79 Cash Flows from Operating Activities Net cash used in operating activities was $206.5 million for the year ended December 31, 2022. Cash used in operating activities was primarily driven by the increase in net loss during this period due to increased payroll and personnel expenses and manufacturing and clinical trial costs to support overall growth. Cash used in operating activities was also driven by changes in operating assets and liabilities. Cash Flows from Investing Activities Net cash used in investing activities was $336.5 million for the year ended December 31, 2022, was primarily related to net purchases of marketable securities during 2022. Cash Flows from Financing Activities Net cash provided by financing activities was $1.9 million for the year ended December 31, 2022, was primarily due to proceeds from stock option exercises and proceeds from issuances of common stock pursuant to employee stock purchase plans. Material Cash Requirements and Material Known Contractual Obligations and Commitments Operating Leases Operating lease payments represent our commitment for future minimum rent made under non-cancelable leases for our corporate offices in Palo Alto, California, and office and laboratory space in Visp, Switzerland. Total future undiscounted payments for our operating lease obligations as of December 31, 2022 were $117.3 million, of which $15.6 million is due in the next twelve months. Embedded Lease Embedded lease payments represent our commitment for future minimum payment made under the manufacturing agreement with Lonza Ltd. for the clinical and commercial supply of drug substance in a custom-built manufacturing facility. The total future payments relating to our embedded lease, including capital contribution payments, as of December 31, 2022 were approximately 184.5 million Swiss Francs, of which 34.5 million Swiss Francs is expected to be due in the next twelve months. Manufacturing Agreements The Company has entered into service and equipment purchase agreements in the normal course of business with various providers, which can contain minimum commitments or other noncancelable obligations. As of December 31, 2022, the total amount of contractual obligations related to these manufacturing agreements that are subject to cancellation fees, including accrued amounts, was $56.8 million, of which $55.5 million is expected to be due in the next twelve months. For further information on our leases and manufacturing agreements, refer to Note 8 to our consolidated financial statements included in Part II, Item 8 of this Annual Report on Form 10-K. Clinical Agreements The Company may incur potential contingent payments upon our achievement of clinical, regulatory and commercial milestones, as applicable. Due to the uncertainty of the achievement and timing of the events requiring payment under these agreements, the amounts to be paid by us are not fixed or determinable at this time. Critical Accounting Policies, Significant Judgments and Use of Estimates Our consolidated financial statements have been prepared in accordance with U.S. generally accepted accounting principles, or GAAP. The preparation of these consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and liabilities at the date of the consolidated financial statements, as well as the reported expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. We believe that the accounting policies discussed below are critical to understanding our historical and future performance, as these policies relate to the more significant areas involving management’s judgments and estimates.