XERIS BIOPHARMA HOLDINGS, INC. Index to Annual Report on Form 10-K Year Ended December 31, 2021 Page Cautionary Statements for Forward-Looking Information 4 Part I. Item 1. Business 6 Item 1A. Risk Factors 39 Item 1B. Unresolved Staff Comments 75 Item 2. Properties 75 Item 3. Legal Proceedings 76 Item 4. Mine Safety Disclosures 76 Part II. Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 76 Item 6. Selected Financial Data 76 Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations 77 Item 7A. Quantitative and Qualitative Disclosures About Market Risk 86 Item 8. Financial Statements and Supplementary Data 88 Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure 124 Item 9A. Controls and Procedures 124 Item 9B. Other Information 124 Item 9C. Disclosure regarding foreign jurisdictions that prevent inspections 124 Part III. Item 10. Directors, Executive Officers and Corporate Governance 125 Item 11. Executive Compensation 125 Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters 125 Item 13. Certain Relationships and Related Transactions, and Director Independence 125 Item 14. Principal Accountant Fees and Services 125 Part IV. Item 15. Exhibits and Financial Statement Schedules 126 Item 16. Form 10-K Summary 126 Index to Exhibits 127 Signatures 132 Solely for convenience, the trademarks and trade names in this Annual Report on Form 10-K (this “Annual Report”) are referred to without the ® and ™ symbols, but absence of such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto. The trademarks, trade names and service marks appearing in this Annual Report are the property of their respective owners. 3
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