other activities (90) 18Amounts not allocated to segments: Amortization 581 588Other asset impairments, restructuring and other items 1,050 1,388Goodwill impairment - 1,280Intangible asset impairments 259 251Legal settlements and loss contingencies 473 761Other unallocated amounts 384 364Consolidated operating income (loss) 2,157 (303)Financial expenses - net 934 981Consolidated income (loss) before income taxes $1,223 $(1,284) Segment revenues by major products and activitiesUnaudited Three months ended December 31, Percentage Change 2025 2024 2024-2025 (U.S.$ in millions) United States segment Generic products (including biosimilars)$673 $674 §AJOVY 105 63 68%AUSTEDO 725 518 40%BENDEKA/TREANDA 35 41 (14%)COPAXONE 77 63 22%UZEDY 55 43 28%Anda 366 402 (9%)Other* 608 171 255%Total 2,643 1,975 34% *Other revenues in the fourth quarter of 2025 were mainly comprised of development milestone payments of $500 million received in the fourth quarter of 2025, in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A). Other revenues in the fourth quarter of 2024 include the sale of certain product rights. Three months ended December 31, Percentage Change 2025 2024 2024-2025 (U.S.$ in millions) Europe segment Generic products (including biosimilars)$1,033 $979 5%AJOVY 76 58 30%COPAXONE 45 50 (9%)Respiratory products 65 61 6%Other* 96 205 (53%)Total 1,314 1,353 (3%) *Other revenues in the fourth quarter of 2025 and 2024 include the sale of certain product rights. Three months ended December 31, Percentage Change 2025 2024 2024-2025 (U.S.$ in millions) International Markets segment Generic products (including biosimilars)$422 $497 (15%)AJOVY 30 22 40%AUSTEDO 9 7 29%COPAXONE 6 9 (31%)Other* 60 126 (52%)Total 528 661 (20%) *Other revenues in the fourth quarter of 2025 and 2024 include the sale of certain product rights. Segment revenues by major products and activitiesAudited Year ended December 31, Percentage Change 2025 2024 2025-2024 (U.S.$ in millions) United States segment Generic products (including biosimilars) $3,657 $3,599 2%AJOVY 295 207 42%AUSTEDO 2,217 1,642 35%BENDEKA / TREANDA 147 168 (13%)COPAXONE 255 242 6%UZEDY 191 117 63%Anda 1,496 1,536 (3%)Other* 929 523 78%Total 9,186 8,034 14% * Other revenues in 2025 were mainly comprised of development milestone payments of $500 million received in the fourth quarter of 2025, in connection with the initiation of Phase 3 studies for duvakitug (anti-TL1A) (see note 2 to our consolidated financial statements). Other revenues in 2024 include the sale of certain product rights. Year ended December 31, Percentage Change 2025 2024 2025-2024 (U.S.$ in millions) Europe segment Generic products (including biosimilars) $4,044 $3,926 3%AJOVY 270 216 25%COPAXONE 181 213 (15%)Respiratory products 227 244 (7%)Other* 319 504 (37%)Total 5,040 5,103 (1%) *Other revenues in 2025 and 2024 include the sale of certain product rights. Year ended December 31, Percentage Change 2025 2024 2025-2024 (U.S.$ in millions) International Markets segment Generic products (including biosimilars) $1,721 $1,937 (11%)AJOVY 108 84 28%Austedo 43 46 (6%)COPAXONE 32 48 (34%)Other* 259 349 (26%)Total 2,162 2,463 (12%) *Other revenues in 2025 and 2024 include the sale of certain product rights. Free cash flow reconciliationUnaudited Three months ended December 31, 2025 2024 (U.S. $ in millions) Net cash provided by (used in) operating activities 1,158 575Beneficial interest collected in exchange for securitized account receivables 282 340Purchases of property, plant and equipment and intangible assets (142) (129)Proceeds from divestitures of businesses and other assets - 4Free cash flow$1,298 $790 Free cash flow reconciliationAudited Year ended December 31 2025 2024 (U.S. $ in millions) Net cash provided by (used in) operating activities 1,649 1,247Beneficial interest collected in exchange for securitized account receivables 1,214 1,291Purchases of property, plant and equipment and intangible assets (501) (498)Acquisition of businesses, net of cash acquired - (15)Proceeds from divestitures of businesses and other assets 34 43Free cash flow$2,396-$2,068 Net debt reconciliationAudited Year ended December 31, 2025 2024 (U.S. $ in millions) Short-term debt 1,820 1,781Senior notes and loans 14,986 16,002Total debt 16,807 17,783 Net of cash and cash equivalents 3,556 3,300 Net debt$13,251-$14,482

编者按：随着研发技术的不断进步，新一代共价药物的开发已成为业界高度关注的方向。截至目前，已有超过50种共价药物成功获批上市，并在多个疾病领域展现出显著疗效。值得关注的是，新一代共价药物正不断突破局限，向可逆性共价结合及靶向半胱氨酸以外氨基酸残基的方向快速拓展，为攻克“不可成药”靶点带来全新契机。依托端到端的CRDMO赋能平台，药明康德致力为全球合作伙伴提供覆盖共价药物发现与开发的一体化解决方案。本文将回顾2025年共价小分子领域的最新进展，并介绍药明康德在共价药物发现领域的技术与能力。 临床与监管进展 2025年，美国FDA共批准四款共价药物。7月，美国FDA加速批准迪哲医药（Dizal [Jiangsu] Pharmaceutical）研发的Zegfrovy（sunvozertinib），用于治疗携带表皮生长因子受体（EGFR）第20号外显子插入突变（exon20ins）的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者。Zegfrovy是一款口服、不可逆、针对多种EGFR突变亚型的高选择性EGFR酪氨酸激酶抑制剂（TKI），此前已获FDA授予突破性疗法认定，用于全线治疗EGFR exon20ins NSCLC患者。紧接着在8月，FDA又加速批准勃林格殷格翰（Boehringer Ingelheim）口服、不可逆HER2酪氨酸激酶抑制剂Hernexeos（zongertinib）上市，用于治疗肿瘤携带HER2酪氨酸激酶结构域（TKD）激活性突变、且已接受过系统治疗的不可切除或转移性非鳞状NSCLC成人患者。同月，赛诺菲（Sanofi）的可逆布鲁顿酪氨酸激酶（BTK）共价抑制剂Wayrilz（rilzabrutinib）也获批用于治疗既往治疗应答不足的持续性或慢性免疫性血小板减少症（ITP）成人患者。随后在9月，诺华（Novartis）旗下BTK共价抑制剂Rhapsido（remibrutinib）获FDA批准，用于治疗H1抗组胺药不能充分控制症状的慢性自发性荨麻疹（CSU）成人患者。 除了新药获批之外，2025年多款共价小分子药物也迎来监管进展。例如，阿斯利康（AstraZeneca）的BTK共价抑制剂Calquence（acalabrutinib）在1月获得FDA扩展适应症批准，可联合苯达莫司汀和利妥昔单抗，用于治疗不适合自体造血干细胞移植的初治成人套细胞淋巴瘤（MCL）患者。同时，大鹏药品工业株式会社（Taiho Pharmaceutical）、Taiho Oncology与Cullinan Therapeutics也在11月底针对其联合开发、靶向EGFR激活性突变体的共价小分子zipalertinib，向美国FDA滚动递交新药申请（NDA），用于治疗既往接受过含铂化疗、携带EGFR exon20ins的局部晚期或转移性NSCLC患者。该疗法此前已获FDA授予突破性疗法认定。 值得关注的是，自KRAS G12C抑制剂sotorasib和adagrasib获批以来，共价小分子在攻克癌症领域“不可成药”靶点方面的潜力愈发受到产业界广泛重视。2025年，多款KRAS G12C共价抑制剂陆续获得FDA授予的突破性疗法认定，用于治疗NSCLC，其中包括olomorasib、RAS（ON）G12C选择性抑制剂elironrasib（RMC-6291），以及RAS（OFF）G12C选择性抑制剂D3S-001。需要说明的是，RAS（ON）与RAS（OFF）分别指RAS分子处于活性与非活性状态。 除KRAS G12C之外，其他KRAS靶向共价抑制剂的研发也在加速推进。例如，RAS（ON）G12D选择性抑制剂zoldonrasib（RMC-9805）的临床前研究成果已于2025年7月发表在《科学》杂志上，目前这一疗法也已进入临床阶段。公开数据显示，在18例可评估疗效、携带KRAS G12D突变的经治NSCLC患者中，其客观缓解率（ORR）达到61%，疾病控制率（DCR）为89%。此外，Vividion Therapeutics开发的一款共价抑制剂也在2025年10月登上《科学》期刊，该分子可与PI3K p110α共价结合，从而阻断RAS对PI3Kα活性的激活。在临床前实验中，该药物可减缓携带RAS突变与HER2过表达肿瘤的生长。该疗法目前已进入1期临床试验阶段。 除KRAS外，其他靶点的共价抑制剂研发同样持续推进。例如，评估潜在“best-in-class”口服共价Werner解旋酶抑制剂MOMA-341的1期临床试验近日完成首例患者给药，该研究主要面向具有高微卫星不稳定性（MSI-H）和/或DNA错配修复缺陷（dMMR）的晚期或转移性实体瘤患者，包括结直肠癌、胃癌和子宫内膜癌等。同时，由Biomea Fusion开发的menin共价抑制剂icovamenib也在2期试验中展现出治疗糖尿病的积极信号。在重度胰岛素缺乏型糖尿病患者中，即使在停药9个月（第52周）后，icovamenib仍维持治疗获益，其糖化血红蛋白（HbA1c）较安慰剂校正后平均下降1.8个百分点。在皮肤病领域，ITK/JAK3双靶点抑制剂ATI-2138在治疗中重度特应性皮炎（AD）的2a期试验中达到主要及关键次要终点，其疗效与活性对照药物相当，并展现出良好安全性，研发方计划进一步评估其在斑秃及机制相关疾病中的潜在疗效。 研发合作与融资进展 共价药物领域的活跃也体现在研发合作与资本投入上。7月，诺华（Novartis）与Matchpoint Therapeutics达成金额最高约10亿美元的独家选择权与许可协议，双方将合作开发并商业化一款靶向炎症相关转录因子的口服共价抑制剂。根据协议，Matchpoint将依托其Advanced Covalent Exploration（ACE）平台推进早期研究，直至完成候选化合物筛选。此外，Odyssey Therapeutics也在9月完成2.13亿美元融资，计划通过人工智能及共价化学平台加速自身免疫疾病新药研发。 与此同时，Flagship Pioneering在10月宣布成立历经三年孵化的Expedition Medicines公司，并提供首轮5000万美元资金支持。该公司专注于构建生成式共价化学（generative covalent chemistry）平台，旨在实现靶向多种疾病相关靶点的小分子药物发现，并推进其在肿瘤学、免疫学等领域的项目布局。此外，在Flagship与辉瑞（Pfizer）的战略合作框架下，Expedition已启动多靶点探索合作，以识别具有潜力的前列腺癌创新疗法。 总体来看，共价抑制剂已从肿瘤领域逐步扩展至免疫、炎症等多类疾病，其独特结合机制、持久活性以及高选择性特点，正在为多种疾病治疗带来新的可能。随着技术平台持续成熟、产业协同不断深化，这一领域有望在未来数年迎来更多临床与商业化突破。 药明康德助力加速共价药物开发 为帮助全球合作伙伴加速下一代共价药物的研发——从早期发现到IND申报，药明康德建立了一体化发现平台。该平台融合了三大互补技术：共价DNA编码化合物库（cDEL）、共价片段药物发现（cFBDD）以及共价高通量筛选（cHTS），为共价药物发现提供了高效的解决方案。 cDEL是一项功能强大的筛选技术，能够高效探索庞大的化学空间，大幅提升发现多样化共价分子及其结合弹头的可能性。通过将DNA标签作为“分子条形码”，该平台可在仅需极少量蛋白和化合物的条件下，实现快速且具成本效益的苗头化合物发现，在化学多样性至关重要的早期研发阶段尤为突出。 药明康德的cFBDD平台则基于一个经过严格筛选的化合物库，包含超过2600个结构多样化的片段。该平台以小而低复杂度的分子片段为核心，高效探索结合位点，并通过引入带有亲电基团的片段，快速识别可作为优化起点的共价结合物。结合高通量质谱以及X射线晶体学、核磁共振（NMR）等结构生物学方法，cFBDD能够在原子水平提供片段–蛋白相互作用的深度洞察，从而支持理性设计与系统优化。 药明康德的cHTS平台是集合了药明康德cHTS共价库和多种筛选方法的高通量筛选平台。药明康德的cHTS共价库约有6万9千个分子，涵盖50多种不同类型的共价弹头，反应活性范围多样。这些化合物能够作用于九类不同的氨基酸残基，将共价药物发现的范围从半胱氨酸扩展至丝氨酸、赖氨酸以及其他残基专属的化合物库。 在共价药物筛选平台之外，药明康德还建立了一整套早期药物发现技术平台，涵盖生物物理学、生物化学及细胞学检测，为全球合作伙伴共价药物的开发提供坚实的支持。依托端到端的一体化CRDMO赋能平台，药明康德致力于加速突破性疗法的开发，帮助合作伙伴将创新成果高效转化为造福全球患者的解决方案，以践行“让天下没有难做的药，难治的病”的愿景。 From Science to Breakthrough Therapy Designation: Covalent Small Molecules Broaden the Innovation Landscape in 2025 With advances in biopharmaceutical research and development, next-generation covalent drugs have emerged as a major focus across the industry. To date, more than 50 covalent drugs have been approved for clinical use, demonstrating substantial value across a broad range of therapeutic areas. Importantly, these next-generation therapies are advancing toward reversible covalent binding and targeting amino acid residues beyond cysteine, thereby opening new possibilities for addressing previously “undruggable” targets. Leveraging its fully integrated, end-to-end CRDMO enabling platform, WuXi AppTec provides global partners with comprehensive solutions for covalent drug discovery and development. Here, we summarize key developments in the covalent small molecules space in 2025 and highlight WuXi AppTec’s capabilities and strengths in enabling innovation in covalent drug discovery. Clinical and Regulatory Progress In 2025, the U.S. FDA approved four covalent medicines. In July, the FDA granted accelerated approval to Zegfrovy (sunvozertinib), developed by Dizal (Jiangsu) Pharmaceutical, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutations. Zegfrovy is an oral, irreversible, and highly selective EGFR tyrosine kinase inhibitor (TKI) designed to target multiple EGFR mutation subtypes. The therapy had previously received Breakthrough Therapy Designation (BTD) from the FDA for the treatment of EGFR exon20ins NSCLC across all lines of therapy. This was followed in August by the FDA’s accelerated approval of Boehringer Ingelheim’s Hernexeos (zongertinib), an oral irreversible HER2 tyrosine kinase inhibitor, for the treatment of adult patients with unresectable or metastatic non-squamous NSCLC whose tumors harbor activating HER2 tyrosine kinase domain (TKD) mutations and who have received prior systemic therapy. Also in August, Sanofi’s reversible covalent Bruton’s tyrosine kinase (BTK) inhibitor Wayrilz (rilzabrutinib) was approved for the treatment of adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to prior therapy. In September, Novartis received FDA approval for Rhapsido (remibrutinib), a BTK covalent inhibitor indicated for adult patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1-antihistamine treatment. Beyond new approvals, multiple covalent small-molecule therapies also advanced through regulatory milestones during the year. For example, AstraZeneca’s BTK covalent inhibitor Calquence (acalabrutinib) received an expanded FDA indication in January for use in combination with bendamustine and rituximab to treat adult patients with previously untreated mantle cell lymphoma (MCL) who are not candidates for autologous stem cell transplantation. In addition, Taiho Pharmaceutical, Taiho Oncology, and Cullinan Therapeutics initiated rolling submission of New Drug Application (NDA) to the FDA in late November for zipalertinib, a jointly developed covalent small molecule targeting activated EGFR mutations. The filing seeks approval for the treatment of locally advanced or metastatic NSCLC harboring EGFR exon20ins mutations in patients previously treated with platinum-based chemotherapy. The therapy had earlier been granted BTD by the FDA. Importantly, since the approvals of sotorasib and adagrasib targeting KRAS G12C mutations, covalent small molecules have gained increasing industry recognition for their potential to address historically “undruggable” cancer targets. In 2025, several KRAS G12C covalent inhibitors have received BTD for NSCLC, including olomorasib, the RAS (ON) G12C-selective inhibitor elironrasib (RMC-6291), and the RAS (OFF) G12C-selective inhibitor D3S-001. Notably, “RAS(ON)” and “RAS (OFF)” refer to active and inactive conformational states of the RAS protein. Beyond KRAS G12C, development of KRAS-targeted covalent inhibitors continues to accelerate. For example, preclinical findings for the RAS (ON) G12D-selective inhibitor zoldonrasib (RMC-9805) were published in Science in July, and the therapy has now advanced into clinical development. Data published to date show that among 18 evaluable, previously treated NSCLC patients harboring KRAS G12D mutations, the objective response rate (ORR) reached 61%, with a disease control rate (DCR) of 89%. In addition, a covalent inhibitor developed by Vividion Therapeutics was also featured in Science in October. The molecule covalently binds PI3K p110α, thereby blocking RAS-mediated activation of PI3Kα. In preclinical testing, the therapy demonstrated tumor growth inhibition in models harboring RAS mutations and HER2 overexpression, and it has now entered Phase 1 clinical development. Progress is also being seen across other covalent drug targets. A Phase 1 clinical study evaluating MOMA-341, an investigational oral covalent Werner helicase inhibitor with best-in-class potential, completed first-patient dosing. The trial is enrolling patients with advanced or metastatic solid tumors characterized by high microsatellite instability (MSI-H) and/or mismatch repair deficiency (dMMR), including colorectal, gastric, and endometrial cancers. Meanwhile, menin covalent inhibitor icovamenib, developed by Biomea Fusion, has demonstrated encouraging clinical activity in Type 2 diabetes during Phase 2 evaluation. Among patients with severe insulin-deficient diabetes, icovamenib continued to deliver clinical benefit even nine months (Week 52) after treatment cessation, achieving a placebo-adjusted mean HbA1c reduction of 1.8%. In dermatology, the dual ITK/JAK3 inhibitor ATI-2138 achieved its primary and key secondary endpoints in a Phase 2a study in moderate-to-severe atopic dermatitis (AD). The therapy demonstrated efficacy comparable to active control with a favorable safety profile, and the developer plans further evaluation in alopecia areata and other mechanistically related diseases. R&D Collaboration & Financing Progress Industry interest in covalent medicines is also reflected in partnership and investment activity. In July, Novartis and Matchpoint Therapeutics entered into an exclusive option and license agreement valued at up to approximately $1 billion to jointly develop and commercialize an oral covalent inhibitor targeting a transcription factor implicated in multiple inflammatory diseases. Under the agreement, Matchpoint will leverage its Advanced Covalent Exploration (ACE) platform to progress early-stage discovery through candidate selection. In September, Odyssey Therapeutics announced completion of a $213 million financing round to advance new medicines for autoimmune diseases powered by artificial intelligence and covalent chemistry platforms. Meanwhile, in October, Flagship Pioneering unveiled Expedition Medicines — a company incubated over three years — and provided an initial $50 million investment. Expedition is building a generative covalent chemistry platform designed to enable small-molecule discovery across a wide spectrum of disease-relevant targets, while advancing programs in oncology, immunology, and other defined diseases. In addition, under Flagship’s strategic collaboration framework with Pfizer, Expedition has initiated a multi-target discovery partnership aimed at identifying novel therapeutic candidates for prostate cancer. Overall, covalent inhibitors continue to expand beyond oncology into immune-mediated and inflammatory disease settings. Their unique binding mechanisms, durable activity, and high selectivity are opening new therapeutic possibilities across multiple indications. As enabling technologies mature and cross-industry collaboration deepens, the field is expected to see further clinical and commercial breakthroughs in the years ahead. WuXi AppTec Empowers the Development of Covalent Drugs To help global partners accelerate the development of next-generation covalent drugs, from early discovery through IND-enabling studies, WuXi AppTec has established an integrated platform. By combining three complementary, state-of-the-art technologies—covalent DNA-Encoded Library (cDEL), covalent Fragment-Based Drug Discovery (cFBDD), and covalent High-Throughput Screening (cHTS)—the platform provides a highly efficient solution to advance covalent drug discovery. cDEL is a powerful screening technology that enables the efficient exploration of vast chemical libraries, greatly increasing the likelihood of identifying covalent binders with diverse warheads. Leveraging DNA tags as molecular barcodes, the platform allows rapid and cost-effective deconvolution of hits while requiring only minimal quantities of protein and compound. This makes it particularly valuable in the early discovery stage, where broad chemical diversity is essential. WuXi AppTec’s cFBDD platform builds on a rigorously curated library of more than 2,600 structurally diverse fragments. By focusing on small, low-complexity molecules, the platform efficiently probes binding sites and, through the incorporation of electrophilic fragments, identifies covalent hits that serve as highly effective starting points for optimization. Leveraging high-throughput mass spectrometry together with structural biology methods such as X-ray crystallography and NMR, cFBDD provides atomic-level insights into fragment–protein interactions, enabling rational design and systematic growth of covalent inhibitors. The cHTS platform from WuXi AppTec is a platform that incorporates various screening strategies. The covalent HTS library has approximately 69,000 covalent molecules featuring more than 50 distinct warhead chemotypes across a range of reactivities. Our library is purpose-built to engage with nine different amino acid residues, extending covalent drug discovery beyond cysteine to include serine-, lysine-, and other residue-focused libraries. Complementing its advanced screening capabilities, WuXi AppTec offers a comprehensive suite of early discovery technology platforms—including biophysical, biochemical, and cellular assays—to support global partners in advancing covalent drug development. Backed by an integrated, end-to-end CRDMO enabling platform, WuXi AppTec is committed to accelerating the development of transformative therapies that deliver meaningful benefits to patients worldwide—fulfilling its vision that “Every drug can be made and every disease can be treated.” 参考资料： [1] Vividion Announces Publication in Science of Preclinical Data on Covalent Inhibitors of RAS-PI3K that Block Tumor Growth. Retrieved December 24, 2025 from https://vividion.com/news/vividion-announces-publication-in-science-of-preclinical-data-on-covalent-inhibitors-of-ras-pi3k-that-block-tumor-growth/ [2] Biomea Fusion Announces Positive 52-Week Results from Phase II COVALENT-111 Study in Type 2 Diabetes Demonstrating Non-Chronic Treatment with Icovamenib Benefits Two Distinct Patient Populations. Retrieved December 24, 2025 from https://www.globenewswire.com/news-release/2025/10/06/3162080/0/en/Biomea-Fusion-Announces-Positive-52-Week-Results-from-Phase-II-COVALENT-111-Study-in-Type-2-Diabetes-Demonstrating-Non-Chronic-Treatment-with-Icovamenib-Benefits-Two-Distinct-Patie.html [3] Flagship Pioneering Unveils Expedition Medicines to Expand the Boundaries of Small Molecule Medicines with Generative Design. Retrieved December 24, 2025 from https://www.prnewswire.com/news-releases/flagship-pioneering-unveils-expedition-medicines-to-expand-the-boundaries-of-small-molecule-medicines-with-generative-design-302590755.html 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，传递医学新知