What changed in this filing

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Item 1A. Risk Factors

2025-05-08 compared with 2024-11-07 · 624 added, 526 removed, 1288 unchanged (47% of the section changed)

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Risks Related to our Financial Position, Need for Additional Capital and Growth Strategy

We have incurred significant losses since our inception, and anticipate that we will continue to incur losses and cannot guarantee when, if ever, we will become profitable or attain positive cash flows.

We have incurred significant losses since our inception, and anticipate that we will continue to incur losses and cannot guarantee when, if ever, we will become and remain profitable.

Investment in pharmaceutical product development and commercialization is highly speculative because it requires upfront capital expenditures and significant research and development, or R&D , expenses.

Despite the investment in assets and R&D, there is significant risk that a product candidate will fail to gain marketing approval or that an approved product will not be commercially viable.

Since our inception, we have devoted most of our resources to R&D, including our preclinical and clinical development activities, commercializing Auryxia and providing general and administrative support for these operations.

Since our inception, we have devoted most of our resources to R&D, including our preclinical and clinical development activities, commercializing Auryxia and Vafseo and providing general and administrative support for these operations.

We have funded our operations principally through product sales, payments received from our collaboration and licensing partners, borrowings under term loans, sales of our common stock, including through our employee stock purchase plan, a working capital payment from Vifor (International) Ltd.

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Prior to our 2018 merger, or the Merger , with Keryx Biopharmaceuticals, Inc., or Keryx , whereby Keryx became our wholly owned subsidiary, we had no products approved for commercial sale and had not generated any revenue from the sale of products.

We are not currently profitable, and we have incurred net losses each year since our inception, including a net loss of $20.0 million for the three months ended September 30, 2024.

As of September 30, 2024, we had an accumulated deficit of $1.7 billion.

We cannot guarantee when, if ever, we will become profitable.

We currently have two commercial products and believe that our existing cash resources and the cash we expect to generate from product, royalty, supply and license revenues are sufficient to fund our current operating plan for the foreseeable future, including to commercialize Vafseo and Auryxia, pursue label expansion for Vafseo, and advance our other existing programs.

However, we have incurred net losses each year since our inception, and although we generated net income of $6.1 million for the three months ended March 31, 2025, we cannot guarantee when, if ever, we will become and remain profitable.

As of March 31, 2025, we had an accumulated deficit of $1.7 billion.

In March 2022, we received a complete response letter, or CRL , from the United States, or U.S.

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On March 27, 2024, the FDA approved our NDA for vadadustat under the trade name Vafseo for the treatment of anemia due to CKD in adults who have been receiving dialysis for at least three months.

However, we expended significant additional resources to obtain the approval of Vafseo and the commercialization of Vafseo was delayed, which had and could continue to have an adverse effect on our business.

Our ability to generate product revenue and achieve profitability depends on our ability to manage expenses and the overall success of Auryxia, Vafseo and any current or future product candidates, including those that may be in-licensed or acquired, which depends on several factors, including:

• obtaining adequate or favorable pricing and reimbursement from private and governmental payors for Auryxia, Vafseo and any other product or product candidate, including those that may be in-licensed or acquired;

However, we expended significant additional resources to obtain the approval of Vafseo, the commercialization of Vafseo was delayed and Vafseo was approved for a narrower indication than we initially pursued, which had and could continue to have an adverse effect on our business.

Our ability to generate product revenue and achieve and maintain profitability depends on our ability to manage expenses and the overall success of Auryxia, Vafseo and any current or future product candidates, including those that may be in-licensed or acquired, which depends on several factors, including:

• obtaining and maintaining adequate or favorable pricing and reimbursement from private and governmental payors for Auryxia, Vafseo and any other product or product candidate, including those that may be in-licensed or acquired;

• obtaining and maintaining market acceptance of Auryxia, Vafseo and any other product candidate, including those that may be in-licensed or acquired;

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• the size of any market in which Auryxia, Vafseo and any other product or product candidate, including those that may be in-licensed or acquired, receives approval and obtaining adequate market share in those markets;

• the timing and scope of marketing approvals for Vafseo and any other product candidate, if approved, including those that may be in-licensed or acquired;

• maintaining marketing approvals for Auryxia, Vafseo and any other product, including those that may be in-licensed or acquired;

• our ability to successfully contract with dialysis organizations for the sale of Auryxia and Vafseo in the U.S.;

• obtaining regulatory approval for any label expansion for Vafseo, including the timing and scope thereof;

• our ability to maintain contracts with dialysis organizations for the sale of Auryxia and Vafseo in the U.S.;

• actual or perceived advantages or disadvantages of our products or product candidates as compared to alternative treatments, including their respective safety, tolerability and efficacy profiles, the potential convenience and ease of administration and cost;

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• the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies, based, in part, on their perception of our clinical trial data and/or the actual or perceived safety, tolerability and efficacy profile;

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• the timing and scope of marketing approvals for any product candidate, if approved, including those that may be in-licensed or acquired;

• establishing and maintaining supply and manufacturing relationships with third parties that can provide adequate supplies of products that are compliant with good manufacturing practices, or GMPs , to support the clinical development and the market demand for Auryxia, Vafseo and any other product and product candidate, including those that may be in-licensed or acquired;

• the potential impact of geopolitical pressures or the BIOSECURE Act on our ability to conduct our business as currently conducted;

• the potential impact of geopolitical pressures, including tariffs and global trade policies, or the BIOSECURE Act on our ability to conduct our business as currently conducted;

• current and future restrictions or limitations on our approved or future indications and patient populations or other adverse regulatory actions or in the event that the FDA requires Risk Evaluation and Mitigation Strategies, or REMS , or risk management plans that use restrictive risk minimization strategies;

• the effectiveness of our collaborators' and our sales, marketing, manufacturing and distribution strategies and operations;

• competing effectively with any products for the same or similar indications as our products;

• competing effectively with any products for the same or similar indications as our products (including generics);

• maintaining, protecting and expanding our portfolio of intellectual property rights, including patents and trade secrets;

• the adverse impact of the recent COVID-19 pandemic on CKD patients and the phosphate binder market in which we compete.

• the adverse impact of the COVID-19 pandemic on CKD patients and the phosphate binder market in which we compete.

Our collaboration, license and other revenue also depends on our partners’ ability to successfully market and sell Vafseo and Auryxia in the territories in which they have licensed our products.

For example, in May 2023, we entered into a license agreement with MEDICE Arzneimittel Pütter GmbH & Co.

KG, or Medice , pursuant to which we granted Medice an exclusive license to market and sell Vafseo for the treatment of anemia in patients with CKD in the European Economic Area, or the EEA , the United Kingdom, or UK , Switzerland and Australia, or Medice Territor y.

KG, or Medice , pursuant to which we granted Medice an exclusive license to develop and commercialize Vafseo for the treatment of anemia in patients with CKD in the European Economic Area, or the EEA , the United Kingdom, or UK , Switzerland and Australia, or collectively, the Medice Territory .

Vafseo is currently marketed and sold by Medice in certain countries in the Medice Territory.

If Medice’s launch of Vafseo in the Medice Territory is delayed or their sales are lower than anticipated, we may not receive the revenue that we expect from Medice on the timing anticipated, or at all.

If Medice’s launch of Vafseo in certain countries in the Medice Territory is delayed or their sales are lower than anticipated, we may not receive the revenue that we expect from Medice on the timing anticipated, or at all.

In July 2024, we entered into a Termination and Settlement Agreement with CSL Vifor, or the Vifor Termination Agreement .

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As a result, we have regained our rights to sell Vafseo to Fresenius Kidney Care North America and its affiliates and certain other third-party dialysis organizations in the U.S.

If we are not successful in contracting with dialysis organizations and commercializing Vafseo in a timely manner, or at all, our expected revenue related to Vafseo would be adversely impacted.

Pursuant to the Vifor License Agreement, CSL Vifor contributed $40.0 million to a working capital facility, or Working Capital Fund , established to partially fund our costs of purchasing Vafseo from our contract manufacturers.

Pursuant to the terms of the Vifor Termination Agreement, we have agreed to repay the Working Capital Fund to CSL Vifor through quarterly tiered royalty payments ranging from 8% to 14% of our net sales of Vafseo in the U.S., or the WCF Royalty Payments .

Pursuant to the terms of

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the Vifor Termination Agreement, we have agreed to repay the Working Capital Fund to CSL Vifor through quarterly tiered royalty payments ranging from 8% to 14% of our net sales of Vafseo in the U.S., or the WCF Royalty Payments .

The WCF Royalty Payments will commence on July 1, 2025, and will continue until the earlier of (i) the cumulative total of the WCF Royalty Payments equals $40.0 million, or (ii) May 31, 2028.

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If the cumulative total of the WCF Royalty Payments paid to CSL Vifor on any given WCF Royalty True-Up Date is less than the respective WCF Royalty True-Up Payment, we will pay CSL Vifor a one-time payment equal to the difference between the WCF Royalty True-Up Payment and the cumulative total of the WCF Royalty Payments paid by us through such WCF Royalty True-Up Date.

If we are not successful in contracting with dialysis organizations and commercializing Vafseo in a timely manner, we may be unable to repay all or part of the WCF Royalty Payments, which could have a material adverse impact on our consolidated financial statements.

Our ability to achieve profitability also depends on our ability to manage our expenses.

If we are not successful in commercializing Vafseo, including maintaining contracts with dialysis organizations on favorable terms, or at all, our expected revenue related to Vafseo would be adversely impacted and we may be unable to repay all or part of the WCF Royalty Payments, which could have a material adverse impact on our consolidated financial statements and our ability to achieve and maintain profitability.

Our ability to achieve and maintain profitability also depends on our ability to manage our expenses.

We expect to continue to incur substantial additional operating expenses, including additional R&D expenses related to our pipeline, additional R&D and selling, general and administrative expenses for ongoing development and commercialization of Auryxia and Vafseo, which could lead to operating losses for the foreseeable future.

We will continue to incur substantial expenditures relating to continued commercialization and post-marketing requirements for Auryxia, Vafseo and any other products, including those that may be in-licensed or acquired, as well as costs relating to the R&D of Vafseo and any other product candidate, including those that may be in-licensed or acquired.

Our prior losses have had, and expected future losses will continue to have, an adverse effect on our stockholders’ deficit and working capital.

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In addition to any further costs not currently contemplated in our operating plan, our ability to achieve profitability and our financial position will depend, in part, on the rate of our future expenditures, the timing of our product, collaboration, license and other revenue, the timing and amount of any repayment of the WCF Royalty Payments, our continued compliance with the terms of the Agreement for the Provision of a Loan Facility, as amended, or the BlackRock Credit Agreement , with Kreos Capital VII (UK) Limited , which are funds and accounts managed by BlackRock Inc., collectively, BlackRock , and our ability to obtain additional funding, should it be needed.

Our prior losses have had, and expected future losses will continue to have, an adverse effect on our stockholders’ (deficit) equity and working capital.

In addition to any further costs not currently contemplated in our operating plan, our ability to achieve and maintain profitability and our financial position will depend, in part, on the rate of our future expenditures, the timing of our product, collaboration, license and other revenue, the timing and amount of any repayment of the WCF Royalty Payments, our continued compliance with the terms of the Agreement for the Provision of a Loan Facility, as amended, or the BlackRock Credit Agreement , with Kreos Capital VII (UK) Limited , which are funds and accounts managed by BlackRock Inc., collectively, BlackRock , and our ability to obtain additional funding, should it be needed.

In addition, we expect to continue to incur significant expenses if and as we:

• continue our commercialization activities for Auryxia, Vafseo and any other product or product candidate for which we obtain approval, including those that may be in-licensed or acquired;

• seek regulatory approval for any label expansion for Vafseo;

• conduct and enroll patients in any clinical trials, including post-marketing studies or any other clinical trials for Auryxia, Vafseo or any other product or product candidate, including those that may be in-licensed or acquired;

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• engage in transactions, including strategic, merger, collaboration, acquisition and licensing transactions, pursuant to which we would market and develop commercial products, or develop and commercialize other product candidates and technologies;

• repay, and pay any associated pre-payment penalties, if applicable, the term loans in an aggregate principal amount of up to $55.0 million, or the Term Loans , that were made available to us pursuant to the BlackRock Credit Agreement ;

• repay, and pay any associated pre-payment penalties, if applicable, the term loans in an aggregate principal amount of $55.0 million, or the Term Loans , that were made available to us pursuant to the BlackRock Credit Agreement ;

• make royalty, milestone or other payments under our current and any future in-licensing agreements;

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• experience any additional delays or encounter issues with any of the above.

We have expended and may in the future expend significant resources on our legal proceedings, including any legal proceedings that may be brought by or against us in the future.

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We have expended and may in the future expend significant resources on our legal proceedings, as described above under Part II, Item 1.

Legal Proceedings, including any legal proceedings that may be brought by or against us in the future.

Our expenses could increase beyond expectations if we are required by the FDA, the European Medicines Agency, or the EMA , or other regulatory authorities, or if we otherwise believe it is necessary, to change our manufacturing processes or assays, to amend or replace our study protocols, to perform studies different from or larger than those currently planned, to conduct any additional clinical trials, whether in order to obtain approval or as a post-approval study, including the post-approval studies required for Vafseo and any other additional clinical trial that we decide to conduct for Vafseo, or if there are any delays in completing any of these activities.

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In addition, our ability to generate revenue would be negatively affected if dialysis organizations are un willing to include Auryxia or Vafseo in their formulary or the size of our addressable patient population is not as significant as we estimate, the indication approved by regulatory authorities is narrower than we sought or the patient population for treatment is narrowed by competition, physician choice, coverage or reimbursement, or payor or treatment guidelines.

Even though we generate product revenue from Auryxia and royalties from Riona and Vafseo in Japan, may generate royalties from Vafseo in Europe and other territories where it is approved, may generate product and collaboration revenue from Vafseo in the U.S., and may generate revenue and royalties from the sale of any products that may be approved in the future, including those that may be

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in-licensed or acquired, we may never generate revenue and royalties that are significant enough for us to become and remain profitable, and we may need to obtain additional financing to continue to fund our operating plan.

Even though we generate product revenue from Auryxia and royalties from Riona (ferric citrate hydrate) and Vafseo in Japan, generate product revenue from Vafseo in the U.S., generate royalties from Vafseo in Europe and other territories where it is approved, and may generate revenue and royalties from the sale of any products that may be approved in the future, including those that may be in-licensed or acquired, we may never generate revenue and royalties that are significant enough for us to become and remain profitable, and we may need to obtain additional financing to continue to fund our operating plan.

We may require substantial additional financing to fund our business.

A failure to obtain this necessary capital when needed, or on acceptable terms, could force us to delay, limit, reduce or terminate our product development or commercialization efforts.

As of September 30, 2024, our cash and cash equivalents were $34.0 million.

We expect to continue to expend substantial amounts of cash for the foreseeable future as we continue to commercialize Auryxia;

As of March 31, 2025, our cash and cash equivalents were $113.4 million.

We expect to continue to expend substantial amounts of cash for the foreseeable future as we continue to commercialize Auryxia in the U.S.;

develop and commercialize Vafseo in the U.S.;

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• the outcome of our efforts to obtain marketing approval for any product candidates, including those that may be in-licensed or acquired, including any additional clinical trials or post-approval commitments imposed by regulatory authorities;

• the timing of, and the costs involved in obtaining, marketing approvals for any product candidate, including those that may be in-licensed or acquired, including to fund the preparation, filing and prosecution of regulatory submissions;

• the timing of, and the costs involved in obtaining, label expansion for Vafseo or marketing approvals for any product candidate, including those that may be in-licensed or acquired, including to fund the preparation, filing and prosecution of regulatory submissions;

• the costs of maintaining marketing approvals for Auryxia, Vafseo or any other product, including those that may be in-licensed or acquired;

• the number of generic versions of Auryxia that enter the market following loss of exclusivity, or LoE , for Auryxia in March 2025, and the timing of, and the magnitude of, the impact on the product revenue from Auryxia, including the impact on the price of Auryxia;

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• the timing and number of additional generic versions of Auryxia that enter the market following loss of exclusivity, or LoE , for Auryxia in March 2025, the pricing of generic versions of Auryxia and the timing of, and the magnitude of, the impact on the product revenue from Auryxia, including the impact on the price of Auryxia;

• the cost of securing and validating commercial manufacturing for any of our product candidates, including those that may be in-licensed or acquired, and maintaining our manufacturing arrangements for Auryxia and Vafseo or any other product, including those that may be in-licensed or acquired, or securing and validating additional arrangements;

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• the extent to which we engage in transactions, including strategic, merger, collaboration, acquisition and licensing transactions, pursuant to which we could develop and market commercial products, or develop other product candidates and technologies.

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We may need to obtain substantial additional financing to fund our business.

If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our R&D programs or any future commercialization efforts.

However, if our operating performance deteriorates significantly from the levels expected in our operating plan, it would have an adverse effect on our liquidity and capital resources and could affect our ability to continue as a going concern in the future.

We believe our existing cash resources and the cash we expect to generate from product, royalty, supply and license revenues are sufficient to fund our current operating plan for the foreseeable future, including to commercialize Vafseo and Auryxia, pursue label expansion for Vafseo and advance our other existing programs.

However, if our operating performance deteriorates significantly from the levels expected in our long-term operating plan, it would have an adverse effect on our liquidity and capital resources and could affect our ability to achieve or maintain profitability or continue as a going concern in the future.

Our forecast of the period of time through which our financial resources will be adequate to support our operations is a forward-looking statement and involves numerous risks and uncertainties, and actual results could vary as a result of a number of factors, many of which are outside our control.

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In addition, raising funds in the current economic environment may present additional challenges.

For example, any sustained disruption in the capital markets from adverse macroeconomic conditions and an uncertain geopolitical environment, such as rising inflation, increasing interest rates, slower economic growth or recession, global supply chain disruptions, the Russia-Ukraine war, Israel-Hamas war and the war in the Middle East and tensions between China and Taiwan, could negatively impact our ability to raise capital, and we cannot predict the extent or duration of such macroeconomic disruptions.

For example, any sustained disruption in the capital markets from adverse macroeconomic conditions and an uncertain geopolitical environment, such as tariffs, rising inflation, increasing interest rates, slower economic growth or recession, global trade policies, global supply chain disruptions, the Russia-Ukraine war, the Israel-Hamas war and the war in the Middle East and tensions between China and Taiwan, could negatively impact our ability to raise capital, and we cannot predict the extent or duration of such macroeconomic disruptions.

If we are unable to raise additional capital in sufficient amounts when needed or on terms acceptable to us, we may have to significantly delay, scale back or discontinue the development and/or commercialization of Auryxia, Vafseo and any other products or product candidates, including those that may be in-licensed or acquired.

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We expect to finance future cash needs through product revenue and royalty and license revenue, and we may seek to sell public or private equity, enter into new debt transactions, explore potential strategic transactions or a combination of these approaches or other strategic alternatives.

To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interests of our common stockholders will be diluted, our fixed payment obligations may increase, any such securities may have rights senior to those of our common stock, and the terms may include liquidation or other preferences and anti-dilution protections that adversely affect the rights of our common stockholders.

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include liquidation or other preferences and anti-dilution protections that adversely affect the rights of our common stockholders.

For example, since September 12, 2024 (the date our shelf registration statement on Form S-3 went effective) through December 31, 2024, we sold 14,271,631 shares of our common stock in an at-the-market offering with gross proceeds of $24.3 million, and during the three months ended March 31, 2025, we sold 9,437,364 shares of our common stock under this program with gross proceeds of $18.7 million.

In addition, on March 21, 2025, we sold 25,000,000 shares of our common stock in an underwritten public offering with net proceeds of $46.5 million, and on April 22, 2025, we sold an additional 850,000 shares of our common stock in connection with the partial exercise of the underwriters' 30-day option to purchase additional shares in such underwritten public offering with net proceeds of $1.6 million.

Additional debt financing, if available, may involve agreements that would restrict our operations and potentially impair our competitiveness, such as limitations on our ability to incur additional debt, make capital expenditures, declare dividends, acquire, sell or license intellectual property rights, and other operating restrictions that could adversely impact our ability to conduct our business.

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If we are unable to raise additional funds when needed, we may not be able to pursue planned development and commercialization activities and we may need to grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

If we fail to comply with the continued listing requirements of Nasdaq, our common stock may be delisted and the price of our common stock and our ability to access the capital markets could be negatively impacted.

We must satisfy Nasdaq’s continued listing requirements, including, among other things, a minimum closing bid price of $1.00 per share and timely filing of all periodic financial reports, or risk delisting, which would have a material adverse effect on our business.

If we fail to maintain compliance with Nasdaq’s continued listing requirements, it could affect our ability to raise capital on acceptable terms, or at all.

In the event we are delisted from Nasdaq, the only established trading market for our common stock would be eliminated, and we would be forced to list our shares on the OTC Markets or another quotation medium, depending on our ability to meet the specific listing requirements of those quotation systems.

As a result, an investor would likely find it more difficult to trade or obtain accurate price quotations for our shares.

Delisting would likely

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also reduce the visibility, liquidity, and value of our common stock, reduce institutional investor interest in our Company, and may increase the volatility of our common stock.

Delisting could also cause a loss of confidence of potential industry partners, lenders, and employees, which could further harm our business and our future prospects.

On May 9, 2023, we received a letter from Nasdaq stating that we had not regained compliance with the minimum bid price rule during the compliance period and were subject to delisting.

On May 22, 2023, we received a letter from the Office of General Counsel of Nasdaq informing us that Nasdaq confirmed that we had regained compliance with the $1.00 per share minimum bid price requirement.

On August 11, 2023, we received a notification letter from Nasdaq informing us that since we had not yet filed our Quarterly Report on Form 10-Q for the three months ended June 30, 2023, we were not in compliance with Nasdaq’s listing rule requiring timely filing of all required periodic financial reports with the U.S.

Securities and Exchange Commission, or the SEC .

On August 30, 2023, we received a letter from the Office of General Counsel of Nasdaq informing us that Nasdaq confirmed that we had regained compliance with Nasdaq’s listing rule requiring timely filing of all required periodic financial reports with the SEC.

Although the minimum bid price deficiency and Nasdaq periodic reporting requirement matters are now closed, there can be no assurance that we will be able to continue to comply with the Nasdaq continued listing requirements.

We may not be successful in our efforts to identify, acquire, in-license, discover, develop and commercialize additional products or product candidates or our decisions to prioritize the development of certain product candidates over others may not be successful, which could impair our ability to grow.

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Our spending on current and future R&D programs and product candidates for specific indications may not yield any commercially viable products.

Because our internal research capabilities are limited, we may be dependent upon other pharmaceutical and biotechnology companies, academic scientists and institutions, and other researchers to sell or license product candidates, products or technology to us.

As a result, our rights to these product candidates may be limited or we may be required to make future

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payments to such third parties if we are successful in developing such product candidates.

As a result, our rights to these product candidates may be limited or we may be required to make future payments to such third parties if we are successful in developing such product candidates.

The success of this strategy depends partly upon our ability to identify, select, and acquire promising product candidates and products.

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Any of the foregoing could have a detrimental effect on our business, results of operations and financial condition.

For example, on June 4, 2021, we entered into a license agreement, the Cyclerion Agreement , with Cyclerion Therapeutics Inc., or Cyclerion , pursuant to which Cyclerion granted us an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an investigational oral soluble guanylate cyclase stimulator.

Although we have progressed preclinical studies for praliciguat, we need to do additional work to manufacture product for clinical trials than originally anticipated before we can initiate the trials, and when the clinical trials are started, we may be unsuccessful in developing praliciguat.

For example, on June 4, 2021, we entered into a license agreement, or the Cyclerion Agreement , with Cyclerion Therapeutics Inc., or Cyclerion , pursuant to which Cyclerion granted us an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an investigational oral soluble guanylate cyclase stimulator.

In December 2024, we entered into an amendment to the Cyclerion Agreement, pursuant to which we amended the terms of the Cyclerion Agreement, and we now control all clinical and commercial manufacturing of praliciguat, which will be conducted by a third-party manufacturer.

Although we have progressed preclinical studies for praliciguat, we needed to do additional work to manufacture product for clinical trials than originally anticipated before we could initiate the trials, and when the clinical trials are started, we may be unsuccessful in developing praliciguat.

If any of the assumptions that we made in valuing the transaction, including the costs or timing of development of praliciguat as a result of the additional manufacturing work or otherwise, or the potential benefits of praliciguat, were incorrect, we may not recognize the anticipated benefits of the transaction and our business could be harmed.

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• higher than expected acquisition and integration costs;

• difficulty in integrating operations, processes, systems and personnel of any acquired business;

• increased amortization expenses or, in the case of a write-down of the value of acquired assets, impairment losses, such as the Auryxia intangible asset impairment in the second quarter of 2020 and corresponding adjustments to the estimated useful life of the developed product rights for Auryxia;

• impairment of relationships with key suppliers or customers of any acquired business due to changes in management and ownership;

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• difficulty in integrating operations, processes, systems and personnel of any acquired business;

• increased amortization expenses or, in the case of a write-down of the value of acquired assets, impairment losses, and corresponding adjustments to the estimated useful life of the developed product rights for Auryxia;

• impairment of relationships with key suppliers or customers of any acquired business due to changes in management and ownership;

• inability to retain personnel, customers, distributors, vendors and other business partners integral to an in-licensed or acquired product, product candidate or technology;

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Our obligations in connection with the BlackRock Credit Agreement and requirements and restrictions in the BlackRock Credit Agreement could adversely affect our financial condition and restrict our operations.

We entered into the BlackRock Credit Agreemen t , which provides for a senior secured term loan facility, in the aggregate principal amount of up to $55.0 million, or the Term Loan Facility .

The initial tranche of $37.0 million, or the Tranche A Loan , closed on January 29, 2024, or the Closing Date, and an additional amount of $8.0 million, or the Tranche B Loan , was drawn on April 19, 2024.

An additional $10.0 million is available under the Term Loan Facility in a single draw through December 31, 2024, or the Tranche C Loan and, together with the Tranche A Loan and the Tranche B Loan, the Term Loans .

We entered into the BlackRock Credit Agreemen t , which provides for a senior secured term loan facility, in the aggregate principal amount of $55.0 million, or the Term Loan Facility .

The initial tranche of $37.0 million, or the Tranche A Loan , closed on January 29, 2024, or the Closing Date, an additional amount of $8.0 million, or the Tranche B Loan , was drawn on April 19, 2024, and an additional $10.0 million was drawn on February 3, 2025, or the Tranche C Loan and, together with the Tranche A Loan and the Tranche B Loan, the Term Loans .

See Note 7, Indebtedness , to our unaudited condensed consolidated financial statements in Part I, Item 1.

Financial Statements of this Form 10-Q for additional information regarding our obligations under the BlackRock Credit Agreement.

The Tranche C Loan is subject to various conditions precedent, including (x) the absence of any defaults or events of default and our continued compliance with the terms and provisions of the BlackRock Credit Agreement and (y) receipt of a certain amount of cumulative gross cash proceeds after the Closing Date in the form of equity or equity linked securities in one or more series of transactions.

The Term Loan Facility had an initial maturity date of March 31, 2025, which was automatically extended to January 29, 2028, or the Maturity Date , since we received FDA approval for Vafseo prior to June 30, 2024.

The Term Loan Facility had an initial maturity date of March 31, 2025, which was automatically extended to January 29, 2028, or the Maturity Date , because we received FDA approval for Vafseo prior to June 30, 2024.

The BlackRock Credit Agreement contains certain representations and warranties, affirmative covenants, negative covenants, financial covenants, events of default and other provisions and conditions that are customarily required for similar financings.

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During the continuance of any payment event of default under the BlackRock Credit Agreement, the interest rate on such overdue sum will automatically increase by an additional 3.0% per annum, and may be subject to an additional late fee of 2.0% of such overdue sum.

The Term Loan Facility does not amortize during the period commencing on the Closing Date and ending on December 31, 2025 (which was extended to December 31, 2026 at our option), or the Interest Only Period .

The Term Loan Facility does not amortize during the period commencing on the Closing Date and ending on December 31, 2026 (as extended at our option), or the Interest Only Period .

We are required to pay interest and, after the Interest Only Period, principal on the first calendar day of each month.

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In addition, our obligations in connection with the BlackRock Credit Agreement could have additional significant adverse consequences, including, among other things:

• restricting our activities, including limitations on transferring certain of our assets, engaging in certain transactions, terminating certain agreements, incurring certain additional indebtedness, creating certain liens, paying cash dividends or making certain other distributions and investments;

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• limiting our flexibility in planning for, or reacting to, changes in our business and our industry;

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Our business is substantially dependent on the commercial success of Auryxia and Vafseo.

If we are unable to continue to successfully commercialize Auryxia and commercially launch Vafseo, our results of operations and financial condition will be materially harmed.

If we are unable to continue to successfully commercialize Auryxia and Vafseo, our results of operations and financial condition will be materially harmed.

Our business and our ability to generate product revenue largely depend on our, and our collaborators’, ability to successfully commercialize Auryxia and Vafseo.

Our ability to generate revenue depends on our ability to execute on our commercialization plans, and the size of the market for, and the level of market acceptance of, Auryxia, Vafseo and any other product or product candidate, including those that may be in-licensed or acquired.

If we are not able to execute and/or maintain contracts with dialysis organizations and other customers for the sale of Auryxia and Vafseo on favorable terms, in a timely manner, or at all, our revenue and results of operations will be adversely affected.

If we are not able to maintain contracts with dialysis organizations and other customers for the sale of Auryxia and Vafseo on favorable terms, or at all, our revenue and results of operations will be adversely affected.

If the size of any market for which a product or product candidate is approved decreases or is smaller than we anticipate, our revenue and results of operations could be materially adversely affected.

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This limitation could affect the level of market acceptance of Vafseo.

Given the concentration of dialysis clinics in large networks, with DaVita, Inc., or DaVita , and Fresenius Kidney Care Group LLC, accounting for a vast majority of the dialysis population in the U.S., treatment is usually driven by medical protocols that are implemented across the entire network of clinics.

We had exclusive rights under a series of patents and patent applications to commercialize Auryxia in the U.S.

that protected us from generic drug competition until March 20, 2025.

Following LoE, the number of generic versions of Auryxia that enter the market, and the timing thereof, will adversely affect our revenue from Auryxia.

The impact of LoE on future Auryxia revenues will depend on many factors, including our ability to maintain contracts with dialysis organizations, the timing and number of additional generics and the pricing of generics and other products on the market that compete with Auryxia.

In addition, we believe the dynamics of Auryxia reimbursement being included in the ESRD bundle and Auryxia LoE could result in the buying pattern of certain customers in 2025 and future years being different than their historical practices.

If Auryxia sales decline faster than we anticipate following LoE, our results of operations and financial condition will be materially harmed.

Given the concentration of dialysis clinics in large networks, with DaVita, Inc., or DaVita , Fresenius Kidney Care Group LLC, or Fresenius , and U.S.

Renal Care, or USRC , accounting for a vast majority of the dialysis population in the U.S., treatment is usually driven by medical protocols that are implemented across the entire network of clinics.

Dialysis organizations require large data sets to adopt medical protocols.

If dialysis organizations do not add Vafseo to their medical protocols in a timely manner, or at all, our operations could be materially adversely affected.

If oral-only phosphate binders, including Auryxia, are included in the end-stage renal disease, or ESRD , Prospective Payment System, or PPS , bundle payment, beginning in January 2025 as we currently anticipate, it will take time for dialysis organizations to implement internal mechanisms to dispense phosphate binders which could divert their attention from focusing on other therapeutic areas such as anemia management, which in turn could negatively impact the market for phosphate binders, including Auryxia.

In addition, dialysis organizations may choose lower cost binders over Auryxia, or binders that may have features or benefits more aligned with the dialysis organization’s operational activities, which could negatively impact Auryxia revenue.

In addition, we currently have exclusive rights under a series of patents and patent applications to commercialize Auryxia in the U.S.

that protect us from generic drug competition until March 2025.

Following LoE, in March 2025, the number of generic versions of Auryxia that enter the market will affect our revenue from Auryxia.

We believe the Centers for Medicare & Medicaid Services', or CMS, decision to include phosphate binders in the dialysis bundle could potentially lead to higher sales of Auryxia after the LoE date than in other LoE scenarios, and plan to work with dialysis organizations, other customers and providers to seek to continue the use of Auryxia beyond LoE.

However, our ability to continue to generate revenue from sales of Auryxia following LoE will depend on many factors, including our ability to successfully contract with dialysis organizations, the timing and number of generics that enter the market and other products on the market that compete with Auryxia.

If dialysis organizations do not add Vafseo to their medical protocols in a timely manner, or at all, or do not keep Vafseo on their medical protocols, or if the protocols service smaller populations than the current label, our results of operations could be materially adversely affected.

For example, in the quarter ended March 31,

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are unable to maintain sales of Auryxia following LoE, our results of operations and financial condition will be materially harmed.

We believe our revenue growth has been negatively impacted by the recent COVID-19 pandemic since 2021 primarily as the CKD patient populations that we serve experienced both high hospitalization and mortality rates due to COVID-19, and the pandemic had an adverse impact on the phosphate binder market in which Auryxia competes.

2025, most Vafseo revenue was driven by mid-sized dialysis organizations.

If we are unable to increase sales to the large and small dialysis organizations, our results of operations will be negatively impacted.

Oral-only phosphate binders, including Auryxia, are included in the end-stage renal disease, or ESRD, Prospective Payment System, or PPS , bundle payment, as of January 2025, however, it will take time for dialysis organizations to implement internal mechanisms to dispense phosphate binders which could negatively impact the market for phosphate binders, including Auryxia, and divert dialysis organizations' attention from focusing on other therapeutic areas such as anemia management, which in turn could negatively impact the market for Vafseo.

In addition, dialysis organizations may choose lower cost binders over Auryxia, or binders that may have features or benefits more aligned with the dialysis organization's operational activities, which could negatively impact Auryxia revenue.

We believe our revenue growth for Auryxia has been negatively impacted by the COVID-19 pandemic since 2021 primarily as the CKD patient populations that we serve experienced both high hospitalization and mortality rates due to COVID-19, and the pandemic had an adverse impact on the phosphate binder market in which Auryxia competes.

Labor shortages and costs have also adversely impacted dialysis providers.

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We believe this and potentially other factors, led to the reduction in the phosphate binder market, which has not experienced growth since early 2020.

While we are unable to quantify the impact of the recent COVID-19 pandemic on future revenues and revenue growth, the recent COVID-19 pandemic and the ongoing impacts from the recent COVID-19 pandemic continue to adversely and disproportionately impact CKD patients and the phosphate binder market.

Therefore, we expect the impacts from the pandemic to continue to have a negative impact on our revenue growth for the foreseeable future.

While we are unable to quantify the impact of the COVID-19 pandemic on future Auryxia revenues and revenue growth, the COVID-19 pandemic and the ongoing impacts from the COVID-19 pandemic continue to adversely and disproportionately impact CKD patients and the phosphate binder market.

Therefore, we expect the impacts from the pandemic to continue to have a negative impact on our Auryxia revenue growth for the foreseeable future.

Market acceptance is also critical to our ability to generate significant product revenue.

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• the availability of discounts and rebates to dialysis organizations to facilitate access for patients;

• use at dialysis organizations and their willingness to include or continue to include Auryxia or Vafseo in their formulary or protocols and the scope of such protocols;

• the safety and efficacy of the product, as demonstrated in clinical trials and in the post-marketing setting;

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• acceptance by physicians and patients of the product as a safe and effective treatment and the willingness of the target patient population to try new therapies and of physicians to prescribe new therapies;

• use at dialysis organizations and their willingness to include Auryxia or Vafseo in their formulary or protocols starting in 2025;

• the cost, safety and efficacy of the product in relation to alternative treatments;

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• the restrictions on the use of the product together with other medications, if any.

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In addition, our ability to generate net product revenue depends on our ability to control the expenses associated with commercializing a product, including internal expenses, manufacturing costs, rebates, product returns and other adjustments.

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In addition, our net product revenue requires judgement and includes estimates for rebates and product returns, which can fluctuate from quarter-to-quarter and year-over-year.

If our net product revenue is lower than anticipated, including as a result of higher expenses, our business could be harmed.

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Several healthcare facilities, including DaVita, have previously restricted access for non-patients as a result of the recent COVID-19 pandemic, resulting in restricted access for certain members of our sales force.

As a result, we continue to engage with some healthcare providers and other customers virtually where possible.

The restrictions on our customer-facing employees’ in-person interactions with healthcare providers have, and could continue to, negatively impact our access to healthcare providers and ultimately our sales, including with respect to Vafseo.

If our net product revenue is lower than anticipated, including as a result of higher expenses or product returns, our business could be harmed.

Several healthcare facilities, including DaVita, have previously restricted access for non-patients as a result of the COVID-19 pandemic, resulting in restricted access for certain members of our sales force.

Such precautionary measures have since been relaxed at certain healthcare facilities and, as a result, members of our sales force have resumed in person interactions with those customers.

Nevertheless, some restrictions remain, and more restrictions may be put in place again due to a resurgence in COVID-19 cases, including those involving new variants of COVID-19, which may be more contagious and more severe than prior strains of the virus.

Given this uncertain environment and the disproportionate impact of the recent COVID-19 pandemic on CKD patients, we are actively monitoring the demand in the U.S.

Nevertheless, some restrictions remain and restrictions on our customer-facing employees’ in-person interactions with healthcare providers have, and could continue to, negatively impact our access to healthcare providers and ultimately our sales, including with respect to Vafseo.

In addition, restrictions may be put in place due to a resurgence in COVID-19 cases, including those involving new variants of COVID-19, which may be more contagious and more severe than prior strains of the virus, or due to outbreak of other infectious diseases, such as H1N1 virus (Swine Flu) and H5N1 virus (bird flu).

Given this uncertain environment and the disproportionate impact of the COVID-19 pandemic on CKD patients, we are actively monitoring the demand in the U.S.

for Auryxia and Vafseo, including the potential for further declines or changes in prescription trends and customer orders, which could have a material adverse effect on our business, results of operations, and financial condition.

If we are unable to maintain or expand, or, with respect to Vafseo, initiate, sales and marketing capabilities or enter into additional agreements with third parties, we may not be successful in commercializing Auryxia, Vafseo or any other product candidates that may be approved.

If we are unable to maintain or expand sales and marketing capabilities or enter into additional agreements with third parties, we may not be successful in commercializing Auryxia, Vafseo or any other product candidates that may be approved.

In order to market Auryxia, Vafseo and any other approved product, we intend to continue to invest in sales and marketing, which will require substantial effort and significant management and financial resources.

We have built a commercial infrastructure and sales force in the U.S.

for Auryxia, which we believe that we can leverage in the U.S.

for Vafseo as well, with incremental additional hires in our sales force.

for Auryxia and Vafseo.

If the sales and marketing team cannot successfully commercialize Auryxia or Vafseo, it could have a material adverse effect on our product revenue and our financial condition.

Additionally, training a sales force to successfully sell and market a new commercial product is expensive and time-consuming and could delay any commercial launch of such product candidate or distract the current sales force from promoting Auryxia.

We may underestimate the size of the sales force required for a successful product launch, and we may need to expand our sales force to a greater extent or earlier than we currently plan and at a higher cost than we anticipated.

Additionally, training a sales force to successfully sell and market a new commercial product is expensive and time-consuming and could delay any commercial launch or market acceptance of such product.

We may underestimate the size of the sales force required for a successful product launch, and we may need to expand our sales and marketing team to a greater extent than we already have, which would increase our costs more than we anticipated.

We devote significant effort to recruiting individuals with experience in the sales and marketing of pharmaceutical products.

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• potential inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;

• potential lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines, especially as a result of the delay in the approval of Vafseo following receipt of the CRL;

• potential lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines;

• costs and expenses associated with maintaining our own sales and marketing organization.

If we are unable to maintain our own sales and marketing capabilities, we will not be successful in commercializing Auryxia, Vafseo and any other product candidate that may be approved.

I f we are unable to maintain our own sales and marketing capabilities, we will not be successful in commercializing Auryxia, Vafseo and any other product candidate that may be approved.

Also, if we are unable to maintain our arrangements with third parties with respect to sales and marketing, if we are unsuccessful in entering into additional arrangements with third parties to sell and market our products or we are unable to do so on terms that are favorable to us, or if such third parties are unable to carry out their obligations under such arrangements, it will be difficult to successfully commercialize our product and product candidates, including Vafseo.

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Our, or our partners', failure to obtain or maintain adequate coverage, pricing and reimbursement for Auryxia, Vafseo or any other future approved products, could have a material adverse effect on our or our collaboration partners’ ability to sell such approved products profitably and otherwise have a material adverse impact on our business.

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Even if we obtain coverage for an approved product, third party payors may not establish adequate reimbursement amounts, which may reduce the demand for our product and prompt us to have to reduce pricing for the product.

If reimbursement is not available or is limited, we may not be able to successfully commercialize

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certain of our products.

If reimbursement is not available or is limited, we may not be able to successfully commercialize certain of our products.

Coverage and reimbursement by a governmental authority, dialysis organization, third-party payor or PBMs may depend upon a number of factors, including the determination that use of a product is:

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Within Medicare, for oral drugs dispensed by pharmacies and also administered in facilities, coverage and reimbursement may vary depending on the setting.

CMS, local Medicare administrative contractors, Medicare Part D plans and/or PBMs operating on behalf of Medicare Part D plans, may have some responsibility for determining the medical necessity of such drugs, and therefore coverage, for different patients.

CMS, local Medicare administrative contractors, Medicare Advantage and/or Part D plans and/or PBMs operating on behalf of such plans, may have some responsibility for determining the medical necessity of such drugs, and therefore coverage, for different patients.

Different reimbursement methodologies may apply, and CMS may have some discretion in interpreting their application in certain settings.

As an oral drug, Auryxia is covered by Medicare under Part D for the treatment of p atients with hyperphosphatemia .

As an oral drug, Auryxia was covered by Medicare under Part D until January 1, 2025, for the treatment of p atients with hyperphosphatemia .

In January 2011, CMS implemented the ESRD PPS, a prospective payment system for dialysis treatment.

Under the ESRD PPS, CMS generally makes a single bundled payment to the dialysis facility for each dialysis treatment that covers all items and services routinely required for dialysis treatments furnished to Medicare beneficiaries in Medicare-certified ESRD facilities or at their home.

The inclusion of oral medications without injectable or intravenous equivalents such as Auryxia in the bundled payment was initially delayed by CMS until January 1, 2014, and through several subsequent legislative actions has been delayed until January 1, 2025.

Absent further legislation or regulation on this matter, beginning in January 2025, oral ESRD-related drugs without injectable or intravenous equivalents, including Auryxia and all other phosphate lowering medications, will be included in the ESRD bundle and separate Medicare payment for these drugs will no longer be available, as is the case today under Medicare Part D.

ESRD facilities may nonetheless receive a Transitional Drug Add-on Payment Adjustment, or TDAPA , for new renal dialysis drugs and biological products that meet certain criteria for a period of at least two years.

The TDAPA will provide separate payment based on the drug’s Average Sales Price, or ASP , that will be in addition to the base rate in order to facilitate the adoption of innovative therapies.

In July 2023, the U.S.

House of Representatives introduced the Kidney Patient Access to Technologically Innovative and Essential Nephrology Treatments (PATIENT) Act (H.R.

5074), or the Patient Act , and the Senate advanced a similar bill (S.

4510), which legislation, if passed and enacted into law prior to January 1, 2025, would delay the inclusion of phosphorus lowering drugs in the bundled payment.

In addition, in July 2024, Ardelyx, Inc., or Ardelyx , filed a complaint in the United States District Court for the District of Columbia against the U.S.

Department of Health and Human Services, or HHS , CMS and other parties, which alleged that CMS’s plan to include oral-only phosphate lowering therapies in the ESRD PPS violated its statutory and regulatory authority under the Medicare Improvements for Patients and Providers Act, which established the ESRD PPS bundled payment system for dialysis services in 2008.

In October 2024, Ardelyx filed for a preliminary injunction to enjoin CMS from including oral-only phosphate lowering therapies in the ESRD PPS.

CMS had earlier filed a motion to dismiss the complaint.

The court has not scheduled a date for oral argument on these motions and, instead, indicated that it may address these motions on the papers alone.

If the Patient Act is passed and enacted into law prior to January 1, 2025 or Ardelyx is successful in its claims, oral-only phosphate lowering therapies, including Auryxia, may not be included in the ESRD bundle in 2025 or at all, which could reduce anticipated revenue for Auryxia.

Even if Auryxia is included in the ESRD bundle, the TDAPA reimbursement amount for Auryxia may be lower than anticipated or revenue for sales of Auryxia could be significantly less in the TDAPA period than anticipated or than it would be if Auryxia is not bundled into the ESRD PPS, which would have an adverse impact on our revenue.

In the post-TDAPA period, CMS currently expects to increase the single bundled payment base rate paid to the dialysis facility for each dialysis treatment to reflect that oral only phosphate lowering drugs will be reimbursed as part of the single bundled payment for Medicare patients.

However, there can be no assurances that any increase in the single bundled payment base rate will be sufficient to adequately reimburse the dialysis facilities for Auryxia at a price that allows us to continue to sell Auryxia at a profit.

In addition, in September 2018, CMS decided that Auryxia would no longer be covered by Medicare for the treatment of iron deficiency anemia, or IDA , in adult patients not on dialysis, or NDD-CKD .

While this decision does not impact CMS coverage for the control of serum phosphorus levels in adult patients with anemia due to CKD in patients on dialysis, or DD-CKD , or the Hyperphosphatemia Indication , it requires Part D Plan sponsors to impose prior authorization or other steps to ensure that

In addition, dialysis organizations will receive a Transitional Drug Add-on Payment Adjustment, or TDAPA , payment for claims that include phosphate binders for the next two years.

Vafseo, which we began selling in January 2025, is also included in the ESRD bundle and ESRD facilities will receive a TDAPA for Vafseo as a new renal dialysis drug meeting certain criteria for a period of at least two years starting on January 1, 2025.

TDAPA provides separate payment based on the drug’s Average Sales Price, or ASP , that will be in addition to the base rate in order to facilitate the adoption of innovative therapies.

If the TDAPA reimbursement amount for Auryxia or Vafseo is lower than anticipated, or if the TDAPA is eliminated, it would have an adverse impact on our revenue.

Additionally, in the post-TDAPA period, CMS currently expects to increase the single bundled payment base rate paid to the dialysis facility for each dialysis treatment to reflect that bundled drugs will be reimbursed as part of the single bundled payment for Medicare patients.

However, there can be no assurances that any increase in the single bundled payment base rate will be sufficient to adequately reimburse the dialysis facilities for Auryxia or Vafseo at a price that allows us to continue to sell Auryxia or Vafseo at a profit.

In July 2024, Ardelyx, Inc., or Ardelyx , filed a complaint in the United States District Court for the District of Columbia against the U.S.

In October 2024, Ardelyx filed a motion for a preliminary injunction to enjoin CMS from including oral-only phosphate lowering therapies in the ESRD PPS.

CMS had earlier filed a motion to dismiss the complaint on jurisdictional grounds.

On November 8, 2024, the district court denied Ardelyx’s motion for a preliminary injunction and it granted the government’s motion to dismiss.

Thereafter, Ardelyx moved for reconsideration, but the district court also denied that request.

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Auryxia is reimbursed only for the Hyperphosphatemia Indication.

We decided beginning in 2022 to terminate certain Part D contracts, as patients no longer had the access benefit given the prior authorization requirement.

Now p atients must go through a medical exemption process, which is very similar to a prior authorization review.

While we believe this had, and may continue to have, a negative impact on our overall sales volume, we believe it had a significant positive impact on our net selling price.

However, if we experience additional negative impacts on our sales volume as a result of this change, it could have a negative impact on our product revenue.

December 26, 2024, Ardelyx filed a notice of appeal with the US Court of Appeals for the DC Circuit.

If Ardelyx is successful in its claims, oral-only phosphate lowering therapies, including Auryxia, may be removed from the ESRD bundle, which could reduce anticipated revenue for Auryxia.

Medicaid reimbursement of drugs varies by state.

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In addition, dialysis organizations, GPOs, third party payors, PBMs and/or other entities that purchase our products may impose restrictions on our ability to raise prices for our products over time without incurring additional costs.

Four distributors, Fresenius Medical Care Rx, McKesson Corporation, Cardinal Health, Inc.

and Cencora, Inc., formerly known as AmerisourceBergen Drug Corporation, in the aggregate, accounted for a significant percentage of our gross revenue during the three and nine months ended September 30, 2024 and the year ended December 31, 2023.

If we are not able to maintain our arrangements with these key distributors on favorable terms, on a timely basis or at all, or if there is any adverse change in one or more of these distributors’ business practices or financial condition, it would adversely impact the market opportunity for Auryxia, our product revenues and operating results.

Vafseo will be included in the bundled reimbursement model for Medicare beneficiaries and, in October 2024, CMS determined that Vafseo will receive a TDAPA for at least two years starting on January 1, 2025.

However, if there are updates to the TDAPA rule that decrease the basis for reimbursement or if the TDAPA is eliminated, then our profitability may be adversely affected.

For example, the Medicare Payment Advisory Commission, an independent legislative branch advisory body to Congress on issues related to the Medicare program, has recommended that TDAPA not be provided to newly approved drug products considered to fall within “functional categories” for which costs are already accounted for in the bundled reimbursement model, such as for anemia management drugs.

Further, Vafseo will be included in the fixed reimbursement model for a bundle of dialysis services, which will require us to enter into contracts to supply Vafseo to specific dialysis providers, instead of through distributors, which we believe could be challenging.

The dialysis market is unique and is dominated by two providers:

DaVita and Fresenius Medical Care, which account for a vast majority of the dialysis population in the U.S.

Under the Vifor Termination Agreement, we have regained our rights to sell Vafseo to Fresenius Medical Care North America and its affiliates, including Fresenius Kidney Care Group LLC, to certain third-party dialysis organizations approved by us, to independent dialysis organizations that are members of group purchasing organizations, and to certain non-retail specialty pharmacies in the U.S.

See Note 8, Liability Related to Settlement Royalties, Working Capital Fund Liability and Liability Related to Sale of Future Royalties , to our unaudited condensed consolidated financial statements in Part I, Item 1.

Financial Statements of this Form 10-Q for additional information regarding the Vifor Termination Agreement.

If we are not able to enter into supply agreements with dialysis organizations for the sale of Vafseo on favorable terms, in a timely matter or at all, our business may be materially harmed.

Three distributors, DaVita, Fresenius Medical Care Rx and USRC, in the aggregate, accounted for a significant percentage of our gross revenue during the three months ended March 31, 2025.

Due to a variety of factors, including coverage of our products in the ESRD bundle and to support commercial availability of Vafseo in 2025, there were changes to the manner in which we distributed our products, which we implemented in January 2025.

This included, for example, reducing the number of mainline wholesalers in our distribution network, distribution of products through specialty distributors, and an increased focus on direct sales through contracts with dialysis organizations.

If we are not able to enter into and maintain agreements with wholesalers, specialty distributors, the dialysis organizations and other purchasers for the sale of our products on favorable terms, on a timely basis or at all, if dialysis organizations or other purchasers do not purchase as much product as we anticipate or terminate our arrangements, or if due to changes in distribution, dialysis organizations and/or specialty pharmacies are not able to meet market demand causing slower dispensing times and potentially impacting refill rates, it would adversely impact the market opportunity for our products, our product revenues and operating results.

Furthermore, the U.S.

dialysis market is unique and is dominated by three providers:

DaVita, Fresenius and USRC, which account for a vast majority of the dialysis population in the U.S.

If we are not able to maintain supply agreements with these, and other, dialysis organizations for the sale of Vafseo and Auryxia on favorable terms, in a timely matter or at all, our business may be materially harmed.

Similar to how payor coverage may affect the sales of a product, formulary status within dialysis organizations may affect what products are prescribed within that specific organization.

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Further, one dialysis organization’s determination to add a product to their formulary does not assure that other dialysis organizations will also add the product to theirs.

There is always a risk a dialysis organization will not contract with a drug manufacturer for a specific product, resulting in that product not being on that organization’s formulary.

If any dialysis organization does not add Vafseo to the formulary, our business may be materially harmed.

There is always a risk a dialysis organization will not contract with a drug manufacturer for a specific product, or will terminate their contract, resulting in that product not being on that organization’s formulary.

If any dialysis organization does not add Auryxia or Vafseo to the formulary, or removes Auryxia or Vafseo from the formulary, our business may be materially harmed.

In addition, we may be unable to sell Auryxia or Vafseo to dialysis providers on a profitable basis if CMS significantly reduces the level of reimbursement for dialysis services and providers choose to use alternative therapies or look to re-negotiate their contracts with us.

Our profitability may also be affected if our costs of production increase faster than increases in reimbursement levels.

Adequate coverage and reimbursement of our products by government and private insurance plans are central to patient and provider acceptance of any products for which we receive marketing approval.

Adequate coverage and reimbursement of our products by government and private insurance plans, including Medicare Advantage plans, are central to patient and provider acceptance of any products for which we receive marketing approval.

Existing competitive products may enter into sole source agreements with dialysis providers that impact the ability for new product innovations and new competitors may face price pressure based on existing contracts with dialysis providers.

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Further, in many countries outside the U.S., a drug must be approved for reimbursement before it can be marketed or sold in that country.

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However, the failure to obtain reimbursement in one jurisdiction may negatively impact our ability to obtain reimbursement in another jurisdiction.

In addition, we plan to rely on a partner to obtain approval by reimbursement authorities outside the U.S.

In addition, we plan to rely on partners to obtain approval by reimbursement authorities outside the U.S.

Our partners may not be able to obtain such reimbursement approvals on a timely basis, if at all, and favorable pricing in certain countries depends on a number of factors, some of which are outside of our partners' control.

Vafseo was approved in Japan for the treatment of adult patients with anemia due to CKD and is being marketed by MTPC in Japan under the trade name Vafseo.

Vafseo was approved in Japan for the treatment of adult patients with anemia due to CKD and is being marketed by MTPC in Japan under the trade

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Pricing and reimbursement strategy is a key component of MTPC’s commercialization plans for Vafseo in Japan.

If coverage and reimbursement terms change, MTPC may not be able to, or may decide not to, continue commercialization of Vafseo in Japan.

Furthermore, Vafseo was approved in Europe and Australia for the treatment of anemia due to CKD in DD-CKD patients.

Furthermore, Vafseo was approved in Europe and Australia for the treatment of anemia due to CKD in patients on dialysis, or DD-CKD, or the Hyperphosphatemia Indication .

In Europe, reimbursement is obtained on a country-by-country basis and it is a time consuming process.

In May 2023, we entered into the license agreement with Medice, pursuant to which we granted Medice an exclusive license to develop and commercialize Vafseo for the treatment of anemia in patients with CKD in the Medice Territory.

Medice launched Vafseo in certain countries in Europe and is working on securing pricing and reimbursement for Vafseo in markets across Europe.

Medice launched and has received pricing and reimbursement for Vafseo in certain countries in Europe and is working on launching and securing pricing and reimbursement for Vafseo in other markets across Europe.

There is no guarantee of the timing or extent of reimbursement that they will receive in each country, if at all.

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Our future success depends on our ability to demonstrate and maintain a competitive advantage with respect to the development and commercialization of Auryxia, Vafseo and any other product or product candidate, including those that may be in-licensed or acquired.

Our objective is to successfully commercialize Auryxia and commercially launch Vafseo and develop and commercialize new products with clinically proven efficacy, convenience, tolerability and/or safety.

Our objective is to successfully commercialize Auryxia and Vafseo and develop and commercialize new products with clinically proven efficacy, convenience, tolerability and/or safety.

In many cases, any approved products that we commercialize will compete with existing, market-leading products.

If existing or new competitors of Auryxia or Vafseo take market share from us, it could have an adverse impact on our revenue and our business.

We had exclusive rights under a series of patents and patent applications to commercialize Auryxia in the U.S.

that protected us from generic drug competition until March 20, 2025.

Following LoE, the number of additional generic versions of Auryxia that enter the market, and the timing thereof, will affect our revenue from Auryxia.

We and our licensors, Panion & BF Biotech, Inc., or Panion , and, as applicable, Dr.

Hsu, entered into settlement agreements with all of the third parties who submitted Paragraph IV certification notice letters regarding Abbreviated New Drug Applications, or ANDAs , submitted to the FDA, pursuant to which we granted licenses to market a generic version of Auryxia in the U.S.

beginning on March 20, 2025 (subject to FDA approval).

On February 5, 2025, we entered into an Authorized Generic Distribution and Supply Agreement with Mylan Pharmaceuticals, Inc., or AG Partner , pursuant to which, since March 20, 2025, they began selling an authorized generic version of Auryxia.

In addition, we believe the dynamics of Auryxia reimbursement being included in the ESRD bundle and Auryxia LoE could result in the buying pattern of certain customers in future years being different than their historical practices.

If Auryxia sales decline faster than we anticipate following LoE, our results of operations and financial condition will be materially harmed.

Auryxia is competing in the hyperphosphatemia market in the U.S.

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In October 2023, the FDA approved XPHOZAH® (tenapanor), a phosphate absorption inhibitor that is marketed by Ardelyx and indicated to reduce serum phosphorus in adults with CKD on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy, which may adversely impact the market for Auryxia.

Auryxia is competing in the IDA market in the U.S.

Auryxia is competing in the iron deficiency anemia, or IDA , market in the U.S.

with over-the-counter oral iron, ferrous sulfate, other prescription oral iron formulations, including ferrous gluconate, ferrous fumerate, and polysaccharide iron complex, and intravenous iron formulations, including Feraheme® (ferumoxytol injection), Venofer® (iron sucrose injection), Ferrlicit® (sodium ferric gluconate complex in sucrose injection), Injectafer® (ferric carboxymaltose injection), and Triferic® (ferric pyrophosphate citrate).

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for the treatment of IDA in July 2021.

In Japan, our Japanese sublicensee, Japan Tobacco International, or JT , and its subsidiary, Torii Pharmaceutical Co., Ltd., or Torii , commercialize Riona (ferric citrate hydrate).

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In Japan, our Japanese sublicensee, Japan Tobacco International, or JT , and its subsidiary, Torii Pharmaceutical Co., Ltd., or Torii , commercialize Riona.

In the hyperphosphatemia market, Riona competes with Fosrenol® (lanthanum carbonate hydrate) marketed by Bayer Yakuhin Ltd., generic lanthanum carbonate hydrate products, and Phozevel® (tenapor hydrochloride) marketed by Kyowa Kirin Co., Ltd.

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Furthermore, Auryxia’s commercial opportunities may be reduced or eliminated if our competitors develop and market products that are less expensive, more effective, safer or offer greater patient convenience than Auryxia.

Other companies

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have product candidates in various stages of preclinical or clinical development to treat diseases and complications of the diseases for which we are marketing Auryxia.

In addition, we and our licensors, Panion & BF Biotech, Inc., or Panion , and, as applicable, Dr.

Hsu, entered into settlement agreements with all but one of the third parties who submitted Paragraph IV certification notice letters regarding Abbreviated New Drug Applications, or ANDAs , submitted to the FDA, pursuant to which we granted licenses to market a generic version of Auryxia in the U.S.

beginning in March 2025 (subject to FDA approval), or earlier under certain circumstances customary for settlement agreements of this nature.

While we expect that the availability of generic versions of Auryxia will negatively impact our net product revenue for Auryxia and our results of operations, it is difficult to estimate the impact of generics on Auryxia net product revenue, and if the impact is greater than we currently anticipate, it may materially adversely impact our business and results of operations.

Other companies have product candidates in various stages of preclinical or clinical development to treat diseases and complications of the diseases for which we are marketing Auryxia.

Drugs that may compete with Vafseo include Epogen® (epoetin alfa) and Aranesp® (darbepoetin alfa), both commercialized by Amgen, Procrit® (epoetin alfa) and Eprex® (epoetin alfa), commercialized by Johnson & Johnson in the U.S.

and Europe, respectively, Mircera® (methoxy PEG-epoetin beta), commercialized by CSL Vifor in the U.S.

and Roche Holding Ltd., or Roche , outside of the U.S., Evrenzo® (roxadustat) in Europe commercialized by Astellas Pharma Inc., Eporatio® (epoetin theta) in Europe commercialized by Teva Pharmaceuticals Ltd., Silapo® (epoetin zeta) in Europe commercialized by Stada Arzneimittel AG, Epoetin Alfa Hexal® (epoetin alfa) in Europe commercialized by Hexal AG, Binocrit® (epoetin alfa-biosimilar) in Europe commercialized by Sandoz, and NeoRecormon® (epoetin beta) in Europe commercialized by Roche.

and Roche Holding Ltd., or Roche, outside of the U.S., Evrenzo® (roxadustat) in Europe commercialized by Astellas Pharma Inc., or Astellas, Eporatio® (epoetin theta) in Europe commercialized by Teva Pharmaceuticals Ltd., Silapo® (epoetin zeta) in Europe commercialized by Stada Arzneimittel AG, Epoetin Alfa Hexal® (epoetin alfa) in Europe commercialized by Hexal AG, Binocrit® (epoetin alfa-biosimilar) in Europe commercialized by Sandoz, and NeoRecormon® (epoetin beta) in Europe commercialized by Roche.

We and our partners may also face competition from potential new anemia therapies.

There are several other oral hypoxia-inducible factor prolyl hydroxylase inhibitor product candidates in various stages of development for anemia indications that may be in direct competition with Vafseo if and when they are approved and launched commercially.

There are several other oral hypoxia-inducible factor prolyl hydroxylase inhibitor product candidates in various stages of development for anemia indications in territories outside the U.S.

that may be in direct competition with Vafseo if and when they are approved and launched commercially.

These candidates are being developed by companies such as JT and Bayer HealthCare AG, or Bayer .

For example, FibroGen filed an NDA for its product candidate, roxadustat, with the FDA, to which the FDA issued a complete response letter indicating the FDA will not approve the NDA in its present form and requested that an additional clinical trial for roxadustat be conducted prior to resubmission of the NDA or additional response to the FDA’s complete response letter.

In Europe however, roxadustat is approved for the treatment of anemia in patients with CKD.

If roxadustat is approved by the FDA, then roxadustat will compete with Vafseo.

Furthermore, certain companies are developing potential new therapies for renal-related diseases that could potentially reduce injectable erythropoiesis stimulating agent, or ESA , utilization and thus limit the market potential for Vafseo if they are approved and launched commercially.

In Europe, roxadustat is approved for the treatment of anemia in patients with CKD.

Furthermore, certain companies are developing potential new therapies for the treatment of renal-related diseases that could potentially reduce injectable erythropoiesis stimulating agent, or ESA , utilization and thus limit the market potential for Vafseo if they are approved and launched commercially.

Other new therapies are in development for the treatment of conditions inclusive of renal anemia that may impact the market for anemia-targeted treatment.

In addition, other new therapies for the treatment of patients with CKD not on dialysis, or NDD-CKD, may slow the progression of NDD-CKD patients becoming DD-CKD patients thereby reducing the DD-CKD patient population which may impact the market opportunity for Vafseo.

In Japan, vadadustat is sold under the name Vafseo, which is approved for patients with CKD, including both DD-CKD and NDD-CKD , and competes with roxadustat, daprodustat and enarodustat.

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The introduction of biosimilars into the injectable ESA market in the U.S.

will constitute additional competition for Vafseo if we are able to commercially launch Vafseo.

will constitute additional competition for Vafseo.

In the U.S., Pfizer’s biosimilar version of injectable ESAs, Retacrit® (epoetin alfa-epbx), was approved by the FDA in May 2018 and launched in November 2018 and several biosimilar versions of injectable ESAs are available for sale in the EU.

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In Japan and certain other countries in Asia, we granted MTPC exclusive rights to commercialize Vafseo, which has been approved and is being marketed by MTPC in Japan under the trade name Vafseo.

We also granted Averoa SAS, or Averoa , an exclusive license to develop and commercialize ferric citrate in the EEA, Turkey, Switzerland, UK, Balkans, and certain countries in Eastern Europe and the Middle East, or the Averoa Territory .

In 2023, the marketing authorization for Vafseo was granted by the EMA, the United Kingdom Medicines and Healthcare Products Regulatory Agency, the Swiss Agency for Therapeutic Products, or Swissmedic , and the Australian Therapeutic Goods Administration, or TGA .

Pursuant to the license agreement, we transferred the marketing authorization issued by the EMA, UK, Swissmedic and Australia to Medice.

Pursuant to the license agreement, we transferred the marketing authorization issued by the EMA, UK, the Swiss Agency for Therapeutic Products and the Australian Therapeutic Goods Administration to Medice.

In addition, we have conducted and in the future may conduct clinical trials outside of the U.S.

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In addition, we receive revenues from royalty payments converted to U.S.

dollars based on net sales of Riona and Vafseo in Japanese yen.

The exchange rates between the Japanese yen on the one hand, and the U.S.

dollars based on net sales of Riona and Vafseo in Japanese yen, the Euro, the Pound Sterling and the Swiss Franc.

The exchange rates between these currencies on the one hand, and the U.S.

dollar, on the other hand, have changed substantially in recent years and may fluctuate substantially in the future.

Our results of operations could be adversely affected over time by certain movements in exchange rates, particularly if the Japanese yen depreciates against the U.S.

Our results of operations could be adversely affected over time by certain movements in exchange rates, particularly if these currencies depreciate against the U.S.

Any of these factors may, individually or as a group, have a material adverse effect on our business and results of operations.

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Failure can occur at any time during the process.

We may be unable to successfully complete clinical trials of Auryxia, Vafseo and our product candidates or to successfully obtain approval of label expansion for Vafseo or of our product candidates, if the results of those trials and studies are not positive or are only modestly positive, or if there are concerns with the product profile due to efficacy or safety.

We may be unable to successfully complete clinical trials of Auryxia, Vafseo and our product candidates or to successfully obtain approval of label expansion for Vafseo or approval of our product candidates, if the results of those trials and studies are not positive or are only modestly positive, or if there are concerns with the product profile due to efficacy or safety.

Further, the results of preclinical studies and early clinical trials of our product candidates may not be predictive of the results of later-stage clinical trials, interim results of a clinical trial do not necessarily predict final results, and results of Phase 3 clinical trials for one indication may not be predictive of results of Phase 3 clinical trials for another indication.

For example, we announced positive results from the INNO 2 VATE program;

however, while Vafseo achieved the primary and key secondary efficacy endpoint in each of the two PRO2TECT studies, the PRO2TECT program did not meet the primary major adverse cardiovascular event, or MACE, safety endpoint.

however, while Vafseo achieved the primary and key secondary efficacy endpoints in each of the two PRO 2 TECT studies, the PRO 2 TECT program did not meet the primary major adverse cardiovascular event, or MACE , safety endpoint.

Many companies in the biopharmaceutical industry have suffered significant setbacks in late-stage clinical trials after achieving positive results in early-stage development, and we may face similar setbacks.

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For example, in March 2022, we received the CRL for Vafseo indicating that the FDA had determined that it could not approve the NDA in its present form, thus delaying any potential approval of Vafseo.

Following submission of the FDRR to the FDA in 2022, we filed a resubmission to our NDA for vadadustat in 2023.

Following submission of the FDRR to the FDA in 2022, we filed a resubmission to our NDA for vadadustat for the treatment of anemia due to CKD only in adult DD-CKD patients in 2023.

On March 27, 2024, the FDA approved our NDA for vadadustat under the trade name of Vafseo for the treatment of anemia due to CKD in adults who have been receiving dialysis for at least three months.

However, we expended significant additional resources to obtain the approval of Vafseo, the approved indication is limited to the treatment of anemia due to CKD in adults who have been receiving dialysis for at least three months and the commercialization of Vafseo was delayed, which had and could continue to have an adverse effect on our business.

We have several lifecycle management and label expansion opportunities currently under evaluation for Vafseo, one of which is the potential for alternative dosing, and another of which is label expansion for the treatment of adult patients with NDD-CKD.

However, we will be required to complete additional clinical trials before seeking approval for label expansion for the treatment of adult patients with NDD-CKD and we may be required to generate additional clinical data before seeking approval for alternative dosing.

Clinical trials are time consuming and expensive, and even though Vafseo is approved as a treatment for anemia due to CKD for dialysis dependent patients, we may not be successful in any of our lifecycle management or label expansion opportunities in the timeframe anticipated by us, or at all.

Clinical trials are time consuming and expensive, and even though Vafseo is approved for adult patients with anemia due to CKD on dialysis for at least three months, we may not be successful in any of our lifecycle management or label expansion opportunities in the timeframe anticipated by us, or at all.

For example, we plan to start a Phase 3 trial in the second half of 2025 to potentially expand Vafseo label to include the treatment of late-stage NDD-CKD patients;

however, the FDA may not agree with our study design or we may not successfully demonstrate safety and/or efficacy needed to obtain regulatory approval or we may be unable to successfully complete the trial when anticipated, or at all.

If the clinical trials for our label expansion opportunities are not successful or take longer than anticipated, or if we do not obtain FDA approval of label expansion for Vafseo for the treatment of adult patients with NDD-CKD or for alternative dosing in a timely manner, or at all, it could impact future revenue and have an adverse effect on our business.

In addition, it is impossible to predict when or if any of our other product candidates will prove effective or safe in humans or will receive marketing approval or on what terms.

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• the number of patients required for clinical trials may be larger than we anticipate;

• enrollment in our clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials at a higher rate than we anticipate;

• our third party contractors, such as our CROs, may fail to comply with regulatory requirements, perform effectively, or meet their contractual obligations to us in a timely manner, or at all, or we may fail to communicate effectively or provide the appropriate level of oversight of such third party contractors;

• the supply or quality of our starting materials, drug substance and drug product necessary to conduct clinical trials of our product candidates may be insufficient or inadequate;

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noncompliance with regulatory requirements, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using our product candidate, or a finding that the participants are being exposed to unacceptable health risks;

• enrollment in our clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials at a higher rate than we anticipate;

• our third-party contractors, such as our contract research organizations, or CROs , may fail to comply with regulatory requirements, perform effectively, or meet their contractual obligations to us in a timely manner, or at all, or we may fail to communicate effectively or provide the appropriate level of oversight of such third-party contractors;

• the supply or quality of our starting materials, drug substance and drug product necessary to conduct clinical trials of our product candidates may be insufficient or inadequate;

• regulators, independent data monitoring committees, institutional review boards, safety committees, or ethics committees, may require that we suspend or terminate our clinical trials for various reasons, including noncompliance with regulatory requirements, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using our product candidate, or a finding that the participants are being exposed to unacceptable health risks;

• clinical trials of our product candidates may produce negative or inconclusive results or results that may be interpreted in a manner different than we interpret them, and we may decide, or regulators may require us, to conduct additional clinical trials, repeat a clinical trial or abandon product development programs;

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• we may fail to initiate, delay or fail to complete a clinical trial as a result of an Investigational New Drug application, or IND , being placed on clinical hold by the FDA, the EMA, the PMDA, or other regulatory authorities, or for other reasons, such as failure to recruit or enroll suitable patients or patients' failure to return for post-treatment follow up;

• we may determine to change or expand a clinical trial, including after it has begun;

• we may determine to expand or otherwise change a clinical trial, including after it has begun;

• clinical trial sites and investigators deviating from the clinical protocol, failing to conduct the trial in accordance with regulatory requirements, or dropping out of a trial, or failure by us or our CROs to communicate effectively or provide the appropriate level of oversight of such clinical sites and investigators;

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• we may obtain approval for indications or patient populations that are not as broad as intended or desired;

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• we may obtain approval with labeling that includes significant use or distribution restrictions or safety warnings that would reduce the potential market for any approved product or inhibit our ability to successfully commercialize any approved product;

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Our preclinical studies or clinical trials may need to be restructured or may not be completed on schedule, or at all.

Significant preclinical or clinical trial delays also could shorten any periods during which we may have the

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exclusive right to commercialize Vafseo for potential future indications or any product candidate that is approved, including those that may be in-licensed or acquired, or allow our competitors to bring products to market before we do.

Significant preclinical or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize Vafseo for potential future indications or any product candidate that is approved, including those that may be in-licensed or acquired, or allow our competitors to bring products to market before we do.

This could impair our ability to successfully commercialize our product candidates and may harm our business and results of operations.

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We may not be able to initiate or complete clinical trials in a timely manner, or at all, if we cannot enroll a sufficient number of eligible patients to participate in the clinical trials required by regulatory agencies.

If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may need to delay, limit or terminate ongoing or planned clinical trials, any of which may delay approval, or result in failure to maintain or obtain approval, of our products or product candidates, which would have a material adverse effect on our business.

If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may need to delay, limit or terminate ongoing or planned

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clinical trials, any of which may delay approval, or result in failure to maintain or obtain approval, of our products or product candidates, which would have a material adverse effect on our business.

Further, if we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies governing clinical trials, our development plans may be impacted.

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These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA-regulated products.

Specifically, action plans must include the sponsor’s goals for enrollment, the underlying rationale for those goals, and an explanation of how the sponsor intends to meet them.

In June 2024, as mandated by FDORA, the FDA issued draft guidance outlining the general requirements for DAPs.

Unlike most guidance documents issued by the FDA, the DAP guidance when finalized will have the force of law because FDORA specifically dictates that the form and manner for submission of DAPs are specified in FDA guidance.

In addition, the regulatory landscape related to clinical trials in the European Union recently evolved.

The EU Clinical Trials Regulation, or CTR , which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022.

While the Clinical Trials Directive required a separate clinical trial application, or CTA , to be submitted in each member state, to both the competent national health authority and an independent ethics committee, the CTR introduces a centralized process and only requires the submission of a single application to all member states concerned.

The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state.

The assessment procedure of the CTA has been harmonized as well, including a joint assessment by all member states concerned, and a separate assessment by each member state with respect to specific requirements related to its own territory, including ethics rules.

Each member state’s decision is communicated to the sponsor via the centralized EU portal.

Once the CTA is approved, clinical study development may proceed.

We have conducted and intend to conduct certain of our clinical trials globally.

However, there are additional risks unique to conducting trials outside of the U.S., and the FDA and other foreign equivalents may not accept data from such trials, in which case our development plans may be delayed, which could materially harm our business.

We have conducted and intend to continue conducting certain of our clinical trials globally.

The acceptance by the FDA or other regulatory authorities of data from clinical trials conducted outside their jurisdiction may be subject to certain conditions or may not be accepted at all.

In cases where data from foreign clinical trials are intended to serve as the sole basis for marketing approval in the United States, the FDA will generally not approve the application on the basis of foreign data alone unless (i) the data are applicable to the U.S.

population and U.S.

medical practice, (ii) the trials were performed by clinical investigators of recognized competence and pursuant to good clinical practice, or GCP, regulations and (iii) the data may be considered valid without the need for an on-site inspection by the FDA, or if the FDA considers such inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other appropriate means.

In addition, even where foreign clinical trial data are not intended to serve as the sole basis for approval, the FDA will not accept the data as support for an application for marketing approval unless the clinical trial is well-designed and well-conducted in accordance with GCP requirements and the FDA is able to validate the data from the trial through an onsite inspection if deemed necessary.

Many foreign regulatory authorities have similar approval requirements.

In addition, such foreign trials would be subject to the applicable local laws of the foreign jurisdictions where the trials are conducted.

There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the United States or the applicable jurisdiction.

If the FDA or any comparable foreign regulatory authority does not accept such data, it could result in the need for additional trials, which could be costly and time-consuming, and which may result in current or future product candidates that we may develop not receiving approval for commercialization in the applicable jurisdiction.

Conducting clinical trials outside the United States also exposes us to additional risks, including risks associated with:

⦁ additional foreign regulatory requirements;

⦁ foreign exchange fluctuations;

⦁ compliance with foreign manufacturing, customs, shipment and storage requirements;

⦁ cultural differences in medical practice and clinical research;

⦁ diminished protection of intellectual property in some countries;

⦁ interruptions or delays in our trials resulting from geopolitical events, such as war or terrorism.

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Conducting clinical trials outside of the U.S., as we have done historically and as we may decide to do in the future, presents additional risks and complexities and, if we decide to conduct a clinical trial outside of the U.S.

in the future, we may not complete such trials successfully, in a timely manner, or at all, which could affect our ability to obtain regulatory approvals.

Our ability to successfully initiate, enroll and complete a clinical trial in any country outside of the U.S.

is subject to numerous additional risks unique to conducting business in jurisdictions outside the U.S., including:

• difficulty in establishing or managing relationships with qualified CROs, physicians and clinical trial sites;

• difficulty in complying with different local standards for the conduct of clinical trials;

• difficulty in complying with various and complex import laws and regulations when shipping drug to certain countries;

• the potential burden of complying with a variety of laws, medical standards and regulatory requirements, including the regulation of pharmaceutical and biotechnology products and treatments.

Data obtained from studies conducted in the U.S.

may not be accepted by the EMA, the PMDA and other regulatory authorities outside of the U.S.

Also, certain jurisdictions require data from studies conducted in their country in order to obtain approval in that country.

Further, when a foreign clinical trial is not conducted under an IND, the sponsor must ensure that the study complies with certain regulatory requirements of the FDA in order to use the study as support for an IND or application for marketing approval.

Specifically, the studies must be conducted in accordance with GCP, including undergoing review and receiving approval by an independent ethics committee, and seeking and receiving informed consent from subjects.

Thus, to the extent that we rely on data from foreign clinical trials that are not the subject of an IND but are used to support of an NDA, there is a risk that FDA may not review such data in connection with its review of the NDA.

If we or our collaboration partners have difficulty conducting future clinical trials in jurisdictions outside the U.S.

as planned, we may need to delay, limit or terminate such clinical trials, any of which could have an adverse effect on our business.

Auryxia, Vafseo or any other product or product candidate, including those that may be in-licensed or acquired, may cause undesirable side effects or have other properties that may delay or prevent marketing approval or limit their commercial potential.

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• we may decide to, or be required to, send drug warnings or safety alerts to physicians, pharmacists and hospitals (or the FDA or other regulatory authorities may choose to issue such alerts), or we may decide to conduct a product recall or be requested to do so by the FDA or other regulatory authority;

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• reformulation of the product, additional non-clinical or clinical trials, restrictive changes in labeling or changes to or re-approvals of manufacturing facilities may be required;

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In addition, any of these events could substantially increase our costs, and could significantly impact our ability to successfully commercialize Auryxia, Vafseo or any other product and product candidate, including those that may be in-licensed or acquired, and generate product revenue.

The patient populations treated with Auryxia and the projected patient populations that will be treated with Vafseo have CKD, a serious disease that increases the risk of cardiovascular disease including heart attacks and stroke and, in its most severe form, results in, kidney failure and the need for dialysis or kidney transplant.

The patient populations treated with Auryxia and Vafseo have CKD, a serious disease that increases the risk of cardiovascular disease including heart attacks and stroke and, in its most severe form, results in, kidney failure and the need for dialysis or kidney transplant.

Many patients with CKD are elderly with comorbidities making them susceptible to significant health risks.

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Serious TEAEs were lower in Vafseo-treated patients at 49.7% compared to 56.5% for darbepoetin alfa treated patients.

The incidence of TEAEs during the prevalent dialysis patient study ( Conversion ) in the Vafseo-treated patients was 88.3%, and 89.3% in darbepoetin alfa treated patients.

The incidence of TEAEs during the prevalent dialysis patient study (Conversion) in the

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Vafseo-treated patients was 88.3%, and 89.3% in darbepoetin alfa treated patients.

During the study, the most common TEAEs reported in Vafseo/darbepoetin alfa treated patients were diarrhea (13.0%/ 10.1%), pneumonia (11.0%/ 9.7%), hypertension (10.6%/ 13.8%), and hyperkalemia (9.0%/ 10.8%).

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Serious adverse events related to Vafseo, including those noted in the CRL and label, and any other product candidates could have material adverse consequences on the development and potential label expansion of Vafseo or the approval of our other product candidates and our business as a whole.

Our understanding of adverse events in prior clinical trials of our product candidates may change as we gather more information, the FDA may not agree with our assessment of adverse events and additional unexpected adverse events may be observed in future clinical trials or in the market.

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Our understanding of adverse events in prior clinical trials of Vafseo or our product candidates may change as we gather more information, the FDA may not agree with our assessment of adverse events and additional unexpected adverse events may be observed in future clinical trials or in the market.

Any of the above safety data or other occurrences could delay or prevent us from achieving or maintaining marketing approval, harm or prevent sales of Auryxia, Vafseo or any other product or product candidate, including those that may be in-licensed or acquired, increase our expenses and impair or prevent our ability to successfully commercialize Auryxia, Vafseo or any other products or product candidates.

In addition, any post-marketing clinical trials conducted, if successful, may expand the patient populations treated with Auryxia, Vafseo or any other product we acquire or for which we receive marketing approval, within or outside of their current indications or patient populations, which could result in the identification of previously unknown undesirable effects, increased frequency or severity of known undesirable effects, or result in the identification of unexpected safety signals.

In addition, as Vafseo and any other products are commercialized, they will be used in significantly larger patient populations, in less rigorously controlled environments and, in some cases, by less experienced and less expert treating practitioners, than in clinical trials, which could result in increased or more serious adverse effects being reported.

In addition, Vafseo and any other products are commercialized, they will be used in significantly larger patient populations, in less rigorously controlled environments and, in some cases, by less experienced and less expert treating practitioners, than in clinical trials, which could result in increased or more serious adverse effects being reported.

As a result, regulatory authorities, healthcare practitioners, third party payors or patients may perceive or conclude that the use of Auryxia, Vafseo or any other products are associated with serious adverse effects, undermining our commercialization efforts.

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and in other jurisdictions, only a small percentage successfully complete the FDA’s and other regulatory jurisdictions’ marketing approval processes and are commercialized.

Accordingly, even if we are able to obtain the requisite capital to continue to fund our development efforts, we may be unable to successfully obtain regulatory approval for any label expansion for Vafseo or for any product candidate, including those that may be in-licensed or acquired.

Accordingly, even if we are able to obtain the requisite capital to

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continue to fund our development efforts, we may be unable to successfully obtain regulatory approval for any label expansion for Vafseo or for any product candidate, including those that may be in-licensed or acquired.

Further, any product candidate may not receive marketing approval in the U.S.

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On March 27, 2024, the FDA approved our NDA for vadadustat under the trade name Vafseo for the treatment of anemia due to CKD in adults who have been receiving dialysis for at least three months.

Vafseo is currently approved as a treatment for anemia due to CKD for dialysis dependent patients in the U.S., European Union, United Kingdom, Switzerland and Australia.

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In Taiwan and South Korea, Vafseo is approved for the treatment of symptomatic anemia due to CKD in adult patients on chronic maintenance dialysis.

We are not permitted to market Vafseo in any additional jurisdictions until the requisite approval from regulatory authorities in such jurisdiction is received.

We are not permitted to market Vafseo in any additional jurisdictions or other indications until the requisite approval from regulatory authorities in such jurisdiction is received.

As a condition to receiving marketing approval for Vafseo in additional territories or for other indications, we may be required by regulatory authorities to conduct additional preclinical studies or clinical trials.

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However, we may be required to complete additional clinical trials before seeking approval for additional indications, which are time consuming and expensive, and even though Vafseo is approved as a treatment for anemia due to CKD for dialysis dependent patients, we may not be successful in any of our lifecycle management or label expansion opportunities in the timeframe anticipated by us, or at all.

For example, we plan to start a Phase 3 trial in the second half of 2025 to potentially expand the Vafseo label to include the treatment of late-stage NDD-CKD patients, however, we may not successfully demonstrate safety and/or efficacy needed to obtain regulatory approval or we may be unable to complete the trial when anticipated or at all.

If we do not obtain the approval of label expansion for the treatment of adult patients with NDD-CKD or for alternative dosing in a timely manner, or at all, it could impact future revenue and have an adverse effect on our business.

Obtaining marketing approval in the U.S.

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Pursuant to the sunset clause under EU law, the EC’s approval of Fexeric in the EU was contingent on, among other things, our commencing marketing of Fexeric within three years;

although we successfully negotiated an extension to December 23, 2019, we did not commence marketing

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Fexeric by such date and therefore the Fexeric approval in the EU has ceased to be valid.

In April 2024, our partner Averoa submitted its marketing authorization application for ferric citrate in Europe and the application is still under review.

although we successfully negotiated an extension to December 23, 2019, we did not commence marketing Fexeric by such date and therefore the Fexeric approval in the EU has ceased to be valid.

In April 2024, our partner Averoa submitted its marketing authorization application for ferric citrate in Europe.

In March 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion recommending the European Commission, or EC , to approve Averoa’s marketing authorization.

The final EC decision is expected on June 1, 2025.

Safety concerns with a given product may impact marketing approval.

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or certain other jurisdictions or for some or all of the indications for which we seek approval.

Changes in or the enactment of additional statutes, promulgation of regulations or issuance of guidance during preclinical or clinical development, or comparable changes in the regulatory review process for each submitted product application, may cause delays in the approval or rejection of an application.

For example, in December 2022, with the passage of FDORA, Congress required sponsors to develop and submit a diversity action plan, or DAP , for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product.

These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA-regulated products.

In June 2024, as mandated by FDORA, the FDA issued draft guidance outlining the general requirements for DAPs.

Further, on January 31, 2022, the new Clinical Trials Regulation (EU) No 536/2014 became applicable in the EU and replaced the prior Clinical Trials Directive 2001/20/EC.

The new regulation aims at simplifying and streamlining the authorization, conduct and transparency of clinical trials in the EU.

Under the new coordinated procedure for the approval of clinical trials, the sponsor of a clinical trial to be conducted in more than one EU Member State will only be required to submit a single application for approval.

The submission will be made through the Clinical Trials Information System, a new clinical trials portal overseen by the EMA and available to clinical trial sponsors, competent authorities of the EU Member States and the public.

We have not previously secured authorization to conduct clinical studies in the EU pursuant to this new regulation and, accordingly, there is a risk that we may be delayed in commencing such studies.

The FDA or other regulatory authorities may delay, limit or deny approval of any product candidate for many reasons including, among others:

• the results of our clinical trials may only be modestly positive, or there may be concerns with the profile due to efficacy or safety;

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• the results of our clinical trials may not meet the level of statistical or clinical significance required by the relevant regulatory authority for review and/or marketing approval;

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• the relevant regulatory authority may grant approval contingent on the performance of costly post-marketing clinical trials;

• the relevant regulatory authority’ s onsite inspections may be delayed due to the recent COVID-19 pandemic or otherwise;

• the relevant regulatory authority 's onsite inspections may be delayed;

• we, or our CROs or other vendors, may fail to comply with GxP or fail to pass any regulatory inspections or audits;

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• the relevant regulatory authority could deem that our financial relationships with certain pr incipal investigators constitute a conflict of interest, such that the data from those principal investigators may not be used to support our applications;

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• as part of any future regulatory process, the FDA may ask an Advisory Committee to review portions of the NDA, the FDA may have difficulty scheduling an Advisory Committee meeting in a timely manner or, if convened, an FDA Advisory Committee could recommend non-approval, conditions of approval or restrictions on approval, and the FDA may ultimately agree with the recommendations;

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• the policies or regulations of the relevant regulatory authority may significantly change in a manner that renders our clinical data insufficient for approval or requires us to amend or submit new clinical protocols.

Finally, our ability to develop and market new drug products may be impacted by litigation challenging the FDA’s approval of another company’s drug product.

Moreover, principal investigators for our future clinical trials may serve as scientific advisors or consultants to us and receive compensation in connection with such services.

Under certain circumstances, we may be required to report some of these relationships to the FDA or comparable foreign regulatory authorities.

The FDA or a comparable foreign regulatory authority may conclude that a financial relationship between us and a principal investigator has created a conflict of interest or otherwise affected interpretation of the study.

The FDA or comparable foreign regulatory authority may therefore question the integrity of the data generated at the applicable clinical trial site and the utility of the clinical trial itself may be jeopardized.

This could result in a delay in approval, or rejection, of our marketing applications by the FDA or comparable foreign regulatory authority, as the case may be, and may ultimately lead to the denial of marketing approval of one or more of our product candidates.

In addition, we could be adversely affected by several significant administrative law cases decided by the U.S.

Supreme Court in 2024.

In Loper Bright Enterprises v.

Raimondo, for example, the court overruled Chevron U.S.A., Inc.

Natural Resources Defense Council, Inc., which for 40 years required federal courts to defer to permissible agency interpretations of statutes that are silent or ambiguous on a particular topic.

Supreme Court stripped federal agencies of this presumptive deference and held that courts must exercise their independent judgment when deciding whether an agency such as the FDA acted within its statutory authority under the Administrative Procedure Act, or the APA.

Additionally, in Corner Post, Inc.

Board of Governors of the Federal Reserve System, the court held that actions to challenge a federal regulation under the APA can be initiated within six years of the date of injury to the plaintiff, rather than the date the rule is finalized.

The decision appears to give prospective plaintiffs a personal statute of limitations to challenge longstanding agency regulations.

Another decision, Securities and Exchange Commission v.

Jarkesy, overturned regulatory agencies’ ability to impose civil penalties in administrative proceedings.

These decisions could introduce additional uncertainty into the regulatory process and may result

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in additional legal challenges to actions taken by federal regulatory agencies, including the FDA and CMS, that we rely on.

In addition to potential changes to regulations as a result of legal challenges, these decisions may result in increased regulatory uncertainty and delays and other impacts, any of which could adversely impact our business and operations.

Further, our ability to develop and market new drug products may be impacted by litigation challenging the FDA’s approval of another company’s drug product.

In April 2023, the U.S.

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District Court for the Northern District of Texas challenging the FDA’s actions.

On January 16, 2025, the district court agreed to allow these states to file an amended complaint and continue to pursue this challenge.

Depending on the outcome of this litigation, our ability to develop new drug product candidates and to maintain approval of existing drug products could be delayed, undermined or subject to protracted litigation.

Products approved for marketing are subject to extensive post-marketing regulatory requirements, including post-approval pediatric studies for Auryxia and Vafseo, and could be subject to post-marketing restrictions or withdrawal from the market, and we may be subject to penalties, including withdrawal of marketing approval, if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products, or product candidates, when and if approved.

If we are unable to obtain or maintain marketing approval in jurisdictions outside the United States, we and our partners will not be able to market any of our products or product candidates outside of the United States.

In order to market and sell our products and product candidates in the European Union, Japan and many other jurisdictions, we or our partners must obtain or maintain separate marketing approvals and comply with numerous and varying regulatory requirements.

Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA.

The approval procedure varies among countries and can involve additional testing.

In addition, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries.

The time required to obtain or maintain approval may differ substantially from that required to obtain or maintain FDA approval.

The regulatory approval process outside the United States generally includes all of the risks associated with obtaining or maintaining FDA approval.

In addition, in many countries outside the United States, it is required that the product be approved for reimbursement before the product can be approved for sale in that country.

We and our partners may not obtain or maintain approvals from regulatory authorities outside the United States on a timely basis or at all.

Additionally, we and our partners could face heightened risks with respect to obtaining or maintaining marketing authorizations in the UK as a result of the withdrawal of the UK from the EU, commonly referred to as Brexit.

The UK is no longer part of the European Single Market and EU Customs Union.

As of January 1, 2025, the Medicines and Healthcare Products Regulatory Agency, or MHRA , is responsible for approving all medicinal products destined for the United Kingdom market (i.e., Great Britain and Northern Ireland).

At the same time, a new international recognition procedure, or IRP , will apply, which intends to facilitate approval of pharmaceutical products in the UK.

The IRP is open to applicants that have already received an authorization for the same product from one of the MHRA’s specified Reference Regulators, or RRs.

The RRs notably include EMA and regulators in the EEA member states for approvals in the EU centralized procedure and mutual recognition procedure as well as the FDA (for product approvals granted in the U.S.).

However, the concrete functioning of the IRP is currently unclear.

Any delay in obtaining, maintaining or an inability to obtain or maintain, any marketing approvals may force us or our partners to restrict or delay efforts to seek regulatory approval in the UK for our product candidates, which could significantly and materially harm our business.

In addition, foreign regulatory authorities may change their approval policies and new regulations may be enacted.

For instance, the EU pharmaceutical legislation is currently undergoing a complete review process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020.

The European Commission’s proposal for revision of several legislative instruments related to medicinal products (potentially reducing the duration of regulatory data protection, revising the eligibility for expedited pathways, etc.) was published on April 26, 2023.

On April 10, 2024 the European Parliament adopted a position on the proposal requesting several amendments to the package.

The proposed revisions remain to be agreed and adopted by the European Parliament and European Council and the proposals may therefore be substantially revised before adoption, which is not anticipated before early 2026.

The revisions may, however, have a significant impact on the pharmaceutical industry and our business in the long term.

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regulatory requirements or if we experience unanticipated problems with our products, or product candidates, when and if approved.

Marketing approvals may be subject to limitations on the approved indicated uses for which the product may be marketed, other conditions of approval, or contain requirements or commitments for potentially costly post-marketing studies and surveillance to monitor the safety and efficacy of the product, including REMS, or registries or observational studies.

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In October 2024, we received a letter from the FDA regarding our non-compliance with PREA due to our failure to complete the IDA post-approval pediatric study, and we submitted our response, including a proposal to waive the PMR with regard to the IDA Indication, to the FDA on November 1, 2024.

If the FDA denies our waiver of the PMR with regard to the IDA Indication, or we are unable to complete these studies successfully or have further delays in completing these studies, we will need to inform the FDA, have

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further discussions and, if the FDA finds that we failed to comply with pediatric study requirements, in violation of applicable law, it could institute enforcement proceedings to seize or enjoin the sale of Auryxia, seek civil penalties or other adverse consequences, which would have a material adverse impact on our ability to commercialize Auryxia and our ability to generate revenues from Auryxia.

In March 2025, the FDA granted our waiver of the PMR with regard to the IDA Indication.

If we are unable to complete the study with respect to the Hyperphosphatemia Indication successfully or have further delays in completing the study, we will need to inform the FDA, have further discussions and, if the FDA finds that we failed to comply with the pediatric study requirement with regard to the Hyperphosphatemia Indication, in violation of applicable law, it could institute enforcement proceedings to seize or enjoin the sale of Auryxia, seek civil penalties or other adverse consequences, which would have a material adverse impact on our ability to commercialize Auryxia and our ability to generate revenues from Auryxia.

In addition, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for Auryxia, Vafseo and any other product for which we receive regulatory approval will be subject to extensive and ongoing regulatory requirements and guidance.

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• restrictions on the labeling or marketing of a product;

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• fines, restitution or disgorgement of profits or revenues;

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• anti-corruption and anti-bribery laws, including the FCPA, the UK Bribery Act and various other anti-corruption laws in countries outside of the U.S.;

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• data privacy laws existing in the U.S., the EU, the UK and other countries in which we operate, including the U.S.

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• international trade laws, which are laws that regulate the sale, purchase, import, export, re-export, transfer and shipment of goods, products, materials, services and technology.

In addition, our relationships with healthcare providers, physicians and third party payors expose us to broadly applicable fraud and abuse laws that may constrain the business or financial arrangements and relationships through which we market, sell and distribute Auryxia, Vafseo and any other products for which we may obtain marketing approval.

In addition, our relationships with healthcare providers, physicians and third party payors expose us to broadly applicable fraud and abuse laws that may constrain the business or financial arrangements and relationships through which we market, sell and distribute Auryxia and Vafseo and any other products for which we may obtain marketing approval.

As such, these arrangements are subject to applicable anti-kickback, fraud and abuse, false claims, transparency, health information privacy and security, and other healthcare laws and regulations at federal, state and international levels.

These restrictions include, but are not limited to, the following:

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• the Food, Drug and Cosmetic Act of 1938, as amended, or FDCA , which among other things, strictly regulates drug product marketing and promotion and prohibits manufacturers from marketing such products for off-label use;

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state laws restricting interactions with healthcare providers and other members of the healthcare community or requiring pharmaceutical manufacturers to implement certain compliance standards, which vary from state to state.

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Because of the breadth of these U.S.

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It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations.

If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations, any of which could materially adversely affect our business and would result in increased costs and diversion of management attention and could negatively impact the development, regulatory approval and commercialization of Auryxia or Vafseo, any of which could have a material adverse effect on our business.

If our operations are found to be in violation of any of these laws or any other governmental regulations that may

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apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations, any of which could materially adversely affect our business and would result in increased costs and diversion of management attention and could negatively impact the development, regulatory approval and commercialization of Auryxia or Vafseo, any of which could have a material adverse effect on our business.

Further, if any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from participation in government funded healthcare programs.

In addition, we could be adversely affected by several significant administrative law cases decided by the U.S.

Supreme Court in 2024.

In Loper Bright Enterprises v.

Raimondo , for example, the court overruled Chevron U.S.A., Inc.

Natural Resources Defense Council, Inc ., which for 40 years required federal courts to defer to permissible agency interpretations of statutes that are silent or ambiguous on a particular topic.

The Supreme Court stripped federal agencies of this presumptive deference and held that courts must exercise their independent judgment when deciding whether an agency such as FDA acted within its statutory authority under the Administrative Procedure Act, or APA .

Additionally, in Corner Post, Inc.

Board of Governors of the Federal Reserve System , the court held that actions to challenge a federal regulation under the APA can be initiated within six years of the date of injury to the plaintiff, rather than the date the rule is finalized.

The decision appears to give prospective plaintiffs a personal statute of limitations to challenge longstanding agency regulations.

These decisions could introduce additional uncertainty into the regulatory process and may result in additional legal challenges to actions taken by federal regulatory agencies, including the FDA and CMS, that we rely on.

We will incur significant liability if it is determined that we are promoting any “off-label” use of Auryxia, Vafseo or any other product we may develop, in-license or acquire or if it is determined that any of our activities violates the federal Anti-Kickback Statute.

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for use in any indications other than the Hyperphosphatemia Indication and the IDA Indication, and Vafseo for the treatment of anemia due to CKD in adults who have been receiving dialysis for at least three months, and all promotional claims must be consistent with the FDA-approved labeling for Auryxia or Vafseo, as applicable.

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Promoting a drug off-label is a violation of the FDCA and can give rise to liability under the federal False Claims Act, as well as under additional federal and state laws and insurance statutes.

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Notwithstanding the regulatory restrictions on off-label promotion, the FDA and other regulatory authorities allow companies to engage in truthful, non-misleading, and non-promotional scientific communications concerning their products in certain circumstances.

For example, in October 2023, the FDA published draft guidance outlining the agency’s non-binding policies governing the distribution of scientific information on unapproved uses to healthcare providers.

This draft guidance calls for such communications to be truthful, non-misleading, factual, and unbiased and include all information necessary for healthcare providers to interpret the strengths and weaknesses and validity and utility of the information about the unapproved use.

In addition, under some relatively recent guidance from the FDA and the Pre-Approval Information Securities Exchange Act of 1934, as amended, or the Exchange Act, signed into law as part of the Consolidated Appropriations Act of 2023, or the Consolidated Appropriations Act , companies may also provide information that is consistent with a product’s FDA-approved labeling and proactively speak to formulary committee members of payors regarding data for an unapproved drug or unapproved uses of an approved drug.

For example, in January 2025, the FDA published final guidance outlining the agency’s non-binding policies governing the distribution of scientific information on unapproved uses of approved products to healthcare providers.

This final guidance calls for such communications to be truthful, non-misleading, factual, and unbiased and include all information necessary for healthcare providers to interpret the strengths and weaknesses and validity and utility of the information about the unapproved use.

In addition, under some relatively recent guidance from the FDA and the Pre-Approval Information Securities Exchange Act of 1934, as amended, or the Exchange Act , signed into law as part of the Consolidated Appropriations Act of 2023, or the Consolidated Appropriations Act , companies may also provide information that is consistent with a product's FDA approved-labeling and proactively speak to formulary committee members of payors regarding certain types of data and information for an unapproved drug or unapproved uses of an approved drug.

We intend to engage in these discussions and communicate with healthcare providers, payors and other constituencies in compliance with all applicable laws, regulatory guidance and industry best practices.

Although we believe we have put in place a robust compliance program and processes designed to ensure that all such activities are performed in a legal and compliant manner, such program and processes may not be sufficient to deter or detect all violations, and we will need to carefully navigate the FDA’s various regulations, guidance and policies, along with recently enacted legislation, to ensure compliance with restrictions governing promotion of our products.

In addition, if a company’s activities are determined to have violated the federal Anti-Kickback Statute, this can also give rise to liability under the federal False Claims Act and such violations can result in significant fines, criminal and civil remedies, and exclusion from Medicare and Medicaid.

In addition, if a company’s activities are determined to have violated the federal Anti-Kickback Statute, this will also give rise to liability under the federal False Claims Act and such violations can result in significant fines, criminal and civil remedies, and exclusion from Medicare and Medicaid.

There is increased government focus on relationships between the pharmaceutical industry and physicians, pharmacies (especially specialty pharmacies), and other sources of referrals.

Common industry activities, such as speaker programs, insurance assistance and support, relationships with foundations providing copayment assistance, and relationships with patient organizations and patients are receiving increased governmental attention.

If any of our relationships or activities is determined to violate applicable federal and state anti-kickback laws, false claims laws, or other laws or regulations, the company and/or company executives, employees, and other representatives could be subject to significant fines and criminal sanctions, imprisonment, and potential exclusion from Medicare and Medicaid, and could harm our reputation or result in significant legal expenses and distraction of management.

Disruptions at the FDA, regulatory authorities outside the U.S.

and other government agencies caused by global health concerns or funding shortages could prevent new products and services from being developed or commercialized in a timely manner, which could negatively impact our business.

The ability of the FDA and regulatory authorities outside the U.S.

to review and approve new products can be affected by a variety of factors, including global health concerns, government budget and funding levels, staffing shortages, statutory, regulatory, and policy changes and other events that may otherwise affect the FDA’s or other regulatory authorities’ ability to perform routine functions.

Average review times at the FDA have fluctuated in recent years as a result of certain of these factors.

In addition, government funding of other government agencies that fund R&D activities is subject to the political process, which is inherently fluid and unpredictable.

Disruptions at the FDA and other agencies may increase the time necessary for new drugs to be reviewed or approved by necessary government agencies, which would adversely affect our business.

If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our, or our collaboration partners’, regulatory submissions, which could have a material adverse effect on our business.

If a prolonged government shutdown occurs, or if global health concerns prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

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our relationships or activities is determined to violate applicable federal and state anti-kickback laws, false claims laws, or other laws or regulations, the company and/or company executives, employees, and other representatives could be subject to significant fines and criminal sanctions, imprisonment, and potential exclusion from Medicare and Medicaid, and could harm our reputation or result in significant legal expenses and distraction of management.

Disruptions at the FDA and other government agencies from funding cuts, personnel losses, regulatory reform, government shutdowns and other developments could hinder our ability to obtain guidance from the FDA regarding our clinical development program and develop and secure approval of our product candidates in a timely manner, which would negatively impact our business.

The FDA and comparable regulatory agencies in foreign jurisdictions, such as the EMA and The Committee for Medicinal Products, play an important role in the development of our product candidates by providing guidance on our clinical development programs and reviewing our regulatory submissions, including INDs, requests for special designations and marketing applications.

If these oversight and review activities are disrupted, then correspondingly our ability to develop and secure timely approval of our product candidates could be impacted in a negative manner.

For example, the recent loss of FDA leadership and personnel could lead to disruptions and delays in FDA guidance, or review and approval of our products and product candidates.

Pursuant to President Trump's E.O.

14210, “Implementing the President’s ‘Department of Government Efficiency’ Workforce Optimization Initiative,” the Secretary of HHS announced on March 27, 2025, a reorganization and reduction in force across HHS of approximately 20,000 employees (82,000 to 62,000), with FDA’s workforce to decrease by 3,500 full-time employees.

Shortly thereafter, thousands of employees at the FDA were terminated on April 1, 2025.

Subsequently, there have been reports from the preliminary budget memorandum for HHS that the administration will propose an additional 30% cut in the overall budget for HHS, with a reduction of $700 million in funding at the FDA ($7.2 billion to $6.5 billion) for the 2026 federal fiscal year.

Further, while the FDA’s review of marketing applications and other activities for new drugs and biologics is largely funded through the user fee program established under PDUFA, it remains unclear how the administration’s reduction in force and budget cuts will impact this program and the ability of the FDA to provide guidance and review our product candidates in a timely manner.

For example, while the FDA reduction in force did not reportedly specifically target FDA reviewers, many operations, administrative and policy staff that help support such reviews were affected and those losses could lead to delays in PDUFA reviews and related activities.

In addition, while currently unclear, there is a risk that the reduction in force and budget cutbacks could threaten the integrity of the PDUFA program itself.

That is because, for the FDA to obligate user fees collected under PDUFA in the first place, a certain amount of non-user fee appropriations must be spent on the process for the review of applications plus certain other costs during the same fiscal year.

There is also substantial uncertainty as to how regulatory reform measures being implemented by the Trump Administration across the government will impact the FDA and other federal agencies with jurisdiction over our activities.

For example, since taking office, the President has issued a number of executive orders that could have a significant impact on the manner in which the FDA conducts its operations and engages in regulatory and oversight activities.

These include E.O.

14192, “Unleashing Prosperity Through Deregulation,” January 31, 2025;

14212, “Establishing the President’s Make America Healthy Again Commission,” February 13, 2025;

14219, “Ensuring Lawful Governance and Implementing the President’s ‘Department of Government Efficiency” Deregulatory Initiative,” February 21, 2025.

If these or other orders or executive actions impose constraints on the FDA’s ability to engage in oversight and implementation activities in the normal course, our business may be negatively impacted.

Similarly, actions by the U.S.

government have significantly disrupted the operations of U.S.

government agencies such as the National Institutes of Health, National Science Foundation, Centers for Disease Control and Prevention and FDA, which have traditionally provided funding for basic research, R&D, and clinical testing.

government actions have included, among other things, suspending, terminating and withholding of disbursements of funds owed under ongoing contracts, grants, and other financial assistance agreements;

declining to continue multi-year research projects for additional annual budget periods;

canceling or delaying solicitations for new contract, grant and other financial assistance awards;

canceling or delaying proposal evaluation processes and issuance of such new awards;

substantially reducing federal agency staff responsible for managing contract and financial assistance programs;

eliminating agency information and resources for facilitating research activity;

delaying or terminating federal agency procedures for authorizing international transactions;

initiating aggressive enforcement actions that may disrupt the operations of major research universities that are significant contributors to life sciences research in the U.S., and threatening access to federal agency contracts and other funding awards based on companies’ otherwise lawful corporate policies and choice of counsel.

government actions could, directly or indirectly, significantly disrupt, delay, prevent, or increase the costs of our research and product commercialization programs, including our ability to develop new product candidates, conduct clinical trials, implement research collaborations with other companies or institutions, and obtain approvals to market and sell new products.

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In addition, government funding of the SEC and other government agencies on which our operations may rely, including those that fund R&D activities, is subject to the political process, which is inherently fluid and unpredictable.

For example, over the last several years, the U.S.

government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities.

If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions and could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.

At the same time, disruptions at the FDA and other government agencies may result from public health events similar to the COVID-19 pandemic.

For example, during the pandemic, a number of companies announced receipt of complete response letters due to the FDA’s inability to complete required inspections for their applications.

In the event of a similar public health emergency in the future, the FDA may not be able to continue its current pace and review timelines could be extended.

Regulatory authorities outside the United States facing similar circumstances may adopt similar restrictions or other policy measures in response to a similar public health emergency and may also experience delays in their regulatory activities.

Accordingly, if any of the foregoing developments and others impact the ability of the FDA to provide us with guidance regarding our clinical development programs or delay the agency’s review and processing of our regulatory submissions, including INDs and NDAs, our business would be negatively impacted.

Further, any future government shutdown could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.

Compliance with privacy and data security requirements could result in additional costs and liabilities to us or inhibit our ability to collect and process data globally, and the failure to comply with such requirements could subject us to significant fines and penalties, which may have a material adverse effect on our business, financial condition or results of operations.

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Following the withdrawal of the UK from the EU, the UK Data Protection Act 2018 applies to the processing of personal data that takes place in the UK and includes parallel obligations to those set forth by GDPR.

In relation to data transfers, both the UK and the EU have determined, through separate “adequacy” decisions, that data transfers between the two jurisdictions are in compliance with the UK Data Protection Act and the GDPR, respectively.

In relation to data transfers, both the UK and the EU have determined, through separate “adequacy” decisions, that data transfers between the two jurisdictions

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are in compliance with the UK Data Protection Act and the GDPR, respectively.

The UK and the U.S.

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Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the EU to the U.S.

However, some privacy advocacy groups have already challenged or suggested that they will be challenging the EU-U.S.

However, some privacy advocacy groups have challenged or suggested that they will be challenging the EU-U.S.

Data Privacy Framework.

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Given the breadth and depth of changes in data protection obligations, complying with the GDPR’s requirements is rigorous and time intensive and requires significant resources and a review of our technologies, systems and practices, as well as those of any third party collaborators, service providers, contractors or consultants that process or transfer personal data collected in the EU.

The GDPR and other changes in laws or regulations associated with the enhanced protection of certain types of

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sensitive data, such as healthcare data or other personal information from our clinical trials, could require us to change our business practices and put in place additional compliance mechanisms, may interrupt or delay our development, regulatory and commercialization activities and increase our cost of doing business, and could lead to government enforcement actions, private litigation and significant fines and penalties against us and could have a material adverse effect on our business, financial condition or results of operations.

The GDPR and other changes in laws or regulations associated with the enhanced protection of certain types of sensitive data, such as healthcare data or other personal information from our clinical trials, could require us to change our business practices and put in place additional compliance mechanisms, may interrupt or delay our development, regulatory and commercialization activities and increase our cost of doing business, and could lead to government enforcement actions, private litigation and significant fines and penalties against us and could have a material adverse effect on our business, financial condition or results of operations.

Similar privacy and data security requirements are either in place or underway in the U.S.

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If we violate any consent order that we reach with the FTC, we may be subject to additional fines and compliance requirements.

New laws also are being considered at both the state and federal levels.

Laws also are being considered at both the state and federal levels.

For example, the CCPA, which went into effect on January 1, 2020, and the CPRA, which amends CCPA by expanding the scope and applicability, while also introducing new privacy protections, is creating similar risks and obligations as those created by GDPR.

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Some of the provisions of these laws may apply to our business activities.

There are also states that are strongly considering or have already passed comprehensive privacy laws during the 2023 legislative sessions that will go into effect in 2025 and beyond, including New Hampshire and New Jersey.

Other states will be considering these laws in the future, and Congress has also been debating passing a federal privacy law.

There are also states that are strongly considering or have already passed comprehensive privacy laws during the 2024 legislative sessions that will go into effect in 2025 and beyond.

Other states will be considering similar laws in the future,

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and Congress has also been debating passing a federal privacy law.

There are also states that are specifically regulating health information that may affect our business.

For example, Washington state passed a health privacy law in 2023 that regulates the collection and sharing of health information, and the law also has a private right of action, which further increases the relevant compliance risk.

Connecticut and Nevada have also passed similar laws regulating consumer health data and additional states (including Vermont) are considering such legislation for 2024.

For example, the State of Washington passed the My Health My Data Act in 2023 which specifically regulated health information that is not otherwise regulated by the HIPAA rules, and the law also has a private right of action, which further increases the relevant compliance risk.

Connecticut and Nevada have also passed similar laws regulating consumer health data, and more states are considering such legislation.

These laws may impact our business activities, including our identification of research subjects, relationships with business partners and ultimately the marketing and distribution of our products.

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The rise in these types of lawsuits creates potential risk for our business.

A broad range of legislative measures also have been introduced at the federal level.

Accordingly, failure to comply with current and any future federal and state laws regarding privacy and security of personal information could expose us to fines and penalties.

We also face a threat of potential consumer class actions related to these laws and the overall protection of personal data.

Even if we are not determined to have violated these laws, investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our reputation and our business.

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If we fail to comply with applicable privacy laws, including applicable HIPAA privacy and security standards, we could face civil and criminal penalties.

HHS enforcement activity can result in financial liability and reputational harm, and responses to such enforcement activity can consume significant internal resources.

In recent months, the Officer of Civil Rights, or OCR , has been especially active in enforcing the HIPAA rules.

In addition, state attorneys general are authorized to bring civil actions seeking either injunctions or damages in response to violations that threaten the privacy of state residents.

We cannot be sure how these regulations will be interpreted, enforced or applied to our operations.

In addition to the risks associated with enforcement activities and potential contractual liabilities, our ongoing efforts to comply with evolving laws and regulations at the federal and state level may be costly and require ongoing modifications to our policies, procedures and systems.

Additionally, OCR is looking to amend the HIPAA Security Rule, which (if and when finalized) could create additional compliance obligations and risk for our business.

There are also increased restrictions at the federal level relating to transferring sensitive data outside of the U.S.

to certain foreign countries.

For example, in 2024, Congress passed H.B.

815, which included the Protecting Americans’ Data from Foreign Adversaries Act of 2024.

This law creates certain restrictions for entities that disclose sensitive data (including potential health data) to countries such as China.

Failure to comply with these rules can lead to a potential FTC enforcement action.

Additionally, the Department of Justice recently finalized a rule implementing Executive Order 14117, which creates similar restrictions related to the transfer of sensitive US data to countries such as China.

These data transfer restrictions (and others that may pass in the future) may create operational challenges and legal risks for our business.

Given the breadth and depth of changes in data protection obligations, complying with the GDPR’s requirements is rigorous and time intensive and requires significant resources and a review of our technologies, systems and practices, as well as those of any third-party collaborators, service providers, contractors or consultants that process or transfer personal data collected in the European Union.

The GDPR and other changes in laws or regulations associated with the enhanced protection of certain types of sensitive data, such as healthcare data or other personal information from our clinical trials, could require us to change our business practices and put in place additional compliance mechanisms, may interrupt or delay our development, regulatory and commercialization activities, and could lead to government enforcement actions, private litigation and significant fines and penalties against us, all of which could increase our cost of doing business and have a material adverse effect on our business, financial condition or results of operations.

Similarly, failure to comply with federal and state laws regarding privacy and security of personal information could expose us to fines and penalties under such laws.

Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our reputation and our business.

Further, we cannot assure you that our third-party service providers with access to our or our customers’, suppliers’, trial patients’ and employees’ personally identifiable and other sensitive or confidential information in relation to which we are responsible will not breach contractual obligations imposed by us, or that they will not experience data security breaches or attempts thereof, which could have a corresponding effect on our business, including putting us in breach of our obligations under privacy laws and regulations and/or which could in turn adversely affect our business, results of operations and financial condition.

We cannot assure you that our contractual measures and our own privacy and security-related safeguards will protect us from the risks associated with the third-party processing, storage and transmission of such information.

Legislative and regulatory healthcare reform may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain for any products that are approved in the U.S.

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and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of any product candidate, restrict or regulate post-approval activities and affect our ability to profitably sell Auryxia and Vafseo.

The pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by legislative initiatives.

The pharmaceutical industry has

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been a particular focus of these efforts and has been significantly affected by legislative initiatives.

Current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and additional downward pressure on the price that we receive for any FDA approved product, such as Auryxia or Vafseo or any reimbursement that physicians receive for administering any approved product.

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At the federal level, Congress and the current administration have each indicated that it will continue to seek new legislative and/or administrative measures to control drug costs.

For example, the former administration issued several executive orders intended to lower the costs of prescription products and certain provisions in these orders have been incorporated into regulations.

These regulations include an interim final rule implementing a most favored nation model for prices that would tie Medicare Part B payments for certain physician-administered pharmaceuticals to the lowest price paid in other economically advanced countries, effective January 1, 2021.

That rule, however, has been subject to a nationwide preliminary injunction and, on December 29, 2021, CMS issued a final rule to rescind it.

With issuance of this rule, CMS stated that it will explore all options to incorporate value into payments for Medicare Part B pharmaceuticals and improve beneficiaries’ access to evidence-based care.

In addition, in October 2020, the HHS and the FDA published a final rule allowing states and other entities to develop a Section 804 Importation Program to import certain prescription drugs from Canada into the U.S.

That regulation was challenged in a lawsuit by the Pharmaceutical Research and Manufacturers of America, or PhRMA , but the case was dismissed by a federal district court in February 2023 after the court found that PhRMA did not have standing to sue HHS.

Seven states (Colorado, Florida, Maine, New Hampshire, New Mexico, Texas and Vermont) have passed laws allowing for the importation

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of drugs from Canada.

Seven states (Colorado, Florida, Maine, New Hampshire, New Mexico, Texas and Vermont) have passed laws allowing for the importation of drugs from Canada.

North Dakota and Virginia have passed legislation establishing workgroups to examine the impact of a state importation program.

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The state will also need to relabel the drugs and perform quality testing of the products to meet FDA standards.

Further, on July 9, 2021, President Biden signed Executive Order 14063, which focuses on, among other things, the price of pharmaceuticals.

The Order directs HHS to create a plan within 45 days to combat “excessive pricing of prescription pharmaceuticals and enhance domestic pharmaceutical supply chains, to reduce the prices paid by the federal government for such pharmaceuticals, and to address the recurrent problem of price gouging.” On September 9, 2021, HHS released its plan to reduce pharmaceutical prices.

The key features of that plan are to:

(a) make pharmaceutical prices more affordable and equitable for all consumers and throughout the health care system by supporting pharmaceutical price negotiations with manufacturers;

(b) improve and promote competition throughout the prescription pharmaceutical industry by supporting market changes that strengthen supply chains, promote biosimilars and generic drugs, and increase transparency;

and (c) foster scientific innovation to promote better healthcare and improve health by supporting public and private research and making sure that market incentives promote discovery of valuable and accessible new treatments.

As an oral drug, Auryxia was covered by Medicare under Part D until January 1, 2025.

In January 2011, CMS implemented the ESRD PPS, a prospective payment system for dialysis treatment.

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As of January 2025, oral ESRD-related drugs without injectable or intravenous equivalents, including Auryxia and all other phosphate lowering medications, are included in the ESRD bundle and separate Medicare payment for these drugs are no longer available, but ESRD facilities will receive a TDAPA for Auryxia for a period of at least two years starting on January 1, 2025.

The TDAPA provides separate payment based on the drug's ASP that will be in addition to the base rate in order to facilitate the adoption of innovative therapies.

If the TDAPA reimbursement amount for Auryxia or Vafseo is lower than anticipated, or if TDAPA is eliminated, it would have an adverse impact on our revenue.

In July 2024, Ardelyx filed a complaint in the United States District Court for the District of Columbia against HHS, CMS and other parties, which alleged that CMS’s plan to include oral-only phosphate lowering therapies in the ESRD PPS violated its statutory and regulatory authority under the Medicare Improvements for Patients and Providers Act, which established the ESRD PPS bundled payment system for dialysis services.

In October 2024, Ardelyx filed a motion for a preliminary injunction to enjoin CMS from including oral-only phosphate lowering therapies in the ESRD PPS.

CMS had earlier filed a motion to dismiss the complaint on jurisdictional grounds.

On November 8, 2024, the district court denied Ardelyx’s motion for a preliminary injunction and it granted the government’s motion to dismiss.

Thereafter, Ardelyx moved for reconsideration, but the district court also denied that request.

On December 26, 2024, Ardelyx filed a notice of appeal with the US Court of Appeals for the DC Circuit.

If Ardelyx is successful in its claims, oral-only phosphate lowering therapies, including Auryxia, may be removed from the ESRD bundle, which could reduce anticipated revenue for Auryxia.

On August 16, 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law by President Biden.

The new legislation has implications for Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for outpatient prescription drug coverage.

The legislation has implications for Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for outpatient prescription drug coverage.

Among other things, the IRA imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023);

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However, there are many variables that are outside of our control and if we increase the price of Auryxia or Vafseo faster than the pace of inflation, we would be subject to additional rebates under Medicare, which could have a material adverse effect on our product revenues.

As an oral drug, Auryxia is covered by Medicare under Part D.

In January 2011, CMS implemented the ESRD PPS, a prospective payment system for dialysis treatment.

ESRD facilities may nonetheless receive a TDAPA for new renal dialysis drugs and biological products that meet certain criteria for a period of at least two years.

The TDAPA will provide separate payment based on the drug's ASP that will be in addition to the base rate in order to facilitate the adoption of innovative therapies.

In July 2023, the U.S.

House of Representatives introduced the Patient Act and the Senate advanced a similar bill, which legislation, if passed and enacted into law prior to January 1, 2025, would delay the inclusion of phosphorus lowering drugs in the bundled payment.

In addition, in July 2024, Ardelyx filed a complaint in the United States District Court for the District of Columbia against HHS, CMS and other parties, which alleged that CMS’s plan to include oral-only phosphate lowering therapies in the ESRD PPS violated its statutory and regulatory authority under the Medicare Improvements for Patients and Providers Act, which established the ESRD PPS bundled payment system for dialysis services in 2008.

In October 2024, Ardelyx filed for a preliminary injunction to enjoin CMS from including oral-only phosphate lowering therapies in the ESRD PPS.

CMS had earlier filed a motion to dismiss the complaint.

The court has not scheduled a date for oral argument on these motions and, instead, indicated that it may address these motions on the papers alone.

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Specifically, with respect to price negotiations, Congress authorized Medicare to negotiate lower prices for certain costly single-source drug and biologic products that do not have competing generics or biosimilars and are reimbursed under Medicare Part B and Part D.

With respect to price negotiations, Congress authorized Medicare to negotiate lower prices for certain costly single-source drug and biologic products that do not have competing generics or biosimilars and are reimbursed under Medicare Part B and Part D.

CMS may negotiate prices for ten high-cost drugs paid for by Medicare Part D starting in 2026, followed by 15 Part D drugs in 2027, 15 Part B or Part D drugs in 2028, and 20 Part B or Part D drugs in 2029 and beyond.

This provision applies to drug products that have been approved for at least 9 years and biologics that have been licensed for 13 years, but it does not apply to drugs and biologics that have been approved for a single rare disease or condition.

The first cycle of negotiations for the Medicare Drug Price Negotiation Program commenced in the summer of 2023.

On August 15, 2024, HHS published the results of the first Medicare drug price negotiations for ten selected drugs that treat a range of conditions, including diabetes, CKD and rheumatoid arthritis.

The prices of these ten drugs will become effective January 1, 2026.

On October 2, 2024, in final guidance, CMS indicated that it will announce the selection of up to 15 additional drugs covered by Part D for the second cycle of negotiations by February 1, 2025.

Subsequently, on January 17, 2025, HHS announced its selection of 15 additional drugs covered by Part D for the second cycle of negotiations.

This second cycle of negotiations with participating drug companies will occur during 2025, and any negotiated prices for this second set of drugs will be effective starting January 1, 2027.

CMS issued a public statement on January 29, 2025, declaring that lowering the cost of prescription drugs is a top priority of the new administration and CMS is committed to considering opportunities to bring greater transparency in the negotiation program.

Further, the legislation subjects drug manufacturers to civil monetary penalties and a potential excise tax for failing to comply with the legislation by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law or for taking price increases that exceed inflation.

The legislation also requires manufacturers to pay rebates for drugs in Medicare Part D whose price increases exceed inflation.

The new law also caps Medicare out-of-pocket drug costs at an estimated $4,000 a year in 2024 and, thereafter beginning in 2025, at $2,000 a year.

The law also caps Medicare out-of-pocket drug costs at an estimated $2,000.

On June 6, 2023, Merck & Co.

filed a lawsuit against HHS and CMS asserting that, among other things, the IRA’s Drug Price Negotiation Program for Medicare constitutes an uncompensated taking in violation of the Fifth Amendment of the Constitution.

filed a lawsuit against the HHS and CMS asserting that, among other things, the IRA’s Drug Price Negotiation Program for Medicare constitutes an uncompensated taking in violation of the Fifth Amendment of the Constitution.

Subsequently, a number of other parties, including the U.S.

Chamber of Commerce, Bristol Myers Squibb Company, the PhRMA, Astellas, Novo Nordisk, Janssen Pharmaceuticals, Novartis, AstraZeneca and Boehringer Ingelheim, also filed lawsuits in various courts with similar constitutional claims against HHS and CMS.

Chamber of Commerce, Bristol Myers Squibb Company, the PhRMA, Astellas, Novo Nordisk, Janssen Pharmaceuticals, Novartis, AstraZeneca, Boehringer Ingelheim, and

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Teva also filed lawsuits in various courts with constitutional and Administrative Procedure Act claims against the HHS and CMS.

There have been various decisions by the courts considering these cases since they were filed.

HHS has generally won the substantive disputes in these cases, and various federal district court judges have expressed skepticism regarding the merits of the legal arguments being pursued by the pharmaceutical industry.

Certain of these cases are now on appeal and oral arguments were held on October 30, 2024.

We expect that litigation involving these and other provisions of the IRA will continue, with unpredictable and uncertain results.

Accordingly, while it is currently unclear how the IRA will be effectuated, we cannot predict with certainty what impact any federal or state health reforms will have on us, but such changes could impose new or more stringent regulatory requirements on our activities or result in reduced reimbursement for our products, any of which could adversely affect our business, results of operations and financial condition.

The HHS has generally won the substantive disputes in these cases or succeeded in getting claims dismissed for lack of standing.

Most of these cases are now on appeal.

On October 30, 2024, the U.S.

Court of Appeals for the Third Circuit heard oral argument in three of these cases.

In April 2025, the U.S.

Court of Appeals for the Second Circuit and the U.S.

Court of Appeals for the Third Circuit heard argument in an additional three cases.

More recently, on April 15, 2025, President Trump issued an Executive Order which directs HHS to take steps to reduce the prices of pharmaceutical products.

The new Order repeats many of the proposals advanced during the first Trump Administration, including directing the FDA to streamline and improve its existing drug importation program so as to make it easier for states to obtain approval without sacrificing the safety or quality of drug products.

Other provisions of the Order relate to the 340B program.

Specifically, one provision calls on the Secretary of HHS to determine the hospital acquisition cost for covered outpatient drugs at hospital outpatient departments and to consider and propose any appropriate adjustments for Medicare payment.

The other provision directs HHS to condition grant funding to certain health centers on those centers passing through the 340B discounts they receive on insulin and injectable epinephrine products to patients who meet certain requirements.

With respect to the IRA’s Medicare drug pricing program, the Order, among other things, calls for alignment in “the treatment of small molecule prescription drugs with that of biological products, ending the distortion that undermines relative investment in small molecule prescription drugs, coupled with other reforms to prevent any increase in overall costs to Medicare and its beneficiaries.”

At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access, marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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• the level of taxes that we are required to pay.

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In addition, in some countries, including EU Member States, the pricing of prescription pharmaceuticals is subject to governmental control.

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Publication of discounts by third party payors or government authorities may lead to further pressure on the prices or reimbursement levels.

If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, the commercial launch of our product and/or product candidates could be delayed, possibly for lengthy periods of time, we or our collaborators may not launch at all in a particular country, we may not be able to recoup our investment in one or more product candidates, and there could be a material adverse effect on our business.

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periods of time, we or our collaborators may not launch at all in a particular country, we may not be able to recoup our investment in one or more product candidates, and there could be a material adverse effect on our business.

Our reporting and payment obligations under the Medicaid Drug Rebate Program, Medicare and other governmental drug pricing programs are complex and may involve subjective decisions.

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Failure to make necessary disclosures and/or to identify contract overcharges can result in allegations against us under the FDCA and other laws and regulations.

Unexpected refunds to the government, and

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responding to a government investigation or enforcement action, would be expensive and time-consuming, and could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

Unexpected refunds to the government, and responding to a government investigation or enforcement action, would be expensive and time-consuming, and could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

Our collaborators are also subject to similar requirements outside of the U.S.

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With the passage of the CREATES Act, we are exposed to possible litigation and damages by competitors who may claim that we are not providing sufficient quantities of our approved products on commercially reasonable, market-based terms for testing in support of their ANDAs, 505(b)(2) NDAs and biosimilar product applications.

In December 2019, former President Trump signed legislation intended to facilitate the development of generic and biosimilar products.

The bill, previously known as the CREATES Act, authorizes sponsors of ANDAs, 505(b)(2) NDAs or biosimilar product applications to file lawsuits against companies holding NDAs or BLAs that decline to provide sufficient quantities of an approved reference drug or biological product on commercially reasonable, market-based terms.

In December 2019, President Trump signed legislation intended to facilitate the development of generic and biosimilar products.

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approved reference drug or biological product on commercially reasonable, market-based terms.

Drug or biological products on FDA’s drug shortage list are exempt from these new provisions unless the product has been on the list for more than six continuous months or the FDA determines that the supply of the product will help alleviate or prevent a shortage.

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We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.

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In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations.

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Risks Related to our Reliance on Third Parties

We depend on collaborations with third parties for the development and commercialization of Auryxia, Riona and Vafseo and if these collaborations are not successful or if our collaborators terminate their agreements with us, we may not be able to capitalize on the market potential of Auryxia, Riona and Vafseo, and our business could be materially harmed.

We depend on collaborations with third parties for the development and commercialization of Auryxia, including an authorized generic version of Auryxia, Riona and Vafseo and, if these collaborations are not successful or if our collaborators terminate their agreements with us, we may not be able to capitalize on the market potential of Auryxia, Riona and Vafseo, and our business could be materially harmed.

We sublicensed the rights to commercialize Riona to JT and Torii in Japan.

We also entered into a collaboration agreement with MTPC to develop and commercialize Vafseo in Japan and certain other Asian countries.

In addition, we granted to Averoa an exclusive license to develop and commercialize ferric citrate in the Averoa Territory.

Furthermore, in May 2023, we entered into a license agreement with Medice, pursuant to which we granted Medice an exclusive license to develop and commercialize Vafseo for the treatment of anemia in patients with CKD in the Medice Territory.

With respect to Vafseo, we entered into a

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collaboration agreement with MTPC to develop and commercialize Vafseo in Japan and certain other Asian countries.

Furthermore, we granted Medice an exclusive license to develop and commercialize Vafseo for the treatment of anemia in patients with CKD in the Medice Territory.

We may form or seek other strategic alliances, joint ventures, or collaborations, or enter into additional licensing arrangements with third parties that we believe will complement or augment our and our partners' commercialization efforts with respect to Auryxia, Riona, Vafseo and any other product candidates.

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This termination by Otsuka may have delayed the launch of Vafseo in Europe or other territories previously licensed to Otsuka or adversely affected how we are perceived in scientific and financial communities.

For example, in August 2023, Medice informed us that their launch of Vafseo in certain countries in the Medice Territory was going to be later than previously anticipated due to the activities required to enable the launch.

For example, in August 2023, Medice informed us that their launch of Vafseo in certain countries in the Medice Territory was going to be later than previously anticipated due to some prerequisite activities required to enable the launch.

If we are unable to maintain our collaborations, we may not be able to capitalize on the market potential of our products or product candidates, and our business could be materially harmed.

In February 2025, in advance of the market entry of generic competition to our branded Auryxia following LoE, we entered into an Authorized Generic Distribution and Supply Agreement with our AG Partner, pursuant to which, on March 20, 2025, our AG Partner began selling an authorized generic version of Auryxia.

We will be relying on our AG Partner for the commercialization of this authorized generic.

If competition, including from generics other than our AG Partner, capture sales or if generics other than our authorized generic are sold at a greater discount to Auryxia’s price than anticipated, it could materially and adversely affect our expected revenues.

In addition, we are responsible for supplying product to our AG Partner, and if there are problems in the supply chain, we could be subject to certain penalties, which could be substantial.

In addition, our current and any future collaborations may not be successful due to a number of important factors, including the following:

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• collaborations may not lead to development or commercialization of products and product candidates, if approved, in the most efficient manner or at all;

• inefficiencies or structural changes in internal operations or processes of our collaborators may lead to increased expenses associated with commercializing a product, including manufacturing costs, rebates, returns and other adjustments which would negatively impact net product revenue;

• inefficiencies or structural changes in internal operations or processes of our collaborators may lead to increased expenses associated with commercializing a product, including manufacturing costs, rebates, product returns and other adjustments which would negatively impact net product revenue;

• a significant change in the senior management team, a change in the financial condition or a change in the business operations, including a change in control or internal corporate restructuring, of any of our collaborators, could result in delayed timelines, re-prioritization of our programs, decreasing resources or funding allocated to support our programs, or termination of the collaborations;

• collaborators may not comply with all applicable regulatory and legal requirements.

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in delayed timelines, re-prioritization of our programs, decreasing resources or funding allocated to support our programs, or termination of the collaborations;

• collaborators may not comply with all applicable regulatory and legal requirements.

If any of these events occur, the market potential of Auryxia, Riona or Vafseo where approved, and any other products or product candidates, could be reduced, and our business could be materially harmed.

If any of these events occur, the market potential of Auryxia, including our authorized generic, Riona or Vafseo, where approved, and any other products or product candidates, could be reduced, and our business could be materially harmed.

Collaborations may also divert resources, including the attention of management and other employees, from other parts of our business, which could have an adverse effect on other parts of our business, and we cannot be certain that the benefits of the collaboration will outweigh the potential risks.

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The royalty revenues under the MTPC Agreement may fluctuate considerably because they depend upon, among other things, the rate of growth of sales of Vafseo in the territory covered by the MTPC Agreement.

Negative fluctuations in these royalty revenues could delay, diminish or eliminate our ability to receive 85% of the Royalty Interest Payments after the Annual Cap is

Negative fluctuations in these royalty revenues could delay, diminish or eliminate our ability to receive 85% of the Royalty Interest Payments after the Annual Cap is achieved in a given calendar year, or our ability to receive 100% of the Royalty Interest Payments after the Aggregate Cap is achieved.

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achieved in a given calendar year, or our ability to receive 100% of the Royalty Interest Payments after the Aggregate Cap is achieved.

We rely upon third parties to conduct all aspects of our product manufacturing and commercial distribution, and in many instances only have a single supplier or distributor, and the loss of these manufacturers or distributors, their failure to supply us on a timely basis, or at all, or their failure to successfully carry out their contractual duties or comply with regulatory requirements, cGMP requirements or guidance could cause delays in or disruptions to our supply chain and substantially harm our business.

supply us on a timely basis, or at all, or their failure to successfully carry out their contractual duties or comply with regulatory requirements, cGMP requirements or guidance could cause delays in or disruptions to our supply chain and substantially harm our business.

We do not have any manufacturing facilities and do not expect to independently manufacture any products or product candidates.

We currently rely, and expect to continue to rely, on third-party manufacturers to produce all of our commercial, clinical and preclinical supply.

We also utilize third parties for the commercial distribution of Auryxia, including wholesale distributors and certain specialty pharmacy providers, and we will utilize third parties for the commercial distribution of Vafseo.

We also utilize third parties for the commercial distribution of Auryxia and Vafseo, including wholesale distributors and certain specialty pharmacy providers.

Our reliance on third-party manufacturers, who have control over the manufacturing process, increases the risk that we will not have or be able to maintain or distribute sufficient quantities of Auryxia, Vafseo or any of our product candidates or the ability to obtain such quantities at an acceptable cost or quality, which could delay, prevent or impair our and our partners' development or commercialization efforts.

We currently rely on a single source supplier for each of Auryxia drug substance and drug product and Vafseo drug substance and drug product, and alternate sources of supply may not be readily available.

We have also engaged Cardinal Health, Inc.

as the exclusive third-party logistics distribution agent for commercial sales of Auryxia.

We currently rely on a single source supplier for Auryxia drug substance and drug product, including our authorized generic, and alternate sources of supply may not be readily available.

We have also engaged Cardinal Health, Inc., as the exclusive third-party logistics distribution agent for commercial sales of Auryxia and Vafseo.

If any of the following occurs, we may not have sufficient quantities of Auryxia, Vafseo or our product candidates to support our clinical trials, development, commercialization, or obtaining and maintaining marketing approvals, which could materially and adversely impact our business and results of operations:

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• any of our third-party distributors fail to perform or encounter any damage or other disruption at their facilities.

If we, or any of our third party manufacturers or distributors cannot or do not perform as agreed or expected, or any of our customers were to experience further shutdowns, delays or other business disruptions, including as a result of catastrophic events, including pandemics, terrorist attacks, wars or other armed conflicts, geopolitical tensions or natural disasters, if they misappropriate our proprietary information, if they terminate their engagements with us, if we terminate our engagements with them, or if there is a significant disagreement, we may be forced to manufacture or distribute the materials ourselves, for which we currently do not have the capabilities or resources, or enter into agreements with other third party manufacturers or distributors, which we may not be able to do in a timely manner or on favorable or reasonable terms, if at all.

If any of these events occur, especially with respect to one of our sole source suppliers, we may not have sufficient quantities of product for the commercialization of Auryxia and/or Vafseo or may experience delays in the development of our products or product candidates, which could materially and adversely impact our business and results of operation.

For example, one of our manufacturers has notified us that it will be discontinuing operations at one site at a future date and then we will only be able to manufacture at their other site.

If we, or any of our third-party manufacturers or distributors cannot or do not perform as agreed or expected, or any of our customers were to experience further shutdowns, delays or other business disruptions, including as a result of catastrophic events, including pandemics, terrorist attacks, wars or other armed conflicts, geopolitical tensions, tariffs, trade agreement disputes, or natural disasters, if they misappropriate our proprietary information, if they terminate their engagements with us, if we terminate our engagements with them, or if there is a significant disagreement, we may be forced to manufacture or distribute the materials ourselves, for which we currently do not have the capabilities or resources, or enter into agreements with other third-party manufacturers or distributors, which we may not be able to do in a timely manner or on favorable or reasonable terms, if at all.

If any of these events occur, especially with respect to one of our sole source suppliers, we may not have sufficient quantities of product for the commercial distribution of Auryxia and/or Vafseo or may experience delays in the development of our products or product candidates, which could materially and adversely impact our business and results of operation.

In addition, if we do not have sufficient quantities of Auryxia, including our authorized generic, or Vafseo to satisfy the requirements of our customer and supply contracts, we may be subject to contractual penalties, which could be substantial.

In some cases, there may be a limited number of qualified replacement manufacturers, or the technical skills or equipment required to manufacture a product or product candidate may be unique or proprietary to the original manufacturer and we may have difficulty transferring such skills or technology to another third party, or a feasible alternative may not exist.

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The delays and costs associated with the qualification of a new manufacturer and validation of manufacturing processes would negatively affect our ability to supply clinical trials, obtain and maintain marketing approval, or commercialize or satisfy patient demand for Auryxia and Vafseo, where approved, in a timely manner, within budget, or at all.

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In addition, the cost of obtaining Auryxia and Vafseo is subject to adjustment based on our third-party manufacturers’ costs of obtaining raw materials and producing the product.

We have limited control over the production costs of Auryxia and Vafseo, including the costs of raw materials, and have seen increases in the production costs of Auryxia and Vafseo, and any significant increase in the cost of obtaining our products could materially adversely affect our revenue for Auryxia and Vafseo.

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Moreover, issues that may arise in any scale-up and technology transfer and continued commercial scale manufacture of our products may lead to significant delays in our development, marketing approval and commercial timelines for new products or affect commercial supply of Auryxia or Vafseo and negatively impact our financial performance.

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This supply interruption was resolved, and we have taken and continue to take actions designed to prevent future interruptions in the supply of Auryxia.

However, we had experienced issues in manufacturing Auryxia, and if we experience manufacturing issues going forward, or incur additional costs, or our actions to prevent future interruptions are not successful, we may experience additional supply issues.

However, we have experienced issues in manufacturing Auryxia, and if we experience manufacturing issues going forward, or incur additional costs, or our actions to prevent future interruptions are not successful, we may experience additional supply issues.

In addition, before we can manufacture product at a new site, we must validate the process at that site.

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If any of these events occur, our reputation and financial condition would be negatively and materially impacted.

In addition, during the year ended December 31, 2022, we had higher write-downs to inventory reserves related to Auryxia drug substance that will not be forward processed into drug product.

If we have additional write-downs to inventory reserves in the future, it could negatively impact our ability to supply Auryxia, and our financial condition could be harmed.

If the FDA, EMA or other regulatory authorities withdraws any approval of the facilities being used to manufacture Auryxia, Vafseo or any of our product candidates, we may need to find alternative manufacturing facilities, which would significantly impact our ability to continue commercializing Auryxia or Vafseo in Japan, or to commercialize Vafseo in Europe and other countries, or to develop, obtain marketing approval for or market Vafseo or our other product candidates, if approved.

Moreover, our failure or the failure of our third party manufacturers or distributors to comply with applicable regulations or guidance, or our failure to oversee or facilitate such compliance, could result in sanctions being imposed on us or our third party manufacturers or distributors, including, where applicable, clinical holds, fines, injunctions, civil penalties, delays in, suspension of or withdrawal of approvals, license revocation, seizures or recalls of Auryxia or Vafseo in Japan, operating restrictions, receipt of a Form 483 or warning letter, or criminal prosecutions, any of which could significantly and adversely affect the supply of Auryxia or Vafseo.

In addition, if we have high amounts of write-downs to inventory reserves in the future, it could negatively impact our ability to supply Auryxia or Vafseo, and our financial condition could be harmed.

Moreover, our failure or the failure of our third-party manufacturers or distributors to comply with applicable regulations or guidance, or our failure to oversee or facilitate such compliance, could result in sanctions being imposed on us or our third-party manufacturers or distributors, including, where applicable, clinical holds, fines, injunctions, civil penalties, delays in, suspension of or withdrawal of approvals, license revocation, seizures or recalls of Auryxia or Vafseo in the U.S., Japan or Europe, operating restrictions, receipt of a Form 483 or warning letter, or criminal prosecutions, any of which could significantly and adversely affect the supply of Auryxia or Vafseo.

For example, we previously conducted three limited, voluntary recalls of Auryxia.

These and any other recalls or any supply, quality or manufacturing issues in the future and any related write-downs of inventory or other consequences could result in significant negative consequences, including reputational harm, loss of customer confidence, and a negative impact on our financials, any of which could have a material adverse effect on our business and

Also, if our starting materials, drug substance or drug product are damaged or lost while in our or our third-party manufacturers’ or distributors' control, it may adversely impact our ability to supply Auryxia or Vafseo, and we may incur significant financial harm.

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results of operations, and may impact our ability to supply Auryxia or Vafseo for clinical and commercial use.

Also, if our starting materials, drug substance or drug product are damaged or lost while in our or our third party manufacturers’ or distributors' control, it may adversely impact our ability to supply Auryxia or Vafseo, and we may incur significant financial harm.

In addition, Auryxia, Vafseo and our product candidates may compete with other products and product candidates for access to third-party manufacturing facilities.

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In addition, in the event that the owners and/or licensors of the rights we license were to enter into bankruptcy or similar proceedings, we could potentially lose our rights to Auryxia or our rights could otherwise be adversely affected, which could prevent us from continuing to commercialize Auryxia.

We currently rely on third parties in China for the manufacture of raw materials, drug substance and drug product for the commercial supply of Vafseo and for early-stage research services.

Our commercialization of Vafseo, or our development of our product candidates could be delayed, prevented or impaired if there are disruptions or delays in obtaining these products or services.

The manufacturing of our drug substance and drug product for commercial supply of Vafseo takes place in China through a third-party manufacturer.

Currently, we rely on a third-party contract manufacturer in China, STA Pharmaceutical Hong Kong Limited, a subsidiary of WuXi AppTec, or WuXi STA , for the manufacture of Vafseo drug substance and drug product for commercial use and will likely continue to rely on foreign CMOs in the future.

Changes in and uncertainty surrounding U.S.

trade policy on tariffs could have a material adverse impact on our business, financial condition and results of operations.

The Trump Administration has recently imposed a series of tariffs on U.S.

trading partners.

On April 2, 2025, the President issued an Executive Order announcing a “baseline” reciprocal tariff of 10% on all U.S.

trading partners effective April 5, 2025, and higher individualized reciprocal tariffs on 57 countries (with certain product exemptions for pharmaceutical-related products, among others).

Previously, the administration had imposed a 25% tariff on Canada and Mexico for goods not covered by the United States-Mexico-Canada Agreement, or USMCA , and tariffs equaling 20% on China.

In response, several countries threatened retaliatory measures, including Canada and China, which then imposed retaliatory tariffs.

Prior to when the country-specific reciprocal tariffs were scheduled to take effect, the administration delayed the effective date of such tariffs for all countries except China.

Sustained uncertainty about, or the further escalation of, trade and political tensions between the United States and China could result in a disadvantageous research and manufacturing environment in China, particularly for U.S.

based companies, including retaliatory restrictions that hinder or potentially inhibit our ability to rely on contract development and manufacturing organizations, or C DMO s, and other service providers that operate in China.

Separately, on April 16, 2025, the U.S.

Department of Commerce, or the Commerce Department , announced an investigation under Section 232 of the Trade Expansion Act of 1962 into imports of pharmaceuticals and pharmaceutical ingredients, including finished drug products, medical countermeasures, critical inputs such as active pharmaceutical ingredients, and key starting materials, and derivative products of those items.

The investigation will examine the impact of these imports on U.S.

national security culminating in a decision by the President whether to take action to remedy any identified threats, including by imposing additional tariffs.

The statute provides that the Commerce Department report must be completed within 270 days of initiation of the investigation and that the President must decide whether to act within 90 days of receiving the report.

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As a result of changes in tariffs that have been announced and/or implemented, and the underlying uncertainty currently surrounding international trade, we could experience a negative impact to our costs of materials and production processes, and supply chain disruptions and delays as a result of any new tariff policies or trade restrictions.

If we are unable to obtain necessary raw materials or product components in sufficient quantity and in a timely manner due to disruptions in the global supply chain caused by macroeconomic events and conditions, the development, testing and clinical trials of our product candidates may be delayed or infeasible, and regulatory approval or commercial launch of any resulting product may be delayed or not obtained, which could significantly harm our business.

We cannot yet predict the effect of the recently imposed U.S.

tariffs on future imports, or the extent to which other countries will impose quotas, duties, tariffs, taxes or other similar restrictions upon imports or exports in the future, nor can we predict future trade policy or the terms of any renegotiated trade agreements and their impact on our business.

Changes in the geopolitical environment, including U.S.

and international trade policies, particularly with respect to China, Europe or Canada, may adversely impact our business and operating results.

Many of our manufacturers and suppliers for Auryxia and Vafseo are located in China, Europe and Canada, and we will likely continue to rely on foreign CMOs in the future.

The manufacturing of our drug product for commercial use of both Auryxia and Vafseo takes place in Canada through a third-party manufacturer, Patheon Inc., or Patheon .

The manufacturing for commercial use of both Auryxia and Vafseo drug substance takes place in France and Spain, respectively.

Also, the manufacturing of our drug substance and drug product for commercial supply of Vafseo takes place in China through a third-party manufacturer, STA Pharmaceutical Hong Kong Limited, a subsidiary of WuXi AppTec, or WuXi STA .

We also rely on third parties in China for the supply of raw materials used in the manufacture of Vafseo and for certain early-stage research services.

Any disruption in production or inability of our manufacturers in China to produce adequate quantities to meet our needs or to perform research services, whether as a result of changes in the regulatory framework in the U.S.

or China, trade war, political unrest or unstable economic conditions in China, or other causes could impair our ability to commercialize Vafseo or to develop our product candidates.

For example, in January 2024, the U.S.

House of Representatives introduced the BIOSECURE Act (H.R.

7085) and the Senate advanced a substantially similar bill (S.3558), which legislation, if passed and enacted into law, would have the potential to restrict the ability of U.S.

biopharmaceutical companies like us to purchase services or products related to biological materials from, or otherwise collaborate with, certain Chinese biotechnology companies “of concern” without losing the ability to contract with, or otherwise receive funding from, the U.S.

It is possible some of our contractual counterparties, including WuXi STA, could be impacted by this legislation, which, depending on the scope of the final legislation if enacted, could adversely affect our business.

Trade tensions and conflicts between the U.S.

and China, Europe, Canada or other countries have recently been escalating and, as such, we are exposed to the possibility of product supply disruption and increased costs and expenses in the event of changes to the laws, rules, regulations and policies of the governments of the U.S., China, Europe, Canada or other countries, trade agreement disputes or due to geopolitical unrest and unstable economic conditions.

In addition, certain Chinese biotechnology companies may become subject to trade restrictions, sanctions, other regulatory requirements or proposed legislation by the U.S.

government, which could restrict or even prohibit our ability to work with such entities, thereby potentially disrupting their supply of material to us.

For example, in February 2024, U.S.

lawmakers called for investigations into and the imposition of possible economic sanctions against Chinese biotechnology companies WuXi AppTec and WuXi Biologics, or collectively WuXi , over alleged ties to the Chinese military.

Escalating tensions between the United States and China may prevent or hinder the export of materials or technical information between us and our CDMO and third parties, such as pharmaceutical manufacturers.

These third parties may voluntarily require compliance or supply chain requirements that go above and beyond potential legislation to address perceived risk of “pass through,” which would make it difficult for us to operate our business.

In addition, in September 2024 during the 118 th Congress, the U.S.

House of Representatives passed the BIOSECURE Act (H.R.

This bill names the following as biotechnology companies of concern:

BGI, MGI, Complete Genomics, WuXi AppTec, and WuXi Biologics.

The Senate advanced a substantially similar bill (S.

3558) but it did not pass.

The Senate bill named the following as biotechnology companies of concern:

BGI, MGI, Complete Genomics, WuXi AppTec, and any subsidiary, parent affiliate, or successor of such entities.

If this legislation had been enacted into law, and while both bills had certain grandfather provision, the legislation would have potentially restricted the ability of U.S.

biotechnology companies like ours to purchase services or products from, or otherwise collaborate with, specifically named Chinese biotechnology companies, including WuXi, and it would have authorized the U.S.

government to impose such restrictions on entities' transactions with additional Chinese biotechnology companies as a condition of U.S.

government contract, grant and loan funding.

We anticipate these bills will be reintroduced during the 119 th Congress but, as of February 20, 2025, they have not been introduced in either chamber.

If these bills become law, or similar laws are passed, they would have the potential to severely restrict the ability of companies like ours to contract with certain Chinese biotechnology companies of concern without losing the ability to contract with, or otherwise receive funding from, the U.S.

Such disruptions could have adverse effects on our ability to commercialize Auryxia and Vafseo or the development of our product candidates and our business operations.

Any unfavorable government policies on international trade, such as export controls, capital controls or tariffs, may increase the cost of manufacturing our products and product candidates, affect the demand for our products, the competitive position of our products or product candidates, and import or export of raw materials and finished product candidate used in our preclinical studies and clinical trials, particularly with respect to any product candidates and materials that we import from China and Canada, including pursuant to our manufacturing service arrangements with WuXi STA and Patheon.

If any new tariffs, export controls, legislation and/or regulations are implemented, or if existing trade agreements are renegotiated or, in particular, if either the U.S., Chinese, European, Canadian or other government takes retaliatory trade actions due to the

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The biopharmaceutical industry in China is strictly regulated by the Chinese government.

Changes to Chinese regulations or government policies affecting biopharmaceutical companies are unpredictable and may have a material adverse effect on our service providers in China, which could have an adverse effect on our business, financial condition, results of operations and prospects.

Evolving changes in China’s public health, economic, political, and social conditions and the uncertainty around China’s relationship with other governments, such as the United States and the UK, could also negatively impact our ability to manufacture Vafseo or other product candidates or have an adverse effect on our ability to secure government funding, which could adversely affect our financial condition and cause us to delay the commercialization of Vafseo or other product candidates.

recent trade tensions, such changes could have an adverse effect on our business, financial condition and results of operations.

Risks Related to our Intellectual Property

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The laws of the European Patent Convention, for example, provide for post-grant opposition procedures that permit competitors to challenge, or oppose, our European patents administratively at the European Patent Office, or EPO.

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post grant review, interference proceedings or other patent office proceedings or litigation, in the U.S.

We may become involved in addressing patentability objections based on third party submission of references, or we may become involved in defending our patent rights in oppositions, derivation proceedings, reexamination, inter partes review, post grant review, interference proceedings or other patent office proceedings or litigation, in the U.S.

or elsewhere, challenging our patent rights or the patent rights of others.

An adverse result in any such proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow third parties to commercialize our technology or products and compete directly with us, without payment to us.

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The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may be challenged on such a basis in the courts or patent offices in the U.S.

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Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage for our products and product candidates from the intellectual property that we develop or license.

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The intellectual property that we own or have licensed and related non-patent exclusivity relating to our current and future products is, and may be, limited, which could adversely affect our ability to compete in the market and adversely affect the value of Auryxia, Vafseo or other future products.

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For example, a third party may design around our owned or licensed composition of matter patent claims or market a product for the methods of use not covered by our owned or licensed patents.

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Obtaining proof of direct infringement by a competitor for a method of use patent requires us to demonstrate that the competitors make and market a product for the patented use(s).

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In addition, any limitations of our patent protection described above may adversely affect the value of our drug product and may inhibit our ability to obtain a collaboration partner at terms acceptable to us, if at all.

In addition to patent rights in the U.S., we may seek non-patent exclusivity for Vafseo and other future products under other provisions of the FDCA such as new chemical entity, or NCE , exclusivity, or exclusivity for a new use or new formulation, but there is no guarantee that Vafseo or any other future products will receive such exclusivity.

In addition to patent rights in the U.S., we may seek non-patent exclusivity for any approved or future products under other provisions of the FDCA such as new chemical entity, or NCE , exclusivity, or exclusivity for a new use or new formulation, but there is no guarantee that any products will receive such exclusivity.

The FDCA provides a five-year period of non-patent exclusivity within the U.S.

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A drug is an NCE if the FDA has not previously approved any other new drug containing the same active moiety, which consists of the molecule(s) or ion(s) responsible for the action of the drug substance (but not including those portions of the molecule that cause it to be a salt or ester or which are not bound to the molecule by covalent or similar bonds).

Vafseo was granted NCE status following its approval in March 2024 and received a five-year NCE exclusivity.

During the exclusivity period, the FDA may not accept for review an ANDA or a 505(b)(2) NDA submitted by another company for another version of such drug where the sponsor does not own or have a legal right of reference to all the data required for approval.

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In addition to NCE, in the U.S., the FDA has the authority to grant additional regulatory exclusivity protection for approved drugs where the sponsor conducts specified testing in pediatric or adolescent populations.

If granted, this pediatric exclusivity may provide an additional six months which are added to the term of any non-patent exclusivity that has been awarded as

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well as to the regulatory protection related to the term of a relevant patent, to the extent these protections have not already expired.

If granted, this pediatric exclusivity may provide an additional six months which are added to the term of any non-patent exclusivity that has been awarded as well as to the regulatory protection related to the term of a relevant patent, to the extent these protections have not already expired.

In addition, foreign regulatory authorities may change their approval policies and new regulations may be enacted regarding non-patent exclusivity.

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The EC’s proposal for revision of several legislative instruments related to medicinal products, which may reduce the duration of regulatory data protection and exclusivity periods for orphan drugs, and revise the eligibility for expedited pathways in addition to other changes, was published on April 26, 2023.

On April 10, 2024, the European Parliament adopted a position on the proposal requesting several amendments to the package.

On April 10, 2024, the European Parliament adopted a position on the proposal

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requesting several amendments to the package.

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Although the composition and use of Auryxia is currently claimed by 3 issued patents that are listed in the FDA’s Orange Book, or OB , and the composition and use of Vafseo is currently claimed by 13 issued patents that are listed in the OB, we cannot assure you that we will be successful in defending against third parties attempting to invalidate or design around our patents or asserting that our patents are invalid or otherwise unenforceable or not infringed, or in competing against third parties introducing generic equivalents of Auryxia, Vafseo or any of our potential future products.

If our Orange Book-listed patents are successfully challenged by a third party and a generic version of Auryxia or Vafseo is approved and launched sooner than we anticipate, revenue from Auryxia or Vafseo, respectively, could decline significantly, which would have a material adverse effect on our sales, results of operations and financial condition.

If our OB-listed patents are successfully challenged by a third party and a generic version of Auryxia or Vafseo is approved and launched sooner than we anticipate, revenue from Auryxia or Vafseo, respectively, could decline significantly, which would have a material adverse effect on our sales, results of operations and financial condition.

We previously received Paragraph IV certification notice letters regarding ANDAs submitted to the FDA requesting approval for generic versions of Auryxia tablets (210 mg ferric iron per tablet).

We filed complaints for patent infringement relating to such ANDAs, and subsequently entered into settlement and license agreements with all such ANDA filers that allow such ANDA filers to market a generic version of Auryxia in the U.S.

beginning on March 20, 2025.

We filed complaints for patent infringement relating to such ANDAs, and subsequently entered into settlement and license agreements with all such ANDA filers that allowed such ANDA filers to market a generic version of Auryxia in the U.S.

as of March 20, 2025.

It is possible that we may receive Paragraph IV certification notice letters from additional ANDA filers and may not ultimately be successful in an ANDA litigation.

While we expect that the availability of the authorized generic version of Auryxia and any additional generic versions of Auryxia will negatively impact our net product revenue for Auryxia and our results of operations, it is difficult to estimate the impact of generics on Auryxia net product revenue, and if the impact is greater than we currently anticipate, it may materially adversely impact our business and results of operations.

Generic competition for Auryxia or any of our potential future products could have a material adverse effect on our sales, results of operations and financial condition.

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Our commercial success depends in part on our avoiding infringement of the patents and proprietary rights of third parties.

However, there may be patents of third parties of which we are currently unaware with claims to compounds, materials,

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formulations, methods of manufacture or methods for treatment related to the use or manufacture of our product candidates.

However, there may be patents of third parties of which we are currently unaware with claims to compounds, materials, formulations, methods of manufacture or methods for treatment related to the use or manufacture of our product candidates.

Also, because patent applications can take many years to issue, there may be currently pending patent applications which may later result in issued patents that our product candidates may infringe.

The pharmaceutical and biotechnology industries are characterized by extensive litigation over patent and other intellectual property rights.

We have in the past and may in the future become a party to, or be threatened with, future adversarial litigation or other proceedings regarding intellectual property rights with respect to our product and product candidates.

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in the past and may in the future become a party to, or be threatened with, future adversarial litigation or other proceedings regarding intellectual property rights with respect to our product and product candidates.

As the pharmaceutical and biotechnology industries expand and more patents are issued, the risk increases that our product candidates may give rise to claims of infringement of the patent rights of others.

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There can be no assurance they do not, however, and competitors or other parties may assert that we infringe their proprietary rights in any event.

FibroGen has filed patent applications in the U.S.

FibroGen, Inc., or FibroGen , has filed patent applications in the U.S.

and other countries directed to purportedly new methods of using previously known heterocyclic carboxamide compounds for purposes of treating or affecting specified conditions, and some of these applications have since issued as patents.

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Interference proceedings provoked by third parties or brought by the USPTO may be necessary to determine the priority of inventions with respect to our patents or patent applications.

Various administrative proceedings are also available for challenging patents, including interference, reexamination, inter partes review, and post-grant review proceedings before the USPTO or oppositions and other comparable proceedings in

Competitors may initiate an administrative proceeding challenging our issued patents or pending patent applications, which can be expensive and time-consuming to defend.

An adverse result in any current or future defense proceedings could put one or more of our patents at risk of being invalidated, held unenforceable, or interpreted narrowly

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foreign jurisdictions.

Competitors may initiate an administrative proceeding challenging our issued patents or pending patent applications, which can be expensive and time-consuming to defend.

An adverse result in any current or future defense proceedings could put one or more of our patents at risk of being invalidated, held unenforceable, or interpreted narrowly and held not infringed and could put our patent applications at risk of not issuing.

and held not infringed and could put our patent applications at risk of not issuing.

In addition, an unfavorable outcome in any current or future proceeding in which we are challenging third party patents could require us to cease using the patented technology or to attempt to license rights to it from the prevailing party.

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Even if we are successful, participation in interference or other administrative proceedings before the USPTO or a foreign patent office may result in substantial costs and distract our management and other employees.

We are currently involved in an opposition proceeding in the Indian Patent Office.

The proceeding may be ongoing for a number of years and may involve substantial expense and diversion of employee resources from our business.

We are currently involved in opposition proceedings in the Indian Patent Office and the European Patent Office.

The proceedings may be ongoing for a number of years, may be resolved in a manner adverse to the Company and may involve substantial expense and diversion of employee resources from our business, which could have an adverse effect on our business.

In addition, we may become involved in additional opposition proceedings or other legal or administrative proceedings in the future.

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Risks Related to our Business and Managing Growth

If we fail to attract, retain and motivate senior management and qualified personnel, we may be unable to successfully develop and commercialize Auryxia or Vafseo.

If we fail to attract, retain and motivate senior management and qualified personnel, we may be unable to successfully develop and commercialize Auryxia, Vafseo or any of our product candidates.

Recruiting and retaining qualified personnel is critical to our success.

We are also highly dependent on our executives, certain members of our senior management and certain members of our commercial organization.

We are also highly dependent on our executives, certain members of our senior management and certain key personnel.

The loss of the services of our executives, senior managers or other employees could impede the achievement of our research, development, regulatory and commercialization objectives and seriously harm our ability to successfully implement our business strategy.

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In November 2022, we also implemented a reduction of our workforce, by approximately 14% consisting of individuals within our commercial organization as a result of our decision to shift to a strategic account management focused model for our commercial efforts.

In addition, uncertainty related to the outcome of regulatory decisions, could increase attrition.

Losing members of management and other key personnel subjects us to a number of risks, including the failure to coordinate responsibilities and tasks, the necessity to create new management systems and processes, the impact on corporate culture, and the retention of historical knowledge.

Losing members of management and other key personnel could subject us to a number of risks, including the failure to coordinate responsibilities and tasks, the necessity to create new management systems and processes, the impact on corporate culture, and the retention of historical knowledge.

Furthermore, replacing executives, senior managers and other key employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to successfully develop and commercialize Auryxia, Vafseo and any product candidates.

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To that end, we must be able to hire, train, integrate, and retain additional qualified personnel with sufficient experience.

We may be unable to hire, train, retain or motivate these personnel on acceptable terms

We may be unable to hire, train, retain or motivate these personnel on acceptable terms given the intense competition for our personnel from our competitors and other companies throughout our industry, particularly in our geographic region.

Over the last several years, the challenges in recruiting and retaining employees across the pharmaceutical and biotechnology industries have increased substantially due to current industry job market dynamics.

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given the intense competition for our personnel from our competitors and other companies throughout our industry, particularly in our geographic region.

In addition, we rely on contractors, consultants and advisors, including scientific and clinical advisors, to assist us in formulating and executing our R&D and commercialization strategy.

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If additional members of management or other personnel leave, or we are unable to continue to attract and retain high quality personnel, our ability to grow and pursue our business strategy will be limited.

Our cost savings plan and the associated workforce reductions implemented in April, May and November 2022 may not result in anticipated savings, could result in total costs and expenses that are greater than expected and could disrupt our business .

Following receipt of the CRL we implemented a reduction in workforce in April and May 2022 by approximately 42% across all areas of our Company, including several members of management.

The reductions in workforce reflected our determination to refocus our strategic priorities around our commercial product, Auryxia, and our development portfolio, and were steps in a broader cost savings plan to significantly reduce our operating expense profile.

We may not realize, in full or in part, the anticipated benefits, savings and improvements in our cost structure from our restructuring efforts due to unforeseen difficulties, delays or unexpected costs.

We recorded a restructuring charge of approximately $0.2 million and $15.9 million in the years ended December 31, 2023 and 2022, respectively, primarily related to contractual termination benefits including severance, non-cash stock-based compensation expense, healthcare and related benefits.

If we are unable to realize the expected operational efficiencies and cost savings from the restructuring, our operating results and financial condition would be adversely affected.

We also cannot guarantee that we will not have to undertake additional workforce reductions or restructuring activities in the future.

Furthermore, our cost savings plan may be disruptive to our operations, including our commercialization of Auryxia and Vafseo, which could affect our ability to generate product revenue.

In addition, our workforce reductions could yield unanticipated consequences, such as attrition beyond planned staff reductions, or disruptions in our day-to-day operations.

Our workforce reductions could also harm our ability to attract and retain qualified management, scientific, clinical, manufacturing and sales and marketing personnel who are critical to our business.

Any failure to attract or retain qualified personnel could prevent us from successfully commercializing Auryxia and Vafseo, and from successfully developing and commercializing our product candidates in the future.

We will need to hire additional employees to support the commercialization of Vafseo in the U.S., and if we are unsuccessful or delayed in doing so, the potential launch of Vafseo could be delayed.

We may encounter difficulties in managing our growth, including with respect to our employee base, and managing our partnerships and operations successfully.

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These relationships are complex and create numerous risks as we deal with issues that arise.

For example, we supply or have agreed to supply, as applicable, Auryxia in Europe, Vafseo in Japan, Europe, the U.S.

and other territories where it is approved for commercial and clinical use to MTPC, Medice and Averoa, which will require us to successfully manage our limited financial and managerial resources.

For example, we supply or have agreed to supply, as applicable, Auryxia in Europe, Vafseo in Japan, Europe and other territories where it is approved for commercial and clinical use to MTPC, Medice and Averoa, which will require us to successfully manage our limited financial and managerial resources.

In addition, we may not be able to obtain the raw materials or product that we need, or the cost of the raw materials or product may be higher than expected.

If we are unable to successfully manage our supply obligations, our ability to commercialize our products or supply such products to our partners could have a material adverse effect on our relationships with our partners and our results of operations.

Our future financial performance and our ability to commercialize Auryxia and Vafseo where approved, and to compete effectively will depend, in part, on our ability to manage any future growth effectively.

Our future financial performance and our ability to commercialize Auryxia and Vafseo, if and where approved, and to compete effectively will depend, in part, on our ability to manage any future growth effectively.

This future growth will impose significant added responsibilities on the business and members of management.

To manage any future growth, we must continue to implement and improve our managerial, operational and financial systems, procedures and processes.

We may not be able to implement these improvements in an efficient or timely manner and may discover deficiencies in existing systems, procedures and processes.

For example, we recently transitioned to a new enterprise resource planning system and if we encounter any difficulties or issues with the new system it could affect our ability to close our books and complete our financial reporting in a timely manner.

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may not be able to implement these improvements in an efficient or timely manner and may discover deficiencies in existing systems, procedures and processes.

Moreover, the systems, procedures and processes currently in place or to be implemented may not be adequate for any such growth.

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We may not be able to accomplish these tasks, and our failure to accomplish any of them could prevent us from successfully managing and, as applicable, growing our Company.

In addition, we may need to further adjust the size of our workforce as a result of changes to our expectations for our business, which can result in management being required to divert a disproportionate amount of its attention away from our day-to-day activities and devote a substantial amount of time to managing these growth-related activities and related expenses.

In addition, we may need to adjust the size of our workforce as a result of changes to our expectations for our business, which can result in management being required to divert a disproportionate amount of its attention away from our day-to-day activities and devote a substantial amount of time to managing these growth-related activities and related expenses.

Further, we rely on independent third parties to provide certain services to us.

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In addition, any testing by us, as and when required, conducted in connection with Section 404 of the Sarbanes-Oxley Act, or Section 404, or any testing by our independent registered public accounting firm may reveal deficiencies in our internal control over financial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to our consolidated financial statements or identify other areas for further attention or improvement.

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As previously disclosed in our 2024 Form 10-K, we identified a material weakness in our internal control over financial reporting as of December 31, 2024.

A material weakness is a deficiency, or combination of deficiencies, in internal control over financial reporting, such that there is a reasonable possibility that a material misstatement of our annual or interim consolidated financial statements will not be prevented or detected on a timely basis.

Specifically, our management concluded that we did not design and maintain effective controls over the completeness and accuracy of accounting for inventory and inventory related transactions, including inventory reconciliations, calculation of overheads, presentation of inventory in our balance sheet between short-term and long-term and our liabilities related to the calculation of firm purchase commitments.

Our management concluded that we did not design and maintain effective controls over inventory.

Specifically, we did not maintain effective review controls that operated with a sufficient level of precision to evaluate the completeness, accuracy and reasonableness of the product sales forecast, which is used in the evaluation of excess inventory, including the calculation of excess firm purchase commitments and the classification of current and non-current inventory.

For further discussion of the material weakness, see Part I, Item 4, “Controls and Procedures.”

We have taken and plan to continue to take actions to remediate this material weakness, including (i) implementing and documenting new processes and controls to help ensure the completeness and accuracy of our inventory reconciliations, (ii) engaging additional third-party subject matter experts and accounting personnel with U.S.

GAAP experience specific to inventory accounting, (iii) enhancing the accuracy of key reports used to calculate the firm purchase commitment liability and (iv) establishing effective monitoring and oversight controls to help to ensure the completeness and accuracy of inventory included in our financial statements and related disclosures.

We have taken and plan to continue to take actions to remediate this material weakness:

increasing the level of precision of our review controls that support the completeness, accuracy and reasonableness of the sales forecast used to support our inventory evaluations, including the identification and consideration of contrary evidence that could detect a potential error in the sales forecast.

However, we cannot provide assurance that we will be able to correct this material weakness in a timely manner or that our remediation efforts will be adequate to allow us to conclude that our internal control over financial reporting will be effective in the future.

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In addition, our conclusion that we have a material weakness could give rise to increased scrutiny, review, audit and investigation over our accounting controls and procedures, which could then lead to additional areas of deficiency or errors in our financial statements.

We will need to continue to dedicate internal resources, engage outside consultants and maintain a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to remediate the material weakness relating to our accounting for inventory and inventory related transactions described above and any future control deficiencies or material weaknesses, and improve control processes as appropriate, validate through testing that controls are functioning as documented and maintain a continuous reporting and improvement process for internal control over financial

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If we are not able to correct material weaknesses or deficiencies in internal controls in a timely manner or otherwise comply with the requirements of Section 404 in a timely manner, our ability to record, process, summarize and report financial information accurately and within applicable time periods may be adversely affected, and we could be subject to sanctions or investigations by the SEC, the Nasdaq Stock Market or other regulatory authorities as well as stockholder litigation which, even if resolved in our favor, would require additional financial and management resources and could adversely affect the market price of our common stock.

If we are not able to correct material weaknesses or deficiencies in internal controls in a timely manner or otherwise comply with the requirements of Section 404 in a timely manner, our ability to record, process, summarize and report financial information accurately and within applicable time periods may be adversely affected, and we could be subject to sanctions or investigations by the Securities Exchange Commission, or the SEC , the Nasdaq Stock Market or other regulatory authorities as well as stockholder litigation which, even if resolved in our favor, would require additional financial and management resources and could adversely affect the market price of our common stock.

Any failure to maintain or implement required effective internal control over financial reporting, or any difficulties we encounter in their implementation, could result in additional material weaknesses, cause us to fail to meet our reporting obligations or result in material misstatements in our financial statements.

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Inferior internal controls could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our common stock and could also affect our ability to raise capital to fund future business initiatives.

Security breaches and unauthorized use of our information technology systems and information, or the information technology systems or information in the possession of our collaborators and other third parties, could damage the integrity of our clinical trials, impact our regulatory filings, compromise our ability to protect our intellectual property, and subject us to regulatory actions that could result in significant fines or other penalties.

Security breaches and unauthorized use of our information technology systems and information, or the information technology systems or information in the possession of our collaborators, contractors and other third parties, could damage the integrity of our clinical trials, impact our regulatory filings, compromise our ability to protect our intellectual property, and subject us to regulatory actions that could result in significant fines or other penalties.

We, our collaborators, contractors and other third parties rely significantly upon information technology, and any failure, inadequacy, interruption or security lapse of that technology, including any cybersecurity incidents, could harm our ability to operate our business effectively.

In addition, we and our collaborators, contractors and other third parties rely on information technology networks and systems, including the Internet and artificial intelligence based software, to process, transmit and store clinical trial data, patient information, and other electronic information, and manage or support a variety of business processes, including operational and financial transactions and records, personal identifying information, payroll data and workforce scheduling information.

We purchase most of our information technology from vendors, on whom our systems depend.

We purchase most of our information technology from vendors or service providers, on whom our systems depend.

We rely on commercially available systems, software, tools and monitoring to provide security for the processing, transmission and storage of company and customer information.

In the ordinary course of our business, we and our third party contractors maintain personal and other sensitive data on our and their respective networks, including our intellectual property and proprietary or confidential business information relating to our business and that of our clinical trial patients and business partners.

In the ordinary course of our business, we and our third-party contractors maintain personal and other sensitive data on our and their respective networks, including our intellectual property and proprietary or confidential business information relating

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to our business and that of our clinical trial patients and business partners.

In particular, we rely on CROs and other third parties to store and manage information from our clinical trials.

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The secure maintenance of this sensitive information is critical to our business and reputation.

Companies and other entities and individuals have been increasingly subject to a wide variety of security incidents, cyber-attacks and other attempts to gain unauthorized access to systems and information.

These threats can come from a variety of sources, ranging in sophistication from individual hackers to state-sponsored attacks.

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Cyber threats may be broadly targeted, or they may be custom-crafted against our information systems or those of our vendors or third-party service providers.

A security incident, cyber attack or other unauthorized access to our systems, could affect our ability to operate our business or the ability of our vendors or third-party service providers to provide services pursuant to their contractual obligations.

A security breach, cyberattack or unauthorized access of our clinical data or other data could damage the integrity of our clinical trials, impact our regulatory filings, cause significant risk to our business, compromise our ability to protect our intellectual property, and subject us to regulatory actions, including under the GDPR and CCPA discussed elsewhere in these risk factors and the privacy or security rules under federal, state, or other local laws outside of the U.S.

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Although we take steps to manage and avoid these risks and to be prepared to respond to attacks, our preventive and any remedial actions may not be successful and no such measures can eliminate the possibility of the systems’ improper functioning or the improper access or disclosure of confidential or personally identifiable information such as in the event of cyberattacks.

Security breaches, whether through physical or electronic break-ins, computer viruses, ransomware, impersonation of authorized users, attacks by hackers or other means, can create system disruptions or shutdowns or the unauthorized disclosure of confidential information.

Although we believe our collaborators, vendors and service providers, such as our CROs, take steps to manage and avoid information security risks and respond to attacks, we may be adversely affected by attacks against our collaborators, vendors or service providers, and we may not have adequate contractual remedies against such collaborators, vendors and service providers to remedy any harm to our business caused by such event.

Additionally, outside parties may attempt to fraudulently

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induce employees, collaborators, or other contractors to disclose sensitive information or take other actions, including making fraudulent payments or downloading malware, by using “spoofing” and “phishing” emails or other types of attacks.

Security breaches, whether through physical or electronic break-ins, computer viruses, ransomware, impersonation of authorized users, attacks by hackers or other means, can create system disruptions or shutdowns that impact our business operations or the unauthorized disclosure of confidential information.

Although we believe our collaborators, vendors and service providers, such as our CROs, take steps to manage, mitigate and avoid information security risks and respond to attacks, we may be adversely affected by attacks against our collaborators, vendors or service providers, and we may not have adequate contractual remedies against such collaborators, vendors and service providers to remedy any harm to our business caused by such event.

Additionally, outside parties may attempt to fraudulently induce employees, collaborators, or other contractors to disclose sensitive information or take other actions, including making fraudulent payments or downloading malware, by using “spoofing” and “phishing” emails or other types of attacks.

Our employees may be targeted by such fraudulent activities.

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• divert the attention of our management and key information technology resources.

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Any failure to maintain proper functionality and security of our internal computer and information systems could result in a loss of, or damage to, our data or marketing applications or inappropriate disclosure of confidential or proprietary information, interrupt our operations, damage our reputation, subject us to liability claims or regulatory penalties, under a variety of federal, state or other applicable privacy laws, such as HIPAA, the GDPR, or state data protection laws including the CCPA, harm our competitive position and delay the further development and commercialization of our products and product candidates, or impact our relationships with customers and patients.

Our employees, independent contractors, principal investigators, CROs, CMOs, consultants and vendors may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements and insider trading.

In addition, l aws and regulations governing any international operations we have or may have in the future may require us to develop and implement costly compliance programs.

In addition, laws and regulations governing any international operations we have or may have in the future may require us to develop and implement costly compliance programs.

We are exposed to the risk that our employees, independent contractors, principal investigators, CROs, CMOs, consultants and vendors may engage in fraudulent conduct or other illegal activity.

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equivalents, including those related to insider trading.

We hold a marketing authorization for Vafseo from the TGA, and we conducted our global clinical trials for Vafseo, and may in the future conduct additional trials, in countries where corruption is prevalent, and violations of any of these laws by our personnel or by any of our vendors or agents, such as our CROs or CMOs, could have a material adverse impact on our clinical trials and our business and could result in criminal or civil fines and sanctions.

We conducted our global clinical trials for Vafseo, and may in the future conduct additional trials, in countries where corruption is prevalent, and violations of any of these laws by our personnel or by any of our vendors or agents, such as our CROs or CMOs, could have a material adverse impact on our clinical trials and our business and could result in criminal or civil fines and sanctions.

We are subject to complex laws that govern our international business practices.

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companies and their intermediaries, such as CROs or CMOs, from making improper payments to foreign government officials for the purpose of obtaining or keeping business or obtaining any kind of advantage for the company.

The FCPA also requires companies to keep accurate books and

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records and maintain adequate accounting controls.

The FCPA also requires companies to keep accurate books and records and maintain adequate accounting controls.

A number of past and recent FCPA investigations by the Department of Justice and the SEC have focused on the life sciences sector.

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We are also exposed to risks in connection with any insider trading violations by employees or others affiliated with us.

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The internal controls, policies and procedures, and training and compliance programs we have implemented to deter prohibited practices may not be effective in preventing our employees, contractors, consultants, agents or other representatives from violating or circumventing such internal policies or violating applicable laws and regulations.

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If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, or if any such action is instituted against our employees, consultants, independent contractors, CROs, CMOs, vendors or principal investigators, those actions could have a significant impact on our business, including the imposition of civil, criminal and administrative penalties, damages, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, curtailment of our operations, disclosure of our confidential information and imprisonment, any of which could adversely affect our ability to operate our business and our results of operations.

Our financial statements include long-lived assets, including goodwill and an intangible asset as a result of the Merger.

The intangible asset has become impaired and could become further impaired in the future under certain conditions.

In addition, other long-lived assets, including property and equipment, right-of-use assets or goodwill could become impaired in the future under certain conditions.

Any potential future impairment of property and equipment, our right-of-use assets, goodwill or intangible asset may significantly impact our results of operations and financial condition.

As of September 30, 2024, we had approximately $68.1 million in the aggregate of goodwill and a definite lived intangible asset from the Merger, $2.5 million of property and equipment and $9.3 million right-of-use assets.

In accordance with ASC 350, Goodwill and Other , we are required annually for goodwill, or more frequently upon certain indicators of impairment, to review our estimates and assumptions underlying the fair value of our goodwill and intangible asset.

In addition, under ASC 360, Property, Plant and Equipment , we are required to review our property and equipment and right-of-use assets whenever

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events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable.

Our financial statements include long-lived assets, including goodwill as a result of the Merger.

Other long-lived assets, including property and equipment, right-of-use assets or goodwill, could become impaired in the future under certain conditions.

Any potential future impairment of property and equipment, our right-of-use assets or goodwill may significantly impact our results of operations and financial condition.

As of March 31, 2025, we had approximately $59.0 million of goodwill from the Merger, $1.9 million of property and equipment and $7.1 million right-of-use assets.

In addition, under ASC 360, Property, Plant and Equipment , we are required to review our property and equipment and right-of-use assets whenever events or changes in circumstances indicate that the carrying amount of an asset or asset group may not be recoverable.

Events giving rise to impairment of long-lived assets are an inherent risk in the pharmaceutical industry and often cannot be predicted.

Conditions that could indicate impairment and necessitate such a review include, but are not limited to, Auryxia’s commercial performance, our inability to execute on our strategic initiatives, the deterioration of our market capitalization such that it is significantly below our net book value, a significant adverse change in legal factors, unexpected adverse business conditions, and an adverse action or assessment by a regulator.

Conditions that could indicate impairment and necessitate such a review include, but are not limited to, Auryxia’s and Vafseo's commercial performance, our inability to execute on our strategic initiatives, the deterioration of our market capitalization such that it is significantly below our net book value, a significant adverse change in legal factors, unexpected adverse business conditions, and an adverse action or assessment by a regulator.

To the extent we conclude our long-lived assets have become impaired, we may be required to incur material write-offs relating to such impairment and any such write-offs could have a material impact on our future operating results and financial position.

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Financial Statements and Supplementary Data of this Form 10-Q.

If these estimates, judgments and assumptions change in the future, including if Auryxia does not meet its current forecasted projections, additional impairment charges related to plant and equipment, right-of-use assets, goodwill or our intangible asset could be recorded in the future and additional corresponding adjustments may need to be made to the estimated useful life of the developed product rights for Auryxia, which could materially impact our financial position, certain of our material agreements, and our future operating results.

If these estimates, judgments and assumptions change in the future, additional impairment charges related to plant and equipment, right-of-use assets or goodwill could be recorded in the future and additional corresponding adjustments may need to be made to the estimated useful life of the developed product rights for Auryxia, which could materially impact our financial position, certain of our material agreements, and our future operating results.

If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of Auryxia or Vafseo.

We face an inherent risk of product liability as a result of the clinical and commercial use of Auryxia and Vafseo.

For example, we may be sued if Auryxia or Vafseo allegedly causes injury or is found to be otherwise unsuitable during clinical trials, manufacturing, marketing or sale.

We face an inherent risk of product liability as a result of the clinical and commercial use of Auryxia and Vafseo and our product candidates.

For example, we may be sued if Auryxia, Vafseo or our product candidates allegedly causes injury or is found to be otherwise unsuitable during clinical trials, manufacturing, marketing or sale.

Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product or product candidate, negligence, strict liability and breach of warranties.

Claims could also be asserted under state consumer protection acts.

If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required to limit commercialization of Auryxia or Vafseo.

Even a successful defense would require significant financial and management resources.

If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required to limit commercialization of Auryxia or Vafseo or affect the development of our product candidates.

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successful defense would require significant financial and management resources.

Regardless of the merits or eventual outcome, product liability claims may result in:

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• delay or termination of clinical trials;

• our inability to continue to develop Auryxia or Vafseo;

• our inability to continue to develop Auryxia, Vafseo or our product candidates;

• significant costs to defend the related litigation;

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Consequently, a product liability claim may result in losses that could be material to our business.

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We will continue to incur increased costs as a result of operating as a public company, and our management will be required to devote substantial time to compliance initiatives and corporate governance practices.

As a public company, we operate in a demanding regulatory environment, and we have and will continue to incur significant legal, accounting, auditing and other expenses.

As a public company, we operate in a demanding regulatory environment, and we have and will continue to incur significant legal, accounting, auditing, directors and officers insurance and other expenses.

The Sarbanes-Oxley Act of 2002, or the Sarbanes-Oxley Act , the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of The Nasdaq Capital Market and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and certain corporate governance practices.

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Claims for indemnification by our directors and officers may reduce our available funds to satisfy successful third-party claims against us and may reduce the amount of money available to us .

Our Ninth Amended and Restated Certificate of Incorporation, as amended, or Charter, and our Second Amended and Restated Bylaws, or Bylaws , as amended to date, contain provisions that eliminate, to the maximum extent permitted by the General Corporation Law of the State of Delaware, or DGCL , the personal liability of our directors and executive officers for monetary damages for breach of their fiduciary duties as a director or officer.

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monetary damages for breach of their fiduciary duties as a director or officer.

Our Charter and our Bylaws also provide that we will indemnify our directors and executive officers and may indemnify our employees and other agents to the fullest extent permitted by the DGCL.

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Future changes in our stock ownership, many of which are outside of our control, could result in an additional ownership change under Section 382.

As a result, if we generate taxable income, our

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ability to use our pre-change NOL carryforwards to offset federal taxable income may be subject to limitations, which could potentially result in increased future tax liability to us.

As a result, if we generate taxable income, our ability to use our pre-change NOL carryforwards to offset federal taxable income may be subject to limitations, which could potentially result in increased future tax liability to us.

At the state level, state net operating losses generated in one state cannot be used to offset income generated in another state and there may be periods during which the use of NOL carryforwards is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.

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This choice of forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers or other employees, which may discourage such lawsuits against us and our directors, officers and employees.

Alternatively, if a court were to find these provisions of our Charter inapplicable to, or unenforceable with respect to, one or more of the specified types of actions or proceedings, we may incur additional costs associated with resolving such matters in other jurisdictions, which could adversely affect our business and financial condition.

Alternatively, if a court were to find these provisions of our Charter inapplicable to, or unenforceable with respect to, one or

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more of the specified types of actions or proceedings, we may incur additional costs associated with resolving such matters in other jurisdictions, which could adversely affect our business and financial condition.

Risks Related to our Common Stock

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The stock market in general and the market for similarly situated biopharmaceutical companies specifically have experienced extreme volatility that has often been unrelated to the operating performance of particular companies, such as rising inflation and increasing interest rates.

Since our initial public offering in March 2014, the price of our common stock as reported on The Nasdaq Stock Market has ranged from a low of $0.24 on October 24, 2022 to a high of $31.00 on June 20, 2014.

The daily closing market price for our common stock varied between a high price of $1.55 on August 26, 2024 and August 30, 2024 and a low price of $0.94 on July 5, 2024 in the three-month period ending on September 30, 2024.

During that time, the price of our common stock ranged from an intra-day low of $0.91 per share to an intra-day high of $1.58 per share.

The market price of shares of our common stock could be subject to wide fluctuations in response to many risk factors listed in this section, including, among others, developments related to and results of our research or clinical trials, developments related to our regulatory submissions and meetings with regulatory authorities, commercialization of Auryxia, Vafseo, and any other product candidates, announcements by us or our competitors of significant transactions or strategic collaborations, negative publicity around Auryxia or Vafseo, regulatory or legal developments in the U.S.

and other countries, developments or disputes concerning our intellectual property, the recruitment or departure of key personnel including as a result of our reductions in workforce, actual or anticipated changes in estimates as to financial results, changes in the structure of healthcare payment systems, market conditions in the biopharmaceutical sector, potential delisting from The Nasdaq Stock Market and other factors beyond our control.

The market price of shares of our common stock could be subject to wide fluctuations in response to many risk factors listed in this section, including, among others, developments related to and results of our research or clinical trials, developments related to our regulatory submissions and meetings with regulatory authorities, commercialization of Auryxia, Vafseo, and any other product candidates, announcements by us or our competitors of significant transactions or strategic collaborations, market entry of generic competition to Auryxia, negative publicity around Auryxia or Vafseo, regulatory or legal developments in the U.S.

and other countries, developments or disputes concerning our intellectual property, the recruitment or departure of key personnel, actual or anticipated changes in estimates as to financial results, changes in the structure of healthcare payment systems, market conditions in the biopharmaceutical sector, potential delisting from The Nasdaq Stock Market and other factors beyond our control.

As a result of this volatility, our stockholders may not be able to sell their common stock at or above the price at which they purchased it.

In addition, securities class actions, shareholder derivative lawsuits and other legal proceedings are often brought against companies for any of the risks described in this Form 10-Q following a decline or volatility in the market price of their securities.

See Part I, Item 3.

Legal Proceedings of the 2023 Form 10-K for information concerning securities class action initiated against Keryx and certain current and former directors and officers of ours and Keryx’s.

We could be the target of such litigation or other legal proceedings in the future.

Class actions, shareholder derivative lawsuits and other legal proceedings, whether successful or not, could result in substantial costs, damage or settlement awards and such costs and

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any related settlements or judgments may not be covered by insurance.

Class actions, shareholder derivative lawsuits and other legal proceedings, whether successful or not, could result in substantial costs, damage or settlement awards and such costs and any related settlements or judgments may not be covered by insurance.

Monetary damages or any other adverse judgment would have a material adverse effect on our business and financial position.

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We could also suffer an adverse impact on our reputation, negative publicity and a diversion of management’s attention and resources, which could have a material adverse effect on our business.

If we fail to maintain compliance with Nasdaq's continued listing requirements, it could affect our ability to raise capital on acceptable terms, or at all.

As a result, an investor would likely find it more difficult to trade or obtain accurate price quotations for our shares.

Delisting would likely also reduce the visibility, liquidity, and value of our common stock, reduce institutional investor interest in our Company, and may increase the volatility of our common stock.

Delisting could also cause a loss of confidence of potential industry partners, lenders, and employees, which could further harm our business and our future prospects.

The issuance of additional shares of our common stock or the sale of shares of our common stock by any of our directors, officers or significant stockholders will dilute our stockholders’ ownership interest in Akebia and may cause the market price of our common stock to decline.

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As such, sales of a substantial number of shares of our common stock in the public market could occur at any time.

These sales, or the perception in the market that the holders of a large number of stockholders intend to sell such shares, could reduce the market price of our common stock.

As of September 30, 2024, and based on the amounts reported in the most recent filing made by BlackRock under Section 13(g) of the Exchange Act, BlackRock beneficially owned approximately 7.2% of our outstanding shares of common stock.

By selling a large number of shares of common stock, BlackRock could cause the price of our common stock to decline.

The shares beneficially owned by CSL Vifor have not been registered pursuant to the Securities Act and were issued and sold in reliance upon the exemption from registration contained in Section 4(a)(2) of the Securities Act and Rule 506 promulgated thereunder, but if they are registered in the future, those shares would become freely tradable and, if a large portion of such shares are sold, could cause the price of our common stock to decline.

In addition, we entered into a warrant agreement with Kreos Capital VII Aggregator SCSp, an affiliate of Kreos, or the Warrant Holder , pursuant to which (i) we issued a warrant to the Warrant Holder to purchase 3,076,923 shares of our common stock, at an exercise price per share of $1.30 (subject to standard adjustments for stock splits, stock dividends, rights offerings and pro rata distributions), or the Exercise Price , and (ii) if we drawdown the Tranche C Loan, at that time we will issue a warrant to the Warrant Holder to purchase 1,153,846 shares of our common stock, at an exercise price per share equal to the Exercise Price.

These sales, or the perception in the market that the holders of a large number of shares intend to sell such shares, could reduce the market price of our common stock.

As of March 31, 2025 and based on the amounts reported in the most recent filings made under Section 13(g) of the Exchange Act, BlackRock beneficially owned approximately 5.8% of our outstanding shares of common stock and the Vanguard Group, or Vanguard , beneficially owned approximately 4.8% of our outstanding shares of common stock.

By selling a large number of shares of common stock, BlackRock or Vanguard could cause the price of our common stock to decline.

In addition, as of March 31, 2025, CSL Vifor beneficially owned 7,571,429 shares of common stock, which have not been registered pursuant to the Securities Act and were issued and sold in reliance upon the exemption from registration contained in Section 4(a)(2) of

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the Securities Act and Rule 506 promulgated thereunder, but if they are registered in the future, those shares would become freely tradable and, if a large portion of such shares are sold, could cause the price of our common stock to decline.

Further, we entered into a warrant agreement with Kreos Capital VII Aggregator SCSp, an affiliate of Kreos, or the Warrant Holder , pursuant to which (i) we issued a warrant to the Warrant Holder to purchase 3,076,923 shares of our common stock, at an exercise price per share of $1.30 (subject to standard adjustments for stock splits, stock dividends, rights offerings and pro rata distributions), or the Exercise Price , and (ii) we issued a warrant to the Warrant Holder to purchase 1,153,846 shares of our common stock, at an exercise price per share equal to the Exercise Price.

Each warrant is exercisable for eight years from the date of issuance.

If any or all of the warrants are exercised, our stockholders could realize dilution, and the value of their shares could decrease.

We have a significant number of shares that are subject to outstanding options and restricted stock units, and in the future we may issue additional options, restricted stock units, or other derivative securities convertible into our common stock.

The exercise or vesting of any such options, restricted stock units, or other derivative securities, and the subsequent sale of the underlying common stock, could cause a further decline in our stock price.

We have a significant number of shares that are subject to outstanding options, restricted stock units and other securities convertible into our common stock, and in the future we may issue additional options, restricted stock units, or other securities convertible into our common stock.

The exercise or vesting of any such options, restricted stock units, or other securities, and the subsequent sale of the underlying common stock, could cause a further decline in our stock price.

These sales also might make it difficult for us to sell equity securities in the future at a time and at a price that we deem appropriate.

3 unchanged sentences

Our executive officers, directors and principal stockholders maintain the ability to significantly influence all matters submitted to stockholders for approval.

As of September 30, 2024, our executive officers, directors and principal stockholders, in the aggregate, beneficially owned shares representing a significant percentage of our capital stock.

As of March 31, 2025, our executive officers, directors and principal stockholders, in the aggregate, beneficially owned shares representing a significant percentage of our capital stock.

As a result, if these stockholders were to choose to act together, they would be able to significantly influence all matters submitted to our stockholders for approval, as well as our management and affairs.

1 unchanged sentence

This concentration of voting power could delay or prevent an acquisition of our Company on terms that other stockholders may desire.

Akebia Therapeutics, Inc.

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Provisions in our organizational documents and Delaware law may have anti-takeover effects that could discourage an acquisition of us by others, even if an acquisition would be beneficial to our stockholders, and may prevent attempts by our stockholders to replace or remove our current management.

9 unchanged sentences

• provide that our directors may be removed only for cause;

Akebia Therapeutics, Inc.

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• provide that vacancies on our Board of Directors may be filled only by a majority of directors then in office, even though less than a quorum;

8 unchanged sentences

As a result, capital appreciation, if any, of our common stock will be our stockholders’ sole source of gain for the foreseeable future.

Unregistered Sales of Equity Securities and Use of Proceeds.

Sales of Unregistered Securities

During the quarter ended September 30, 2024, we did not have any sales of unregistered securities.

Defaults Upon Senior Securities.

Not applicable.

Mine Safety Disclosures.

Not applicable.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 1A. Risk Factors