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| Item 1. | | Business | | 4 |
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| Item 1A. | | Risk Factors | | 35 |
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| Item 1B. | | Unresolved Staff Comments | | 58 |
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| Item 1C. | | Cybersecurity | | 58 |
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| Item 2. | | Properties | | 59 |
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| Item 3. | | Legal Proceedings | | 59 |
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| Item 4. | | Mine Safety Disclosures | | 59 |
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| PART II | | | | |
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| Item 5. | | Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities | | 60 |
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| Item 6. | | Reserved | | 62 |
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| Item 7. | | Management’s Discussion and Analysis of Financial Condition and Results of Operations | | 62 |
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| Item 7A. | | Quantitative and Qualitative Disclosures about Market Risk | | 76 |
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| Item 8. | | Financial Statements and Supplementary Data | | 77 |
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| Item 9. | | Changes in and Disagreements with Accountants on Accounting and Financial Disclosure | | 112 |
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| Item 9A. | | Controls and Procedures | | 112 |
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| Item 9B. | | Other Information | | 114 |
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| Item 9C. | | Disclosure Regarding Foreign Jurisdictions that Prevent Inspections | | 114 |
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| PART III | | | | |
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| Item 10. | | Directors, Executive Officers, and Corporate Governance | | 114 |
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| Item 11. | | Executive Compensation | | 114 |
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| Item 12. | | Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters | | 114 |
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| Item 13. | | Certain Relationships and Related Transactions, and Director Independence | | 114 |
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| Item 14. | | Principal Accountant Fees and Services | | 115 |
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| PART IV | | | | |
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| Item 15. | | Exhibits, Financial Statement Schedules | | 115 |
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| SIGNATURES | 121 | |
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PART I
This Annual Report on Form 10-K contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). All statements other than statements of historical fact, including statements concerning our plans, objectives, goals, strategies, future events, future revenues or performance, financing needs, expectations, plans or intentions relating to clinical development, product candidates, the regulatory approval process, products and markets, and business trends and other information referred to under the sections entitled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” are forward-looking statements. These statements are subject to substantial known and unknown risks, uncertainties and other factors that may cause our actual results, outcomes, performance or achievements, or the timing of such results, outcomes, performance or achievements, to be materially different from any results, outcomes, performances or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “anticipates,” “assumes,” “believes,” “commitments,” “could,” “estimates,” “expects,” “forecasts,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “targets,” “will,” “would,” “seeks” and similar expressions intended to identify forward-looking statements. Forward-looking statements reflect our current views with respect to future events, are based on assumptions, and are subject to risks, uncertainties and other important factors, including, among other things, the potential for our programs; the timing, initiation, progress and expected results of our clinical trials and research and development programs, including enrollment, data, costs and regulatory submissions; our cash runway; our ability to advance product candidates into, and successfully complete, non-clinical studies and clinical trials; the potential for eventual regulatory approval and commercialization of our product candidates; the commercialization of our product candidates, if approved; our ability and the potential to successfully manufacture and supply our product candidates for clinical trials and for commercial use, if approved; the pricing, coverage, and reimbursement of our product candidates, if approved; our potential receipt of milestone payments and royalties under our collaboration agreements; future operating results; our ability to generate sales, income or cash flow; our estimates regarding expenses, capital requirements, and needs for additional financing and our ability to obtain additional capital; our ability to retain the continued service of our key executives and to identify, hire, and retain additional qualified professionals, the impact of any future outbreaks of disease, epidemics and pandemics; ongoing military conflicts, including between Ukraine and Russia and in the Middle East; rising tensions between China and Taiwan; developments relating to our competitors and our industry, including competing product candidates and therapies; inflationary pressure and the availability of credit. Forward-looking statements involve risks, uncertainties and assumptions that are beyond our ability to control or predict, including those risks, uncertainties and assumptions discussed in Part I, Item 1A, of this Annual Report on Form 10-K. These statements are based on information available to us as of the date of this Annual Report and, while we believe such information provides a reasonable basis for these statements, the information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. Given these risks, uncertainties and other important factors, you should not place undue reliance on these forward-looking statements. Also, forward-looking statements represent our estimates and assumptions only as of the date of this Annual Report. Except as required by law, we assume no obligation to update any forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in any forward-looking statements, whether as a result of new information, future developments, changes in assumptions or otherwise. We caution investors that our business and financial performance are subject to substantial risks and uncertainties. “Protagonist,” the Protagonist logo and other trademarks, service marks and trade names of Protagonist are registered and unregistered marks of Protagonist Therapeutics, Inc. in the United States and other jurisdictions.
Summary of Risk Factors
Below is a summary of the principal factors that make an investment in our common stock speculative or risky. This summary does not address all of the risks and uncertainties that we face. Additional discussion of the risks and uncertainties summarized in this risk factor summary, and other risks and uncertainties that we face, can be found below under the heading Item 1A,“Risk Factors” and should be carefully considered, together with other information in this Annual Report on Form10-K and our other filings with the SEC, before making an investment decision regarding our common stock.
| ● | We have no approved products and no historical commercial revenue, which makes it difficult to assess our future prospects and financial results. |
| ● | We are heavily dependent on the success of our product candidates in clinical development. |
| ● | Clinical development is a lengthy and expensive process with an uncertain outcome, and failure can occur at any stage of clinical development. |
| ● | Our product candidates may cause undesirable side effects or have other properties adversely impacting safety that delay or prevent their regulatory approval, restrict their approved labeling, or otherwise limit their commercial opportunity, including being required by an independent data monitoring committee or regulatory authorities to delay or halt or clinical trials, or if such side effects or adverse events are sufficiently severe or prevalent, to suspend or cease altogether further development of our product candidates. |
| ● | We have incurred a cumulative net loss since our inception and anticipate that we may incur significant losses in the future. |
| ● | We have never generated any revenue from product sales and may never be profitable. |
| ● | Unstable market and macroeconomic conditions including elevated and sustained inflation and changes in trade policies, including tariffs or other trade restrictions or the threat of such actions, may have serious adverse consequences on our business, financial condition and stock price. |
| ● | We may require additional funding. |
| ● | Raising additional capital may cause dilution to our existing stockholders. |
| ● | We rely on J&J Innovative Medicines (“JNJ”) to continue the development of product candidates subject to our license and collaboration with JNJ, and to successfully commercialize any resulting products, and we rely on Takeda Pharmaceuticals USA, Inc. (“Takeda”) to successfully commercialize any products resulting from our collaboration agreement with Takeda. |
| ● | Our existing or future collaborations with third parties may not be successful. |
| ● | We rely on third parties to conduct our pre-clinical studies and clinical trials and are subject to risks associated with their businesses and performance of their obligations to us. |
| ● | We rely on third-party contract manufacturers to manufacture our drug substance and clinical drug product. |
| ● | If we are ultimately unable to obtain regulatory approval for our product candidates in the United States or other jurisdictions, our business will be substantially harmed. |
| ● | If our partners do not satisfy their obligations under our agreements with them, or if they terminate our partnerships with them, we may not be able to develop or successfully commercialize our partnered product candidates successfully. |
| ● | We face significant competition from other biotechnology and pharmaceutical companies. |
| ● | We may face risks to our business arising from outbreaks of disease, epidemics and pandemics, including risks to our ongoing and planned clinical trials and pre-clinical and discovery research. |
| ● | Unstable market and economic conditions, including elevated and sustained inflation, may have serious adverse consequences on our business, financial condition and stock price. |
| ● | Our success depends on our ability to attract, retain and motivate qualified executives and other personnel. |
| ● | We may experience difficulties in managing the growth of our organization. |
| ● | We are subject to risks associated with information technology systems or breaches of data security. |
| ● | Any misconduct by our employees, independent contractors, principal investigators, consultants and vendors could have a material adverse effect on our business. |
| ● | Our headquarters is located near known earthquake fault zones. |
| ● | If we are unable to obtain or protect intellectual property rights related to our product candidates and technologies, we may not be able to compete effectively in our markets. |
| ● | We may be involved in lawsuits to protect or enforce our intellectual property, which could be expensive, time consuming and ultimately unsuccessful. |
| ● | Patents covering our product candidates could be found invalid or unenforceable. |
| ● | Third-party claims of intellectual property infringement may prevent or delay our drug discovery and development efforts. |
| ● | Our stock price has been and will likely continue to be volatile and may decline, regardless of our operating performance. |