Raxibacumab

Second Quarter 2026 Total Revenues of $234.3 million, an improvement of 66% versus prior year Second Quarter 2026 Net Loss of $180.2 million worsening 1,402% versus prior year, largely due to a $191.3 million non-cash impairment charge Second Quarter 2026 Adjusted Net Income of $30.9 million improved 134% versus prior year Second Quarter 2026 Gross Margin % of 50% and Adjusted Gross Margin % of 58%, an expansion of 1400 bps and 900 bps, respectively, versus prior year Second Quarter 2026 Adjusted EBITDA of $96.5 million and Adjusted EBITDA Margin of 41%, an improvement of 1,800 bps versus prior year Restructuring business operations to align resourcing to current needs; expected to result in annualized savings of approximately $40 million when fully implemented GAITHERSBURG, Md., Aug. 05, 2026 (GLOBE NEWSWIRE) -- Emergent BioSolutions Inc. (NYSE: EBS) today reported financial results for the second quarter ended June 30, 2026. “Emergent delivered a strong second quarter, significantly exceeding the high end of our guidance range with revenues of $234 million, primarily driven by accelerated MCM/biodefense contract modifications secured with the U.S. government. This performance reflects the focus, discipline and commitment of our teams, and it reinforces the strength of our mission, our portfolio and the steadiness of our multi-year plan toward transformation," said Joe Papa, CEO of Emergent. "However, alongside of these strong results, we are at a critical juncture in our turnaround and transformation, primarily stemming from our naloxone business. Today we are implementing an organizational restructuring plan and taking proactive steps to strengthen our financial foundation, align the company to the realities of the naloxone business and preserve our ability to invest in the areas that matter most for Emergent’s future. Additionally, we seek to collaborate with AI partners for bioterrorism preparedness.” FINANCIAL HIGHLIGHTS (1) Q2 2026 vs. Q2 2025 ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); ($ in millions, except per share amounts) Q2 2026 Q2 2025 % Change Total Revenues $ 234.3 $ 140.9 66 % Net Loss $ (180.2 ) $ (12.0 ) (1,402)% Net Loss per Diluted Share $ (3.49 ) $ (0.22 ) (1,486)% Adjusted Net Income (2) $ 30.9 $ 13.2 134 % Adjusted Net Income per Diluted Share (2) $ 0.60 $ 0.24 150 % Adjusted EBITDA (2) $ 96.5 $ 33.1 192 % Net Loss Margin (77)% (9)% Adjusted EBITDA Margin (2) 41 % 23 % Gross Margin % 50 % 36 % Adjusted Gross Margin % (2) 58 % 49 % Year to Date ("YTD") 2026 vs YTD 2025 ($ in millions, except per share amounts) YTD 2026 YTD 2025 % Change Total Revenues $ 390.4 $ 363.1 8 % Net Income (Loss) $ (173.4 ) $ 56.0 (410)% Net Income (Loss) per Diluted Share $ (3.35 ) $ 0.99 (438)% Adjusted Net Income (2) $ 42.8 $ 55.4 (23)% Adjusted Net Income per Diluted Share (2) $ 0.83 $ 0.98 (15)% Adjusted EBITDA (2) $ 132.0 $ 112.2 18 % Net Income (Loss) Margin (44)% 15 % Adjusted EBITDA Margin (2) 34 % 31 % Gross Margin % 46 % 45 % Adjusted Gross Margin % (2) 56 % 55 % RECENT BUSINESS UPDATES Secured contract modification from U.S. government and completed delivery of approximately $52.7 million of ACAM2000 ® (Smallpox and Mpox (Vaccinia) Vaccine, Live) Executed $64.5 million for BAT ® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) – (Equine)) contract modification with U.S. government Secured two new strategic manufacturing partnerships with: SAB Biotherapeutics to advance its type 1 diabetes candidate, SAB-142 Substipharm Biologics to support its Japanese Encephalitis vaccine in the United States; Refinanced term loan with new $150 million facility and amended asset-backed loan facility Announced partnership with British Columbia to supply NARCAN ® Nasal Spray for the launch of the expanded BC Take Home Naloxone Program Supported National Naloxone Awareness Day to increase awareness of life-saving naloxone Partnered with professional baseball player Davis Schneider to raise awareness of NARCAN ® Nasal Spray in Canada Announced launch of new NARCAN ® Nasal Spray Carrying Case and multipack configurations to expand opioid overdose preparedness following U.S. FDA approvals on supplemental new drug applications Received Saudi Food and Drug Authority Approval for ACAM2000 ® (Smallpox and Mpox (Vaccinia) Vaccine, Live) Received approval from Singapore Health Sciences Authority for expanded indication of ACAM2000 ® (Smallpox and Mpox (Vaccinia) Vaccine, Live) to include mpox Announced participation in several international preparedness conferences RESTRUCTURING UPDATES Efforts aim to improve overall cost structure, drive efficiencies and align resourcing to the current needs of the organization; includes reduction of approximately 90 roles Creation of a new Growth organization that integrates the capabilities of R&D, Business Development, Strategy into one function led by Stephanie Duatschek, Senior Vice President, Chief Global Strategy & Franchise Development Officer, who will assume the role of Executive Vice President, Chief Growth Officer, with responsibility for the Company’s strategic growth SECOND QUARTER 2026 FINANCIAL PERFORMANCE (1) Revenues The Company uses the following categories in discussing revenues: Naloxone — comprises contributions from NARCAN ® Nasal Spray and KLOXXADO ® Nasal Spray Anthrax MCM — comprises contributions from CYFENDUS ® , BioThrax ® , ANTHRASIL ® , and Raxibacumab Smallpox MCM — comprises contributions from ACAM2000 ® , CNJ-016 ® (VIGIV) and TEMBEXA ® Other Products — comprises contributions from BAT ® All Other Revenues — comprises revenues from the Services operating segment and contracts and grants revenues ($ in millions) Q2 2026 Q2 2025 $ Change % Change Product sales, net: (3) Naloxone $ 52.4 $ 67.5 $ (15.1 ) (22)% Anthrax MCM 12.3 11.6 0.7 6 % Smallpox MCM 101.6 40.6 61.0 150 % Other Products 54.1 6.2 47.9 NM Total Product sales, net $ 220.4 $ 125.9 $ 94.5 75 % All other revenues $ 13.9 $ 15.0 $ (1.1 ) (7)% Total revenues $ 234.3 $ 140.9 $ 93.4 66 % Product Sales, net (3) Naloxone For Q2 2026, revenues from Naloxone products decreased $15.1 million, or 22%, as compared with Q2 2025. The decrease was primarily attributable to lower sales of OTC NARCAN ® , mostly driven by an unfavorable price-volume mix in the U.S. public interest channels, partially mitigated by increases in Canadian sales of branded NARCAN ® and KLOXXADO ® sales. Anthrax MCM For Q2 2026, revenues from Anthrax MCM products increased $0.7 million, or 6%, as compared with Q2 2025. The increase was primarily attributable to a more favorable pricing mix driven by international sales of BioThrax ® . This increase was partially offset by the absence of international sales of ANTHRASIL ® in the current period, compared to international sales in the prior-year period. Anthrax vaccine product sales are primarily made under annual purchase options exercised by the USG. Fluctuations in revenues result from the timing of the exercise of annual purchase options, the timing of USG purchases, the availability of governmental funding and the Company’s delivery of orders that follow. Smallpox MCM For Q2 2026, revenues from Smallpox MCM products increased $61.0 million, or 150%, as compared with Q2 2025. The increase was primarily attributable to higher USG sales of ACAM2000 ® due to timing, higher CNJ-016 ® (VIGIV) sales with a more favorable price and volume mix of U.S. and international sales and higher TEMBEXA ® international sales due to timing. Fluctuations in revenues from Smallpox MCM result from the timing of the exercise of annual purchase options in the existing procurement contracts, the timing of USG purchases, the availability of governmental funding and the Company’s delivery of orders that follow. Other Products For Q2 2026, revenues from Other Product sales increased $47.9 million as compared with Q2 2025. The increase was primarily due to higher USG and international BAT ® sales due to timing. All Other Revenues Services For Q2 2026, revenues from Services increased $2.0 million, or 45%, as compared with Q2 2025. The increase was primarily attributable to production activity at the Company’s Winnipeg facility. Contracts and Grants For Q2 2026, revenues from contracts and grants decreased $3.1 million, or 29%, as compared with Q2 2025. The decrease was primarily due to lower Ebanga ® related development work, reflecting timing and nature of work performed. Operating Expenses ($ in millions) Q2 2026 Q2 2025 $ Change % Change Cost of product and services sales, net $ 97.1 $ 66.9 $ 30.2 45 % Research and development (“R&D”) 9.2 12.5 (3.3 ) (26)% Selling, general and administrative (“SG&A”) 44.6 43.7 0.9 2 % Amortization of intangible assets 17.2 16.2 1.0 6 % Impairment of long-lived assets 191.3 — 191.3 NM Total operating expenses $ 359.4 $ 139.3 $ 220.1 158 % Cost of Product and Services Sales, Net For Q2 2026, cost of product and services sales, net increased $30.2 million, or 45%, as compared with Q2 2025. The increase was driven by higher cost of MCM Product sales of $27.0 million and cost of Services of $3.3 million, partially offset by a decrease in cost of Commercial Product sales of $0.1 million. Research and Development Expenses For Q2 2026, R&D expenses decreased $3.3 million, or 26%, as compared with Q2 2025. The decrease was primarily due to lower project spend on Ebanga ® related development work. Selling, General and Administrative Expenses For Q2 2026, SG&A expenses increased $0.9 million, or 2%, as compared with Q2 2025. The increase was primarily due to lower insurance reimbursement benefits recognized in the current year period compared with the prior year period, partially offset by lower compensation, marketing and administrative support expenses. Impairment of Long-Lived Assets For Q2 2026, impairment of long-lived assets was $191.3 million. This was the result of a non-cash impairment charge in the second quarter of 2026 related to our NARCAN ® asset group within the Commercial reporting unit. ADDITIONAL FINANCIAL INFORMATION (1) Capital Expenditures ($ in millions) Q2 2026 Q2 2025 % Change Capital expenditures $ 2.1 $ 2.9 (28)% Capital expenditures as a % of total revenues 1 % 2 % For Q2 2026, capital expenditures decreased largely due to reduced development activities across the Company’s facilities. REPORTABLE SEGMENT INFORMATION The Company manages the business with a focus on three operating segments: (1) a Commercial Products segment consisting of NARCAN ® Nasal Spray and KLOXXADO ® Nasal Spray; (2) a MCM Products segment consisting of Anthrax - MCM, Smallpox - MCM and Other products and (3) a services segment consisting of our Bioservices offerings (“Services”). Commercial Products and MCM Products are our two reportable segments. The Services operating segment no longer meets the quantitative thresholds of a reportable segment and did not meet the aggregation criteria set forth in Accounting Standards Codification 280, Segment Reporting, and as such is categorized within “All other revenues” along with “Contracts and Grants”. The Company evaluates the performance of these reportable segments based on revenues and segment adjusted gross margin, which is a non-GAAP financial measure. Segment revenue includes external customer sales but does not include inter-segment services. The Company does not allocate contracts and grants revenue, R&D, SG&A, amortization of intangible assets, interest and other income (expense) or taxes to its evaluation of the performance of these segments. SECOND QUARTER 2026 REPORTABLE SEGMENT RESULTS ($ in millions) Commercial Products Quarter Ended June 30, 2026 2025 $ Change % Change Revenues $ 52.4 $ 67.5 $ (15.1 ) (22)% Cost of sales 36.3 36.4 (0.1 ) — % Intangible asset amortization 9.4 9.4 — — % Gross margin * $ 6.7 $ 21.7 $ (15.0 ) (69)% Gross margin % * 13 % 32 % Add back: Intangible asset amortization $ 9.4 $ 9.4 Severance and restructuring costs — 0.2 Stock-based compensation expense 0.1 — Segment adjusted gross margin ** $ 16.2 $ 31.3 $ (15.1 ) (48)% Segment adjusted gross margin % ** 31 % 46 % * Gross margin is calculated as revenues less cost of sales and intangible asset amortization. Gross margin % is calculated as gross margin divided by revenues. ** Segment adjusted gross margin, which is a non-GAAP financial measure, for our Commercial Products segment is calculated as gross margin plus intangible asset amortization, severance and restructuring costs and the portion of stock-based compensation expense that is recorded as cost of sales. Segment adjusted gross margin percentage, which is a non-GAAP financial measure, is calculated as segment adjusted gross margin divided by revenues. The Company’s management utilizes segment adjusted gross margin and segment adjusted gross margin percentage for purposes of evaluating our ongoing operations and for internal planning and forecasting purposes. In calculating these measures, we began excluding stock-based compensation that is recorded as cost of sales in the first quarter of 2026, as this reflects a non-cash expenditure that is not related to segment operating performance. As reflected in the table above, we have recast our 2025 results to also reflect this adjustment. We believe that these non-GAAP operating measures, when reviewed collectively with our GAAP financial information, provide useful supplemental information to investors in assessing our operating performance. NM - Not meaningful Cost of Commercial Products sales decreased $0.1 million to $36.3 million for the quarter ended June 30, 2026. Despite decreases in U.S. sales volumes of OTC NARCAN ® compared with the prior year period, cost of sales remained substantially flat due to increased costs and volumes associated with KLOXXADO ® sales and Canadian sales of branded NARCAN ® . Commercial Products gross margin decreased $15.0 million, or 69%, to $6.7 million for the quarter ended June 30, 2026. Commercial Products gross margin percentage decreased 19 percentage points to 13% for the quarter ended June 30, 2026. The decrease was largely due to an unfavorable price and volume mix of OTC NARCAN ® across most U.S. sales channels, partially offset by lower product costs related to Canadian sales. Commercial Products segment adjusted gross margin in the current year period excludes the impact of intangible asset amortization of $9.4 million and the portion of stock-based compensation expense recorded as cost of sales of $0.1 million. ($ in millions) MCM Products Quarter Ended June 30, 2026 2025 $ Change % Change Revenues $ 168.0 $ 58.4 $ 109.6 188 % Cost of sales 52.8 25.8 27.0 105 % Intangible asset amortization 7.8 6.8 1.0 15 % Gross margin * $ 107.4 $ 25.8 $ 81.6 NM Gross margin % * 64 % 44 % Add back: Intangible asset amortization $ 7.8 $ 6.8 Inventory step-up provision 0.2 — Severance and restructuring benefit — (0.4 ) Stock-based compensation expense 0.7 0.3 Segment adjusted gross margin** $ 116.1 $ 32.5 $ 83.6 NM Segment adjusted gross margin %** 69 % 56 % * Gross margin is calculated as revenues less cost of sales and intangible asset amortization. Gross margin % is calculated as gross margin divided by revenues. ** Segment adjusted gross margin, which is a non-GAAP financial measure, for our MCM Products segment is calculated as gross margin plus intangible asset amortization, inventory step-up provision, severance and restructuring benefit and the portion of stock-based compensation expense that is recorded as cost of sales. Segment adjusted gross margin percentage, which is a non-GAAP financial measure, is calculated as segment adjusted gross margin divided by revenues. The Company’s management utilizes segment adjusted gross margin and segment adjusted gross margin percentage for purposes of evaluating our ongoing operations and for internal planning and forecasting purposes. In calculating these measures, we began excluding stock-based compensation that is recorded as cost of sales in the first quarter of 2026, as this reflects a non-cash expenditure that is not related to segment operating performance. As reflected in the table above, we have recast our 2025 results to also reflect this adjustment. We believe that these non-GAAP operating measures, when reviewed collectively with our GAAP financial information, provide useful supplemental information to investors in assessing our operating performance. NM - Not Meaningful Cost of MCM product sales increased $27.0 million, or 105%, to $52.8 million for the quarter ended June 30, 2026. The increase was primarily attributable to higher product sales volumes for BAT ® , ACAM2000 ® , CNJ-016 ® (VIGIV), BioThrax ® , and TEMBEXA ® , as well as a significant non-recurring manufacturing cost related to the production of CYFENDUS ® . These increases were partially offset by a decrease in cost of sales for ANTHRASIL ® driven by lower sales volumes. MCM Products gross margin increased $81.6 million to $107.4 million for the quarter ended June 30, 2026. MCM Product gross margin percentage increased 20 percentage points to 64% for the quarter ended June 30, 2026. The increase in gross margin percentage was primarily driven by a more favorable sales mix and increased sales volumes, which improved absorption of fixed manufacturing costs. These improvements were partially offset by a significant non-recurring manufacturing cost related to the production of CYFENDUS ® . MCM Product segment adjusted gross margin in the current year period excludes the impacts of intangible asset amortization of $7.8 million, the portion of stock-based compensation expense recorded as cost of sales of $0.7 million and inventory step-up provision of $0.2 million. YTD 2026 REPORTABLE SEGMENT RESULTS ($ in millions) Commercial Products Six Months Ended June 30, 2026 2025 $ Change % Change Revenues $ 95.3 $ 112.8 $ (17.5 ) (16)% Cost of sales 63.1 60.9 2.2 4 % Intangible asset amortization 18.9 18.9 — — % Gross margin * $ 13.3 $ 33.0 $ (19.7 ) (60)% Gross margin % * 14 % 29 % Add back: Intangible asset amortization $ 18.9 $ 18.9 Severance and restructuring costs — 0.2 Stock-based compensation expense 0.1 — Segment adjusted gross margin ** $ 32.3 $ 52.1 $ (19.8 ) (38)% Segment adjusted gross margin % ** 34 % 46 % * Gross margin is calculated as revenues less cost of sales and intangible asset amortization. Gross margin % is calculated as gross margin divided by revenues. ** Segment adjusted gross margin, which is a non-GAAP financial measure, for our Commercial Products segment is calculated as gross margin plus intangible asset amortization, severance and restructuring costs and the portion of stock-based compensation expense that is recorded as cost of sales. Segment adjusted gross margin percentage, which is a non-GAAP financial measure, is calculated as segment adjusted gross margin divided by revenues. The Company’s management utilizes segment adjusted gross margin and segment adjusted gross margin percentage for purposes of evaluating our ongoing operations and for internal planning and forecasting purposes. In calculating these measures, we began excluding stock-based compensation that is recorded as cost of sales in the first quarter of 2026, as this reflects a non-cash expenditure that is not related to segment operating performance. As reflected in the table above, we have recast our 2025 results to also reflect this adjustment. We believe that these non-GAAP operating measures, when reviewed collectively with our GAAP financial information, provide useful supplemental information to investors in assessing our operating performance. NM - Not Meaningful Cost of Commercial Product sales increased $2.2 million, or 4%, to $63.1 million for the six months ended June 30, 2026. The increase was primarily due higher KLOXXADO ® sales and Canadian sales of branded NARCAN ® , largely offset by lower sales volumes of OTC NARCAN ® in the U.S. Commercial Products gross margin decreased $19.7 million, or 60%, to $13.3 million for the six months ended June 30, 2026. Commercial Products gross margin percentage decreased 15 percentage points to 14% for the six months ended June 30, 2026. The decrease was largely due to an unfavorable price and volume mix of OTC NARCAN ® across all U.S. sales channels and product mix due to the introduction of KLOXXADO ® , partially offset by lower product costs related to the Canadian sales. Commercial Products segment adjusted gross margin in the current year period excludes the impact of intangible asset amortization of $18.9 million and the portion of stock-based compensation expense recorded as cost of sales of $0.1 million. ($ in millions) MCM Products Six Months Ended June 30, 2026 2025 $ Change % Change Revenues $ 269.8 $ 215.0 $ 54.8 25 % Cost of sales 89.6 76.0 13.6 18 % Intangible asset amortization 14.8 13.6 1.2 9 % Gross margin * $ 165.4 $ 125.4 $ 40.0 32 % Gross margin % * 61 % 58 % Add back: Intangible asset amortization $ 14.8 $ 13.6 Severance and restructuring benefit — (1.2 ) Inventory step-up provision 0.3 1.8 Stock-based compensation expense 1.2 0.6 Segment adjusted gross margin ** $ 181.7 $ 140.2 $ 41.5 30 % Segment adjusted gross margin % ** 67 % 65 % * Gross margin is calculated as revenues less cost of sales and intangible asset amortization. Gross margin % is calculated as gross margin divided by revenues. ** Segment adjusted gross margin, which is a non-GAAP financial measure, for our MCM Products segment is calculated as gross margin plus intangible asset amortization, inventory step-up provision, severance and restructuring benefit and the portion of stock-based compensation expense that is recorded as cost of sales. Segment adjusted gross margin percentage, which is a non-GAAP financial measure, is calculated as segment adjusted gross margin divided by revenues. The Company’s management utilizes segment adjusted gross margin and segment adjusted gross margin percentage for purposes of evaluating our ongoing operations and for internal planning and forecasting purposes. In calculating these measures, we began excluding stock-based compensation that is recorded as cost of sales in the first quarter of 2026, as this reflects a non-cash expenditure that is not related to segment operating performance. As reflected in the table above, we have recast our 2025 results to also reflect this adjustment. We believe that these non-GAAP operating measures, when reviewed collectively with our GAAP financial information, provide useful supplemental information to investors in assessing our operating performance. NM - Not Meaningful Cost of MCM product sales increased $13.6 million, or 18%, to $89.6 million for the six months ended June 30, 2026. The increase was primarily due to higher cost of sales of BAT ® , CNJ-016 ® (VIGIV) and BioThrax ® , reflecting increased sales volumes as well as increased non-recurring manufacturing costs related to production of CYFENDUS ® . These increases were partially offset by lower cost of sales for ANTHRASIL ® and TEMBEXA ® due to lower unit sales volume. MCM Product gross margin increased $40.0 million, or 32%, to $165.4 million for the six months ended June 30, 2026. MCM Product gross margin percentage increased 3 percentage points to 61% for the six months ended June 30, 2026. The increase in gross margin percentage was primarily due to a favorable sales volume and product mix which was weighted more heavily towards higher margin products, the margin improvements were partially offset by non-recurring manufacturing costs mentioned above. MCM Product segment adjusted gross margin in the current year period excludes the impacts of intangible asset amortization of $14.8 million, the portion of stock-based compensation expense recorded as cost of sales of $1.2 million and inventory step-up provision of $0.3 million. 2026 FINANCIAL FORECAST The Company provides the following updated financial forecast for full year 2026, reflecting management's expectations based on the most current information available. METRIC ($ in millions ) Updated Range (as of 08/05/2026) Action Previous Range (as of 04/30/2026) Total revenues $645 - $675 REVISED $720 - $760 Net loss $(245) - $(225) REVISED $(30) - $(10) Adjusted net income (2) $10 - $30 REVISED $45 - $65 Adjusted EBITDA (2) $130 - $150 REVISED $155 - $175 Adjusted gross margin % (2) 42% - 44% REVISED 45% - 47% Key Assumptions ($ and shares in millions) Updated Range (as of 08/05/2026) Interest expense ~$40 R&D ~6% of Revenues SG&A ~27% to 28% of Revenues Weighted avg. fully diluted share count ~52 Stock-based compensation expense ~$19 Capex ~$17 Depreciation & amortization ~$82 Q2 2026 METRIC ($ in millions ) Q3 2026 Forecast Total revenues $110 - $130 FOOTNOTES (1) All financial information included in this release is unaudited. (2) See “ Non-GAAP Financial Measures” and the “Reconciliation of Non-GAAP Financial Measures” tables for the definitions and reconciliations of Company-wide non-GAAP financial measures to the most closely related GAAP financial measures. Reconciliations of segment non-GAAP financial measures are included within the reportable segment tables. In the first quarter of 2026 we revised our calculations of these measures to exclude the impact of stock-based compensation expense, as this is a non-cash expense that is not related to our operating performance. The updated ranges for our 2026 forecast reflect this adjustment. (3) Product sales, net are reported net of variable consideration including returns, rebates, wholesaler fees and prompt pay discounts in accordance with GAAP. CONFERENCE CALL, PRESENTATION SUPPLEMENT AND WEBCAST INFORMATION Company management will host a conference call at 5:00 pm eastern time today, August 5, 2026, to discuss these financial results. The conference call and presentation supplement can be accessed from the Company's website or through the following: By phone Advanced registration is required. Visit to register and receive an email with the dial-in number, passcode and registrant ID. By webcast Visit A replay of the call can be accessed from the Emergent website. ABOUT EMERGENT BIOSOLUTIONS INC. At Emergent, our mission is to protect and save lives. For over 25 years, we’ve been at work preparing those entrusted with protecting public health. We deliver protective and life-saving solutions for health threats like smallpox, mpox, botulism, Ebola, anthrax and opioid overdose emergencies. To learn more about how we help prepare communities around the world for today’s health challenges and tomorrow’s threats, visit our website and follow us on LinkedIn, X, Instagram, Apple Podcasts and Spotify. NON-GAAP FINANCIAL MEASURES In the accompanying analysis of financial information, we sometimes use information derived from consolidated and segment financial information that may not be presented in our financial statements or prepared in accordance with generally accepted accounting principles in the United States (“GAAP”). Certain of these financial measures are considered not in conformity with GAAP (“non-GAAP financial measures”) under the United States Securities and Exchange Commission (“SEC”) rules. Specifically, we have referred to the following non-GAAP financial measures: Adjusted Net Income Adjusted Net Income per Diluted Share Adjusted EBITDA Adjusted EBITDA Margin Adjusted Gross Margin Adjusted Gross Margin % Segment Adjusted Gross Margin Segment Adjusted Gross Margin % We define Adjusted Net Income and Adjusted Net Income per Diluted Share, which are non-GAAP financial measures, as net income (loss) and net income (loss) per diluted share, respectively, excluding the impact of non-cash amortization charges, impairments, severance and restructuring costs (benefits), inventory step-up provision, acquisition and divestiture costs, loss on assets held for sale, contingent consideration milestones, changes in fair value of financial instruments, stock-based compensation expense, loss on debt extinguishment, other, net, and tax effects. In the first quarter of 2026 we revised our calculation of these measures to exclude the impact of stock-based compensation expense, as this is a non-cash expense that is not related to our operating performance. We use Adjusted Net Income for the purpose of calculating Adjusted Net Income per Diluted Share. Management uses Adjusted Net Income per Diluted Share to assess total Company operating performance on a consistent basis. We believe that these non-GAAP financial measures, when considered together with our GAAP financial results and GAAP financial measures, provide management and investors with an additional understanding of our business operating results, including underlying trends. We define Adjusted EBITDA, which is a non-GAAP financial measure, as net income (loss) before depreciation and amortization, income taxes, total interest expense, net, impairments, inventory step-up provision, changes in fair value of financial instruments, severance and restructuring costs (benefits), acquisition and divestiture costs, loss on assets held for sale, contingent consideration milestones, stock-based compensation expense, loss on debt extinguishment, and other, net. We define Adjusted EBITDA Margin, which is a non-GAAP financial measure, as Adjusted EBITDA divided by Total Revenues. In the first quarter of 2026 we revised our calculation of these measures to exclude the impact of stock-based compensation expense, as this is a non-cash expense that is not related to our operating performance. We believe that these non-GAAP financial measures, when considered together with our GAAP financial results and GAAP financial measures, provide management and investors with a more complete understanding of our operating results, including underlying trends. In addition, EBITDA is a common alternative measure of operating performance used by many of our competitors. It is used by investors, financial analysts, rating agencies and others to value and compare the financial performance of companies in our industry, although it may be defined differently by different companies. Therefore, we also believe that this non-GAAP financial measure, considered along with corresponding GAAP financial measures, provides management and investors with additional information for comparison of our operating results with the operating results of other companies. We define Adjusted Gross Margin, which is a non-GAAP financial measure, as Gross Margin, excluding the impact of intangible asset amortization, stock-based compensation expense, severance and restructuring costs (benefits) and inventory step-up provision. We define Adjusted Gross Margin %, which is a non-GAAP financial measure, as Adjusted Gross Margin as a percentage of Products and services sales, net. In the first quarter of 2026 we revised our calculation of these measures to exclude the impact of stock-based compensation expense, as this is a non-cash expense that is not related to our operating performance. We define Segment Adjusted Gross Margin, which is a non-GAAP financial measure, as a segment's Gross Margin excluding the respective impact of intangible asset amortization, severance and restructuring costs (benefits), stock-based compensation expense and inventory step-up provision. We define Segment Adjusted Gross Margin %, which is a non-GAAP financial measure, as Segment Adjusted Gross Margin as a percentage of a segment's revenues. In the first quarter of 2026 we revised our calculation of these measures to exclude the impact of stock-based compensation expense, as this is a non-cash expense that is not related to segment operating performance. Non-GAAP financial measures are not defined in the same manner by all companies and may not be comparable with other similarly titled measures of other companies. The determination of the amounts that are excluded from these non-GAAP financial measures are a matter of management judgment and depend upon, among other factors, the nature of the underlying expense or income amounts. Non-GAAP financial measures should be considered in addition to, but not as a substitute for or superior to, the information contained in our Consolidated Statements of Operations and Consolidated Statements of Cash Flows. Reconciliations of these non-GAAP financial measures to the most directly comparable GAAP financial measures are included in the financial tables accompanying this press release. SAFE HARBOR STATEMENT This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. All statements, other than statements of historical fact, including statements regarding the future performance of the Company or any of our businesses, our business strategy, future operations, future financial position, future revenues and earnings, our ability to achieve the objectives of our restructuring initiatives, acquisitions and divestitures, including our future results, projected costs, prospects, plans and objectives of management, are forward-looking statements. We generally identify forward-looking statements by using words like “anticipate,” “believe,” “can,” “continue,” “could,” “estimate,” “expect,” “confident,” “commit,” “forecast,” “future,” “outlook,” “goal,” “intend,” “may,” “plan,” “position,” “possible,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would,” and similar expressions or variations thereof, or the negative thereof, but these terms are not the exclusive means of identifying such statements. These forward-looking statements are based on our current intentions, beliefs, assumptions and expectations regarding future events based on information that is currently available. You should realize that if underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could differ materially from our expectations. Readers are, therefore, cautioned not to place undue reliance on any forward-looking statement contained herein. Any such forward-looking statement speaks only as of the date of this press release, and, except as required by law, we do not undertake any obligation to update any forward-looking statement to reflect new information, events or circumstances. There are a number of important factors that could cause our actual results to differ materially from those indicated by such forward-looking statements, including, among others, the availability of USG funding for contracts related to procurement of our medical countermeasures (“MCM”) products, including CYFENDUS ® (Anthrax Vaccine Adsorbed (AVA) Adjuvanted), previously known as AV7909, ACAM2000 ® (Smallpox and Mpox (Vaccinia) Vaccine, Live), CNJ-016 ® (Vaccinia Immune Globulin Intravenous (Human) (VIGIV)), BAT ® (Botulism Antitoxin Heptavalent (A,B,C,D,E,F,G)-(Equine)), BioThrax ® (Anthrax Vaccine Adsorbed) Ebanga ® (ansuvimab-zykl) and/or TEMBEXA ® (brincidofovir) among others, as well as contracts related to development of medical countermeasures; our ability to meet our commitments to quality and compliance in all of our manufacturing operations; our ability to negotiate additional USG procurement or follow-on contracts for our MCM products that have expired or will be expiring; the commercial availability and impact of a generic and competitive marketplace on future sales of NARCAN ® (naloxone HCL) Nasal Spray, over-the-counter NARCAN ® Nasal Spray and KLOXXADO ® Nasal Spray; our ability to perform under our contracts with the USG, including the timing of and specifications relating to deliveries; the ability of our contractors and suppliers to maintain compliance with current good manufacturing practices and other regulatory obligations; our ability to collect reimbursement for raw materials and payment of service fees from our Bioservices customers; the results of pending government investigations and their potential impact on our business; our ability to satisfy the conditions of our litigation settlement agreements, and the potential impact of such agreements, including the funds to resolve related litigation, on our business; our ability to comply with the operating and financial covenants required by (i) our term loan facility under the Credit Agreement, dated April 16, 2026, by and among the Company, the lenders from time to time party thereto, and OrbiMed Royalty & Credit Opportunities V, LP, as administrative agent, (ii) our revolving credit facility under a credit agreement, dated September 30, 2024, among the Company, certain subsidiary borrowers, the lenders from time to time party thereto and Wells Fargo, National Association, as Agent, and (iii) our 3.875% Senior Unsecured Notes due 2028; our ability to maintain adequate internal control over financial reporting and to prepare accurate financial statements in a timely manner; our ability to maintain sufficient cash flow from our operations to pay our substantial debt, both now and in the future; our ability to invest in our business operations as a result of our current indebtedness; the impact of our share and debt repurchase programs; the procurement of our product candidates by USG entities under regulatory authorities that permit government procurement of certain medical products prior to FDA marketing authorization, and corresponding procurement by government entities outside the United States; the success of our commercialization, marketing and manufacturing capabilities and strategy; our ability to identify and acquire companies, businesses, products or product candidates that satisfy our selection criteria; our ability to attract and retain qualified personnel; our ability to adequately secure and protect our intellectual property rights; the impact of cybersecurity incidents, including the risks from the unauthorized access, interruption, failure or compromise of our information systems or those of our business partners, collaborators or other third parties; and the accuracy of our estimates regarding future revenues, expenses, capital requirements and need for additional financing. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ materially from our expectations in any forward-looking statement. In addition, other risks and uncertainties not presently known to us or that we currently believe to be immaterial could affect the accuracy of any forward-looking statements. Readers should consider this cautionary statement, as well as the risks identified in our periodic reports filed with the Securities and Exchange Commission, when evaluating our forward-looking statements. Trademarks Emergent ® , BioThrax ® , BaciThrax ® , BAT ® , Trobigard ® , ANTHRASIL ® , CNJ-016 ® , ACAM2000 ® , ​NARCAN ® , CYFENDUS ® , TEMBEXA ® and any and all Emergent BioSolutions Inc. brands, products, services and feature names, logos and slogans are trademarks or registered trademarks of Emergent BioSolutions Inc. or its subsidiaries in the United States or other countries. All other brands, products, services and feature names or trademarks are the property of their respective owners, including KLOXXADO ® , which is a registered trademark of Hikma Pharmaceuticals USA Inc. Investor Contact Rich Lindahl Executive Vice President, Chief Financial Officer lindahlr@ebsi.com Media Contact Assal Hellmer Vice President, Communications mediarelations@ebsi.com Emergent BioSolutions Inc. Consolidated Balance Sheets (in millions, except per share data) June 30, 2026 December 31, 2025 (unaudited) ASSETS Current assets: Cash and cash equivalents $ 139.7 $ 205.4 Restricted cash 1.2 3.7 Accounts receivable, net 190.0 84.2 Inventories, net 303.6 343.4 Prepaid expenses and other current assets 25.4 25.8 Assets held-for-sale 6.1 — Total current assets 666.0 662.5 Property, plant and equipment, net 178.0 205.4 Intangible assets, net 261.8 436.5 Other assets 11.0 14.2 Total assets $ 1,116.8 $ 1,318.6 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable $ 50.2 $ 55.6 Accrued expenses 17.1 12.2 Accrued compensation 26.2 41.8 Deferred revenue 15.0 5.0 Current tax liability 4.4 6.8 Other current liabilities 9.9 10.8 Total current liabilities 122.8 132.2 Debt 581.8 572.1 Deferred tax liability 35.4 37.8 Other liabilities 35.4 53.9 Total liabilities $ 775.4 $ 796.0 Stockholders’ equity: Preferred stock, $0.001 par value per share; 15.0 shares authorized, no shares issued and outstanding — — Common stock, $0.001 par value per share; 200.0 shares authorized, 61.9 and 60.9 shares issued; 51.3 and 52.1 shares outstanding, respectively. 0.1 0.1 Treasury stock, at cost, 10.7 and 8.7 common shares, respectively (270.5 ) (252.6 ) Additional paid-in capital 951.8 942.4 Accumulated other comprehensive loss, net (6.8 ) (7.5 ) Accumulated deficit (333.2 ) (159.8 ) Total stockholders’ equity $ 341.4 $ 522.6 Total liabilities and stockholders’ equity $ 1,116.8 $ 1,318.6 Emergent BioSolutions Inc. Consolidated Statements of Operations (unaudited, in millions, except per share data) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 Revenues: Product and services sales, net $ 226.8 $ 130.3 $ 376.5 $ 339.4 Contracts and grants 7.5 10.6 13.9 23.7 Total revenues 234.3 140.9 390.4 363.1 Operating expenses: Cost of product and services sales, net (1) 97.1 66.9 169.1 155.4 Research and development 9.2 12.5 19.7 27.6 Selling, general and administrative 44.6 43.7 91.2 96.1 Amortization of intangible assets 17.2 16.2 33.7 32.5 Impairment of long-lived assets 191.3 — 191.3 — Total operating expenses 359.4 139.3 505.0 311.6 Income (loss) from operations (125.1 ) 1.6 (114.6 ) 51.5 Other income (expense): Interest expense (10.0 ) (14.7 ) (21.0 ) (29.4 ) Loss on assets held-for-sale (10.7 ) — (10.7 ) (12.2 ) Loss on debt extinguishment (20.5 ) — (20.5 ) — Other, net — (3.7 ) 13.9 66.0 Total other income (expense), net (41.2 ) (18.4 ) (38.3 ) 24.4 Income (loss) before income taxes (166.3 ) (16.8 ) (152.9 ) 75.9 Income tax provision (benefit) 13.9 (4.8 ) 20.5 19.9 Net income (loss) $ (180.2 ) $ (12.0 ) $ (173.4 ) $ 56.0 Earnings (loss) per common share Basic $ (3.49 ) $ (0.22 ) $ (3.35 ) $ 1.03 Diluted $ (3.49 ) $ (0.22 ) $ (3.35 ) $ 0.99 Weighted average shares outstanding Basic 51.6 54.2 51.7 54.3 Diluted 51.6 54.2 51.7 56.7 (1) Exclusive of intangible asset amortization Emergent BioSolutions Inc. Consolidated Statements of Cash Flows (unaudited, in millions) Six Months Ended June 30, 2026 2025 Operating Activities Net income (loss) $ (173.4 ) $ 56.0 Adjustments to reconcile net income to net cash provided by operating activities: Stock-based compensation expense 8.8 6.1 Depreciation and amortization 47.5 48.9 Amortization of deferred financing costs 3.4 4.7 Deferred income taxes (2.4 ) 4.7 Noncash loss on assets held-for-sale 10.7 12.2 Change in fair value of warrant liability (8.9 ) (6.6 ) Impairment of long-lived assets 191.3 — Loss on disposal of assets 2.0 1.3 Other 19.8 (9.1 ) Changes in operating assets and liabilities: Accounts receivable (107.7 ) 45.2 Inventories 39.8 (26.9 ) Prepaid expenses and other assets (0.6 ) 29.2 Accounts payable (4.4 ) (15.8 ) Accrued expenses and other liabilities 1.2 (28.3 ) Long-term incentive plan accrual 0.4 1.6 Accrued compensation (16.0 ) (26.3 ) Income taxes receivable and payable, net 4.3 (1.6 ) Contract liabilities 6.5 (0.1 ) Net cash provided by operating activities 22.3 95.2 Investing Activities Purchases of property, plant and equipment (4.5 ) (6.5 ) Proceeds from sale of property, plant and equipment 0.2 38.2 Milestone payment from prior asset acquisition (50.4 ) — Milestone proceeds from prior asset divestiture — 50.0 Purchase of convertible note receivable — (5.0 ) Net cash provided by (used in) investing activities (54.7 ) 76.7 Financing Activities Purchases of treasury stock (18.0 ) (6.9 ) Proceeds from stock-based compensation activity 1.4 0.8 Taxes paid for stock-based compensation activity (3.2 ) (0.7 ) Repayment of prior term loan facility (150.0 ) — Proceeds from the issuance of debt, net of lender fees 145.5 — Debt issuance and extinguishment costs (11.5 ) — Net cash used in financing activities: (35.8 ) (6.8 ) Effect of exchange rate changes on cash, cash equivalents and restricted cash — 0.3 Net change in cash, cash equivalents and restricted cash (68.2 ) 165.4 Cash, cash equivalents and restricted cash, beginning of period 209.1 105.6 Cash, cash equivalents and restricted cash, end of period $ 140.9 $ 271.0 Supplemental cash flow disclosures: Cash paid for interest $ 16.6 $ 24.8 Cash paid for income taxes, net of refunds $ 9.6 $ 16.6 Non-cash investing and financing activities: Purchases of property, plant and equipment unpaid at period end $ 2.6 $ 2.2 Loss on extinguishment of debt $ (20.5 ) $ — Excise tax liability accrued for treasury stock purchases $ 0.2 $ — Reconciliation of cash and cash equivalents and restricted cash: Cash and cash equivalents $ 139.7 $ 267.3 Restricted cash 1.2 3.7 Total $ 140.9 $ 271.0 Emergent BioSolutions Inc. Reconciliation of Non-GAAP Financial Measures Reconciliation of Net Income (loss) and Net Income (loss) per Diluted Share to Adjusted Net Income and Adjusted Net Income per Diluted Share (1) ($ in millions, except per share data) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 Source Net income (loss) $ (180.2 ) $ (12.0 ) $ (173.4 ) $ 56.0 Adjustments: Inventory step-up provision $ 0.2 $ — $ 0.3 $ 1.8 Cost of product and services sales, net Severance and restructuring costs (benefits) 0.5 0.5 0.7 (0.8 ) Cost of product and services sales, net, SG&A and R&D Stock-based compensation expense 6.9 4.6 8.8 6.1 Cost of product and services sales, net, SG&A and R&D Acquisition and divestiture costs — — — 0.2 SG&A Non-cash amortization charges 18.8 18.7 37.2 37.2 Amortization of intangible assets ("IA"), Other Income Impairments 191.3 — 191.3 — Impairment of long-lived assets Loss on assets held-for-sale 10.7 — 10.7 12.2 Other Income (Expense) Contingent consideration milestones — — (5.0 ) (50.0 ) Other Income (Expense) Changes in fair value of financial instruments (0.5 ) 2.9 (9.0 ) (6.6 ) Other Income (Expense) Loss on debt extinguishment 20.5 — 20.5 — Other Income (Expense) Other, net — 5.0 (0.3 ) (2.9 ) Other Income (Expense) Tax effect (37.3 ) (6.5 ) (39.0 ) 2.2 Total adjustments: $ 211.1 $ 25.2 $ 216.2 $ (0.6 ) Adjusted net income $ 30.9 $ 13.2 $ 42.8 $ 55.4 Net income (loss) per diluted share $ (3.49 ) $ (0.22 ) $ (3.35 ) $ 0.99 Adjustments: Inventory step-up provision $ — $ — $ 0.01 $ 0.03 Cost of product and services sales, net Severance and restructuring costs (benefits) 0.01 0.01 0.01 (0.01 ) Cost of product and services sales, net, SG&A and R&D Stock-based compensation expense 0.13 0.08 0.17 0.11 Cost of product and services sales, net, SG&A and R&D Acquisition and divestiture costs — — — — SG&A Non-cash amortization charges 0.36 0.35 0.72 0.66 Amortization of IA, Other Income Impairments 3.71 — 3.70 — Impairment of long-lived assets Loss on assets held-for-sale 0.21 — 0.21 0.22 Other Income (Expense) Contingent consideration milestones — — (0.10 ) (0.88 ) Other Income (Expense) Changes in fair value of financial instruments (0.01 ) 0.05 (0.17 ) (0.12 ) Other Income (Expense) Loss on debt extinguishment 0.40 — 0.40 — Other Income (Expense) Other, net — 0.09 (0.01 ) (0.05 ) Other Income (Expense) Tax effect (0.72 ) (0.12 ) (0.76 ) 0.03 Total adjustments: $ 4.09 $ 0.46 $ 4.18 $ (0.01 ) Adjusted net income per diluted share $ 0.60 $ 0.24 $ 0.83 $ 0.98 Diluted shares used in computing Adjusted net income per diluted share 51.6 54.2 51.7 56.7 (1) Amounts for fiscal year 2025 have been revised from those previously reported to reflect the exclusion of stock-based compensation expense. Emergent BioSolutions Inc. Reconciliation of Net Income (loss) and Net Income (loss) Margin to Adjusted EBITDA and Adjusted EBITDA Margin (1) ($ in millions) Three Months Ended June 30, Six Months Ended June 30, 2026 2025 2026 2025 Net income (loss) $ (180.2 ) $ (12.0 ) $ (173.4 ) $ 56.0 Adjustments: Depreciation & amortization $ 24.0 $ 23.5 $ 47.5 $ 48.9 Income taxes 13.9 (4.8 ) 20.5 19.9 Total interest expense, net 9.2 13.4 19.4 27.4 Inventory step-up provision 0.2 — 0.3 1.8 Severance and restructuring costs (benefits) 0.5 0.5 0.7 (0.8 ) Stock-based compensation expense 6.9 4.6 8.8 6.1 Acquisition and divestiture costs — — — 0.2 Impairments 191.3 — 191.3 — Loss on assets held-for-sale 10.7 — 10.7 12.2 Contingent consideration milestones — — (5.0 ) (50.0 ) Changes in fair value of financial instruments (0.5 ) 2.9 (9.0 ) (6.6 ) Loss on debt extinguishment 20.5 — 20.5 — Other, net — 5.0 (0.3 ) (2.9 ) Total adjustments $ 276.7 $ 45.1 $ 305.4 $ 56.2 Adjusted EBITDA $ 96.5 $ 33.1 $ 132.0 $ 112.2 Total revenues $ 234.3 $ 140.9 $ 390.4 $ 363.1 Net income (loss) margin (77)% (9)% (44)% 15 % Adjusted EBITDA margin 41 % 23 % 34 % 31 % (1) Amounts for fiscal year 2025 have been revised from those previously reported to reflect the exclusion of stock-based compensation expense. Emergent BioSolutions Inc. Reconciliations of Total Revenues to Product and Services Sales, Net and of Gross Margin and Gross Margin % to Adjusted Gross Margin and Adjusted Gross Margin % (1) Three Months Ended June 30, Six Months Ended June 30, ($ in millions) 2026 2025 2026 2025 Total revenues $ 234.3 $ 140.9 $ 390.4 $ 363.1 Contracts and grants 7.5 10.6 13.9 23.7 Product and services sales, net $ 226.8 $ 130.3 $ 376.5 $ 339.4 Cost of product and services sales, net 97.1 66.9 169.1 155.4 Intangible asset amortization 17.2 16.2 33.7 32.5 Gross margin $ 112.5 $ 47.2 $ 173.7 $ 151.5 Gross margin % 50 % 36 % 46 % 45 % Add back: Intangible asset amortization $ 17.2 $ 16.2 $ 33.7 $ 32.5 Stock-based compensation expense 0.9 0.3 1.4 0.6 Severance and restructuring costs (benefits) 0.1 (0.1 ) 0.1 (1.0 ) Inventory step-up provision 0.2 — 0.3 1.8 Adjusted gross margin $ 130.9 $ 63.6 $ 209.2 $ 185.4 Adjusted gross margin % 58 % 49 % 56 % 55 % (1) Amounts for fiscal year 2025 have been revised from those previously reported to reflect the exclusion of stock-based compensation expense. Emergent BioSolutions Inc. Reconciliation of Net Loss Forecast to Adjusted Net Income Forecast ($ in millions) 2026 Full Year Forecast Source Net loss $(245) - $(225) Adjustments: Inventory step-up provision $4 Cost of products and services, net Severance and restructuring costs 11 Cost of products and services, net, SG&A and R&D Stock-based compensation expense 19 COGS, R&D and SGA Non-cash amortization charges 63 Amortization of IA and Other Income (Expense) Impairments 191 Impairment of long-lived assets Loss on assets held-for-sale 11 Other Income (Expense) Contingent consideration milestones (10) Other Income (Expense) Changes in fair value of financial instruments (9) Other Income (Expense) Loss on debt extinguishment 21 Other Income (Expense) Tax effect (46) Total adjustments: $255 Adjusted net income $10 - $30 Reconciliation of Net Loss Forecast to Adjusted EBITDA Forecast ($ in millions) 2026 Full Year Forecast Net loss $(245) - $(225) Adjustments: Depreciation & amortization $82 Income taxes 15 Total interest expense, net 40 Inventory step-up provision 4 Severance and restructuring costs 11 Stock-based compensation expense 19 Impairments 191 Loss on assets held-for-sale 11 Contingent consideration milestones (10) Changes in fair value of financial instruments (9) Loss on debt extinguishment 21 Total adjustments $375 Adjusted EBITDA $130 - $150 Emergent BioSolutions Inc. Reconciliations of Forecasted Total Revenues to Forecasted Product and Services Sales, Net and of Forecasted Gross Margin and Gross Margin % to Forecasted Adjusted Gross Margin and Adjusted Gross Margin % ($ in millions) 2026 Full Year Forecast Total revenues $645 - $675 Contracts & Grants $(25) - $(25) Product and services sales, net $620 - $650 Cost of product and services sales, net $365 - $369 Intangible asset amortization 55 Gross margin $200 - $226 Gross margin % 32% - 35% Add back: Intangible asset amortization $55 Inventory step-up provision 4 Severance and restructuring costs 1 Stock-based compensation expense 3 Adjusted gross margin $263 - $289 Adjusted gross margin % 42% - 44%

抗生素耐药性日益增长的趋势使得新的抗感染治疗策略成为必要。基于数十年的广泛研究和开发，单克隆抗体在治疗抗生素耐药性细菌感染方面具有巨大潜力。在这篇对该领域的全面综述中，研究人员总结了快速新兴的单克隆治疗领域，这些方法提供了针对对人类健康构成严重关切的细菌病原体的替代策略。研究人员按物种和分子靶点组织研究结果，讨论了已证明有治疗潜力的抗体以及未能提供疗效的抗体，为未来高疗效治疗药物的设计和发现提供了新见解。此外，研究人员讨论了分子生物学的最新进展，这些进展彻底改变了单克隆抗体作为治疗药物的实施、效力和实用性，并持续推动着抗菌单克隆抗体将迈入一个激动人心的时代。**1 引言**抗生素耐药性（AMR）正日益成为人类健康和福祉的严重威胁。小分子药物表现出强烈的选择压力，导致逃逸突变，引发AMR并消除药物的效用。单克隆抗体（mAbs）提供了一种替代方法，通过多种宿主介导的保护机制（如血清杀菌活性和调理吞噬活性）间接杀死细菌。尽管逃逸突变也可能因mAb治疗而发生，但其选择压力与小分子不同，使治疗性mAb成为减少耐药性发生的有价值的策略。数十年的抗细菌mAb研究和开发已产生了大量用于预防和治疗多种病原体感染候选药物。尽管取得了这些进展，但仅有少数抗细菌mAb获批临床使用，包括obiltoxaximab和raxibacumab用于治疗炭疽杆菌毒素暴露，以及bezlotoxumab用于治疗艰难梭菌胃肠道感染。在这篇广泛的综述中，研究人员总结了抗细菌mAb发现和开发的大部分历程，重点关注关键细菌病原体以及针对其特定表位的众多mAb。**2 艰难梭菌**艰难梭菌是一种革兰氏阳性厌氧胃肠道细菌，通过孢子形式经粪-口途径传播。毒素A（TcdA）和毒素B（TcdB）被认为是艰难梭菌发病机制中的主要毒力因子。它们通过多步骤过程使宿主细胞中毒，包括结合特异性受体、内吞、在酸化内体中形成孔道、易位和葡萄糖基化宿主GTPases。艰难梭菌感染（CDI）每年在美国估计导致462,100例病例，12,800例死亡和10亿美元医疗费用。早期尝试使用高免疫牛初乳进行口服治疗，显示出治疗潜力，但因制造复杂性而未能进一步开发。**2.1 艰难梭菌：抗毒素mAbs**Medarex首次报告了抗毒素mAbs，后授权给默克。两种全人源IgG1κ mAbs，抗TcdA（CDA1/actoxumab）和抗TcdB（CDB1/bezlotoxumab）被选出。Bezlotoxumab通过识别TcdB CROPs结构域上的两个不同位点，阻止TcdB与宿主细胞表面受体CSPG4结合。两项全球III期研究（MODIFY I和MODIFY II）显示，与安慰剂相比，bezlotoxumab显著降低了rCDI。Bezlotoxumab已获批用于预防高风险CDI患者复发。不幸的是，Zinplava?于2025年1月停产。阿斯利康正在开发另一种抗TcdB mAb，AZD5148，该抗体通过YTE替换（Fc区M252Y/S254T/T256E三重突变）延长半衰期。AZD5148结合TcdB的GTD结构域，阻止TcdB酶活性递送进入宿主细胞。该抗体表位高度保守，正在PRISM研究（NCT07285213）中评估其预防CDI复发的有效性和安全性。**3 金黄色葡萄球菌**金黄色葡萄球菌是一种革兰氏阳性菌，是医院获得性感染的主要原因，2019年全球约导致100万人死亡。该菌依靠大量分泌和表面表达的毒力因子来穿透组织、促进粘附和损害宿主免疫反应。毒力基因表达在感染过程中受时间和空间调控，且许多毒力因子功能冗余。尽管已有几种抗毒力mAbs在临床前模型中产生并验证，但只有少数进入临床试验。**3.1 金黄色葡萄球菌：针对成孔毒素的mAbs**金黄色葡萄球菌拥有六种溶细胞性成孔毒素，包括α毒素（Hla）和双组分杀白细胞素。Hla通过与受体ADAM10相互作用表现出广泛的细胞向性。人源抗Hla mAb LC10经YTE替换工程改造后产生suvratoxumab（MEDI4893），在II期SAATELLITE研究中与安慰剂相比使呼吸机相关性肺炎相对减少31.8%。Tosatoxumab（AR-301）在重症监护室患者严重金黄色葡萄球菌肺炎的随机I/II期研究中显示缩短了通气持续时间。ASN100（ASN1和ASN2组合）在非人灵长类模型中显示出保护作用，但在II期研究中因无效而终止。**3.2 金黄色葡萄球菌：针对其他分泌蛋白的mAbs**金黄色葡萄球菌的补体抑制剂和趋化抑制蛋白通过干扰补体激活级联来促进免疫逃逸。人源mAb 6D4在体外抑制金黄色葡萄球菌补体抑制剂活性。针对金黄色葡萄球菌超抗原（SAgs），特别是葡萄球菌肠毒素B（SEB），已开发出人源化IgG2抗SEB mAbs，在金黄色葡萄球菌诱导的败血症模型中保护小鼠免受致死性SEB中毒。此外，针对中毒性休克综合征毒素-1的几种有效中和mAbs已在临床前模型中显示出疗效。**3.3 金黄色葡萄球菌：针对表面蛋白的mAbs**金黄色葡萄球菌表达大量细胞壁锚定蛋白，其中MSCRAMM（识别粘附基质分子的分子表面组分）数量最多。凝集因子A（ClfA）存在于所有分离株中，结合纤维蛋白原促进凝集和粘附。小鼠mAb Aurexis及其人源化版本tefibazumab在II期临床试验中显示出潜在益处，但未进一步进行更大统计学效力的试验。AZD7745是另一种人源IgG1抗ClfA mAb，结合高度保守的表位，在体外介导调理吞噬杀伤（OPK）活性，并在小鼠致死性菌血症模型中提供保护。AZD7760是suvratoxumab和AZD7745的多机制mAb组合，正在I/IIa期临床研究中评估。金黄色葡萄球菌蛋白A（SpA）通过其Fcγ和Fab结合能力损害IgG效应功能。抗SpA mAb 3F6的人源化版本抑制人IgG与SpA结合，并表现出更好的稳定性。脂磷壁酸是另一种主要细胞壁成分，抗脂磷壁酸的pagibaximab在III期研究中未能在早产儿中显著降低迟发性败血症。**3.4 金黄色葡萄球菌：针对营养和铁摄取的mAbs**金黄色葡萄球菌表达参与营养摄取的表面暴露脂蛋白。铁调节表面决定簇（Isd）系统从宿主中清除血红素铁。抗IsdA和抗IsdH mAbs在小鼠败血症模型中提供保护。最近描述了一种骆驼科纳米抗体，能交叉反应结合IsdH和IsdB的血红素结合口袋，降低三种致病性MRSA菌株的体外生长。几种抗锰转运蛋白C（MntC）mAbs在体外诱导中性粒细胞呼吸爆发，减少小鼠菌血症中的细菌负荷，并在幼年大鼠模型中提供保护。**4 铜绿假单胞菌**铜绿假单胞菌是一种革兰氏阴性杆菌，是机会性病原体，因其耐药性和显著毒力而成为新药开发的长期目标。**4.1 铜绿假单胞菌：靶向PcrV的mAbs**III型分泌系统的针尖蛋白PcrV是理想的mAb靶点。2002年开发的小鼠mAb结合PcrV C末端，阻断细胞毒素易位。该mAb成为KB001的基础，这是一种人源化聚乙二醇化Fab抗体。在II期研究中，KB001降低了囊性纤维化患者的气道炎症标志物，但未能减少需要抗生素治疗的时间。随后使用多种方法开发了其他抗PcrV mAbs，包括从恢复期或慢性感染患者血浆B细胞分离的全人源mAbs。**4.2 铜绿假单胞菌：靶向Psl外多糖的mAbs**通过使用目标非依赖性筛选策略，研究人员鉴定了靶向Psl外多糖的mAbs。最有效的抗体Cam003对表型和地理多样的铜绿假单胞菌菌株表现出显著广度和效力。Cam003介导浓度依赖性OPK活性，并阻断铜绿假单胞菌粘附于培养的上皮细胞。在临床前模型中，Cam003对致死性肺炎、热损伤和角膜感染提供剂量依赖性预防保护。**4.3 铜绿假单胞菌：靶向Psl和PcrV的双特异性mAb Gremubamab**Gremubamab（MEDI3902）是一种首创的二价双特异性人源IgG1κ mAb，同时靶向Psl外多糖和PcrV。与任一亲本抗体或其组合相比，该抗体表现出更优效力。在临床前模型中，MEDI3902对急性肺炎、呼吸机相关性肺炎等多种模型提供剂量依赖性保护。I期研究证实参与者耐受性良好。II期研究（EVADE）在整体人群中未达到减少院内肺炎发病率的主要终点，但事后分析提示在基线炎症标志物较低的患者亚组中可能存在获益。在GREAT-2试验中，针对慢性定植铜绿假单胞菌的支气管扩张症患者，500 mg剂量显著降低肺部细菌水平，1500 mg剂量显著减少急性加重频率。**4.4 铜绿假单胞菌：靶向脂多糖的mAbs**脂多糖（LPS）是革兰氏阴性菌的关键毒力因子。人源IgM mAb panobacumab针对铜绿假单胞菌血清型O11 LPS，在II期研究中作为医院获得性肺炎的辅助治疗，与安慰剂相比显著缩短临床缓解时间。另一种研究小组开发了针对血清型O5 LPS的IgG2b mAbs混合物，在小鼠肺炎模型中减轻炎症和气道菌落形成单位（CFUs）。LPS血清型的多样性对所有靶向LPS的mAbs的广度构成挑战。**4.5 铜绿假单胞菌：靶向其他结构的mAbs**Aridis Pharmaceuticals开发的AR-105靶向藻酸盐，但在II期研究中未减少感染患者达到临床治愈的时间。另一个小组开发了靶向IV型菌毛PilQ-PilA二硫键（QA）区域的mAb，与抗生素联用时显示出辅助疗效。靶向铁载体FpvA的mAb和靶向鞭毛主要蛋白亚基FliC的mAb均显示出一定的体内保护效力。靶向外膜蛋白OprF的IgG2a mAb在体外减少生物被膜形成，但在小鼠急性肺炎模型中未提供保护。**5 鲍曼不动杆菌**鲍曼不动杆菌是一种广泛耐药革兰氏阴性杆菌，世界卫生组织宣布其对新疗法开发构成严重关切。**5.1 鲍曼不动杆菌：靶向外膜蛋白的mAbs**外膜蛋白A（OmpA）是潜在的疫苗候选物。Russo小组的研究表明，OmpA仅能在无荚膜的突变菌株中被mAb结合，而在具有完整荚膜的临床分离株中则不能。遗传性消除荚膜可恢复抗OmpA mAbs的活性。针对OmpA的小鼠IgG2a mAbs在小鼠致死性肺炎模型中提供保护，但样本量小且生存跟踪时间短。**5.2 鲍曼不动杆菌：靶向荚膜的mAbs**由于荚膜可能屏蔽关键抗原，多个研究小组将重点转向靶向荚膜本身。Spellberg实验室通过使用活细菌免疫小鼠开发了多种mAbs，事后确定这些mAbs靶向荚膜多糖。人源化IgG1 mAbs在血液和肺部感染小鼠模型中表现出高效保护效力，与粘菌素联用显示协同作用，且连续传代后未检测到逃逸突变。这些mAbs后来被用于产生人源化双特异性mAb，靶向多种荚膜类型。第三种抗荚膜mAb靶向伪氨基糖，在鲍曼不动杆菌的血液和软组织感染模型中展示出广泛体外结合和强效体内活性。**6 肺炎克雷伯菌**肺炎克雷伯菌是一种普遍存在的高度耐药革兰氏阴性病原体。**6.1 肺炎克雷伯菌：靶向LPS O抗原的mAbs**O抗原的靶向在早期工作中显示可穿透荚膜。Arsanis Biosciences生产的IgG1κ mAb显示，结合和中和LPS能在兔菌血症模型中提供保护，且其保护机制可独立于补体沉积和调理吞噬作用。阿斯利康开发了靶向O1型LPS的mAb KPE33，但在另一常见血清型O2上无活性。随后通过使用目标非依赖性筛选方法，他们发现了人源化IgG1 mAb B39，该抗体结合O1和O2型LPS共有的表位，显著提高了结合广度，并在体内模型中对有荚膜的野生型O1和O2菌株表现出强大效力。**6.2 肺炎克雷伯菌：靶向表面蛋白的mAbs**阿斯利康通过目标非依赖性发现，确定了3型菌毛主要亚基MrkA是一个有效靶点，该靶点不被荚膜排除且独立于O血清型。靶向MrkA的mAbs在体内肺炎模型中有效。另一个研究小组最近发现了人源化IgG mAbs，能交叉反应大肠杆菌和肺炎克雷伯菌的FimH抗原，有效抑制菌毛介导的粘附，在UTI小鼠模型中对两种病原体均提供保护。**6.3 肺炎克雷伯菌：靶向荚膜的mAbs**Fries实验室开发了靶向K1荚膜的mAbs，以及靶向ST258菌株荚膜的IgG3 mAbs，后者能促进调理吞噬、中性粒细胞介导的杀伤和小鼠肺炎模型中肺部CFUs减少。他们还开发了具有交叉枝系活性的IgG2b mAb。另一个研究小组最近发现了靶向常见于高毒力肺炎克雷伯菌的K64型荚膜的mAb，在菌血症模型中具有预防效力。由于存在超过140种基因预测的荚膜类型，靶向荚膜多糖在临床上仍具有挑战性。**7 结核分枝杆菌**结核分枝杆菌是一种专性人类病原体，是结核病的病原体。**7.1 围绕结核分枝杆菌抗体的教条转变**过去认为抗体无效，因为M. tuberculosis居于细胞内。但研究表明，抗体通过Fc介导机制对其他胞内病原体如沙门氏菌提供保护。系统水平分析显示，抗体质量（包括Fc受体结合、糖基化和效应功能）而非数量决定感染控制。在非人灵长类中，静脉注射BCG后鉴定出抗原特异性IgM抗体是保护的最强相关因素之一。**7.2 结核分枝杆菌：靶向表面抗原的mAbs**针对肝素结合血凝素粘附素的抗体4057 D2在小鼠模型中降低致死率和脾脏播散。α-晶体蛋白特异性IgA也通过限制肺部M. tuberculosis生长提供保护。针对脂阿拉伯甘露聚糖的mAb SMITB在致死性攻击中强效保护动物。这些LAM特异性抗体通过调理吞噬作用驱动抗菌控制。**7.3 多种靶点mAbs以Fc依赖性方式限制结核分枝杆菌**一项跨比较研究测试了24种M. tuberculosis特异性mAbs，强调了针对多种分泌毒素、表面蛋白和多糖的抗体能在体内控制细菌。保护性M. tuberculosis特异性mAbs通过Fc依赖性方式，要求与肺部免疫细胞交叉通讯，挑战了胞内定位排除抗体功效的观点。**8 生物被膜**微生物生物被膜保护微生物免受抗菌药物和免疫活性攻击。**8.1 生物被膜：靶向DNABII的mAbs**DNABII蛋白家族在真细菌中普遍存在，在生物被膜中协调胞外DNA。靶向胞外DNABII的抗体导致DNABII解离，引起生物被膜结构崩塌。Bakaletz小组开发的DNABII结合尖端mAbs混合物在体外崩溃四种病原体的胞外DNA基质，并在动物模型中改善感染结果。这项技术正在由Clarametyx Biosciences临床开发为CMTX-101。Trellis Biosciences开发的TRL1068能破坏MRSA和铜绿假单胞菌的生物被膜，在植入物感染模型中增强达托霉素治疗，I期临床研究显示消除3/11患者假体污染。**8.2 生物被膜：靶向其他结构的mAbs**聚-N-乙酰葡糖胺（PNAG）是生物被膜的结构成分。两种靶向乙酰化和去乙酰化PNAG的人源IgG1 mAbs在小鼠金黄色葡萄球菌感染模型中协同拯救90%小鼠。靶向Curli淀粉样纤维的mAbs抑制鼠伤寒沙门氏菌生物被膜形成，与氨苄西林协同消除CFU负担，并在小鼠植入模型中促进吞噬反应。针对金黄色葡萄球菌生物被膜的人源IgG1 mAbs可同时靶向浮游细胞和生物被膜结构。**9 单域抗体**骆驼科单域抗体（VHH）大小12-15 kDa，具有出色稳定性，可进入隐藏的保守表位。针对艰难梭菌毒素的VHH，如VNA2（四价VHH四聚体），在小鼠、仓鼠和悉生仔猪模型中提供保护。其他VHH已成功针对金黄色葡萄球菌IsdH/IsdB和ClfA开发。靶向脂质A的VHH能结合天然细菌并促进膜不稳定性。**10 抗体-抗生素偶联物**抗体-抗生素偶联物（AACs）通过可裂解连接子将抗生素连接到mAb，仅在吞噬溶酶体中释放抗生素。首个AAC是靶向细胞壁磷壁酸的THIOMAB，连接新型利福平类抗生素，在小鼠菌血症模型中优于万古霉素。I期研究显示DFA曲线类似传统mAb。另一项研究将万古霉素偶联到抗SpA mAb，在假体关节感染模型中需与游离万古霉素联用才有效。针对铜绿假单胞菌LPS O抗原的AAC使用G2637，能在吞噬后使巨噬细胞内抗生素浓度提高约26倍。**11 体内表达生物制剂**治疗性mAb生产费时且昂贵。体内表达生物制剂平台使用核酸编码的mAb序列，将身体作为自身的生物反应器。**12 基于AAV的mAb递送**腺相关病毒（AAV）可维持长期表达，但只能包裹<3.3 kb DNA，限制了可递送的mAb形式。AAV递送的抗毒素mAbs在炭疽和艰难梭菌毒素疾病模型中提供保护。但AAV平台存在免疫原性问题，且大多数人对某些AAV血清型有抗体滴度。**13 基于DNA质粒的mAb递送**非病毒DNA质粒通过电穿孔递送，可递送大段DNA序列，不引发病载体免疫。DNA-based mAb（DmAb）递送在临床前模型中显示血清表达治疗性mAb水平。Weiner实验室在I期试验中验证了DmAb平台的临床可行性，峰值浓度达1.61 μg/mL，持续表达超过72周。但峰值表达通常延迟14-21天，且需要电穿孔设备。**14 基于mRNA的mAb递送**mRNA/LNP递送在约24小时内达到峰值表达，适合需要即时保护的被动免疫。通过mRNA优化策略可延长表达时间。临床前研究显示静脉注射后功能性IgG表达达170 μg/mL。mRNA-1944（抗基孔肯雅IgG）在I期研究中显示24小时内血清水平>1 μg/mL，持续长达16周。但静脉给药不便。冻干技术使mAb编码的mRNA/LNP可在室温下储存一个月。**15 其他新兴技术****15.1 Fc工程**Fc工程包括Fc“沉默”和半衰期延长策略。YTE平台（M252Y/S254T/T256E）和LS平台（M428L/N434S）用于半衰期延长。点突变可调整Fcγ受体和补体接合以增强调理吞噬等效应功能。对于金黄色葡萄球菌SpA逃逸问题，Fc修饰可能有益。**15.2 计算发现与设计**计算设计可优化mAb结合域，且最近已能完全在计算机内从头设计mAb候选物，包括靶向艰难梭菌TcdB的ScFv和VHH。该领域虽仍处于初期，但潜力巨大。**16 结论**靶向细菌病原体的mAb开发是抗击AMR的一个有前景但复杂的领域。抗毒素mAb的成功以及多特异性方法的进展验证了mAb疗法的潜力。挑战包括细菌表面抗原结构多样性、毒力因子差异调控、表位屏蔽和广菌株覆盖需求。未来抗体工程进步，包括半衰期延长、合理Fab和Fc设计、多特异性格式和新型递送方法，正在扩大其效用。mAbs将在AMR时代对致命性细菌感染的治疗库中发挥日益重要的作用。