Protagonist Therapeutics, Inc 10-Q

ITEM 1A. RISK FACTORS Our business, results of operations and financial condition are subject to various risks. These risks are described elsewhere in this Quarterly Report on Form 10-Q and in our other filings with the SEC, including our Annual Report on Form 10-K for the year ended December 31, 2025. Except as disclosed below, there have been no material changes from the risk factors identified in the Company’s Annual Report on Form 10-K for the year ended December 31, 2025. We are dependent on Takeda for the commercialization of rusfertide. Failure by Takeda to commercialize rusfertide could result in a material adverse effect on our business and operating results. Pursuant to the terms of the Takeda Collaboration Agreement, following our exercise of our right to opt out of the U.S. profit and loss sharing arrangement in April 2026, Takeda has an exclusive worldwide license to develop and commercialize rusfertide, and we are eligible to receive tiered royalties ranging from 14% to 29% on annual worldwide 31 Table of Contents net sales, with an approximate weighted-average royalty rate of 21% at $1.5 billion in annual net sales and a rate of 29% for incremental annual net sales over $1.5 billion. In addition, under the agreement, we are eligible to receive up to $775.0 million in sales milestone payments. A substantial portion of our total revenue may be based on royalties and milestones received from Takeda. The commercial success of rusfertide, if approved, including our potential royalties, depends on, among other things, the efforts and allocation of resources of Takeda, which we do not control. Our partnership with Takeda may not be successful, and we may not realize the expected benefits from such partnership, due to a number of important factors, including but not limited to the following: • Takeda may change the focus of its commercialization efforts or pursue higher priority programs; • Takeda may fail to manufacture or supply sufficient drug product of rusfertide in compliance with applicable laws and regulations, which could result in program delays or lost revenue; and • We may disagree with Takeda regarding the development or commercialization of rusfertide, or other matters under the Takeda Collaboration Agreement, or Takeda could breach or terminate the Takeda Collaboration Agreement. Unstable market and macroeconomic conditions, including geopolitical instability and tariffs or trade policy, may have serious adverse consequences on our business, financial condition and stock price. As has been widely reported, we are currently operating in a period of macroeconomic uncertainty and capital markets disruption, which has been significantly impacted by domestic and global monetary and fiscal policy, trade regulations, including changes in trade policies, tariffs or other trade restrictions or the threat of such actions, geopolitical instability, including ongoing military conflicts in the Middle East and between Russia and Ukraine, rising tensions between China and Taiwan, and high interest rates. In particular, the conflicts in the Middle East and Ukraine have exacerbated market disruptions, including significant volatility in commodity prices, as well as supply chain interruptions, and have contributed to inflation globally. The U.S. Federal Reserve and other central banks may be unable to contain inflation through more restrictive monetary policy and inflation may increase or continue for a prolonged period of time. Inflationary factors, such as increases in the cost of clinical supplies, interest rates, overhead costs and transportation costs may adversely affect our operating results. In addition, in September 2025, the United States announced the imposition of up to 100% tariffs on imported branded or patented pharmaceuticals, subject to certain exceptions. In early April 2026, the current administration issued a proclamation under Section 232 of the Trade Expansion Act of 1962 determining that imports of certain pharmaceutical products, including patented pharmaceuticals, associated active pharmaceutical ingredients and related materials could threaten U.S. national security and authorized the imposition of tariffs of up to 100% on covered imports, effective July 31, 2026. Imports of certain listed products from specific partner countries, including South Korea and the European Union, may be subject to reduced tariff rates. Certain tariff exemptions or zero-rate treatment may be available for products where all approved indications are designated as orphan, subject to applicable determinations, conditions and implementation guidance. There remains substantial uncertainty as to whether such tariffs would apply to the importation of active pharmaceutical ingredients or bulk drug products that are intended for use in clinical trials and, more generally, about the duration of existing tariffs, tariff levels, implementation of announced tariffs, litigation challenging tariffs and whether additional tariffs or retaliatory actions may be imposed, modified or suspended. Although we do not believe that the macroeconomic factors discussed above have had a material impact on our financial position or results of operations to date, our financial position or results of operations may be adversely affected in the future due to these factors, and such factors may lead to increases in the cost of manufacturing our product candidates and delays in initiating trials. In addition, global credit and financial markets have experienced extreme volatility and disruption in the past several years and the foregoing factors have led to and may continue to cause diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, uncertainty about economic stability and continued inflation. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. A future recession or market correction or other significant geopolitical events could materially affect our business and the value of our common stock. Our general business strategy may be adversely 32 Table of Contents affected by any such economic downturn, volatile business environment or continued unpredictable and unstable market conditions. If the current equity and credit markets deteriorate, or do not improve, it may make any necessary debt or equity financing more difficult, more costly, and more dilutive. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our growth strategy, financial performance and stock price and could require us to delay or abandon clinical development plans. In addition, there is a risk that one or more of our current service providers, manufacturers and other partners may not survive these difficult economic times, which could directly affect our ability to attain our operating goals. ITEM 2. UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS Recent Sales of Unregistered Securities None. Repurchases of Shares or of Company Equity Securities None. ITEM 3. DEFAULTS UPON SENIOR SECURITIES None. ITEM 4. MINE SAFETY DISCLOSURES Not applicable.